TY - JOUR
AB - 1 Jewell Carter, and 1 R. Edward Hogan ( 1 Neurology, Saint Louis University, St. Louis, MO ) Rationale: Of the more than 2 million persons in the United States with epilepsy, 400,000–600,000 are refractory to antiepileptic medication. Of these, 100,000–300,000 persons may have an epileptic region that can be surgically removed. It has already been established that the length of time a patient is referred to a tertiary epilepsy center is about 20 years. Once referred, the question becomes, what additional factors motivate a person to proceed with epilepsy surgery. Epilepsy surgery remains an underused treatment modality. To investigate factors associated with subjects who do or do not undergo epilepsy surgery, we compared two groups of subjects with refractory TLE, comparing subjects with and without a history of epilepsy surgery. Methods: We retrospectively reviewed all subjects who were evaluated at The Greater Midwest Epilepsy Treatment Center at Saint Louis University during the period of 1990–2001. The epilepsy surgery group was selected by consecutive review of subjects with a diagnosis of mesial temporal lobe epilepsy due to mesial temporal sclerosis who underwent epilepsy surgery. Subjects were matched, on a case by case basis, with subjects with chronic intractable temporal lobe epilepsy with no history of epilepsy surgery. The groups were matched for age, gender and total lifetime seizures. Using Fisher's Exact test, we compared marital status, insurance, race, and employment between the groups. For the epilepsy surgery subjects, all clinical data was taken from the pre‐surgical evaluation. Results: There were 15 men and 15 women in each group. Mean ages were 34.8 for surgery and 37.7 for non‐surgery groups (p = 0.34). Total lifetime seizures between groups were comparable (p = 0.25). Employment between the groups was significantly different (the surgery group being more likely to be employed), p = 0.0127. Defining insurance as Medicaid with or without Medicare, there was a near‐significant finding (the non‐surgery group being more likely to have Medicaid), p = 0.0692. Race (defined as white/non‐white) (p = 0.47), and marital status (p = 0.79) were non‐significant. Conclusions: Employment is associated with subjects who underwent epilepsy surgery. While there are many factors that may lead patients to undergo epilepsy surgery, our findings are suggestive that the wish to sustain employment is an important factor, regardless of severity of epilepsy. Of note, a U.S. Department of Health and Human Services research findings, identified that a major concern of persons with disabilities receiving SSDI and/or SSI was this: “SSDI and/or SSI benefits were not sufficient to live on, but fear of loss of benefits discouraged work attempts for some, and for others the benefits disappeared too soon after first work attempts were made.” This may indicate possible hesitancy on the part of some with epilepsy to proceed with surgery. 1 Laura L. Jurasek, 1 Daphne Quigley, 1 D. Barry Sinclair, 1 Syed Nizam Ahmed, and 1 Donald W. Gross ( 1 Comprehensive Epilepsy Program, University of Alberta Hospital/Stollery Childrens Hospital, Edmonton, AB, Canada ) Rationale: Transition from pediatric to adult health care services can be difficult for patients and families. Barriers to transition have been identified in the literature, with little pertaining to epilepsy. The University of Alberta Comprehensive Epilepsy Program encompasses both pediatric and adult services within the same facility. Adolescent and family needs can be addressed within the nursing scope of practice. The purpose of this project was to develop and evaluate a transition program for adolescents with epilepsy and their families who are being transferred from a pediatric to an adult epilepsy program. Methods: All patients referred from the pediatric to adult epilepsy clinic were included in this study. Patient independence and the learning needs of both patients and parents were evaluated with standardized questionnaires. During the transition clinic visit (which occurred prior to the first appointment with the adult neurologist), a standardized education program was provided with patient and family needs incorporated into teaching. Evaluations were completed following the transition appointment and after the adult neurologist initial visit. Results: To date six patients have completed the transition process (one of which had significant developmental delay). The majority of adolescents had minimal knowledge to manage their own healthcare (i.e. name and dosage of medications) and lacked basic information regarding epilepsy (i.e. first aid). In identifying their own learning needs, considerable discrepancies were observed between adolescents and parents in particular relating to the areas of driving, alcohol and birth control. Patients and parents were unanimous regarding the benefits of going through the transition clinic. Conclusions: Our findings support the benefits of a formalized transition process between pediatric and adult epilepsy programs. The development and implementation of a nurse‐led adolescent epilepsy transition program provides an opportunity to educate, encourage independence and alleviate fears during a period of time when other natural transitions are occurring. 1 Marian J. Kolodgie, 1 Audrey H. Scully, 1 Joan A. Conry, 1 Jay Salpekar, and 1 Andrew Renuart ( 1 Neurology, Children's National Medical Center, Washington, DC ) Rationale: Children with epilepsy may benefit from single‐daily dose Depakote ER. In the presence of developmental delay parents may have concerns regarding their child's ability to swallow extended release tablets. We developed a training protocol aimed at teaching parents how to transition their child from Depakote Sprinkles to Depakote ER tablets. Methods: Subjects included 10 children diagnosed with epilepsy and developmental delay, and their parents. Subjects had no known diagnoses of feeding disorders, swallowing problems, or food aversion. Parents underwent a three step training program; 1.) Parents were interviewed about their child's swallowing abilities and previous pill‐taking history. 2.) Parents received instruction on swallowing mechanics and behavior modification techniques. 3.) Pill administration was modeled by the clinic nurse and/or epilepsy nurse practitioner with each child. Mock tablets of incremental size were used during the training sessions. Children were allowed to swallow the pills with soft food or liquid but were not permitted to chew the tablets. Parents were instructed to practice with their child at home and provide a return demonstration at follow‐up clinic visits. Results: Nine subjects completed the protocol successfully and transitioned from sprinkles to extended release tablets within the study timeframe. The tenth child acquired pill‐taking skills shortly after the last study visit and is now taking extended release tablets. None of the subjects experienced choking, gagging, or other serious symptoms of distress. Conclusions: Developmental delay need not be an exclusionary factor in considering children's ability to swallow medication in pill form. Children with epilepsy and developmental difficulties can learn to swallow tablets through structured behavioral interventions. The ability to swallow tablets may contribute to overall compliance with treatment. (Supported by Abbott Laboratories.) 1 Sheila Koutsogiannopoulos, 1 Francine Adelson, and 1 Frederick Andermann ( 1 Nursing, Montreal Neurological Hospital, Montreal, QC, Canada; Social Work, Montreal Neurological Hospital, Montreal, QC, Canada; and Neurology, Montreal Neurological Hospital, Montreal, QC, Canada ) Rationale: To explore circumstances around the emergence of a first seizure in adult onset epilepsy; i.e.what trends, if any, exist in the quality and quantity of life events occurring in the 12 months preceding the onset of an initial epileptic seizure. Research suggests that how individuals adjust to significant life events may explain the time of onset of a disease or chronic disorder. (Holmes, T.H., Rahe, R. The Social Readjustment Rating Scale, J Psychosom Res. 1967. 11:213–218). Although stress is recognized as a major precipitant for seizures in patients with a known seizure disorder, few studies, in any, have explored the cluster of life events associated with the onset of a first seizure in adult onset epilepsy. We also explored patients' beliefs about the causes of their epilepsy, their knowledge of seizure triggers and their sense of control. Methods: A qualitative study using a phenomenological approach. Patients were selected prospectively from the M.N.H. epilepsy clinic and monitoring unit. Interviews were audio‐taped using a semi‐structured interview guide and a life experiences survey. Interviews continued until data saturation was achieved and themes identified. Results: All patients reported significant life events experienced in the 12 months prior to the onset of their first seizure. Different themes were noted between men and women and among women of different age groups. All male responders reported primarily work related stressors prior to their first seizure. When significant others were present during the interviews, family stresses were also identified. Young women in their 20's identified a perception of diminished self efficacy in completing developmental tasks. Middle aged women described major losses and disruption in family relationships. None of the respondents reported irrational beliefs about the cause of their epilepsy. 93% of respondents were able to identify their seizure triggers and planned strategies to control them. The majority of patients also expressed the belief that stress increased the frequency of their attacks. Conclusions: A positive relationship between significant life events and timing of a first seizure in adult onset epilepsy was demonstrated in this limited sample. A larger sample is needed to further evaluate this finding. The majority of the patients interviewed believe that stress and seizures are related. This adds to what has been reported in other studies (Antebi, D., Bird, J. The Facilitation and Evocation of Seizures. Br J Psych. 1993.162: 759–64). The patients had the perception of high self control, were able to identify a relationship between their seizures and likely triggers, and discuss strategies to control such triggers. This study highlights the need to specifically inquire about stressors which may be present and may play a role in the triggering of adult onset epilepsy. (Supported by Savoy Foundation.) 1 Angela M. McNelis, 1 Jennifer E. Myers, 1 Joan K. Austin, and 2 David W. Dunn ( 1 School of Nursing, Indiana University, Indianapolis, IN ; and 2 School of Medicine, Indiana University, Indianapolis, IN ) Rationale: Parents of children with epilepsy often lack seizure management skills due to inaccurate or incomplete information and knowledge about their children's seizure conditions. Moreover, parents have a great number of fears and worries associated with their child's condition. The purpose of the study was to test the effectiveness of a psychoeducational intervention designed to improve seizure management skills by reducing concerns and fears and improving knowledge about seizures. Methods: A quasiexperimental design was used to examine the effectiveness of the Be Seizure Smart intervention in a sample of parents of children with new‐onset seizures. Based on each individual's pre‐assessment, customized information was sent to meet the individual's unique needs. Once the information was received, a series of four 30‐minute phone calls approximately one week apart were made to address the parent's identified areas of need. Pre and post assessment measures included general concerns and fears about seizures (9 items), concerns about seizure management (8 items), psychosocial care needs (6 items on information and 8 items on support), uncertainty (31 items), knowledge about seizures (20 items), mood associated with their child's seizure condition (10 items), and satisfaction with family functioning (5 items). Results: The sample consisted of 22 mothers, 2 fathers, and 1 grandmother. The children (14 females and 11 males) ranged in age from 5 to 13 years, with a mean age of 8.2 years. Parents had significantly lower scores for concerns and fears (p < .001), concerns about seizure management (p < .001), need for information and support (p < .001), and uncertainty in illness (total uncertainty (p < .001), ambiguity (p < .001), lack of clarity (p < .001), and lack of information (p < .05)) after the intervention than before. As predicted, parents had significantly higher scores post intervention for knowledge about seizures (p < .001) and mood (p < .001). Although parent scores on satisfaction with family functioning were more positive and scores on unpredictability were lower, results did not reach statistical significance. Conclusions: Overall, Be Seizure Smart was a successful intervention program. A major strength of the program was that it was tailored to meet each parent's individual needs, allowing parents to discuss specific concerns with the research nurse. The program can be easily transferable to the clinical setting as the pre‐assessment takes only 10 minutes and the 1‐page fact sheets are already developed. Follow‐up phone calls to discuss the written materials could prove to be cost effective by decreasing the number of office visits and physician calls. (Supported by: Funded by grant # P30 NR05035 (PI: Austin, Joan K.) from the National Institute of Nursing Research (NINR) to the Center for Enhancing Quality of Life in Chronic Illness at Indiana University School of Nursing.) 1 Christine A. Restivo‐Pritzl, 1 Christopher M. Inglese, 1 Veronica N. Sosa, and 1 George L. Morris III ( 1 Regional Epilepsy Center, St. Luke's Medical Center, Milwaukee, WI ) Rationale: Health‐related quality of life (H‐RQOL) is a middle range nursing theory that reflects the nursing profession's emphasis upon holistic and individualized patient care. Simply defined, the concept of H‐RQOL may represent an individual's satisfaction with a specific area of life that he or she has identified as vital. Wilson and Cleary identify five determinants that influence and are influenced by overall QOL to produce an individual's H‐RQOL: biological and physiological variables, symptoms, functional status (including the physical, social, role, and psychological/spiritual domains), and general health perceptions. This model illustrates how the diagnosis of epilepsy may exert influence that is far‐reaching and pivotal upon all aspects of an individual's life. Children and adolescents are in the midst of vital developmental stages, with the desired end result being the attainment of a sense personal and interpersonal competence as well as personal identity. Anxiety related to the fear of experiencing seizures in public, feelings of “different‐ness” from peers, dependence upon others, and the stigma that plagues the diagnosis of epilepsy may present a significant obstacle to an individual's psychosocial development, and may result in problems that affect every aspect of every day living. The purpose of this project is to explore the actual impact of the epilepsy diagnosis upon the H‐RQOL among the children and adolescents care for at a regional epilepsy center, as well as to determine the necessity of including an abbreviated H‐RQOL evaluation as part of the nursing assessment at clinic visits. Methods: An abbreviated H‐RQOL assessment tool was developed based upon the QOLIE‐31 scale. Questions were selected to represent areas of life that were deemed significant to children of school age and adolescents–self‐concept, family life, social life, and medications. During scheduled appointments, as part of the interval nursing assessment, patients were provided a scoring tool and asked scripted questions by a registered nurse. Results: To date, five children have been interviewed, ranging from 10 to 15 years of age. When asked to rate their current life satisfaction on a Likert scale of 1 (“Very unhappy with life right now”) to 5 (“Very happy”), the average response was 2.4. All of the respondents stated that they worry about having a seizure, as well as feel that having seizures affects their grades. Two of the children interviewed stated that their epilepsy makes them feel different from others. Conclusions: Data collection is ongoing, and it is impossible to draw accurate conclusions with such a small sample size. However, it is clear from these few responses that the diagnosis of seizures is one that affects many areas of a child's life, and inclusion in the nursing assessment may be crucial to limit negative impact upon psychosocial development. 1 Deborah L. Shulman, 1 Bryn M. Corbett, 1 Patricia H. Miller, 1 Luann C. Helepololei, 1 Lisa M. Tapsell, 1 Katherine H. Noe, 1 Joseph F. Drazkowski, and 1 Joseph I. Sirven ( 1 Neurology, Mayo Clinic Hospital, Phoenix, AZ ) Rationale: A considerable amount of information is presented to the patient prior to their EMU admission. Much of the information is provided in an educational booklet that all patients receive from the physician during their medical appointment or in the mail after the admission date has been scheduled. Many patients have stated during their admission that they were not informed of certain issues pertaining to an EMU stay. These issues include but are not inclusive to; memory testing, use of a safety belt, and the necessity of staying in their room while being closely monitored. Some patients become upset about not being aware of aspects of their stay and become frustrated when they realize the implication of how being on the EMU affects them. A comprehensive EMU booklet is given to every patient preadmission, however, it is unclear if the information within the booklet was presented but not processed or if it was presented at all. A brief questionnaire was constructed to help guide the formation of an educational tool. This will enable us to provide adequate patient education and set appropriate expectations to promote better health outcomes Methods: Patients who were admitted to the EMU in April 2006 were surveyed by a 12 question instrument designed to assess expectations prior to the admission. Surveys were conducted by telephone retrospectively. Some aspects of the survey included; assessment of knowledge of the use of safety belts, memory testing, use of sleep deprivation to invoke seizures, use of an intravenous cannula, and if the patient received the information booklet. Results: 12 surveys were completed, 4 male and 8 female with the age range being 37–77 years and 52 the average age of respondents. Fifty‐eight percent had received and read the EMU information booklet, however, these same patients all claimed they did not know they would have memory testing. 42% claimed they did not know about the use of a safety belt, and 85% did not know they would be sleep deprived. This information is contained in the booklet, and 75% of all respondents felt they were able to ask questions and discuss expectations prior to the admission. Conclusions: It would appear that adequate patient education is provided but not necessarily understood despite receiving an EMU booklet and having the opportunity to discuss its contents. This approach may not be enough to insure positive EMU outcomes that we seek. Supplementary education is needed which could include a tour of the EMU prior to admission or assessing how patients themselves define the best method for them to learn. This may assist with setting appropriate expectations to promote better health outcomes. A larger population based study is needed to define how to best structure educational programs relating to diagnostic epilepsy procedures in order to meet the needs of our patients. 1 Siv Skarstein, 1 Vibeke Snarseth, and 2 Erik Taubøll ( 1 National Centre for Epilepsy, Division of Clinical Neuroscience, Rikshospitalet‐Radiumhospitalet, Oslo, Norway ; and 2 Department of Neurology, Division of Clinical Neuroscience, Rikshospitalet‐Radiumhospitalet, University of Oslo, Oslo, Norway ) Rationale: Patients with epilepsy and autism represent a complex group that require specialist treatment and care. At the National Centre for Epilepsy we experienced a high readmission rate for this patient group. Carers expressed uncertainty on how best to manage these patients and their seizures. The aim of this study was to develop an educational program to increase competence among carers, thereby reducing readmission to a specialist epilepsy hospital. Methods: Sixteen consecutive adult patients (7 women, 9 men) with autism and difficult to treat epilepsy admitted to the National Centre for Epilepsy, Sandvika, Norway, from 01.01.2004 to 12.31.2005 were included. A three‐phase, standardized program was designed. This consisted of: 1) a pre‐hospitalization visit to establish patient needs with regard to the management of epilepsy and psychosocial problems, 2) a hospitalization phase where the individual needs of the patient revealed in phase 1 were further defined. The carers were given specialized and individualized information about epilepsy and behavioural/psychosocial problems relating to their patient, and 3) a post‐hospitalization phase consisting of an individual plan and a follow‐up visit at home. A survey for carer satisfaction was performed 1 month after discharge. Results: The main finding in this study is that only 1 of the 16 patients have so far been readmitted to the hospital (Mean observation time: 16.4 months, range: 8–33 months). The survey for carer satisfaction revealed that in 9 cases the carers felt that they managed the problems related to the patient's epilepsy better. In 11 cases, the initiatives suggested by the hospital were implemented at home. In 15 cases, the carers found that the defined needs of the patient established in the pre‐hospital phase were adhered to. Conclusions: A new educational program aimed at increasing competence among carers of patients with epilepsy and autism was shown to be effective. The readmission rate to hospital was dramatically reduced. Carers and staff felt more secure and competent when dealing with this complex patient group. 1 Pamela L. Smith, 1 Jennifer M. Burgos, 1 George L. Morris, 1 Christopher M. Inglese, and 1 Veronica N. Sosa ( 1 Regional Epilepsy Center, Saint Luke's Medical Center, Milwaukee, WI ) Rationale: Lamictal is an approved antiepileptic drug used as add‐on‐therapy for partial seizures in the adult and pediatric population. It has also been approved as initial monotherapy in adults newly diagosed with seizures, as well as conversion of Lamictal add‐on‐therapy to monotherapy in adults with partial sizures. Serious rashes requiring hospitalization and discontinuation of treatment, have been reported with the use of Lamictal. The incidence of these rashed is about 0.8% in the pediatirc population (age 16 and under) and 0.3% in adults receiving Lamictal as adjunctive therapy for epilepsy. Other then age, there are no known factors that could be identifyers in predicting the rash occurrence. Nearly all cases of serious rashes have occurred within 2–8 weeks of initiation of treatment. However, rare cases have been reported after prolonged treatment. Methods: To date, a retrospective analysis of 151 medical records identified 22 adults and 4 pediatric patients (age 16 and under) on Lamictal therapy admitted for inpatient VEEG monitoring since November 2002. Results: The 22 adults or 14.57% of the admitted population, had an average hospital length of stay of 3.2 days and were receiving an average daily dose of Lamictal 400 mgm. The 4 pediatric patients or 2.65% of the admitted population, had an average hospital lenth of stay of 7.2 days and were receiving an average daily dose of Lamictal 450 mgm. Upon discharge and dose resumption, none of the patients displayed any evidence of rash. Conclusions: In this study, we saw that both adult and pediatric patients can have their Lamictal dose discontinued and reintroduced without the emergence of a serious rash. Data collection is ongoing and needs to have similar outcomes to validate these outcomes. 1 Chase A. Allen, and 1 Malachy L. Bishop ( 1 Rehabilitation Psychology and Special Education, University of Wisconsin‐Madison, Madison, WI; and Special Education and Rehabilitation Counseling, University of Kentucky, Lexington, KY ) Rationale: The problematic employment situation for people with epilepsy has been well established. The unemployment rate experienced by people with epilepsy has frequently been shown to be higher than that found in the general population. Numerous efforts at understanding the employment problems faced by persons with epilepsy have revealed a complex interrelationship of causes and explanations, including seizure‐related variables, psychosocial factors, negative employer attitudes and discrimination, and fear of stigma and discrimination. In an effort to further clarify the situation and update understanding of changing employer attitudes, this research explored employer attitudes toward epilepsy as compared to other chronic conditions, and the implications of describing one's epilepsy using different terms (seizure condition, seizure disorder, epilepsy). Methods: In this survey‐based research we surveyed 50 human resources professionals and employers in a Southeastern United State. We presented the employers and HR professionals with several descriptions of hypothetical applicants with various chronic conditions (e.g., AIDS, epilepsy, mental retardation, cancer, heart disease) and asked them to rank and rate the applicants based on their willingness to hire a similar individual at their company. The influences of work experience, education, and other demographic variables were controlled. In addition, we varied the use of the terms seizure condition, seizure disorder, and epilepsy in describing the individual with epilepsy. Analysis of variance and descriptive statistics were used to analyze the results. Results: Data collection is currently ongoing, and full results will be presented, however results to date are consistent with prior similar research concerning employers' attitudes toward epilepsy and hiring individuals with epilepsy, relative to other conditions. The use of the term epilepsy appears to be less positive from the employers' perspective that the alternatives, however the results are not yet conclusive. Conclusions: The results have important implications for epilepsy professionals engaged in assisting persons with epilepsy in seeking and maintaining employment. The present study highlights, in particular, the ongoing concern about epilepsy‐related stigma in the area of employment. 1 Malachy L. Bishop, and 1 Chase A. Allen ( 1 Special Education and Rehabilitation Counseling, University of Kentucky, Lexington, KY; and Rehabilitation Psychology and Special Education, University of Wisconsin‐Madison, Madison, WI ) Rationale: Epilepsy, perhaps more than any other chronic illness, has the potential to impact experience across the range of physical, psychological, and social domains of living. Understanding the mechanisms through which epilepsy affects psychosocial function, and the processes that people employ to adapt to this impact are a critical focus of epilepsy research toward effective clinical intervention. This research evaluates the disability centrality model, a multi‐dimensional quality of life‐based model of psychosocial impact and adaptation among persons with epilepsy. Methods: This research employed a web‐based survey methodology to test the assumptions of the disability centrality model. Adults were recruited through Epilepsy Foundation affiliates in the Southeast United States. A total of 42 adults with epilepsy completed a questionnaire that included the Disability Centrality Scale, which assesses the respondents' level of satisfaction, epilepsy‐related impact, perceived control, and the level of importance ascribed to each of ten empirically derived quality of life domains. Additionally, demographic information, duration since diagnosis, and two well‐established measures of quality of life and psychosocial adaptation were employed. Hypothesized relationships among these variables, based on the model, were assessed in a series of multiple regression analyses. Results: A number of elements of the proposed model were supported. Domain control and satisfaction mediated the relationship between perceived impact and overall QOL, and psychosocial adaptation. Domain importance moderated the relationship between epilepsy‐impact and adaptation. The relationships between QOL, adaptation, and duration and demographic variables were also explored. Conclusions: The results of this preliminary investigation are consistent with larger scale investigations among persons with multiple sclerosis and other chronic conditions, and support the proposed model. There are a number of important clinical and research implications. The results suggest that the psychosocial impact of epilepsy is experienced multidimensionally, across a range of life domains. Perceived domain control over the impact of epilepsy acts as an important mediator in the relationship between the experiences associated with epilepsy and one's overall QOL. In addition, the individual's perception of the personal importance of the domains moderates the impact of epilepsy. The results suggest two important venues for clinical intervention in enhancing quality of life among individuals with epilepsy: interventions aimed at enhancing perceived control, such as self‐management and patient education, as well as those that expand the individual's means of attaining satisfaction. 1 Peggy Crawford, 1 Farrah M. Thomas, and 2 Noah Webster ( 1 Department of Neurology, Cleveland Clinic, Cleveland, OH ; and 2 Department of Sociology, Case Western Reserve University, Cleveland, OH ) Rationale: Major depression is a frequently unrecognized and untreated comorbidity in chronic epilepsy. In particular, the psychological status of patients undergoing epilepsy surgery is a critical issue in clinical management and a major factor in quality of life. Changes in mood both positive and negative and psychiatric status have been noted with surgery. Multiple factors have been implicated in mood changes after surgery including epilepsy‐specific variables such as laterality, location of seizures, and seizure outcome as well as psychosocial variables including personality traits. The purpose of this study is to investigate the mental health of epilepsy patients prior to surgery in order to identify disorders and symptoms amenable to treatment. Methods: Participants are two hundred and twenty‐five adults (44% male, 88% Caucasian, 44% married, 42.1% employed full or part‐time) aged 18–75 with medically intractable epilepsy undergoing evaluation for surgery at the Cleveland Clinic. They participated in a Health Psychology evaluation that included chart review for demographic, disease, and health‐related information; clinical interview concerning current and past psychological status; and self‐report measures of mood, fatigue, and daytime sleepiness Results: Based on self‐report, 65% reported a positive mental health history including depression in 50.2%, anxiety 15.6%, bipolar disorder 1.3% and psychosis 2.7%. Regarding treatment, 43.8% had previously seen a mental health professional and 41.8% had used psychotropic medication. Based on pre‐operative Beck Depression Inventory responses, 16.9% were mildly depressed, 27.9% moderately depressed, and 11.5% severely depressed. In contrast, only 5.8% were taking psychotropic medication. Pre‐operatively, both employment (full or part‐time) and marital status (married) were associated with lower depression scores. Although patients who had ever used psychotropic medication were more likely to have higher pre‐operative depression scores, those currently taking psychotropic medication were not. Conclusions: Comparable to previous studies, we found high rates of depression including almost 40% of patients reporting moderate to severe depression. In spite of this, many patients had never seen a mental health professional and even fewer had taken psychotropic medication (only 5.8% at the time of the evaluation) both known to be effective treatments for depression. It is not clear why patients are not being identified and/or treated. One possibility is that both professionals and patients assume that depression is common with medically intractable epilepsy and consequently treatment is not recommended or sought. These findings support the routine assessment of all patients being considered for epilepsy surgery in order to identify and initiate treatment of depression regardless of whether or not patients have surgery. 1 Manjari Tripathi, 1 Sandra Dewar, 1 Itzhak Fried, 1 Zhiyi Sha, 1 David Millet, 1 Andres Gonzales, 1 Kathleen Langlois, 1 John Stern, 1 Schrader Lara, 1 Soss Jason, and 1 Engel Jerome ( 1 Department of Neurology, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; Department of Surgery, Division of Neurosurgery, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; Department of Neurology, UCLA, Los Angeles, CA; and Department of Neurology, UCLA, Los Angeles, CA ) Rationale: Older age at surgery is considered to carry higher surgical risk. There are few reports on surgical outcome in this age group. We report a series of 51 patients over 45 years of age who had surgery between 1992 and 2005 at UCLA. A prospective seizure outcome data collection was done. Methods: The inclusion criteria were intractable epilepsy, a minimum of 12 months follow‐up, and patients 45 years and older at surgery. The last follow‐up, done in 2006 for all patients included a computer assisted telephonic interview of the life fulfillment satisfaction scale (Liverpool QOL questionnaire). The following factors were considered: Satisfaction with surgery, life changes in the spheres of health, driving, working, adjustment issues, patients perception to general health and reasons for delay in obtaining surgery. Results: The mean age of surgery in the series was 52 years (range 45–74). The mean follow up was 4.3 years (range 1–11 years.) Mean duration of epilepsy was 29.3 years (range 2–55 yrs). Most patients would have had surgery earlier but gave failure to refer and lack of knowledge about surgery as reasons for delay. The age of onset was divided into 3 groups those between 1–10 years (n = 18), 11–20 years (n = 12) and more than 21 years (n = 22). Forty patients (80%) had an Engel class I outcome. Four had an outcome of II, the rest had a poor outcome. Impact of nocturnal seizures only (n = 3) (Engel class II) was high, contrary to expectations. The life fulfillment scores averaged 38 (range 16 to 49) out of a total of 52 and did not correlate to the patients perceived satisfaction with surgery and were lower for those patients with poor social recovery and multiple adjustment issues. There were 5 deaths in this group, only one of these was directly related to surgery and occurred 3 wks after surgery. Conclusions: Seizure outcome was excellent but poor social recovery and low life satisfaction scores were frequently recorded. Age should not limit access to surgery; however, the missed opportunity for psychosocial improvement, reducing the impact and promoting healthy aging and life satisfaction should prompt early surgery. 3 Kristin P. Guilliams, 2 Jesus F. Martinez, and 1 Nathan B. Fountain ( 1 Neurology, University of Virginia, Charlottesville, VA ; 2 Neurology, Hospital Nacional Rosales, San Salvador, El Salvador ; and 3 Pediatrics, Washington University, St. Louis, MO ) Rationale: Perceptions may directly or indirectly influence the quality of care physicians provide. This is particularly true in epilepsy, as misperceptions and prejudices have been noted by the Global Campaign Against Epilepsy and targeted in their “Out of the Shadows” campaign. Physicians are a major source of health information; their beliefs have a trickle‐down effect to the general population. A physician's own comfort level treating certain diseases may also influence the quality of care he or she is able to provide. We surveyed physicians in El Salvador about their perceptions and comfort levels of treating patients with epilepsy. Methods: We surveyed 27 physicians in San Salvador, El Salvador. Eight practiced in neurology‐related fields (neurology, pediatric neurology, or neurosurgery). Nineteen were in primary care fields (generalist or gynecology). All reported treating patients with epilepsy. Surveys were conducted at educational meetings in San Salvador. Part A asked participants to rate their agreement on a scale from 1 to 5 where 1 indicates disagreement and 5 indicates agreement for 11 statements in reference to persons with epilepsy. Part B was identical to A, except it specifically referred to persons with well‐controlled epilepsy. Part C asked participants to rate their comfort level in treating patients with epilepsy on a scale from 1 to 5. It also requested age, field of medicine, and years in practice. Results: The average sum on Part A for neurology related physicians (NRP) was 45.63 out of 55; the average for primary care physicians (PCP) was 42.84. The average sum on Part B for NRPs was 49.25; the average sum for primary care physicians was 47.79. Statements with a difference of greater than 1 point between the two groups include: Part A, “Persons with epilepsy should be open about their disease with others,” NRPs averaged 3.25 on a scale from 1 to 5. PCPs averaged 4.35 on the same statement. On the same statement in Part B, NRPs averaged 3.5, and PCPs averaged 4.7. In Part B “Persons with well‐controlled epilepsy should not be obligated to inform schools or employers of disease,” NRPs averaged 2.88 on a scale of 1 to 5, whereas PCPs averaged 3.94. The average comfort score for NRPs was 4.63, and 2.79 for PCPs. Conclusions: Salvadoran physicians appear to have positive perceptions of persons with epilepsy. Although both NRPs and PCPs treat patients with epilepsy, PCPs are significantly less comfortable treating patients with epilepsy. Further research is needed to determine patients' perceptions of physician and general population attitudes towards epilepsy. Further education is warranted to give PCPs information and confidence to become more comfortable in managing the treatment of their patients with epilepsy. (Supported by Center for Global Health at the University of Virginia.) 1 Elena T. Harlan Drewel, 1 Debora J. Bell, and 2 Joan K. Austin ( 1 Department of Psychological Sciences, University of Missouri‐Columbia, Columbia, MO ; and 2 School of Nursing, Indiana University, Indianapolis, IN ) Rationale: Children with epilepsy are at risk for long‐term psychosocial problems compared to healthy children or children with other health conditions, which may be due to peer difficulties. Peer relationships influence children's immediate and lifelong social and emotional well‐being, and research shows that children with epilepsy have more peer difficulties than do healthy children or children with other health conditions. Few studies investigate variables related to peer problems in children with epilepsy. Inattentive behavior, anxious behavior, and academic difficulties are linked to peer problems among healthy children; these same variables are likely related to peer problems among children with epilepsy. Yet, also examining if epilepsy‐related factors such as neuropsychological functioning and seizure characteristics are associated with peer difficulties is important because it may clarify why children with epilepsy are at greater risk for peer problems compared to other children. Hence, the current study determined if epilepsy‐related factors such as neuropsychological deficits, greater seizure frequency, and earlier age at epilepsy onset as well as behavioral/academic factors such as inattentive behavior, anxious behavior, and academic difficulties are related to peer problems in children with epilepsy. Methods: Participants were 173 children with epilepsy, ages 8–15. Correlations among predictor and outcome variables were examined to determine their interrelations with one another; structural equation modeling was used to investigate simultaneous interrelations among latent factors. Results: The measurement model indicated that correlations among the behavioral, academic, epilepsy‐related, and peer difficulty factors were significant and in the predicted direction. The structural model revealed that the neuropsychological factor mediated the relation between age at epilepsy onset and the behavioral, academic, and peer difficulty factors; anxious behavior and inattentive behavior mediated the relation between the neuropsychological and peer difficulty factors; anxious behavior mediated the relation between seizure frequency and the peer difficulty factor. Conclusions: Neuropsychological deficits and greater seizure frequency may have a direct influence on behavior problems in children with epilepsy and, therefore, may affect their peer relations. Thus, when treating behavioral and peer difficulties in children with epilepsy, mental health professionals may wish to consult with neuropsychologists and physicians regarding the potential influence of neuropsychological and seizure‐related variables. (Supported by National Institute of Nursing Research grant PHS R01 NR04536 awarded to Joan K. Austin, DNS, RN, FAAN.) 1 Bosil Kim, 1 Hee Jin Kang, 1 Hee Jin Kim, 1 Geon Ha Kim, 2 Eun Jung Chung, 2 Eui Jung, and 1 Hyang Woon Lee ( 1 Neurology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea ; and 2 Psychiatry, College of Medicine, Ewha Womans University, Seoul, Republic of Korea ) Rationale: Epilepsy may have a significant impact on the intelligence and emotions especially in childhood and adolescent ages. The objective of this study was to elucidate the clinical factors influencing the patient's intelligence, anxiety and depression in children and adolescents with epilepsy. Methods: Subjects were 90 epilepsy patients between the ages of 6 and 17 years (mean 11.8 ± 3.9 years) and their parents. We acquired simplified neuropsychological tests including verbal, performance and full scale IQ, the Stroop and the Trail‐making test (TMT) from each patient. They also filled up the Impact of Childhood Illness Scale (ICIS), the State‐Trait Anxiety Inventory (STAI), the Revised Children's Manifest Anxiety Scale (RCMAS), the Children's Depression Inventory (CDI), the Questionnaire on Resources and Stress (QRS), the Family Adaptability and Cohesion Evaluation Scales (FACES) in children with epilepsy and their families. We compared the differences across patient groups according to the clinical factors such as seizure frequency, epilepsy types and duration, mono‐ or polytherapy, etc. Results: Full scale IQ was lower in patients with poor seizure control than seizure free group (75.0 ± 29.0 vs. 101.6 ± 23.1; p = 0.029), and in patients with polytherapy than monotherapy (72.6 ± 27.4 vs. 102.7 ± 22.1; p = 0.029). ICIS, QRS, CBCL and Conners scale were higher when patients had poor seizure control (p = 0.011, 0.027, 0.047 and 0.075, respectively), and took more than one antiepileptic drugs (p = 0.008, 0.003, 0.022 and 0.033). STAI and RCMAS were higher in patients with epilepsy within the first 2 years or longer than 4 years (p = 0.023 and 0.043). Increased parental anxiety based on STAI were correlated with increased ICIS, RCMAS, CDI, and Conners scale (p = 0.002, 0.002, 0.009, and 0.004). Conclusions: Epilepsy patients in childhood and adolescent ages have significant impacts on their intelligence and emotions if they have poorly controlled seizures or take more than one antiepileptic medications. 1 Yolanda C. Leon, 3 Joseph Sesta, 2 Selim Benbadis, and 2 William O. Tatum ( 1 Clinical Research, Pediatric Epilepsy and Neurology Specialists–PENS, Tampa, FL ; 2 Neurology, University of South Florida/Tampa General Hospital, Tampa, FL ; and 3 Suncoast Neuropsychology Labs, Riverview, FL ) Rationale: In recent years, increasing interest in the emotional experience of patients with seizure disorders has stimulated investigation of various emotional states. Considerable emphasis has been placed on the study of depression and anxiety. Of the studies available, relatively few, if any, have investigaged the construct of anger among patiens with seizures. Although previous studies have examined differences between patients with spileptic seizures (ES) and patients with Psychogenic non‐epileptic seizures (PNES), the emphasis has been on the assessment of depression and anxiety. The primary goal of this preliminary study was to examine the experience, expression and control of anger in patients with seizures utilizing the most widely researched, standardized and validated Anger measure that utilized in behavioral health settings, the State Trait Anger Expression Inventory (STAXI‐2). A secondary goal of the study was to compare Anger measures of patients with ES and PNES. Methods: Subjects were drawn from a series of adult patients referred for long‐term video EEG monitoring as part of a comprehensive evaluation for refractory seizures at the USF College of Medicine–Tampa General Hospital Comprehensive Epilepsy Program. Patients with a definitive diagnosis of either ES or PNES as determined by EEG video Monitoring were included. Only those patients that did not complete the STAXI‐2 were excluded. Results: Patients with ES and PNES have higher Trait Anger scores and higher Anger Expression scores than those of the normative sample. Patients with PNES have higher Trait Anger Reaction and Anger‐In scores than patients with ES or the normative sample. Conclusions: The findings of the preliminary study suggest that there are significant differences in the way patients with seizures experience and express anger. Further, there are differences between patients with ES and PNES. These findings suggest that the STAXI‐2 successfully differentiates ES patients from PNES patients in terms of their suppression and expression of anger. Future research is needed to investigate how different types of epilepsy patients experience anger, how it motivates their behavior and impacts their health. The implications for psychotherapeutic intervention and treatment planning should be explored. 1 Sophia Macrodimitris ( 1 Clinical Neurosciences, Calgary Health Region, Calgary, AB, Canada ) Rationale: Community samples of epilepsy patients experience higher rates of depression (9–25%) and anxiety (10–25%) disorders than the general population (depression 2–9%; anxiety 2.5–6.5%). In treatment resistant epilepsy, estimates are even higher (e.g., depression 25–55%). Despite these issues, many epilepsy programs do not adequately assess for or address mental health problems. This paper describes program development and referral practices during the first year of a clinical psychology service devoted to epilepsy patients. Methods: Participants: 132 consecutive SMU admissions over 10 months were explored for clinical psychology and psychiatry referrals. 1657 consecutive outpatient visits over 6 months were explored for clinical psychology referrals. All referrals were from epileptologists (n = 7). Procedure: The Clinical Psychology Service was developed separately from Neuropsychology in two phases: Phase I: Seizure Monitoring Unit (SMU); Phase II: Outpatient. Phase I SMU: Neurologists and nurses completed a referral package: referral form, patient history, and patient‐completed background information questionnaire. Nurses contacted the psychologist when the referral was completed. Referrals were reviewed by the psychologist for appropriateness. Phase II Outpatient: Referral package (same as SMU) was forwarded to the psychologist for one of three possible services: assessment only; assessment and brief (up to 6 sessions) therapy; and therapy only. Clinical psychology referral information was tracked in an excel database. Overall SMU admission rates were obtained from the master SMU admission list. Number of outpatient visits for each epileptologist was provided by the Clinical Neurosciences program manager. Results: SMU: 52.5% (n = 72) received a clinical psychology assessment; 18.5% (n = 24) received a psychiatry assessment. Overlap in referrals to clinical psychology and psychiatry occurred in the first month. Psychology referrals increased in months 3–5. Referrals reduced in later months. OUTPATIENT: 2.4% (n = 40) of clinic visits to epileptologists were referred for outpatient services. Referral rates ranged from 0–4.7% per neurologist. Rates varied according to years of experience (i.e., junior neurologists referred more often) and number of visits (i.e., junior neurologists with more visits referred more often). Conclusions: Clinical psychology services are well‐integrated into the SMU but referrals to the outpatient service remain low, particularly when compared to the established rates of mental health problems in epilepsy patients. The low referral rates may reflect the “newness” of the resource. It may also reflect poor mental health assessment practices at clinic visits. Despite the low outpatient referral rate, the clinical psychology service maintains a 3–4 month waiting list, suggesting that more outpatient resources (e.g., groups) are required prior to increasing the number of referrals to the program. 1 Edna A. Monteiro, 1 Sandra S. Funayama, 1 Ricardo Guarnieri, 1 Otávio I. De Faria, 1 Vera C. Terra‐Bustamante, 1 Tonicarlo R. Velasco, 1 Veriano Alexandre Jr., 1 Lauro Wichert‐Ana, 2 João A. Assirati Jr., 2 Carlos G. Carlotti Jr., 3 Li M. Li, 1 Marino M. Bianchin, 1 Américo C. Sakamoto, and 1 Jaime E. Hallak ( 1 CIREP‐Department of Neurology, Psychiatry, and Medical Psychology, Ribeirão Preto School of Medicine, University of Sao Paulo, Ribeirão Preto, São Paulo, Brazil ; 2 Department of Neurosurgery, Ribeirão Preto School of Medicine, University of Sao Paulo, Ribeirão Preto, São Paulo, Brazil ; and 3 Department of Neurology, University of Campinas–UNICAMP, Campinas, São Paulo, Brazil ) SHE scales scores according to seizure frequency Seizure Frequency Work and activity Social and personal Physical Self‐ perception Life‐ satisfaction Changes Seizure‐free group (n = 36) (versus not seizure free) 88*(81,95) 82*(74,90) 77*(71,84) 77*(70,85) 72*(67,77) 75*(69,80) SPS or < 1 sz/month (n = 18) (versus >or = 1 sz/month) 81*(71,91) 83*(71,94) 70*(61,80) 72*(62,83) 69*(62,76) 66*(58,74) 1–4 sz/month (n = 71) (versus > 4 sz/month) 55*(50,60) 65 (59,71) 52 (48,57) 45 (39,50) 61 (57,65) 55*(51,59) > 4 sz/month (n = 94) 44 (39,48) 56 (51,61) 45 (41,49) 36 (31,40) 56 (53,59) 47*(44,50) SPS = simple partial seizures, Sz = seizure. *(p < 0.05 or less). Rationale: Health quality of life evaluations have been used to improve our capacity to assess the impact of diseases to the individuals. Because quality of life evaluations might be greatly dependent on subjective aspects, tools designed to assess these aspects are interesting. Donoghue and collegues (Brain 1998; 121:317–43) have designed and validated a tool to evaluate the subjective handicap of epilepsy. However, it has been validated in patients from UK, but it is uncertain whether it could be successfully used in other populations with diverse culture and distinct subjective values. Methods: The Subjective Handicap of Epilepsy scale (SHE) was translated to Portuguese and back‐translated to English. After test‐retest, the SHE was administered to 219 adult patients (115 men and 104 women, mean age of 35.4 (18–66) years‐old with focal symptomatic epilepsy, not submitted to epilepsy surgery. Patients were divided in 4 sub‐groups according to seizure frequency. Data was analyzed by a Multivariate Analysis of Variance (MANOVA), using Wilks' Lambda as the multivariate test and Student‐Newman‐Keuls as a post hoc test for multiple comparisons between the six sub‐scales scores of SHE. Results are expressed in mean SHE‐scale scores (95% C.I.). Results: Multivarate analysis reveled a significant difference of SHE‐sub‐scales means among the four groups of seizure control (Wilks' Lambda = 0.57; F= 579.23; p < 0.0001). The results of post‐hoc comparisons are presented in Table. Conclusions: Here, we validate the SHE scale to Brazilian Patients. SHE scores are similar in Brazilian patients when compared to England patients. Thus, we concluded that SHE is reliable and applicable to evaluate the long‐term consequences of epilepsy in our population. (Supported by FAPESP.) 1 Christine O'Dell, 1 Shlomo Shinnar, 2 Avital Cnaan, 1 David Masur, 2 Mayadah Shabbout, 3 Paul M. Levisohn, 4 Deborah Hirtz, 5 Peter C. Adamson, 6 Tracy A. Glauser, and 7CAE Study Team ( 1 Neurology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY ; 2 Division of Biostatistics and Epidemiology, The Children's Hospital of Philadelphia, Philadelphia, PA ; 3 Neurology, The Children's Hospital, Denver, CO ; 4 National Institute of Neurological Disorders and Stroke, Rockville, MD ; 5 The Children's Hospital of Philadelphia, Philadelphia, PA ; and 6 Neurology, Cincinnati Children's Hospital, Cincinnati, OH ) Rationale: Childhood Absence Epilepsy (CAE) is associated with a high incidence of adverse behavioral and cognitive outcomes. As part of a large, multi‐center trial of CAE we are obtaining a variety of behavioral and quality of life information using the Child Behavior Checklist (CBCL) and the Quality of Life in Childhood Epilepsy (QOLCE) at baseline and regular intervals thereafter. We present the baseline CBCL and QOLCE findings. Methods: To date, 153 subjects with newly diagnosed, untreated CAE have been enrolled. Included were 36 (24%) children under 6 year of age and 117 (76%) age 6 or older. All CBCL scores were reviewed by a central scorer (CO) to ensure accuracy and that problems were not counted twice. Results were then entered in a central database and computer scored. Baseline CBCL data has been coded and scored in 102 cases including 21 under age 6 and 81 age 6 or older. QOLCE scores were available in 33 (23%) children < 6 years and 109 children (77%) > age 6. Results: The mean overall CBCL scores were 53.6 (s.d.11.6), with 20 (20%) of children with abnormal scores and 12 (12%) with borderline scores. Scores were similar for both the internalizing and externalizing groupings of syndromes. For the internalizing scale 17 (17%) of children had abnormal scores and 12 (12%) had borderline scores. Similarly, for the externalizing scale 17 (17%) had abnormal scores and 5 (5%) had borderline scores. There were no major differences in scores in younger versus older children. Attentional issues were the most commonly identified complaints though they only met DSM criteria in the older children. The mean QOLCE scores in our sample were 72 and were similar in both younger and older children. These scores are substantially higher, indicating a better quality of life, than the mean score of 51 reported in the sample of children with intractable epilepsy on which the scale was normed. Conclusions: Approximately 30% of children with newly diagnosed CAE demonstrate abnormal or borderline scores on the CBCL indicating a high rate of potential problems. The QOL scores indicate less concerns than in children with refractory epilepsy. Long term follow‐up of the cohort will demonstrate whether the problems in behavior and QOL improve or worsen with time and whether or not they will improve if seizures are successfully treated. (Supported by grants NS 045911 and NS 045803 from NINDS.) 1 Ada Piazzini, 2 Giovanna Ramaglia, 1 Rosanna Chifari, 1 Katherine Turner, 1 Elisabeth El Kiky, 1 Aglaia Vignoli, 1 Alessia Goracci, 1 Valentina Chiesa, 1 Raffaele Canger, and 1 Maria Paola Canevini ( 1 Epilepsy Center, St. Paolo Hospital, Milan, Italy ; and 2 Department of Educational Sciences, University of Turin, Turin, Italy ) Rationale: The aim of the study is to verify whether patients with drug resistant epilepsy and those with seizure free epilepsy adopt different coping styles in dealing with pathology, and to correlate the results to their psycho‐social adjustment. Methods: The administered instruments were the following: the Raven's Coloured Progressive Matrices (non verbal intelligence), the Echelle Toulousaine de Coping –ETC‐ (Coping styles), the Self‐esteem Questionnaire (self‐esteem), the Self‐efficacy Questionnaire (social self‐efficacy), a Quality of Life measure and a semi‐structured interview on psycho‐social adjustment. All these measures were administered to 50 drug resistant epilepsy and to 50 seizure‐free patients. Results: We found a significant difference in coping responses between the two groups: drug resistant patients adopted more the “denial” and the “exclusion” strategies (p < 0.05), on the contrary, seizure‐free subjects used more the “control” (p < 0.05). A significant correlation between disengagement patterns and poorer social outcomes was pointed out, while “control” was associated with a better social adaptation. Conclusions: Our findings provide evidence of the importance of coping assessment, considering the influence of these strategies on patients' well‐being. The possibility to offer to epilepsy patients a psychological support which orientates their coping styles, in order to alter them from the ineffective to the more efficacious ones should be considered. 1 M. Pramuka, 2 R. Hendrickson, 3 A. Zinski, and 2,4 A.C. Van Cott ( 1 Dept of Rehab Science and Technology, University of Pittsburgh, PGH, PA ; 2 Dept of Neurology, University of Pittsburgh, PGH, PA ; 3 Dept of Health Behavior, University of Alabama, Birmingham, AL ; and 4 Neurology Division, VAPHCS, PGH, PA ) Rationale: Self management approaches to reduce disability and increase emotional well being have been helpful in the treatment of chronic medical conditions. We developed a 6 week group‐based self management‐intervention (SMI) for IWE. We hypothesized that subjects who participated in the intervention would show an improved quality of life (QOL) compared to those in the treatment as usual group. Methods: Individuals aged ≥18 years treated for epilepsy at the University of Pittsburgh Epilepsy Center or its VA Hospital were eligible to participate. 61 adults (43 men, 18 women; age range 21–79) consented and were randomized to treatment in the SMI (31) or treatment as usual (24). Measures included the Quality of Life in Epilepsy‐89 (QOLIE‐89), Washington Psychosocial Seizure Inventory (WPSI), Locus of Control (LOC), and Epilepsy Self‐Efficacy Scale‐2000 (ESES). We followed an intent‐to‐treat study design; 6 withdrew prior to baseline testing and 13 did not follow up after baseline assessment. Treatment analysis included 19 controls and 19 IWE who participated in the SMI and completed baseline and follow up testing. SPSS 13.0 was used for analysis. Mean differences and their 95% confidence intervals were examined between groups using ANCOVA controlling for baseline scores. Partial Eta2 effect size estimates were examined. Results: There was no significant difference between patient demographics at the two sites or the two groups, although IWE with later seizure onset and men were over represented at the VA. Statistically significant differences were not found in overall QOL or other primary outcome measures, and effect sizes were small (≤0.05). The treatment group showed a statistically significant improvement (p = 0.039) in QOLIE‐Role Limitations Emotional score at follow up compared to the change in the control group. Strong and significant correlations were observed between QOL and self‐efficacy (r = 0.523), QOL and psychosocial/medical function as measured by the WPSI (r =−0.768) and between QOL and locus of control (r = 0.458). Conclusions: There was no significant change in overall QOL following SMI and effect sizes were small. A statistically significant positive change was demonstrated in one parameter of QOL (Role Limitations Emotional), although this might not be clinically meaningful. The strengths of this study were: a) the development of a SMI program targeting IWE b) use of a control group and randomization c) successful recruitment of a larger sample size compared to prior studies and d) the strong associations among outcome measures. Limitations included recruitment challenges, attrition, and insufficient power to detect meaningful change. Future projects will examine alternative methods of administering SMIs to IWE. (Supported by Centers for Disease Control and Prevention (CDC).) 1 Tatiana I. Silva, 2 Joyce A. Cramer, 1 Neide B. Alonso, 1 Luis Otavio S.F. Caboclo, and 1 Elza Marcia T. Yacubian ( 1 Unidade de Pesquisa E Tratamento Das Epilepsias (UNIPETE)–Department of Neurology and Neurosurgery, Division of Neurology, Federal University of São Paulo (UNIFESP), Sao Paulo, SP, Brazil ; and 2 Department of Psychiatry, Yale University School of Medicine, New Haven, CT ) Rationale: Quality of Life in Epilepsy–31 (QOLIE‐31) has been the most worldwide used instrument due to its concise and easy evaluation. The objective of this work is to describe the cultural adaptation and psychometric properties of the QOLIE‐31 for the Portuguese language. Methods: This study involved 150 outpatients: 50 pre‐surgical patients with diagnosis of refractory temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS); fifty with juvenile myoclonic epilepsy (JME) and uncontrolled seizures; and 50 seizure‐free TLE patients, with seizure remission of at least 6 months. The patients completed the following questionnaires: QOLIE‐31, Nottingham Health Profile (NHP), Beck Depression Inventory (BDI), Adverse Events Profile (AEP) and a neuropsychological evaluation. Patients answered the QOLIE‐31 twice on the first day (interviewers 1 and 2) and after 7 days (interviewer 1). Translation and cultural adaptation into Portuguese had the following phases: translation into Portuguese by two independent parallel translators; back‐translation by two independent native English‐speaking teachers, fluent in Portuguese; creation of a final version by a panel of experts. This was tested in a study including 30 outpatients with epilepsy. Results: One question needed modification: item 28 needed complementary information. It was added: “Social Limitations, in other words, fell that you can't go out or live together with different people.” Among the 150 subjects (53% women) the mean age was 31 and the mean duration of epilepsy was 15 years. Concerning socio‐demographic characteristics, 59 (39%) had primary school, 68 (45%) secondary and 23 (16%) higher education. In relation to seizure frequency, 68 (52%) had no seizures in the last 6 months, 53 (35%) 1–5, 15 (10%) 6–10 and 4 (3%) more than 10/month. High internal consistency showed by Cronbach's alpha coefficient ranging from 0.746 to 0.932. Inter‐rater reliability was strong with ICC ranging from 0.933 (Overall Quality of Life) to 0.997 (Medication Effects, Seizure Worry and Social Function). After one week, the reliability was also high with ICC ranging from 0.917 (Overall Quality of Life) to 0.995 (Medication Effects). There was a high association between QOLIE‐31 and BDI (Spearmann's correlations) (p ≤ 0.005). QOLIE‐31 and NHP had an association as well as neuropsychological evaluation. The responsiveness of QOLIE‐31 between the groups showed significant changes (p > 0.005). Conclusions: Our results support the psychometric properties of the Portuguese version of the QOLIE‐31 as a measure of HRQL. (Supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo).) 2.024 Comparison of Quality of Life and Burden over Caregivers of Patient with Temporal Lobe Epilepsy and Juvenile Myoclonic Epilepsy Ana Carolina Westphal‐Guitti, Neide Barreira Alonso, Tatiana Indelicato da Silva, Luís Otávio Sales Ferreira Caboclo, and Elza Márcia Targas Yacubian (UNIPETE (Unidade de Pesquisa E Tratamento Das Epilepsias), Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil) Rationale: The impact of chronic diseases in the family can result in burden and decrease of the caregiver's quality of life (QOL). Epilepsy in general and mainly drug those resistant, represents great impact over caregiver's QOL . Objective: To evaluate and compare QOL and burden over caregivers of patients with temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS) and patient with juvenile myoclonic epilepsy (JME). Methods: We evaluated 50 caregivers of patients with TLE due to MTS and 50 caregivers of patients with JME. We used Brazilian version of Zarit Caregiver Burden Scale (ZCBS) to assess burden over caregivers; this scale provides scores from 0 (no burden) to 88 (maximum burden). QOL was evaluated using the Medical Outcomes Study Inventory 36–Item Short‐Form Health Survey (SF‐36)–which evaluates different domains of QOL. A socio‐demographic questionnaire was applied to characterize the population. Results: The mean age and duration of disease of patient with TLE were respectively 36.42 and 25.6 and for patients with JME were 25.48 and 14.32. There was mild to moderate burden in both groups, with ZCBS average score of 25.5 for the JME group and 30.7 for the TLE. There was a significant association among all domains of SF‐36 and the burden over caregivers of patients with JME: general health (p = 0.000); functional capacity (p = 0.003); physical role (p = 0.022); emotional role (p = 0.000); bodily pain (p = 0.025); social aspects (p = 0.020); vitality (p = 0.001); mental health (p = 0.000). However in the caregivers of patients with TLE the only associations observed were seen in the domains emotional role (p = 0.011), vitality (p = 0.008) and mental health (p = 0.002), suggesting interference of emotional problems in the daily activities in the caregiver's life. No difference was observed when comparing the domains of SF‐36 Inventory and ZCBS between JME and TLE in the comparison of the groups. Conclusions: Our results show significant compromising in QOL of caregivers of patient with TLE and JME. Caregivers of patients of both groups are similarly burdened. There was no difference in the QOL between the two groups studied. (Supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior)/CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).) 1 Eishi Asano ( 1 Pediatrics and Neurology, Children's Hospital of Michigan, Wayne State University, Detroit, MI ) Rationale: BLOG (Web Log) is a new internet media system characterized by a frequent, chronological publication of personal thoughts with multiple Web links. The author investigated whether a ‘fiction novel’ on BLOG describing a girl undergoing epilepsy surgery can potentially facilitate familiarity to epilepsy surgery among the general internet users in Japan. The author also assessed whether BLOG can serve as a survey tool in psychosocial research. Methods: The author's BLOG (URL: http://blogs.yahoo.co.jp/eishi_asano_md_phd) was used to publish a serial novel and to conduct a survey among internet users. The serial novel was initiated on July 13, 2005 and ended on December 4, 2005, and consisted of 125 chapters with a number of illustrations. A survey designed to measure familiarity with epilepsy surgery was prospectively conducted using the BLOG. A single questionnaire was posted on the survey section of the BLOG on November 28, 2005. It was announced that the survey would be closed on December 4, 2005, regardless of the number of responders. None of the responders were rewarded for taking part in this survey. In addition, the number of daily public accesses to the BLOG and the Official Web Site of the Japan Epilepsy Society (JES) were measured during the survey period. Results: The BLOG obtained about 80–500 daily public accesses without any external funding support, and the total number of accesses to the BLOG from July 13 to December 4, 2005 was 20,718. The mean of daily accesses during the survey period was 135 for the BLOG and 181 for the JES Web site. A total of 27 users responded to the questionnaire during the survey period. Sixteen responders indicated that this novel facilitated awareness of epilepsy surgery, and eight indicated that they have been already aware of epilepsy surgery even before reading the novel. Conclusions: A public outreach in epilepsy surgery may be possible using BLOG, but the magnitude of public outreach in this project has been quite small. Major advantages of BLOG as a tool for outreach and survey include a small cost and high speediness. Technical limitations of BLOG‐based surveys include limited coverage, non‐response bias, and incompatible hardware or software. A better outreach system may be required to increase the number of patients with uncontrolled seizures benefiting from epilepsy surgery. (figure 1) 1,2 Ann M.E. Bye, 2 Anne M. Connolly, 3 Clare Netherton, 3 Peter Looker, 2 Annette Burgess, and 4 Amy Lonergan ( 1 Department of Neurology, Sydney Children's Hospital, Sydney, New South Wales, Australia ; 2 School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia ; 3 The Learning and Teaching Unit, University of New South Wales, Sydney, New South Wales, Australia ; and 4 Telemetry Unit, Sydney Children's Hospital, Sydney, New South Wales, Australia ) Rationale: Changing clinical practice, increasing demands on academic staff, and advances in information technology that alter student learning practices present serious challenges to medical teaching. These factors demand exploration of current teaching approaches to ensure desired outcomes of learning are achieved. The present study investigated learner perceptions of interest, clinical confidence and usefulness of lecture content in the teaching of childhood epilepsy. Methods: The presentation of the lecture was modelled on an interactive lecturing approach utilizing open questioning, illustration of history taking with clinical cases, simulations, role plays and video. Seven lectures to fifth year medical students (n = 113) and junior doctors (n = 36) were evaluated using pre‐ and post‐lecture rating scales, open‐ended questions and focus group discussions. Critical reflection by the lecturer and observational data by independent learning consultants were also collected. Results: There were significant pre‐ to post‐lecture increases in interest in the topic of childhood epilepsy (p = 0.001), and clinical confidence in recognizing a seizure (p < 0.0005). Females demonstrated a larger mean increase in interest following the lecture (p = 0.014). Local participants (p = 0.031) and junior doctors (p = 0.001) found the lecture content more interesting. Seventy percent of participants found the lecture very useful in assisting learning. Participants who completed their previous education in Australia (p = 0.043) and junior doctors (p = 0.001) found the lecture more useful. Open‐ended questions and focus group discussion showed that videos were the most useful tool. A structured approach to the classification of epilepsy and the interactive commentary provided by the lecturer were also helpful. Lecturer reflection and peer observation supported participant data. Conclusions: The outcome measures of interest, clinical confidence and usefulness are key components in learning evaluation and important parameters that influence student perceptions of medical training. The use of video and a structured approach to teaching childhood epilepsy within an interactive lecturing format promoted interest, clinical confidence and usefulness of the lecture content in assisting learning. Determining what teaching approach is effective in achieving optimal outcomes in these three domains has broad implications for medical training beyond the topic of childhood epilepsy. 1 Angelia M. Paschal, 2,3 Liow Kore, 1 Suzanne R. Hawley, 1 Jamilia Sly, and 1 Craig A. Molgaard ( 1 Preventive Medicine and Public Health, University of Kansas School of Medicine‐Wichita, Wichita, KS ; 2 Internal Medicine, University of Kansas School of Medicine‐Wichita, Wichita, KS ; and 3 Comprehensive Epilepsy Center, Via Christi Regional Medical Center, Wichita, KS ) Rationale: A paucity of information exists in the literature about perspectives on epilepsy educational campaigns from the patients' point of view. Information is lacking on their opinions about what should be featured in such initiatives, how these awareness efforts should be conducted, and to whom to aim them. The purpose of this study was to gain a better understanding of epilepsy patients' opinions and preferences on these issues. Methods: A survey was administered to 165 adults treated for epilepsy. Subjects were 18 years of age and older and were mostly female (62%) and Caucasian (82%). The 48‐item survey included questions about the patient's thoughts on misperceptions of epilepsy in the general public and among other epilepsy patients, and what could be done to address these misperceptions. Descriptive frequencies were run for each variable, as well as measures of central tendency for continuous variables. Correlations and independent samples t‐tests were run on selected variables. Results: Results indicated that almost two‐thirds (65%) of the sample believed that stress and problems in their lives would be alleviated if the public was better educated about epilepsy and seizures. Survey respondents thought the general public lacked adequate knowledge about epilepsy (90%) and that education and awareness is needed. Common misperceptions in the public pertained to inappropriately reacting to seizures, believing that all epilepsy patients suffered from severe seizures, and that epilepsy is associated with a mental illness. Educational venues considered to be most effective for the public included television ads, medical offices, and workplace programs. Patients indicated that it was very important to include information about reacting to seizures and about epilepsy in general. Additional findings are provided. The respondents (88%) were almost equally desirous of a campaign for individuals with epilepsy. The information perceived to be most useful in an education campaign for epilepsy patients pertained to treatment options and modalities, self‐management of epilepsy, and general information about epilepsy. Medical offices and brochures were perceived to be the most effective modes of education promotion. Additional results are discussed. Conclusions: In summary, the need for epilepsy education and awareness campaigns among the general public as well as epilepsy patients is needed to help decrease stigma, according to the respondents in this study. The current study of patients' views about epilepsy education and awareness needs provides a new perspective as well as an important foundation for the development of interventions. 1 Amy R. Loomis‐Roux, 1 Tina Smith‐Bonahue, and 2 Paul R. Carney ( 1 Educational Psychology, University of Florida, Gainesville, FL ; and 2 Pediatrics, University of Florida, Gainesville, FL ) Rationale: Epilepsy has the potential to profoundly impact a child's adjustment to school. A large body of literature documents that children with epilepsy are at increased risk for cognitive impairment, learning disabilities, special education placement, and behavioral and emotional problems (Williams, 2004). The importance of successful adjustment to school for children with chronic illnesses is also well supported by the literature, yet many children with epilepsy continue to experience difficulties with school adjustment, even in the absence of cognitive impairment or learning disabilities (Madan‐Swain, Katz, & LaGory, 2004). Parent perceptions of their child's school experiences are critical to identifying barriers to successful school adjustment, and these perceptions can often vary dramatically from those of educators (Lynch, Lewis, & Murphy, 1993). Yet, parent perceptions of school problems in children with epilepsy have not been emprically investigated. The current study hopes to aid in the development of a reliable and validated measure to examine school concerns specifically for parents of children with epilepsy, as well as provide information about the types of school‐related problems that parents of children with epilepsy find most salient. Methods: The School Concerns Questionnaire for Parents of Children with Epilepsy (SCPCE) was administered to 50 parents of children (ages 5–17) with epilepsy. This questionnaire was developed to assess potential concerns about school for parents of children with epilepsy. After the questionnaires were administered, statistical analyses were run on the data in order to test the questionnaire's reliability. Additionally, information about the content validity of the SCPCE was obtained by completing an additional feedback form with a subset of 10 parents asked for feedback regarding parents' satisfaction with the format and relevance of the SCPCE. Responses of parents were also exmained to determine what parents of children with epilepsy identified as the most salient school‐related issues for their children. Results: Support for the content validity and reliability of the SCPCE was found. Additionally, Parents indicated conisitently that the following problems were most prevalent for their children at school: lack of attempt to explain epilepsy to child's peers at school, teachers are uncomfortable with managing a seizure in class, teachers are not adequately educated about epilepsy, parent feels that school doesn't know how to help child with learning problems. Conclusions: Preliminary results suggest that the SCPCE is a psychometrically sound instrument that is useful in gaining parents' perspectives on school problems for children with epilepsy. Parents consistently identified concerns about school in four specific areas that have not been previously identified. Knowledge about parent concerns may help improve school outcomes for children with epilepsy. 1 Andrew N. Wilner ( 1 Neurology, Goat Island Neurology, Newport, RI ) Rationale: For clinicians who care for people with epilepsy and researchers in many parts of the world, consultation with their peers may not be readily available. Access to colleagues' knowledge and opinions via the Internet may provide a means to improve communication regarding the management of difficult clinical cases and advances in epilepsy research. Methods: In an effort to increase the ease of communication between its members, the International League Against Epilepsy Website Task Force launched a professional online Discussion Group in February, 2006, which was announced in medical publications and ILAE meetings. The Discussion Group is moderated by an epileptologist and available 24 hours a day, 7 days a week. All posts are archived and may be searched by topic. The Discussion Group is available at no cost. Results: Usage of the Discussion Group will be presented regarding the choice of topics and number and geographic distribution of participants. Conclusions: The International League Against Epilepsy has provided a professional online Discussion Group for the use of its members with the aim of improving the care of people with epilepsy. (Supported by International League Against Epilepsy.) 1 Karine J. Abou Khaled, 1 Cigdem I. Akman, 1 Lawrence J. Hirsch, 1 James P. Lowe, 1 Daniel Alschuler, and 1 Ronald G. Emerson ( 1 Neurology, Columbia University, New York, NY ) Rationale: The significance of Generalized Periodic Discharges (GPDs), also known as generalized periodic “epileptiform” discharges (GPEDs), is unknown in the pediatric population. The purpose of this study was to determine the frequency and clinical significance of GPDs in children and their association with seizures. Methods: All patients found to have GPDs on continuous EEG monitoring (CEEG) between 01/2000 and 05/2006 were retrospectively identified. We then reviewed the demographic data, etiology, medications, occurrence of seizures (convulsive and nonconvulsive), status epilepticus (SE), and clinical outcome. Results: Among 900 pediatric patients who underwent EEG/video monitoring, twelve were found to have GPDs. None of the patients was identified with isolated triphasic waves. Mean age was 8.9 years (3 months to 18 years). Four were males and eight were females. Five had a history of epilepsy, three had viral encephalitis, four had metabolic etiologies, one had anoxic‐ischemic injury and one had intracranial hemorrhage. All patients had convulsive seizures prior to the diagnosis of GPDs. Seizures occurred in 10 patients following the recognition of GPDs. Additionally, 10 patients had non‐convulsive seizures and 8 were in SE. At the time of diagnosis of GPDs, 8 (67%) were on barbiturates or midazolam infusion. Three patients died. Two patients were still in non‐convulsive status epilepticus at the time of death. Four patients had favorable outcome with mild disability and the rest had moderate to severe disability. Conclusions: Clinical features and outcome of GPDs are different in children. It was found that in adults, almost half of patients with GPDs do not have associated seizures. However in children we noted that GPDs are always associated with convulsive seizures and /or SE. Continuous EEG/video recording is valuable for the diagnosis of this EEG pattern and to optimize and monitor the efficacy of the treatment. 1 Andrea V. Andrade, 1 Susan T. Arnold, and 1 Rana R. Said ( 1 Dept of Neurology, UT Southwestern Medical School, Dallas, TX ) Rationale: Hypsarrhythmia is an electrographic pattern typically seen in young children with infantile spasms. EEGs of children with hypsarrhythmia were reviewed to determine the relationship between EEG characteristics, age and etiology, and to examine the evolution of these findings over time. Methods: In a 4.5 year period, more than 8000 pediatric EEGs were recorded at UT Southwestern/Children's Medical Center, Dallas. Database review identified 41 patients with 1 or more EEGs showing hypsarrhythmia. Additional medical record review identified associated etiology and neuroimaging findings. Results: Of 41 children with hypsarrhythmia 18 were female, 23 male (M:F ratio 0.7:1). Median age at first EEG with hypsarrhythmia was 8 months (range 0.5 to 132). Etiology was cryptogenic in 11 (26.8%) and symptomatic in 30 (73.2%). 12 children had cortical dysplasia, 9 had hypoxic‐ischemic encephalopathy (HIE), 3 had Down Syndrome and 6 had other etiologies (trauma, CMV, mitochondrial, IVH, gliosis). Median age at first diagnosis with hypsarrhythmia did not differ significantly by etiology (cryptogenic: 7 months, dysplasia: 8.5 months, HIE: 9 months). However, 7/12 patients with dysplasia presented at age ≥12 months vs. 5/29 without dysplasia (X2 = 6.9, p ≤ 0.01) and vs. 2/11 cryptogenic patients (X2= 3.9, p ≤ 0.05). 37 of 41 initial EEGs with hypsarrhythmia included a sleep sample. Only 5/28 children age < 12 months had any identified sleep architecture vs. 4/9 older children (not significant, p < 0.2). There was no correlation between sleep architecture and etiology. 8 patients had prior EEGs before their first diagnosis of hypsarrhythmia (3 normal, 5 epileptiform). 23 patients had follow‐up EEGs of which 19 were epileptiform, 2 non‐epileptiform/slow and 2 normal. Of the 14 EEGs done after >6 months follow‐up, 11 were epileptiform (3 focal, 3 generalized, 4 multifocal and 1 hypsarrhythmia), 2 non‐epileptiform/slow and 1 normal. Follow up EEGs were epileptiform in 6/6 children with dysplasia vs. 13/17 patients without dysplasia (not significant, p < 0.2). Conclusions: In our sample of children with hypsarrhythmia, older age at diagnosis was significantly associated with presence of cortical dysplasia. 58% of patients with dysplasia were ≥ age 12 months at first EEG with hypsarrhythmia compared to 17% of children with other etiologies. Limited sample size and short follow up prevented detailed analysis of the characteristics and evolution of hypsarrhythmia, although preservation of sleep architecture tended to be more common in older children. Hypsarrhythmia was transient, and rarely seen after >6 months follow up. However, most children continued to have epileptiform EEGs, including all those with cortical dysplasia. Our findings suggest that older children presenting with hypsarrhythmia should undergo an aggressive search for CNS malformations, and suggest that the risk for persistent epilepsy may be highest in children with cortical dysplasia. 1 Susan T. Arnold, 1 Rana R. Said, and 1 Andrea V. Andrade ( 1 Dept of Neurology, UT Southwestern Medical School, Dallas, TX ) Rationale: Influenza encephalopathy is associated with acute seizures, significant mortality and high risk for long term neurological sequelae. Little information exists about EEG patterns in this condition or their relationship to prognosis. EEG findings and seizure characteristics in children treated for influenza encephalopathy were reviewed to determine association with clinical course and outcome. Methods: In the past 3 years 6 children with influenza encephalopathy were treated at UT Southwestern Medical Center/Children's Medical Center, Dallas. Medical records were reviewed to identify the incidence and clinical characteristics of seizures, neuroimaging findings and EEG abnormalities. When possible information regarding neurological outcome was also obtained. Results: 3 boys and 3 girls with influenza encephalopathy were identified. Ages ranged from 6 months to 9 years. All had clinical seizures within 4 days after onset of influenza symptoms. The oldest child was on immunosuppressive steroid therapy which may explain her severe course and fatal outcome. She presented with hallucinations, hepatic failure and hypotensive shock and developed seizures on the second hospital day. The other 5 children all presented with seizures at the time of hospital admission, 4 with status epilepticus, and 1 with 3 seizures within 24 hours. In 2 cases the seizures had focal features. Of the 5 survivors, 2 had no evident disability, 1 had transient speech and cognitive slowing which resolved within 6 weeks, and 2 had significant disability with loss of speech and ambulation and were transferred to a rehabilitation facility. EEG was performed within 2 days of hospital admission in all cases. All EEGs showed abnormal slowing of the background activity. The 3 cases with favorable outcome had either sleep spindles or an awake posterior dominant rhythm. The 3 cases with poor outcome lacked these features and showed diffuse delta activity with poor reactivity to external stimuli. None of the acute EEGs had epileptiform findings. Only the 2 survivors with poor outcomes had recurrent seizures and required chronic antiepileptic therapy. Neuroimaging showed basal ganglia infarction in 4 cases (including 1 with transient disability but favorable outcome), diffuse atrophy in 1 and was normal in 2 (both with good outcome). Conclusions: Influenza encephalopathy commonly presents with seizures or status epilepticus, but epileptiform activity is not present on EEGs performed acutely. The presence of any normal awake or sleep EEG patterns was associated with a favorable outcome in our series, even when basal ganglia infarction was seen on MRI. In the absence of these features outcome was poor with significant neurological disability and epilepsy in surviving children. These finding suggest that EEG may be helpful in determining prognosis, especially when combined with neuroimaging results. 1 Todd M. Arthur, 1 Ton J. DeGrauw, 2 Cynthia S. Johnson, 3 David W. Dunn, and 4 Joan K. Austin ( 1 Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH ; 2 Division of Biostatistics, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN ; 3 Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN ; and 4 Department of Environments for Health, Indiana University School of Nursing, Indianapolis, IN ) Rationale: Scant information exists regarding the effect of EEG or MRI findings on seizure recurrence in neurologically normal children. Our goal was to refine patient classification into high and low risk of seizure recurrence for normal children by defining risk factors based on EEG and MRI findings. Methods: Children were prospectively recruited at the parent institutions as part of a study of child and family adaptation to epilepsy and followed to 27 months after enrollment. Inclusion criteria: children 6–14 years old who had their first recognized afebrile seizure within 3 months of recruitment and who had both EEG and MRI data. Exclusion criteria: presence of a chronic neurological illness affecting activities of living, abnormal neurologic or developmental exam, or scoring <80 on the Kaufman Brief Intelligence Test. Absence and atonic seizure patients were excluded. These criteria left 85 patients for the study. Each child was assigned a predominant seizure type based on the ILAE classifications. EEG data was classified by a) overall interpretation, b) epileptiform discharges, c) slowing. Epileptiform activity and slowing were defined as focal or diffuse. MRI images were classified for the presence of cortical or white matter lesions, encephalomalacia, enlarged lateral ventricles, atrophy, hemorrhage, vascular lesion, prominence of extra‐axial fluid spaces > 1 cm, or “other” findings. The children were followed as clinically appropriate and had an interview every 9 months to update seizure semiology and frequency. Recurrence was defined as a 2nd unprovoked seizure occurring >24 hours after the first seizure. X2 analysis was used to compare recurrence with EEG and MRI findings. Results: A recurrent unprovoked seizure occurred in 65.9% of patients. EEG and MRI were abnormal in 64.7% and 32.9% of patients, respectively. A significant abnormality occurred in 10.6% of MRI's. No association was found between recurrence of seizures and the baseline EEG (X2 p = 0.71), between recurrence of seizures and a normal MRI (X2 p = 0.23), or between recurrence of seizures and an abnormal MRI with significant abnormalities (X2 p = 0.12). Conclusions: Our EEG and MRI findings in neurologically normal children lend support to the current practice of using the clinical course to dictate the treatment plan. Although it appears that MRI abnormalities are not predictive of seizure recurrence, a trend toward significance is noted for significant MRI abnormalities. (Supported by Grant PHS R01 NS22416 from the National Institute of Neurological Disorders and Stroke to JKA.) 1 Kristin A. Bakke, 1 Ann‐Sofie Eriksson, and 2 Wilson John ( 1 Pediatric Department, National Centre for Epilepsy, Sandvika, Norway ; and 2 Department of Neurodiagnostics, National Centre for Epilepsy, Sandvika, Norway ) Rationale: The EEG pattern of CSWS (continuous spike waves during slow sleep) may influence language or cognitive functions. Recently, we have seen many children with a CSWS‐like EEG pattern. The aim of this study was to assess school performance and behavior in such children treated with levetiracetam (LEV). Methods: We performed a prospective open label intervention study in 50 children (age: 5–12 yr) in whom 24‐h EEG showed a vast increase of epileptiform activity during slow wave sleep. We employed a new method for assessment of nocturnal epileptiform discharges developed at our epilepsy centre. The children had spike‐indexes of 30–90% of slow wave sleep. 25–35% of them was either seizure free or had never experienced epileptic seizures. Language/dyslectic problems, ADHD or concentration‐ and behavioral problems appeared to be the most common clinical disabilities. Moreover, some patients had symptoms within the autism spectrum disorders (ASD). LEV treatment was given (usually as add on) in doses 20–25 mg/kg/day, after 4–8 weeks of titration. 24‐hour EEG was performed after 3–7 months of treatment. A reduction in epileptiform activity was assessed as either reduction in percentage time of spiking or as bifocal epileptiform activity becoming monofocal. Parents were asked about changes in the children's behavior, cognitive functions or school performance. Results: LEV caused a reduction in epileptiform activity in 24‐h EEG in 65% of the patients. 24‐h EEG became normal within 6 months in 25% of the cases. Parents reported positive clinical effects in more than half of those cases with an improved or normalized EEG. Conclusions: Children may benefit from treatment of sleep‐related epileptiform activity in EEG, also when such activity are less prominent than in classical CSWS. Perhaps CSWS is only the “tip of the iceberg”? We believe that our observations call for further studies within this exciting field. (Supported by National centre for epilepsy, Norway.) 1 Anne T. Berg, 2 Barbara G. Vickrey, 3 Francine M. Testa, 3 Susan R. Levy, 4 Shlomo Shinnar, 3 Susan N. Smith, 3 Barbara Beckerman, and 5 Francis DiMario ( 1 Biology, NIH, DeKalb, IL ; 2 Neurology, UCLA, Los Angeles, CA ; 3 Pediatrics, Yale University, New Haven, CT ; 4 Neurology, Montefiore Hospital, Bronx, NY ; and 5 Neurology, CCMC, Hartford, CT ) Rationale: Seizure outcomes are usually studied at one point in time and assumed to be static. Increasing evidence indicates this is not the case. Methods: In a prospective study of 613 children with epilepsy newly diagnosed in 1993–97, patterns of remission, relapse, and poor outcome were characterized in those children with idiopathic/cryptogenic (I/C) epilepsy and followed ≥8y. Syndromes were grouped as idiopathic localization‐related (ILRE), cryptogenic focal (CFE), idiopathic generalized (IGE), and undetermined (UND). The minimum time seizure‐free to be considered a remission was 1y, and remission of ≥5y was considered a good outcome. Results: 437 children had I/C epilepsy of whom 393 (90%) were followed ≥8 y (max 13y). The best possible outcome, no seizures since diagnosis, occurred in 69 (18%) and the worst, failure of 2 AEDs and never achieved 5y seizure‐free at any time, occurred in 36 (9%). An additional 148 (38%) were at least 5y seizure‐free at last contact after having seizures during the first one (n = 99) through several years (n = 49) after initial diagnosis. Another 63 (16%) had episodes of repeated brief remissions (1–2 years long) with relapses but are now ≥5y seizure‐free. Finally 24 (6%) had achieved a 5y remission at some point but then relapsed, and 59 (15%) had achieved multiple briefer (1–3y) periods of remission with repeated relapse but were never 5y seizure‐free. Syndrome group was strongly associated with the seizure outcome pattern (p < 0.0001). Most of the effect was due to the ILRE group having much better outcomes than the other three groups which were generally indistinguishable from each other. The IGE group, however, was significantly less likely to have the best outcome than any of each of the other three groups (all p = < 0.01). In a total of 616 ≥1year remission periods experienced by the 393 children, 272 remission periods ended in a relapse: 35% without any apparent provocation, 12% in association with noncompliance, 6% during tapering of AEDs, 33% after all AEDs were stopped, 3% in association with illness, and 11% in other settings. Conclusions: Although most children with I/C epilepsy achieve prolonged periods seizure‐free, seizure outcome patterns over many years are complex and dynamic. A simple characterization at one point in time may not be the most informative approach for studying determinates of seizure outcome or for studying the effects of seizures on social, educational, and other endpoints of interest in young people with epilepsy. (Supported by NIH NINDS‐RO1‐NS31146.) 1 Rachel Berman, 2 Michiro Negishi, 3 Marissa Spann, 4 Miro Enev, 2 R. Todd Constable, 3,4,5 Edward J. Novotny, and 1,3,4 Hal Blumenfeld ( 1 Neuroscience, Yale University, New Haven, CT ; 2 Diagnostic Radiology, Yale University, New Haven, CT ; 3 Neurosurgery, Yale University, New Haven, CT ; 4 Neurology, Yale University, Fairfax, CT ; and 5 Pediatrics, Yale University, Fairfax, CT ) Rationale: Absence seizures consist of brief 5–10 s episodes of unresponsiveness, associated with a 3–4 Hz “spike‐wave” discharges on EEG. The fundamental mechanisms of impaired attention in childhood absence epilepsy (CAE) are not known. By understanding the mechanisms and brain regions crucial for impaired attention in this patient population, new treatments may be developed with the goal of blocking seizures and preserving attention. Mechanisms of impaired attention in this form of epilepsy may have implications for treating other types of epilepsy as well. Methods: We have used simultaneous EEG and fMRI while testing attentional vigilance with a continuous performance task (CPT) in pediatric patients with typical absence seizures. To increase the chance of recording absence seizures, medications were held for up to 48 hours. Simultaneous EEG‐fMRI data were acquired using a 3T MR system with continuous EPI BOLD sequence. EEG artifact was removed by post‐processing using temporal PCA‐based gradient noise removal. fMRI data was analyzed using SPM2. Results: We found significant ictal BOLD signal increases in bilateral thalamus. Moderate increases were also seen in the cingulate, lateral frontal, and parietal cortex. Decreased BOLD signal was present in the retrosplenial cortex, and to a lesser degree in the bilateral frontoparietal cortex. When testing CAE patients with CPT during the interictal period, significant BOLD signal increases were seen in the bilateral fronto‐polar cortex, anterior cingulate, dorsolateral frontal and parieto‐occipital cortex, left fusiform gyrus, bilateral medial thalamus, upper brainstem, and cerebellum. Decreases during CPT were seen in bilateral orbital frontal cortex, precuneus, and large areas of the lateral cerebral hemispheres. Our behavioral measurements indicate ictal omission errors in 5 of 7 absence seizures that occurred during the CPT task. Omission error rate (% missed target letter X on CPT) was significantly higher in CAE patients than controls, 3.05% in CAE patients off meds, and 0.89% in controls (p = 0.04, two‐tailed t‐test). Variability in performance was also higher in the CAE group, where omission error rate varied from 0% to 11% between trials, while in controls it varied from 0% to 5%. Conclusions: These results demonstrate the feasibility of obtaining high quality EEG‐fMRI during behavioral testing in pediatric patients with CAE. As in adult patients, increases and decreases were seen in frontoparietal and thalamic networks. Our initial findings also suggest that the attentional networks involved in CPT overlap with thalamocortical networks affected by CAE. (Supported by Betsy and Jonathan Blattmachr fund.) 1 Ghassan Hmaimess, 1 Fabrice Wallois, and 1 Patrik Berquin ( 1 Pediatrc Department, St George Hospital, Beirut, Ashrafieh, Lebanon; Pediatric Neurology Unit, Hopital Nord, Amiens, Somme, France, Metropolitan; and Unite D Exploration Fonctiopnnelle, Hopital Nord, Amiens, Somme, France, Metropolitan ) Rationale: We report a tow new cases of “peri‐oral myoclonia with absence,” a rare epileptic syndrome recently described by Panayiotopoulos et al (1994), with no effective treatment. Methods: Patient 1: A 15‐years teenager with no particular personal and family history was referred to our center for ‘absence’ seizures that were refractory to treatment with lamotrigine. Clinical and neurological examinations were normal. His mother highlighted that during the ‘absence’ fits, she noticed labial shivering and twitching. It is also noteworthy that a month after the onset of ‘absence’ seizures, he presented a tonico‐clonic fit. Cerebral T2‐weighted MRI showed bilateral frontal hypersignal. A video electroencephalogram revealed that peri‐oral myoclonia was concomitantly associated with generalised 3–4 Hz spike‐waves. We added Sodium valproate to his base‐line treatment with lamotrigine. Lamotrigine was subsequently withdrawn. Patient 2: A 14‐years old male (with history of generalised fit at age of 5 years treated with sodium valpoate for 7 years) presented for perioral myoclonia with loss of consciousness followed, 3 weeks later, by one episode of GTCS. A video electroencephalogram revealed a peri‐oral myoclonia associated with generalised 3–4 Hz spike‐waves; Cerebral MRI was normal. At presentation he was treated with sodium valproate. The GTCS was stopped but he has persistence of absence seizures. We added lamotrigine without improvement. Finally the levetiracetam decreased the rate of seizures by 50%. Results: One month after starting sodium valproate, the first patient had no more absences, and the EEG became normal. The second patient showed 50% reduction of absence after starting levetiracetam. Conclusions: We report an ‘atypical’ and typical new case of “peri‐oral myoclonia with absence” in one of them abnormal cerebral MRI changes were detected.It could be argued if the first patient is a variant of the condition described by Panayiotopoulos as “peri‐oral myoclonia with absence,” with the additional finding of cerebral MRI frontal disorders. Conversely, this patient may be viewed as a case with frontal cerebral abnormalities presenting with peri‐oral myoclonia and absence. At the present state of knowledge, it is not known if such a distinction makes any valid difference. However, this observation probably widens the spectrum of findings in this newly described entity. Furthermore, while this condition is known to be refractory to treatment. The first patient respond favourably to sodium valproate and the second to levetiracetam. Our follow‐up should, however, be continued beyond the few‐month window of opportunity. 1 Marlene A. Blackman, 1,2 Elaine C. Wirrell, and 1,2 Lorie D. Hamiwka ( 1 Pediatric Neurology, Alberta Childrens Hospital, Calgary, AB, Canada ; and 2 Pediatrics and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada ) Rationale: To determine the frequency of atypical clinical or electrographic features in children with BREC seen in a tertiary care children's hospital. Methods: All children diagnosed with BREC seen through the Neurology Clinic of the Alberta Children's Hospital over an 8 year period were retrospectively identified. Charts were reviewed for the presence of atypical clinical and electrographic features. Atypical clinical features included daytime only seizures, atypical semiology, status epilepticus, developmental delay or learning problems, seizures refractory to ≥2 AEDs, seizure number >25 over the course of their epilepsy. Atypical electrographic features included background slowing or location of spikes outside the centrotemporal region. Results: 66 children were identified (mean age at seizure onset 7 yrs, range 3–12, gender 45M:21F). AED treatment was initiated in 39 (59%). Atypical clinical features were present in 27 (41%) and included daytime only seizures in 10, atypical semiology in 3, status epilepticus in 2, developmental delay/learning disorders in 11, refractory seizures in 2 and high seizure number in 5. Atypical electrographic features were present in 15 (23%) including atypical location in 13 and background slowing in 2. No patient had more than one atypical electrographic feature. Atypical electrographic features did not occur more commonly amongst those with atypical clinical features (p = 0.14). Patients with atypical clinical or electrographic features were neither more likely to be treated with AEDs (p = 0.40) nor less likely to achieve a period of 1 year seizure‐freedom at last follow‐up (p = 0.47) compared to those without these features. Conclusions: Atypical clinical and electrographic features are commonly seen in children with BREC but do not appear to adversely affect prognosis. (Supported by Alberta Childrens Hospital Foundation.) 1 D.F. Clarke, 1 J.W. Wheless, and 2 D. Carpenter ( 1 Pediatric Neurology, University of Tennessee, Memphis, TN ; and 2 Comprehensive NeuroSciences, Inc., White Plains, NY ) Rationale: Over the past 12 years, many new epilepsy treatments have been approved. For most pediatric epilepsy syndromes no trials compare active therapies, further compounding treatment decisions. We sought to address the shortcomings by using the expert consensus method, and conducted the first European survey in pediatrics. Methods: Forty‐two pediatric epilepsy experts completed the Pediatric Epilepsy Consensus Survey. The experts answered 33 questions, with 418 possible answers. Topics addressed were 1) overall treatment strategy (sequencing both drug and non‐pharmacologic treatment) for common childhood epilepsies; and, 2) specific treatment choices for common childhood epilepsies. Results: Valproate was the drug of choice and the only agent felt to be first line therapy for the treatment of symptomatic myoclonic and generalized tonic clonic seizures. Vigabatrin was the drug of choice for infantile spasm secondary to tuberous sclerosis complex (TSC) and for symptomatic infantile spasms. Valproate was the drug of choice in treating astatic seizures in a child with Lennox‐Gastaut Syndrome (LGS); however, if this was not successful, then topiramate and lamotrigine were considered first line therapy. Valproate was the first choice for treatment of childhood absence epilepsy (CAE), whereas ethosuximide and lamotrigine were considered first line choices. Valproate was the drug of choice for juvenile absence epilepsy, and lamotrigine was a first line choice. Valproate was the only first line agent and considered the drug of choice for the treatment of benign rolandic epilepsy of childhood. Carbamazepine, oxcarbazepine, and valproate were all considered first line choices to treat cryptogenic complex partial seizures of childhood. Valproate and lamotrigine were considered first line agents to treat juvenile myoclonic epilepsy in an adolescent male or female. Rectal diazepam was the first choice for the acute treatment of a febrile seizure, while valproate was considered the first choice for preventative therapy. The treatment sequence for either complex partial or generalized tonic clonic status epilepticus (S.E.) was either intravenous (IV) diazepam or lorazepam, followed by IV phenytoin or fosphenytoin, if needed. The treatment sequence for absence SE was IV diazepam, followed by IV valproate, if needed. Phenobarbital was the first choice in treating neonatal seizures. Conclusions: The results of the first European Pediatric Epilepsy Expert Survey can be used to develop overall treatment strategies and choices of specific medications for seizure emergencies in childhood, and specific childhood epilepsy syndromes. These can be used to help guide future comparative multi‐centered treatment trials in pediatric epilepsy and in specific epilepsy syndromes unique to pediatrics. (Supported by Abbott, Cyberonics, Novartis, Ortho‐McNeil, GSK, UCB, and Shire.) 1 Joy M. Fairbanks, 1 Natalie C. Cunningham, 1 Philip S. Fastenau, 2 Susan M. Perkins, 3 David W. Dunn, and 4 Joan K. Austin ( 1 Psychology, Indiana University Purdue University Indianapolis, Indianapolis, IN ; 2 Biostatistics, Indiana University School Medicine, Indianapolis, IN ; 3 Psychiatry, Indiana University School of Medicine, Indianapolis, IN ; and 4 Environments for Health, Indiana University School of Nursing, Indianapolis, IN ) Rationale: Children with epilepsy are at risk for behavioral problems. Attention deficit‐hyperactivity disorder (ADHD) has been reported more frequently than any other problem. Even though children with epilepsy have higher prevalence rates of ADHD, it remains unclear if they are at risk for being under‐identified and under‐treated for the disorder. We sought to determine whether the proportions of children with epilepsy were identified as having ADHD equally by the school and by measures incorporating DSM criteria. Methods: Participants were 86 children with chronic epilepsy. Children were assessed at baseline, 12 months, and 24 months. The mean age at 24 months was 13.73 (SD = 1.97), age of seizure onset was 6.25 (SD = 3.64), 50% were females, and 15.1% were left‐handed. Parents completed an educational services survey, on which they indicated whether the child was currently classified by their school as having ADHD (yes/no). In addition, parents completed the Child Symptom Inventory (CSI) or Adolescent Symptoms Inventory (ASI) symptom checklists with severity scores that may be used for diagnosis of ADHD based on DSM IV criteria. Results: McNemar's test was conducted to determine whether there were similar rates of ADHD classification by the CSI/ASI and educational services survey over the 24 months. Forty eight percent of the children were classified as ADHD by CSI/ASI criteria, whereas only 29% were classified as ADHD in the educational services survey (McNemar's chi‐square = 8.33, p‐value = .004). There were 27 total discrepancies between the classification types. Of these 27, 6 (22%) were children not meeting the CSI/ASI criteria who were classified as ADHD by the survey (false positives), and 21 (78%) were classified as ADHD by CSI/ASI but were not classified as ADHD in the schools (false negatives). Conclusions: These findings suggest that ADHD is a common problem for children with epilepsy and careful monitoring is important. It appears children with epilepsy might be at risk for under‐identification of ADHD when symptoms are present. Hence, children that could benefit from additional educational services might not have access to these important resources. (Supported by PHS R01 NR04536 from NIH/NINR to J.K.A.) 1 Laura A. Filimon, 2 Justin M. Keener, 1 H. Steve White, 1 Karen S. Wilcox, and 2 Joanna Beachy ( 1 Pharmacology and Toxicology, University of Utah, Salt Lake City, UT ; and 2 Pediatrics, University of Utah, Salt Lake City, UT ) Rationale: Neonatal hypoxia‐ischemia (HI) insults have been associated with periventricular leukomalacia (PVL). As a result, affected patients are at an increased risk for developing mental retardation, epilepsy and/or cerebral palsy. The Levine model of HI has been modified such that the degree and length of hypoxia (6% for 1 hour) leads to a specific reduction in myelin basic protein (MBP) and decreased seizure threshold to kainic acid (KA) at P11 (Levine Am J Pathol 1960;36:1–17;Follett et al JNeurosci 2004;24:4412–20; Koh et al Epilepsia 2004;45:569–75). Thus, using this 6% rat model of PVL we evaluated the effect of HI on KA‐induced seizure threshold and amygdala kindling aquisition. Additionally animals were monitored for the presence of spontaneous ictal discharges. Methods: Post‐natal day 7 (P7) Sprague‐Dawley rat pups were anesthetized with isoflurane and their right carotid artery ligated. Pups were allowed to recover for at least 1.5 hours and were then placed in a 6% O2 chamber for one hour; body temperature was maintained at 35°C using a heating pad. Males and females from several litters were divided into HI‐lesioned and naive controls. Two pups were sacrificed at P11 and MBP damage was confirmed by immunohistochemistry. The remaining animals (P90–120) were subjected to either 10 mg/kg KA (males: HI n = 8, naive n = 12; females: HI n = 6, naive n = 10) or amygdala kindling (males: HI n = 5; naive n = 6; females: HI n = 9; naive n = 14). At 9 months of age five animals were monitored for the presence of spontaneous seizures using implanted surface electrodes. Results: HI at P7 resulted in significant loss of MBP at P11. To assess KA susceptibility the following endpoints were measured: latency to 1st, 2nd, 3rd, 4th seizures, latency to wet dog shakes, total seizure number, number of stage III and V seizures, latency to stage III and V seizures, and incidence of death. Among these endpoints no difference in KA seizure threshold was evident between HI and naive rats regardless of sex. There was no significant difference in amygdala kindling aquisition (male or female). However, the after‐discharge threshold of male HI rats was lower than that of naive rats (HI = 140 mA ± 53; naive = 207 mA ± 21). Three (2 males and 1 female) of the 5 rats (3 males and 2 females) exhibited spontaneous electrographic bursts. Conclusions: Consistent with previous reports, we observed marked damage to MBP four days post HI (P11). Furthermore, HI‐injured rats displayed a reduced amygdala after‐discharge threshold. Consistent with a previous report using the Levine model, HI rats displayed spontaneous electrographic bursting (Williams et al Epilepsia 2004;45:1210–1218). Future video‐EEG studies will evaluate the ontogeny of EEG bursts and assess the severity of clinical seizures. (Supported by Pediatric Pharmacology Program, Department of Pediatrics, University of Utah (LAF).) 1 L. Matthew Frank, 2 Dale C. Hesdorffer, 3 Christine O'Dell, 4 John M. Pellock, 5 Douglas R. Nordli, 6 Darrell V. Lewis, 4 Anthony Marmarou, 3 Shlomo Shinnar, and FEBSTAT Study Team ( 1 Department of Pediatrics, Eastern Virgnia Medical School, Norfolk, VA ; 2 GH Sergievsky Center, Columbia University, New York, NY ; 3 Neurology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY ; 4 Virginia Commonwealth University, Richmond, VA ; 5 Pediatric Neurology, Children's Memorial Hospital, Chicago, IL ; and 6 Neurology, Duke University Medical Center, Durham, NC ) Rationale: In children with a prolonged febrile seizure, a lumbar puncture is indicated to exclude the possibilty of an intracranial infection. There is a common belief that some degree of pleocytosis is expected simply as a result of the prolonged seizure and fever. We evaluated the CSF findings in a prospective multicenter study of febrile status epilepticus in children. Methods: FEBSTAT is a prospective multicenter study of febrile status epilepticus (≥30 min) designed to determine whether prolonged febrile seizures cause acute hippocampal damage with mesial temporal sclerosis. Although not part of the research protocol, many of these children had a lumbar puncture performed. CSF results were coded and analyzed. More than 20 WBCs in the CSF was an exclusion criterion, but no child was excluded solely as a result of having more than 20 WBCs. Results: Of the first 102 children enrolled, 80 (78%) had a lumbar punture performed. At present, CSF data on 73 of these 80 is available for analysis. Of these 73 CSF specimens, 22 (30%) had zero WBCs, 29 (40%) had one WBC, 11 (15%) had two WBCs, 4 (5%) had three WBCs and one (1%) had 4 WBCs. Six (8%) specimens had 5 or more WBCs (two with 6 WBCs, two with 8 WBCs and one each with 11 and 16 WBCs.) However, of the six cases with 5 or more WBCs, 5 were traumatic with 5100 to 51,000 RBCs. In all 5 cases, the number of WBCs was fully consistent with the RBC count. Thus there was only one atraumatic lumbar punture with more than 5 WBCs (6 WBCs) and only 2 children with more than 3 WBCs. The protein and glucose were unremakable in these children. The number of WBCs was not affected by duration of the seizure (<60 minutes vs >60 minutes,) seizure focality, the age of the child (<18 months vs ≥18 months) or peak temperature. Conclusions: CSF pleocytosis is very uncommon following even prolonged febrile seizures in children. A finding of more than five WBCs in the CSF from a nontraumatic lumbar punture should be a cause for concern in any child with a seizure and fever. (Supported by: Funded by grant NS 43209 “Consequences of Prolonged Febrile Seizures in Childhood” NINDS.) 1 Felicia Gliksman, 1 Li Kan, and 1 Joseph Maytal ( 1 Division of Pediatric Neurology, Schneider Children's Hospital, New Hyde Park, NY ) Rationale: The purpose of this study was to assess the efficacy and safety of levetiracetam in children with idiopathic generalized epilepsy. A previous review showed levetiracetam to be most effective in children with partial onset seizures as well as being well tolerated with few reported side effects. Preliminary studies show levetiracetam to be effective for treating idiopathic generalized epilepsy in adult patients but few results are available in children with generalized idiopathic epilepsy. Methods: A retrospective chart review was performed in a tertiary center on children ages 2–18 years old with idiopathic generalized epilepsy that have been treated with levetiracetam up until May 2006. The data included patients with idiopathic generalized epilepsy for example, myoclonic, tonic, and atonic seizures. Pure absence seizures were excluded but absence mixed with other convulsive types were accepted. Also excluded were patients with symptomatic and partial seizures. Data was recorded on: patient age, gender, type of epilepsy, existing anti‐epileptic therapy, dose and duration of treatment with levetiracetam, patient/caregiver assessment of seizure frequency, and adverse events. Results: A total of 15 patients fulfilled the inclusion criteria of this study. Daily levetiracetam dose ranged from 9.1 to 73.2 mg/kg/day (average 35.2 mg/kg/day). The mean number of concomitant use of other anti‐epileptic drug (AED) was 0.9 which included lamotrigine, primidone, oxcarbazepine, valproic acid, carbamazepine, phenytoin, topiramate. The mean number of total AEDs per patient was 1.6. The demographic characteristics included: Age: 2.3–18 years (mean, 10.6 years), Sex: 9 females, 6 males, Generalized tonic clonic 11/15 (73.3%), Absence (mixed type) 6/15 (40%), Myoclonic 5/15 (33.3%), Tonic 1/15 (6.7%), Atonic 2/15 (13.3%). Nine out of fifteen patients (60%) showed a good response to levetiracetam with reduction in seizure frequency. Four out of fifteen patients (26.7%) became seizure free and 5/15 (33.3%) patients had fewer seizure frequency with therapy. Five out of fifteen patients (33.3%) had no response to therapy. Of those with generalized tonic clonic epilepsy, 4/11 (36.4%) had become seizure free, 3/11 (27.2%) had a decrease in seizure frequency, and 3/11 (27.2%) showed no response. Adverse effects occurred in four children (26.6%) including behavioral change (1/15), tiredness (1/15), decrease appetite (1/15), and reason unknown (1/15) (child was seen as an in‐patient and followed at an outlying hospital). Conclusions: Treatment with levetiracetam resulted in reduction of seizure frequency in 60% of the patients included in this study. Levetiracetam was efficacious and safe for use in children with idiopathic generalized epilepsy with few, mild side effects reported. (Supported by UCB Pharma.) 1 Oksana V. Globa, 2 Elena G. Sorokina, 1 Natalya G. Zvonkova, 1 Natalya A. Basarnaya, and 3 Elena L. Semikina ( 1 Neurology, Scientific Center of Child Health, RAMS, Moscow, Russian Federation ; 2 Laboratory of Membranology and Genetic Group, Scientific Center of Child Health, RAMS, Moscow, Russian Federation ; and 3 Laboratory of Clinical Diagnostic, Scientific Center of Child Health, RAMS, Moscow, Russian Federation ) Rationale: We searched for the immunity changing and autoimmunity correlation in epilepsy patients. Glutamate is a major excitatory neurotransmitter that also triggers a neurodegeneration as a result of excessive stimulation of postsynaptic receptors in epilepsy, brain ischemia and CNStrauma. This process was hypothesized as the major cause for the neuronal loss, chronic inflammatory changes in neurological patients and may leads to the autoantibodies(aAB) to glutamate receptors(GluRs) synthesis. Clinical and experimental data support the role of immune mechanisms during epilepsy pathogenesis. Methods: The serum level of lymphocyte subpopulations (obtained by immunocytochemical methods) and the serum level of GluRs‐aAB (ELISA, synthetic peptides‐analogues of GluR1(AMPA) and NR2A(NMDA) subunits were used as antigens) were estimated in pediatric patients with epilepsy(Epi), mild brain trauma(BT), mitochondrial diseases(MD) and in 20 children of control group(CG). Results: In Epi(n = 60) GluRs‐aAB level was significantly higher vs CG(GluR1179 ± 15,3c.u.,NR2A161,4 ± 14c.u.)(p < 0.05). In follow‐up studies GluR1aAB level was decreased in E remission, NR2A was still elevated. In acute period of BT(n = 20) the GluRs‐aAB was high(p < 0,05) but the elevation of NR2AaAB was higher than GluR1.In 6–12 mnths follow‐up studies GluR1aABlevel was significantly elevated in children with repeated BT and posttraumatic epilepsy. In patients with MD(n = 15), even without seizures, the GluRs‐aAB was high. Epileptic seizures is the common sign of MD. We have found the significant increase of CD8+lymphocytes, in activation markersCD122+, CD16 + 56+ and decrease in CD19+ in Epi patients(n = 20).We have also found the high level of CD122+, low level of CD19+ in MDpatients(n = 5), the decrease in Tlymphocytes subpopulations and the increase of CD122+ in children with BT(n = 7). The most immunological deteriorations were related to the temporal lobe focus. We did not find correlation between the immunological changes and the GluRs‐aAB levels. Conclusions: Data obtained show that in E, BT and MD glutamate receptors are damaged as a result of excititoxicity. NMDARs dysfunction is observed in all diseases mentioned above. AMPARs damage is more specific for E and the elevation of GluR1aAB level is a risk for E developed in BT and MD. Changes in immological parameters in pediatric patients with epilepsies were not correlated with the glutamate‐mediated autoimmunity. 1 Peter Gradisnik, and 2 Vlatka Mejaski‐Bosnjak ( 1 Pediatric Department, General Hospital, Maribor, Slovenia ; and 2 Neuropediatric Department, Djecja Klinika, Zagreb, Croatia ) Rationale: Studies discussing neurological outcome with prematurely born children are mainly oriented towards motor development evaluation. It is now accepted that damage to brain‐tissue partly occurs due to prenatal pathological occurrences. The present research was aimed at establishing whether antepartally developed periventricular damage of brain‐tissue with prematures can cause development of epilepsy in the early ages. Methods: The research included 105 high‐risk prematures with completed brain ultrasound during the first week. Following the medical documentation we categorised their ultrasound readings according to the measure of brain damage as well as regarding the approximate time of the occurrence of the damage. The potential prognostic factors were compared with the incidence of epilepsy. By the binary logistic regression method, the relative risk of the occurrence was established for the potential factors. Results: During the 6–8 years of following the cases up we have ascertained epileptic occurrence with 11.4% of our patients. Most frequent form of epilepsy was the West syndrome, occurring with 5.7% of all patients. Gestational age, birth‐weight, presence of perinatal asphyxia and intrauterine growth retardation proved to be statistically unconnected with epileptic occurrences. Employment of tocolitic therapy was correlated with increased risk of epilepsy, but the difference still isn't statistically significant. Correlation of a subsequent epileptic occurrence and of hemorrhagic as well as ischemic white matter damage proved to be statistically significant (p < 0.05); however, when perinatal lesions were divided, based upon the ultrasound criteria, into antepartal and postnatal subgroups and when their respective correlation with the outcome was ascertained, the only statistically significant brain‐damage related to epilepsy proved to be such as originating before birth. Conclusions: The presence of prenatal brain pathology is mostly important for the development of epilepsy in prematurely born children. The concluding process of brain cortex formation going on during the final trimester of pregnancy is likely to be opening possibility of secondary cortical brain damage following the primary exposure of white matter. 1 Sara Y. Tsuchie, 1 Marilisa M. Guerreiro, 1 Eunice Chuang, 1 Carlos E. Baccin, 1 Maria A. Montenegro, and 1 Carlos A. Guerreiro ( 1 Neurology, State University of Campinas, Campinas, Sao Paulo, Brazil ) Rationale: It is known that epilepsy has a severe impact in the quality of life of the patients; however, it affects the lives of all family members. The psychosocial repercussions of epilepsy are often of greater significance than the seizures themselves. Methods: This was a prospective study, conducted from January 2005 to December 2005 at the pediatric epilepsy clinic of our University Hospital. Parents were interviewed by one of the authors according to a structured questionnaire that included questions about the impact of epilepsy in the life of the patients and their family, especially their siblings. Results: One hundred and twenty‐seven children, siblings of 78 patients with epilepsy were evaluated. From the 127 siblings of children with epilepsy, 60 were girls and 67 were boys. Ages ranged from 5 to 18 years‐old (mean = 11.7 years). After the diagnosis of epilepsy the siblings had only negative feelings toward the disease, mostly sadness and fear. Conclusions: Our data showed that the impact of epilepsy in the lives of siblings of children with epilepsy is much more severe than previously suspected. (Supported by: Eunice Chuang and Sara Y. Tsuchie are medical students and received a scholarship from CNPq.) 1 Eunice Chuang, 1 Marilisa M. Guerreiro, 1 Sara Y. Tsuchie, 1 Angelica Santucci, and 1 Maria A. Montenegro ( 1 Neurology, State University of Campinas, Campinas, Sao Paulo, Brazil ) Rationale: Although overtreatment with antiepileptic drugs contributes to the morbidity associated with epilepsy, many children still are overtreated. The objective of this study was to evaluate if the withdrawal of at least one antiepileptic drug (AED) in children with refractory epilepsy using polytherapy enable a better seizure control. Methods: This was a prospective study. Children with refractory epilepsy using at least two AEDs were included. Once the patient, or guardian, agreed to participate in the study, one or more AED were slowly tapered off. The remaining AEDs dosages could be adjusted as needed, but a new AED could not be introduced. Results: Fifteen patients were evaluated, three girls; ages ranging from 3 to 18 (mean = 8.7 years). After at least one AED withdrawal, two (13.5%) patients became seizure free, seizures improved > 50% in 5 (33.5%) patients, did not change in 5 (33.5%), and seizure frequency became worse in 3 (20%). Adverse events improved in 12 patients (80%). Conclusions: We conclude that the withdrawal of at least one AED is a valuable option in the treatment of selected children with refractory epilepsy. (Supported by: Eunice Chuang and Sara Y. Tsuchie are medical students and received a scholarship from CNPq.) 1 Laura M.F.F. Guilhoto, 1 Denise Ballester, and 1 Alfredo E. Gilio ( 1 Pediatrics, University of Sao Paulo Hospital, Sao Paulo, SP, Brazil ) Rationale: Recurrence of single non‐provoked epileptic seizure is generally studied in tertiary hospitals where the Universities are based. The aim of this paper is to report the evolution of first non‐provoked epileptic seizure in children from the community followed in a secondary care University hospital in Sao Paulo, SP, Brazil. Methods: We performed pediatric neurological prospective and consecutive follow‐up of 51 children with non‐provoked single epileptic seizure, aged 17 months to 15 years (mean 8.4) referred from the Pediatric emergency sector of the University of Sao Paulo Hospital, a secondary care regionalized unit which receives patients from Butanta district in Sao Paulo city, Brazil. All have performed brain CT and EEG. The EEG was read by the same neurologist who took care of the patients in the out‐patient unit. Results: There were 29 boys and 22 girls. Seizures occurred in wakefulness in 29, sleep in 18, and on arousal in 4. Only one patient had a seizure lasting more than 10 min and 5 had multiple seizures (>1/24h). Focal seizures occurred in 29, generalized in 14, and not classified in 8. Only one had had previous febrile seizures (FS); 5 had relatives (first grade) with epilepsy, and 2 with FS. Mild mental retardation was present in 3. EEG was abnormal in 36, showing focal paroxysms in 20 (rolandic in 6, parietotemporal 5, occipital 3, frontal 3, and hemispheric in 2), multifocal in 1 (after a while, rolandic) and generalized in 9. Two had abnormal brain CT (arachnoid cist and non specific abnormality, not confirmed by MRI). Electroclinical analysis revealed idiopathic generalized epileptic syndrome in 8 (7 juvenile absence and 1 juvenile myoclonic epilepsy) who received VPA; CBZ was prescribed in 2 patients because of very frequent frontal discharges; 4 patients had had remote seizure and were medicated; 5 were receiving DAE since the emergency unit and the family preferred to keep it; and finally 32 remained without DAE. Eleven of these (34.4%) had seizure recurrence and AED was prescribed. The etiology was idiopathic in 40, symptomatic in 1 (frontal remote encephalic trauma) and cryptogenic in 10 (3 with mild mental retardation and 7 learning disability). The second seizure recurred in a mean time of 80 days (15 days‐14 months); risk factors were male sex, focal seizures and occurrence in sleep. Conclusions: Recurrence after non‐provoked single epileptic seizure in children from the community was similar to that of tertiary hospitals. This might be due to an inadequate distribution of health professionals in some peripheral areas. There is a need for specialists in these units in order to correctly perform the diagnosis of epileptic syndromes of low remission, such as juvenile absence and myoclonic epilepsies, as well as, to give the patients a better standard care, and consequently decrease the stigma of epileptic seizures in the population. 1 Barbara E. Hallinan, 1 Argirios Dinopoulos, and 1 Antonius DeGrauw ( 1 Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH ) Rationale: We report a young man followed in the Neurology Clinic at the Cincinnati Children's Hospital Medical Center (CCHMC) for partial epilepsy who developed Landau‐Kleffner Syndrome at the age of 14 years. The patient was admitted to our hospital in July 2004 for observation following a seizure characterized by left hand clenching, head shaking and unresponsiveness for one minute. The patient was drowsy but at his mental status baseline following the episode. Further history revealed that the patient had had two other seizures in the 18 month period prior to admission. The patient's initial EEG revealed frequent high amplitude 2 Hz independent bitemporal spike and wave discharges with no clinical correlate. Neuroimaging was normal. The patient was discharged on valproic acid with close follow‐up planned. Six months later, the family reported a steady decline in school performance and behavior. The EEG showed electrographic seizures, generalized in onset, with a L > R bitemporal predominance. Lamotrigine was added. Nine months after initial admission, specific deficits in receptive and expressive language were noted. An overnight EEG revealed abnormal activity originating in the left temporal region during wakefulness. Continuous spike‐wave activity during stage III sleep was noted consistent with electrical status epilepticus of slow wave sleep. Valium was added to the patient's regimen. Sixteen days later, the EEG normalized with clinical improvement in language function. Valium was tapered and a subsequent 24 hour EEG was normal. Two years after the initial diagnosis of epilepsy, the patient remains seizure‐free on valproic acid and lamotrigine with some persistence of slow expressive speech. To our knowledge, this is the first case of Landau‐Kleffner Syndrome in a teenager. 1 Lorie D. Hamiwka, 1 Neetu K. Singh, 1 Jodie Niosi, and 1 Elaine C. Wirrell ( 1 Pediatrics and Clinical Neurosciences, Alberta Children's Hospital/University of Calgary, Calgary, AB, Canada ) Rationale: Although the diagnosis of seizures are common in pediatric neurology practice, first presentation is a particularly frightening event for the child and their family members. Accurate differentiation of a seizure from a non‐epileptic event, such as convulsive syncope and breath holding is important, as prognosis, life style modifications and social stigma differ between these diagnoses. The goals of this study is to determine (a) the range of diagnoses presenting to a first seizure clinic, and (b) the prevalence of previous seizures in children presenting to a first seizure clinic. Methods: 127 children were seen in a tertiary care First Seizure Clinic. Inclusion criteria were age 1 mo–17 yrs with an unprovoked event suggestive of seizure. Data collected included referring physician specialty, child's age, gender, developmental status and clinical diagnosis of epileptologist (non‐epileptic vs epileptic). For those with epileptic events, seizure type, syndrome (if identifiable), presumed etiology (idiopathic, cryptogenic, symptomatic), presence of prior afebrile and febrile seizures, provoking factors, family history, pre/perinatal complications and EEG results were recorded. Results: The diagnosis was epileptic in 94 (74%), non‐epileptic in 31 (24%) and unclassifiable in 2 (2%). Pediatricians were more likely to refer true epileptic events (92%) than ED physicians (76%) or Family Physicians (65%). Mean age at presentation was 8 years. Fifteen percent of children were developmentally delayed and neurological examination was abnormal in 11%. For those diagnosed with epileptic events, 32 presented with generalized while 62 presented with partial onset seizures. An epilepsy syndrome was identifiable in 15 cases. Thirty eight percent experienced a prior probable seizure which was recognized by the referring physician in only one case. An EEG was done in all children with seizures and was abnormal in 41%. Conclusions: Diagnostic inaccuracy is common in first seizure. One quarter of children were incorrectly diagnosed as having a seizure while the diagnosis of epilepsy was missed in over 1/3 of children. First seizure clinics conducted by epilepsy specialists is important in the diagnosis, treatment and counseling in this group of children. 1 Allen Hauser, 1 Cigdem I. Akman, 1 Lawrence J. Hirsch, 1 Nathalie Jette, and 1 Ronald Emerson ( 1 Neurology, Comprehensive Epilepsy Center, Columbia University, College of Physician & Surgeons, New York, NY ) Rationale: Refractory Status Epilepticus (RSE) refers to a subgroup of Status Epilepticus (SE) with continuous seizure activity persisting for 60 minutes or more despite the first and/or second line medical and anticonvulsant therapy. We review clinical features, treatment response, seizure recurrence and EEG findings in children with RSE. Methods: Retrospective chart review of patients < 18 y.o who were admitted to a pediatric Intensive Care Unit with a diagnosis of RSE between 2001 and 2005 to determine demographic features, clinical course, treatment response and short term outcome. Results: Twenty‐four episodes of RSE were identified in 23 patients (age 13d‐194m). Etiology was cryptogenic in 1, symptomatic in 23 (14 acute, 4 remote, 5 progressive). Specific causes included CNS infection in 7 (30%), progressive encephalopathy in 3 (13%), toxic metabolic in 3 (13%), CNS tumor in 2 (8.6%), change in AED dose in 2 (8.6%), other causes in 2. Duration of seizures until the 1st AED was < 30 min in 5; 30–60 min in 5; >60 min in 1; repetitive clusters of seizures in 10 and missing in 3. First AED administered at the time of diagnosis included lorazepam (LRZ) in 14 (58%), diazepam (DZP) in 5 (20.8%) and phenytoin (PHT) in 3 (12.5%). Twenty‐three children received a 2nd AED: LRZ in 12 (52%), DZP in 2 (8.6%), PHT in 4 (17.3%), and phenobarbital (PB) in 3 (13%). A third AED was administered to 18: PHT 9 (50%), DZP in 6 (33%) and PB in 3 (16.6%). A Fourth AED was used in 12 (50%), a 5th AED in 4(16.6%). All patients ultimately received continuous infusion of midazolam (MDZ) 23/24 or pentobarbital (PTB) 9/24. MDZ was effective in 15, maximum dose 0.06–1.2 mg/kg/hr and average duration of 4.4 days. PTB was effective in 6, maximum dose was 3–15 mg/kg/h with average duration of 18 days. RSE was controlled only with ACTH in 1 and high dose PB in 1 after failing MDZ and PTB infusion. In 20 patients, EEG was obtained within 24 hrs. Burst suppression was noted in 11 (45%) with MDZ or PTB infusion. Non‐convulsive seizures were seen in 7 RSE cases (29%) during the course of treatment. RSE was controlled in all but one patient, 14 responded in < 2 days, 6 in 2–4d, 3 in >15d. Seizures recurred in 7 cases within 1 week of discontinuation of infusion. At discharge, mild neurological deficit was seen in 12, and severe disability in 9. Thirteen patients were released home, 5 to rehabilitation, 3 to the local hospital, and 2 expired during the course of RSE. Conclusions: This study demonstrates that etiology, recurrence of seizures and mortality rate are different in children with RSE compared to adults with RSE. CNS infection was the most common single cause, and mortality was lower than in adults. Further studies are needed to identify risk factors and optimal treatment for RSE in children. 1 Patel Hema, 1,2 Dunn W. David, 2 Scott L. Eric, and 1 Garg P. Bhuwan ( 1 Section of Pediatric Neurology, Department of Neurology, Indiana University Medical Center, Indianapolis, IN ; and 2 Section of Child Psychiatry, Department of Psychiatry, Indiana University, Medical Center, Indianapolis, IN ) Rationale: Limited information is available on phenomenology of childhood non‐epileptic seizures (NES) by developmental stages. We have studied the clinical characteristics of non‐epileptic seizures (NES) in children to determine if the clinical manifestations are different in children younger than 13 years age as compared to the older children. Methods: Retrospective review of medical records and video‐EEGs of all patients with NES confirmed on video‐EEG monitoring at Indiana University from April 2002 to December 2005. Results: 1,967 patients were monitored in the video‐EEG unit during this period. 68 patients (3.5%) had a clinical diagnosis of NES. We present data on 59/68 patients who had their habitual event recorded during the video‐EEG monitoring; 9 patients did not have their habitual event during the Video‐EEG study. Mean age at the time of the video‐EEG diagnosis was 13.3 years (range 5years 6 months to 19 years 6 months). Mean duration of symptoms prior to the diagnosis of NES was 6.8 months (range 3days to 3 years). In our study 37 of the 59 patients (62%) were females. 22 patients were less than 13 years of age (group A) and 37 were 13 years and older (group B). In group A male to female ratio was equal (11 patient each) while in group B there were more females (26 females and 11 males). Interpersonal conflicts, school related stress and family discord were the most frequent stressors in both groups. Sexual abuse was the least frequent. Cognitive dysfunction was present in 15/22 (68%) in group A and 7/37 (19%) in group B. 2/22 (9%) in group A had depression as compared to 13/37 (35%) in group B who were depressed. 15/22 (68%) in group A had epilepsy (partial epilepsy in 80%) in contrast to 11/37 (29%) in group B (partial in 45%). Prominent motor activity was more likely with NES in group B (32/37, 86%). Conclusions: We found that there were more females with NES in the older than 13 yrs age group while this gender difference was not seen in the younger children. In addition the clinical characteristics of NES are different in younger children as compared to older children. Distinct risk factors for the younger age group included cognitive dysfunction and diagnosis of epilepsy, whereas for the older children, depression and prominent motor activity were associated with NES. These findings have implications for the identification of non‐epileptic seizures in children and their management in this age group. 1 Angel W. Hernandez, 1 David Donahue, 1 Saleem I. Malik, and 1 C. Thomas Black ( 1 Comprehensive Epilepsy Program, Cook Children's Medical Center, Fort Worth, TX ) Rationale: Vagus nerve stimulation (VNS) therapy is the first device‐based treatment option for both epilepsy and depression. On the basis of pre‐clinical trials, the manufacturer of the VNS Therapy System (Cyberonics, Inc; Houston, TX) recommends that stimulation be started 2 weeks after the device is implanted to allow for surgical recovery time. We intend to show that stimulation activation in the operating room immediately after implantation is safe and well tolerated in children and adolescents regardless of output current, pulse width, and frequency. Methods: A retrospective chart analysis was performed on 104 patients aged 8 months to 20 years (median age 7.9 years) with pharmacoresistant epilepsy and implanted with the VNS therapy device between 2001 and mid‐2005. All devices were activated intraoperatively. Forty‐nine devices were activated using the following stimulation parameters: output current of 0.25 mA, pulse width of 500 μsec, and frequency of 30 Hz. Fifty‐five devices were activated using the following parameters: output current of 0.25 mA, pulse width of 250 μsec, and frequency of 20 Hz. All devices were set to a duty cycle of 5 minutes Off and 30 seconds On. Results: All patients tolerated intraoperative VNS activation. Adverse changes in blood pressure, pulse rate, or electrocardiogram (EKG) did not occur at the time of activation or thereafter. No unexpected side effects were reported acutely. Conclusions: Intraoperative activation of the VNS therapy device appears to be safe and well tolerated in children and adolescents regardless of output current, pulse width, and frequency. 1 Eila A. Herrgard, and 2 Laila Luoma ( 1 Department of Pediatrics, Division of Pediatric Neurology, Kuopio University and University Hospital, Kuopio, Finland ; and 2 Department of Psychiatry, Kellokoski Hospital, Hospital District of Helsinki and Uusimaa, Finland ) Rationale: Only few pre‐, peri‐ and neonatal risk factors are recognized for febrile seizure. In some studies febrile seizures are shown to be associated with preterm birth, pre‐eclampsia, respiratory distress syndrome (RDS), hyperbilirubinemia, long neonatal intensive care, sepsis and low birth weight. The aim of our study was to evaluate risk factors for febrile seizures in the study group of children including both preterm and term children. Methods: Pre‐, peri‐ and neonatal data of 60 prospectively followed children born at or before 32 weeks of gestation, and of 60 matched term controls from the two year birth cohort were available from earlier phases of the study. Seizure data were obtained from questionnaires completed by parents, and from hospital records and parent interviews. Risk factor analysis was done by logistic regression. Results: Febrile seizures were found in 8 /60 (13%) children born at ≤ 32 weeks of gestation and in 3/60 (5%) children born at term. Fourteen of 120 children (12%) were born to pre‐eclamptic mothers, 30/120 children (25%) were small for gestational age (SGA), 48 children (40%) had a neonatal intensive care longer than 28 days; neonatal sepsis was found in 4/120 (3%), respiratory or other infections during neonatal period in 26/120 (22%) and RDS in 30/120 children (25%). Risk for febrile seizures was 2.9 (CI 0.74–11.619) in the children born preterm compared to the term children. Risk for febrile seizures in offsprings of mothers with pre‐eclampsia was low (OR 0.7, CI 0.09–6.25). Respectively, risk for febrile seizures in SGA children was low (OR 1.1, CI 0.28–4.60). Risk for febrile seizures in RDS children (OR 2.8, CI 0.79–9.95) and in children who had long neonatal intensive care (OR 2.9, CI 0.80–10.52) was parralel. Sepsis and other infections during neonatal period and later febrile seizures were not encountered in the same children. Conclusions: Rate of febrile seizures was increased in children born preterm. Pre‐eclampsia, intrauterine growth retardation, sepsis or other neonatal infections were not risk factors for febrile seizures. However, the size of the study group sets its own limitations in evaluations of risks. 1 Dale C. Hesdorffer, 1 Veronica J. Hinton, 2 Christine O'Dell, 2 David M. Masur, 3 Douglas Nordli, 4 Jack Pellock, 4 Anthony Marmarou, 5 Darrell V. Lewis, 6 L.M. Frank, 2 Shlomo Shinnar, and the FEBSTAT Study Team ( 1 GH Sergievsky Center, Columbia University, New York, NY ; 2 Department of Neurology, Montefiore Medical Center, Bronx, NY ; 3 Department of Neurology, Children's Memorial Hospital, Chicago, IL ; 4 Department of Neurology, Virginia Commonwealth University, Richmond, VA ; 5 Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA ; 6 Department of Pediatrics, Duke University Medical Center, Chapel Hill, NC ; and 7 Department of Neurology, Eastern Virginia Medical School, Norfolk, VA ) Rationale: Febrile status epilepticus (FSE) may be associated with the development of mesial temporal sclerosis and intractable temporal lobe epilepsy. If ongoing prospective studies support this, then prevention of FSE becomes a central concern. We, therefore, undertook an analysis to identify risk factors for FSE. Methods: This analysis combines data from two prospective studies, employing almost identical protocols and questionnaires: children with incident FSE (n = 73) from the FEBSTAT study; and children with incident simple (n = 105) and complex (n = 46) febrile seizures (FS) that were not FSE from the Columbia University Febrile Seizure study. At identification, parents were questioned about potential FS antecedents and an MRI was performed within 72 hours. Within one month of the FS, children received a neurological examination and developmental testing. Logistic regression was used to evaluate potential FSE risk factors, comparing FSE to simple FS and complex FS (not FSE) to simple FS. Results: Compared to children with simple FS, children with febrile SE were less likely to be 18 months and older (OR = 0.5; 95% CI = 0.2–0.8) and less likely to have fevers of 104.0 or more (OR = 0.2; 95% CI = 0.1–0.5). Similar non‐significant results were seen for other complex FS vs. simple FS. Smoking during pregnancy was strongly associated with FSE compared to simple FS (OR = 3.6, 95% CI = 1.4–9.4) as was drinking during pregnancy (OR = 9.6, 95% CI = 1.1–82.3). Smoking was also associated with a 2.1‐fold non‐significant increased risk complex FS compared to simple FS. No associations were observed for family history of febrile seizure, neurological abnormality, or day care attendance. Conclusions: Risk factors appear to be different for both FSE and other complex FS compared to simple FS. The reason for the robust association between smoking during pregnancy and FSE deserves further study. (Supported by R01 HD 36867 and R01 NS043209.) 1,2 Sudha V. Kilaru, 1 Anuradha Venkatasubramanian, and 1 Dennis J. Dlugos ( 1 Neurology, Children's Hospital of Philadelphia, Philadelphia, PA ; and 2 Neurology, Columbia University Medical Center, New York, NY ) Rationale: Clinical features of an epileptic seizure (seizure semiology) can provide important information regarding localization of the ictal onset zone. Understanding seizure semiology, and its concordance with EEG and imaging data, is particularly important in the evaluation of epilepsy surgery patients. The inter‐rater reliability (IRR) of pediatric seizure semiology, with an emphasis on the order of appearance of clinical signs, has not been extensively studied. As part of a continuous quality improvement initiative in an epilepsy monitoring unit, we designed a form to record and code components of seizure semiology, and tested its usability and IRR. Methods: Based on expert opinion and a literature review of lateralizing signs in adults and children, a form was constructed listing lateralizing and nonlateralizing signs commonly seen in seizures. Four major categories–eye signs, face signs, trunk/limb signs, and other signs–were delineated. Within these 4 categories, specific elements were described and lateralized. Two investigators independently reviewed and coded the video records of 33 seizures from subjects aged 2 to 18 years. The primary outcome of interest was percent agreement when identifying the first three clinical signs, including lateralization when appropriate. Across all seizures, 95 clinical signs were assessed. Percent agreement corrected for chance agreement (Kappa statistic) was explored, but correction was minimal (less than 1%) due to the large number of possible choices. Results: Agreement on behavioral state prior to the seizure occurred in 85% of records. Agreement on the presence of clinical signs occurred in 73/95 (77%) of clinical signs assessed. Lateralizing features were found in 65/95 (68%) of clinical signs assessed. In records with such features, agreement on lateralization occurred in 77% of records. Eighteen percent of lateralization disagreements (n = 2) were due to rater errors. The other disagreements were disputes of whether signs were unilateral versus bilateral (n = 7), or present or absent (n = 2). All but two disagreements on lateralization were resolved in a consensus conference. We observed that 49% of initial signs had lateralizing features, while 76% of second signs were lateralizing, and 83% of third signs were lateralizing. Conclusions: We designed a practical, easy‐to‐use form for coding the semiological components of individual seizures recorded on video. IRR was good‐to‐excellent, and most lateralization disagreements were resolved on consensus conference. The second or third signs during a seizure were more often lateralizing than the first. Based on additional experience, this form will be optimized for greater ease‐of‐use and reliability. Future work could correlate the order of appearance of lateralizing signs with EEG data, imaging data and outcome in children being evaluated for epilepsy surgery. 1 Hoon‐Chul Kang, 2 Baik‐Lin Eun, 2 Chang Wu Lee, 2 Han Ku Moon, 2 Joon‐Sik Kim, 2 Dong Wook Kim, 2 Joon Soo Lee, 2 Kyu Young Chae, 2 Byung Ho Cha, 2 Eun Sook Suh, 2 Jung Chae Park, 2 Kyunghwa Lim, 2 Eun Hye Ha, and 3 Heung Dong Kim ( 1 Pediatrics, Epilepsy Center, Inje University College of Medicine, Sanggye Paik Hospital, Seoul, Korea ; 2 Korean Pediatric Topiramate Study Group, Korea ; and 3 Pediatrics, Pediatric Epilepsy Clinics, Severance Children's Hospital, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea ) Rationale: This study compares the cognitive and behavioral effects of topiramate with those of carbamazepine using efficacious doses of each drug when used as monotherapy in children with benign rolandic epilepsy. Methods: The study is a multicenter, randomized, observer‐blinded, parallel‐group clinical trial with topiramate or carbamazepine given as first‐line therapy. Topiramate is introduced at 25 mg per day. The target dosages are 50 mg per day in 30 kg > weighted patients and 75 mg or 100 mg per day in 30 kg < weight patients in 4 weeks. Carbamazepine is started at 10 mg/kg per day and the target dosage is 20 mg/kg per day in 4 weeks. The primary outcome measure is the difference between the treatments (topiramate versus carbamazepine) in change of the cognitive and behavioral function from baseline to end point (after 28 weeks of treatment), using a 95% confidence interval approach. Results: For the 22 baseline‐to‐end point cognitive and the 13 baseline‐to‐end point behavioral comparisons, one test measuring Verbal Intelligence Quotient yields a statistically significant difference between the treatments (p = 0.019), showing worsening for topiramate and improvement of scores for carbamazepine and one additional test also shows a statistically significant difference, again for a test measuring arithematics (p = 0.043), showing a larger change in the negative direction for topiramate. None of the behavioral tests shows statistically significant differences between the treatments. However, integrated functions, verbal comprehension factor including information, similarities, vocabulary and comprehension as well as attention and concentration including arithmetics, digital span and coding do not show statistically significant differences between the treatments, although those scores are in the negative direction for topiramate. Conclusions: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that the differences between two treatments are compensated in the integrated functions. (Supported by JANSSEN, KOREA LIMITED, a Johnson & Johnson company.) 1 Won Seop Kim, and 1 Eun Ju Lee ( 1 Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, Korea ) Rationale: Acute Symptomatic Seizures differ from epilepsy in that they have a clearly identifiable proximate cause and they are not characterized by tendency to recur spontaneously. But we hypothesized that acute symptomatic seizures with status epilepticus (SE) have an increased risk of subsequent seizure than those without status epilepticus. Methods: We retrospectively studied five hundred and twelve children with seizures visited our hospital from January 1998 to December 2003. Among those children, 167 patients were determined as provoked seizures, and the patients were followed up for 2 years. Results: One hundred and nine children had acute symptomatic seizures. The ages of first seizures were 1.58 ± 2.53 years. Causes in order of frequency were acute gastroenteritis (31.0%), minor infections (23.9%), CNS infections (7.0%), encephalopathy (7.0). At two year follow‐up, the incidence of the unprovoked seizure was 31.1% for children with acute symptomatic seizures. The risk of the unprovoked seizure was significantly greater for children with acute symptomatic seizures with SE (56.3%) than those without SE (25.2%). Conclusions: The leading cause of acute symptomatic seizures was acute gastroenteritis. The incidence of subsequent unprovoked seizure was highest in the group of encephalitis/encephalopathy. The risk of for subsequent unprovoked seizure was greater for those with SE than those without SE. The risk of subsequent unprovoked seizures is determined by underlying precipitation factors and children with acute symptomatic seizures with SE should be followed up carefully. 1 Da Eun Jung, 1 Heung Dong Kim, 1 Joon Soo Lee, 2 Ju Young Chung, and 2 Hoon Chul Kang ( 1 Department of Pediatrics, Pediatric Epilepsy Clinic, Severance Children's Hospital, Yonsei Univeristy College of Medicine, Seoul, Republic of Korea ; and 2 Department of Pediatrics, Epilepsy Center, Inje University College of Medicine, Sanggyepaik Hospital, Seoul, Republic of Korea ) Rationale: The objectives of this study were to investigate the proportion of abnormal endoscopic lesions in intractable epilepsy children prior to KD and to reveal their relationship to patient's dietary tolerability and to know how to increase tolerability of KD in patients with abnormal endoscopic lesions. Methods: Thirty‐five patients were enrolled in this study at the Epilepsy Center, Sanggye Paik Hospital, Inje University College of Medicine, from March 2002 to August 2003. Informed consents were obtained from their parents of all the patients. Gastrofiberscopy were done to all patients prior to initiation of KD. Patients with abnormal endoscopic lesions were treated with H2 receptor blocker, proton pump inhibitor, and/or prokinetics for initial 4 weeks of the KD. We observed the incidence of G‐I disturbance symptoms such as nausea, vomiting, unusual irritability or cramping abdominal pain, and diet refusal for over a day in patients with abnormal endoscopic findings, as compared with the patients without such G‐I lesions. We also observed the proportion of patients who showed improvement on tolerability after the active G‐I medications. Results: Of the 35 patients in this study, 18 were boys and 17 were girls. The mean (±SD) age of the patients at the beginning of the diet was 62.9 (±42.5) months. Various kinds of epilepsies and epileptic syndromes were subjected for this study including infantile spasm and Lennox‐Gastaut syndrome. Polypharmacy with more than 4 AEDs were used in 14 patients. Sixteen patients were treated with prednisolone for more than 1 month. Twenty patients (57%) revealed abnormal endoscopic lesions, showing 10 cases of erosive gastritis, 4 duodenitis, 3 hemorrhagic gastritis, 2 esophagitis, and 1 duodenal ulcer. The incidences of abnormal endoscopic lesions were higher by 78% (11/14) in polypharmacy group, and 81% (13/16) in steroid consumers. Symptoms from G‐I disturbance such as nausea, vomiting, unusual irritability or cramping abdominal pain, and diet refusal for over a day, were complicated in 17 cases (85.0%) in patients with positive endoscopic lesions, and in 5 case (33.3%) in patients without endoscopic lesions. After the active management with G‐I medications, G‐I disturbing symptoms were subsided in most cases, except a patients who were discontinued KD from the intolerability. Conclusions: G‐I disturbing symptoms were more frequently associated in patients with positive abnormal endoscopic lesions. Active management with G‐I medications could increase tolerability of KD in patients treated with multiple AEDs and steroids. 1 Emily T. Klatte, 1,2 Juliann M. Paolicchi, 1 Sheri L. Hart, and 2,3 Debbie Terry ( 1 Neurology, Ohio State University, Columbus, OH ; 2 Comprehensive Epilepsy Center, Children's Hospital, Columbus, OH ; and 3 Nursing, Ohio State University, Columbus, OH ) Rationale: Treatment of Benign Rolandic Epilepsy (BRE), which is 15% of childhood epilepsy, is not standardized, and typically, balances benefit and medication toxicity. Data has suggested that BRE patients can suffer neuropsychiatric deficits. This study examined treatment trends, cognitive/behavioral issues, and factors predictive of neuropsychiatric problems. Methods: From 9/04–4/06, 55 patients met BRE clinical and electrographic criteria at our institution. Medical charts were reviewed for demographics and cognitive and behavioral issues. Statistical analysis included Chi Square and Somers'd. Results: Mean patient age was 6 years (2–13), 69% male. Neuroimaging was performed in 89% of subjects; 12 (24.5%) were abnormal. The average number of ER visits per subject for seizures was 1.2 (0–5). 16 (29%) required admissions: seizures (10), status (2), or long term monitoring (6). EEG findings demonstrated that 25.5% had left, 18% right, and 55% bilateral discharges. 10 (18%) had additional EEG findings, including occipital and generalized discharges. 17(30%) were not treated with AEDs. Subjects averaged 3.6 seizures (1–15) prior to initiation of treatment. Of the 38 treated, the majority were on oxcarbamazepine (14) or carbamazepine (17). 15 subjects required a change in AEDs due to seizures or side effects, and 2 were treated with 2 AEDs. Seizure frequency varied from 1 to >20 seizures; 41% had >10 seizures. 33(60%) reported comorbidities (may be more than 1 reported): 11(20%) headaches, 15(27.3%) language difficulties, 22(40%) trouble in school, 26(43.6%) behavioral problems, 18(32.7%) attention problems, 11(20%) ADHD, and 7(12.8%) other psychiatric diagnosis. Problems in school and bilateral discharges on EEG were statistically significant (p < 0.025), but the side of discharge was not. No association existed between discharge location and language, behavior, attention, or ADHD. Of the 55 subjects, 11 (20%) had low seizure frequency (defined as 1–2 seizures), 22 (40%) medium (3–9), and 22 (40%) high (≤10). There was a significant association of higher seizure frequency and reported trouble in school (p < 0.002), ADHD (p < 0.015), attentional problems (p < 0.025), and language problems (p < 0.028). There was no association between seizure frequency and behavior or discharge location. Conclusions: BRE is less “benign” than historically considered. Comorbidities are present in 60% of patients, the most common are behavioral problems, trouble in school, and attention impairments. The presence of bilateral EEG discharges is a significant risk factor for trouble in school. Children with high seizure frequency have an increased risk of having trouble in school, attention problems, ADHD, and language problems. Children with BRE, whether AEDs are indicated or not, should be screened for possible cognitive, behavioral, and learning disabilities. 1 Elisabeth Korn‐Merker, and 1 Heilwig Fischbach ( 1 Klinik Kidron, Epilepsy Center Bethel, EvKB, Bielefeld, NRW, Germany ) Rationale: Psychogenic seizures (PS) often are underdiagnosed–especially in epileptic patients.We report about 31 adolescents referred to our epilepsy center for pharmacoresistant epilepsy. We present clinical features, EEG findings, precipitants for PS, comorbidities and treatment results. Methods: 25 girls and 6 boys (aged from 12 to 23 years) with PS were identified from our inpatient records in 2003–2005. Admission diagnosis was difficult to treat epilepsy and multiple pharmacoresitance. In nearly all of them PS were not suspected. All patients had routinely EEG with sleep, hyperventilation and photostimulation. 2/3 had Video‐EEG too, MRI only those with focal EEG findings. Seizures and clinical events were observed and documented (video too) by nurses and allied staff, followed by classification as epileptic or nonepileptic. Precipitating neurologic comorbidities and psychiatric diagnosis were analysed as well as the short term impact of psychotherapeutic measures. Results: 17 patients had an active epilepsy too (9 focal, 7 generalized, 1 with focal and generalized signs). 18 patients were mentally handycapped, 9 had a positive familiy history of epilepsy. Clinically PS were clearly different from epileptic seizures and frequently dramatic. Common precipitating factors were school failure, anxiety disorder, sexual abuse and intrafamilial conflicts. A clinical setting structured by a multiprofessional team helped patients to identfy stressors, gain insight into their emotional reactions and develop coping skills (supportive milieu therapy). All patients had a significant reduction of PS. 2 were “seizure free” on discharge and 9 after 22 months, all of them continouing psychotherapy post discharge for 6 months minimum. Conclusions: Establishing a correct diagnosis is a vital step for treating PS in adolescents. Identification of stressors and early multidisciplinary stabilization yields good long term results for control of PS. Coaching the whole familiy to increase motivation for psychotherapy after discharge ameliorates the rate of seizure freedom. 1 Florise A. Lambrechsten, and 2 Jeffrey R. Buchhalter ( 1 Rijksuniversiteit Groningen & International School of Hepatology and Tropical Medicine, University Medical Center, Groningen, Groningen, Netherlands ; and 2 Neurology, Mayo Clinic, Rochester, MN ) Rationale: Relatively little data exists regarding refractory status epilepticus (RSE) in children. We aimed to determine: (i) the frequency of RSE in children, (ii) factors associated with the development of RSE, and (iii) predictors of outcome in children with RSE. Methods: Patients less than 18‐years‐old, hospitalized at the Mayo Clinic, Rochester, 1994–2004, were included. Medical records with an ICD‐9 diagnostic code of status epilepticus (SE) (345.3 and 345.2), epilepsy partialis continua (345.7), petit mal status (345.2), or grand mal status (345.3) were reviewed. In addition we reviewed EEG lab admission logs for diagnoses of SE. The study was IRB approved. Univariate analysis and Cox's‐proportional hazards models were used for statistical analysis. Results: We identified 178 children with possible SE, 24 of which were excluded because they did not meet our inclusion criteria or had incomplete data. Of the remaining 154 children with SE, 60 (39.0%) had RSE and 94 (61%) had non‐RSE. In the RSE group, 13 children (21.7%) had a family history of seizures compared to 3 children (3.2%) in the non‐RSE group (p < 0.001). A previous diagnosis of epilepsy was present in 44 children (73.3%) with RSE and in 67 children (71.2%) with non‐RSE. Children with RSE and a diagnosis of epilepsy used a significantly higher number of anti‐epileptic drugs (AED's) prior to the prolonged seizure episode than children with non‐RSE (5 vs. 3 AED's; P < 0.001) and had a significantly higher seizure frequency score (8.53 vs 6.34; P < 0.001). Clinical factors associated with the development of RSE were non‐convulsive SE and focal motor seizures at onset. Etiologies did not differ significantly between RSE and non‐RSE. Mean duration of follow‐up was 3.89 years (range 0.8–12.2 years). Ten children (6.5%) died during hospitalization and 9 (5.8%) during follow‐up. Overall mortality was significantly higher in the RSE group (20%) than in the non‐RSE group (7.4%; p = 0.021). Survivors with RSE had a higher risk for developing new neurological deficits (HR 2.45; 95% CI 1.5–3.9; P < 0.001). This risk was lower if age at admission was >10 years compared to < 4 years (HR 0.57; 95% CI 0.3–1.0; P= 0.05). At 4 years after dismissal, 30% of children with RSE developed epilepsy compared to 10% of children with non‐RSE. This was associated with an acute symptomatic etiology (HR 2.43, 95% CI 1.2–5.0, P 0.02). Conclusions: Factors associated with RSE were identified: positive family history of seizures and in cases of diagnosed epilepsy, higher seizure frequency and number of previously used AED's. Clinical factors associated with RSE were non‐convulsive SE and focal motor seizures at onset. Further studies are needed to determine if more aggressive treatment strategies in children with SE at risk for developing RSE can improve outcome, particularly in those with younger age at admission and acute symptomatic etiology. (Supported by Marco Polo Fund, Netherlands.) 1 Pramote Laoprasert, 2 Michael Handler, 1 Julie Parsons, and 1 Kevin Staley ( 1 Pediatrics and Neurology, The Children's Hospital, University of Colorado Health Science Center, Denver, CO ; and 2 Pediatrics and Neurosurgery, The Children's Hospital, University of Colorado Health Science Center, Denver, CO ) Rationale: Focal transmantle dysplasia (FTD) is a specific malformation of cortical development (MCD) with abnormality extending from the wall of lateral ventricle to the cortical surface. FTD varies from a linear band to an entirely malformed lobe and probably associated with maldifferentiation of the stem cells generated in the germinal zone. FTD was first described in 1997 and seen in 4% of MCDs in childhood. FTD usually occurs as an isolated finding although has rarely been reported in neurofibromatosis type 1 and tuberous sclerosis complex. There has been no report of FTD caused by prenatal vascular insult (PVI). Methods: We retrospectively reviewed the clinical, EEG, and neuroimages of 3 patients with FTD caused by PVI, 2 from intraventricular hemorrhage (IVH) and 1 from cerebral ischemia. 1 patient underwent epilepsy surgery. Results: Patient 1 is a 6‐year‐old‐left‐handed‐twin B girl who was born at 28 weeks GA with IVH grade 4 and required ventilator supports for 3 months. She had multiple types of seizures including myoclonic, secondarily generalized tonic‐clonic, absence, and asymmetric tonic seizures. Four MRI scans were interpreted as ischemic injury in the left frontal region. FTD was diagnosed during presurgical evaluation. EEG showed epileptic focus in the left frontal and frontal vertex regions. Ictal SPECT showed left mesial frontal hyperperfusion. Resection of FTD and epileptogenic zone after subdural EEG implantation led to seizure free. Pathology revealed focal cortical dysplasia. Patient 2 is a 23‐month‐old‐left handed girl who was born at 24 weeks GA. She had fetal distress due to abruption placenta with subsequent global developmental delay (GDD) and one seizure described as right‐sided clonic jerks at age 23 months. MRI was interpreted as periventricular nodular heterotopias but apparently it was FTD in the left frontal region. Her seizure has been well controlled with oxcarbazepine. Patient 3 is a 14‐year‐old‐right‐handed girl who was born at 36 weeks GA to a mother who had severe hyperemesis requiring total parenteral nutrition at 15 weeks GA. The patient had GDD, ADHD, severe left hemiparesis, and focal epilepsy. MRI showed extensive polymicrogyria in the right fronto‐centro‐temporal and FTD in the right frontal region. She was found having electrical status epilepticus during slow sleep (ESES). Her cognition improves dramatically with diazepam. Conclusions: Our report suggests that PVI, either ischemia or hemorrhage, can cause FTD. FTD is probably underrecognizable as it is a relatively new type of MCD and can have varieties of clinical courses. This report may help neurologists to expand the scope and better understand the pathophysiology of FTD and to be more aware of this condition. Adequate treatment of PVI may prevent the development of FTD. 1 Jeehun Lee, 2 Dae Won Seo, 2 Seung Bong Hong, 3 Seung Chul Hong, 4 Yeon Lim Suh, and 1 Munhyang Lee ( 1 Pediatrics, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea ; 2 Neurology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea ; 3 Neurosurgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea ; and 4 Pathology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea ) Rationale: Dysembryoplastic neuroepithelial tumors (DNTs) are often associated with medically intractable epilepsy in childhood, but also with favorable outcome after epilepsy surgery. Aim of this study is to delineate the clinical characteristics of DNTs and to find an adequate method of epilepsy surgery of DNTs in childhood. Methods: A retrospective analysis was done on the clinical, pathologic, and radiological data of 19 patients, who were presented with seizure and had been found to have DNTs after surgery, between Jan 1996 and April 2005. Epilepsy surgery was performed using intraoperative electrocorticography or subdural electrodes in all patients except one. Results: Mean follow‐up duration after surgery was 28 months. Of the 19 patients (mean age at surgery 12 year 6 months), All patients showed a favorable outcome (class I–18, class II–1). Temporal lobe was the most frequent site of tumor involvement (15 cases). All the lesions showing active epileptogenicity were resected with the tumor. There was associated cortical dysplasia (CD) on pathology of the resected lesion besides tumor in 12 cases. Conclusions: We found that the DNT was frequently associated with CD and the active epileptogenic lesions were associated with CD. So the precise presurgical localization of epileptic focus, perioperative brain mapping, and radical resection of the epileptogenic lesion including tumor would be the essential requirement for the favorable surgical outcome in childhood DNTs. 1 Young Mock Lee, 1 Joo Hee Seo, 2 Hoon Chul Kang, 1 Joon Soo Lee, and 1 Heung Dong Kim ( 1 Department of Pediatrics, Institute for Handicapped Children, Yonsei University College of Medicine, Seoul, Korea ; and 2 Department of Pediatrics, Inje University College of Medicine, Sang‐gye Paik Hospital, Seoul, Korea ) Rationale: This study aimed to characterize clinical and laboratory features in children with epilepsy diagnosed as mitochondrial respiratory chain enzyme complexes (MRC) defects and to provide newly postulated etiology in various epileptic condition. Methods: We retrospectively reviewed clinical and laboratory features of 21 patients with epilepsy who showed defects in MRC activity, confirmed by biochemical assay from spectrophotometry in muscle tissue. Results: 1) Mean age was 5.63 ± 3.49 years and sex ratio was 1:1.1. 2) Fourteen (66.7%) were MRC I deficiency, 5 (23.8%) of VI deficiency, 1 (4.8%) of II deficiency, and 1 case of combined deficiency of I and IV. 3) Four cases (19.0%) were classified as Leigh syndrome, 1 case (4.8%) each as MELAS and Alpers disease, but 15 cases (71.4%) were not clinically categorized for specific disease criteria. 4) Epileptic diagnoses included generalized seizure disorders in 7 cases (33.3%), partial seizure disorders in 4 cases (19.0%), Lennox‐Gastaut syndrome in 6 cases (28.6%) and infantile spasm in 4 cases (19.0%). 5) Mean seizure onset age was 2.34 ± 2.20 years. 6) Brain MRI showed diffuse cortical atrophy in 15 (71.4%), basal ganglia signal changes in 8 (38.1%) and thalamus sinal changes in 6 cases (28.6%). 7) Positive rate for laboratory studies were: 90.5% in lactic acidosis, 72.2% in urine organic acid assay, 29.4% in serum amino acid assay, and 53.3% in MR spectroscopy. 8) Mitochondrial cocktail with coenzyme Q10 and multi‐vitamin therapy showed clinical improvements in 71.4% of patients. Conclusions: MRC defect can be the important cause of epilepsy. Treatments with coenzyme and multi‐vitamine have shown considerable benefits. 1 Paul M. Levisohn, 2 Samuel M. Shirk, 3 Ken R. Winston, and 1 Lisa M. Gustas ( 1 Pediatrics and Neurology, University of Colorado Health Science Center, Denver, CO ; 2 Neurology and Neurodiagnostics, The Children's Hospital, Denver, CO ; and 3 Neurosurgery, University of Colorado Health Science Center, Denver, CO ) Rationale: Intermittent stimulation of the left vagus nerve is an approved adjunctive therapy for medically intractable partial onset epilepsy in children 12 years and older. Management of children less than 12 years of age with intractable epilepsy, particularly those with epileptic encephalopathies remains challenging despite the availability of new drugs. This study reports outcomes on 100 patients, aged 2–22 at implantation, including 56 ‘ < 12’ between 1/98 and 4/06. Methods: Data were gathered using retrospective chart review. Variables included seizure frequency at the surgical visit, seizure frequency at 12 month follow‐up, seizure frequency at 24 month follow‐up, and seizure frequency at last visit. Frequencies were recorded as number per week, and were extrapolated from records in the patient's chart. We documented prior number of medications and post number of medications. Post operative complications were noted. Results: The average age at implantation was 10.6 years (SD = 4.9). The average reduction of seizures was 45% (SD = 40); percent reduction was defined as 100*(1‐ number of post seizures/number of prior seizures). 14 patients were lost to follow‐up. 33 patients had incomplete data and were excluded from this calculation. 15 patients had >89% seizure reduction; 3 became seizure‐free with VNS, 1 post resection. We also devised a qualitative improvement rating scale: significant improvement (70% reduction or greater), moderate improvement (1–69% reduction), no improvement (0%). 26/77 had significant, 18/77 had moderate, and 33/77 had no improvement (9 had incomplete data). An analysis of medication reduction showed no decrease. We saw no difference between the < 12 age group and the >12 group. Percent reduction showed no difference (42%,SD = 41: 46%, SD = 39). In the < 12, 13/41 had significant, 10/41 had moderate, 18/41 had no improvement. In the >12, 13/36 had significant, 8/36 had moderate, 15/36 had no improvement. 5 ‘>12’ and 9 ‘ < 12’ were lost to follow‐up. 28 ‘ < 12’ were treated with the ketogenic diet, compared to 14 ‘>12’. 6 patients had their VNS removed (3 due to infection), 6 stimulators were replaced. 5 patients had post‐implant callosotomies (all < 12 group). 2 patients died, one from failure to thrive, one from status epilepticus. Conclusions: VNS has efficacy in children under age 12 years with generalized epilepsies. Although clearly not a cure or a sole therapy for most patients, our data support the position that VNS is a safe and effective adjunctive therapy for pharmacoresistant epilepsy in children < 12 years of age. We observed no difference in the efficacy and outcomes of children < 12 treated with VNS when compared to the >12 group. 1,2 Yeou‐mei Christiana Liu, 2 Amy Haw, 2 Kent Campbell, 1,2 Jeff Kobayashi, 1 Elizabeth J. Donner, 2 Olivia Lugue, 2 Susan Cohen, and 1 Rosalind Curtis ( 1 Neurology, The Hospital for Sick Children, Toronto, ON, Canada ; and 2 Child Development Program, Bloorview Kids Rehab, Toronto, ON, Canada ) Rationale: The objective of this study is to assess the long term growth and lipid status of children treated with the classic and medium‐chain triglyceride (MCT) ketogenic diets. There are 5 articles that reported ketogenic diet patients' growth status and only one with short term prospective growth status, but there is no long‐term prospective study that examines the children's growth and lipid status. Methods: A prospective, nonrandomized study design was used to measure growth and lipid status of children, age 1 to 16 years (mean = 5.9 ± 3.7), with intractable epilepsy before and after 12 months treatment with the classic or MCT ketogenic diet. None of the children had been on earlier dietary regimens. Forty‐eight consents were obtained between January, 2000 and May 2005. Thirty‐three children were on the classic diet and fifteen children were on the MCT diet. Paired t tests were done on weight percentile, height percentile, percentage of ideal body weight (IBW), total cholesterol, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL) and triglycerides (TG). Results: Thirty‐two children completed 12 months on the ketogenic diet. Percentile heights, weights and percentage of IBW at 12 months follow‐up were compared to pre‐diet data. In the classic diet group (n = 21), the percentile heights and weights were significantly changed from the baseline measurements (p < 0.05). Mean weight percentile was decreased by 5.2 and height percentile decreased by 10.7. There was no significant change in percentage of IBW. In MCT diet group (n = 11), the mean percentile height was significantly lower than baseline measurement (p < 0.05) with a 17 percentile reduction. The percentile weights and percentage of IBW in the MCT diet group showed no significant change. Both diets treatments resulted in height growth retardation. Only the classic diet group demonstrated weight growth retardation. For both diet groups, there was no significant increase in total cholesterol, LDL and TG at 12 months of diet when compared with their pre‐diet measurements. With intensive follow‐up of biochemical indexes and elevated levels corrected with polyunsaturated fat intake for both the classic and MCT diet, it appears children are able to maintain a healthy lipid level. Conclusions: Both the classic and MCT ketogenic diets result in significant height growth retardation in children at 12 months follow‐up. Only the classic ketogenic diet is associated with a significant weight growth retardation. The MCT diet does not have a negative effect on weight growth. Neither diet treatment produced an increased lipid level at 12 months follow‐up. Eighteen and twenty‐four months data are in the preliminary analysis to be concluded in the near future. 1 Paul Maertens, 1 Renay Drinkard, and 2 Eyal Fabien ( 1 Neurology, Unversity of South Alabama, Mobile, AL ; and 2 Pediatrics, Unversity of South Alabama, Mobile, AL ) Rationale: The objective of this study is to evaluate the efficacy and tolerability of levetiracetam monotherapy in neonates with acute stroke. Methods: This is a single center open‐label study of 3 neonates (less than 24 hour of age). In all cases, focal seizures were confirmed by EEG. The focal seizures were in all three children the result of an acute perinatal stroke (non hemorrhagic in 2; hemorrhagic in one). A loading dose of 50 mg/kg of levetiracetam was administered through a nasogastric tube while children were actively seizing and only benzodiazepines were given concomitantly. Seizure control and side effects were monitored while on once a day dosing. Results: No patient stopped levetiracetam due to side effect or lack of efficacy. No other anticonvulsant had to be added to the regimen to maintain seizure control. Feeding difficulties were initially seen but cleared after a few days. Levetiracetam level was still high twelve hours after the first dose (50 mcg/dL in one child). No other adverse event was observed. All three patients were left without neurological sequellae and the follow‐up imaging studies in our patients with acute brain injury showed a complete resolution of their lesion. Conclusions: Levetiracetam given once a day in neonates is well tolerated. We believe that, in neonates with acute stroke, levetiracetam has neuroprotective properties explaining the complete recovery of our patients. 1 Yu‐tze Ng, and 2 Rama K. Maganti ( 1 Pediatric Neurology, Barrow Neurological Institute/St. Joseph's Hospital, Phoenix, AZ ; and 2 Neurology, Barrow Neurological Institute, Phoenix, AZ ) Rationale: To describe a possibly new variant of childhood idiopathic localization‐related epilepsy. Methods: Seven children were reviewed in consultation who presented with similar clinical histories of distinctive, partial‐onset seizures. Typically their seizures would begin as simple partial seizures involving one of their feet and/or lower limb and often progress to secondarily generalized tonic‐clonic seizures. These patients were studied prospectively and their charts reviewed in detail. Results: All patients were cognitively and neurologically normal. Their average age of first seizure was 10.4 (range 4–13) years. There were four girls. Although six patients had a total of less than 20 seizures, one patient had had about 500 seizures. A typical history involved the patient being fully aware of sensory (burning/tingling) changes involving one foot and/or shaking of that limb before secondary generalization either immediately following or with independant generalized tonic‐clonic seizures. All patients underwent brain MRI scans (five on the 3‐Tesla machine) which were all normal. All patients also had at least one EEG. All were normal or had normal background. Two patients showed generalized spike wave epileptiform discharges (one with left temporal also) consistent with an idiopathic epilepsy. All patients are currently doing well. Conclusions: These seven patients appear to be have consistent histories of localization‐related epilepsy beginning with simple partial seizures involving one foot/lower limb. Their normal cognition and investigations as well as two “positive” EEGs and excellent prognoses would suggest that this may be a new, childhood idiopathic localization‐related epilepsy. Patients' clinical and investigation characteristics Patient Age (1st seizure) Sex Number of seizures Brain MRI EEG 1 4 F 500 N (3‐T) N 2 9 F 10 N (3‐T) N 3 11 M 8 N (3‐T) N 4 14* M 3 N (3‐T) Single GSW 5 13 F 10 N LT & GSW 6 14 M 15 N (3‐T) N 7 8 F 4 N N N = Normal; 3‐T = 3‐Tesla; *Previous febrile seizure; GSW = Generalized spike wave; LT = Left temporal. 1,2 Marian Majoie, 3 Marcel Punte, 4 Willem Berfelo, and 3 Silvia Evers ( 1 Neurology, Epilepsy Centre Kempenhaeghe, Heeze, Netherlands ; 2 Neurology, Research Institute Brain and Behavior, University Maastricht, Maastricht, Netherlands ; 3 Department of HOPE, University Maastricht, Maastricht, Netherlands ; and 4 Neurosurgery, University Hospital Maastricht, Maastricht, Netherlands ) Rationale: To evaluate long‐term cost‐effectiveness of Vagus Nerve Stimulation (VNS) in children with refractory epilepsy. Methods: The study presents a cohort design. Patients served as their own control. Measurements are taken before (baseline) and during treatment with VNS. Nineteen children are included with refractory epilepsy; they are not eligible for resective surgery. Data are collected for a period of thirty months. A sensitivity analysis is carried out. Results: The response rate of the cost diary was 95.74%. Within the category “healthcare costs,” the costs are significantly lower during the treatment with VNS in comparison with usual care costs. The total costs of the intervention are €11.576 for each patient. The seizure diary response rate was 100%. The number of seizures is significantly lower and dropped to an average of 422 per month, a decrease of more than 17%. The cost‐effectiveness ratio is 127. The results of this study show that the additional costs of the intervention are recuperated within 15 months. The results of the sensitivity analysis shows that the individual cost items have a marginal influence on the cost‐effectiveness ratio. Conclusions: The incremental cost effectiveness is expressed in a cost effectiveness ratio. This ratio is 127 which means that any suppressed seizure will cost €127,–when resulting from VNS. If the one time investment of €11.576,–(the total costs of the intervention) is divided by the cost reduction (€764,–per month), the additional costs of the intervention will be recuperated within 15 months. On the long run, the costs of VNS in children with therapy resistant epilepsy are lower as compared to the costs of usual care. (Supported by Epilepsy Center Kempenhaeghe; University Hospital Maastricht; Dutch National League against Epilepsy; Cyberonics (Webster, TX).) 1 Amy D. Malphrus, 1 Rebecca J. Schultz, and 1 Angus A. Wilfong ( 1 Baylor College of Medicine Department of Neurology, Texas Childrens Hospital, Houston, TX ) Rationale: Reflex epilepsy is defined as seizures that are objectively and consistently evoked by a specific afferent stimulus or by activity of the patient. The afferent stimuli or activity may be elementary or elaborate(1). Reflex seizures can be characterized by either focal or generalized seizures seizures. They are classified according to the precipitating stimuli(2). The commonest form of reflex epilepsy is seizures triggered by flickering light. However, numerous other triggers have been described including visual stimuli, flickering light, patterns, thinking, praxis, reading, somatosensory, eating, music, and startle. The prevalence is unknown but felt to be rare. We describe two patients with symptomatic epilepsy with seizures induced by eating with a spoon. Methods: Through the comprehensive epilepsy clinic, two patients were identified with reflex epilespy with a stimuli being a spoon. They were an 11 year‐old left‐handed male with a chromosome 15 duplication and MRI findings of frontoparietal periventricular white matter lesions and a 5 year‐old right‐handed male with lissencephaly type I. Results: One patient had EEG/video monitoring performed and revealed a seizure from the left central region while being fed with a spoon. Conclusions: Eating epilepsy is characterized by seizures closely related to one or several actions of eating, and the triggers are specific and stereotyped for each patient. The seizures are typically focal motor seizures and almost always related to a symptomatic epilepsy. The epileptiform activity seen on EEG is typically localized to temporolimbic structures or suprasylvian regions. Generalized EEG activity is rare. Many patients have seizures activated by combinations of stimuli. Patients with suprasylvian lesions may be triggered by other oral activities induced by proprioceptive or by somatosenosory stimulation. These patients are, also, more likely to report that they prevent seizures by altering the characteristics of the stimulus. (3) These two patients have a form of relex epilepsy induced by a combination of eating and the use of a spoon. Both had rapid habituation with only a transient reduction in seizures following a change in feeding utensils. Alteration of the stimulus did decrease the frequency of the events but only transiently. One patient with video EEG monitoring revealed a focal seizure onset. They are both poorly controlled with underlying symptomatic etiologies. 1 Warren T. Blume—Chair, Hans O. Lüders, Eli Mizrahi, Carlo Tassinari, Walter van Emde Boas, Jerome Engel, Jr. Epilepsia 2001 Sep; 42(9): 1212–8. “Glossary of Descriptive Terminology for Ictal Semiology: a report of the ILAE task force on classification and terminology” 2 Xue, LY, Ritaccio, AL American Journal of Electrodiganostic Technology 2006 Mar; 46(1): 39–48. “Reflex seizures and reflex epilepsy.” 3 Zifkin, BG, Andermann, F. http://www.ILAE.com Mar 29,2003. “Precipitating Stimuli for Reflex Seizures.” 1 Lobna Mansour, 2 Sherine M. Wagih, and 3 Dorria Salem ( 1 Pediatric ; 2 Nuclear Medicine ; and 3 Radiodiagnosis, Cairo University ) Rationale: Intractable epilepsy is defined as the persistence of seizures despite adequate trial of antiepileptic drugs with a minimum of two first line drugs either as monotherapy or in combination as appropriate to the epileptic syndrome. Rationale of the study: The aim of this work is to assess the role of ictal and interictal SPECT in evaluation of patients with intractable epilepsy & to compare the localizing value of SPECT imaging, for epileptic forci, with that of EEG, MRI and clinical seizune semiology. Methods: The study included 39 children (22 males and 17 females) who all had intractable epilepsy. All cases were subjected to full history taking, general and neurological examination, fundus exam, EEG, MRI brain, interictal Single Photon Emission Computed Tomography (SPECT) and ictal SPECT (for 13 cases). Results: Cases were classified into 2 groups: group A (23 patients with generalized epilepsy) and group B (16 patients with partial epilepsy). Myoclonic epilepsy was the most common subtype of seizures encountered and constituted (38.4%). Epileptic syndromes were described in 9 patients (23%): childhood absence (2 cases), Dravet syndrome (2), myoclonic astatic (1), Lennox‐Gastairt (1) and West syndrome (3) Neurocutaneous disorders were 5 cases; storage Weber S. (2), tuberous sclerosis (2) and NFI (1). It was found that in group A, the EEG was sensitive in detecting abnormalities in 78.2%, MRI in 39.1%, intercital SPECT in 56.5% While in group B, EEG was diagnostic in 75%, MRI in 81.2% and interictal SPECT in 87.5%. Ictal SPECT (13 cases) was localizing in 69.2%, interictal SPECT in 38.5%, MRI in 30.7% and EEG in 23.1%. Ictal SPECT was diagnostic and localizing in 4 of 8 cases (50%) in whom MRI was normal. Conclusions: Ictal SPECT was the most sensitive modality in detecting abnormalities in 76.9% compared to 69.2%, 38.5% and 46.2 with EEG, MRI and interical SPECT respectively. (Supported by: This study was carried out in the children hospital, Cairo University, Neuropediatric unit.) 1 Anthony Marmarou, 1 John M. Pellock, 1 Lori L. Davis, 1 Thomas E. Cason, 1 James P. Agnew, 2 Shlomo Shinnar, 2 Christine O'Dell, 3 Darrell V. Lewis, 4 Douglas R. Nordli, 5 L. Matthew Frank, 6 Dale C. Hesdorffer, 1,2,3,4,5,6in addition to the FebSTAT Study Team ( 1 Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA ; 2 Neurology, Montefiore Medical Center, Bronx, NY ; 3 Neurology, Duke University Medical Center, Durham, NC ; 4 Neurology, Children's Memorial Hospital, Chicago, IL ; 5 Neurology, Children's Hospital of the King's Daughters, Norfolk, VA ; and 6 Epidemiology, Columbia University, New York, NY ) Rationale: A Web‐based relational database management system (RDBMS) for electronic entry of paper Case Report Forms (CRFs) transmitted by 6 study centers were linked dynamically to a series of databases for prospective and retrospective cohorts (48.6% Female, 52.3% Caucasian, 41.1% Black, and 17.8% Hispanic with a median age of 16.7 months) of children experiencing febrile seizures. Methods: The FebSTAT study includes 5500 data elements. Included are demographics, neuropsychological scoring, MRI structural analysis, EEG clinical assessment, virology, genetics, medications, seizure start and stop, continuous intermittent seizure type and follow up data. A relational database allowing entry tracking and data reporting was designed utilizing enterprise database software residing on a Dell PowerEdge 350 server. Over 150 entity‐ relationship tables address form data and samples including error and submission tracking. All data transmissions were HIPAA compliant. Archiving and backups of the complete database are performed nightly. Results: The system promotes efficiency of personnel via the automation of tasks such as form, sample, and data error tracking. Status of data transmission and receipt can be viewed by the investigators and study coordinators. The system eliminates the need of personnel to manually re‐query outstanding data by using programmatic means (SQL) to re‐query on a preset schedule. The database reflects the most recent updates of information at all times, rather than obsolete or older data which can result from the manual entry of data updates by personnel. The system is capable of performing analysis to find trends such as persistently missed questions, study center performance and CRF design problems The query system for quality control has resulted in 0.30% error rate and of 2441 queries, only 53 (2.0%) remain unresolved. Conclusions: Despite the large number of variables, the FebSTAT database optimized for this study was achievable and allows easy access for analysis and study by the FebSTAT Investigators. (Supported by NINDS – R01 NS43209 Consequences of Prolonged Febrile Seizures in Childhood.) 1 Nadia M. McKenny‐Fick, 2 Colin D. Ferrie, 2 John H. Livingston, and 3 Richard G. Feltbower ( 1 Leeds Medical School, Leeds University, Leeds, West Yorkshire, United Kingdom ; 2 Paediatric Neurology, Leeds General Infirmary, Leeds, West Yorkshire, United Kingdom ; and 3 Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, West Yorkshire, United Kingdom ) Rationale: There is little published data on the expected duration of depressed consciousness following epileptic seizures. A previous study from our group found that median recovery time in children from epileptic seizures involving impaired consciousness was 43 minutes, with febrile seizures recovering more quickly (median 15 minutes). There was a trend for recovery time following symptomatic seizures to be longer than that following idiopathic and febrile seizures, but patient numbers were too small to demonstrate this conclusively. This paediatric prospective cohort study investigates recovery time following symptomatic seizures, compared to those of other aetiologies. Methods: Children aged 1–16 years presenting to two Accident and Emergency departments and paediatric wards in Leeds hospitals (United Kingdom), suffering a witnessed seizure in which consciousness was impaired, were studied. Hourly coma scores were performed, using the Modified Paediatric Coma Scale, until a score of 15 was reached. Seizures were classified as febrile, idiopathic, remote and acute symptomatic. Factors which affect recovery time were investigated using the Poisson Regression model (p < 0.05). Results: Data from 99 seizures suffered by 75 children (33 males) was obtained. Seizures were classified as: acute symptomatic seizures (n = 26); remote symptomatic (n = 49); and idiopathic (n = 24). Recovery in hours was significantly prolonged in those children (n = 40) receiving emergency antiepileptic medication, 4.66 ± 1.64–9.21 (median hours ± interquartile range) versus 1.0 ± 0.3–2.0 in those (n = 59) not receiving medication (95% confidence interval (CI) 1.11–1.68, p = 0.003). Acute symptomatic seizures took longer to recover (1.94 ± 0.2–9.12) than those of other aetiologies (remote symptomatic 1.5 ± 0.92–6.31, idiopathic 0.83 ± 0.3–2.68). When acute symptomatic seizures were compared with data for febrile seizures from our previous study (n = 59), recovery was significantly longer (0.3 ± 0.15–0.7, 95% CI 0.46–0.95, p = 0.024). Acute symptomatic seizures occurring in children with prior neurological abnormalities (acute on remote) took longer to recover than all other groups (4.0 ± 0.89–10.5). Age, sex, type and duration of seizure had no affect on recovery time. Conclusions: Symptomatic seizures take longer to recover than seizures of other aetiologies, particularly febrile seizures. The ‘acute on remote’ group has not been previously identified and warrants further investigation. It is recommended that a child who presents with a seizure and a fever, who has not fully recovered within 1 hour, should be investigated for an acute symptomatic aetiology. 1 Sabiha Merchant, 2 Cynthia Harden, 3 Ronald G. Crystal, 3 Stefan Worgall, 1 Gail Solomon, 2 Douglas R. Labar, 3 Neil Hackett, 4 Michael Kaplitt, 3 Dolan Sondhi, 4 Mark Souweidane, and 1 Barry E. Kosofsky ( 1 Pediatrics, Weill Medical College of Cornell University, New York, NY ; 2 Neurology, Weill Medical College of Cornell University, New York, NY ; 3 Genetic Medicine, Weill Medical College of Cornell University, New York, NY ; and 4 Neurosurgery, Weill Medical College of Cornell University, New York, NY ) Rationale: LINCL is a fatal, neurodegenerative, childhood, autosomal recessive lysosomal storage disease resulting from mutations in the CLN2 gene. The present study assesses EEG abnormalities before and 2 wk after therapy. Methods: Five subjects (2 female, 3 male, ages 3.5 to 6 yr, median 5.5) underwent direct CNS administration (2 × 1012 particle units) of AAV2CUhCLN2 through 6 burr holes. Sixteen channel video‐EEG recording was performed for 24 hours: 4 days prior to treatment and 14 days after treatment. Quantitative spike analysis was performed during wakefulness for 1 hr of each video‐EEG study by 2 readers unblinded as to treatment status. All subjects had a history of generalized convulsions. Results: The initial EEGs showed generalized moderate to high amplitude spike and wave discharges with maximum amplitude occipitally. The background was characterized by diffuse 3–5 Hz rhythmic activity. Features of normal sleep patterns were generally preserved. No patients had electrographic seizures while on monitoring. This EEG background did not change significantly when assessed 2 wk post‐gene therapy. The mean spike frequency over 1 hr in 5 subjects prior to gene therapy was 56.6 ± 15.5 (SD) and the mean spike frequency 2 wk after gene therapy was 38.8 ± 16.7 (SD; paired samples t‐test p = 0.006). Conclusions: Initial evaluation of the effect of AAV2CUhCLN2 on EEGs as assessed by quantitative spike analysis suggests a decrease of epileptiform discharges 14 days post‐vector administration. Longer follow‐up for assessment of the impact of gene therapy on clinical seizure occurrence is underway. (Supported by Nathan's Battle Foundation, Greenwood, Indiana.) 1 Avani C. Modi, and 2 Tracy A. Glauser ( 1 Pediatrics – Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH ; and 2 Pediatrics – Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH ) Rationale: Adherence to medical regimens is a significant problem for children with chronic illnesses and their families. The average estimate of non‐adherence is 50% to long‐term treatments. Non‐adherence estimates in pediatric epilepsy range from 14 to 43% based on the measurement method (e.g., self‐report, blood levels). However, these methods have proven to be unreliable compared to more objective electronic monitoring methods. The purpose of the current study was to document the course of adherence using MicroElectronic Monitoring System (MEMS) for pediatric patients with newly diagnosed epilepsy. Methods: Data collection is ongoing and to date, participants include six children with new‐onset epilepsy (M = 8.1 years; 50% females, 50% African American/33% Caucasian/17% Biracial) and their parents. Children were diagnosed with partial (50%), absence (33%), and non‐absence generalized (17%) epilepsy. Parents were asked to use the MEMS TrackCaps to assess daily medication taking to either carbamazepine or valproic acid. Results: Preliminary data regarding one‐month adherence indicated that “taking compliance” (number of doses taken/number of doses prescribed) ranged from 84.8 – 100% (M = 93%). Patients were adherent to their medications on 87.8% of days. Patients who were 90% adherent or higher appeared to have only 1–2 seizures after initiation of medication compared to patients who had multiple seizures with adherence rates lower than 90%. Longitudinal data over a 7‐month period will also be presented. Conclusions: Preliminary data suggest that one‐month adherence rates for children with new‐onset epilepsy, using an objective method of measurement, are significantly higher than what has previously been reported in the pediatric literature. Understanding the longitudinal course of adherence over time is important because it is likely that adherence rates will decrease over time. One important area of future research is to assess adherence and barriers to effective disease management for children with epilepsy in a longitudinal, systematic manner. (Supported by: Funding supported by an NIH T32 training grant (DK063929) and the Department of Pediatrics at Cincinnati Children's Hospital Medical Center.) 1 Lakshmi Nadiminti, 1 Deepa Sirsi, 2 Jeffrey M. Perlman, 1 Maurine A. Packard, and 1 Gail E. Solomon ( 1 Child Neurology, New York Presbyterian Hospital – Cornell, New York, NY ; and 2 Neonatology, New York Presbyterian Hospital – Cornell, New York, NY ) Rationale: Intracranial hemorrhage is the cause of neonatal seizures in 17% full term infants, and is more commonly seen following vaginal delivery assisted with forceps or vacuum extraction. However, only some infants with intracranial hemorrhage come to clinical attention. The etiology of the intracranial hemorrhage and the compartments involved determine the clinical presentation and outcome. Previous studies have identified that primary intraparenchymal hemorrhages are the site of bleeding resulting in the greatest proportion of physical and cognitive disabilities. Right temporal lobe hemorrhage and resulting apneic seizures in a full term neonate has been reported previously, but there are very few cases reported in the literature. We report 2 neonates with apneic seizures as the initial manifestation of temporal lobe hemorrhage. Methods: Retrospective record review of 2 full term male neonates with no significant perinatal complications who presented with apneic seizures and temporal lobe hemorrhage. Results:– One full term neonate presented on day 1 of life with episodes of apnea and desaturations. CT scan and MRI revealed a left temporal intraparencymal and extra‐axial hemorrhage with surrounding edema and a 4mm left to right midline shift. On day 2, conjugate eye deviation to the right was associated with the apneic events requiring intubation and mechanical ventilation. EEG monitoring demonstarted multiple left hemispheric seizures, which clinically corelated with apnea and rightward eye devation. Seizures resolved after phenobarbital was loaded and there were no further apeneic events. No specific etiology for the intracranial bleed could be determined on further imaging and coagulation studies. ‐ The second neonate presented on day 1 of life with episodes of cyanosis unrelated to feeding and on day 2 had multiple episodes of apnea and desaturations requiring bagging. He appeared well between episodes. MRI demonstrated a posterior right temporal lobe hemorrhage, with an overlying subdural hematoma, as well as a right sigmoid sinus thrombosis.Evaluation for hypercoagulable states was unrevealing. A clinical diagnosis of apneic seizures was made, phenobarbital was loaded, no further apneic episodes occurred. Subsequent continuous EEG monitoring showed slowing in the right hemisphere. Conclusions: Apnea as the sole manifestation of a seizure is rare. It is important to recognize that although uncommon, full term neonates may present with apneic seizures as the initial manifestation of either left or right temporal lobe intracranial hemorrhage. Continous EEG monitoring should be considered in a full term neonate with unexplained apnea. Early detection of seizures can lead to investigation into the etiology of the hemorrhage, facilitate prompt management, which may help reduce the degree of ensuing neuro‐developmenatl disablity. 1 Kathleen J. Nolan, 2 Carol S. Camfield, and 2 Peter R. Camfield ( 1 Class of 2008, Dalhousie University Medical School, Halifax, NS, Canada ; and 2 Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, NS, Canada ) Rationale: Basic research about Dravet Syndrome proves that this severe epilepsy is related to an SCN1A gene mutation; however, the effect of this syndrome on families has not been studied. We investigated how parents cope with and care for a child with Dravet syndrome, a catastrophic epilepsy with three distinct stages. Stage 1 begins in the first year of life with repeated episodes of febrile status epilepticus. Stage 2 starts in the second year with uncontrollable seizures of multiple types, behaviour problems, and developmental stagnation or regression. Stage 3 begins in adolescence with fewer seizures and developmental stability. Mortality is 10–15%. Methods: Participants were North American parents of children with Dravet syndrome: 24 parents participated in semi‐structured interviews and 17 completed “Impact of Childhood Neurologic Disability” (ICND) scales – a validated questionnaire assessing the impact of epilepsy on families in 4 domains: epilepsy, cognition, behaviour, and physical/neurological function. Children included 11 males and 13 females aged 2–24 years (mean = 10.2 y, SD = 5.7). Results: Stage 1: Stage 1 was the most difficult stage for parents (p = 0.03). Uncertainty about the diagnosis was the primary stressor. Seizure control was rated as worst during this time. Most parents (54%) recalled no positive experiences in caring for their child, and many negative interactions with health care. Stage 2: Seizure control was reported as slightly better in Stage 2 but remained the primary stressor (p < 0.001). Developmental stagnation and severe hyperactivity emerged. Impressive negative effects were noted on parents' relationships with family (38%), friends (63%), and spouse (54%). Parents tended to report more external coping mechanisms, such as support groups, friends, and family. Stage 3: Stage 3 brought improved seizure control (p < 0.001) but decreased cognitive level and worsening behavioral problems (p < 0.03). Parents reported increased social isolation and tended to rely on internal coping mechanisms, such as religious prayer, activities outside the home, and personal education about Dravet syndrome. Respite and relief care were extremely difficult to obtain at each stage. ICND scores at each stage mirrored the findings of the interviews. Conclusions: All three stages of Dravet syndrome present specific serious challenges for parents, based on interviews and a concurrent validated questionnaire (ICND). Seizures are persistent and severe but developmental, behavioral, and sleep issues add to the stress. In the absence of truly successful medical treatment, attention needs to shift toward helping families cope. Specific emergency protocols, assistance in locating respite care, and psychological or social work intervention for families may help. (Supported by summer student bursaries from Epilepsy Canada and Dalhousie University.) 1 Magda L. Nunes, and 1 Bianca H.B. Batista ( 1 Neurology, Pontificia Universidade Catolica do RS, Porto Alegre, Rio Grande do Sul, Brazil; and Neurology, Pontificia Universidade Catolica do RS, Porto Alegre, Rio Grande do Sul, Brazil ) Rationale: Sleep disturbances are a common complain among patients with epilepsy. Studies assessing the relationship between sleep and epilepsy during infancy are scarce. The purpose of this study was to evaluate sleep quality in children with epilepsy. Methods: Cross sectional study where two questionnaires regarding sleep quality, were applied to children with and without epilepsy. Data about sleep characteristics and epilepsy were also collected (type of seizure, epileptic syndrome, number of seizures, use of anticonvulsant drugs). Results: In the age group of children from 2 to 6 years old, we have observed that children with epilepsy have worst sleep habits than children without epilepsy (p < 0,05). Among the epilepsy group, children having nocturnal seizures present more frequently worse sleep habits when compared to the children with daytime seizures (p < 0,04). Children who use a single AED have better sleep habits than children with polytherapy (p < 0,01). As the delay of the neuropsychomotor development was worst, the frequency of the worst sleep habits were greater (p < 0,04). Children with epilepsy presenting an Engel score equal or greater than 7 have greater frequency of worst sleep habits when compared to children with better controled seizures (p < 0,001). Children with benign epilepsies present more frequently better sleep habits when compared to children with bad prognosis epilepsy (p < 0,04). In the group of children 7 to 14 years old, patients with epilepsy have a worst sleep quality when compared to the control group. In the group of children with epilepsy, the mean score of the questionnaire in patients with daytime seizures was lower than the group with nocturnal seizures (p < 0,001). There was no significant difference for the scores of the sleep questionnaires among the types of used drugs (p = 0,13); however, the comparison between monotherapy and polytherapy showed that the group under polytherapy had a greater score in the sleep questionnaire or worse sleep quality (p < 0,001). Children with epilepsy and neuropsychomotor developmental delay have a mean sleep score greater than children with epilepsy without delay (p < 0,001). We have observed a positive correlation among high scores of sleep questionnaire and high scores of the Engel scale (p < 0,001), meaning that patients with bad seizure control have worse quality of sleep. The analyses of seizure type showed worse quality of sleep in patients with generalized seizures (p = 0,04). Patients with severe epileptic syndromes have worse quality of sleep (p < 0,001). Conclusions: Our results showed that children with epilepsy presented greater incidence of sleep problems when compared to children without epilepsy. In the group of epileptic patients we observed that night seizures, polytherapy, developmental delay, refractory epilepsy, generalized seizures, and epileptic syndromes with unfavourable outcome were predictors for worse sleep quality. (Supported by CAPES.) 1 Dominique Parain, 2 Genevieve Demarquay, 3 Sylviane Peudenier, 4 Jean Luc Schaff, 5 Louis Vallée, and 6 Anne Lortie ( 1 Service de Neurophysiologie, Hôpital Charles‐Nicolle, Rouen, France ; 2 Unité d'Epileptologie, Hôpital Neurologique, Lyon, France ; 3 Unité d'Epileptologie, Hôpital Universitaire, Brest, France ; 4 Unité d'Epileptologie, Hôpital Universitaire, Nancy, France ; 5 Unité d'Epileptologie, Hôpital Universitaire, Lille, France ; and 6 Service de Neurologie, CHU Mère‐Enfant Sainte‐Justine, Montreal, Canada ) Rationale: Absence seizures may be seen in a variety of epileptic syndromes in childhood. Approximately 5–10% of the patients will have medically refractory seizures. Vagus nerve stimulation (VNS) Therapy may reduce the frequency of absence seizures in treatment‐resistant patients and/or improve their quality of life. Methods: 16 patients (9 males, 7 females) were treated with adjunctive VNS Therapy for medically refractory absence seizures. All patients had the diagnosis of childhood absence epilepsy. Mean age at implantation was 8 years (± 1.30; range, 6–12 years). Absence seizures were counted at baseline using 24‐hour EEG recordings. The same evaluation was repeated every 6 months after implantation during the follow‐up period of 18 months. Patients were treated with an average of 1.8 antiepileptic drugs (AEDs) per patient at baseline. No changes in AEDs were allowed. Results: There was a total seizure reduction of 31% after 6 months (p‐value = 0.0071; paired T test), 67% after 12 months (p‐value < 0.0001; paired T test) and 76% after 18 months (p‐value = 0.0156; Wilcoxon's paired signed rank test). Seizure reductions ≥ 50% were observed in 38% of the patients after 6 months, in 92% after 12 months and in 88% after 18 months of treatment. Three patients (18.7%) remained seizure free, and one patient (6.2%) showed no response to VNS Therapy at 18 months. Improvement in alertness (“better” or “much better”) was observed in 60% of the patients. Seizures became worse when stimulation stopped in one patient due to a lead break, and in two other patients due to end of battery life, with improvement after restauration of the stimulation. Conclusions: Adjunctive VNS Therapy was effective for the treatment of medically refractory absence seizures in this patient population, allowing a seizure reduction of 76% after 18 months. The percentage of patients showing seizure reductions increased over the 18 months of treatment. Alertness improved in 60% of the patients. These results are encouraging and worth further investigation. 1 Jorge G. Burneo, 1 Asuri N. Prasad, 2 Bradley Corbett, and 3 Xuelian Sang ( 1 Epilepsy Programme, University of Western Ontario, London, ON, Canada ; 2 Research Data Centre, University of Western Ontario, London, ON, Canada ; and 3 Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada ) Rationale: Epidemiological studies of childhood epilepsy are of importance to compare incidence and prevalence rates, age distribution, inheritance, seizure types, epilepsy syndromes and treatment strategies. Few data exist on the frequency and burden of childhood epilepsy in Canada and on the impact of childhood epilepsy in the general population. We assess the point prevalence of childhood epilepsy in Canada. Methods: We analyzed data from two cycles of the National Longitudinal Survey of Children and Youth (NLSCY, N = 17,832 for cycle 2, and N = 27,668 for cycle 2). Each cycle was done over a 2‐year period (cycle 2: 1996–1997, cycle 3: 1998–1999). The NLSCY captured, in a longitudinal manner, sociodemographic information, as well as age, sex, education, ethnicity, household income, and labor force status of participants since birth to 11 years old. The presence of epilepsy was probed by the use of specific questions in the survey. In the survey the following specific question was asked of the person most knowledgeable in the household. The answers were refered to conditions that have lasted or are expected to last 6 months or more. Does any of the children in the house have any of the following long‐term conditions that have been diagnosed by a health professional? The list of responses included “Epilepsy” and certain comorbid conditions (Allergies? Bronchitis? Heart condition or disease? Cerebral Palsy? Kidney Condition or disease? Mental handicap?). In addition, a subsequent question identified whether the condition was treated by means of a specific anticonvulsant medication.(Anticonvulsants or anti‐epileptic pills?). Prevalence was age‐adjusted by using national standard populations at the time of each survey. Results: In cycle 2, 35 of 17,832 subjects were described to have the diagnosis of epilepsy, yielding a weighted point prevalence of 3.67 per 1,000. In cycle 3, 59 of 27,668 children were described as having epilepsy, yielding a weighted point prevalence of 3.59 per 1,000. Relatively small sample sizes in the individual cycles precluded the calculation of rates stratifed by age, sex and socioeconomic variables. Conclusions: The overall results are in keeping with those obtained in other developed countries by using different ascertainment methods. We discuss methodologic aspects related to the ascertainment of epilepsy in both surveys, and to the validity and implications of our findings. (Supported by Department of Clinical Neurological Sciences, University of Western Ontario, Academic Development Fund (JGB).) 1 Rajesh RamachandranNair, 2 Jennifer Evans, 1 William Logan, and 1 Elizabeth J. Donner ( 1 Division of Neurology, Hospital for Sick Children, Toronto, Canada ; and 2 Division of Functional Neuroimaging, The Hospital for Sick Children, Toronto, Canada ) Clinical profile and f MRI activation pattern No Onset of Epilepsy years Duration years MRI Localization Areas of activation Anterior LI Posterior LI 1 15 0.25 L‐F DNET L‐F L‐IF,MF,MTG,STG,R‐MF,MTG +0.99 +0.8 2 6.5 2 L‐F Glioma L‐F L‐IF,MF,STG,MTG,AG,SMG,R‐IF,STG,MTG +0.92 +0.88 3 7 4 N L‐FC L‐IF,MF,STG,MTG,R‐IF,MF,STG,MTG +0.8 −0.93 4 9 1 L Hemi volume loss L‐Hemi L‐IF,MF,STG,MTG +1.0 +1.0 5 9 2 L‐T Glioma L‐T L‐IF,MF,STG,MTG,R‐IF,MF,STG,MTG +0.93 −0.66 6 3 6 L‐ Mesial Temporal Sclerosis L‐T L‐MF,STG,MTG,R‐IF,MF −0.39 +1.0 7 1 12 N L‐T L‐IF,MF,STG,MTG,AG,R‐IF,MF,STG,MTG +0.64 −0.16 8 15 1 L‐ T Gliosis L‐T L‐IF,MF,STG,MTG +1.0 +1.0 9 15.5 1 L‐T Glioma L‐T L‐IF,MF,STG,MTG +1.0 +1.0 10 3 8 L‐ F CD L‐F L‐IF,MF,STG,MTG,AG,R‐IF,MF,STG,MTG +0.59 +0.77 11 3 13 N L‐T L‐IF,MF,STG,SMG +1.0 +1.0 12 14 0.6 L‐T Ganglioglioma L‐T L‐IF,MF,STG,MTG,SMG,R‐IF,MF,STG +0.94 −0.23 13 9 7 L‐TO CD L‐TO L‐IF,MF,R‐IF,MF,STG,MTG −0.75 −1.0 14 13.5 1.5 R‐T DNET R‐T L‐IF,MF,MTG,STG,AG +1.0 +1.0 15 6 3 N R‐ Rolandic L‐IF,MF,MTG,STG,AG,SMG,R‐IF,MF,MTG,STG,AG,SMG +0.67 +0.06 16 0.25 14 R‐F CD R‐F L‐IF,MF,MTG,STG,SMG,R‐MF,MTG,STG,AG +0.79 +0.64 17 7 3 R‐ P CD R‐FP L‐IF,MF,STG,MTG,SMG,R‐IF,MF,STG,MTG,SMG +0.68 +0.34 18 12 2.5 R‐F Gliosis R‐F L‐MF,STG +1.0 +1.0 19 10 4.5 R‐T Cavernoma R‐T L‐IF,MF,STG, R‐MF +0.46 +1.0 20 12 5 R‐T Glioma R‐T L‐IF,MF,MTG,R‐MF +0.97 +1.0 Rationale: To study patterns of language representation in right handed (RH) children with refractory epilepsy using functional MRI (fMRI) Methods: 20 children with refractory epilepsy referred for language lateralization by fMRI completed 2 of 3 standardized block design language tasks (verb generation, fluency, object naming).Rregion of interest (ROI) analysis was applied to the task which produced activation of both anterior (frontal) and posterior (temporal) language areas using AFNI. An Asymmetry Index (AI) for anterior and posterior language areas was calculated (AI =−0.1 –+0.1; mixed dominance). Results: 9/13 children with left hemisphere (LH) seizure focus (SF) (Group A) and 4/7 with R‐hemisphere (RH) focus (Group B) had bilateral language activation. 6 children (46%) in group A had RH dominance; mean anterior AI +0.67, mean posterior AI +0.34 (p = 0.25). No children in group B had RH dominance. Mean posterior AI in group A did not statistically differ from the mean posterior AI in group B (p = 0.26). Neither age of epilepsy onset or pathology affected AI. Conclusions: Bilateral language activation was seen irrespective of the side of SF; however, only children with L‐SF had RH dominance. Posterior language area shifted more frequently than anterior area. Thus, while atypical patterns of language activity are common in this group of RH children with refractory epilepsy, true RH dominance was only seen in the presence of a left SF. 1 V. Reed, 1 M. Brunner, 1 R. Sälke‐Kellermann, 1 S. Novak, 1 J. Kröll, 1 M. Fuchs, 1 G. Krämer, and 1 H. Jokeit ( 1 Neuropsychology, Swiss Epilepsy Center, Zürich, CH, Switzerland ) Rationale: A high comorbidity between attention deficit/hyperactivity disorder (ADHD) and epilepsy has been noted in the literature. Prevalence rates and associations between type of epilepsy and ADHD are disputed. To estimate the need for better‐tailored health care, we screened pediatric outpatient admissions to the Swiss Epilepsy Center for possible ADHD using translations of the Conners' Parent Rating Scale – Revised (CPRS‐R) and, to assess a wider range of behavioral problems, the Strengths and Difficulties Questionnaire (SDQ). Our goal was to determine the frequency and severity of attentional disorders in referrals to our clinic. We also investigated type of epilepsy, age and gender as possible associated risk factors. Methods: Parents of children with epilepsy aged 4–16 were requested to complete both questionnaires. Inclusion criteria were: a diagnosis of epilepsy, no mental impairment, and fluency in German. All children underwent a neuropediatric examination with EEG. Epilepsy was diagnosed using ICD‐10 criteria. The SDQ is a screening questionnaire for 4 ‐16 year‐olds that assesses positive and negative behavioral attributes. The CPRS‐R rates 27 behavioral attributes relating to ADHD. We used a cut‐off of T score ≥ 66 in the CPRS‐R to indicate probable presence of ADHD and a score of ≥ 17 total difficulties score in the SDQ as abnormal. Results: Completed questionnaires were obtained from 51 patients. The most frequent reasons for exclusion were no epilepsy diagnosis (10%) and mental impairment (4%). The most frequent type of epilepsy was symptomatic epilepsy (45%), followed by generalized idiopathic epilepsy (10%). The mean age was 11.2 years with 27 females and 24 males. 29 children (57%) did not exceed the critical values in either questionnaire. 19 (37%) were above the cut‐off on the CPRS and 11 (22%) in both questionnaires, thus meeting strict criteria for the probably presence of ADHD. The two scales were moderately correlated (r = 0.526), with the CRS‐R being the more sensitive instrument. We found no correlation in either questionnaire with age, sex or type of epilepsy and critical scores. Conclusions: Parents' ratings of ADHD symptoms in their children were highly elevated as compared to base rates. We found 22% to meet strict criteria for probable presence of ADHD. The majority with critical CPRS values also scored in the critical range on the SDQ, suggesting a wider spectrum of behavioral problems than merely ADHD symptoms exist in this population. We found no effects of age or type of epilepsy on critical scores in either questionnaire. Whereas a sex bias in favor of males is found in non‐epileptic ADHD populations, we found no such association. Our findings of high rates of ADHD symptoms in children with epilepsy highlights the need for increased awareness of the comorbidity of these disorders as well as for targeted medical or psycho‐behavioral treatment. 1 Frank J. Ritter, 1 Jason Doescher, 1 Michael D. Frost, and 1 Mary Gustafson ( 1 Minnesota Epilepsy Group PA, Minnesota Epilepsy Group, St. Paul, MN ) Rationale: Levetiracetam is approved for the treatment of partial seizures in children age 4 years and older. We investigated the use of initial monotherapy in children 1 month to 8 years old. There is little know about the initial treatment in children, with regard to efficacy and tolerability. Methods: This is a retrospective chart audit of 20 children who were randomly selected from a larger group of children less than 10 years old, who were initially treated for epilepsy with levetiracetam monotherapy. Charts were reviewed for demographics, efficacy, and tolerability. Results: There were 13 males and 7 females, mean age 3.8 years, with a mean follow up of 2.1 years. All had partial onset with or without secondarily generalized seizures. Nineteen of 20 had abnormal EEG. The dose of levetiracetam was between 10 and 70 mg/kg/day. Sixteen (80%) were seizure free. Of these, 5 discontinued due to adverse behavioral side effects. Three of these 5 had adverse behavior with the next medication tried. Four did not gain seizure control with levetiracetam monotherapy, but were controlled with the next medication tried. Conclusions: Initial monotherapy with levetiracetam was an effective treatment for partial onset seizures in children. Additional controlled trials would be beneficial. 1 Rana R. Said, 1 Andrea V. Andrade, and 1 Susan Arnold ( 1 Pediatric Neurology, Epilepsy and Clinical Neurophysiology, University of Texas Southwestern Medical Center, Dallas, TX ) Rationale: Pseudoseizures are a well described clinical entity in adolesent and adult populations. However, little is know about etiologies, co‐morbity, and outcome of pseudoseizures in children less than 12 years old. Methods: Review of the Epilepsy/EEG database at Children's Medical Center at Dallas, revealed 12 children less than 12 years old with psychogenic non‐epileptic paroxysmal events. Chart review and review of EEG and Video‐EEG data was then done to assess age of onset, associated co‐morbidities, EEG patterns, MRI findings, and psycho‐social history. Follow‐up data was available on 11/12 children. Results: Of the twelve children identified, 6 were girls. Age of onset of non‐epileptic events ranged from 3.5 years to 11 years old (median 8 years old). 7/12 had a previous history of epilepsy and were on antiepileptic medications. One child was on Depakote for 5 years despite all events since onset likely representing non‐epileptic events. The most common semiology for this younger age group was staring ahead/unresponsive to verbal stimulation, all with a volitional component and apparent secondary gain. Less frequent patterns included myoclonic jerking (1/12), pelvic thrusting (1/12), generalized shaking (1/12) and focal right arm “waving” (1/12). In three of the 12 children, interictal EEG abnormaliteis were present, including focal discharges and generalized spike and slow wave discharges. In one child, both epileptic and non‐epileptic seizures were captured during a single 36 hour prolonged video‐EEG monitoring period. Significant psychosocial stressor were identified in nearly all children, with 2/12 having had recent sexual abuse, 3/12 associated with parental separation/divorce, 1/12 recently placed under Child Protective Services custody for maternal Munchausen by proxy, and the remainder having various other stressors including school bullying. Conclusions: Although likely less common than pseudoseizures in older children and adolescents, non‐epileptic seizures are not rare in the younger child, seen to occur in our series in children as young as 3.5 years old for secondary gain or with a volitional component. The most common semiology in the younger child appears to be more bland, with the majority demonstrating periods of staring/unresponsive to verbal stimulation. Psychologic/psycho‐social stressors must be thoroughly evaluated in the child to assist in management and treatment of pseudoseizures in this age group. 1 Justin C. Sanchez, 1 Zhao Liu, and 1 Paul R. Carney ( 1 Department of Pediatrics, University of Florida, Gainesville, FL ) Rationale: Surgical evaluation of intractable epilepsy often involves continuous intracranial subdural recording in which the goal is to determine the seizure onset zone. A difficulty with this approach is that the epileptologist must collect a sufficient number of seizures to evaluate if the patient is a candidate for resective surgery. Methods for interically identifying the seizure onset zone may shorten the phase 2 subdural monitoring and improve outcome. The goal of this research is to compare the interictal amplitude modulations of slow potentials, gamma, fast gamma, and neural ensemble activity for quantitatively locating the seizure onset zone. Methods: The subject participating in the study was undergoing extraoperative subdural grid evaluation for the treatment of intractable neocortical epilepsy. Multichannel subdural potentials were collected (IRB approved) while the patient was quietly awake. Neuronal activity indicated by the dashed box in Fig. 1 was recorded at 12 kHz and bandpass filtered from 1–6 kHz. To compare the seizure onset zone identification in multiple frequency bands, we define the amplitude modulation as the sum of the power of the ECoG voltage signal during interictal segments of recording (compared 10s‐60min). The seizure onset zone quantified was compared to the zone as determined independently by two certified pediatric epileptologists (PRC, ZL). Results: The amplitude modulations in the ECoG data indicates that the seizure onset zone demarcation is dependent upon the frequency band. Both the gamma bands presented similar regions of maximal amplitude modulations in electrodes 45, 46, and 47. The slow potential amplitude modulations were not as distinct but modulation was posterior and temporal to the gamma bands. Neural ensemble modulation indicating the activation of large neuronal networks presented in electrodes 49–52, 25–28, and were merging into the gamma onset zones. Conclusions: A direct correspondence was found between the quantitative analysis and the visually identified seizure onset zone. Clinically, this preliminary result indicates that analysis of brief (10s‐30min) ECoG recordings could potentially be used to make efficient recommendations for epilepsy surgery and could shorten phase 2 monitoring. Neurophysiologically, the primary seizure onset zone was most clearly defined by gamma and fast gamma activity implicating the potential role of dendritic activiy in ictogenesis. However, the spread of epileptic activity was primarily identified by the neural ensemble activity corresponding to the axonal output of cortical neurons. (figure 1) (Supported by Children's Miracle Network and Wilder ERC.) 1 Dewi V. Schrader, 2 Paul Steinbok, and 1 Mary B. Connolly ( 1 Division of Pediatric Neurology, University of British Columbia, Vancouver, BC, Canada ; and 2 Department of Surgery, University of British Columbia, Vancouver, BC, Canada ) 1 Patient 1 Patient 2 Patient 3 Patient 4 Age at seizure onset 1 Day 5 Months 9 Months 33 Months Gender Female Female Male Male Etiology Focal cortical dysplasia Focal encephalitis Focal cortical dysplasia Rasmussen's and cortical dysplasia Number of AED's prior to status 9 10 16 Nil (presented in status) Age at status epilepticus 1 day 6 years 19 months 33 months Duration of staus 45 days 14 days 30 days 2 months Medications for status Phenobarbital Phenytoin Nitrazepam ACTH IV Midazolam Propofol Lorazepam Chlormethiazole Oral AEDs IV Midazolam, Propofol, Ketogenic diet, Oral AEDs IV Midazolam Thiopental Steroids IVIG Ketogenic diet 14 other AEDs Surgery 1) Left frontal resection 2) Peri‐insular hemispherotomy 1) Left temporoparietal occipital resection 2) resection of the occipital pole 1) Multiple subpial transactions in the left motor cortex 2) Left frontal resection Left occipital resection Duration of follow up 7 years 6 years 1 year 10 months Seizure frequency Seizure free 5–6 seizures per month on one AED Seizure free on 2 AEDs Weekly seizures on 5 AEDs Rationale: Over the years, case reports in the literature have suggested that a small percentage of patients with status epilepticus of focal origin may be successfully treated with resective surgery. The most common etiologies in reported cases are Rasmussen's encephalitis, cortical dysplasia and hemimegalancephaly. Methods: We reviewed our epilepsy surgery database since 1992 for cases where urgent resective surgery was performed for medically refractory status epilepticus. Results: We reviewed a total of 205 surgeries for refractory epilepsy. Four patients had urgent surgery as treatment for refractory status epilepticus. Details of the study population are described in Table 1.The duration of status before surgery was from 14 to 45 days. MR imaging demonstrated cortical dysplasia in one patient, white matter abnormalities in another, and was normal in two. EEGs showed focal seizures originating from one hemisphere in three of the patients. In the patient with cortical dysplasia and Rasmussen's encephalitis, seizures were recorded independently from both hemispheres but arose most frequently from the left occipital area. Surgery was performed with the aim of terminating status. In follow up, three patients have developmental delay and one is making developmental progress. No patient had complications related to their surgery aside from the predicted neurological deficits such as hemiparesis. Conclusions: In our experience, the number of patients in true status epilepticus at the time of surgery was very low. Following surgery, three of four patients experienced resolution of status epilepticus and had a significant reduction in seizures; two patients were seizure free. In all cases, surgery provided a specific diagnosis that was invaluable in directing management. 1 Gregory B. Sharp, 3Andrea E. Van Lierop, 1 Rolla M. Shbarou, 2Mary E. Atherton, 1 Bassem H. El‐Nabbout, 1 Bernadette M. Lange, and 1 Cristian M. Ionita ( 1 Pediatrics, University of Arkansas Medical Sciences, Little Rock, AR ) Rationale: To evaluate the clinical efficacy and safety of levetiracetam as initial monotherapy for children with a diagnosis of new onset epilepsy. Methods: A retrospective review of medical records was performed to identify children up to 18 years who were given a new diagnosis of epilepsy and were treated with levetiracetam as initial maintenance therapy. Treatment was initiated between January 1, 2003 and October 1, 2005. All patients were initially evaluated by a pediatric neurologist at Arkansas Children's Hospital. Outcome was determined by review of the last clinic follow‐up and/or by telephone interview. The primary outcome measure was the achievement of seizure freedom for a minimum period of 6 months. Questions were asked concerning adverse effects during treatment with levetiracetam. Treatment was started following a single or prolonged seizure with electroencephalogram (EEG) findings supportive of a diagnosis of epilepsy, or following recurrent seizures with a supportive or normal EEG. Patients could have been treated with medications emergently for seizures prior to starting levetiracetam. Patients who had been treated previously with a maintenance antiepileptic drug were not included. Parents or caregivers were specifically asked if they had noted changes in behavior or other adverse events. Results: 82 children between the ages of 10 months and 17 years of age (mean 6.0 years) were identified who were treated initially with levetiracetam monotherapy for epilepsy. There were 46 males and 36 females. Seizure freedom was achieved for a period of at least 6 months in 70 patients (85.4%). Twelve patients were considered treatment failures due to peristent seizures in eight, or discontinuation of medication due to adverse effects in four (worsened behavior in 2, ataxia in 1, and rash in 1). The total dose ranged from 200 to 3000 mg per day and was divided bid. In the group with controlled seizures for a minimum of 6 months, the dose ranged from 10–36.9 mg/kg/day (mean 21.3 mg/kg/day). In the failure group, the dose ranged from 10.5–51.4 mg/kg/day (mean 25.0 mg/kg/day). There were no serious adverse events. Mild adverse events were reported in 24 patients (29.3%). Deterioration in behavior or mood was reported in 16 patients (19.5%). Behavioral problems resolved in 2 of 3 patients treated with pyridoxine, and in an additional 5 simply over time. Improved behavior was reported in one patient. Additional adverse events included sleepiness (1), dizziness (1), ataxia (1) and rash (1). Conclusions: Levetiracetam appears to be very effective and safe as initial monotherapy for children with epilepsy. Adverse effects are generally mild. Behavioral side effects were reported in almost 20% of patients, but only 2 patients discontinued the medication due to behavioral issues. Prospective evaluation of levetiracetam as monotherapy in children is warranted. 1 Silvia Vincentiis, 2 Clovis A. Silva, 2 Marilia Febronio, 2 Rosa Pereira, 3 Albertina Takiuti, 2 Maria Saito, and 1 Kette Valente ( 1 Psychiatry, USP, Sao Paulo, SP, Brazil ; 2 Pediatrics, USP, Sao Paulo, SP, Brazil ; and 3 Gynecology, USP, Sao Paulo, SP, Brazil ) Rationale: Female adolescents with chronic disorders have their sexual‐related issues ignored by health‐related professionals and parents.It is assumed that sexual concerns do not represent a concern for these individuals.However, recent studies showed that adolescents with chronic conditions become sexually involved as their peers.The objective of the present study was to evaluate and compare the sexual behaviors,sexual orientation and pregnancy rates in female adolescents with epilepsy, a chronic stigmatizing condition and compared with female adolescents with systemic lupus erythematosus (SLE),a visible and disabling disease,without stigma. Methods: A standard questionnaire was applied for consecutive 75 female adolescents,23 with epilepsy (G1) and 52 with SLE (G2), ages between 11 to 20 ys of age. All interviews were performed by the same physician with previous knowledge of the patients' clinical history and ancillary exams.Data regarding the 1st part of the questionnaire was obtained by direct interview addressing personal issues (social and economic class, age and schooling) and epilepsy data.The 2nd part of the questionnaire investigated gynecologic data (menarche,menstrual cycles,periodicity, dysmenorrhea,pregnancy,miscarriage,delivery,post‐partum and newborn children.The 3rd and 4th parts addressed sexual behavior information and counseling, respectively. Results: G1 mean age was16.1 ys and in G2 mean age was 16.17 ys. Both groups did not present statistical differences for their demographic data, except for socio‐economic‐educational level.Mean age for menarche was later in G2 (12.8 ys) compared to G1 (11.6 ys) (p = 0.016).Age of the first sexual intercourse was similar in both groups.Nine patients (39.1%) out of the G1 were sexually active whereas 12 in G2(23.1%) were likewise (p = 0.1534). Mean sexual intercourse frequency per month was 2.8 in G1 and 4.3 in G2. Libido was reported by 71.4% in G1 and 100% reported attained orgasm. In G2,66.7% had libido and 50% reported orgasm (p = 0.0436).Regarding counseling, 72.7% from G1 and 83.3% from G2 reported contraceptive use,although most without appropriate orientation.Seven girls (63.6%) in G1 had at least one previous pregnancy, while only one (8.3%) in G2 had been pregnant (p = 0.0094). Conclusions: Although epilepsy is a chronic albeit not visible disorder, it is stigmatizing to the patient. On the other hand, SLE is a chronic, debilitating disorder.Despite that, questionnaire applied failed to produce a statistically difference in sexual‐related behaviors between adolescents with lupus and epilepsy.Several sexual behavior landmarks were identical despite significant demographic social and academic differences. However, patients with epilepsy had a higher risk for unplanned pregnancies, suggesting that these patients have unmet counseling needs related to the stigma of this disorder. (Supported by FAPESP05/03527–3.) 1 Joan V. Skluzacek, and 2 Beverly S. Wical ( 1 Administration, IDEA League, Afton, MN ; and 2 Pediatric Neurology, Gillette Children's Specialty Healthcare, St. Paul, MN ) Rationale: Dravet syndrome is a devastating epileptic syndrome with onset very early in childhood. Major progress has been made in understanding the genetic foundation of the disorder; yet much work remains to identify co‐morbid conditions commonly associated with Dravet's. Appropriate care of affected children must include identification and management of these disorders to permit optimal health and enhance our understanding of the disorder. Methods: Dravet syndrome is a rare disorder that makes systematic study of associated conditions difficult. The Dravet syndrome/SMEI Group, a support group for parents with affected children, is associated with the International Dravet syndrome Epilepsy Action League (IDEA League). At the time of data collection in 2005, 65 families participated in surveys. Not all familes answered each question. Participation was voluntary. Questions were chosen by group leaders to investigate whether other children had been affected by problems similar to their own. Questions were asked regarding: immune dysregulation and susceptibility to infections; growth, metabolic or endocrine disorders; and autism spectrum disorder. Despite the uncontrolled nature of data collection, trends emerged that are suggestive of significant co‐morbid conditions occurring in the majority of children with Dravet's. Results: Of 61 respondents, 46 (75%) reported their children are prone to infection. Recurring/chronic otitis media, sinusitis, or bronchitis occurred in 50%. Fourteen of the 61 (23%) had been assessed by an immunologist, allergist, or infectious disease specialist. No child evaluated was found to have any specific immune deficiency. Thirty‐eight of 61 (61%) reported their children had been assessed for endocrine, metabolic or absorbtion disorders. Mitochondrial disorders NOS had been diagnosed in 4/61 (6%). All 61 reported their children have difficulty regulating body temperature. The majority of children (38/61–61%) are underweight. Autism spectrum disorder was of concern to 35 (78%) of the 44 that responded to questions about behaviors. Autism has been diagnosed in 24% of these children. An additional 49% of children have autistic traits. 100% have communication disorders. Conclusions: Intractable epilepsy, significant cognitive impairment, and movement abnormalities are well recognized in Dravet's Syndrome. Our preliminary data suggest aspects of the syndrome go well beyond these features. Careful investigation of associated disorders in immune regulation and infection is needed. Documentation of pattern of infections is needed to separate out a true increased incidence from an apparent increase (due to increased awareness of infection as seizure trigger). Growth and nutritional assessment should be part of each child's coordinated care. Specific evaluation for autism spectrum disorders seems indicated. Associated symptoms must be sought in a prospective way to facilitate understanding of the manifestations of this complex disorder. 1 Jürgen Sperner, 2 Ingrid Tuxhorn, and 3the German Pediatric VNS Study Group ( 1 Neuropediatric Department, University Clinic Schleswig‐Holstein, Lübeck, Germany ; 2 Betriebsstätte Krankenhaus Mara, Krankenhaus Bielefeld, Bielefeld, Germany ; and 3 Neuropediatric Department, University Clinic Schleswig‐Holstein, Lübeck, Germany ) Rationale: Pharmacoresistant epilepsy is a serious burden in approximately 20% of children with seizures. Nonpharmacologic, adjunctive treatments like the ketogenic diet and vagus nerve stimulation (VNS) Therapy are helpful, although our knowledge of their long‐term efficacy in children still remains limited. Methods: We evaluated the long‐term outcome (up to 24 months) of VNS Therapy in severely disabled children and adolescents with pharmacoresistant epilepsy in a multicenter, prospective, open label, non‐randomized trial. From a total of 156 patients (58% male), 90% had learning disabilities and 89% developmental delay. Median age at implantation was 10 years (range, 2.5–18), and 89 patients (57%) were younger than 12 years. Median age at onset of epilepsy was 1 year (range, 0–12). Median duration of epilepsy was 7.8 years (range, 1.6–18). Epileptic syndromes were diagnosed in 53% of the patients; acquired lesions in 23%; and genetic syndromes in 5%. Etiology was unknown in 19% of the patients. Before VNS Therapy, 60% of the patients were evaluated for epilepsy surgery, and 14% were operated (2 callosotomies, 17 lobectomies and 3 other types of epilepsy surgery). Patients were eligible after failure of at least 5 AEDs, and were evaluated at baseline and at 3, 6, 12 and 24 months after implantation. Efficacy and safety results, magnet use and quality of life (QoL) data were analyzed. Results: A total of 75 patients (48.1%) had 24 months follow‐up. Seizure reductions ≥ 50% occurred in 32% of the patients after 3 months, and in 51% after 24 months follow‐up (p = 0.01). Compared to baseline, there was a statistically significant seizure reduction at every follow‐up interval (p = 0.0001). In most cases, side effects were well tolerated and could be minimized by reducing pulse width or stimulation frequency. Between 8% and 12% of the patients reported that the magnet was “always” or “most of the time” effective in aborting or reducing the intensity and/or duration of their seizures. Decreasing magnet effects were observed over time, except in a small group of patients (10%) where constantly satisfactory magnet effects were reported. More than 50% of the patients had improvements in alertness. Conclusions: These results demonstrate the outstanding long‐term efficacy of VNS Therapy in this population of young and severely disabled children and adolescents with up to 24 months follow‐up. VNS Therapy was also well tolerated and associated with QoL improvements. 1 Tammy L. Still, 1 Jodie R. Niosi, 1 Neetu K. Singh, 1 Nancy Thornton, 1 Elaine C. Wirrell, and 1 Lorie D. Hamiwka ( 1 Pediatric Neurology, Alberta Children's Hospital, Calgary, AB, Canada ) Rationale: Witnessing seizures can be frightening for both onlookers and families. There is often a fear of death or permanent brain damage. The goal of this study was to explore the responses of families to a suspected first seizure event. Methods: A prospective cohort of 127 consecutive children with a probable first seizure referred the Alberta Children's Hospital between 01/01/2004 and 30/08/2005 were invited to participate in the study. One hundred and four families agreed. The database for the study was created prior to its initiation. Families were interviewed prior to the visit with the epileptologist and were asked open ended questions and their responses recorded. Information was documented with regards to: How parents felt at the time of the first seizure, where they went for information and the kind of resources they used, and their perceptions regarding the impact of the first seizure on the relationship with their child. Results: Seventy‐four percent of children were diagnosed with epileptic events, 24% with non‐epileptic events and in 2% the events were unclassifiable. Responses were similar between epileptic and non‐epileptic families. The majority of parents described their responses to their child's first seizure as “scared,”“terrified,”“panicked,”“helpless,” feeling “useless,”“confused,”“very upset,”“horrible,”“anxious,”“shocked,”“worried,”“frightened,”“stressed,” and “freaked out.” One third of the families did not seek further information after their child's event; 24 (23%) relied solely on oral or written information provided by health care providers (emergency physicians, family physicians, pediatricians, paramedics, and nurses), 11 parents (11%), relied on information from the internet, 4 (4%) used library and text books, and 8 (8%) asked family and friends. Twenty‐two (21%) used a combination of sources. Sixty‐seven (64%) of the parents reported that the relationship between the parent and child changed. Conclusions: A presumed first seizure is clearly an emotional event for families and onlookers. A significant proportion of families did not seek further information regarding their child's event. The most common single source of information for families is health care providers. Over two thirds of families reported providing closer supervision of their children and restriction of activities. 1 Richard Tang‐Wai, 1 Prakash Kotagal, 2 Ann Warbel, 1 Elaine Wyllie, and 2 William Bingaman ( 1 Neurology, Pediatric Epilepsy and Sleep Disorders, Cleveland Clinic, Cleveland, OH ; and 2 Neurosurgery, Cleveland Clinic, Cleveland, OH ) Rationale: There is limited experience with the use of bitemporal depth electrodes in children with refractory epilepsy. We report our experience in 10 children with temporal lobe epilepsy who underwent EEG monitoring with bitemporal depth electrodes to evaluate its role in seizure localization and correlate with information from other modalities. Methods: Patients were identified from the epilepsy surgery database and a systematic, retrospective chart review was carried out of children with temporal lobe epilepsy who underwent bitemporal depth electrode evaluation between 1990 and 2005. Variables analyzed included (1) patient age at initial seizure and at time of surgery; (2) post‐operative follow‐up period; (3) seizure semiology; (4) ictal and interictal findings on scalp EEG; (5) brain imaging; (6) the indication for depth electrodes; (7) depth electrode interical and ictal findings; (8) type of surgery performed; (9) surgical pathology; and (10) seizure outcome. Results: Ten children (6 females) underwent bitemporal depth electrode evaluation. Only 1 of these patients underwent a simultaneous subdural grid evaluation. Indications for invasive evaluation included: (1) evidence of bitemporal EEG seizure patterns without localizing seizure semiology (7 patients); (2) possible neocortical onset (1 patient); (3) EEG focus and lesion incongruence (1 patient); (4) non localizable EEG ictal pattern with a lesional MRI (1 patient). Nine children (ages 11–18 years) underwent focal resection: 8 had standard anterior temporal lobectomy with resection of mesial temporal structures. The post‐operative follow‐up period ranged from 3 months to 26 months (mean 14.6 months). Of these, 8 remain seizure free (Engel I) and 1 patient remains refractory (Engel IV). This latter patient had a normal MRI and was found to have a lateral temporal focus; he underwent surgical resection of the superior temporal structures. The patient who did not undergo surgery was found to seizures arising independently from either temporal region without clear side predominance. Six patients were found to have hippocampal sclerosis on pathology. Conclusions: Bitemporal depth electrodes are useful diagnostic tools for children with temporal lobe epilepsy and unclear seizure localizations. In conjunction with imaging data, their use has been successful in achieving excellent surgical outcomes in the pediatric population. 1 Silvia Vincentiis, 2 Clovis Silva, 2 Maria I. Saito, and 1 Kette D. Valente ( 1 Psychiatry, USP, Sao Paulo, SP, Brazil ; and 2 Pediatrics, USP, Sao Paulo, SP, Brazil ) Rationale: Knowledge obtained with women with epilepsy is used to understand adolescents with epilepsy (AWE). Therefore, it is assumed that AWE have decreased libido, more anovulatory cicles and higher infertility rates. The purpose of the present study was to analyze sexuality in AWE. We also intended to evaluate whether the counseling received by these patients met their needs. Methods: We included AWE, from 10 to 20 ys, with the diagnosis of epilepsy, according to ILAE guidelines. Patients were enrolled in a standard questionnaire. All interviews were applied by the same physician with a previous knowledge of the patients' epilepsy history and ancillary exams. Data regarding the first part of the questionnaire was obtained by direct interview addressing personal issues (social and economic class, age, schooling) and epilepsy data. The second part referred to gynecologic data, such as age of menarche, menstrual cycles, periodicity, dysmenorrhea, pregnancy, miscarriage, delivery, post‐partum and newborn children. The third and fourth parts consisted of a self‐applicable questionnaire, addressing sexual behavior information and counseling, respectively. Results: Twenty‐four AWE were enrolled in this study. The mean age was 15.9 ys. Epilepsy onset occurred during adolescence in 18 (75%) and in 6 (25%) during childhood. Four (15.3%) had focal symptomatic epilepsy, 15 (57.7%) focal cryptogenic and 5 (27%) had idiopathic generalized epilepsy. Sixteen (61.5%) patiens were under monotherapy. Mean age of menarca was 11.7 ys. Eight (32%) patients had irregular menstrual cycles. Eleven patients (42.3%) used folinic acid. Nine (34.6%) AWE were sexually active. Mean age of the first intercourse was 14.6 ys. Seven (77.7%) AWE had an unplanned pregnant and in 3, it was recurrent. Two patients became pregnant during the study.Miscarriage occurred in 2.A suspected abortion occurred in 1 patient.One newborn had a post‐natal death. Regarding counseling, school was responsible for orientation for sexual activity and contraception in 8 cases (30.7%) and gynecologists in 3 (11.5%). One patient was guided by the neurologist and another by a health professional. Contraceptive methods were used by 8 patients, only 4 with appropriate guidance. From the contraceptive methods used: 7 patients used preservative in all intercourses, 1 used preservatives sporadically and none used oral contraceptives. Seven (26,9%)AWE received no counseling. Conclusions: Adolescents with epilepsy have active sexual life, despite their disease. As a result, they suffer consequences from an unconcealed sexual activity with unplanned pregnancies. It is interesting that these patients have more access to physicians than normal adolescents. However, they have less counseling, which is probably related to the fact that patients with chronic diseases are assumed as non‐sexually actives. Sexual aspects and contraception requires special attention by the specialists attending adolescents with epilepsy. (Supported by FAPESP05/03309–6.) 1 Roy Wade, and 2 Richard P. Morse ( 1 Department of Pediatrics and Neurology, Dartmouth Medical School, Hanover, NH ; and 2 Department of Pediatrics and Neurology, Dartmouth‐Hitchcock Medical Center, Lebanon, NH ) Rationale: Pyridoxine dependent seizures are rare, with fewer than 150 cases reported worldwide. The diagnosis has been difficult to confirm and has required a challenge‐rechallenge approach in the past. Recently the genetic basis has been described as well as biochemical markers that may be used to confirm the suspected diagnosis in the newborn period. In the literature of this rare disorder, seizures are often described as generalized tonic‐clonic. Methods: We report a case of confirmed pyridoxine‐dependent seizures in a newborn and an analysis of the seizures with video‐EEG correlation. We describe the confirmation of the diagnosis by measurement of serum pipecolic acid. Results: The infant's clinical presentation was dominated by early onset irritability/encephalopathy within a few hours of delivery, and seizures which began at 22 hours of life. Seizures were described as generalized tonic‐clonic by the neonatologists but on close analysis of video‐EEG were either R or L‐sided during clinical clonic seizures. In addition to clonic seizures, the infant had myoclonic, “shuddering” events associated with generalized EEG discharges but these too had a hemispheric predominance. The baby had a rapid resolution of the encephalopathy with a single dose of pyridoxine 50 mg. Diagnosis was confirmed by measurement of serum pipecolic acid. Conclusions: Pyridoxine‐dependent seizures are a rare occurrence and are described in the literature as generalized tonic‐clonic events in the majority of infants. Close analysis of video‐EEG suggests that these are not generalized tonic‐clonic seizures but partial seizures. Encephalopathy is an underemphasized feature and may obscure seizures or precede them. Rapid and reliable diagnosis can be accomplished with measurement of serum markers for the disorder, which remain elevated even after treatment. Genetic testing will be available in the near future as well. Outcome can depend on early identification and treatment and a low threshold for an empiric trial of pyridoxine in neonatal seizures should continue to be our practice. 1 Ozge U. Soyuer, 2 Guzide Turanli, 2 Dilek Yalnizoglu, 2 Emel E. Bakar, and 2 Meral Topcu ( 1 Deptartment of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey ; and 2 Deptartment of Pediatrics, Section of Pediatric Neurology, Hacettepe University Medical Faculty, Ankara, Turkey ) Rationale: This prospective study was performed to classify absence seizures in childhood with respect to seizure semiology and epilepsy syndrome, and evaluate treatment and outcome. Methods: Patients were referred to our pediatric neurology clinic with a diagnosis of absence epilepsy based on clinical and/or EEG features. Initial evaluation included detailed history obtained from parents, physical and neurological examination, and routine EEG, followed by video‐EEG monitoring, neuroimaging, and psychometric analysis. Patients were followed up at 1, 3, 6 and 12 months after initiation of antiepileptic drug (AED) treatment. Results: 32 patients were studied. Age at initial symptom ranged between 10 months‐15 years 5 months (mean: 8 years 9 months ± 4 years 1 month). Age at the time of diagnosis ranged between 5 years 2 months‐15 years 6 months. Neuroimaging studies were available in 30 patients, 29 patients had MRI (9 were abnormal) and one had CT. Psychometric analysis was available in 17 patients and showed normal IQ results; they did not show a significant difference at follow up. Video‐EEG monitoring was available in 23 patients; a total of 202 ictal recordings were obtained. 25 patients had typical absence seizures (TAS); they were classified as childhood absence epilepsy (n:8), juvenile absence epilepsy (n:10), juvenile myoclonic epilepsy (n: 3), eyelid myoclonia with absences (n:2), perioral myoclonia with absences (n:1), diffuse epileptic EEG with eye closure (n:1). The remaining 7 patients without TAS were diagnosed with symptomatic/cryptogenic absence epilepsy (n: 6) and benign epilepsy with centrotemporal spikes (n:1). 27 patients were followed for 1–17 months (mean:7,8 months), 5 had shorter follow‐up periods. One patient showed poor compliance and dropped out of study at 6 months. Otherwise all patients with TAS were reportedly seizure‐free and showed EEG improvement. 19 patients were started on an AED for the first time, others received add on therapy. 53.1% of the patients were on valproate, 34.4% were on ethosuximide, 9.4% were on lamotrigine, and 3.1% were on clobazam. Conclusions: Clinical evaluation, including history, physical examination, and routine EEG along with neuroimaging studies, provide major clues in the diagnosis of absence epilepsy. However video‐EEG monitoring with ictal recordings are essential for precise subclassification of patients with absence seizures. Correct classification of seizures and epilepsy syndromes are crucial in determining treatment plans and prognosis. (Supported by the Hacettepe University Research Fund (01 G 010, PI: Meral Topcu). D.Y. is supported by NIMH ICORTHA Fogarty International Center Mental Health and Developmental Disabilities Research Training Program (D43TW05807) at Children's Hospital Boston, PI: Kerim M. Munir.) 1 Mi‐Sun Yum, 2 Jung Kyo Lee, 3 Su Jeong You, 4 Deok‐Soo Kim, and 1 Tae‐Sung Ko ( 1 Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea ; 2 Department of Neurosurgery, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea ; 3 Department of Pediatrics, Epilepsy Center, Inje University College of Medicine, Sang‐gye Paik Hospital, Seoul, Korea ; and 4 Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea ) Rationale: In spite of multiple treatment modalities, the outcome has been known as very poor in Lennox‐Gastaut syndrome patients. We have tried callosotomy in pediatric Lennox‐Gastaut syndrome and Lennox‐like syndrome patients and have got successful outcomes. But some patients showed no response. We analyzed the preoperative EEG, pathologic findings and extent of callosotomy in order to identify any relationship with the postoperative outcome of seizure. Methods: We retrospectively reviewed 26 patients (19 male patients; mean age at callosotomy, 6.8 years) who were managed as Lennox‐Gastaut syndrome (n = 22) and Lennox‐like syndrome (n = 4) at Asan Medical Center from Apr.1993 to Dec, 2005. All the patients had multiple seizure types and mental retardation. The EEG shows generalized spike and slow waves (GSSW) or general paroxysmal fast activities (GPFA) in patients of LGS and intermittent multi‐focal spike discharges (IMSD) in patients with Lennox‐like syndrome. All of them were refractory to antiepileptic drugs or ketogenic diet. Pre‐ and post‐callosotomy seizure counts were obtained from monthly diary annotation by the family or caregivers at 1, 6 and 12 months. Results: Seizure freedom over 1 year was noted in 6 patients of 26 patients (23.1%). Mean seizure reduction rate at 1, 6 and 12 months were 74.8%, 62.2%, 58.4% respectively. The existence of family history of epilepsy, abnormal findings on brain MRI, past history of infantile spasms or febrile convulsions had no effect on seizure outcomes after callosotomy. In preoperative EEGs, 19 of 26 patients (73.1%) had generalized slow spike and wave discharges, and others have only GPFA or IMSD. Patients with GSSW discharges achieved significantly better post‐operative seizure outcomes at 1 month follow‐up (p < 0.05). But no outcome difference was observed between these groups at 6 and 12 months' outcomes. The patients with total callosotomy showed better seizure reduction than patients with partial callosotomy, but the difference did not reach statistical significance (p > 0.05). Conclusions: Though we had got relatively successful outcomes after callosotomy in LGS and Lennox‐like syndrome patients, we could not find any predictive indicator for better final surgical outcomes. The existence of GSSW in preoperative EEG may predict immediate postoperative outcomes only. Further studies should be required to know the predictive factors for post‐callosotomy outcomes in LGS patients. 1 Guojun Zhang, 1 YogendraSinh H. Raol, and 1,2 Amy R. Brooks‐Kayal ( 1 Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA ; and 2 Pediatrics and Neurology, University of Pennsylvania, Philadelphia, PA ) Rationale: Development of spontaneous seizure following prolonged status‐epilepticus (SE) is age dependent and a number of molecular and morphological changes occur following SE have been suggested to contribute to development of spontaneous seizures. Astrogliosis is one such prominent feature of epileptic brain and may play an important role in epileptogenesis. In the present study, we assessed the effect of prolonged SE induced at different ages on GFAP mRNA expression in dentate gyrus (DG). Methods: SE was induced in P10, P20 and adult rats using either lithium/pilocarpine (Li/Pilo) or kainic acid (KA). One, seven and 21 days after SE induction, rats were sacrificed and GFAP mRNA expression was examined in acutely dissected DG using antisense RNA amplification (aRNA) technique. Results: GFAP mRNA expression in DG was increased 3 fold in the adult rats 7 days after Li/Pilo‐induced SE and remained high at 21 days. In P20 rats, GFAP mRNA expression was increased 2 fold 1 day after SE and 3 fold 7 days after Li/Pilo or KA induced SE. In contrast, in P10 rats, GFAP mRNA expression did not change at any time point (1 and 7 days) studied following KA induced SE. Conclusions: This study shows that GFAP mRNA expression in DG after SE is age dependent but not model specific. Further, as increase in GFAP occurs prior to and in association with development of epilepsy after SE, these findings support the hypothesis that astrogliosis may be related to epileptogenesis. (Supported by NIH NS38595 to ABK.) 1 Sameer M. Zuberi, 2 Rachael Birch, 2 Louise Conlin, and 2 Susan A.R. Stenhouse ( 1 Fraser of Allander Neurosciences Unit, Royal Hospital for Sick Children, Glasgow, Scotland, United Kingdom ; and 2 Duncan Guthrie Institute of Medical Genetics, Royal Hospital for Sick Children, Glasgow, Scotland, United Kingdom ) Rationale: Mutations in the SCN1A gene are associated with severe myoclonic epilepsy in infancy (SMEI) and several related epilepsy phenotypes commencing in early infancy. These infantile epilepsies are typically refractory to standard anti‐epileptic medication (AED) and may result in an epileptic encephalopathy with progressive cognitive impairment. Syndrome specific reports have suggested three medications or combinations which may be helpful. These are sodium valproate and topirimate, the bromides and stiripentol. Certain medications may exacerbate symptoms such as myoclonus. In November 2005 a service looking for mutations in SCN1A was established in our institution. Our aim was to determine if knowledge of a child's mutation status influenced prescription patterns. Methods: This service was available in Scotland at inception and UK wide in May 2006. SCN1A has 26 exons (7848bp) which are amplified in 40 fragments. A pre‐screen is performed using Conformational Sensitive Capillary Electrophoresis (CSCE) and fragments containing apparent changes are sequenced. A detailed pre‐test questionnaire helps us to attempt a syndromic classification. A joint molecular genetic and paediatric epileptology report is issued. Results: To date we have tested and reported on 51 casese of infantile onset epilepsy and selected parents. To date all 5 cases of classical SMEI have identified mutations. 1/2 cases of SMEB have mutations and one child with a focal epilepsy has a mutation. All mutations are de novo. 5 individuals have had their medication altered as a result of the analysis. There is clinical improvement in 3 to date with reduction in seizure frequency and increased levels of alertness. Follow up is too short to comment on call cases. Conclusions: Identification of a mutation not only allows a family of a child with a devastating epilepsy to begin to understand why their child is affected but also allows consideration of medication changes both specific additions and withdrawals. Appropriate medication can reduce seizure frequency, potentially ameliorating the epileptic encephalopathy therefore reducing the acquired learning disability. This may be particulaly relevant to the young infant with suspected SMEI and frequent seizures who does not yet fulfill all the syndrome criteria. Prospective studies are ongoing with the use of the detailed questionnaire to determine phenotype and target testing to the most appropriate cases. (Supported by: Muir Maxwell Trust purchased the gene sequencer used for the analysis.) 1 Ebru A. Dogan, 1 Rengin Bilgen, 1 Burcu Ekmekci, and 1 Berrin Aktekin ( 1 Neurology, Akdeniz University School of Medicine, Antalya, Turkey ) Rationale: To assess the effectiveness, tolerability and side effects of oxcarbazepine (OXC) in adult epilepsy patient population. Methods: A total of 194 (108 male, 17–81years) patients, 139 new‐onset epilepsy, were studied. The demographic variables, reasons and date of OXC administration and/or cessation of the drug, dosages and seizure outcomes (total seizure freedom, partial improvement or poor seizure control) were recorded. The approximate follow‐up period was 25.6 months (minimum 3, maximum 144 months). Mean administered dose of oxcarbazepine was 951.03 ± 349 miligrams. 164 patients (84.5%) received OXC as monotherapy and 30 patients (15.5%) were add on a second antiepileptic drug because of poor seizure control despite maximum tolerable dose of first antiepileptic drug. Patients were divided into 3 subgroups; symptomatic, cryptogenic and unclassified. Symptomatic group consisted of ischeamic or hemorrhagic cerebrovascular diseases, central nervous system infections (menengitis/meningoencephalitis), intracerebral tumours, cortical development abnormalities, mesial temporal sclerosis and post‐traumatic etiologies. 116 patients (59.8%) were in the symptomatic group, 67 patients were in the cryptogenic group (34.5%) and 11 patients were in the unclassified group (5.7%). Results: When the efficacy is considered; total seizure remission was achieved at 149 patients (76.8%), number of patients with > 50% seizure decrease was 29 (14.9%), number of patients with partial remission was 8 (4.1%) and number of patients with no response was 8 (4.1%). OXC dosage was decreased or ceased at 29 patients for several reasons. Reasons for cessation were; symptomatic hyponatremia (n = 3), liver enzyme abnormalities (n = 7), severe anaflactic reactions (n = 2), intolerability of the patient due to dizziness, somnolans, nausea and/or vomitting (n = 7), additional medication need for concomittant medical problems which may interfere with OXC (n = 4) and pregnancy (n = 6). Conclusions: OXC provides a remarkable efficacy for seizure control or significant improvement with ignorable and rare side effects. 1 Mohammad S. Al‐Humayyd ( 1 Pharmacology, College of Medicine, Riyadh, Central, Saudi Arabia ) Rationale: The objective of this study was to characterize the pharmacokinetic profile of carbamazepine (CBZ) in adult Saudi epileptic patients in order to improve on dosing schedules. Methods: One hundred and fifty two steady‐ state serum CBZ concentration measurements were collected during normal routine care of 76 patients receiving CBZ (100–1000 mg/day) in monotherapy. Steady‐ state trough CBZ serum concentrations, CBZ dosing history and associated information were collected prospectively. Data were analyzed by the non‐ linear mixed‐ effect modeling (NONMEM) technique with a one‐ compartmental model of first‐ order absorption and elimination. The apparent clearance (CL/F) and apparent volume of distribution (V/F) and their inter‐individual variabilities were estimated using the program. Results: The population estimates for clearance (CL; modeled independently of dose) and volume of distribution were 12.6 ± 0.5 l/h and 535 ± 40 l, respectively. However, CL increased as a function of dosing rate and consequently was modeled as a linear function of steady‐ state concentration. In order to validate these results, the predictions of the population model were tested against data from 14 further patients subjected to the same inclusion criteria but who were not included in the original analysis. The predictions were good, being unbiased (p = 0.29), and had an average deviation from the observed values of 16%. Conclusions: The observed covariate regression model reasonably predicted concentrations in the separate validation Saudi patient data set. The correlation between CBZ clearance and patient‐ specific characteristics may thus allow dosage adjustment to be made to achieve target steady‐ state plasma concentrations. (Supported by: This study was funded by King Saud University (KSU), Riyadh, Saudi Arabia. Ethical clearance permission to conduct this study was obtained from the Ethics Committee of the College of Medicine, KSU and written consent was obtained from all patients.) 1 Luis Almeida, 2 Amílcar Falcão, 1 Joana Maia, 1 Manuel Vaz‐da‐Silva, and 1 Patrício Soares‐da‐Silva ( 1 Department of Research and Development, BIAL (Portela & Ca SA), S Mamede do Coronado, Portugal ; and 2 4Health Limited, Cantanhede, Portugal ) Rationale: Eslicarbazepine acetate (ESL), formely known as BIA 2–093, is a new CNS‐active drug currently in development for the treatment of epilepsy and bipolar disorder. This study aimed to investigate the steady‐state pharmacokinetics of ESL once‐daily (qd) and twice‐daily (bid) regimens in healthy subjects. Methods: Single centre, open‐label, randomised, crossover study in 12 (6 males and 6 females) healthy volunteers. The study consisted of 8‐day treatment periods separated by a washout period of 10–15 days. On each treatment period, the volunteers received either an oral dose of ESL 900 mg qd or ESL 450 mg bid. Results: ESL was extensively and rapidly metabolized to eslicarbazepine (S‐licarbazepine, BIA 2–194), the main active metabolite. Plasma levels of the parent drug (ESL) were systematically below the limit of quantification of the assay. Following the last dose of the 8‐day ESL 900 mg qd and 450 mg bid regimens, the eslicarbazepine pharmacokinetic parameters are presented in Table 1. 1 Eslicarbazepine pharmacokinetic parameters following ESL 900 mg qd and ESL 450 mg bid Dosage regimen Cmax (ng/mL) tmax (h) AUCτ (ng.h/mL) t1/2 (h) ESL 900 mg qd 22210 (7257) 3.0 (1.5–4.0) 294019 (58364) 9.12 (1.19) ESL 450 mg bid 16667 (3981) 2.0 (1.0–2.0) 142080 (25933) 9.17 (1.49) Cmax– maximum observed plasma concentration; tmax – time to Cmax; AUCτ– are under the curve of plasma concentrations versus time during the dosing interval (24 h and 12 h in case of the qd and bid regimens, respectively); t1/2 – apparent elimination half‐life. Results are expressed as arithmetic means with the corresponding standard deviations (SD) in parentheses. tmax values are median with range values in parentheses The rate of systemic exposure to eslicarbazepine, as assessed by Cmax, was 33% higher following ESL 900 mg qd in comparison with ESL 450 mg bid. Extent of systemic exposure to eslicarbazepine during a 24‐h interval, as assessed by comparing the AUCτ of the ESL 900 mg qd regimen (AUC0–24h) with 2 times the AUCτ of the ESL 450 mg bid regimen (2 x AUC0–12h), was 3% higher following ESL 900 mg qd in comparison with ESL 450 mg bid. Incidence and characteristics of treatment‐emergent adverse events or drug‐related adverse events were similar with both treatment alternatives. Conclusions: The extent of exposure to eslicarbazepine during a 24‐h interval was similar following ESL 900 mg qd and ESL 450 mg bid regimens, but the rate of exposure was 33% higher following ESL 900 mg qd in comparison with ESL 450 mg bid. Tolerability was similar between qd and bid regimens. (Supported by BIAL (Portela & Ca SA).) 1 Shahram Amina, 1 Ignacio Pita, and 1 Mary Ann ( 1 Comprehensive Epilepsy Program, Neurologic Institute, University Hospitals of Cleveland, Case Western Rerserve University, Cleveland, OH ) Rationale: Levetiracetam (LEV) is an antiepileptic drug (AED) with many advantages such as high safety margin, broad spectrum seizure activity, and simple pharmacokinetics. It has nearly 100% bioavailability with peak absorption about 1.3 hours post dose, insignificant protein binding and renal excretion. Current recommendations are to begin LEV at 1000 mg per day in divided dose and increasing 1000 mg/day every two weeks. A recent study starting LEV at 500 mg bid for one day and increasing to 1000 mg bid the next day, found efficacy on the second treatment day correlating with serum concentration. Single doses of LEV in healthy volunteers showed linearity of plasma‐time curves over a range of 500 mg −5000 mg. A single 1,000 mg dose achieved peak concentrations of 31 μg/mL, within the steady‐state range common for the treatment of epilepsy. We have investigated the effects of a1500 mg loading dose of LEV in epilepsy patients on the epilepsy monitoring unit (EMU), who needed adequate AED therapy prior to discharge, and ICU, where they were undergoing treatment of status epilepticus, for tolerability and efficacy. Methods: Patients were given LEV 1500 mg PO or via NG tube with serum concentrations checked two hours after load. Patients were monitored for mental status changes and adverse effects. Additionally gender, weight, height, and creatinine were noted. Post loading EEG was compared to the baseline in all cases. Results: Twelve epilepsy patients, 10 women and 2 men, 18–92 years old (Mean 54 y/o) have been studied. Three were being treated for status epilepticus in the ICU and nine on the EMU for rapid reinstitution of AEDs. Only one patient was previously on LEV. Eleven received oral loading and one ICU patient received loading via NGT. Two hours post loading dose, all patients achived a serum concentration common to the treatment of epilepsy. Serum concentration ranged from 12.8 to 41.2 μg/mL (Mean 31.7; STD 10.4). Weight ranged from 43–146 kg (Mean 84 kg; STD 29). A morbidly obese patient weighing 146 kg (IBW 70 kg) also received LEV via NGT and had a two hour serum concentration of 23 μg/mL. All patients in the EMU were alert before and after load and reported no adverse events. No patients on the EMU had any seizure within 24 hours after load. LEV was well‐tolerated in the ICU patients hemodynamically. All were obtunded prior to addition of LEV. Conclusions: Our data suggest that serum concentrations of LEV typical for the treatment of epilepsy may be obtained rapidly and safely after a 1500 mg loading in adults with epilepsy. These data also suggest that oral loading may be used to hasten discharge from the EMU or as adjunctive therapy in status epilepticus though additional study is needed. Loading dose also achieved a therapeutic level in morbid obesity consistent with the high water solubility of the drug. 1 Gennaro Barbato, 1 Pasquale Alfieri, 1 Rossana Arlomede, 2 Giacomo Visco, and 3 Annamaria M. Terracciano ( 1 Neurologia, ASLNA1, Napoli, Napoli, Italy ; 2 Neurologia, ASLNA5, Sorrento, Napoli, Italy ; and 3 Neuropsichiatria, Clinica SantaMaria Del Pozzo, Somma Vesuviana, Napoli, Italy ) Rationale: Epilepsy in the elderly is often cryptogenic and the seizure occor without a defined provoking factor or a remote or current neurological pathology clinically or instrumentally evident.Aim of this open label trial is to evaluate the efficacy and safety of low doses of Levetiracetam as monotherapy in elderly patients with cryptogenic epilepsy. Methods: 14 patients more 60 years old (mean age 68 years) with newly diagnosis of cryptogenic epilepsy have been enrolled in the study, with at least 2 seizures before entering the study. 10 out 14 had CPC, 4 out 14 had GTCS. 8 patients received 1000 mg/die (500 × 2) of LEV starting with 250 mg/die for a week, uptitrared of 250 mg of everyweek up to 1000 mg/die; 6 patients received 2000 mg/die. Every 3 months all patients performed a visit to access efficacy and safety through neurological examination,seizure diary,EEG,complete blood test, MMSE,SF12,NPI. 8 patients suffered from hypertension, 4 patients fron diabets and 2 osteoporosis. Results: After follow‐up of 12 months all patients were seizure free: 8 patients at 1000 mg/die and 6 patients needed for a higher dose(to 2000 mg/die). After LEV treatment, all patients showed an improvement in quality of life as the level of autonomy and relationships is increased. LEV was well tolerated without any interaction with others concomitants treatments. Sonnolence,dizziness,headache,agitation and irritability, all mild and temporary(few days). All patients completed the Study. Conclusions: Levetiracetam as monotherapy showed a good efficacy and safety for Cryptogenic Epilepsy in the Elderly,even at low doses,without interactions with others concomitant therapies and without persistent side effects. 1 Michel J. Berg, and 1 Robert A. Gross ( 1 Strong Epilepsy Center, University of Rochester School of Medicine, Rochester, NY ) Rationale: Issues surrounding the substitution of generic anti‐epileptic drugs (AEDs) in the US are not fully understood. In addition, current experiences of US physicians have not been thoroughly examined. Here, views of patients and physicians toward generic substitution of AEDs and insights into physicians' current experiences across the US are reported. Methods: Online‐based surveys were carried out with 550 adult patients diagnosed with epilepsy and 606 physicians treating epilepsy from the US. Results: The efficacy of generic AEDs was a concern to 75% of physicians and 65% of patients. The vast majority (90%) of physicians agreed that generic substitution of a controlled patients' regular, effective AED may cause the onset of breakthrough seizures. Fully 65% of physicians reported that they had had a patient experience a breakthrough seizure caused by a switch from a branded to a generic AED. Additionally, one‐third (34%) of patients think that substitution with a generic AED is linked to breakthrough seizures. Almost two‐thirds (62%) of patients surveyed and 75% of physicians surveyed were aware that pharmacists may substitute a branded AED for a generic without physician consent. But less than half (43%) of physicians were aware of mandatory generic substitution laws for branded prescription medications. Eighty‐one percent of patients and 87% of physicians agreed that the pharmacist should only be able to substitute an AED with a generic with physician consent. Half (53%) of physicians surveyed would be uncomfortable prescribing a generic medication to treat their patients' epilepsy. Over half of physicians (64%) and patients (57%), in general, prefer generic AEDs if there were a potential cost savings. Among those surveyed, fewer physicians (52%) and patients (44%) were concerned about efficacy of generic medications for acute care. Concerns about safety of generic AEDs existed amongst 56% physicians, compared with 40% for generic acute care medications. Ninety‐four percent of patients would require at least a small amount of education or counseling from a healthcare professional if they were to switch their current AED for a generic. Conclusions: Both patients and physicians are concerned about the efficacy and safety of unrestricted generic AED substitution and nearly two‐thirds of physicians reported that they had a patient experience a breakthrough seizure due to generic substitution. However, generic substitution practices are not well‐understood by patients or by physicians. Physicians and patients recognize the cost savings of generic AEDs, but the perception that generic drugs are less effective may outweigh the cost benefit in many cases. The findings raise questions about the value of mandatory generic substitution requirements for medications with narrow therapeutic windows, such as AEDs. (Supported by GlaxoSmithKline.) 1 Jean M. Bidlack, and 2 Harold H. Morris III ( 1 Pharmacology and Physiology, University of Rochester, Rochester, NY ; and 2 Neurology, University of Vermont, Burlington, VT ) Rationale: To correlate the appearance of phenobarbital (PB) withdrawal seizures in a patient with a decrease in the number of GABAA receptors (GABAR) seen during PB withdrawal in PB‐dependent rats. Methods: A patient, seizure‐free for three years following removal of a cavernous angioma of her right anterolateral temporal lobe, had been taking PB for 11 years before surgery and was maintained on PB 150 mg/d for 3 years after surgery. The patient had a baseline of one psychic aura every two weeks. The decision was made to taper PB and to replace it with a non‐inducing anti‐epileptic drug. The patient kept accurate daily records of auras and seizures on a long‐term continuous basis. Results: A gradual reduction of PB was started and lamotrigine (LTG) slowly titrated, but typical complex seizures occurred when PB taper reached 60 mg/d. Conversion to LTG failed because of rash. PB was increased back to 90 mg/d and levetiracetam (LEV) was initiated and titrated to a dose of 500 mg BID. PB was then reduced by 15 mg every three weeks. When the patient was on PB 45 mg/d and LEV 500 mg BID, the frequency of auras increased, and LEV was increased to 750 mg BID. Seizures appeared when the patient was on PB 30 mg/d and LEV 750 mg BID. During the first week after PB was stopped and the patient was on LEV 1000 mg BID, there were 4 seizures. The seizures continued for 3 weeks after PB was stopped. After this time, there were no additional seizures and the dose of LEV remained constant at 1000 mg BID. The patient experienced anxiety and insomnia during the slow PB taper. Conclusions: This case demonstrates a “threshold” for PB withdrawal seizures at 45 to 60 mg/d and cessation of withdrawal seizures following PB discontinuation. At a dose of PB 90 mg/d, the patient had a plasma PB level of 11 mcg/ml. Assuming clearance did not change, withdrawal seizures appeared when the PB level was 5–8 mcg/ml. Withdrawal seizures were not controlled by LEV but ceased three weeks post complete withdrawal. Our data are explainable by a “resetting” of her GABAR. (3H)Muscimol binding to GABAR in rat brain homogenates was reduced by 25% in withdrawing animals for up to 10 days after chronic PB exposure (Tanaka et al., 1991). Similarly, there was a decrease in the α1 subunit of the GABAR in rat pups that had been exposed to PB for 30 days (Raol et al., 2005). Attenuation in the number of GABAR during PB withdrawal may account for the presence of PB withdrawal seizures in a patient who had been seizure‐free. Termination of the withdrawal seizures may be associated with a resetting of the levels and types of GABAR. (figure 1) 1 Leonilda Bilo, 2 Roberta Meo, 1 Patrizia Ruosi, 1 Maria Fulvia de Leva, 3 Roberto De Simone, and 1 Salvatore Striano ( 1 Epilepsy Center, Department of Neurological Sciences, Federico II University, Naples, Italy ; 2 Neurology Outpatients Service, Azienda Sanitaria Locale Napoli 1, Naples, Italy ; and 3 Department of Neurological Sciences, Federico II University, Naples, Italy ) Rationale: The aim of this study was to evaluate efficacy and safety of levetiracetam (LEV) in patients with epilepsy and chronic liver disease. Methods: Eleven patients with epilepsy and chronic liver disease entered the study. Eight suffered from Focal Epilepsy and three from Generalized Epilepsy. Liver disease consisted of HCV‐related epatopathy in 6 cases (2 of whom had cirrhosis), HBV‐related epatopathy in 4 (2 of whom with colesthasis) and porphyria cutanea tarda in 1. At study entry all patients were already treated with antiepileptic drugs (AEDs) in mono‐ or polytherapy; all had uncontrolled seizures. In all patients LEV was initially given as add‐on therapy, with a slow titration. Contemporarily, the associated AED treatment was slowly reduced, resulting in complete withdrawal in 3 cases. A laboratory work‐up, including blood count and evaluation of liver function, was serially performed during titration and follow‐up; seizure frequency was also serially evaluated, considering as baseline frequency the mean seizure frequency reported in the 6 months preceding study entry. Results: Three patients dropped out of the study because of adverse effects (2 patients, with drop out during titration) or because of adverse effects and worsening of seizures (1 patient, during follow‐up). All the remaining 8 patients were responders to LEV treatment in add‐on or monotherapy, with a >50% reduction of seizure frequency in 6 cases and complete disappearance of seizures in 2. None of these 8 patients showed worsening of liver function during follow‐up. In all these patients follow‐up lasted at least 12 months. Conclusions: With the limitations due to the small number of patients, our study suggests that LEV may be a good choice for epileptic patients with liver disease. Due to the absence of liver metabolism, LEV can be employed in high dosages, resulting in improved seizure control without liver toxicity. 1 Eric Bourne, 1 Kevin Nanry, 2 Herndon Harding, 1 James Graham, 1 Jeremy Roberts, and 1 Robert Leadbetter ( 1 Psychiatry, GlaxoSmithKline, RTP, NC ; and 2 Psychiatry, Florida State University, Winter Park, FL ) Rationale: The current analysis evaluated changes in weight and body‐mass index (BMI) in patients treated with lamotrigine in the presence and absence of concomitant valproate or antipsychotics. Methods: A post hoc analysis was conducted from a prospective, open‐label study of lamotrigine in 1175 patients with bipolar I disorder designed to assess the rate of rash in patients with or without specific dermatological precautions. Lamotrigine was administered for 12 weeks, including a 5‐week titration period (target dosage 200 mg/day). Weight and BMI was measured at baseline, week 5 and week 12 visits. Results: Baseline weight was statistically significantly higher in patients taking concomitant valproate versus without (199.1 ± 49.07 versus 184.7 ± 47.53 lb, p < 0.0001) and was statistically significantly higher in patients taking concomitant antipsychotics versus without (192.7 ± 47.31 versus 186.1 ± 48.48 lb, p < 0.05). Statistically significant changes in weight were not observed between treatment groups. Weight changes from baseline to week 12 were −0.2 ± 6.82 lb with valproate, 0.0 ± 8.40 lb without valproate, −0.4 ± 7.99 lb with antipsychotics, and 0.0 ± 8.14 lb without antipsychotics (p > 0.05 for all group comparisons). Statistically significant changes in BMI were not observed between treatment groups. BMI changes from baseline to week 12 were 0.0 ± 1.07 with valproate, 0.0 ± 1.41 without valproate, −0.1 ± 1.34 with antipsychotics, and 0.0 ± 1.34 without antipsychotics (p > 0.05). Conclusions: These results are consistent with previous findings that lamotrigine is weight neutral in patients with bipolar disorder and suggest that lamotrigine may be given to patients with concomitant medications that are frequently associated with increased body weight without causing additional weight gain. (Supported by GlaxoSmithKline.) 1 Richard Brannegan, 1 Serge J.C. Pierre‐Louis, and 2 Arthur Evans ( 1 Division of Neurology, Stroger Hospital of Cook County, Chicago, IL ; and 2 Department of Medicine, Stroger Hospital of Cook County, Chicago, IL ) Rationale: After FDA approval of once‐a‐day DepakoteER for the treatment of epilepsy, the pharmacy at our county hospital stopped carrying delayed release Depakote(DR). Since the majority of our adult epilepsy out‐patients obtain their medications at no cost from the hospital pharmacy, a cohort of patients were switched from Depakote(DR) to DepakoteER in a relatively short period of time. We monitored this group prospectively for changes in seizure frequency, medication adverse effects and preparation preference and now report those findings. Methods: At the patient's index visit, we obtained data on seizure frequency over the previous 6 months, as well as information about possible medication side effects (fatigue, GI upset, hair loss and weight change). Patients completed a scored 20 item questionaire about the effect, if any, of hand tremor on various daily activities and were asked to copy an Archimedes spiral. The patient was weighed. At this initial visit, Depakote(DR) was switched to DepakoteER (with an approximately 20% increase in total dose). The same information was obtained at 3 and 6 month follow‐up visits. Change in seizure frequency was analyzed using the Wilcoxon signed‐rank test. Before and after questions concerning specific side effects were analyzed using McNemar's test. Spirals were graded on a 1 to 5 scale (best to worst) by 2 trained, blinded raters. The pateints were asked which Depakote preparation they preferred and what schedule they actually used for DepakoteER. Results: Forty seven patients were enrolled. Thirty eight completed all 3 visits, 5 completed 2 visits and 4 were lost to follow‐up after the initial evaluation. There was no significant change in seizure frequency in the 6 month period following the switch to DepakoteER (a non‐significant trend for improvement in seizure frequency was observed, P = 0.08). Concerning side effects, before and after questions about fatigue, GI upset and hair loss indicated no change (p > 0.2) after the switch to DepakoteER. There was no significant weight change at 6 months (p = 0.4). Scoring of Archimedes spirals showed no significant change at 3 or 6 months. The questionaire about hand tremor in various activities showed significant improvement at 3 (p = 0.03) and 6 (p = 0.05) months using the paired T‐test. Most patients (62%) preferred DepakoteER but more than a quarter used it more than once daily (10 twice, 2 three times a day). Conclusions: DepakoteER was as effective as Depakote(DR) for control of seizures. Side effect measurements were unchanged except for improvement in patients' perception of hand tremor in daily activities. Most patients preferred DepakoteER, though some continued to use BID or TID dosing. (Supported by Abbott Laboratories.) 1 Martin J. Brodie, 2 Pedro Gonzales, 1 Graeme J. Sills, 2 Stuart Parks, and 2 David Keating ( 1 Epilepsy Unit, Division of Cardiovascular & Medical Sciences, Western Infirmary, Glasgow, Lanarkshire, United Kingdom ; and 2 Electrodiagnostic Imaging Unit, Gartnavel General Hospital, Glasgow, Lanarkshire, United Kingdom ) Rationale: This study was designed to differentiate between retinal dysfunction associated with vigabatrin (VGB) therapy and non‐specific visual field defects in people with treated epilepsy. Methods: A total of 204 people with epilepsy were grouped according to antiepileptic drug therapy as follows: current VGB treatment (n = 56), previous VGB treatment (n = 49), current GABAergic treatment (no VGB exposure; n = 46) and current non‐GABAergic treatment (no VGB exposure; n = 53). Groups were matched for age, sex, seizure‐type, and seizure frequency. All patients underwent wide‐field multifocal electroretinography (WF‐mfERG)1, logMar visual acuity testing, colour vision assessment, static perimetry (Humphrey) and ISCEV standard electroretinography. Results: When assessed by static perimetry, bilateral visual field constriction was observed in 33 current‐VGB patients (59%) and 21 of the previous VGB group (43%). However, clinically significant abnormalities were also demonstrated in 24 patients (24%) with no prior exposure to VGB. Assessment of retinal function by WF‐mfERG revealed abnormal responses in 25 current VGB patients (48%) and 11 previous‐VGB patients (22%), but none (0%) of the patients with no exposure to VGB. By way of comparison, 21 VGB‐exposed patients (20%) demonstrated visual field abnormalities with no associated retinal dysfunction, whereas only 3 patients (3%) had demonstrable retinal dysfunction with no apparent visual field problems. Unlike with visual field abnormalities, the incidence of retinal dysfunction segregated according to median VGB drug load (dysfunction, n = 31, 9012g versus no dysfunction, n = 40, 5065g; p = 0.0035). There was no difference between groups in terms of visual acuity, colour vision and standard electroretinography assessments. Conclusions: Visual field abnormalities are common in the treated epilepsy population, irrespective of drug history. Bilateral concentric visual field constriction may be a surrogate clinical marker of the neuroretinal toxicity associated with VGB use, but its assessment by conventional static perimetry is neither sufficiently sensitive nor specific to reliably identify all affected individuals. Patients with current or previous exposure to VGB should be considered for WF‐mfERG, which is more likely to reflect retinal toxicity associated with vigabatrin usage. (Supported by a research grant from the Chief Scientist Office, Scotland.) 1 Joyce A. Cramer, 2 Nancy A. Brandenburg, 3 Montserrat Vera‐Llonch, 3 Gerry Oster, and 4 Xiao Xu ( 1 Psychiatry, Yale University School of Medicine, West Haven, CT ; 2 Pfizer Inc, NY, NY ; 3 PAI Inc, Boston, MA ; and 4 Covance Inc, Gaithersburg, MD ) Rationale: To examine the perceived impact of seizure versus selected medication adverse effects (AE) in patients with partial‐onset epilepsy. Methods: A cross‐sectional survey was conducted with 201 adult patients with partial‐onset epilepsy receiving 2+ antiepileptic drugs (AEDs) and with 1+ seizure in the past year. Patients were asked to rate their health state by recording a number from 0 (worst) to 100 (best) based on their health today, hypothetical health if they were to experience a seizure today, and hypothetical health if they were to experience selected AEs today (incoordination, diplopia, dizziness, fatigue, weakness, headache, nausea, sleepiness, poor concentration, anomia). Decrements in health rating (HLTH) with a seizure today or an AE today were calculated as change from HLTH today. To contrast the relative impact of having a seizure to an AE, differences in decrements related to each AE (SZ‐AE) were calculated. Higher positive SZ‐AE values indicate a greater perceived decline in health status associated with experiencing a seizure; negative SZ‐AE values indicate the AE negatively impacts health status more than a seizure does. Analyses were based on seizure frequency and recency. Results: Overall health status ratings declined as seizure frequency increased (mean (SD) HLTH: once/6–12 months 76.2 (18), once/1–3 months 73.3 (20), 1+/week 65.6 (21); p = 0.01). Mean (SD) perceived decrements in HLTH with a seizure were greatest for patients with the least frequent seizures (once/6–12 months 37.3 (29), once/1–3 months 30.2 (27), 1+/week 21.2 (23); p = 0.001); as well as for seizure recency (last seizure 4+ months ago 36.8 (28), 1 week‐3 months ago 33.5 (30), within the past week 21.4 (20); p = 0.004). Perceived decrements in HLTH associated with having a seizure compared to experiencing an AE (SZ‐AE) differed significantly (p < 0.05 except for incoordination and weakness) across seizure recency groups. Among patients with last seizure 4+ months ago SZ‐AE ratings were 10.1 – 27.0, implying perception of a new seizure was much worse than an AE; with last seizure 1 week‐3 months ago SZ‐AE ratings were 1.3 – 9.3, implying perception of seizure was somewhat worse than an AE; and with seizures within the past week SZ‐AE ratings were −3.2 to −10.4, implying AE symptoms were more troublesome than seizures. Conclusions: Lack of seizure control is associated with decrements in health status. Patients perceived the effects of seizures and AEs differently. Patients with the least recent seizures may be most concerned with maintaining seizure control, while patients with more recent seizures are more sensitive to AED side effects, perhaps because their seizures remain uncontrolled. Our findings should help healthcare providers understand the risk‐benefit concerns of patients when addressing the efficacy and AEs of AEDs. (Supported by Pfizer Inc.) 1 Alan Gevins, 2 Kimford J. Meador, 1 Linda K. McEvoy, 2 David W. Loring, 3 Patty G. Ray, and 1 Brynn M. Evans ( 1 San Francisco Brain Research Institute, SAM Technology, San Francisco, CA ; 2 Department of Neurology, University of Florida, Gainesville, FL ; and 3 Medical College of Georgia, Augusta, GA ) Rationale: The relative cognitive and neurophysiological effects of levetiracetam (LEV) and carbamazepine (CBZ) are uncertain. Methods: This study compared the effects of LEV and CBZ using a randomized, double‐blind, two‐period crossover design in healthy adults. Mean (SD) maintenance doses and blood levels were: LEV mean dose = 2000mg/day (0), LEV mean blood level = 32 mcg/ml (11); CBZ adjusted by blood level to a mean dose = 564 mg (110); CBZ mean blood level = 7.5 mcg/ml (1.5). The results of the primary outcome measures (i.e., 33 variables from 11 standard neuropsychological tests) have been previously reported in abstract form. In this abstract, we report the results of a cognitive neurophysiological test (CNT) of working‐ and episodic memory which included measures of EEG/EP, cognitive performance, and subjective effects (22 variables). Testing was done at screening, baseline pre‐drug treatment, end of each maintenance phase (4 weeks), and end of each washout period after drug treatment. Results: 28 adults (mean age = 33; range = 18–51 years) completed the study. Relative to LEV and non‐drug, CBZ produced both subjective and cognitive performance impairments. In addition, CBZ produced an increase in low frequency (<10Hz) EEG power and changes in ERP measures. Linear discriminant analysis revealed 100% sensitivity and specificity for detection of CBZ relative to either LEV or non‐drug conditions using EEG neurophysiological measures; detection was less accurate when using neuropsychological variables from the CNT or from the original full neuropsychological battery. Conclusions: CBZ produces more untoward neuropsychological and neurophysiological effects than does LEV at the dosages and timeframes employed in this study. EEG neurophysiological measures improve detection of these effects. (Supported by: The cognitive neurophysiological component of this study was supported by a grant from the National Institute of Neurological Diseases and Strokes to Dr. Gevins. The drug administration and neuropsych testing was supported by a grant from UCB Pharma to Dr. Meador.) 1 Michele M.F. Feleppa, 1 Pompilio P.D.C. De Cillis, and 1 Gennaro G.E. Esposito ( 1 Neurosciences, Hospital “G. Rummo,” Benevento, Benevento, Italy ) Rationale: Levetiracetam (LEV) is a well‐tolerated antiepileptic drug used worldwide as an adjunctive treatment in adult patients with partial‐onset seizures. Its efficacy and tolerability were demonstrated in some pivotal clinical studies (1–2), and can be safely initiated at 2,000 mg daily without a titration period (3), but little data exist regarding its use in status epilepticus(SE). Methods: We describe a case of refractory SE requiring 9 days of pharmacological coma with subsequent excellent neurological recovery after adjunctive nasogastric LEV. On December 29th, 2005, a 25‐years old man with SE presented to hour hospital. He had endotracheal intubation and admitted to the emergency unit. SE showed partial crisis as clonic and mioclonic crisis and tonic‐clonic crisis. The patient had a post‐surgery panhypopituitarism for craniopharyngioma and he had never had any convulsions. The treatment protocol started with midazolam 0.2 mg/kg/hour/die e.v. and phenobarbital (PB) 100 mg i.m. SE didn't stop and the day after PB was increased at 200 mg daily. On January 3th, midazolam was substituted with propofol 1 mg/ml i.v., PB was reduced at 100 mg/daily and sodium valproate (sVLP) 25 mg/Kg/daily i.v. was added but without success, so on January 5th, 2006, PB was stopped and nasogastric LEV 1000 mg three times daily, without titration, was added. Results: The patient showed a dramatic recovery when nasogastric LEV was added and while EEG performed on day 4th, showed polyspike‐wave complex on left temporo‐central‐occipital derivations combined with slow activity and burst‐suppressions of short duration (Fig.1a), EEG performed on day 11th, showed low amplitude polyspikes on left fronto‐central derivations (Fig. 1b) and EEG updated on day 40th, showed no epileptiform activity (Fig. 1c). CT scan performed on day 10th (Fig. 1d), and MRI performed on January 3th, 2006 (Fig. 1f) and on January 27th, 2006 (Fig. 1g), showed no differences compared by an MRI performed on june 2005 (Fig. 1e). Conclusions: For our knowledge this is the first case of 3000 mg daily, without titration, nasogastric LEV treatment of refractory SE resistant at midazolam iv plus PB im and sVLP iv, at propofol iv plus sVLP. In fact only the LEV 3,000 mg daily added via nasogastric stopped dramatically status epilepticus. No significant adverse events were noted. In this case‐report we showed that levetiracetam as add‐on, had a rapid protection against clonic and mioclonic seizures. We conclude that adjunctive LEV should be considered for patients with status epilepticus unresponsive to initial therapy. (figure 1) 1 Lauren C. Frey, 1 Laura A. Strom, 1 Archana Shrestha, and 1 Mark C. Spitz ( 1 Neurology, University of Colorado Health Sciences Center, Denver, CO ) Rationale: Specific withdrawal syndromes have been well‐documented following the cessation of treatment with many drugs that affect the central nervous system, including barbiturates, benzodiazepines, tricyclic antidepressants and selective serotonin reuptake inhibitors. Studies have investigated withdrawal symptoms associated with some of the older antiepileptic drugs (AEDs), but the existence of withdrawal syndromes associated with newer AEDs, including lamotrigine, has not yet been investigated. Methods: We reviewed the medication profiles of all patients seen by two of the authors at the University of Colorado epilepsy clinic in a six month period. Patients taking lamotrigine were identified and their charts reviewed for complaints of adverse effects of lamotrigine use. In addition, we reviewed the medication profiles of all patients seen in our epilepsy monitoring unit in the same six month period and identified those patients in whom lamotrigine had been decreased or stopped during the EMU admission. Results: We identified five clinic patients who complained of new psychological symptoms while taking lamotrigine. These symptoms included anxiety, emotional lability, irritability, feeling “out of it” and having racing thoughts. In each case, these symptoms resulted in marked subjective distress and reliably occurred in the one to two hours before the patients were due to take their next dose of medication. All the patients were taking lamotrigine either once or twice a day. In addition, 29 of 84 consecutive EMU patients were taking lamotrigine, either alone or in combination therapy. Of those patients in whom only lamotrigine was withdrawn in the EMU, two complained of symptoms similar to those described by our clinic patients following their reduction in lamotrigine dose. These symptoms also caused notable patient distress. Conclusions: Withdrawal symptoms, although not widely reported in the literature, can occur in patients taking lamotrigine. This withdrawal syndrome consists largely of anxious feelings, irritability, and asthenia and can be very distressing to patients. Lamotrigine withdrawal symptoms can occur as an end‐of dose phenomenon in the outpatient setting and can also complicate inpatient evaluation in the EMU setting. End‐of‐dose withdrawal from lamotrigine is a clinically significant adverse effect that can hamper successful treatment with this medication. Further study of withdrawal symptoms in this medication and the other newer AEDs is clearly needed. 1 Barry Gidal, 2 Jacqueline French, 3 Patricia Grossman, 4 Gwenael Le Teuff, and 5 Celine Bugli ( 1 School of Pharmacy, University of Wisconsin, Madison, WI ; 2 School of Medicine, University of Pennsylvania, Philadelphia, PA ; 3 Global Outcomes Research, UCB, Atlanta, GA ; 4 Keyrus Biopharma, Levallois Perret, France ; and 5 LACO, Diegem, Belgium ) Rationale: While prevalence of antiepileptic drug/non‐antiepileptic drug (AED) concomitant medication and interaction is described for elderly, few data exist regarding gender and age patterns of potentially clinically important PK interactions. Specifically, we report on prevalence of polytherapy across age and gender groups, but also describe patterns of cardiovascular and psychotropic drug. Methods: A retrospective cohort study was conducted in epilepsy patients using a US claims database (1/2001–12/2004). Patients were sub‐grouped: enzyme inducing AEDs (EIAEDs) or non‐inducing (NEIAEDs).Usage of concomitant medications taken during the six month after AED initiation was compared using Chi‐squared tests for: Young Adults (YA)(18–34yo), Adults (A)(35–54), Older Adults (OA)(55–64), Young Old (YO)(65–74), Middle Old (MO)(75–84), Elderly (E)(85+). Results: A total of 9526 patients with epilepsy were identified: 6134 females and 3392 males; 5970 receiving EIAED and 3556 NEIAED. Overall, polytherapy was common and increased with age (table 1). Females are more likely to receive a concomitant medication regardless of AED use: EIAED (86%vs76%,p < 0.001); NEIAED (86%vs79%,p < 0.001). Compared to general population data (Sloan Survey, 2004), epilepsy patients in every age and gender group appeared to be significantly more likely to be receiving at least 5 concomitant medications: 23% of men and 39% of women with epilepsy age18–44 were on 5+ medications vs 2–3% in general population. In men and women age 45–64, this figure was 47–60% vs 10–15% in general population. Most frequent comedications are antipsychotics (YA:10%‐YO:19%), SSRI antidepressants (YA:20%‐YO:28%), TCA antidepressants (YA:7%‐OA:11%), Calcium channel blockers (YA:3%‐E:35%) and statins (YA:2%‐YO:41%). Antidepressants are more common for females (SSRI:25%vs16%;TCA:9%vs5%). Concomitant Medications use in AED users by age and enzyme inducer 18–34 35–54 55–64 65–74 75–84 85+ Female EI 4.1 5.8 7.7 7.4 6.6 6.8 Female NEI 4.0 6.8 8.2 8.8 6.2 7.6 Male EI 2.2 4.1 5.8 6.5 6.7 7.8 Male NEI 2.8 5.2 7.2 7.2 8.9 7.4 Conclusions: Concomitant drug use occurs across all age groups, not simply the elderly. Not surprisingly, the occurrence of polypharmacy with potentially interacting medication appears to steadily increase with age. Discrimination in AED selection based upon potential PK interactions was not seen. While no specific gender differences were seen with cardiovascular medications, differing patterns of gender specific psychotropic drug use may exist. These findings suggest that clinicians must be mindful of polypharmacy and potential non‐AED interactions in all age groups, not only elderly patients. (Supported by UCB INC.) 1 Christoph Helmstaedter, 1 Edgar Kockelmann, 1 Nina Kosanetzky, and 1 Christian E. Elger ( 1 Epileptology, University of Bonn, Bonn, Germany ) Rationale: Levetiracetam (LEV), one of the newer antiepileptic drugs, is considered a save and successful drug against epilepsy in adults and children with symptomatic and also idiopathic epilepsy. Recent observations of aggression and irritability under LEV raised the question as to whether this effect depends on dose or drug load and whether personality traits represent a risk factor for negative behavioral change. Methods: The study comprised 288 consecutive pharmacoresistant epilepsy patients (mean age 38yrs., m/f 145/143) who were chronically on LEV (90% polytherapy). Efficacy and effects on cognition, mood and behavior were evaluated per structured interview, analogue rating scales, questionnaires on personality and impulsiveness, and per file inspection. Incidence and type of positive or negative effects as well as possible mediators like personality traits, dose of LEV, total drug load, seizure control, type of epilepsy, age and gender were of interest. Proxy reports were available from 135 relatives. Results: Good seizure control (no or very rare seizures) under LEV was reported by 40% of the patients, improvement (few remaining seizures) by another 40%, and no benefit by 20% (mean dose ∼1000 mg, mean duration on LEV 2.3 yrs). Good responders had less AED and lower doses of LEV. Patients with symptomatic and idiopathic epilepsy responded equally well. Negative behavioral effects were reported from 37% of the patients (12% severe, 25% moderate), positive effects by 22% (6% very, 16% moderate). Side effects in either direction were independent of the time on LEV, dose, and drug load but they were significantly related to seizure control and personality traits. Positive change corresponded to analogue ratings of better concentration and memory and of greater activity and energy, and negative change to ratings of aggression (physical), agitation, impulsivity or depressed mood. Finally, negative side effects were related to symptoms related to organic brain syndrome and to non‐planning impulsiveness. Analyses of proxy ratings indicated reliability of patient reports. Conclusions: A considerable number of patients subjectively experiences behavioral change under LEV. LEV appears a stimulating agent, which can act in two directions. The negative extension is characterized by reduced impulse control, emotional instability and irritability, where aggression only appears one extreme variant. The positive extension is characterized by increased activation/arousal and by positive effects on cognitive performance. Most importantly behavioral change is closely related to efficacy, in that good responders show more positive and less negative side effects than poor responders. (figure 1) (Supported by UCB Pharma.) 1 Helle Herrman, 1 Erik Taubøll, and 1 Leif Gjerstad ( 1 Department of Neurology, Division of Clinical Neuroscience, Rikshospitalet‐Radiumhospitalet, University of Oslo, Oslo, Norway ) Rationale: Levetiracetam (LEV) is a broad spectrum antiepileptic drug with a favourable safety profile. Haematological side effects including leucopenia and thrombocytopenia are rare, but are potentially serious. This is the first report of a patient who developed reversible trombocytopathia secondary to LEV use. Methods: A 57 year‐old female with generalized tonic‐clonic seizures of unknown etiology since the age of 31 developed marked ecchymoses 1 month after initiation of LEV. The ecchymoses remained as long as she was taking LEV (13 months), but disappeared immediately after cessation of the drug. The patient did not use any other drugs, was otherwise healthy, had never had any haematological diseases or bleeding predisposition before, and there was no family history of such. Results: The platelet count was unchanged during LEV treatment with 244, 276 and 275 × 109/l before, during and after LEV treatment. Bleeding time on LEV treatment, however, was pathologically increased to 12 min (normal value 3–10), compared to 7.5 min without drug. Screening for other haematological parameters including coagulation factors VIII, IX, Von Willebrand factor, Ristocetin Co., white blood cell count, and general haematology was normal. Conclusions: This is the first report of LEV induced thrombocytopathia with increased bleeding time and ecchymoses without thrombocytopenia. Most likely, there has been a direct effect of the drug on trombocyte function. Alternatively, an effect on endothelial cells or vessel wall fragility can not be ruled out. 1,2 Erik Hessen, 1,3,2 Morten I. Lossius, 4 Ivar Reinvang, and 5 Leif Gjerstad ( 1 Helse Øst Health Services, Akershus University Hospital, Oslo, Norway ; 2 Deptartment of Neurology, Akershus University Hospital, Oslo, Norway ; 3 National Center for Epilepsy, Rikshospitalet, Oslo, Norway ; 4 Deptartment of Psychology, University of Oslo, Oslo, Norway ; and 5 Deptartment of Neurology, Rikshospitalet, Oslo, Norway ) Rationale: The main cognitive side‐effects of antiepileptic drugs (AEDs) involve attention/vigilance, psychomotor speed and memory. Traditional neuropsychological testing has been the major method of measuring cognitive function related to the use of AEDs. Uncertainty exists regarding the degree of cognitive effects primarily because many studies do not adhere to basic standards of methodology and design. The aim of this study was to assess the effect of withdrawal of AEDs in patients on monotherapy and to evaluate the usefulness of a computerized assessment package that provide measures of reported side effects like attention, choice reaction time, psychomotor speed and memory. Methods: 150 subjects who had been seizure free > 2 years on drug monotherapy went through a randomised, double blind, placebo controlled study. The patients were included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and seven months after withdrawal. Results: The major finding in this study is that withdrawal of major AEDs significantly improved performance on tests that require complex cognitive processing under time pressure. Most of the subjects were medicated with carbamazepine and valproate. The outcome of withdrawal of carbamazepine was similar to the outcome for the total study population while discontinuation of valproate only revealed a non‐significant tendency in the same direction. Conclusions: The results suggest that seizure‐free epilepsy patients on monotherapy can obtain improvement in cognitive function if they withdraw anti‐epileptic treatment and that computerized cognitive testing is useful in detecting cognitive side effects related to complex cognitive processing under time pressure. (Supported by a grant from Helse Øst, Norway.) 1 Hiba Arif, 2 Richard Buchsbaum, 1 Joanna Ferreri, 1 Michael Whalen, 1 Jessica Sims, 1 Stanley R. Resor Jr., 1 Carl W. Bazil, and 1 Lawrence J. Hirsch ( 1 Comprehensive Epilepsy Center, Department of Neurology, Columbia University, New York, NY ; and 2 Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY ) Rationale: Retention, a measure of antiepileptic drug (AED) “effectiveness,” is the percentage of patients started on a drug who remain on it after a given period of time, and is a composite measure of efficacy & tolerability. Few studies have compared effectiveness of AEDs for use in this population. We compared 12 month retention, seizure freedom & tolerability of newer & older AEDs in older adults with epilepsy. Methods: We reviewed patient background, medical history, AED use and 1‐year retention, seizure‐freedom, & side effects (& whether or not these led to a change in dose) for 413 patients ≥55 years old, newly started on any AED at our center from 1/1/2000 – 12/31/2004. Results were calculated for the overall group & for subgroups with varying degrees of refractoriness, estimated by the number of prior AEDs tried: 0–1: non‐refractory; 3–5: refractory; 5+: very refractory. In each comparison, the individual AED was compared to the average of all other AEDs. Those who were seizure‐free but stopped an AED in < 1 year due to side effects were excluded from the seizure‐freedom analysis. Results: Overall, 319/413 (77.2%) patients remained on at least 1 AED for at least 1 year. The following were 12‐month retention rates for each AED (*= p < 0.05 better, $= p < 0.05 worse, compared to average of other AEDs), listed from most to least effective: LTG* (75.6%; 90/119), LEV* (71.7%; 71/99), VPA (65.0%; 13/20), CLB (64.3%; 9/14), GBP (61.0%; 25/41), ZNS (58.8%; 10/17), TPM (52.4%; 11/21), PHT (50.0%; 7/14), CBZ (46.4%; 13/28), OXC$ (24.2%; 8/33). Relative rates were similar in refractory patients, except VPA (improved to 90.0%; 9/10, p < 0.1) and CBZ$ (dropped to 25%; 2/8). 12‐month seizure‐freedom rates were as follows (*= p < 0.05 better, $= p < 0.05 worse, compared to average of other AEDs), listed from most to least efficacious: LTG* (47.4%; 36/76), LEV (33.3%; 22/66), CBZ (23.1%; 6/26), VPA (20.0%; 3/15), GBP (17.9%; 5/28), TPM (17.6%; 3/17), PHT (16.7%; 2/12), OXC$ (6.5%; 2/31) and ZNS (0.0%; 0/15). Relative rates were similar in refractory & very refractory patients. Tolerability data will be presented. Conclusions: In this study, LTG was the most effective AED as measured by 12 month retention and seizure‐freedom, with LEV a close second; PHT, CBZ & OXC were consistently below average for effectiveness. For the 3 AEDs previously studied in the prospective, randomized, double‐blinded VA cooperative trial of epilepsy in older adults (LTG, GBP and CBZ), our retention results are strikingly similar. (Abbreviations: CBZ = carbamazepine, CLB = clobazam, GBP = gabapentin, LEV = levetiracetam, LTG = lamotrigine, OXC = oxcarbazepine, PHT = phenytoin, TPM = topiramate, VPA = valproic acid, ZNS = zonisamide). (Supported by Elan, GlaxoSmithKline, Novartis, Ortho‐McNeil, Pfizer and UCB Pharma.) 1 Denicia K. Holley, 1 Page B. Pennell, 2 Donald J. Newport, 3 James C. Ritchie, 1 Melanee L. Newman, and 2 Zachary N. Stowe ( 1 Neurology, Emory University School of Medicine, Atlanta, GA ; 2 Psychiatry, Emory University School of Medicine, Atlanta, GA ; and 3 Pathology, Emory Univeristy School of Medicine, Atlanta, GA ) Rationale: The treatment of women with epilepsy during pregnancy necessitates a balance between minimizing fetal exposure to AEDs while maintaining seizure control. Oxcarbazepine (OXC) is the only newer generation AED other than lamotrigine (LTG) with reasonable safety data during pregnancy. Reports of major malformation rates vary between 0–5%. However, EURAPregnancy Registry reported that use of OXC monotherapy was associated with an increased risk for GTCSzs, and the number or dosage of AEDs were most often increased in pregnancies treated with OXC or LTG monotherapy. This observational study did not report on serum concentrations or OXC clearance. About 50% of the metabolism of the 10‐monohydroxy derivative (MHD) of OXC is via glucuronidation, which is especially susceptible to activation by the hormonal changes of pregnancy. MHD Clearance (Cl/F) Across Pregnancy and Postpartum: OXC Daily Dose (mg/kg)/MHD Serum Concentration (mg/L) # of Samples Cl/F (Total) % Change from Baseline Clu/F (Free) % Change from Baseline Postpartum (Baseline) 8 0.7 ± 0.2 1.6 ± 0.4 Trimester 1 2 1.0 ± 0.4 35.2 1.9 ± 1.0 22.7 Trimester 2 9 1.1 ± 0.5 54.9 2.2 ± 0.6 40.6 Trimester 3 8 1.3 ± 0.4 84.5 2.3 ± 0.7 47.3 Clearance reported as Mean ± Standard Deviation (Supported by a Specialized Center for Research P50 MH 68036.) Methods: 5 women (4 epilepsy, 1 bipolar disorder) treated with OXC (doses of 450–3000 mg/day) were consented and followed in a prospective observational study. Serum samples were obtained throughout pregnancy and until 5 months postpartum (n = 27). Postpartum samples were considered the non‐pregnant baseline. Maternal plasma and umbilical cord samples were also collected at delivery (n = 4). Comparisons of the total apparent oral clearance(Cl/F) and free (unbound) apparent oral clearance (Clu/F) were made between the postpartum (baseline) and perinatal stages. Umbilical cord/maternal concentration ratios were calculated for total and free MHD. Results: Cl/F and Clu/F data from the postpartum and perinatal stages are reported in Table 1. Umbilical cord/maternal concentrations demonstrated a mean placental passage of 1.0 ± 0.3 (total) and 1.1 ± 0.2 (free) for MHD. Obstetrical outcome demonstrated mean APGAR scores of 8.5 ± 0.6 at 1 min, 9.0 ± 0.0 at 5 mins, birth weights of 3.2 ± 0.4 kg, and weeks at delivery of 39.4 ± 1.0. No major malformations were detected. Conclusions: During pregnancy, both total MHD Cl/F and free MHD Cl/F increase considerably, although the latter to a lesser degree. Substantial exposure occurs in utero with complete placental passage of OXC. Therapeutic drug monitoring of OXC may be helpful to prevent seizure deterioration during pregnancy and improve maternal and fetal outcomes. 1 Marcia J. Hunt, 1 Eljim P. Tesoro, 1 Jeffery J. Mucksavage, and 2 Yevgenya Kaydanova ( 1 Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL ; and 2 Department of Neurology, University of Illinois at Chicago, Chicago, IL ) Rationale: The use of levetiracetam in the intensive care unit (ICU) has limited data. Phenytoin, a standard antiepileptic drug (AED) has numerous challenges in relation to dosing, administration, and adverse effects. Levetiracetam, a newer antiepileptic agent has a limited side effect profile and does not affect the cytochrome P450 pathway. This retrospective review will look at the use of levetiracetam in the ICU patient population at the University of Illinois Medical Center at Chicago (UIMCC) to date. The primary objective is to determine if levetiracetam is effective in preventing and/or treating seizures clinically and per electroencephalogram (EEG). The secondary objectives are to determine the safety and tolerability, the reasons for initiating, and the usage pattern of levetiracetam in the ICUs at UIMCC. Methods: This study is a retrospective chart review of patients who received levetiracetam while in the ICU. Patients are included in this study if they are initiated on levetiracetam during January 2002 through October 2005 while they are hospitalized in the ICU. Exclusion criteria are patients <18 years of age and pregnant females. Data collected includes patient demographics, renal and liver function, EEG results, observed seizures in daily progress notes, dose of levetiracetam started, final dose of levetiracetam, rate of titration of dose, reason levetiracetam started, other AEDs patients receiving during hospitalization, and adverse events suspected of other AEDs and/or levetiracetam. Patients will be followed until levetiracetam is discontinued, patient is discharged from the hospital, or death occurs. Results: Preliminary results are available for 100 patients. Sixty‐four percent of patients were admitted to the neurosurgical intensive care unit (NSICU). The most frequent initial dose (41%) and the most common final dosage (27%) of levetiracetam was 500 mg every 12 hours. Only 49% of patients had their dosage titrated up during hospitalizations. Most patients were either previously or currently on phenytoin as monotherapy (48%). Fifty‐seven percent of patients were initiated on levetiracetam secondary to drug interactions or adverse effects of traditional AEDs. The most common adverse effect possibly related to levetiracetam was lethargy (8%). Eighty‐seven percent of patients did not have a clinic seizure occur. Preliminary EEG results are available for 47 patients. A trend in reduction of ictal and interictal epileptiform activity was observed after initiation of levetiracetam and it appears EEGs improve as levetiracetam is continued. Conclusions: Levetiracetam is well tolerated in ICU patients and it is frequently initiated because of adverse effects and drug interactions of other AEDs. Based upon preliminary data, levetiracetam appears to have beneficial effects on EEG activity. (Supported by An unrestricted grant from UCB Pharma, Inc.) 1 Dorothee G.A. Kasteleijn Nolst Trenite, 2 Edouard Hirsch, 3 Bernd Schmidt, and 4 Jaqueline A. French ( 1 Pharmacology, NeuroActiveResearch, Bloemendaal, Netherlands ; 2 Neurology, University of Strasbourg, Strasbourg, France ; 3 Neurology, Wittnau, Germany ; and 4 Neurology, University of Pennsylvania, Philadelphia ) Rationale: Despite authoritative reviews in 2005 on the subject of photosensitive patients and their epileptiform EEG responses to intermittent photic stimulation (IPS)(Fisher et al. Covanis, Verrotti et al., Kasteleijn et al.), gleaning the essential components necessary to effectively study a new AED in the photosensitivity model are not readily available. This work proposes a novel rationale for the use of the photosensitivity model in the development of new AEDs and perhaps as a surrogate marker for AED efficacy in epilepsy. The amended FDA laws (1992,1997) permit approval of a new AED on the basis of a AED's effect on a surrogate marker, one that can be reasonably expected to predict the clinical outcome (Katz R. The development of AEDs: regulatory perspective. In AEDs 5th Levy R et al.; Philadelphia 67–68, 2002). Methods: A survey of epileptologists with extensive experience in performance of studies in the photosensitivity model, was conducted to arrive at consensus statements for the clinical utility of the model in assessing the activity of potential new AEDs in epilepsy. Results: Advantages include: 1.The range of photoparoxysmal EEG responses (PPRs) is a stable, repeatable and objective measure of the epileptic state of the brain 2. The procedure of IPS establishing the photosensitivity ranges has been standardised with also clear diminishment of risks to evoke seizures (EU consensus) 3. Only a limited number of patients (20)during a limited time period (number of days 3–5) are necessary to have a reliable outcome 4. AEDs limit, reduce or even abolish the PPRs 5. The results provide some guidance as to the choice to dose in further phase II and III trials 6. Comparison of strength of effect of AEDs in the photosensitive patients 7. Correlation of pharmacodynamic and pharmacokinetic data 8. A first experience of the effect of a new AED on the EEG background can be established 9. Testing in female patients in an early stage of development 10. A PPR is found in patients with generalised as well as focal epilepsy types and syndromes and reflects a general susceptibility to epilepsy 11. AEDs effective in the photosensitivity model are effective also in epilepsy patients in general 12. Compliance is secured as well as monitoring of subjective and objective side‐effects13. Flexibility of design with immediate results. Disadvantages include: 1. Only about 5% of patients above 18 years of age show a PPR 2. Photic stimulation may provoke a seizure 3. Highly skilled centers are necessary to perform such a study. Conclusions: The photosensitivity model offers an excellent way of testing efficacy and tolerability of AEDs in a very standardized, controlled and safe manner in the early development. 1 D. Kastelijn‐Nolst Trenité, 2 B. Abou‐Khalil, 3 J. French, 4 P. Genton, 5 E. Hirsch, 6 P. Masnou, 7 D. Parain, 8 D. Chen, 8 A. Hollis, 9 S. McCabe, 9 M. Troenaru, 9 N. Toublanc, and 9 A. Stockis ( 1 UMCU, Utrecht, Netherlands ; 2 VUMC, Nashville ; 3 U. Pennsylvania, Philadelphia, PA ; 4 Hospital de La Timone, Marseille, France ; 5 CHRU, Strasbourg, France ; 6 CHU Kremlin Bicetre, France ; 7 CHU, Rouen, France ; 8 UCB Inc, Smyrna, GA ; and 9 UCB SA, Braine‐l’Alleud, Belgium ) Rationale: To assess the pharmacodynamics and tolerability of seletracetam (UCB 44212) single doses, a 2‐pyrrolidinone derivative, in photosensitive patients. Seletracetam is an investigational new drug structurally related to levetiracetam (LEV) with a higher affinity and similar high selectivity towards the specific SV2A binding site. LEV and brivaracetam have shown to be effective in this POP model before. Methods: A placebo‐controlled, single blind, single period study, conducted in photosensitive patients with epilepsy, aged 18–60 years, taking no more than 2 other concomitant antiepileptic drugs (AEDs). During a 3 day period (with possible extension to 5 days) patients underwent standardized intermittent photic stimulation (IPS) to define the standard photosensitive range (SPR) at fixed time points. After the 1st day with placebo, single oral doses of seletracetam were given on the 2nd day, starting at 10 mg in a group of patients and testing subsequently lower or higher doses depending on the results of the previous group. Doses tested were 0.5, 1, 2, 4, 10, and 20 mg. SPR was the main parameter to identify the lowest single dose of seletracetam producing maximal decrease or suppression of the IPS evoked photoparoxysmal EEG response (PPR) comparing the SPRs before and after intake of seletracetam. Plasma seletracetam was monitored up to 72 hours post‐dose. Descriptive statistics were used. Results: 28 patients (23 F, 5 M) completed the study. One was excluded from the per protocol analysis due to emesis. 9 patients returned for a 2nd dosing 1–6 months later, providing a total of 36 individual exposures. Overall, 53% (19/36) patients showed a complete suppression of the epileptiform EEG response after seletracetam intake and 36% (13/36) showed an important decrease in SPR. The maximum SPR decrease from time‐matched placebo was dose related and appeared to reach its maximal level at 10 mg. The pharmacokinetic and side‐effect profile was similar to that in healthy volunteers. 18 patients (64%) reported 42 adverse events during the study (5 after placebo and 37 after seletracetam), without specific association with dose. Somnolence (32%), dizziness (21%), headache (14%), feeling drunk (7%) were reported following seletracetam, compared to <5% following placebo. Conclusions: Seletracetam was effective in reducing or even abolishing the photoparoxysmal EEG response in photosensitive patients with epilepsy. Maximal suppression was achieved at relatively low doses of 10 and 20 mg. Seletracetam is more potent in this model, compared to both LEV and brivaracetam. (Supported by UCB funded.) 1 Susan P. Kerls, 1 Anne E. Hammer, 1 Robert P. Kustra, and 2 Steve Chung ( 1 Neurosciences Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC ; and 2 Adult Neurology Clinic, Barrow Neurological Institute, Phoenix, AZ ) Rationale: A recent study evaluated the cognitive effects of lamotrigine (LTG) and topiramate (TPM) adjunctive therapy for refractory partial seizure disorders in adults. This analysis provides further examination of these results in patients over the age of 50. This randomized, double‐blind clinical trial evaluated the cognitive effects of TPM and LTG in addition to the safety and tolerability of TPM and LTG in older adult patients with partial seizures. Methods: Eligible patients had a diagnosis of partial epilepsy and were inadequately controlled by a regimen containing carbamazepine (CBZ) or phenytoin (PHT). Patients were evaluated and administered six cognitive tests at each of the three study phases: Baseline; Escalation (8 weeks) to 500 mg/day LTG or 300 mg/day TPM; Maintenance (8 weeks). An endpoint of the study was change from Baseline in the scores from the six standardized measures of cognition to the end of the Maintenance Phase. Statistical testing was performed using analysis of covariance methods. Results: The most common (>=10%) treatment‐emergent adverse events (AEs) were dizziness (12% LTG, 4% TPM) and nausea (16% LTG, 4% TPM). More patients in the TPM group prematurely discontinued due to an AE (35% TPM, 28% LTG). Two of the thirteen patients in the TPM group that prematurely discontinued due to cognitive decline were considered related (15%). Ten patients in the LTG group that prematurely discontinued due to cognitive decline were not related. Of the 192 patients (96 LTG, 96 TPM) enrolled in the study, there was a statistically significant difference in three of the six cognitive tests in favor of LTG (COWA p < 0.001, Stroop Test p = 0.038, Symbol‐Digit Modalities p < 0.001). Conclusions: Although no significant discontinuation rate was found, treatment with LTG compared to TPM resulted in significantly better cognitive test scores in certain cognitive domains for older adult patients with epilepsy. This finding was consistent with the result reported previously from the overall population in this study. (Supported by GlaxoSmithKline Research and Development.) 1 James F. Knudsen, and 2 Gerald Sokol ( 1 CDER, White Oak Research Facility, Silver Spring, MD ; and 2 H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL ) Rationale: We and others have shown that in vitro, the antiepileptic drugs (AEDs) zonisamide (ZNS) and topiramate (TPM) inhibit the zinc metalloenzyme carbonic anhydrase (CA), an enzyme involved in gluconeogenesis, ion transport, and provision of HCO3−. Hippocampal neuronal GABAergic depolarization is reported to be dependent on HCO3− and thus on intracellular CA activity. We studied some aspects of cognitive impairment among patients exposed to TPM and other AEDs. Methods: We examined the incidence of treatment‐emergent cognitive adverse events in placebo (PBO)‐controlled studies of AEDs that are CA inhibitors (CAIs) (TPM, ZNS) vs. newer AEDs that are not known CAIs (tiagabine, TB; gabapentin, GP; lamotrigine, LG; and levetiracetam, LTA). We used data available from clinical PBO‐controlled randomized add‐on trials for each of the AEDs, because head‐to‐head comparisons of these drugs in premarketing clinical trials were lacking. Two cognitive variables examined were psychomotor slowing and concentration/memory impairment. Results: The incidence of psychomotor slowing was: TPM (n = 414) vs. PBO (n = 291), 21% vs. 2%; ZNS (n = 289) vs. PBO (n = 230), 4% vs. 2%; TB (n = 494) vs. PBO (n = 275), 10% vs. 5%; GP (n = 543) vs. PBO (n = 378), < 1% vs. < 1%; LG (n = 711) vs. PBO (n = 419), 2% vs. <1%; and LTA (n = 769) vs. PBO (n = 439), <1% vs. <1%. The incidence of impaired concentration/memory were: TPM vs. PBO, 28% vs. 5%; ZNS vs. PBO, 12% vs. 4%; and <1% for the remainder. Conclusions: From the clinically significant increase in the incidence of impaired concentration/memory in patients exposed to the CAIs TPM and ZNS vs. PBO and no observed effect of non‐CAI AEDs relative to PBO, we hypothesized that CA and provision of HCO3− are important in neuronal homeostasis. CA acts as a molecular switch in the development of synchronous gamma‐frequency firing of hippocampal pyramidal cells. (Ruusuvuori E., et al. J.Neurosci 2004;24:2699–2707). GABAergic excitation and associated gamma oscillations seem dependent on CA activity, HCO3− availability, membrane pH gradients and provision for ionized calcium (adding H+ to a solution of HCO3− will generate more carbonic, CO2 and H2O). CAI may medicate some aspects of cognition as demonstrated by our report. 1,2 Marianna V. Spanaki, 1,2 Panayiotis N. Varelas, 1 Madhuri L. Koganti, and 1 Brien J. Smith ( 1 Neurology, Henry Ford Hospital, K‐11, Detroit, MI ; and 2 Neurology, Wayne State University, Detroit, MI ) Rationale: Antiepileptic drug (AED) treatment in the elderly represents a challenge due to limited data on their efficacy and side effect profile in older patients, high incidence of co‐morbidities, and age‐related changes in protein binding, gastrointestinal absorption, renal and hepatic clearance. In the last decade new AEDs with improved tolerability and reduced interaction potential have been available. The aim of the study was to determine whether the increased availability of new AEDs has influenced our prescribing habits in elderly epilepsy patients. Methods: We identified new referrals to Henry Ford Hospital epilepsy clinics in the last 3 years by searching our electronic database. We included patients older than 60 with a confirmed diagnosis of epilepsy. We collected data on specialty of referring physician, age at epilepsy onset, etiology, AED upon initial evaluation, seizure control and calcium supplementation. Descriptive statistics and Fisher's exact test were used for the analysis. Results: Of 349 new referrals, 49 (14%) were older than 60 (age range 60 to 91; females = 20). Primary care physicians referred 23 (47%) patients. Community neurologists referred the remainder, except for two referred by neurosurgeons. Thirty four patients (69.4%) were taking either one old or combination of old AEDs. Nineteen patients (38.7%) were on phenytoin monotherapy and 10 (20.4%) on phenytoin polytherapy. Twelve patients (24.5%) were taking carbamazepine as mono or polytherapy while 9 patients (18.4%) were on phenobarbital combination therapy. Only 11 patients (32%) on old AEDs were seizure free. In our patient group only 4 patients (8%) were taking new AED monotherapy. Calcium supplementation was recommended in only 3 patients (6%). There was a trend for primary care physicians (PCP) to prescribe older AEDs (95% of PCP vs 74% of neuro‐specialists, p = 0.09) Conclusions: Our study showed that almost 70% of elderly are still being prescribed phenytoin, phenobarbital and carbamazepine despite their potential of multiple drug interactions, sedative and cognitive side effects, increased neurotoxicity at “therapeutic doses” along with long term side effects such as osteoporosis. In our group, patients were maintained on old AEDs although they were effective in only 32% of them. Guidelines for calcium supplementation were not followed. Ten years after the approval of new AEDs, their use is still very limited in elderly for reasons that need to be further addressed. 1 Gregory Krauss, 2 Elinor Ben‐Menachem, 3 Ruta Mameniskiene, 4 Nerija Vaiciene, 5 Melissa Brock, and 5 John Whitesides ( 1 Department of Neurology, John Hopkins Hospital Epilepsy Center, Baltimore, MD ; 2 Institution for Clinical Neuroscience and Physiology, Shalgrenska University Hospital, Goteborg, Sweden ; 3 Department of Neurology, Vilnius University Hospital, Vilnius, Lithuania ; 4 Clinic of Neurology, Kaunas Medical University Hospital, Kaunas, Lithuania ; and 5 Schwarz Biosciences, Inc., Raleigh, NC ) Rationale: Lacosamide (LCM, SPM 927; formerly harkoseride) is a new chemical entity being developed as an oral and intravenous (iv) formulation for treatment of partial seizures and neuropathic pain. LCM has a favorable pharmacokinetic profile and when given orally twice daily (bid) has been shown to reduce seizure frequency in subjects. LCM solution for iv infusion (10 mg/mL) is being developed as short‐term replacement for oral LCM. Infusion of 200mg iv LCM over 30‐ or 60‐minutes has been shown to be bioequivalent (Cmax, AUC) to 200mg oral LCM. The objectives of SP757 were to investigate whether iv LCM was safe and well tolerated when given bid as short‐term adjunctive therapy in subjects with partial seizures and to identify the appropriate infusion rate(s). Methods: Subjects (n = 101) receiving adjunctive, stable, bid dosing with oral LCM (200 to 600 mg/day) were progressively studied in 3 cohorts: 30‐min infusion (n = 40); 15‐min infusion (n = 41); 10‐min infusion (n = 20). A fourth cohort (15‐min infusion, n = 60) was recently completed and those data are under review. Subjects were administered iv LCM bid for 2–5 days. Treatment duration was at the discretion of the investigator and subject. After trial completion subjects resumed treatment with oral LCM. Safety was evaluated through reported adverse events (AEs); 12‐lead electrocardiogram (ECG) and vital sign data collection; and clinical laboratory data. Seizure data were collected in a diary. A Data Monitoring Committee reviewed safety data from each completed cohort prior to initiation of subsequent cohorts. Results: All subjects were administered 2 days of iv LCM bid; 47 (77%) of subjects from the 15‐ and 10‐min infusion groups were dosed for 3–5 days. A total of 16% of subjects took 200 mg/day, 48% of subjects took 300–400 mg/day and 36% of subjects took 500–600 mg/day LCM. Dizziness was the most commonly reported AE; frequency ranged from 5% in the 15‐ and 10‐min groups to 8% in the 30‐min infusion group. Infusion site related AEs were infrequently reported and did not result in discontinuation of iv LCM. Mean vital sign results remained stable during and following iv LCM infusion. Seizure patterns for individual subjects did not appear to change during the trial period. Conclusions: In this trial, lacosamide solution for intravenous infusion (administered over 10, 15, or 30 minutes) was successfully used as short‐term replacement for oral lacosamide in subjects with partial seizures. (Supported by Schwarz Biosciences, Inc.) 1 Sumeet Kumar, 1 Pinar Miski, and 1 Mercedes P. Jacobson ( 1 Neurology, Temple University Hospital, Philadelphia, PA ) Rationale: To examine possible interactions in patients taking both antiepileptic and psychiatric medications, thereby identifying their impact on non‐compliance with these drugs. Methods: A retrospective study was conducted to identify subjects with epilepsy seen in the past year at the epilepsy clinic of Temple University Hospital. 803 subjects were identified, and 500 were eligible for this study based on a clear diagnosis of epilepsy, use of at least one antiepileptic drug at the last clinic visit, and availability of mental health information in the charts. A psychiatric diagnosis was not required to be in this study. 110 subjects were then randomly selected in proportions that matched the race and gender demographical ratios of the overall epilepsy patient pool at the clinic. Results: Of 110 subjects, 41% were African‐American (AA) (27 F, 18 M), 36% Caucasian (25 F, 15 M), 18% Hispanic (10 F, 10 M), and 5% Asian (3 M, 2 F). 58% of patients were female with an age range of 19 to 77 years. Males ranged from 18 to 71 years. The incidence of concurrent psychiatric and epilepsy diagnoses was 63% (n = 69). Of these, 35% (24 of 69) were non‐compliant with psychiatric medication. Among this group, men had the highest rate of non‐compliance (80% of Hispanics, 36% of Caucasians, 33% of AAs were non‐compliant). Women had lower rates of non‐compliance with psychiatric medication (33% of Caucasians, 32% of AAs, and 13% of Hispanics were non‐compliant). Among compliant subjects (45 of 69), 40% (n = 18) were on antiepileptic and psychiatric medications that were known to have at least one potential interaction with each other. Of these 18 subjects, the groups with the highest prevalence rate of potential medication interactions were AA males (n = 5), Hispanic females (n = 4), AA females (n = 5), Caucasian males (n = 3), Caucasian females (n = 1), and Hispanic males (n = 0). The most common psychiatric diagnosis in patients with epilepsy was depression (52% of all psychiatric diagnoses). Conclusions: In our study, there was a high rate of psychiatric comorbidity in people with epilepsy. Among compliant subjects, there was a high rate of potential interaction between antiepileptic and psychiatric medications. Among the 110 subjects however, there were no recognized clinical events attributed to drug interactions. AA males and Hispanic females were the groups with highest rate for potential interactions, yet were more likely to be compliant with psychiatric medications than other groups. This suggests that drug interactions are not only the reason for medication non‐compliance. Clinicians need to be aware of cultural, gender, and social differences among epileptic persons taking psychiatric medications. Other factors such as insurance coverage, mental health services access, neurology clinic access, communication between Psychiatrists and Neurologists, and efficacy of psychiatric and neurologic medicines will impact compliance. 1 Michael Lamson, 2 Diane Sitki‐Green, 1 Gerald Wannarka, and 3 William Gershon ( 1 Pharmacokinetics, King Pharmaceuticals, Inc., Cary, NC ; 2 Clinical Research, Lineberry Research Associates, RTP, NC ; and 3 Clinical Research, SFBC International, Miami, FL ) Rationale: An autoinjector delivery system for intramuscular (i.m.) administration of diazepam (Vanquix™ Auto‐Injector) is being developed as an alternative to diazepam rectal administration, the only current treatment that can be administered by non‐health care professionals for management of patients with acute repetitive seizures (ARS). Methods: The study was conducted as a 2‐part, randomized, open‐label, single‐dose, crossover design in healthy young (ages 18–40 years) adult volunteers. Part I of the study evaluated the pharmacokinetics (PK) of Vanquix™ 5, and 15 mg administered i.m. into the mid outer thigh. Part II evaluated the relative bioavailability of Vanquix™ 10 mg compared with diazepam rectal gel (Diastat®) 10 mg administered according to the product label. Serial sampling of plasma, vital signs, and adverse event assessments were done a specified times. Treatments were separated by a 2‐week washout period. Results: A total of 48 subjects were enrolled in the study, 24 in each part. In Part I of the study, administration of Vanquix™ 5, 10, and 15 mg i.m. resulted in a proportional increase of the diazepam Cmax and AUC, and a consistent Tmax of 1.0 hour at each dose level. In Part II of the study, i.m. administration of Vanquix™ 10 mg resulted in plasma concentrations of both the diazepam and desmethyldiazepam that were slightly higher and less variable than those observed following diazepam rectal gel 10 mg. Two subjects had negligible absorption of diazepam from the rectal route of administration, which skewed the PK results for the reference drug. Excluding the tow outliers, the geometric mean ratio (Vanquix™ Auto‐Injector/Diastat®) and 90% CIs for diazepam Cmax and AUC(O‐t) were 0.94 (0.84, 1.05) and 1.14 (1.08, 1.21), respectively, indicating that the overal bioavailability of Vanquix™ was approximately 14% higher than that of diazepam rectal gel (Diastat®). Both treatments were generally safe and well‐tolerated. Although the incidence of treatment‐emergent AEs was higher with Vanquix™ Auto‐Injector compared with Diastat® (21.7%versus 13.6%), the difference could be attributed to injection site pain. Injection site pain also correlated with the Vanquix™ dose administered in Part I: 5 mg (4.3%), 10 mg (21.7%), and 15 mg (27.3%). No other AEs correlated with dose, and there was no evidence of respiratory depression with either drug. Conclusions: The results of this study demonstrate that diazepam can be safely and reliably delivered to the systematic circulation using Vanquix™ Auto Injector. The slight (14%) difference in bioavailability between Vanquix™ Auto Injector and diazepam rectal gel is of questionable clinical importance and suggests that the two dosage forms could be interchanged on a mg per mg basis. (Supported by King Pharmaceuticals, Inc.) 1 John Paul Leach, 1 Martin J. Brodie, 1 Graeme Sills, 1 Linda Stephens, and 1 Elaine Butler ( 1 Epilepsy Unit, Western Infirmary, Glasgow, United Kingdom ) Rationale: We undertook a randomised, open‐label study to compare the efficacy, tolerability, and androgenic effects of lamotrigine (LTG) and sodium valproate (VPA) monotherapy in newly diagnosed epilepsy. Methods: A total of 226 patients with a recent diagnosis of epilepsy were randomised (on an equal basis) to receive either LTG or VPA. Median age at recruitment was 35 years (range = 13 to 80 years). Sixty patients presented with idiopathic generalised epilepsy, 149 patients had localisation‐related epilepsy, and 17 remained unclassified. Subjects were followed up at six‐weekly intervals until reaching one of the study end points (1 year seizure freedom, withdrawal due to side effects, or withdrawal due to lack of efficacy). In addition, basic androgenic function was assessed by longitudinal analysis of serum testosterone and androstenedione concentrations. Results: A total of 197 patients reached an end point. Median dose of VPA was 1000 mg/day (range 600 – 3000 mg/day), while the median dose of LTG was 200 mg/day (range 100 – 700 mg/day). Seizure freedom rates were similar for both drugs (67% and 60% for VPA‐ and LTG‐treated patients, respectively). Withdrawal due to side effects was required in 24 VPA patients and 14 LTG patients. Similar numbers were withdrawn due to lack of efficacy (18 VPA, 15 LTG). Longitudinal assessment of androgenic function showed no significant change in either treatment arm. Conclusions: No significant differences were noted in measures of outcome (efficacy or tolerability) in groups of patients with newly diagnosed epilepsy treated with either VPA or LTG. Androgenic function was not affected by either treatment. (Supported by: This study was partly supported by an unrestricted educational grant from Sanofi.) 1 P.T. Leese, 2 D.R. Goldwater, 4R. Hulhoven, 3 E. Salas, 4N. Toublanc, 3 D. Chen, 4M.L. Sargentini‐Maier, and 4A. Stockis ( 1 Phase‐I Services, Quintiles Inc, Lenexa, KS ; 2 Clinical Research Unit, Parexel Inc, Baltimore, MD ; and 3 Clinical Pharmacology, UCB Inc, Smyrna, GA ) Rationale: Seletracetam (UCB 44212) is an investigational new drug structurally related to levetiracetam with a higher affinity and similar high selectivity towards the specific SV2A binding site. The anticipated pharmacologically active dose in humans is around 15 mg based on animal models of epilepsy. Methods: Single and multiple rising dose studies of seletracetam were performed in a randomized, double‐blind, placebo controlled manner. Healthy male volunteers were enrolled. For the single administration, 3 alternating panels of 9 subjects received the following doses: 2, 4, 10, 20, 50, 100, 200, 400, and 600 mg (6 active: 3 placebo). Food effect was assessed in an additional group of 8 subjects. For the multiple dose administration, 3 different panels of 12 subjects (9 active: 3 placebo) received 20, 60 and 200 mg twice daily during 2 weeks. CNS effects were explored with psychomotor tests, rating scales and neurological assessments. Results: The maximum single dose of 600 mg and the maximum repeated dose of 400 mg/day were well tolerated. During multiple dosing, treatment‐emergent adverse events (AEs) occurred in 44%, 89%, 78% and 100% of subjects receiving placebo, 20, 60 and 200 mg b.i.d., respectively. The most frequent were dizziness, drowsiness, euphoria and feeling drunk. Most appeared shortly after first dosing, were of mild or moderate intensity, and lasted for less than 12 hours. In most subjects, the AEs did not reappear when given the next dose. AE severity was mild to moderate. There were no serious AEs and no changes in laboratory, vital signs, ECGs or neurological examinations. Seletracetam pharmacokinetics were linear, dose‐proportional and time invariant, with a plasma half‐life of 8 hours. Co‐administration with a high fat meal resulted in reduced absorption rate and no change in AUC. Conclusions: The maximum tolerated dose of seletracetam was > 600 mg after single dose and >400 mg/day after 2 weeks of repeated dosing. Its favorable pharmacokinetics and good tolerability, with AEs limited to mild to moderate CNS effects at initial dosing, are encouraging for the continued clinical development of this new antiepileptic drug. (Supported by UCB funded.) 1 Xiao‐Yuan Lian, 2 Zhizhen Zhang, and 1 Janet L. Stringer ( 1 Pharmacology, Baylor College of Medicine, Houston, TX ; and 2 College of Forestry, Stephen F. Austin State University, Nacogdoches, TX ) Rationale: Used medicinally for more 2,000 years, ginseng has been shown to have biological activity in a number of systems. The possibility that ginseng may have anticonvulsant activity was first suggested in 2002. The purpose of this study was to test the anticonvulsant activity of three preparations of American ginseng (whole root extract, whole leaves/stems extract and a partially purified extract that concentrates the Rb ginsenosides (Rb extract)) and to identify the active components in the Rb extract. Methods: One hour after treatment with normal saline or one of the ginseng preparations, seizures were induced in adult, male, Sprague‐Dawley rats with kainic acid (10 mg/kg), pilocarpine (300 mg/kg, preceded by methylscopolamine 1 mg/kg sc) or pentylenetetrazol (PTZ, 50 mg/kg ip or 90 mg/kg sc). Time to onset of seizure activity, duration of seizure activity (for PTZ), seizure severity and weight change for KA and pilocarpine were determined for each animal. The brains from animals who had received kainic acid or pilocarpine were examined for neurodegeneration and severe neuronal stress, using fluorojade staining and immunoreactivity for HSP72, respectively. Results: The Rb extract had a dose‐dependent anticonvulsant effect in all three models of chemically‐induced seizures – increasing the latency to the seizures, decreasing the seizure score, weight loss and subsequent neuronal damage after pilocarpine and kainic acid, and shortening the seizure duration and reducing mortality after PTZ. In some animals, the Rb extract completely blocked behavioral seizures after administration of kainic acid. The root preparation increased the mortality rate after administration of pilocarpine, but had no other significant effects. The leaves/stems preparation reduced the weight loss after pilocarpine, but had no other significant effects. The individual ginsenosides significantly increased the latency to onset of seizures after administration of kainic acid. Mixtures of purified Rb1, Rb3 with or without Rd had significant anticonvulsant effects in all three models of acutely‐induced seizures demonstrating that the ginsenosides are the active components in the Rb extract. Conclusions: Ginseng extract made from either the root or leaves/stems are ineffective against chemically‐induced seizures. A partial purification of the whole extract that concentrates the Rb1 and Rb3 ginsenosides has significant anticonvulsant properties. Since no one individual ginsenoside accounted for the majority of the activity of the Rb extract, the results suggest that the most effective anticonvulsant product is a combination of ginsenosides from the Rb group. In addition, the Rb extract and the individual ginsenosides have significant neuroprotective activity beyond the reduction in seizure severity and duration. (Supported by the Epilepsy Research Foundation New Therapies Program.) 1 Michael P. Macken, 2 Michael J. Boyd, 2 Patrick L. Alore, and 2 Robert T. Standring ( 1 Department of Neurology, Loyola University Medical Center, Maywood, IL ; and 2 Loyola University Chicago, Stritch School of Medicine, Maywood, IL ) Rationale: Levetiracetam is a novel anticonvulsant with a side‐effect and pharmacokinetic profile which recommends it use in a number of clinical settings,including the patient who presents to the emergency room with acute onset siezures. Levetiracetam is particularly useful if patients are taking multiple other medications since it is renally excreted, non‐protein‐bound and neither inhibits nor induces hepatic enxzymes. An intravenous formulation of levetiracetam is not yet available for general use and many physicians have concerns regarding oral loading of anticonvulsants in the acute setting. Concerns regarding the need to achieve a rapid therapeutic level of an anticonvulsant were addressed by means of simultaneous intravenous loading of fosphenytoin or phenytoin combined with oral loading of levetiracetam, followed by levetiracetam monotherapy. Methods: Several patients were managed in the manner described above in the acute hospital setting, mainly emergency room admissions and but also some inpatients who suffered seizures in other clinical settings. Intravenous fosphenytoin was given at doses of 15–20 mgs/kg and combined with oral loading doses of levetiracetam ranging from 1000 – 1500 mgs. A retrospective chart review was carried out to assess the efficacy of this approach in terms of short‐term seizure control and side effect profile. Results: A total of 20 patients were identified who were treated according to this protocol. No adverse events were reported related to the use of oral levetiracetam dosing (1000–1500 mgs oral loading dose) although one patient suffered purple‐glove syndrome due to phenytoin infusion. All patients remained seizure free over the 72 hours following combined loading, by which time levetiracetam concentrations had acheived steady‐state concentrations. The majority were discharged on levetiracteam monotherapy and these patients were followed‐up on an out‐patient basis to assess long‐term efficacy and side‐effect profile. Conclusions: An intravenous preparation of levetiracetam will be available in the near future, however approval for intravenous loading as a first line therapy in the acute setting is unlikely to be obtained in the short‐term. The approach outlined in this study combines the safety and experience of intravenous fosphenytoin loading with the pharmacokinetic advantages of maintenance LEV therapy. The use of one loading dose of fosphenytoin addresses the main concern of clinicians in the acute setting, namely the acheivement of immediate theraputic anticonvulsant levels, this is combined with the pharmacokinetic advantages of levetiracetam maintenance therapy. Based on the limited data available in this retrospective analysis, this approach appears to be safe and effective in terms of immediate seizure control and long‐term maintenance therapy. (Supported by UCB Pharmal.) 1 Iratxe Maestro, 2 Albert Molins, 1 Mar Carreño, 1 Antonio Donaire, and 1 Joaquín Castillo ( 1 Neurology, Hospital Clinic, Barcelona, Barcelona, Spain ; and 2 Neurology, Hospital Josep Trueta, Girona, Girona, Spain ) Rationale: Pregabalin (PGB) is a new antiepileptic drug, availabe in Europe since February 2005, which has shown, in randomized clinical trials, efficacy and good tolerability as add‐on treatment in patients with refractory epilepsy. Our objective was to study the efficacy and tolerability of PGB when used in every day clinical practice to treat refractory patients in two tertiary centers. Methods: We retrospectively reviewed 101 patients (60 women, 41 men) who received PGB as add on treatment for refractory seizures, at the Epilepsy Units of Hospital Clínic (Barcelona, Spain) and Hospital Joseph Trueta (Girona, Spain). Mean age was 40 years (16–64), mean time from seizure onset was 22 years (7–53), mean number of concomitant AEDs was 2.8. Most patients had temporal lobe epilepsy (43 patients), followed by frontal lobe epilepsy (29), unlocalized focal epilepsy (23 patients), parieto‐occipital epilepsy (4 patients) and multifocal epilepsy (2). Seizures were highly refractory, with a mean number of seizures per month of 48.5. Mean follow up was 8 months (3–14). Results: Mean PGB dose used was 412.5 mg. Fifty three patients (52%) were responders (had ≥ 50% seizure reduction). A significant number of patients (14, 13.8%) became seizure free. Seizure frequency increased in 4 patients (3.6%). Three patients reported similar number of seizures but less severity (shorter seizures or absence of generalized tonic clonic convulsions). PGB was generally well tolerated. Sixty per cent of patients reported adverse events, being weight gain > 10% the most frequent, seen in 25 patients (24.7%). Dizziness/ataxia was seen in 14 patients (13.8%). Seven patients (6.9%) displayed lower limb edema not accompanied by metabolic disturbance, and 4 patients (3.9%) had dose‐dependent blurred vision. Adverse effects were generally mild to moderate in severity. Twenty two patients discontinued PGB, either because of adverse effects (9 patients), inefficacy (6) or both (7 patients). Prescribing physicians rated 18 patients (17.8%) as “highly improved,” 42 patients (41.5%) as “improved,” 33 patients (32%) as “unchanged,” 6 patients (5.9%) as “worse” and 4 patients as “much worse” (3.9%). Conclusions: PGB, when used in every day clinical practice, is effective and safe as add‐on treatment in refractoy epilepsy. In our series of highly refractory patients, 52% had at least a 50% seizure reduction and 14% of patients became seizure free. Most frequent adverse events were weight gain and dizziness/ataxia. Most patients were rated as highly improved or improved by the prescribing physician. 1 Roberta Meo, 2 Leonilda Bilo, 2 Patrizia Ruosi, and 2 Maria Fulvia de Leva ( 1 Neurology Outpatients Service, Azienda Sanitaria Locale Napoli 1, Naples, Italy ; and 2 Epilepsy Center, Department of Neurological Sciences, Federico II University, Naples, Italy ) Rationale: The aim of this study was to evaluate efficacy and tolerability of levetiracetam (LEV) monotherapy in patients with post‐traumatic epilepsy. Methods: Six patients with post‐traumatic epilepsy entered the study. All presented complex partial seizures, with secondary generalization in 3 cases. At study enter 3 patients were already treated with antiepileptic drugs (AEDs): these patients were seizure free but all reported severe side effects related to AED treatment. The remaining 3 patients were not treated at study entry: two of them had received AEDs in the past, but had discontinued treatment because of side effects, while the last one was a 70‐year old man who had never been treated with AEDs and who reported also severe memory disturbances after the trauma. These 3 patients still presented seizures. LEV was initially given as add on therapy in the 3 treated patients: concomitant AED treatment was slowly withdrawn in the following months and the patients were left on LEV monotherapy. The 3 untreated patients received LEV in monotherapy since the beginning. Follow up with LEV monotherapy was at least 12 months in all patients. Results: In the 3 patients who were already seizure free, switch from previous AED treatment to LEV monotherapy was accompanied by persisting complete control of seizures; side effects related to previous AED treatment disappeared with relevant improvement of quality of life. In the 3 untreated patients LEV resulted in complete seizure control without side effects. The elderly patient showed also a considerable improvement of memory disturbances, possibly related to control of infraclinic seizures. Conclusions: In our small series LEV was effective in treating post‐traumatic seizures, showing also a good tolerability without adverse effects on memory, behaviour and cognitive state. This is particularly important since memory disturbances and cognitive impairment are frequent after severe head trauma. 1 John A. Messenheimer, and 2 Marianne Cunnington ( 1 Neurosciences Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC ; and 2 Epidemiology, GlaxoSmithKline, United Kingdom ) Rationale: To characterize the overall risk of major congenital malformations (MCM) associated with exposure to lamotrigine. The international registry forms part of an epidemiologic safety program monitoring pregnancy outcomes in women exposed to lamotrigine that has been in operation since 1992. Methods: Physicians report exposure to lamotrigine during pregnancy and subsequent outcomes on a voluntary basis. Prospective reporting (prior to any knowledge regarding the possible outcome of the pregnancy) early in pregnancy is encouraged. Major congenital malformations (MCMs) are classified according to the Centers for Disease Control criteria and are reviewed by a paediatrician. The percentage of MCMs is calculated using only prospective first trimester lamotrigine monotherapy and polytherapy exposures. Conclusions are developed and endorsed by a scientific advisory committee. Results: As of September 2005, 20 MCMs were observed among 707 first trimester monotherapy exposures yeilding a risk of 2.8% (95% CI 1.8%– 4.4%). The observed risk among 118 lamotrigine and valproate polytherapy exposures was 11.8% (95% CI 6.8%– 19.3%) and was 2.7% (95% CI 1.2%– 5.8%) among 256 exposures to lamotrigine polytherapy without valproate. The mean and median monotherapy doses for subjects with MCMs respectively were 250.7 and 200 mg/day; the mean and median doses for those without defects were 281.1 and 200 mg/day. No consistent pattern of malformation types was observed. Conclusions: The current data do not indicate any substantial increase in the overall risk of major defects associated with prenatal lamotrigine exposure, though the sample size is insufficient to allow definitive conclusions concerning specific defect types. The higher frequency of major malformations following lamotrigine‐valproate polytherapy exposure was consistent with publications on valproate monotherapy. Continued registration of exposed pregnancies will enhance the statistical power of the study and the data available for physicians to assess the benefit‐risk of lamotrigine use in pregnancy. (Supported by GlaxoSmithKline Research and Development.) 1 Paul H. McCabe, 1 Cathy D. McNew, and 1 Nancy C. Michel ( 1 Neurology, Penn State, Milton S. Hershey Medical Center, Hershey, PA ) Rationale: Weight gain is associated with valproic acid/divalproex sodium therapy. However, long‐term data which quantifies weight changes seen in epilepsy patients receiving the drug is lacking. We report on the long‐term changes that occur in patients taking the drug. Methods: Patients started on valproic acid (VPA) in the form of divalproex sodium at Penn State, Milton S. Hershey Medical Center were offered the opportunity to participate in the study. Initial weights were recorded prior to starting therapy. Weights were recorded at each visit on the same digital scale. Concomitant medications were recorded. Results: Forty‐two patients entered the study. One was lost to follow‐up, leaving 41 patients for analysis. There were 17 female and 24 male patients. Mean age was 33.1 years with a range of 17 to 69 years of age. Focal onset seizures were present in 27 patients, 5 were primary generalized, and 9 patients had features of both, making it difficult to determine the class. Mean VPA dosage was 1659 mg/day with mean VPA doses ranging from 500 – 4846 mg/day. Time on therapy ranged from 12 – 138 months with a mean of 56 months. Mean starting weight was 75.4 kg with a range from 46.4 – 131.8 kg. Weight gain was defined as an increase in weight of 5% or more while on VPA therapy. Weight gain was seen in 26 patients (63.4%) with the mean weight gained at time of maximum weight being 19% of initial body weight. Weight gain ranged from 5.18%– 56.5% of initial weight. Four patients did not maintain maximum weight and by the end of the study, only 22 patients (53.7%) had weights greater than 5% of start weights. Mean time to maximal weight gain was 44.2 months, with a range of 10 – 124 months. Male patients had a higher tendency toward weight gain, with 17 of the 24 males (70.8%) experiencing weight gain. Of 17 female patients, 9 (52.9%) demonstrated weight gain. A comparison based on seizure type was also looked at, but numbers were small. Fifteen of 27 (55.6%) focal onset patients and 3 of 5 (60%) patients with primary generalized onset experienced weight gain. Interestingly, 8 of the 9 patients with features of both focal and generalized onset demonstrated weight gain. Patients with weight gain were on a mean VPA dose of 1791 mg/day, compared to 1429 mg/day in patients without weight gain. Conclusions: Weight gain occurred in 63.4% of patients receiving VPA, although only 53.7% demonstrated weight gain by the end of the study. The mean maximum weight gained was 19% of initial body weight. Mean time to maximum weight was 44.2 months. Weight gain was more likely in male patients and patients on higher dosages of VPA. No significant difference was noted in focal onset versus primary generalized, although numbers for the latter were small. Interestingly, 88.9% of patients with features of both focal onset and primary generalized epilepsy (unclear onset) demonstrated weight gain. 1 James M. Miller, 1 Anne E. Hammer, 1 Robert P. Kustra, and 1 John A. Messenheimer ( 1 Neurosciences Medicine Development Centre, GlaxoSmithKline, Research Triangle Park, NC ) Rationale: Approximately 30% of people with epilepsy (PWE) spontaneously report depressed mood as a significant problem having a negative effect on quality of life (QoL). Within the general population, over half of adults with depression also suffer from a diagnosable anxiety disorder. Increasingly, the literature suggests that PWE may also experience significant symptoms of anxiety. The Profile of Mood States (POMS) evaluates a wide number of mood states, including anxiety, and is useful for evaluating drug therapy interventions. The 31‐item Quality of Life Inventory in Epilepsy (QOLIE‐31) is a validated questionnaire which measures epilepsy‐specific items such as seizure worry and broader items such as emotional well being and social functioning. Lamotrigine (LTG) is an antiepileptic drug (AED) that has been shown to improve mood, social interaction and overall wellbeing in PWE. This analysis investigated the correlation of anxiety with depression and quality of life in PWE and comorbid depressive symptoms, and changes following the addition of LTG to AED therapy. Methods: This was a multicenter open‐label study. Lamotrigine was added onto a stable AED regimen in the adjunctive phase and became a single agent in the monotherapy phase. Patients were eligible if they had epilepsy, exhibited depressive symptoms (Center for Epidemiological Studies Depression Scale (CES‐D) ≥ 12) but excluded if they had a Major Depressive Disorder as determined by a Mini International Neuropsychiatric Interview. Depression was measured with the Beck Depression Inventory (BDI‐II); anxiety and quality of life were measured with the POMS anxiety domain and QOLIE‐31 scale respectively. Evaluations were conducted at baseline, at the end of the adjunctive phase (Week 19) and the monotherapy phase (Week 36). Statistical analysis was done using paired t‐tests and Spearman correlations. Results: A total of 158 PWE (102 women, 56 men) enrolled into the study; 96 patients completed the adjunctive phase and 66 completed monotherapy. Mean baseline, end of adjunctive and monotherapy scores for BDI‐II were 17.4, 11.6, and 7.7; for POMS anxiety, the scores were 14.9, 11.8 and 9.4; for QOLIE‐31 the scores were 53.1, 64.8 and 72.3. POMS anxiety scores correlated with BDI‐II at baseline (0.584) and with QOLIE‐31 (−0.571); after adjunctive therapy, correlations were 0.618 and −0.591. With monotherapy, the correlations were 0.610 and −0.631. All change scores were significant at p < 0.001 and all correlations were significant at p < 0.0001. Conclusions: This evaluation suggests that anxiety is present in PWE who also exhibit depressive symptoms, and may contribute to low QoL scores reported in this population. The addition of LTG to the AED regimen significantly improved measures of both anxiety and depression with resulting improvement in quality of life. (Supported by GlaxoSmithKline Research and Development.) 1 Tracey A. Milligan, and 1 Edward B. Bromfield ( 1 Neurology, Brigham and Women's Hospital, Boston, MA ) Rationale: Early post‐operative seizures are well recognized and antiepileptic drugs (AEDs) are commonly used despite limited evidence of a prophylactic or antiepileptogenic benefit. Phenytoin (PHT), the most commonly used AED, has well known adverse reactions. Levetiracetam (LEV) has a low incidence of serious reactions. However, its safety and efficacy in the perioperative period have not been evaluated. Methods: A research patient database was used to identify nonepileptic patients who had supratentorial neurosurgery at Brigham and Women's or Massachusetts General Hospitals, during a five year period (1/1999–12/2004) and were followed for at least 7 days. The electronic medical records of patients who received LEV monotherapy were analyzed. A control group consisting of PHT monotherapy patients (2:1 vs. LEV) was randomly selected. The following procedures were excluded: pressure measurement devices, external and internal ventricular drainage. Records were reviewed for rate of seizures (at presentation, 1 week postoperatively, and development of epilepsy in those patients followed for at least one year). The other main outcome assessed was rate of adverse reactions during the postoperative period. Chi‐square and Fisher's tests were used for intergroup comparisons. Results: 105 LEV patients were identified. They were 39% male. Mean age was 55 (range 29–88). The 210 PHT patients were 47% male. Mean age was 64 (range 23–95). LEV dose ranged from 500 to 3000 mg/d, with 1000 mg/d used most frequently. The LEV diagnoses were 41% glial tumors, 10% meningiomas, 11% metastases, 21% hemorrhages, 10% vascular malformations, 4% infections, and 3% other. The PHT diagnoses were 27% glial tumors, 17% meningiomas, 13% metastases, 24% hemorrhages, 7% vascular malformations, 2% infections, and 10% other. Of the 105 LEV patients, 33 had presented with a seizure vs 57/210 PHT patients (p = 0.26). 1 LEV patient (1%) had an early postoperative seizure (within the first 7 days), vs 9 PHT patients (4%) (p = 0.28). Mean follow‐up for the LEV group was 12 mo, vs 20 mo for PHT. 42 LEV patients were followed for one year or more and 11/42 (26%) developed epilepsy, vs 42/117 (36%) on PHT (p = 0.32). Adverse reactions prompting a change in AED during the hospitalization occurred in 1/105 (1%) LEV patients (visual hallucinations), vs 38/210 (18%) PHT patients (p < 0.001). These reactions consisted of allergy (2), rash (22), fever (8), tremors (1), cytopenia (3), rhabdomyolysis (1), and cognitive change (1). Of the LEV group with epilepsy followed for at least 12 months, 7/11 remained on levetiracetam (64%) vs 11/42 (26%) on phenytoin (p = 0.025). Conclusions: Both LEV and PHT are associated with a low risk of early post‐operative seizures and a moderate risk of later epilepsy. LEV is associated with significantly fewer adverse reactions, an attractive feature particularly when an agent is being used prophylactically, as well as with a higher retention rate in patients who developed epilepsy. (Supported by UCB Pharma Young Investigators Award.) 1 Navid Mostofi, 1 Mercedes P. Jacobson, 1 Zulfi Haneef, and 2 John O. Elliott ( 1 Neurology, Temple University Hospital, Philadelphia, PA ; and 2 Comprehensive Cancer Center, Ohio State University, Columbus, OH ) Rationale: Osteoporosis (OP) is an important complication of long term anti‐epileptic treatment in patients with epilepsy. Calcium and vitamin D supplementation have been traditionally used to prevent this condition. Although bisphosphonates are approved for treatment and prevention of OP in post‐menopausal women and with men with osteoporosis, there is paucity of evidence measuring the efficacy of this group of medications in men receiving anti‐epileptic treatment. Methods: Retrospective review of charts of all male subjects with epilepsy at our center identified subjects with OP secondary to chronic antiepileptic therapy. Treatment and response to treatment for men with OP were investigated, specifically by looking at response to bisphosphonates as assessed by DEXA scan. Standard practice in our center is to recommend calcium, vitamin D and exercise for all individuals, regardless of bone density. Results: Seventy three male subjects were screened. Twenty six had Osteopenia and 15 had OP. Nine of the OP subjects received bisphosphonates as a part of their treatment. Of these, 5 (mean age 43.6; range 23–69 years) completed a second DEXA scan by 6/1/06. Calcium, vitamin D and exercise were recommended for all 5 subjects, but only 2/5 could perform moderate exercise. Table 1 demostrates the T scores of OP subjects at baseline, and after treatment with bisphosphonates. Comparison of T scores of subjects with OP before and after treatment with bisphosphanates Subject # DEXA 1(spine) DEXA 1(hip) DEXA 2(spine) DEXA 2(hip) Interval (months) 1 −1.8 −3.5 −1.9 −3.5 17 2 −3.6 −2.9 −3.3 −2.9 18 3 −3.7 −1.8 −4.7 −1.4 26 4 −3.0 −2.7 23 5 −4.1 −1.8 −3.2 −1.6 30 As shown in the table, 80% (4/5) of the subjects had either stabilization or increase in their bone density after being treated with bisphosphonates. Of the 4 responders, only on demonstrated increased bone density. Conclusions: Bisphosphonate therapy appears effective in reducing the progression of osteoporosis in men using antiepileptic medications. Specific patient co‐morbidities could contribute to this observation, but it may be important to prevent, screen and treat metabolic bone disease much earlier in men with epilepsy. This is an on‐going study; as more males with OP complete 18 months of bisphosphonate therapy, these results may change. 1 Kevin Nanry, 2 Eugene Ramsay, 3 Martha Sajatovic, 1 Eric Bourne, and 1 Thomas Thompson ( 1 Psychiatry, GlaxoSmithKline, RTP, NC ; 2 International Center Epilepsy, University of Miami, Maimi, FL ; and 3 Psychiatry, Case Western Reserve University, Cleveland, OH ) Rationale: In spite of wide clinical use, there is a paucity of data on anticonvulsant drugs in elderly patients with psychiatric and neurological disorders. The authors conducted a systemized analysis of the literature on lamotrigine (LTG) therapy in elderly patients with BD, epilepsy, or dementia. Methods: The search included electronic databases, meeting abstracts and presentations. Results: Fourteen reports included controlled trials, retrospective analyses, and case studies. Reports of LTG in geriatric BD suggest improvement in depression, core manic symptoms and delay in mood relapse. Mean dose in larger samples was 182–240 mg/day. Controlled trials in geriatric epilepsy demonstrated efficacy and tolerability comparable to gabapentin. Compared to carbamazepine, there were fewer treatment withdrawals and fewer cases of somnolence or rash in the lamotrigine group. Preliminary reports in dementia note improvement in cognition, agitation and depression. While elimination of LTG can be affected by increasing age, disposition is more directly impacted by concurrent anticonvulsant therapy. There is extensive variability in LTG concentration/dose (C/D) ratios across the age‐span, but as a group C/D ratios increase through adulthood. Conclusions: LTG appears effective and was well tolerated in older adults with BD, epilepsy and dementia. Incidence and severity of adverse events appears similar to that established in younger patient populations. (Supported by GlaxoSmithKline.) 1 Wayne M. Alves, 1 Yuhua Li, 2 Virinder Nohria, on behalf of the 212 Study Investigators ( 1 Research & Development, Valeant Pharmaceuticals International, Costa Mesa, CA ; and 2 Clinical Medicine, Emory University, Atlanta, GA ) Rationale: Both weight gain and weight loss have been associated with many antiepileptic drugs (AEDs). AED‐associated changes in weight appear slowly and over the long‐term with therapy. Retigabine is a novel AED that enhances the potassium currents mediated by human KCNQ2/3 and KCNQ3/5 potassium channels and is currently undergoing global phase 3 studies as adjunctive treatment for partial‐onset seizures in adults with refractory epilepsy. In this report data from Study 212, a long‐term open‐label extension of a double‐blind phase 2 trial (1), were analyzed to characterize weight changes with long‐term retigabine adjunctive therapy. Methods: 399 patients (age range: 16–70 years, baseline seizure frequency: ≥4 seizures/month) participated in a multicenter, randomized, double‐blind, placebo‐controlled phase 2 trial. Study design included an 8‐week baseline and 16‐week double‐blind treatment period (8‐week forced titration and 8‐week maintenance). Patients received placebo or retigabine 600, 900, or 1200 mg/day and up to 2 approved AEDs. 279 patients completed the study and 222 enrolled in the open‐label extension (Study 212). Patients could receive 600–1200 mg/day of retigabine. Body weight and adverse events were evaluated over time. Body weight changes and absolute body weight were calculated at various times during the treatment period. Results: Of the 222 patients included in the analysis, 56.8% were male, and mean age was 36.1 years (range: 14–66 years). 47.3% of patients received retigabine 900 mg/day and 23.4% received 1200 mg/day as their maximum dosage. The mean duration of therapy was 352.5 days (range: 5–682 days). Body weight remained stable throughout the long‐term extension study (Table). The mean difference in weight at 1 year was 2.2 kg (73.4–75.6 kg). Increased body weight was reported as a treatment‐emergent adverse event (TEAE) by 3 patients (1.4%), while 2 patients discontinued the study due to increased weight, although in 1 patient this was not considered to be a TEAE. TABLE Absolute Body Weight With Adjunctive Retigabine Therapy Body weight (kg) Open‐Label Extension Study Day Baseline (n = 222) 90 (n = 193) 180 (n = 175) 270 (n = 143) 360 (n = 188) 450 (n = 83) 540 (n = 94) Mean 73.4 75.4 74.9 75.0 75.6 72.1 72.48 Range 47–134 47–136 48–135 45–135 48–136 48–115 49–133 Conclusions: Long‐term adjunctive therapy with retigabine 600 to 1200 mg/day is not associated with weight gain. References 1. Porter P, Alves W, Nohria V, et al. World Congress of Neurology, 2005 ( Sydney , Australia ). (Supported by Valeant Pharmaceuticals International.) 1 Oladotun Okunola, 2 Yong Won Cho, 3 Kimford J. Meador, and 1 Gholam K. Motamedi ( 1 Department of Neurology, Georgetown University Hospital, Washington, DC ; 2 Department of Neurology, Dongsan Medical Center, Keimyung University, Taegu, Republic of Korea ; and 3 Department of Neurology, University of Florida, Gainesville, FL ) Rationale: Patients who have failed treatment with an antiepileptic drug (AED) are less likely to become seizure‐free on monotherapy with any other agent. There is little established evidence regarding the efficacy of specific polytherapy combinations. We compared the efficacy of polytherapy with levetiracetam (LEV) and lamotrigine (LTG) with monotherapy with either one of these agents. Methods: We reviewed antiepileptic drug regimens of 91 patients with epilepsy treated from 2000–2006. The patients' response to monotherapy with LEV (N 42) and LTG (N 37), were compared to polytherapy using LEV+LTG (N 12). These patients had failed other AEDs and were placed on LTG and/or LEV for seizure control. We measured the decrease in seizure frequency per month using paired Student's t‐test. Results: Patients treated with LEV monotherapy showed a significant decrease in mean seizure frequency (from 2.02 to 0.86, p < 0.048). Patients treated with LTG monotherapy had an increase in mean seizure frequency but this difference was not significant (from 2.14 to 3.11, p < 0.56). Patients treated with LEV and LTG polytherapy showed a significant decrease in their mean seizure frequency (from 10.5 to 0.5, p < 0.07). Conclusions: These findings suggest that monotherapy with LEV and polytherapy using LEV and LTG in combination may be more effective than monotherapy with LTG alone. These results could be due to efficacy of either LEV or the LEV‐LTG combination. Direct comparisons of patients sequentially treated with LEV and LTG and then with LEV and LTG together would be needed to determine this. 1 Nicola Paciello, 2 Pier Nicola Marchi, 1 Michele Chiummiento, 3 Salvatore Mazza, and 1 Marcantonio Paciello ( 1 Neuroscience Department, Neurology Unit, San Carlo Hospital, Potenza, Italy ; 2 Neurology Unit, San Giovanni di Dio Hospital, Cagliari, Italy ; and 3 Neuroscience Department, Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy ) Rationale: We describe the efficacy and tolerability of levetiracetam (LEV) versus carbamazepine (CBZ) in treatment of epileptic elderly patients. Methods: The population of the study is composed by 24 consecutive newly diagnosed outpatient, 14 males and 10 females, referred to our epilepsy centres because of at least two unprovoked seizures in last 12 months. Each patient has performed a standard EEG, a brain MRI and a self‐administered quality of life questionnaire (SF‐36) at first visit. All patients have performed an EEG and a SF‐36 questionnaire at 12 weeks, 24 weeks and at 48 weeks of follow up. We divided these patients in two groups: 12 patients out of 24 with LEV at dosage of 1000 mg a day (LEV group) and 12 patients out of 24 with CBZ at dosage of 600 mg a day (CBZ group). Both treatments have been used as monotherapy. Results: 17 patients, 9 out of 17 including in LEV group and 8 out of 17 including in CBZ group, showed minimal MRI abnormalities consisting of point lacunar infarcts of white and/or grey matter of the brain. 9 out of 24 patients, 6 of LEV group and 3 of CBZ group, showed minimal EEG abnormalities at basal evaluation consisting of focal theta waves that have disappeared after 12 weeks of treatment in all patients. All patients have been seizure‐free for 48 weeks of follow up except 3 patients, 2 on CBZ and 1 on LEV that have presented a motor partial seizure: in these patients we have increased the dosage respectively to 800 mg a day and 1500 mg a day. All LEV group have completed the follow up period remaining on original drug with a retention rate of 100%, while 3 patients of CBZ group have discontinued therapy for intolerable side effects: 2 patients showed marked somnolence and one patient showed dizziness. For this reason the retention rate of CBZ group has been 75%. SF‐36 findings showed a poor impact of treatment on quality of life in all LEV group, while data of CBZ group showed a light worsening in some items of the questionnaire in 4 out of 12 patients. Conclusions: Retention in the study has been significantly better for LEV than for CBZ. CBZ caused significantly more side effects than LEV, resulting in earlier termination of treatment. Optimal dose of both drugs may be lower in elderly compared with general epileptic population. The efficacy of LEV and CBZ is very similar, but the impact of drug on quality of life is perceived in pretty different manner by patients. Even though it is necessary a larger population, we believe that LEV should be considered as possible first‐line therapy for new onset seizures in the elderly. 1 Aldo Paggi, 1 Andrea Ortenzi, 1 Nicoletta Foschi, and 1 Sheila Catani ( 1 Epilepsy Center – Department of Neurological Sciences, Azienda Ospedali Riuniti, Ancona, Italy ) Rationale: Some newer antiepileptic drugs (AEDs) such as Levetiracetam (LEV) show a better tolerability and less interaction with concomitant medications than older AEDs. The aim of this study was to evaluate the efficacy and tolerability of LEV as add‐on therapy or as substitutive monotherapy in adolescent and adult patients (pts) with refractory epilepsy (E) or with a poor tolerability of previous AEDs treatment. Methods: prospective, open‐label, not controlled trial in which LEV was given as add on therapy or in substitution of previous monotherapy. LEV was started at 500 mg/day dose and progressively up titrated over 1–2 weeks by 500 mg/day every third day to a maximum dose of 2000–3000 mg/day. We report preliminary data about 30 pts (10 M and 20 F; mean age 42.47, sd = 19.69, min 17 max 86). Pts suffering from symptomatic encephalopathies, general diseases and history of psychiatric disorders and/or pseudo seizures, which could modify the seizure semiology and their frequency, were excluded. In 17 pts LEV was given as add on (group I) and 13 switched from previous AED to LEV monotherapy (group II). The mean follow‐up was 88.15 days (SD = 44.27, min.3, max 160). Demographic and aetiological aspects were comparable in the 2 groups: mean age 41 (group I) vs 43 (group II); pts mainly affected by focal epilepsy in both groups with no cases of Lennox‐Gastaut syndrome; mean seizure frequency at baseline was comparable in both groups.In group I we added LEV without modifying the previous AED therapy (number of AEDs: mean 2.18); in group II we switched previous AED to LEV. Therapy modification in group I was due to inefficacy in 9 pts, AEs in 3 pts and both in 5. In group II it was due to inefficacy in 7 pts, AEs in 3 pts and both in 3. Results: Efficacy: in group I (LEV as add on therapy) 14/17 pts resulted evaluable (2 pts withdrew consent and 1 had a too short follow‐up (<30 days). At cut‐off date (May 31st 2006), 9 pts (64.3%) were seizure‐free, 2 (14.3%) had a > 50% seizure frequency reduction and 3 (21.4%) were unchanged or worsened seizure frequency. In group II (LEV as monotherapy) 11/13 pts resulted evaluable (1 pt withdrew consent and 1 had a too short follow‐up (<30 days). At cut‐off date, 7 pts (63.6%) were seizure‐free, 3 (27.3%) showed a > 50% seizure frequency reduction and 1 (9.1%) remained unchanged. Seizure type or aetiology did not appear correlated to the efficacy of LEV in pts with focal E.Tolerability: 7/30 pts (23.3%) reported AEs, which led to drug discontinuation in 2 cases. The most frequent AE resulted gastralgia (3 pts). Conclusions: These preliminary results (the study foresees the enrollment of 80–100 pts and a follow up period of at least 12 months) suggest the good efficacy and tolerability of LEV in epileptic pts both as add‐on therapy and as monotherapy. The study is currently ongoing and final data will be presented as soon as available. 1 Page B. Pennell, 1 Archana Koganti, 2 Limin Peng, 1 Melanee Newman, 1,3 Denicia Holley, and 3 Zachary Stowe ( 1 Neurology, Emory University School of Medicine, Atlanta, GA ; 2 School of Public Health, Emory University, Atlanta, GA ; and 3 Psychiatry, Emory University School of Medicine, Atlanta, GA ) Rationale: Pregnancy in women with epilepsy (WWE) is accompanied by increased fetal risks due to both antiepileptic drug (AED) exposure and maternal seizures (sz). Relatively low rates of major malformations on lamotrigine (LTG) has led to its increased use during childbearing years. However, observational studies indicate that LTG clearance (Cl) markedly increases during pregnancy, and sz worsening has been reported in 45–75% of women on LTG monotherapy. Maternal seizures, especially of the convulsive type, have been associated with fetal loss, fetal hypoxia, and poor neurodevelopmental outcomes. Methods: WWE on AEDs either during or planning a pregnancy were consented to participate in a prospective study. Subset analysis was performed on all WWE on LTG monotherapy who had adequate baseline information about sz frequency and preconception target LTG concs (n = 30). Although no specific protocol was mandated by the study, results of LTG concs were actively used for therapeutic drug monitoring (TDM). Recommendations to adjust LTG dose were made according to the pt's sz type(s), epilepsy syndrome, sz frequency, history of LTG‐related side effects, gestational age, and what was considered that individual's target conc. For each trimester (TM), we coded relative frequency of all‐type sz's as 1 if number of sz's was greater than baseline, and 0 otherwise. For each TM, we calculated the ratio to target concentration (RTC) as LTG conc/target LTG conc from baseline. Results: Seizures worsened during pregnancy in 28% of pts and convulsive seizures worsened in 10% (Figure 1). RTC values of pts with worsened sz frequency were lower than RTC values of those with stable seizures in the 2nd TM (p < 0.001) and the 3rd TM (p = 0.05) but not the 1st TM. Similar significant findings occurred if definitions were 1.5x and 2x increase in sz frequency. Convulsive seizures doubled in 10% of pregnancies; impact of RTC was not significant. Conclusions: This analysis demonstrates that seizure worsening during pregnancy is associated with a low RTC, and that improved results for sz control can be achieved with an active TDM approach. However, this extent of sz control is not ideal and development of a population pharmacokinetic model that will define a treatment plan and dosing paradigm for LTG use during pregnancy, adaptable to the individual patient, is necessary to improve the maternal and fetal well‐being of our patients further. (figure 1) (Supported by Specialized Center of Research P50 MH 68036.) 1 Jyoti A. Pillai, 1 Ijaz Malik, 1 Kamil J. Detyniecki, and 1 Sigmund Jenssen ( 1 Neurology, Drexel University College of Medicine, Philadelphia, PA ) Rationale: The incidence of osteoporosis varies amongst different ethnic groups, because of variations in skeletal architecture, bone turnover, and bone mass, with genetic factors also playing a role. Osteoporosis is more common amongst Caucasians as compared to African‐Americans. Patients with chronic epilepsy are at greater risk for bone loss, not only due to enzyme inducing anti‐epileptic drugs, but also due to other causes like decreased physical activity, poor dietary intake, and dietary restrictions like the ketogenic diet. The purpose of this study was to evaluate whether African‐Americans with chronic epilepsy are at less risk for developing bone loss as compared to Caucasians. Methods: A retrospective chart review was performed on all patients followed at the Epilepsy Center at Drexel University College of Medicine. Inclusion criteria were: age greater than 18 years, patients on any anticonvulsant medication for at least two years, at least one DEXA scan performed two years after initiation of treatment, and being either of African‐American or Caucasian race. We compared the prevalence of osteopenia/osteoporosis in each ethnic group. Results: 210 charts were reviewed and 49 met the inclusion criteria. Of these 26 were African‐Americans and 23 were Caucasians. Mean age for the entire population was 50.02 years (range 23 to 83), with the mean age for African‐Americans being 52.07 years and for the Caucasian group being 49.6 years. 24 were female (14 of these were African‐American) and 25 were male (11 of these were African‐American). There was no statistically significant difference in the prevalence of osteoporosis/osteopenia between the two ethnic groups, with 17 African‐American patients (8 males) and 15 Caucasian patients (10 males), representing 65% in each group, being found to have decreased bone mineral density on DEXA scan as defined by the WHO criteria (chi square = 0.083; p = 0.773). The average T value (the lowest T value at either the lumbar spine, the femoral neck, or the distal wrist) in Caucasians was −1.98, whereas in African‐Americans, it was −2.33. Of all patients, 20 were treated for more than 10 years with AEDs, 13 of these were African‐Americans. 14 of these 20 (70%) had decreased bone density, 9 of whom were African‐Americans. 18 out of 29 patients on AEDs for less than 10 years had decreased bone mineral density (62%). Duration of treatment did not correlate with bone loss (chi square = 0.32, p < 1). Conclusions: There was no statistically significant difference in bone mineral density between the African‐American and Caucasian patient groups with chronic epilepsy. The most likely reason for this is that decrease in bone mineral density in patients with chronic epilepsy is multifactorial. To investigate if ethnicity is a protective factor against bone loss secondary to chronic AED use, a prospective study needs to be undertaken. 1 John R. Pollard, 1 Susan T. Herman, 1 Brian Litt, 1 Ruth S. Krieger, and 1 Jacqueline A. French ( 1 Department of Neurology, Division of Epilepsy, Hospital of the University of Pennsylvania, Philadelphia, PA ) Rationale: Clinical trials are not designed to detect rare adverse events or adverse events with a long induction time. In contrast, a rigorous prospective post‐marketing study that catalogues data from clinical practice can detect these types of adverse events while avoiding the biases that are sometimes found in retrospective trials. This type of survey was initiated to detect rare or late adverse events caused by the use of pregabalin. Methods: Epilepsy patients started on pregabalin were enrolled prospectively as our center's contribution to the multicenter Post‐marketing Antiepileptic Drug Survey. 40 patients were enrolled at our center so far. Results: 23 patients with partial seizures have three month follow up. The average age was 43.6 years. The mean duration of epilepsy was 25 years, and the mean number of concomitant antiepileptic drugs was 2.7. The initially prescribed titration dose was a median 300mg and at 3 months the median dose was unchanged. 78% reported at least one adverse event. The common adverse events were: weight gain, ataxia or dyscoordination, fatigue, dizziness, headache, myoclonus and edema. One patient reported symptoms consistent with subacute onset of bilateral carpal tunnel syndrome. The median weight gain was 6 lbs, and the mean was 4.6 lbs. 56% of patients were found to have had some weight gain, and those that did gained an average of 8.5 lbs. 22% lost an average of 4.6 pounds. The discontinuation rate was 17.4%. 52.2% of patients reported a decrease in seizure frequency. Conclusions: These results are similar to those described in one of the pivotal clinical trials assessing the efficacy of pregabalin(1). The population of the current study differed from the clinical trial in 2 ways: the patients were older in age by 4 years and the number of concomitant antiepileptic drugs used at initiation was 2.7 versus the 1.7 in the randomized controlled trial. Interestingly, the rate of adverse events was close at similar dosages (78% vs. 84%). The most common adverse events were detected, and the weight gain data are very close to that reported for the highest dose in the clinical trial (4.6 vs. 5.0 lbs). In addition, the discontinuation rate was similar (17.4% vs. 14%). It is very encouraging that these early data so closely parallel that of a published prospective clinical trial. This suggests that the study design is sound and that it will be a sensitive tool for detecting adverse drug events such as those that are rare or that manifest later in treatment. Further follow‐up for the full cohort will be presented at the meeting. (1) French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Dose‐response trial of pregabalin adjunctive therapy in patients with partial seizures.Neurology. 2003 May 27;60(10):1631–7. (Supported by Current funding by Pfizer. Recent funding UCB, Ortho‐McNeil, Glaxo‐Wellcome, Elan Pharmaceuticals, Novartis.) 1 Baralee Prasittisopin, 2 R. Eugene Ramsay, 2 Flavia M. Macias, 3 A. James Rowan, 4 Joseph F. Collins, 1 Richard C. Brundage, and 1 Angela K. Birnbaum ( 1 Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN ; 2 VA Medical Center, Miami, FL ; 3 VA Medical Center, Bronx, NY ; and 4 VA Medical Center, Perry Point, MD ) Rationale: Little information of LTG pharmacokinetics is available in elderly patients. The aims of this study were to 1) estimate the oral clearance (CL/F) of LTG and 2) identify and quantify covariate effects that significantly affect CL/F. Methods: Data from VA Cooperative Study 428, a randomized, double‐blind, parallel group, monotherapy comparison study of carbamazepine (CBZ), gabapentin (GBP), and lamotrigine (LTG), were used for the analysis (n = 593). Patients 60 years and older with newly diagnosed seizures were randomly assigned to one of three treatments. Data from the LTG arm were used in this study. Thirty six patients on PHT at enrollment were gradually withdrawn during the 6‐week titration of LTG. Clinical evaluations including blood samples were obtained at enrollment, biweekly to week 8, monthly to week 28, and bimonthly to the end of the study(week 52). Analyses were performed using NONMEM. A one‐compartment model with first‐order absorption and elimination was used. The absorption rate constant (Ka) could not be estimated and were fixed to the literature values of 3.5 hr−1. Inter‐individual variability was modeled using an exponential error model. The residual unexplained variability was modeled using a combined additive and proportional error model. Covariate selection was done by forward selection (p < 0.01; χ2) and backward elimination (p < 0.001; χ2) using the likelihood ratio test as the model selection criterion. Results: The data consisted of 875 observations from 148 patients. It was found that weight, BUN/creatinine ratio, and phenytoin (PHT) use were significant covariates for clearance in the final model. Race was inititially significant but found to be correlated to BUN/creatinine ratio. The final regression model was determined to be: CL/F =((0.0332 × BUN/creatinine ratio) + (0.0268 × weight))× 1.59(if using phenytoin) Therefore, CL/F was estimated to be 2.64 L/hr, for patients weighing 80 kg, and a BUN/creatinine ratio 15:1. CL/F increased 59% in patients using PHT. Interindividual variability for CL/F of LTG was 34.2%. Percent CV and standard deviation for residual unexplained variability were 19.8% and 0.31 mcg/ml respectively. Conclusions: In our study, weight, BUN/creatinine ratio, and PHT use were significantly predictive of clearance. The effect of BUN/creatinine ratio on CL/F of LTG may be due to a surrogate effect of race. PHT, a known enzyme inducer, increases CL/F of LTG in elderly patients more than 50%. The results from this study may be useful for individualizing dose regimens in this population based on patient‐specific covariates. (Supported by NIH NINDS P50‐NS16308 and the VA Cooperative Study 428.) 1 Eugene R. Ramsay, and 2 Albert T. Leung ( 1 Department of Neurology, University of Miami School of Medicine, Miami, FL ; and 2 Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, NJ ) Rationale: Various antiepileptic drugs (AEDs), particularly cytochrome P450 enzyme inducers, have been linked to increases in bone turnover and decreases in bone mineral density. Collagen degradation that accompanies bone resorption produces amino‐terminal pyridinole cross‐linked telopeptides (NTX) that are excreted into the urine. NTX levels can therefore be used as a biomarker of bone turnover. A double‐blind, placebo‐controlled study of topiramate (TPM) in obese adults with dyslipidemia included measurements of urinary NTX/creatinine (Cr) ratios to evaluate the effect of TPM on bone metabolism in adults. Methods: Obese subjects 18–75 yrs of age with a BMI ≥27 kg/m2 and < 50 kg/m2 and mild‐to‐moderate hypertriglyceridemia were randomized to placebo, 96 mg/day TPM, or 192 mg/day TPM. TPM was titrated in 16 mg/day increments at 2‐wk intervals to the assigned dose or maximum tolerated dose. Urine specimens were obtained at baseline, every 2 wks during the 8‐wk titration phase, and every 4 wks during maintenance. NTX/Cr ratios, expressed as nmol bone collagen equivalent/mmol creatinine, were determined as a part of the study's safety evaluations. Results: Baseline and last‐visit urine samples were available for 29 subjects receiving placebo, 29 assigned to TPM 96, and 34 assigned to TPM 192. 72% of subjects were female, in whom mean age was 46–48 yrs. Median treatment durations were 167 (placebo), 151 (TPM 96), and 161 (TPM 192) days. Mean% changes from baseline NTX/Cr ratios were 18.3%, 26.5%, and 3.3%, respectively. In the placebo group, NTX/Cr ratios increased in 45% of patients; in 52% of the TPM 96 group, and in 44% of the TPM 192 group. Conclusions: In obese adults, bone turnover as measured with the urinary biomarker NTX was similar in TPM and placebo groups during long‐term (∼6 months) exposure. (Supported by Johnson & Johnson Pharmaceutical Research & Development, LLC.) 1 Rory P. Remmel, 1 Jeannine M. Conway, 1 John O. Rarick, 1 Angela K. Birnbaum, 3 Page B. Pennell, 4James R. White, and 1 Ilo E. Leppik ( 1 College of Pharmacy, University of Minnesota, Minneapolis, MN ; 2 Department of Neurology, Emory University, Atlanta, GA ; and 3 MINCEP Epilepsy Care, Minneapolis, MN ) Rationale: Lamotrigine (LTG) is a commonly prescribed antiepileptic drug. We are studying LTG pharmacokinetics (PK) in young and elderly patients with an intravenous, stable‐labeled LTG formulation. This is a preliminary report on the safety and tolerability of the formulation. Methods: Adult patients (>18 years) without significant cardiac problems or interacting co‐medications were enrolled. Patients on steady‐state maintenance LTG therapy were given a single 50 mg replacement dose of the (13C2,15N)‐LTG (SL‐LTG) formulation as part of their daily regimen. The remainder of their daily dose was given orally. Blood pressure (BP) and heart rate (HR) data were collected prior to infusion, every 2 minutes during infusion, and every 15 minutes for the first hour following the completion of the infusion. An EKG was taken before and during the infusion. The mean and standard deviation of HR and BP at baseline, end of infusion, and 30 minutes post‐infusion were determined. A value of p ≤ 0.05 was considered significant. The study nurse monitored the infusion site for inflammation during the infusion and at the time that the indwelling catheter was removed. Patients were asked during the infusion if they were experiencing discomfort at the infusion site or any other symptoms. Results: Five younger women (age 25–48 years) have completed the study. LTG daily doses ranged from 200–800 mg/day. There were no significant changes from baseline in EKG in any of the subjects studied. Table 1 presents the changes in vital signs in subjects as compared to their baseline, pre‐infusion time point. The minimum and maximum observed BP or HR did not occur at the same time in each individual. No subject reported discomfort at the injection site or any adverse events. There was no evidence of inflammation at the site of infusion. Conclusions: Our preliminary data indicate that this intravenous LTG formulation is safe and well tolerated when administered to relatively healthy adult patients. Baseline End of infusion 30 minutes post‐infusion p‐value Mean Systolic (mmHg) 121 ± 15.2 117 ± 12.0 115 ± 16.7 0.84 % change* −2.4 ± 8.3 −4.8 ± 4.1 0.58 Mean Diastolic (mmHg) 74.4 ± 10.3 74.2 ± 12.1 65.2 ± 16.6 0.48 % change 0.05 ± 4.5 −13.0 ± 12.8 0.07 Mean HR (beats per min) 74 ± 4.8 70 ± 8.1 77.2 ± 6.4 0.29 % change −4.3 ± 6.1 −4.5 ± 8.6 0.13 *% change from each individual's baseline measurements (Supported by NINDS P‐50NS16308 and MO1‐RR00400, M01‐RR00039.) 1 William E. Rosenfeld, 1 Susan M. Lippmann, 1 Patty Schaefer, and 1 Diane Vogler ( 1 Neurology, The Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO ) Rationale: The past 15 years have seen the release of several new antiepileptic medications. The last to be released was pregabalin in September 2005. We reviewed the patients that had been started on pregabalin at The Comprehensive Epilepsy Care Center For Children and Adults, St Louis, Mo from September 2005‐May 2006. The patients were evaluated for improvement in sz frequency, as well as for side effects. Methods: All patients that were started on pregabalin were included in the analysis. Efficacy and side effect data were recorded as of patients' last clinic/phone contact. Efficacy was evaluated, particularly as to greater than 50% reduction in sz frequency. Patients could be taking any number of other antiepileptic drugs and/or have a vagus nerve stimulator in place. Results: 50 patients were enrolled consecutively in this study. 4 patients withdrew due to side effects – 1 due to dizziness, 1 due to fatigue, 1 due to hallucinations (patient with previous history of such), and 1 due to reported increased urinary frequency. 2 patients' data were incomplete. 44 patients remained on pregabalin. 23/44 (52%) had greater than 50% reduction in seizures. 7/44 (16%) were seizure free. Mean dosage of pregabalin was 342 mg/day (range 100mg to 700 mg/day). Patients were taking pregabalin on an average of 5.4 months (ranging from 2 to 9 months). Patients were on 2.2 concomitant antiepileptic drugs (ranging from 0 to 4 antiepileptic drugs). 8/48 patients (16.7%) reported dizziness as their most common side effect. This was often transient in the first few days of usage of pregabalin. 6/48 patients (12.5%) reported fatigue. 5/48 patients (10.4%) reported weight gain. Conclusions: Pregabalin appears to be an effective antiepileptic drug in adjuntive therapy. It also appears to be well tolerated. Our findings were fairly consistent with the manufacturer's labeling for the medication. (Supported by the Comprehensive Epilepsy Care Center For Children And Adults, P.C.) 1 Antonio Russi, and 1 Thais Tarancon ( 1 Epilepsy Unit, Centro Medico Teknon, Barcelona, Barcelona, Spain ) Rationale: To compare the safety and tolerability of Levetiracetam (LEV) and Pregabalin (PGB) using one of two titration schedules (fast and slow) as add‐on treatment in patients with refractory partial epilepsy on polytherapy while receiving 3 concurrent marketed AEDs. Methods: A total of 128 patients with refractory partial epilepsy receiving a stable regimen of two or three AEDs were randomized to LEV fast rate, LEV slow rate, PGB fast rate and PGB slow rata dosage adjustment (32 patients × 4 groups). LEV fast rate group was given LEV at a starting dosage of 1000 mg b.i.d with weekly increments of 500 mg. LEV slow rate group was given LEV at a starting dosage of 500 mg b.i.d with weekly increments of 250 mg. PGB fast rate group was given PGB at starting dosage of 300 mg b.i.d with weekly increments of 150 mg. PGB slow rate group was given PGB at starting dosage of 150 mg b.i.d with weekly increments of 75 mg. Primary parameters were rate of withdrawals and rate of continuation to 3000 mg b.i.d LEV and 600 mg b.i.d PGB maximum dosage while reducing previous polytherapeutic dosage. Results: The incidence of adverse events was similar among LEV study groups (fast and slow rate dosage). With fast titration 2 out 32 (6.25%) and with slow titration 1 out 32 (3,12%) reported serious adverse events with discontinuation. In LEV groups 18 out 32 (56.25%) with fast titration and 20 out 32 (62.50%) with slow titration reached maximum LEV dosage (3000 mg b.i.d). These differences were not significant. Twelve patients reported side effects while taking PGB fast titration (37.5%) and only one (3.12%) with slow titration (p < 0.01). In these PGB groups 6 out 32 (18.75%) with fast titration and 20 out 32 (62.5%) with slow titration reached maximum PGB dosage (600 mg b.i.d) while reducing previous polytherapeutic dosage (p < 0.01). Conclusions: Levetiracetam appears to be well tolerated with fast and slow dosage regimen. Pregabalin should be taken with a starting dose of 150 mg b.i.d with weekly increments of 75 mg dosage adjustment as adjunctive treatment in patients with refractory partial epilepsy on excessive polytherapy. 1 Barbara Schauble, 1 Joern‐Roland Wettach, and 2 Andreas Schreiner ( 1 Medical & Scientific Affairs, Janssen‐Cilag, Neuss, Germany ; and 2 Medical & Scientific Affairs, Janssen‐Cilag EMEA, Neuss, Germany ) Rationale: To evaluate seizure frequency and tolerability in patients with epilepsy treated with topiramate (TPM) transitioning from valproic acid (VPA). Methods: Multicenter open‐label non‐interventional study. Patients ≥ 12 years of age with epilepsy previously unsuccessfully treated with VPA were prospectively followed for 20 weeks after transition to TPM. A 12 week retrospective seizure frequency was used as baseline. Results: 147 patients (59% female; mean age 42 year (±SD 19)) were identified. Median duration of epilepsy was 9 years (range, 0–60 years). 77% had seizures during the 12 weeks retrospective baseline. Most frequent seizure types at baseline were generalized tonic‐clonic (52%), complex partial (23%), and simple partial (12%). Main reasons provided for transitioning from VPA to TPM were insufficient efficacy (61%) and/or side effects (81%). Side effects listed as reason for transitioning (≥10%) were weight gain (37%), tremor (29%), fatigue (21%), hair loss (12%) cognitive disorder, hepatic function abnormalities or nausea (10% each). At endpoint, the median TPM dose was 125 mg/day. Mean seizure frequency decreased significantly from 32 (±SD 248) seizures per month during the retrospective baseline to 3 (±SD 16) seizures/month during the maintenance period (p < 0.001). The responder rate (≥ 50% seizure reduction) during the maintenance period was 75%, and 51% patients remained seizure‐free during this period. 16% of patients discontinued TPM, 8% due to an adverse event (AE), and 3% due to insufficient efficacy. Treatment‐emergent adverse events (TEAE) were reported in 14% of patients. TEAE occurring ≥ 3% were paraesthesia (4%) and weight decrease (5%). 70% of patients were on TPM monotherapy at the end of the observation and 77% continued on TPM therapy. Conclusions: After transition from VPA, topiramate was associated with a substantial reduction in seizure frequency, including a high seizure‐free rate, and was well tolerated. (Supported by Janssen‐Cilag Germany.) 1 Mike R. Schoenberg, 1 Mary Ann Werz, 2 Kimford J. Meador, 2 David W. Loring, 3 Victoria J. Vahle, 4 Patty G. Ray, 5 James A. Fessler, 1 Paula Ogrocki, and 6 Mitchell J. Miller ( 1 Neurology, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, OH ; 2 Neurology, University of Florida, Gainesville, FL ; 3 Neurology, Washington University School of Medicine, St. Louis, MO ; 4 Neurology, Medical College of Georgia, Augusta, GA ; 5 Neurology, University of Rochester Medical Center, Rochester, NY ; and 6 Neurology Clinical Development, GlaxoSmithKline, Research Triangle Park, NC ) Rationale: Previously, we reported that drug preference was unrelated to objective neuropsychological performance. This study examined if self‐report rating scales of mood could predict participants' subjective drug preference in a study of healthy volunteers taking lamotrigine (LTG) or topiramate (TPM). Methods: This was a randomized, double‐blind, double‐dummy, two‐period crossover study in healthy adults. A total of 37 (mean age = 38 years) completed preference data. There was no difference in age or IQ between groups (p > .05). Subjects were randomized to receive either LTG or TPM for 12 weeks (7 weeks of dose escalation followed by 4 weeks of maintenance therapy, and then a 1 week taper). Maintenance dose was 300 mg/day for both AEDs. Subjects then received the alternate therapy with the same dosing format. Evaluations were conducted at Screening, end of the First and Second Maintenance Phases, and the Post‐treatment Phase. Side effects were recorded at each evaluation. Measures included mood assessment (QOLIE‐89, SEALS, and POMS), and cognitive tests of attention, memory, language, and executive functioning. Drug preference was assessed at the end of the study. Significantly more participants (26/37, 70%) preferred LTG (LTG‐P). Six (16%) preferred TPM (TPM‐P) and 5 (14%) had no preference (No‐P). Logistic regression was completed with baseline self‐report mood and objective cognitive measures to predict subjective drug preference of LTG versus TPM. Results: An algorithm with QOLIE Attention/Concentration and the SEALS Tiredness, and Dysphoria scales significnatly differed from zero, χ2(3, N = 37) = 15.05, p < .01. Participants were more likely to prefer LTG when baseline attention complaints were less, while those with more complaints of dysphoria and tiredness on the SEALS were 2.5 times more likely to prefer TPM. Using the algorithm, 87% of participants were correctly classified. Conclusions: Fewer attention/concentration problems and less complaints of dysphoria and tiredness was associated with a preference for LTG while the opposite was true in predicting a participants stated preference for TPM. Further studies are needed to more fully delineate factors affecting patient perceptions of medication side effects and how these variables affect attitudes of medication preference and the factors affecting compliance and quality of life. (Supported by GlaxoSmithKline.) 1 Andreas Schreiner, 2 Joern‐Roland Wettach, and 2 Schauble Barbara ( 1 Medical & Scientific Affairs, Janssen‐Cilag EMEA, Neuss, Germany ; and 2 Medical & Scientific Affairs, Janssen‐Cilag GmbH, Neuss, Germany ) Rationale: To evaluate seizure frequency and tolerability in patients with epilepsy treated with topiramate (TPM) transitioning from carbamazepine (CBZ) or oxcarbazepine (OXC). Methods: Multicenter open‐label non‐interventional study. Patients ≥12 years of age with epilepsy previously unsuccessfully treated with CBZ (72,1%) or OXC (27,9%) were prospectively followed for 26 weeks after initiation and transition onto TPM. A 12 week retrospective seizure frequency was used as baseline. Results: 140 patients (53,6% female; mean age 47,1 yrs (SD ± 17,9)) were selected. Median duration of epilepsy was 9,5 years (range, 0–59 years). 84,3% had seizures during the 12 weeks retrospective baseline. Most frequent seizure types at baseline were generalized tonic‐clonic (52%), complex partial (26%), and simple partial (16%). Main reasons provided for transitioning from CBZ/OXC onto topiramate were insufficient efficacy (75%) and/or side effects (80%). Side effects listed as reason for transitioning (>10%) were fatigue (55%), dizziness (29%), headache (20%), weight increase (19%) or abnormal hepatic function (13%). At endpoint, the median TPM dose was 100 mg/day. Mean seizure frequency decreased from 6/month (±SD 20,8) at baseline to 1,4 (±SD 5,1)/month during the full observation period. The responder rate (≥ 50% seizure reduction) during the last 3 months of observation was 91%, and 62% of patients remained seizure‐free during this period. 19% of patients discontinued TPM, in 12% due to an adverse event (AE), and 3% due to insufficient efficacy. The only treatment‐emergent adverse events reported in > 5% were paraesthesia (9%) and weight decrease (8%). Conclusions: After transition from CBZ or OXC, topiramate was associated with a substantial reduction in seizure frequency, including a high seizure‐free rate, and was well tolerated. (Supported by Janssen‐Cilag Germany.) 1 John M. Seeley, 1 Amir Arain, 1 Martin Gallagher, and 1 Bassel Abou‐Khalil ( 1 Department of Neurology, Vanderbilt University, Nashville, TN ) Rationale: More than 30% of patients with partial epilepsy are resistant to standard antiepileptic drugs (AEDs). Those who are not candidates for epilepsy surgery would benefit from add‐on trials of newer AEDs. Pregabalin (PGB) is a new AED with 40–50% responder rate and only 15% drop out rate in add‐on clinical trials. Efficacy and tolerability in clinical practice after marketing can be different. We analyzed efficacy and tolerability of add‐on PGB in all patients started on PGB between September 2005 and February 2006. Methods: The patient records were retrospectively reviewed for all patients who were started on PGB between September 2005 and February 2006 in Dr. Bassel Abou‐Khalil's epilepsy clinic. The records were analyzed to investigate PGB's efficacy, safety, and tolerability in relation to patient demographics, seizure, and epilepsy characteristics, starting dose, titration rate, target dose, and concomitant treatment. In addition, other factors such as age, response to previous treatment, duration of treatment, and adverse experiences were recorded. Outcome was measured in one of the following five categories; seizure free, marked improvement (>90% reduction in seizure frequency), moderate improvement (50–90% reduction in seizure frequency), no significant change (less than 50% reduction in seizure frequency), or worsened seizure frequency. Results: There were 55 patients who were started on PGB between September 2005 and February 2006. The age ranged from 17 to 70 with an average age of 40. 70% of the patients were still taking PGB at the time of last follow up with an average duration of treatment of 25 weeks. 30% of the patients started on PGB were no longer taking it. 25% of the patients who discontinued the medication, did so for ineffectiveness only while the other 75% stopped the medication for either ineffectiveness and adverse effects or adverse effects alone. The average length of treatment for those who discontinued PGB was 11 weeks. The most common adverse effect causing discontinuation was drowsiness (42%), emotional lability and irritability (33%). 52% of the patients complained of an adverse effect. The most common adverse effect overall for the patients was drowsiness (20%) and weight gain (13%). The average number of AEDs when starting PGB was 2.1. The patients had failed an average of 7 AEDs in the past. Seven of the patients had not had follow up as of yet. Of the remaining 48 patients, the responder rate was 49% with 8% of those becoming seizure free. Conclusions: In patients with refractory partial seizures, adjunctive therapy with PGB is effective and well tolerated. The most common adverse effects were drowsiness and weight gain. The most common adverse effect causing discontinuation of therapy was drowsiness and irritability and this was not related to starting dose or titration rate. 1 Renato Segura, 4 Ruthie Nemire, 2 Marinelli Vega, 1,2 Dalia Lorenzo, 3 Barry Gidal, 5 Rory Remmel, and 1,2 R. Eugene Ramsay ( 1 Neurology, Miami VA Medical Center, Miami, FL ; 2 Neurology, University of Miami, Miami, FL ; 3 Pharmacy, University of Wisconsin, Madison, WI ; 4 Pharmacy Services, Nova University, Ft. Lauderdale, FL ; and 5 Neurology, University of Minnesota, Minneapolis, MN ) Rationale: Enzyme induction is a process by which either the quanity or activity of a cytochrome (CYP) enzyume is increased above its baseline. CYP induction results from an increase in gene transcription triggered by selected substances and drugs resulting in an increase in drug clearance and lower plasma concentrations. Once an enzyme inducer is started, it generally takes 2–4 weeks to reach the higher drug clearance although the time course of induction has not been well characterized. When an inducing drug is stopped, the effect is lost and drug clearance returns to baseline. This process is known as de‐induction and the time course has been assumed to be the same as induction. However, there have been no studies which have looked at the time course and the effect of dose of the inducer on de‐induction. The purpose of this project is to determine the time course and the dose at which the induction effect is lost. Methods: The antiepileptic drugs (AEDs) which are potent CYP 3A4/5 and uridine‐diphosphate glucuronyl transferase (UGT) inducers include carbamazepine and phenytoin. LTG is a substrate for primarily for UGT. Patients selected for the study were on stable doses of one of the enzyme inducing AEDs (CBZ or PHT) and were also taking LTG. Patients were included who were to have the inducer discontinued and maintained on LTG monotherapy. Two trough plasma levels for the inducer and LTG were drawn before any changes in dose were made. Unit dose reduction was done biweekly (PHT 100 mg, CBZ 200 mg) and plasma samples were obtained biweekly during the taper. Plasma samples were collected three times a week for three weeks after the inducer was stopped and then weekly for three more weeks. Plasma concentrations were assayed using HPLC. Results: Samples from 17 adult patients have been obtained. Mean LTG clearance (Cl) before dosage reduction of the EI‐AEDs was 131 L. A linear reduction in LTG Cl was seen reaching 84.6 L the day the EI‐AED was stopped. Further reduction in Cl occurred over the next three weeks reaching a mean of 48 L and plateaued at this level for the remainder of the study. Cl and change in Cl was similar across patients with the standard deviation ranging from 7.2 to 18.5 across the sampling times. Conclusions: 1. Approximately half of the de‐induction occurs during the tapering of an EI‐AEDs. The remaining induction effect is lost over the 3 weeks after the EI‐AED is discontinued. Thus even a low dose of an EI‐AED has a significant effect on the activity level of the glucuronidation pathway. The overall induction effect is a 2.5 fold increase in LTG clearance by EI‐AEDs. 1 Archana Shrestha, 1 Lauren Frey, 1 Edward Maa, 1 Laura Strom, and 1 Mark Spitz ( 1 Neurology, University of Colorado Health Sciences Center, Aurora, CO ) Rationale: Side effects are one of the leading limiting factors in the use of anticonvulsant medications. A rash is a known side effect of lamotrigine. However, there is not much information available regarding the relationship between lamotrigine and late onset rash. Is the rash likely to be due to lamotrigine and does it necessitate discontinuation of the medication especially if the medication is effective? Methods: This is a prospective and retrospective case series study evaluating the patients in the Epilepsy Clinic. Pertinent clinical information was collected through a chart review. Patients with onset of rash and on lamotrigine therapy were identified. Late onset rash was defined as rash occurring greater than six months after the initiation of lamotrigine therapy. Patients were evaluated by a Dermatologist or a Primary Care Physician to determine the cause of the rash. Results: There were seven patients identified. The time to onset of rash from initiation of lamotrigine therapy ranged from 9 to 71 months (mean 28.6 months, median 18 months). Four out of the seven patients were on lamotrigine monotherapy with the rest being on polytherapy in combination with different anticonvulsant medications with none however including valproic acid. Two had a diffuse rash with the rest being localized. In three of the patients including the two with the diffuse rash lamotrigine was stopped without resolution of the rash. With the discontinuation of lamotrigine, the majority of these patients experienced an increase in their seizure frequency requiring the reinitiation of lamotrigine therapy once it was determined that the rash was due to another cause. In all the patients that the lamotrigine was continued there was no worsening of the rash or any other medical complications. In all of the cases the cause of the rash was determined to be something other than a lamotrigine induced rash with the most common causes being eczema and cosmetic reaction. Conclusions: Late onset rash in patients taking lamotrigine is not an uncommon occurrence. However, in our case series none of the rashes were determined to be due to lamotrigine. If the rash is severe it is prudent to stop the lamotrigine, but patients should be evaluated to accurately determine the cause of the rash especially if the medication is effective in controlling their seizures. Furthermore, if the rash is limited and the patients are doing well on this medication consideration should be given to continuing the lamotrigine during the evaluation process. 1 Misty D. Smith‐Yockman, 1 Erin M. Grussendorf, 3 Manoj K. Patel, 2 Indrani Choudhury‐Mukherjee, 2 Milton L. Brown, and 1 H. Steve White ( 1 Anticonvulsant Drug Development (ADD) Program, Department of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT ; 2 Department of Neuroscience, Georgetown University, Washington, DC ; and 3 Department of Anesthesiology, University of Virginia, Charlottesville, VA ) Rationale: T‐type calcium channels contribute to neuronal excitability (Chemin et al., J. Physiol. 540: 1, 2002), the regulation of oscillatory firing of thalamic neurons (Perez‐Reyes, Physiol. Rev. 83: 1, 2003), and generation of absence seizures (Huguenard, Epil. Curr. 2: 2, 2002). In addition, T‐type channel blockers, such as ethosuximide, display antinociceptive effects (Barton et al., Eur. J. Pharmacol. 521: 1–3, 2005). These channels may serve as unique targets for the treatment of epilepsy or neuropathic pain. In the present investigation, the novel T‐type calcium channel blocker, ICM‐1–40N (3, 3, 3‐trifluoro‐2‐hydroxy‐2‐phenyl‐propionamide; Choudhury‐Mukherjee et al., J. Med. Chem. 46: 12, 2003) was evaluated for its ability to block therapy‐resistant psychomotor seizures in the 6 Hz model and to limit formalin‐induced inflammatory pain in the formalin test. At 32 and 44 mA, the 6 Hz model displays resistance to phenytoin, carbamazepine, lamotrigine, and topiramate and thus can be used to differentiate novel AEDs (Barton et al., Epil. Res. 47: 3, 2001). Methods: Varying doses of ICM‐1–40N were administered i.p. to male CF‐1 mice. At the time of test (30 min), mice were evaluated for rotorod (6 rpm) toxicity before corneal stimulation (6 Hz, 3 s duration, 32 or 44 mA). Mice not displaying minimal clonic seizures and stereotyped automatistic behaviors were considered protected. Antinociceptive effects were evaluated in the formalin test. Formalin (0.5%) or 0.5% methylcellulose was injected s.c. under the plantar surface of the right hind paw and the time spent licking was compared between experimental and control groups. The total area under the curve (AUC) and percent of control AUC were calculated. Significance was defined as p < 0.05 when compared by one‐way ANOVA. Results: ICM‐1–40N was effective at both 32 and 44 mA (ED50's and (95% CI's): 18.5 (8.4 – 27.8) mg/kg and 45.1 (37.6 – 54.7) mg/kg, respectively). Based on an observed TD50 of 59.4 (40 – 136) mg/kg, the protective index was 3.2 and 1.3 for 32 and 44 mA, respectively. At 70 mg/kg, ICM‐1–40N displayed significant activity against the acute (46.1 ± 17.2% control) and inflammatory (43.8 ± 10.2% control) phases of formalin‐induced pain. Conclusions: The results obtained in the present study demonstrate that the T‐type calcium channel blocker ICM‐1–40N possesses anticonvulsant activity in a model of pharmacoresistant epilepsy and antinociceptive activity in a mouse model of tonic pain. These findings support the further development of this novel therapeutic. (Supported by NO1‐NS‐4–2359 (MDSY & HSW); RO1 CA105435–01 (MLB & MKP).) 1 Julie K. Dagam, 2 George L. Morris, 2 Veronica N. Sosa, and 2 Christopher M. Inglese ( 1 Regional Epilepsy Center/Department of Pharmacy, St. Luke's Medical Center, Milwaukee, WI ; and 2 Regional Epilepsy Center, St. Luke's Medical Center, Milwaukee, WI ) Rationale: To examine our experience with the use of pregabalin as part of the treatment of seizures in adult patients with refractory epilepsy. Methods: Since pregabalin (PGB) became available in 2005, all patients prescribed PGB as part of their anti‐epileptic drug (AED) regimen by one epileptologist at our center were included in data collection. Patients received standard care at our center, including education, therapy rationale/expectations, instructions, side effects, and follow‐up care. PGB and concurrent AED dose titration and adjustments were individualized based on side effects and seizure frequency. As patients were prescribed PGB, data including seizure type and frequency, current and past exposure to AED's, and PGB dosing were recorded. The charts of all patients prescribed PGB therapy were retrospectively reviewed in Feb 2006 and in May 2006 by our center's clinical pharmacist for PGB efficacy, side effects, and reason for discontinuation if applicable. Results: Since Sep 2005, 42 patients have been prescribed PGB as part of their AED regimen. By May 2006, 24/42 (57%) remained on PGB and was discontinued in 18/42 (43%). All patients were prescribed PGB for seizures; 38/42 (90%) for localization‐related and 4/42 (10%) for generalized seizures. At the time PGB was added, 12/42 (29%) were taking > /= 1 AED ± Vagus Nerve Stimulator (VNS) therapy and 30/42 (71%) were taking > /= 2 AED's ± VNS. Previous AED therapy included 4/42 (10%) on < /= 1 AED, 8/42 (19%) on 2–4 AED's, 28/42 (66%) on 5–10 AED's, and 2/42 (5%) on > 10 AED's. The 24 patients continuing PGB as part of their AED regimen as of May 2006 had been taking PGB for a range of 3–8 months. Reported side effects include weight gain in 4/24 (17%), ataxia in 2/24 (8%), and no side effects in 18/24 (75%). Seizure frequency decreased in 6/24 (25%), increased in 4/24 (17%), and did not change in 14/24 (58%). The 18 patients that discontinued PGB by May 2006 had been taking PGB for a range of 3 days‐6 months. Side effects requiring PGB discontinuation include seizure increase in 7/18 (38%); fatigue in 5/18 (27%); ataxia in 2/18 (11%); and headache, weight gain, behavior change, and unfocused thoughts in 1/18 (6%) of each. Overall, seizure frequency decreased in 1/18 (6%), increased in 9/18 (50%), and did not change in 8/18 (44%). Conclusions: These results characterize our center's experience with PGB from Sep 2005‐May 2006. Overall, our center has experienced limited success using PGB as part of the AED regimen to treat seizures in adult patients with refractory epilepsy. In these patients, a regimen containing PGB may be considered, but patients must be monitored for side effects and effect on seizure frequency. In our experience, PGB has been discontinued in a substantial number of patients for reasons including intolerable side effects and lack of efficacy. 1 K. Spiegel, 2 F. Baldinetti, 2 S. Huang, and 2 B. Emir ( 1 CNS, Pfizer Global R&D, Ann Arbor, MI ; and 2 CNS, Pfizer Global Pharmaceuticals, New York, NY ) Rationale: Pregabalin is approved in the US, EU, and elsewhere as adjunct therapy—at dosages of 150 to 600 mg/d1–4—for adult patients with partial‐onset seizures. We evaluated the efficacy, safety, and tolerability of pregabalin 300 mg/d as treatment of partial seizures by combining data from the 2 randomized clinical trials (RCTs) of pregabalin for this indication that included 300‐ mg/d fixed‐dosage arms. Methods: The 2 RCTs shared a similar parallel‐group design, with add‐on treatment administered over 11 weeks. A total of 242 patients received pregabalin 300 mg/d, and 240 received placebo (PBO). All participating patients were ≥12 years of age and refractory to treatment, ie, they had a history of failing two or more AEDs, and their seizures were inadequately controlled despite receiving 1 to 3 marketed AEDs concurrently. The primary efficacy measure was reduction in seizure frequency compared with baseline. Treatment efficacy was also evaluated by measuring the responder rate, ie, patients who experienced seizure reductions ≥50% during treatment versus baseline. Results: The pregabalin 300 mg/d treatment group demonstrated a significant reduction in seizure frequency relative to the PBO group: the treatment difference between pregabalin and placebo in mean seizure reduction was –34.8 (p < .0001). Overall, 36% of patients receiving 300 mg/d pregabalin were responders compared with 20% of patients receiving PBO (p < .05). Adverse events (AEs) associated with 300 mg/d pregabalin treatment were typically mild to moderate in intensity and tended to resolve with treatment. AEs, such as dizziness (14% of patients receiving 300 mg/d pregabalin and 4.6% of patients receiving PBO), somnolence (7.4% and 5%), and weight gain (3.7% and 0%), were evaluated. Conclusions: Pregabalin 300 mg/d was efficacious and generally well‐tolerated as add‐on therapy for partial seizures. At this 300 mg/d dosage, 36% of patients were responders (≥50% reduction in seizures) to pregabalin treatment. However, as previously reported (including a responder rate up to 51%1), some patients may require, and tolerate well, increased dosages of up to 600 mg/d. References: 1French JA, et al. Neurology. 2003;60:1631–1637. 2Arroyo S, et al. Epilepsia. 2004;45:20–27. 3Beydoun A, et al. Neurology. 2005;64:475–480. 4Elger CE, et al. Epilepsia. 2005;46:1926–1936. (Supported by Pfizer.) 1 James P. Valeriano, and 1 Carole L. Lane ( 1 Neurology, Allegheny General Hospital, Pittsburgh, PA ) Rationale: Oxcarbazepine has been approved for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children ages 2 – 16 with epilepsy. In our practive we used oxcarbazepine in an adult population both as initial monotherapy and as conversion to monotherapy in patients with varying seizure types. We also measured oxcarbazepine levels in the form of the monohydroxy metabolite (MHD) thought to be the pharmacologically active moiety of oxcarbazepine. This was done to assess whether or not these levels were clinically relevant. Methods: We have retrospectively reviewed records of 25 patients in which oxcarbazepine was used as monotherapy. Seizure types treated included: simple and complex partial seizures with or without secondarily generalization and generalized seizures. Results: We were able to maintain monotherapy treatment with oxcarbazepine in almost all patients because of the degree of seizure control as well as tolerability. MHD levels varied at given doses between individuals, so these must be titrated on a case to case basis. There was also a wide range of levels which achieved seizure control. Conclusions: Oxcarbazepine proved effective and well tolerated as monotherapy treatment in adults with various seizure types. (Supported by: Funding in the form of a grant through Novartis Pharmaceuticals Corporation.) 1 Vicente Villanueva, and 1 Albert Molins ( 1 Epilepsy Unit, Neurology Service, Hospital La Fe, Valencia, Valencia, Spain; and Epilepsy Unit, Neurology Service, Hospital Josep Trueta, Girona, Girona, Spain ) Rationale: To describe the characteristics and the outcome of a population of patients treated with levetiracetam in monotherapy through the analysis of the epilepsy patients database of two epilepsy Units. Methods: A retrospective analysis of the epilepsy patients database of two epilepsy Units (Hospital Josep Trueta and Hospital La Fe) was performed. In both centers, an epilepsy patients database is routinely filled during daily clinical practice. All the patients in whom levetiracetam was used in monotherapy up to December 2005, and received at least one dose of the drug in monotherapy were included. Monotherapy was achieved from onset, if levetiracetam was estimated to be the best option or after withdrawal of other concomitant antiepileptic drugs if an optimal seizure control was reached with levetiracetam. It was administered twice per day, with a schedule depending of the age and the renal function. The following data were analysed: demographic characteristics, follow‐up, epilepsy type, previous seizure frequency, maintenance dose, efficacy and side effects. Results: Sixty‐two patients with a mean age of 53.67 years (range19–94) were included. The patients were followed a mean of 12.4 months (range 4–38). Epilepsy type was mainly partial (83.8%) and symptomatic (54.8%). The mean previous number of seizures was 8.6 and the mean maintenance dose was 1314.51 mg (250–2000). Fifty‐eight patients (93%) were considered responders (more than a 50% reduction of seizures) with 70.9% of them free of seizures. Side effects were observed in 20 patients with one death considered not related to drug use. There were 9 (14.5%) withdrawals (5 because of side effects, 1 death and 3 non‐responders). Conclusions: Levetiracetam was used in monotherapy in a population relatively old. It proved to be efficient in 93% of the patients. Side effect were severe enough to discontinue levetiracetam in 8% of the patients. 1 Bob Warnock, 1 Gilda P. Womble, and 1 John A. Messenheimer ( 1 Neurosciences Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC ) Rationale: Oral contraceptives have been shown to increase the apparent clearance of lamotrigine (LTG). In addition, the effect of the oral contraceptives on LTG clearance diminished during the “pill free” week, resulting in a transient approximate two‐fold increase in LTG plasma concentrations. Based on these results, data from two large open‐label studies were examined to characterize the safety of LTG at higher concentrations beyond that associated with the current recommended maximum of 500 mg/day. Methods: Study US17 and study US26 were open‐label treatment protocols.In both trials, adjustment of concomitant antiepileptic drugs (AEDs) was permitted, including conversion to monotherapy with LTG and data were obtained every 6 months for the duration of the subject's participation in the study, including a single LTG concentration. Demographics, adverse events (AEs) and exposure were summarized by study and by plasma concentration (<10 mg/mL, > 10 mg/mL), which is the equivalent of 600 mg of lamotrigine as monotherapy. Only subjects with a plasma sample were analyzed for safety. Only AEs that were reported during the period that a patient was exposed to the dose recorded at the time of the PK sample were included in the safety analysis in order to examine the dose‐response relationship. Results: A total of 1602 subjects participated in the 2 trials, with 624 included in the safety analysis. Demographic characteristics were similar between studies. There were 492 patients with LTG concentrations < 10 μg/mL (mean = 5.4 μg/mL, average exposure 15.4 months) and 132 patients ≥ 10 μg/mL (mean = 14.7 μg/mL, average exposure 18.8 months). Adverse events in US 17 and US 26 combined were reported slightly more frequently among the patients with LTG concentrations ≥ 10 μg/mL (34%) than in those < 10 μg/mL (26%). AEs reported at a rate ≥ 5% and more frequently among those with concentrations ≥10 μg/mL are shown below: The term “Any Rash” (includes rash or urticaria) was slightly more frequent (5/132, 4%) at ≥10 μg/mL than < 10 μg/mL (8/492, 2%). There were no cases of serious rash in either group. The rate of serious adverse events was comparable between groups. CNS adverse events were slightly more frequent at concentrations > 10 μg/ml. Conclusions: At mean concentrations of LTG of 14.7 approximating a LTG monotherapy dose of 900 mg qd non‐serious CNS‐related adverse events were slightly more frequent in comparison with a mean concentration of LTG of 5.4μg/ml approximating a LTG dose of 600 mg qd. Doses increases of LTG up to 900 mg qd as monotherapy are well‐tolerated. (Supported by GlaxoSmithKline Research and Development.) Adverse Event < 10μg/mL (n = 492) ≥10μg/mL (n = 132) Headache 40 (8%) 17 (13%) Dizziness 40 (8%) 16 (12%) Diplopia 25 (5%) 12 (9%) Ataxia 15 (3%) 10 (8%) Injury Accident 20 (4%) 9 (7%) Infection 12 (2%) 7 (5%) Tremor 6 (1%) 7 (5%) 1 Gaetano Zaccara, 1 Fabrizio Balestrieri, and 2 Andrea Messori ( 1 Unit of Neurology, S.M. Nuova Hospital, Firenze, Firenze, Italy ; and 2 Osservatorio del Farmaco, Azienda Ospedaliera Careggi, Firenze, Firenze, Italy ) Rationale: To analyse dose dependent CNS adverse effects (CNS‐AE) of new antiepileptic drugs (AEDs) trough an evaluation of key double‐blind studies. Methods: we selected all placebo‐controlled clinical studies with new AEDs. From each study we extracted the number of patients who complained of CNS‐AEs when treated with the active drug (divided for different dose levels) or placebo. For each CNS‐AE we calculated the percentage of CNS‐AE complaining patients (under treatment or placebo) only from those studies in which the frequency of that CNS‐AE was reported. Than we calculated the complaint rate of each CNS‐AE (percent of CNS‐AE patients under active treatment minus the percent of CNS‐AE from patients receiving placebo) (Cramer et al., Epilepsia 1999; 40:590–600). Finally, a summary complaint score (SCS) was calculated for different class of CNS‐AEs. Results: SCS for 4 class of CNS‐AEs: somnolence, tremor, vestibulocerebellar (ataxia, dizziness, diplopia, blurred vision and gait incoordination) and cognitive are reported in the order. Gabapentin: 9.6%, 2.3%, 21%, 0%; Lamotrigine: 0%, 0%, 69%, 0%; Levetiracetam: 7%, 0%, 7%, 0%; Pregabalin: 11.6%, 4%, 41%, 9%; Oxcarbazepine: 14.8%, 4,6%, 76%, 0%; Tiagabine: 0%, 26%, 17%, 5%; Topiramate: 30.3%, 0%, 94%, 67.8%; Zonisamide: 6.3%, 0%, 9%, 0%. From the inspection of data, a relation between dose level and the above reported CNS‐AEs was observed in some cases which will be reported. Conclusions: This analysis gives a clear profile of CNS tolerability of various new AEDSs. Overall, levetiracetam had the best profile. (Supported by a grant from the “Ente Cassa di Risparmio di Firenze,” Florence, Italy.) 1 Gregory L. Krauss, 2 Tracy Glauser, 3 Alexis Arzimanoglou, 4 Carlos A. Perdomo, and 4 Santiago Arroyo ( 1 Johns Hopkins University School of Medicine, Baltimore, MD ; 2 Cincinnati Children's Hospital Medical Center, Cincinnati, OH ; 3 University Hospital Robert Debré, Paris, France ; and 4 Eisai Global Clinical Development, Ridgefield Park, NJ ) Rationale: To evaluate the short‐ and long‐term safety of rufinamide in pediatric patients with epilepsy. Methods: Safety data were derived from all of the short‐term, double‐blind, placebo‐controlled studies and long‐term, open‐label studies of adjunctive rufinamide therapy in pediatric patients with inadequately controlled seizures. Databases from the different trials were integrated into a single database including 212 rufinamide‐treated patients and 197 placebo‐treated patients for short‐term double‐blind trials and 391 patients for long‐term trials. All patients who received ≥1 dose of study drug were included in the analysis. Adverse events (AEs) were analyzed using the Medical Dictionary for Regulatory Activities and were presented by preferred term. Clinical laboratory tests, serious adverse events (SAEs), and AEs leading to study discontinuation were also evaluated. Results: In short‐term, double‐blind trials, the median age was 11 years and the median weight was 35 kg; median duration of exposure was 3.0 months and median daily dose of rufinamide was 41.96 mg/kg per day. The most commonly reported Aes for rufinamide versus placebo patients included somnolence (17.0% vs 8.1%), vomiting (16.5% vs 7.1%), headache (16.0% vs 8.1%), and pyrexia (11.3% vs 10.7%). Most Aes were mild to moderate in severity. A higher percentage of patients in the rufinamide group (7.1%) compared to the placebo group (2.0%) discontinued treatment due to Aes. Serious adverse events were reported in 7.5% of rufinamide‐treated patients and 5.6% of placebo‐treated patients. Serious adverse events led to study discontinuation of 3.3% of rufinamide‐treated patients and 1.0% of placebo‐treated patients. In long‐term therapy (n = 391), the median daily dose of rufinamide administered was 41.67 mg/kg per day and the median duration of rufinamide exposure was 14.5 months; 54% of patients were given the drug for ≥12 months. The most commonly reported AEs during long‐term therapy were vomiting (26.3%), headache (22.3%), pyrexia (18.7%), somnolence (18.7%), and upper respiratory tract infection (17.9%); 86 patients (22.0%) experienced ≥1 severe AE. Adverse events led to the study discontinuation of 12.5% of patients; no single AE led to study discontinuation of > 2.0% of patients. Serious adverse events were reported in 15.6% of patients; 4.9% of patients discontinued treatment due to SAEs. Conclusions: Short‐ and long‐term rufinamide therapy were generally well tolerated in pediatric patients with epilepsy. 1 Daniel Becker, 1 Anup Patel, 1 Bassel W. Abou‐Khalil, and 1 Jesus E. Pina‐Garza ( 1 Neurology, Vanderbilt University Medical Center, Nashville, TN ) Rationale: Subacute Sclerosing Panencephalitis (SSPE) is a devastating progressive degenerative disease of the nervous system presumably caused by a persistent measles virus. Patients commonly present with myoclonia or encephalopathy. There are currently no known curative therapeutic options or effective symptomatic therapy. We present a patient whose encephalopathy and myoclonus responded dramatically to levetiracetam. Methods: A 12 year old boy presented with acute encephalopathy and myoclonus developing over one month. Electroencephalogram (EEG) showed high voltage generalized periodic discharges associated with myoclonic jerks, recurring at intervals of 6–7 seconds. The suspected diagnosis of SSPE was confirmed with very elevated CSF measles antibodies. Results: Treatment with levetiracetam dramatically improved both the myoclonus and encephalopathy within a few days. The EEG pattern showed improvement as well. Conclusions: Levetiracetam was effective in treating both myoclonus and encephalopathy in one patient with SSPE. We speculate that the electrical abnormality demonstrated in the characteristic EEG pattern contributes significantly to the encephalopathy seen in SSPE patients. Levetiracetam appears to improve the abnormal cortical electrical activity and is a promising symptomatic therapy in SSPE. 1 Michaela V. Bonfert, 1 Sybille Armbruster, 1 Bastian Baumgartner, and 1 Florian Heinen ( 1 Department of Pediatric Neurology and Developmental Medicine, Childrens Hospital of the University of Munich, Munich, Germany ) Rationale: To conduct a prospective, open‐label pilot trial to evaluate the efficacy and tolerability of Levetiracetam (LEV) monotherapy in a cohort of 10 children with benign childhood epilepsy with centrotemporal spikes (BECTS) in paying special attention to effects on cognitive function. Methods: Newly diagnosed patients with BECTS and patients with BECTS nonresponding to first‐line monotherapy with Sulthiame (STM) were recruited from our clinics outpatients department. Inclusion criteria were proven diagnosis of BECTS, two ore more seizures in the last six months, age between 3 to 12 years and informed consent by parents. Patients with progressive neurological or systemic disease, other forms of epilepsy and moot compliance of caregivers were excluded from the trial. LEV was titrated up to 20 mg/kg. Efficacy was assessed by analysing changes in seizure frequency and alteration of electroencephalogram (EEG) abnormalities over a 6 months period. Therefore recordings of EEG during wakefulness and sleep were conducted before start of LEV treatment, after 1, 3 and 6 months. Neuropsychological testing of patients took place before start of LEV treatment and is to be repeated after 6 months of treatment. Tolerability was assessed by evaluation of LEV‐associated adverse events (AE). Approval by the local ethics committee was obtained. Results: To date 10 patients have been recruited, aged 3 to 12 years. 6/10 patients received LEV as first‐line monotherapy. 4/10 patients were switched to LEV monotherapy from first‐line monotherapy with STM due to inefficacy (3/4) and hyperventilation (1/4) respectively. At this time all of the LEV treated patients are seizure‐free (8/10 have completed the 6 months period, 2/10 patients are still ongoing). EEG abnormalities showed remarkable reduction in all of the patients. Neuropsychological assessment in 9/10 patients before start of treatment revealed average performance in 7/9 and below average performance in 2/9 patients. In those 8 patients who have by now reached the endpoint of the trial no changes in neuopsychological parameters were seen. AEs were reported in 2/10 patients. 1 patient complaint of agitation within the first week of the LEV treatment, 1 patient developed hyporexia associated to mild weight loss within day 60 to 120 of treatment which resolved spontaneously. Conclusions: These preliminary data show that LEV seems to be an effective and well‐tolerated option in the treatment of children with BECTS. Concerning effects on cognitive function preliminary data are promising. Based on these encouraging results a controlled, randomized, double‐blind multicentre trial to evaluate the application of LEV in a representative cohort of 120 children with BECTS has started in Germany spring 2006 (HEAD‐Study). (Supported by UCB Pharmaceuticals.) 1 Patricia L. Bruno, 1 David A. Lyczkowski, 1 Allison E. Sedgewick, and 1 Elizabeth A. Thiele ( 1 Pediatric Epilepsy Program, Massachusetts General Hospital, Boston, MA ) Rationale: Felbamate (FBM) was approved by the United States Food and Drug Administration in July 1993. From January to October 1994, 33 cases of aplastic anemia and 18 cases of hepatic failure were reported among users of FBM. Despite the risk of idiosyncratic adverse events, FBM appeared to be an effective antiepileptic agent in initial studies. There are limited post‐marketing data available regarding the efficacy, safety and tolerability of FBM in pediatric epilepsy. Methods: We conducted a chart review of patients followed from January 2002 through May 2006 in the Pediatric Epilepsy Program at Massachusetts General Hospital. For each patient treated with FBM, we assessed demographics, seizure type and etiology, current and previous treatments, reported side effects of FBM, complete blood count (CBC) and liver function test (LFT) values, and efficacy of FBM treatment based on parental reports of percent seizure reduction. χ2 and paired‐sample T‐tests were performed with SPSS v. 11.5. Results: Forty‐three (male/female 26/17) had been treated with FBM. Of the 43, 16 had partial onset seizures, nine had generalized seizures, and 18 had mixed seizure disorders. For 26 of the 43 patients, detailed data were available and this population was further evaluated. All of the 26 patients were treated with FBM in combination with other antiepileptic drugs or adjunctive therapy options. Of the 26 patients, 11 patients experienced 50 to 90% reduction in seizures, and four experienced a greater than 90% seizure reduction. Seven patients experienced less than 50% reduction, and four had no change in their seizure frequency. CBC and LFT values at 2 weeks, 1 month, and 3 months showed no significant alterations from baseline (n = 14 at 2 weeks, n = 16 at 1 month, and n = 22 at 3 months) with the exception of the WBC count, which decreased from baseline (7.33 ± 3.27 k/μL) to 1 month (6.22 ± 2.54 k/μL; 2‐tailed P = 0.009). Since this change in WBC was not accompanied by any other significant trends, and since WBC values at 2 weeks and at 3 months were not significantly altered from baseline, the etiology of the WBC decrease is unclear. Two patients reported nausea and vomiting while on FBM. One patient died at 29 months of age while on FBM from respiratory and renal failure. Autopsy results suggested the patient died from a multisystemic disorder, not from an idiosyncratic reaction to FBM. Conclusions: Felbamate has been shown to be effective in the treatment of partial‐onset seizures and Lennox‐Gastaut syndrome. In our limited retrospective study, FBM appears to be well tolerated and efficacious in the treatment of refractory pediatric epilepsy. Although there were not significant side effects in our population, pediatric patients started on FBM should be closely monitored. Additional studies are needed to better define the role of FBM in pediatric epilepsy, both with regard to efficacy as well as tolerability. 1 Michael G. Chez, and 1 Pavan Khanna ( 1 Neurology, Rosalind Franklin University/the Chicago Medical School, North Chicago, IL ) Rationale: Felbamate is a recent anti‐convulsant medication that has been relegated to second‐line therapy due to fear of side effects such as bone marrow or liver failure. These side effects are rare, uncommon, and almost unheard of in children under 13 years of age. Despite this fact, many children who could benefit from this medication have not been given a trial because of the fear of dangerous side effects. We conducted a retrospective review to analyze how effective felbamate was in a refractive epileptic population, and noted whether there were any abnormal blood or liver tests during treatment. Methods: A retrospective chart review of seizure patients treated with felbamate from 1994–2006 was performed. The average duration of therapy, prior failed treatments, laboratory values, and seizure type were reviewed. Average felbamate dose per day was calculated and average therapeutic serum levels were recorded. Patients were evaluated for seizure improvement as becoming seizure free, improvement of greater than 50%, improvement of less than 50%, and worsening of seizures. Reasons for stopping therapy were also recorded along with any perceived side effects. Results: There were 28 patients (18 male, 10 female); average age 7.54 years (range 1.33–17.25 years). Average prior failed treatments was 3.6 drugs (range 1–6) or therapies (3 ACTH or 3 prednisone;6 ketogenic diet; 1 vagal nerve stimulator). The average duration of therapy was 23.6 months (range 2–93 months). Average maximum daily dosage was 1157 mg/day, which was 50.1 mg/kg/day (avg. weight 23.1Kg). The average trough serum level for our population was 55 mg/dl (range 9–140 mg/dl). Seizure types seen in patients were: myoclonic/drop seizures 12; atypical absence seizures 2, Landau‐Kleffner 1; secondary generalized or mixed seizures 13. There were 7 patients that met criteria for Lennox‐Gastaut Syndrome. Outcome for seizure control showed seizure freedom for 5 patients; greater than 50% improvement in 14; less than 50% improvement in 3; and worsened seizures in drop attacks or startles in 4. One patient stopped the medication despite better seizure control because of irritability. Before 1997, four patients stopped treatment from fear of side effects despite good seizure control. Two patients stopped for anorexia, but none stopped for insomnia which was treated by moving doses earlier in the day or lowering the dosage. There were no significant changes in weight, hematology, or liver profiles in any patient during treatment. Conclusions: This retrospective review of felbamate add‐on therapy shows 22/28 pediatric patients with refractive seizures having improved seizure frequency. Only 4/28 patients worsened. The main reason for stopping therapy was the fear of side effects more than actual clinical side effects. This suggests that for intractable seizure patients, especially with mixed or myoclonic seizure types, felbamate should be a rational treatment choice despite known risks of toxicity. 1 Curtis S. Claassen, 1,2 Lorie D. Hamiwka, 1 Marlene A. Blackman, and 1,2 Elaine C. Wirrell ( 1 Pediatric Neurology, Alberta Children's Hospital, Calgary, AB, Canada ; and 2 Pediatrics and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada ) Rationale: To determine the effectiveness and tolerability of home use of buccal lorazepam for break‐through seizures in children. Methods: Children prescribed lorazepam by the Neurology Service at the Alberta Children's Hospital in 2005 were identified retrospectively. Charts were reviewed to determine seizure type(s), frequency, syndrome, prior and current AED use, prior status epilepticus, age at onset, gender, cognitive status and age at prescription of lorazepam. Families were contacted in May 2006 and queried regarding number of lorazepam doses used, effectiveness and adverse effects. Results: Twenty one patients were identified (8M, 13F, mean age 7.1 yrs, range 0.5–15.9) who were prescribed lorazepam. Fourteen (67%) had a history of status epilepticus. Nineteen (90%) had symptomatic partial epilepsy, while 1 patient each had idiopathic generalized epilepsy and febrile status epilepticus. Thirteen patients (62%) received a test dose and the remainder had previous exposure to a therapeutic dose of benzodiazepine either in the ER or given by EMS. At follow‐up, 11 (52%) had used lorazepam (median # doses 2, 25th‐75th%ile 1–9). Therapeutic effectiveness was 100% in 5 (45%), 80% in 2 (18%), 50% in 2 (18%) and 0% in 2 (18%). Of the 9 patients reporting some success with lorazepam, median time to seizure cessation was 4 minutes (25th‐75th%ile 2–9 mins). No child experienced a significant adverse effect. Five had transient, minor irritability and 3 had mild sedation. No child had respiratory problems related to lorazepam, although one child with profound ictal apnea failed to respond to lorazepam and continued to be apneic. Patient age, seizure syndrome, cognitive status or number of prior AEDs were not predictive of response. However, children on prophylactic benzodiazepines tended to have a lower response rate than those not taking these agents (1/3 vs 6/8, p = 0.28). Conclusions: Buccal lorazepam appears to be a safe, efficacious and cost‐effective therapy for home‐use in children with break‐through seizures. Children on prophylactic benzodiazepines may have a lower response rate, however larger subject numbers are needed to confirm this finding. 1 Joan A. Conry, 2 Juliann Paolicchi, 3 Julie C. Stolle, 3 Ashira Johnson, and 3 Stephen D. Collins ( 1 Department of Neurology, Children's National Medical Center, Washington, DC ; 2 Columbus Children's Hospital, Columbus, OH ; and 3 Ovation Pharmaceuticals, Deerfield, IL ) Rationale: Clobazam (CLB) has been approved for the treatment of anxiety and/or the adjunctive treatment of epilepsy in over 100 other countries. Anticonvulsant effects of CLB was first reported on by Gastaut in 1978. CLB is the only 1,5 benzodiazepine used in the treatment of epilepsy and was developed to decrease the side effects of 1,4‐benzodiazepines while maintaining efficacy. This study evaluates the safety and efficacy of CLB as adjunctive therapy in subjects with Lennox‐Gastaut Syndrome (LGS). Methods: Subjects from 2–30 years of age with LGS were enrolled in a randomized, double‐blind, dose‐range finding study. The study consists of a 4‐week baseline, a 3‐week titration and a 4‐week maintenance period. Subjects not continuing into the long term open‐label study have up to a 3‐week taper period. Subjects must be on stable doses of 1–3 AEDs which may include ketogenic diet and VNS. Subjects with ≤2 drop seizures per week are randomized to low dose (target 0.25 mg/kg/day) or high dose (target 1.0 mg/kg/day) with maximum doses of 10 or 40 mg/day, respectively. The primary efficacy variable is a reduction in drop seizures. Safety of CLB is evaluated by lab assessments, electrocardiogram, vital signs, physical and neurological exams and adverse event (AE) assessments. Results: Of the 76 subjects enrolled to date, 49 (64%) have been randomized and have received study drug. Of the randomized subjects, demographic data is available in 51%: 72% male, 28% female; 28% < 5 years of age, 48% 5–10 years of age and 24% > 10 year of age. AEs resulted in 5 premature discontinuations due to drowsiness, hypothermia, increase in seizures, increased behavioral problems and chorea. AEs were reported by 32% of the subjects with the majority mild in severity (66%); 24% were considered not related, 21% unlikely, 24% possibly and 28% probably related to study drug by the investigator; relationship for 1 event was not reported (ear infection). No AEs were considered definitely related. The most frequently reported AEs by ≤2 subjects were constipation (2), ear infection (2), sedation (2), somnolence (2) and increased seizures (3). There were no reports of drooling. One subject reported irritability and 1 reported dysphoria, both mild in severity and considered possibly related. A total of 6 serious adverse events (SAEs) have been reported. Of the SAEs, 4 were treatment‐emergent; 3 (constipation, viral infection and sleep apnea syndrome) were considered not related and 1 (respiratory distress) was considered unlikely related. Conclusions: Of the 49 subjects randomized to date, no SAEs have been attributed to clobazam. Clobazam is a promising agent for the treatment of LGS. (Supported by Ovation Pharmaceuticals.) 1 Angus A. Wilfong, 1 Deanna T. Duggan, and 1 Tina J. Bradshaw ( 1 Pediatrics – Neurology, Baylor College of Medicine, Houston, TX ) Rationale: Pregabalin is a newly available antiepileptic drug (AED) that has been licensed in the U.S. as add‐on therapy in adult patients with partial onset seizures. Studies evaluating the safety and efficacy of pregabalin in individuals less than 18 years of age are limited. This chart review explores the safety, tolerability and efficacy of pregabalin in pediatric patients with intractable epilepsy. Pregabalin is a α2‐δ ligand that has anxiolytic, analgesic and anticonvulsant properties. Methods: This retrospective chart review study includes pediatric patients with intractable epilepsy treated with pregabalin. Safey and tolerability were assessed via patient and/or caregiver report of adverse events. Pregabalin's efficacy was evaluated via subjective patient and/or caregiver reports. In most cases, efficacy, safety and tolerability were assessed within 8 weeks after the initation of pregabalin therapy. Results: Seventeen patients are included in the cohort. The patients range in age from 3 to 19 years, including 8 females and 9 males. Thirteen of 17 patients are diagnosed with localization related epilepsy; 3 of 17 patients are diagnosed with generalized epilepsy and 1 patient is diagnosed with mixed generalized and localization related epilepsy. Doses were initiated between 0.4 to 4 mg/kg/day and titrated up to maintenance doses ranging from 1.4 mg/kg/day to 8.7 mg/kg/day. Patients were treated with pregabalin for a period of 7 days to over 8 months. Three patients reported a side effect of somnolence. Other reported side effects include visual disturbance such as, “unable to focus,” moodiness and worsening balance. Of note, one adolescent patient intentionally overdosed on pregabalin and was hospitalized in an intensive care unit for 2 days. Pregabalin was discontinued in 3 patients due to an increase in seizure frequency. Conclusions: Seven out of 17 patients treated with pregabalin reported increased seizure frequency and/or intensity, and 1 out of 17 patients reported no improvement. However, one patient's caregiver reported an improvement in seizure control since starting pregabalin therapy. All 17 patients in the cohort received treatment from one or more AEDs. Four of the 7 patients with reported increased seizure frequency and/or intensity have localization related epilepsy, whereas 2 of the 7 patients have generalized epilepsy. Reports of increased seizure frequency and/or intensity appears unrelated to daily dose per kilogram. Further studies are necessary to determine the safety, tolerability and efficacy of pregabalin therapy in pediatric patients with intractable epilepsy. 1 Roy D. Elterman, 2 W. Donald Shields, and 3 Stephen Collins ( 1 Clinical Professor of Neurology, UT Southwestern Medical School, Dallas, TX ; 2 David Geffen School of Medicine, UCLA, Los Angeles, CA ; and 3 Ovation Pharmaceuticals, Inc., Deerfield, IL ) Rationale: The Vigabatrin Infantile Spasms Study Group previously demonstrated that vigabatrin produces seizure cessation in patients with infantile spasms, particularly those with spasms secondary to tuberous sclerosis (Neurology 2001;57:1416–1421). This a priori analysis evaluates the efficacy of vigabatrin by etiology of infantile spasms. Methods: A multicenter, randomized, single‐blind study of 14 days with a 3‐year, open‐label, flexible dosing follow‐up in patients with new‐onset infantile spasms. Patients ≤2 years of age and who were naïve to treatment with either adrenocorticotropic hormone, prednisone, or valproate were randomized to receive either high‐dose (100–148 mg/kg/day) or low‐dose (18–36 mg/kg/day) vigabatrin for 14 days. Doses were administered orally (tablets) on a BID regimen. Subgroup analysis of efficacy data was conducted by etiology. Specifically, outcomes of patients by etiology who were spasm free for 7 consecutive days and remained spasm free for the duration of the study based on caregiver assessment were evaluated. Results: Evaluable patients by etiology included 38 tuberous sclerosis (17.2%), 57 cryptogenic (25.8%), and 126 symptomatic‐other (57.0%). Response increased dramatically for all etiologies after approximately 2 weeks of vigabatrin therapy and continued to increase with treatment. Of interest were response rates for spasm cessation for 7 consecutive days and remaining spasm free during of the study period (up to 3 years): 73.7% for tuberous sclerosis, 71.9% for cryptogenic, and 49.6% for symptomatic‐other. The median time to spasm free status (and remaining spasm free during study period) by etiology was 3 weeks for tuberous sclerosis, 9 weeks for cryptogenic, and 14 weeks for symptomatic‐other. Approximate percentage of subjects who became spasm free and remained spasm free by 12 weeks was 32%, 58% and 72%, respectively. The safety profile of vigabatrin by etiology disclosed no differences between groups. Conclusions: Vigabatrin was effective in rapidly producing freedom of spasms for symptomatic, cryptogenic and tuberous sclerosis‐induced infantile spasms. The median onset of spasm freedom for all patients in the study ranged from 3 to 14 weeks, and occurred as early as 3 weeks for patients with tuberous sclerosis. While a significant separation of effect between the etiology categories was seen, with tuberous sclerosis responding slightly faster, all groups exhibited a high and sustained response rate to vigabatrin treatment. Previous studies have suggested efficacy of vigabatrin in tuberous sclerosis‐induced infantile spasms. This large study also suggests efficacy in cryptogenic and symptomatic‐other infantile spasms. These data suggest that vigabatrin may be considered as a first‐line treatment for all etiologies of infantile spasms. (Supported by Ovation Pharmaceuticals, Inc.) 1 Eija Gaily, 1 Henna Jonsson, and 2 Marjatta Lappi ( 1 Hospital for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland ; and 2 Department of Ophtalmology, Helsinki University Hospital, Helsinki, Finland ) Rationale: Vigabatrin has been shown to cause visual field constriction in 40% of treated adults. The risk is less well known in children. There are no previous reports on visual fields in children who received vigabatrin in infancy. Methods: Vigabatrin has been used as the first drug for infantile spasms in our unit since 1994. We have aimed to investigate visual fields in all VGB‐treated children whose age and developmental level allow sufficient cooperation. Eleven such children born in 1993–1999 were available for study. All had infantile spasms during the first year of life, nine with idiopathic and two with symptomatic etiology. Spasms started at a median age of 5.2 (range, 2.9–11.9) months, and lasted for a median of 22 (range, 1–88) days. Ten children have remained seizure‐free and one relapsed with focal seizures. Neuropsychological testing at age 5–6 years showed normal cognitive performance in eight children and mild cognitive dysfunction in three. Visual fields were tested by experienced nurses, using the kinetic Goldman perimeter with standard objects V/4e and I/3e in ten children, and IV and 4 in one. Normal result was defined as the fields extending ≥70 degrees in the temporal meridian. Results: Vigabatrin was started at median age 5.5 (range 3.2–12.5) months and lasted for a median of 23.7 (12.6–29.8) months. The median cumulative dose was 733 (range, 284–995) g. Vigabatrin was the only treatment in six children while five also received ACTH. The results of the first Goldman perimetry performed at a median age of 7.2 (range, 6.0–10.6) years were normal in seven children. Three children showed mildly abnormal or uncertain findings in the first testing but had normal results at the second perimetry at 8.7–10.8 years. Temporal fields of one child who was tested only once at 6.6 years extended to 65 degrees. Conclusions: The risk of visual field constriction after vigabatrin treatment may not be as high in infancy as in adulthood. 1,2 Earl Giller, 1 Julia Tsai, 1 Kenneth Shaw, 3 Vincent Pieribone, 4 Christine Soufflet, and 4 Olivier Dulac ( 1 Marinus Pharmaceuticals Inc., Branford, CT ; 2 Psychiatry ; 3 Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT ; and 4 Hôpital St. Vincent de Paul, Paris, France ) Rationale: The neurosteroid ganaxolone (GNX) is an allosteric modulator of the GABAA receptor complex distinct from the benzodiazepine site. GNX has protective activity in diverse animal seizure models. Previous clinical studies have indicated that oral GNX is safe and well‐tolerated. This study evaluated GNX as add‐on therapy in hospitalized children continuing to have seizures despite treatment with available marketed antiepileptic drugs. Methods: Fifteen children (9 male, 6 female), ages 5 to 15 years, enrolled in an open‐label flexible dose‐escalation study of GNX for the treatment of partial or generalized seizures refractory to conventional antiepileptic drugs. Dosing of GNX ß‐cyclodextrin suspension ranged from a starting dose of 1 mg/kg BID to a maximum maintenance dose of 12 mg/kg TID. Dose titration was conducted during a 16‐day inpatient hospitalization followed by a 2‐month maintenance period, after which patients continued treatment, or withdrew treatment over 2 weeks. Results: Thirteen of the 15 subjects were evaluated at Maintenance Week 4 (MW 4). Two patients were withdrawn prior to evaluation, one due to non‐compliance and one to adverse events. The responses of the 13 patients were substantial (≥ 50% seizure reduction) in 4 (one becoming seizure free), moderate (25–49% reduction) in 3 and insufficient (<25% reduction) in 6 patients. Of the 8 patients evaluated at Maintenance Week 8 (MW 8), the responses were substantial in 4 (one of whom was a nonresponder at MW 4), moderate in 2 and insufficient in 2 patients. Three of the 4 eligible patients continued GNX in extension treatment. A total of 17 adverse events (AEs) were reported during the escalation and maintenance phases, 16 attributable to the central nervous system and 1 to the digestive system. Somnolence was the most frequently reported AE. Severity of AEs was either mild or moderate. One patient with a history of abnormal behavior including frequent episodes of agitation experienced a serious adverse event (agitation, hostility, and hallucination requiring extended hospitalization) after a 3 mg/kg TID dose of GNX. These events were considered moderate in severity and possibly related to GNX. The patient was withdrawn from the study, and the events resolved after 11 days. Conclusions: GNX was well‐tolerated. A portion of the subjects in this drug‐refractory population seemed to respond to GNX (5 of 15 demonstrated at least a 25% decrease in seizure frequency at both time points, and 6 demonstrated at least a 25% decrease in seizure frequency at MW 8). Additional controlled studies are required to confirm the efficacy of GNX for the treatment of children with drug refractory partial or generalized seizures. (Supported by Marinus Pharmaceuticals, Inc.) 1 Meera Gupta, and 2 Dennis J. Dlugos ( 1 School of Medicine, University of Pennsylvania, Philadelphia, PA ; and 2 Division of Neurology, The Children's Hospital of Philadelphia, Pennsylvania, PA ) Rationale: To identify situations where equipoise (uncertainty) exists regarding initiation of AED therapy after two unprovoked seizures in children. This has implications for design of future placebo‐controlled trials for anti‐epileptic drug (AED) monotherapy in children. Methods: A survey with ten case scenarios of new‐onset epilepsy in children was developed. Features varying across scenarios included: age, seizure semiology, seizure duration, post‐ictal state, time between seizures, time since last seizure, EEG and MRI results, and patient comorbidities. The survey was administered to Pediatric health care providers (HCPs). Survey participants were asked two questions about each case: 1) “Initiation of a daily AED is indicated”– answered using a 5 point Likert scale; and 2) “I would consider referring this patient for a clinical trial comparing a standard AED with placebo”– answered as yes/no. Results: To date, 151 HCPs completed the survey. Among the 38 HCPs who identified themselves as Pediatric Neurology or Developmental Pediatrics, 13% to 71% responded they disagreed or were uncertain regarding the need to begin an AED. Among the 113 responders who identified themselves as General Pediatrics, Subspecialty Pediatrics or Adult Neurology, 15% to 74% responded they disagreed or were uncertain regarding the need to begin an AED. Features correlating most strongly with desire to initiate an AED (up to 85% of all participants) included abnormal MRI or EEG results, convulsions, and older age. Seizure duration, post‐ictal state, time interval between seizures, time interval since the last seizure, and patient comorbidities did not correlate with desire to start an AED. With regard to referral for a placebo‐controlled trial, 35–78% of Peds Neuro/Dev Peds respondents were willing to refer, compared to 34–59% of other respondents. Conclusions: Given certain clinical features, equipoise exists regarding the initiation of AED therapy after two unprovoked seizures in children. Placebo‐controlled trials are ethical and possible in children with new‐onset epilepsy if inclusion criteria based on equipoise are carefully crafted. (Supported by a grant from the Child Neurology Foundation to Meera Gupta.) 1 Dominic Heaney, 2 Maeva Germe, and 2 Christian Otoul ( 1 Department of Epilepsy, National Hospital for Neurology and Neurosurgery, London, United Kingdom ; and 2 UCB S.A, Braine‐l’Alleud, Belgium ) Rationale: Epilepsy is a common and chronic neurological disorder of childhood encountered by both general pediatricians and pediatric neurologists. Of the 3.5 million people who develop epilepsy annually, 40% are younger than 15 years and more than 80% live in developing countries. The choice of anti‐epileptic drug (AED) is determined by diagnosis, but also the potential effectiveness and tolerability for an individual child. In the absence of head‐to‐head trials directly comparing AEDs in children with partial epilepsy, a scientific review is performed to compare the efficacy and tolerability of newer AEDs from available data. Levetiracetam is here compared to newer AEDs. Methods: Randomized placebo‐controlled trials of add‐on therapy with levetiracetam, lamotrigine, gabapentin, topiramate and oxcarbazepine in children with partial epilepsy were identified in the Cochrane Library Issue 2, 2006 and Medline (1996 to May 2006). The outcomes considered were the 50% responder rate (efficacy measure) and withdrawal rate (tolerability measure) of levetiracetam and these newer AEDs versus placebo. A fixed‐effects analysis was used to estimate Mantel‐Haenszel's odds ratio (OR) of these outcomes. Safety evaluation between these AEDs was assessed using Summary Complaint Scores (placebo events subtracted from AED events) on adverse events with an incidence of at least 10%. Results: One placebo‐controlled trial was found for each AED. Levetiracetam (OR: 3.30 (95% CI: 1.75; 6.24)) and lamotrigine (OR: 3.82 (95% CI: 1.96; 7.45)) were more effective than gabapentin (OR: 1.36 (95% CI:0.71; 2.58)) and had similar withdrawal rates. Levetiracetam (OR: 0.44 (95% CI:0.17;1.15)) had a lower withdrawal rate than oxcarbazepine (OR: 2.15 (95% CI: 1.00; 4.60)); the efficacy of these drugs was comparable (OR: 2.39 (95% CI: 1.00; 4.60) for oxcarbazepine). Gabapentin (score of 15) and levetiracetam (38) showed a more favorable summary complaint score as compared with lamotrigine (69), topiramate (83) and oxcarbazepine (154). Conclusions: This analysis suggest that add‐on therapy with levetiracetam has a favorable responder and withdrawal rates, and Summary Complaint Scores relative to several AEDs in children with partial epilepsy at doses used in clinical trials. Comparative clinical trials and long‐term studies of these agents are needed to confirm these findings and assist physicians in making the right treatment choice. (Supported by UCB S.A.) 1 Katherine D. Holland, and 1 Tracy A. Glauser ( 1 Neurology, Cincinnati Children's Hospital, Cincinnati, OH ) Rationale: Sparse information exists about the overall effectiveness and dose response curve characteristics for initial antiepileptic drug (AED) monotherapy in children with partial onset seizures. The purpose of this work is to characterize the effectiveness and dose response curve characteristics of carbamazepine (CBZ) initial monotherapy in a cohort of consecutive children with partial onset epilepsy. Methods: A cohort of 100 consecutive children (1–18 years of age) with newly diagnosed partial onset epilepsy treated with CBZ as initial monotherapy was identified from the New Onset Seizure Clinic at Cincinnati Children's Hospital Medical Center. Information from the history, physical examination, MRI, and EEG were used to classify the patient's epilepsy and etiology. Seizure control, adherence, and adverse events were recorded at each visit. CBZ responsiveness was defined as seizure freedom for at least 12‐months on a stable dose of CBZ monotherapy or breakthrough seizures only with missed doses in patients with evidence of compliance from random levels. Non‐responsiveness was defined as the addition or substitution of a second AED because of continued seizures and/or intolerable adverse events. Results: Of the 100 patients studied, 55 became seizure free on CBZ monotherapy, 10 did not tolerate CBZ within the first 3 months of therapy either due to hypersensitivity or intolerable side effects and 35 continued to have seizures. The mean dose in seizure‐free children was 11.1 mg/kg/day (standard deviation 3.4 mg/kg/d). The majority of these children responded at the initial dose. Following achievement of the initial target dose 36% of all patients stopped having seizures. There was a weak but statistically significant correlation between age at time of treatment and dose used to control seizures. In children under 12 years age (n = 44) the average daily dose in seizure‐free children was 11.8 ± 3.4 mg/kg/d. In those 12 years of age and over (n = 11) the average dose was 9.0 ± 3.4 mg/kg/d in seizure‐free children (p < 0.05). The data followed a normal distribution and from this it was determined that over 95% of children < 12 years will respond by 17.5 mg/kg/d and 95% children 12 and over will respond by 15 mg/kg/d. Conclusions: Slightly over half (55%) of children with newly diagnosed partial onset epilepsy become seizure free with initial CBZ monotherapy. A considerable percentage (over one‐third of these) became seizure free as soon as they began taking CBZ. The CBZ dose response curve reaches its upper plateau at doses lower than expected. Children under 12 years of age who continue to have seizures at CBZ doses above 17.5 mg/kg/d and those ≥12 years who continue to have seizures at 15 mg/kg/d are very unlikely to respond to CBZ. Other treatments should be considered when seizures continue at CBZ doses above this even if the child is not experiencing intolerable dose related side‐effects. (Supported by CCHMC Trustee Grant.) 1 Elena Isaeva, 1 Dmytro Isaev, 2 Rustem Khazipov, and 1 Gregory L. Holmes ( 1 Medicine, Dartmouth Medical School, Lebanon, NH ; and 2 INMED, INSERM‐U29, Marseille, France ) Rationale: The anaesthetic agent isoflurane exerts its anticonvulsant effect on the central nervous system by suppressing excitation and enhancing inhibition. Most studies devoted to investigation of the mechanism of isoflurane action have been performed on culture and slice preparations from adult animals. However the mechanism of the anticonvulsant action of isoflurane on the immature brain is unclear. The influence of isoflurane on GABAergic system and neuronal network activity was studied in hippocampal slices from immature rat brain. Methods: Sprague‐Dawley rat pups (postnatal days 8–12) were used throughout the study. Effects of isoflurane (2.5%) were recorded using extracellular and whole‐cell patch technique. All intracellular recordings were performed at 0mV (reversal potential for excitatory synaptic transmission). Results: We studied the effect of isoflurane on multi‐unit activity (MUA), giant depolarizing potentials (GDPs), spontaneous inhibitory postsynaptic currents (sIPSC) and tonic GABA currents recorded from the CA1 pyramidal cell layer while extracellular K+ ((K+)o) was changed in the range of 3.5–6mM. Application of isoflurane on hippocampal slices in normal (K+)o (3.5mM) solution significantly decreases amplitude and increase the inter‐event interval of MUA. In whole‐cell recordings isoflurane significantly increased the tonic GABA conductance; prolong decay and decrease the frequency of sIPSC. Increasing (K+)o to 6 mM led to increasing of frequency of GDPs. Adding of isoflurane to high (K+)o solution had a biphasic effect on GDPs. At first the frequency GDPs were two‐fold increased followed by decreasing in amplitude (59.4 ± 1.1%), increasing in duration (62.8 ± 3.3%) and frequency (43.2 ± 3.4%) of GDPs. There were not significant differences between the effect of isoflurane on MUA, sIPSCs and tonic GABA currents in two studied conditions (normal and high (K+)o solution). Gabazine added to extracellular solution in concentration, which selectively blocks synaptic GABAA receptor (1μM), increased MUA frequency, blocked sIPSCs, GDPs and had no apparent effect on tonic GABA conductance. In 6mM (K+)o solution application gabazine evoked interictal discharges. After application of isoflurane, the frequency of gabazine‐induced interictal events decreased from 0.30 Hz to 0.25 Hz. Outward, bicuculline sensitive currents appeared in the presence of isoflurane simultaneously with interictal discharges. Anticonvulsive effect of isoflurane was completely abolished by adding 15 μM bicuculline into extracellular solution. Conclusions: Our results demonstrate that isoflurane has multiple effects in the immature brain. Even though GABA is depolarizing in the immature brain, this volatile anaesthetic decreases the synchronization of neuronal activity, mainly through enhancing the GABAergic inhibition. (Supported by the Epilepsy Foundation.) 1,2 Jinsook Kim, 1,2,3 Alexei Kondratyev, and 1,2 Karen Gale ( 1 Interdisciplinary Program In Neuroscience, Georgetown University, Washington, DC ; 2 Department of Pharmacology ; and 3 Department of Pediatrics ) Rationale: Several AEDs induce pronounced apoptotic neuronal death in specific brain regions in the neonatal rat (Bittigau et al., PNAS,2002). Moreover, AEDs in doses subthreshold for causing cell death in the neonatal brain, can cause substantial cell death when given in combination with other AEDs. Although newer AEDs such as topiramate (TPM) and levetiracetam (LEV) cause little or no cell death in neonatal rats when given alone, neither has been examined for effects on cell death when combined with other AEDs. This is of particular concern because these drugs are frequently used in polytherapy. Therefore, we examined the neurotoxicity of TPM and LEV alone and in combination with phenytoin (PHT) in rat pups. We also examined the effect of carbamazepine (CBZ), a drug often used during pregnancy and childhood. Methods: TPM (20, 40, 80 mg/kg), LEV (250, 500, 1000 mg/kg) or CBZ (25, 50, 100 mg/kg), was given to Sprague‐Dawley rat pups at postnatal day 7, 24h prior to sacrifice. The following doses were also tested in combination with 50 mg/kg PHT: TPM (20, 40, 80 mg/kg); LEV (500 mg/kg); CBZ (25, 50 mg/kg). In addition, LEV (250, 500 mg/kg) was tested in combination with CBZ (50 mg/kg). Cell death was evaluated by TUNEL and Fluoro‐Jade B staining in 20micron coronal brain sections throughout the forebrain and midbrain. Results: Although TPM (20–80 mg/kg) alone did not induce cell death, it significantly enhanced cell death induced by PHT, even at the lowest dose. CBZ alone did not cause cell death up to 50 mg/kg, but when combined with PHT, 50 mg/kg (but not 25 mg/kg) CBZ significantly enhanced PHT‐induced cell death. Cell death was most marked in thalamus and striatum. LEV (250–1000 mg/kg) alone did not induce cell death, and doses up to 500 mg/kg were without effect on PHT‐induced cell death. No detectable cell death resulted from the combination of LEV (250 mg/kg) with CBZ (50 mg/kg). Conclusions: In comparison to most traditional AEDs, CBZ, TPM and LEV are relatively devoid of a pro‐apoptotic action in the developing brain, when administered in a dose range equivalent to, or higher than, the therapeutic range for seizure control. However, our data indicate that they exhibit distinct profiles of interaction with PHT. Whereas both TPM and CBZ significantly exacerbated PHT‐induced cell death, LEV was devoid of this effect. Our data underscore the importance of evaluating the safety of AEDs given in combinations and not merely extrapolating from the effects of exposure to single drugs. Our data suggest that the combination of CBZ and LEV minimizes neurotoxicity in the developing brain and may therefore hold promise as a potential treatment of choice for AED therapy in pregnancy, preterm infants and neonates. (Supported by Epilepsy Foundation predoctoral fellowship, Partnership for Pediatric Epilepsy Research and NIH (NS 20576, MH 02040, NS 041231, HD047890).) 1 Sun Jun Kim, and 1 Hyuk Lee ( 1 Department of Pediatrics, Chonbuk National University Hospital, Jeonju, Jeonbuk, Republic of Korea ) Rationale: The aim of this study was to verifying the usefulness of noninvasive indicator test (Neurocheck™) to predict hypohidrosis and hypohidrosis‐related symptoms in newly diagnosed pediatric epileptic patients with topiramate. Methods: A total of 46 epileptic patients (22 boys and 24 girls) with topiramate were evaluated in this study at the Department of Pediatrics, Chonbuk National University Hospital. We have measured sweating functions using a noninvasive sweating test (Neurocheck™) before and 3 months later after topiramate initiation. We also made a direct survey for the hypohidrosis and hypohidrosis‐related symptoms during topiramate treatment. Results: The mean age was 7.8 ± 3.2. The mean dosage of topiramate was 4.5 ± 0.8 mg/kg/day. Among the 46 epileptic patients, 17 patients (37.0%) experienced hypohidrosis and hypohidrosis‐related symptoms on survey: 12 (26.1%) have facial flushing, 4 (8.7%) heat intolerance, 1 (2.2%) lethargy, but no one have anhidrosis. Among the 17 patients, 13 patients showed delayed sweat test after medication. Sixteen out of 46 patients (34.8%) showed delayed sweat function test by Neurocheck™ after medication. Thirteen out of these 16 patients had hypohydrosis‐related symptoms. The overall measures of agreement between Neurocheck™ and the survey was 76.5%. Conclusions: The main result indicates that Neurocheck™ could be a useful test to detect and predict the topiramate induced hypohidrosis in pediatric epileptic patients. We recommend that patients who show the delayed, particularly delayed over 3 minutes, in Neurocheck™ test after topiramate initiation should be aware the hypohidrosis and hypohidrosis‐related symptoms. 1 Irina Katz, 2,3 Jinsook Kim, 2,3 Karen Gale, and 1,2,3 Alexei Kondratyev ( 1 Pediatrics, Georgetown University, Washington, DC ; 2 Interdisciplinary Program In Neuroscience, Georgetown University, Washington, DC ; and 3 Pharmacology, Georgetown University, Washington, DC ) Rationale: Several antiepileptic drugs (AEDs) induce pronounced apoptotic neuronal death in specific brain regions during the first two postnatal weeks in rat (Bittigau et al., PNAS, 99:15089, 2002). The corresponding period in humans extends from late gestation through early infancy. Since excessive neuronal loss in late prenatal or early postnatal development may contribute to long‐term adverse effects, it is important to identify treatment regimens that are devoid of this deleterious action. Here we examined the effects of lamotrigine (LTG, 10–100 mg/kg) on cell death in several brain regions of neonatal rats. We also examined the effects of LTG given in combination with either phenytoin or MK801. Methods: LTG (10, 20, 30, 50, 100 mg/kg) was administered to Sprague‐Dawley rat pups at postnatal day 7 (PD7), 24hr prior to sacrifice. The following drug combinations were also tested: LTG 10, 20 or 30 mg/kg + phenytoin (50 mg/kg) and LTG (20 mg/kg) + MK801 (0.5 mg/kg). Phenytoin (50 mg/kg) and MK801 (0.5 mg/kg) given alone were also evaluated. Cell death was evaluated in 20 μm coronal brain sections by TUNEL assay in several brain areas, including striatum, thalamus, multiple cortical regions and the hippocampus. Results: LTG alone administered at doses of 10–30 mg/kg did not induce significant cell death. At a dose of 50 mg/kg, 50% of the animals showed increased cell death in thalamus. Administration of 100 mg/kg resulted in significant increase in cell death in all brain areas examined except frontal cortex. Combined application of LTG (20 mg/kg) with MK‐801 resulted in an enhancement of the MK‐801‐induced cell death effect in multiple regions. A similar enhancement of phenytoin‐induced cell death was observed in the presence of 30 mg/kg LTG. In contrast, the lower dose of LTG (20 mg/kg) significantly attenuated the phenytoin‐induced cell death. The lowest dose of LTG (10 mg/kg) was without effect. Conclusions: Our results indicate that therapeutic doses of LTG alone do not induce cell death in the neonatal rat brain in marked contrast to traditional AEDs such as phenytoin, valproate and phenobarbital. However, when given in combination with other pro‐apoptotic agents LTG may potentiate cell death, depending upon the dose and the specific drug combination. This is similar to the profile we have observed with topiramate in other studies. However, a unique feature of LTG is its ability, in low doses, to attenuate the cell death induced by phenytoin. It will now be of interest to determine whether this protective action of LTG in the neonatal brain can also be seen when LTG is combined with other traditional AEDs. (Supported by GlaxoSmithKline Research Grant, the Epilepsy Foundation, and NIH grants MH02040, U10 HD047890.) 1 Zhihong Lu, 2 Nathan B. Fountain, 3 Joan A. Conry, 4 Ildefonso Rodriguez Leyva, 5 Juvenal Gutierrez Moctezuma, 1 Edubijes Salas, 6 Rene Coupez, and 6 Armel Stockis ( 1 Neuroscience, UCB Inc, Smyrna, GA ; 2 University of Virginia, Charlottesville, VA ; 3 Children's National Medical Center, Washington, DC ; 4 Hospital Central, San Luis Potossi, Mexico ; 5 Centro Medico Nacional 20 de Noviembre, Del. Benito Juarez, Mexico ; and 6 UCB S.A., Braine l’Alleud, Belgium ) Rationale: Levetiracetam has demonstrated efficacy in children but the pharmacokinetics in children are unknown. The purpose of this study was to assess the multiple‐dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in children with partial‐onset seizures and determine whether it is affected by adjunctive carbamazepine or valproate. A secondary objective was to correlate levetiracetam concentrations in plasma and saliva and assess its safety and clinical response. Methods: Design was an open‐label, multicenter study. 21 children (4 to 12 years old) with epilepsy taking carbamazepine (13) or valproate (8) received adjunctive levetiracetam. Levetiracetam was initiated at 20 mg/kg/day and titrated at 2‐week intervals to 40 and then 60 mg/kg/day. Twelve‐hour pharmacokinetics were determined at the end of each 2‐week period. Efficacy was estimated from the partial seizure frequency per week and Global Evaluation Scale. Results: Levetiracetam was rapidly absorbed following oral dosing, with median tmax of 0.5 hour and t1/2 of 4.9 hours. Dose proportional increases were observed for Cmax and AUC(0–12) over the dose range. Pharmacokinetics of levetiracetam and ucb L057 were not markedly different with concomitant carbamazepine or valproate; clearance was 7–13% faster and AUC was decreased by 15–24% in those on carbamazepine compared to valproate. Levetiracetam did not affect trough carbamazepine or valproate. Concentration in saliva and plasma were strongly correlated. Seizure frequency declined by 50% or more in 43% of subjects in the intent‐to‐treat population (n = 21) and in 56% of those with seizures at baseline (n = 16). Marked or moderate improvement occurred in 80% and 75% of patients based on Global Evaluation Scale ratings by investigators and parents/guardians, respectively. Levetiracetam was well tolerated. Conclusions: Levetiracetam exhibits simple pharmacokinetics in children, with rapid absorption and dose‐proportional kinetics. Small but not clinically relevant differences were observed between subjects receiving carbamazepine and valproate, suggesting significant dose adjustment is usually not necessary. This substantiates prior assessments that levetiracetam clearance is higher in children than adults, necessitating a higher dose in children on a mg/kg basis, and suggests it is useful add‐on therapy for children with refractory partial‐onset seizures regardless of baseline therapy. (Supported by UCB Pharma, Inc.) 1 Patricia E. McGoldrick, and 1 Steven M. Wolf ( 1 Neurology, Beth Israel, New York, NY ) Rationale: Parents and caregivers of children with infantile spasms and Landau‐Kleffner syndrome are often concerned re: possible side effects of and use of intramuscular injections for administration of adrenocorticotropic hormone. Methods: A retrospective chart review was used to identify children who were treated with intramuscular adrenocorticotropic hormone. Caregivers were contacted and completed a questionnaire regarding their concerns before and after treatment. Anaysis was done to determine whether or not their fears were warranted; whether or not they would recommend treatment to others and what information they felt would be most helpful for families undertaking the decision‐making process. Results: A total of ten families responded. They overwhelmingly felt that they were happy that they proceeded with treatment despite their initial fears; their biggest concerns before treatment were fear of injecting medciation, side effect they feared most was blood dyscrasias, most troublesome side effects were weight gain, insomnia and irritability. Recommendations were: need for easy access to medical personnel and written and video information regarding the medicaiton. Conclusions: The use of adrenocorticotropic hormone poses challenges when providers are attempting to convince families to use this treatment option. Families felt, in retrospect, that treatment was not as overwhelming as they anticipated and asked for instructional materials and abiity to easily contact providers and other families who could serve as resources. 1 Franklin R. Montero‐Contreras ( 1 Unit of Pediatric Neurology; Child Unit of Epilepsy, Centro Medico Universidad Central del Este, Santo Domingo, Distrito Nacional, Dominican Republic ) Rationale: To determine the efficacy of Leviteracetam (LEV) in the control of clinical convulsive crisis in the epilepsies or epileptics syndromes in children. Although Levetiracetam has been only approved for adults, it has showed to be effect in children. Methods: Between September 2002 and January 2005, twenty‐four chil‐dren of our unit were treated with Levetiracetam (40–50 Mg/Kg/day). Our retrospective‐analytic study was carried out in fifteen patients (age: 12 months – 13 years). All patients had their crisis diary checked before and after the addition of Levetiracetam. The follow up was from 8 to 26 months (average 15 months). The patients were classified in three groups, according to the 1989 ILAE classification. The reduction of crisis was rated in percentage (%). Results: We had seven idiopathic syndromes, three symptomatic syndromes and five cryptogenic syndromes. We had eight patients with partial epilepsies and seven patients with generalized epilepsies. All groups showed significant reduction of epileptic crisis (70% in more than 65% of patients). We observed no severe significants adverses reactions. In all patients the levetiracetam was add to polytherapy. Conclusions: The fact of making a correct diagnosis of the epileptics syndromes goes in favor of taking a better therapy choice. The reduction of frequency of crisis was significant. It was shown that Levetiracetam has a wide range of action. 1 Seth L. Ness, 1 Jeffrey S. Nye, 1 Caryn L. Kurland, 2 Sylvia Stubler, 2 Edward Maseda, 1 Steven Wang, 1 Bindu Murthy, and 1 Lisa Ford ( 1 Johnson & Johnson, Pharmaceutical Research & Development, L.L.C., Titusville, NJ ; and 2 Ortho‐McNeil Neurologics, Inc., Titusville, NJ ) Rationale: Topiramate (TPM) has been evaluated in several double‐blind, randomized, controlled trials of epilepsy in children as young as 2 years of age; studies in infants are currently underway. The dosages of TPM as adjunctive therapy that are currently being evaluated in infants were based, in part, on findings from a survey of neurologists and epileptologists with personal experience in using TPM in infants. Methods: A random sample of neurologists and epileptologists participated in an online survey of TPM dosing practices in infants. A total of 101 physicians met eligibility requirements and completed the survey. The majority (69%) had treated at least 50 infants with epilepsy (mean, 198) during the last 3 years. The majority (94%) also had experience in using TPM in infants; about 1 in 5 (19%) of all infants had been treated with TPM. The survey consisted of 19 questions concerning initial dose when starting infants on TPM; weekly rate of TPM dose increase; maximum TPM dose for infants; typical TPM maintenance dose; and use of blood levels for adjusting TPM therapy. Results: Physicians in this survey generally agreed on ≤3.0 mg/kg/day TPM as a starting dose for infants and on ≤3.0 mg/kg/day as a titration increment. However, maintenance doses, maximum doses, and target blood levels varied widely. Although most physicians (88%) used maintenance doses of ≤15 mg/kg/day, 3% used maintenance doses of 25–50 mg/kg/day; 9% used maximum doses of 40–60 mg/kg/day. Conclusions: Further studies are underway to define weight‐based TPM dosages for infants, which may vary according to age/development. These systematic evaluations of pharmacokinetics and efficacy across a wide range of TPM dosages in infants with epilepsy will close a critical gap in information available to clinicians using TPM to treat epilepsy in children. (Supported by Johnson & Johnson Pharmaceutical Research & Development, LLC.) 1 M. Scott Perry ( 1 Department of Pediatrics, Division of Pediatric Neurology, Emory University, Atlanta, GA ) Rationale: The incidence of epilepsy is highest in the first year of life, and declines throughout childhood and adolescence. While several new antiepileptic medications have been introduced in the last ten years, only three medications have indications for the treatment of children younger than 4 years of age. Levetiracetam is a novel antiepileptic medication approved as add‐on therapy for partial seizures in children older than 4 years of age. Levetiracetam may be tolerable in children younger than 4 years old and, therefore, provide an alternative treatment for patients in this age group. Methods: Retrospective chart review of 587 children less than 4 years old diagnosed with epilepsy and followed at the Emory University Children's Center over a 5 year period yielded 122 patients (age 1–48 months) treated with levetiracetam. Results: Epilepsy types included partial (52%) and generalized (27%) epilepsy, with 21% unclassified. Levetiracetam was initiated as monotherapy in 48 (39%) patients, with 55 patients (45%) on monotherapy by the end of the study period. Levetiracetam was introduced at an average dose of 24 mg/kg/d (range 7–83 mg/kg/d) and titrated to an average maximum dose of 45 mg/kg/d (range 9–187 mg/kg/d). Seizure freedom was achieved for at least 6 months in 56 patients (46%) and greater than 1 year in 38 (31%) of all the patients reviewed. Within the monotherapy group, 24 (50%) remained seizure free for at least 6 months and 17 (35%) remained seizure free over one year. Levetiracetam was well tolerated, as 70% of the patients continued the medication throughout the follow‐up period (range 6–57 months). The most common side effect requiring discontinuation of levetiracetam was irritability (9%). Conclusions: This retrospective review demonstrates levetiracetam is a tolerable medication which may be efficacious in the treatment of epilepsy for children less than 4 years of age. Levetiracetam offers an important treatment alternative in this age group. (Supported by UCB Pharma, Inc. Smyrna, Georgia.) 1 Sigride Thome‐Souza, 2 Nadia Rezende, 2 Wagner Gattaz, and 1,3 Kette Valente ( 1 Clinical Neurophysiology – Psychiatry, University of Sao Paulo, Sao Paulo, SP, Brazil ; 2 Laboratory of Neuroscience‐Psychiatry, University of Sao Paulo, Sao Paulo, SP, Brazil ; and 3 LIM 21 – Psychiatry, University of Sao Paulo, Sao Paulo, SP, Brazil ) Rationale: This study aimed to prospectively evaluate the risks and benefits of valproate/divalproate and lamotrigine co‐administration in a pediatric population with refractory epilepsy. Methods: Seventy‐six patients received an association of valproate and lamotrigine according to Gubermann´s criteria (1993). Results were established in accordance with seizure control, adverse effects and tolerability. Treatment was considered effective when seizure reduction > 50% was obtained. Results: Association of valproate and lamotrigine was considered effective in 69 (90.8%) of all patients. Total seizure control (seizure‐free) was obtained in 45 (59.2%) patients. Although seizure control was considered unsatisfactory (<50%) in the remaining patients, drop‐attacks and secondarily generalized tonic‐clonic seizures were reduced in nine (11.8%) patients, maintained on treatment. Tremor occurred in six (7.9%) patients; urinary incontinence and ataxia in one (1.3%). Skin rash occurred as an early manifestation in six (7.9%) patients, of which all had a previous history of hypersensitivity to anti‐epileptic drugs. Reasons for treatment fall‐out were unsatisfactory seizure control in five (6.6%) and adverse effects in three (3.9%). Conclusions: In this series, seizure control was observed in most children with refractory epilepsy, some of which had a previous history of unsatisfactory response either to lamotrigine or to valproato, both in monotherapy or polytherapy. Adverse effects were infrequent, but skin rash was observed more frequently than in other series in which valproate or lamotrigine were used separately. However, this risk may be minimized by slow introduction and increase of the dosage of lamotrigine and by exclusion of patients with a previous history of hypersensitivity. (Supported by FAPESP 03/07724–2.) 1 Andrew H. Schapiro, 1 Katherine D. Holland, and 1 Tonya M. Phillips ( 1 Neurology, Cincinnati Children's Hospital, Cincinnati, OH ) Rationale: Phenobarbital is widely used for the treatment of neonatal seizures, but is effective in only about one‐third to one‐half of neonates with seizures. Second line treatments such as phenytoin or benzodiazepines have also been of limited effectiveness. In addition, in animal studies, all of these drugs increase neuronal death. Levetiracetam (LEV) potentially represents an alternative option because of its novel mechanism of action and favorable pharmacological profile. However, little is know about the effects of LEV in neonates with seizures. The purpose of this work is to characterize the safety and efficacy of levetiracetam in neonates with seizures. Methods: The effectiveness of LEV was studied retrospectively in a group of neonates with EEG confirmed seizures. Patients were identified from a database of EEGs done in the neonatal intensive care unit at Cincinnati Children's Hospital Medical Center and associated hospitals over the past 18 months. Neonates were included if they had electrographic seizures (with or without clinical correlate) on an initial EEG and in whom LEV was used within the first 52 weeks post‐conceptual age. Gestational age, post‐conceptual age at seizure onset and at time of initiation of LEV, seizure frequency as determined from serial EEGs and clinical course, etiology of seizures, concomitant antiepileptic therapies, dose of LEV, and side effects associated with LEV therapy were recorded. Results: Five neonates met the entry criteria. The average gestational age was 34 weeks (SD 7.1) with the average post‐conceptual age at seizure onset being 39.2 weeks. The etiologies included malformations of cortical development (2), prematurity with intracranial hemorrhage (2) and unknown (1). The median seizure frequency at the time of the initial EEG was 24 per day (range 1–48). All infants were initially treated with and maintained on Phenobarbital. Following initiation of phenobarbital therapy, the median seizure frequency was 7.5 per day (range 1–48). Levetiracetam therapy was initiated at an average postconceptual age of 41.2 weeks (SD 5.3). Doses of LEV were titrated to effect and ranged from 24 to 72 mg/kg/d. No treatment‐related side effects were seen even at the highest LEV dose. During LEV therapy, the median seizure frequency was 1 seizure per day (range 0.3–24). One neonate became seizure free and another had over a 75% reduction in seizure frequency; two infants had a 50–75% reduction in seizure frequency and there was no response to LEV in the remaining infant. In addition to infants that met entry criteria, another 4 infants were treated with LEV within the first 6 months of life. In these infants, levetiracetam doses ranged from 25–86 mg/kg/d. No treatment related side effects were reported. Conclusions: Levetiracetam was well tolerated in neonates, even at high doses. Seizure frequency was reduced in all but one neonate and one infant became seizure‐free. Levetiracetam should be considered in the treatment of neonatal seizures. (Supported by UCB Pharma.) 1 Audrey Scully, 1 Joan A. Conry, 1 Marian J. Kolodgie, 1 Andrew Renuart, 1 Michael Sigman, and 2 Jay Salpekar ( 1 Neurology, Children's National Medical Center, Washington, DC ; and 2 Psychiatry, Children's National Medical Center, Washington, DC ) Rationale: The use of extended release formulation antiepileptic medications has the advantage of once daily dosing, but requires the ability to swallow the tablet without chewing. In pediatric patients with moderate mental retardation, the ability to swallow tablets potentially limits the use of extended release formulations. This study was designed to evaluate the ability of caregivers to teach pediatric patients with moderate mental retardation to swallow Depakote ER tablets. Methods: Pediatric patients taking stable dose Depakote Sprinkles tablets with moderate mental retardation were recruited to participate in a clinical trial which involved transition to Depakote Extended Release (Depakote ER) tablets. A structured protocol to teach patients to swallow tablets was implemented for 4 weeks. Depakote ER tablets were then introduced. The ability to swallow tablets consistently without chewing was the primary outcome measure. Trough serum valproic acid levels were measured prior to transition, and 2–4 weeks post trasition. Child Behavior Checklist (CBCL) and adaptive behavior rating scales were completed initially and at the completion of the 8 week trial. Results: Ten subjects (6 male) with moderate mental retardation (IQ between 40–60) age 11.1 years (mean 7–17 years) were recuited. Two were nonverbal, one was autistic, and one had a tracheostomy. Nine of 10 successfully learned to consistently swallow the tablets in 4 weeks; the last learned in several months. The valproic acid level was stable and remained therapeutic in 5 patients. Three patients had a decrease in valproic acid level 2 weeks after transition, and 2 of those 3 had an increase in seizure frequency. In 2 patients the valproic acid levels were not measured due to a protocol violation. None of the patients had significant choking, gagging or refusal to swallow tablets. Conclusions: Patients with moderate mental retardation can learn to swallow Depakote ER tablets without chewing, allowing the transition from twice daily dosing of Depakote Sprinkles to once daily dosing of Depakote ER tablets. In this population, the convenience of once daily dosing for a chronic daily medication lessens the caregiver burden of medication administration and potentially improves compliance. Monitoring the valproic acid level prior to transition and 2–4 weeks later will ensure adequacy of trough valproic acid level. Developmental delay with moderate mental retardation and/or inability to speak should not preclude the use of extended release formulation of medications. A structured program to teach how to swallow tablets, and careful safety monitoring of patients, can result in successful use of once daily medication dosing. (Supported by Abbott Laboratries.) 1 Raj D. Sheth, and 1 Bruce P. Hermann ( 1 Neurology, University of Wisconsin, Madison, WI ) Rationale: Children and adults with epilepsy experience poor bone mineralization. This mineralization deficit appears to increase with longer duration of epilepsy and/or its treatment. The effect of antiepileptic drug (AED) initial monotherapy compared to polytherapy on bone mineralization has not been examined previously. We determined BMD in children treated with monotherapy (only ever exposed to carbamazepine (CBZ), valpraote (VPA) or lamotrigine (LTG) compared with AED polytherapy and to healthy controls. Methods: Age‐normalized z‐score total body BMD (Lunar®) was compared in patients 6–18 years treated for epilepsy with initial monotherapy with VPA, CBZ or LTG were compared with those patients receiving polytherapy and healthy controls. General exclusion criteria for patients included being non‐ambulatory, treated for co‐morbid disease or consuming known bone‐adverse medications. Exclusions from the monotherapy group included exposure to an AED other than initial and ongoing monotherapy with either VPA, CBZ or LTG. Activity and calcium intake were examined. Statistical analysis included ANOVA and student t‐test. Results: 33 patients (13 ± 3y; 13f, 20m) treated with monotherapy (CBZ = 13, VPA = 15, LTG = 4) were compared to 40 patients (11.7 ± 3.5y; 27f, 13m) recieving AED polytherapy and 36 healthy controls (13 ± 2y.6yr; 22f, 14m). Age, height and weight were not statistically different between groups. Duration of epilepsy for the monotherapy group was 5.2y (CI = 4, 6.4)compared to 6.3y (CI = 5,7.7). Age mean z‐scores for total BMD was (0.5 ± .17) for patients recieving monotherapy and was similar to controls (0.5 ± .15). However, patients receiving AED polytherapy had lower BMD (‐0.04 ± .15) than for patients recieving AED monotherapy or for controls, p < 0.02. Conclusions: AED Polytherapy was associated with significant reduction in BMD compared to patients recieving AED monotherapy. This reduction was far greater than the non‐statistical trend towards the slightly longer treatment duration of polytherapy patients compared to monotherapy patients. Furthermore, while patients recieving AED monotherapy had similar BMD compared to controls, patients recieving AED polytherapy experienced a significant osteopenia when compared to controls. With larger number of patients the specific effect of inidvidual AED on bone health should become apparent. (Supported by Investigator initiated grant from GSK.) 1 Deepa Sirsi, 1 Shrishti Nangia, 1 Jacqueline La Mothe, 1 Barry E. Kosofsky, and 1 Gail E. Solomon ( 1 Child Neurology, New York Presbyterian Hospital – Cornell, New York, NY ) Rationale: Seizures are indicative of underlying neurologic dysfunction in neonates. Repeated seizures may be deleterious to the brain even without disturbances of ventilation or perfusion. Seizures are refractory to first line antiepileptic drugs (AEDs), phenobarbital (PB)and phenytoin (PHT) in 20–50% of children. In neonates AEDs can be even less effective in controlling seizures. Rapid control of status epilepticus with midazolam has been demonstrated in 2 previous studies with complete clinical and electrographic response in neonates who did not respond to PB and PHT. Methods: We report our experience with 3 neonates with status epilepticus secondary to HIE, Group B Streptococcal (GBS) meningitis and Ohtahara syndrome. The age at presentation was 1 day for the neonates with HIE and Ohtahara syndrome. The neonate with GBS meningitis presented at 23 days. Midazolam was initiated on day 2 of seizures for the neonates with HIE and meningitis. The neonate with Ohtahara syndrome initially was started on pentobarbital drip day 2 of seizures; midazolam was initiated day 4 as there was lack of response to PB, PHT and pentobarbital. Results: Seizures in all 3 neonates did not respond to PB (levels of 50–60 mcg/ml) and PHT (18–22 mcg/ml). The neonate with Ohtahara syndrome did not respond to pentobarbital in addition. Seizures in all responded to midazolam infusion. The neonate with meningitis developed hypotension which responded to inotropic support. There were no significant cardio‐vascular side effects in any of the neonates. The neonate with Ohtahara syndrome who had received pentobarbital developed Necrotizing Enterocolitis prior to initiation of midazolam. Midazolam loading dose was used in the neonate with Ohtahara syndrome. Clinical and electrographic seizure control was acheived within a range of 6–72 hours after initiation of midazolam. The maximum dose of midazolam dose used was 0.2 mg/kg/hr. Conclusions: Midazolam was effective in the management of 3 neonates with refractory seizures that did not respond to PB, PHT and pentobarbital. Midazolam may be considered a safe and effective AED in refractory neonatal seizures of diverse etiologies. Midazolam may help acheive relatively rapid clinical and electrographic seizure control. This may be an important factor in decreasing the severity of neurodevelopmental sequelae. 1,2 Pasquale Striano, 2 Maria Margherita Mancardi, 1 Antonietta Coppola, 2 Maria Giuseppina Baglietto, 1 Salvatore Striano, 2 Federico Zara, 2 Roberto Gaggero, and Collaborative Group of Italian League Against Epil ( 1 Department of Neurological Sciences, Federico II University, Napoli, Italy ; and 2 Muscular and Neurodegenerative Disease Unit and Child Neuropsychiatry, Institute G. Gaslini, Genova ) Rationale: Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a catastrophic encephalopathy with onset in the first year of life, more often with febrile hemiclonic or generalized status epilepticus, and secondary developmental delay. Although valproate, topiramate and stiripentol may give some benefit, drug treatment of SMEI is usually disappointing. Levetiracetam (LEV) is a new antiepileptic drug (AED) with a mechanism of action distinct from that of other AEDs and broad spectrum of activity including antimyoclonic activity. We evaluated the efficacy and tolerability of LEV in patients with diagnosis of SMEI. Methods: 10 children (mean age 8.4 years; range 4–16 years) with clinical diagnosis of SMEI were enrolled in a multicentric, prospective, open‐label study. 5 out of 10 patients showed SCN1A mutation. A mean of 2 (range: 1–5) AEDs were tried before LEV trial. LEV was given in add‐on up to the dose of about 50–60 mg/kg/day. Responders were defined as having more than 50% reduction in the frequency of seizures compared with baseline. Results: After a mean period of 8.5 months of treatment (range 6–12 months), 7 patients had more than 50% reduction in seizure frequency. None of the patient was seizure‐free. LEV was generally well‐tolerated. Mild adverse events (i.e., sedation, irritability) occurred in three patients. Conclusions: This pilot study suggests that LEV may be a well‐tolerated drug that may give some benefit in SMEI. Randomized placebo‐controlled studies should be considered to evaluate further this promising therapy. 1 Julia Tsai, 1,2 Earl Giller, 1 Kenneth Shaw, 3 Vincent Pieribone, 4 Christine Soufflet, and 4 Olivier Dulac ( 1 Marinus Pharmaceuticals Inc., Branford, CT ; 2 Psychiatry ; 3 Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT ; and 4 Hôpital St. Vincent de Paul, Paris, France ) Rationale: Ganaxolone (GNX), a neurosteroid, has been evaluated for the treatment of epilepsy in several Phase II clinical trials, including an inpatient trial in children with treatment‐refractory seizures (see companion abstract). The present study evaluated GNX in children with treatment‐refractory seizures in an outpatient setting. Methods: Forty‐five children (25 male, 20 female), ages 2 to 15 years, with seizures refractory to conventional antiepileptic drugs enrolled in an open‐label, flexible dose‐escalation study of GNX. Thirty‐five had epileptic spasms with a historical diagnosis of infantile spasms (IS). After a pre‐dosing observation period (OP), ganaxolone was titrated over a 9‐week period at doses from 1 mg/kg BID to 12 mg/kg TID, followed by an 8‐week maintenance period. Results: Twenty‐seven (60%) of 45 patients completed the study. For all seizure types, twelve (27%) patients were responders (≥50% seizure reduction). Of the 35 with spasms, 1 patient experienced remission and 10 others were responders. Of 9 with absence seizures, 2 experienced remission and 1 other was a responder. Of 6 with partial seizures, 1 experienced remission and 2 others were responders. Of 12 with tonic seizures, 3 were responders. Neither of the patients with myoclonic seizures completed treatment. Central nervous system adverse events (CNS AEs) occurring in ≥ 5% of subjects were agitation (38%), adverse change in seizures (36%) and somnolence (24%). Subjects experienced respiratory/ear infections: pharyngitis (36%), otitis media (16%) and bronchitis (11%). Non‐serious AEs leading to discontinuation were adverse change in seizures (6), agitation (4), increase in seizures and agitation (1), nausea (1), and somnolence (1). One withdrew due to insufficient clinical response. A total of 7 patients reported 9 serious AEs (7 possibly related and 2 unrelated). The majority (6/9) occurring in 5 patients were a change in seizure frequency and/or nature, including 1 who experienced 2 episodes of status epilepticus. Of the 5, 2 discontinued GNX. There was 1 event each of severe otitis, increased seizure frequency plus somnolence, and GNX accidental overdose. Conclusions: A substantial proportion of these drug‐refractory children showed improvement with GNX (overall responder rate 27%; 31% in patients with a historical diagnosis of IS). Controlled trials are necessary to determine whether the worsening seen in some patients is a treatment‐related effect or represents the natural disease course. Many subjects exhibited respiratory and ear infections, which is expected in a pediatric population. Transitory CNS AEs were common, but did not result in discontinuation in the majority of subjects. The results support controlled trials with GNX. (Supported by Marinus Pharmaceuticals, Inc.) 1 Gerard Piñol, 1 Divya S. Khurana, 1 Agustin Legido, 1 Sanjeev V. Kothare, 1 Harold Marks, 1 H. Huntley Hardison, 1 Joseph J. Melvin, and 1 Ignacio Valencia ( 1 Section of Child Neurology, Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA ) Rationale: Levetiracetam (LEV) is a new antiepileptic drug (AED) approved as adjunctive therapy in children older than 4 years with partial or secondary generalized epilepsy. Myoclonic seizures are often difficult to control requiring several AEDs. Studies in juvenile myoclonic epilepsy have shown good response of myoclonic seizures to LEV. The use of LEV in myoclonic seizures due to symptomatic generalized epilepsy in children is scarce. The objective of this study was to evaluate the efficacy and tolerability of LEV in the treatment of this type of seizures in children. Methods: We retrospectively reviewed the records of children with myoclonic seizures due to symptomatic generalized epilepsy, who were treated with LEV at our institution between 2003–2005. Reduction of myoclonic seizures was assessed. Results: Twelve patients (9M, 3F), mean age 7.2 years (range: 2–12) were identified. Two of them had myoclonic seizures only, while ten had additional types of seizures including tonic, tonic‐clonic, complex partial, and drop attacks. Eleven patients had developmental delay, mental retardation or learning disability. Mean LEV dose was 39 mg/kg/day (range: 21–69 mg/kg/day), mean number of previous AEDs 2.6 (range 0–7), and mean number of concomitant AEDs 1.63 (range 0–3). One patient was on monotherapy. Mean follow up was 12 months. Myoclonic seizure reduction was as follows: 100% in 1, 75–99% in 2, 50–74% in 2, 25–49% in 3, and < 25% in 3. Overall, forty two percent of patients had 50% reduction in myoclonic seizures. Side effects included transient drowsiness in 2, and behavioral problems requiring discontinuing LEV within a month of therapy in 1. Conclusions: LEV proved to be effective and safe in our group of children with myoclonic seizures due to symptomatic generalized epilepsy. Further studies are necessary to assess the use of LEV monotherapy or polytherapy in myoclonic seizures in children. 1 Beverly S. Wical, 2 Frank J. Ritter, and 1 Shani K. Norberg ( 1 Pediatric Neurology, Gillette Children's Specialty Healthcare, St. Paul, MN ; and 2 Pediatric Neurology, Minnesota Epilepsy Group, St. Paul, MN ) Rationale: Neonatal seizures continue to lack therapies with proven efficacy and safety. Up to 50% of neonatal seizures are not controlled despite treatment with phenobarbital (PB) or fosphenytoin (fPHT). Concerns about toxicity of antiepileptic drugs (AEDs) in this special population persist. Term infants who fail standard therapy require additional treatment. Levetiractam (LEV) is considered a safe medication, with no significant drug interactions and no known neurotoxicity. We present our experience with LEV in 19 full term newborns. Methods: Retrospective chart analysis was performed: we identified 19 term infants who received LEV in the first 28 days of life. Charts were reviewed for demographics, birth weight, gestational age, age of seizure onset, and day of life LEV started. We reviewed other treatments, etiology of seizures, EEG and MRI results. Initial LEV and maintenance doses were recorded. Adverse events and side effects were reviewed. Number of infants continuing on LEV, and number seizure free were identified. Results: Nineteen infants with gestational ages 38 to 42 weeks receieved LEV for clinical seizures. LEV was administered by oral or nasogastric route. Seven infants were female, 12 male. Etiology for seizures included: cerebral infarction (6), unknown (4), hypoxia (2), congenital brain anomaly (2), extra‐axial hemmorhage (2), mitochondrial disorder (1), bacterial meningitis (1), and prolonged hypoglycemia (1). All had EEG studies and MRI. Prior to starting LEV, 14 infants were treated with PB (level =/ > 30), fPHT (level =/ > 18), or both. One infant received a lower dose of PB; 4 received LEV as initial treatment. Doses of LEV given in the first 24 hr of treatment were 4 mg/kg to 42 mg/kg (mean 16 mg/kg). Maintenence doses ranged from 25 mg/kg/d to 90 mg/kg/d (mean 32 mg/kg/d). No infant had any significant adverse event related to LEV initiation or continued treatment. Transient initial sedation was noted in 3 infants. Prior to reaching optimal dosing, 2 infants discontinued LEV due to side effects. One was irritable, the other was sedated. Three infants stopped LEV due to lack of efficacy; all 3 failed multiple other medications. Fourteen of 19 infants continued LEV therapy beyond the neonatal period. Eleven became seizure free on LEV. Eight discontinued AEDs; 7 have been followed for 34 – 57 mo (mean 32 mo) and remain seizure free. Six infants continue on LEV with excellent seizure control; duration of follow up is 9 to 45 mo (mean 18 mo). Conclusions: No significant adverse events were identified in this retrospective study of 19 term infants who received LEV. The majority (14/19) had difficult to treat seizures. It was well tolerated by 17/19 (90%) of infants. Fourteen of 19 (73%) received benefit from LEV therapy; 11/19 (58%) became seizure free. Our study suggests LEV is a promising therapy for neonatal seizures. Larger studies of safety and efficacy are needed. 1 Jorge G. Burneo, 1 Shareefa Abdool, and 1 Richard S. McLachlan ( 1 Epilepsy Programme, University of Western Ontario—LHSC, London, ON, Canada ) Rationale: The choice of drugs for the management of newly diagnosed epilepsy is based in evidence, that takes into account efficacy and safety. Comparisons between medications for specific syndromes or age‐groups have not been carried out. We conducted a survey on the management of epilepsy among Canadian epileptologists. Methods: We mailed a questionnaire on the treatment of different epilepsy syndromes, to all epileptologists in Canada. Adult and pediatric epileptologists were identified from the Canadian League Against Epilepsy and the Canadian Congress of Neurological Sciences membership lists. Patient‐scenarios were grouped into 13 categories according to epilepsy syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic focal epilepsy, and unclassified epilepsy), and to patient's gender and age group. Physicians were asked to rate treatment options based on a 5‐point scale (“1”= most appropriate to “5”= harmful). The responses were anonymously collected. Results: Forty‐one out of 64 Canadian epileptologists returned the survey. The results suggest a consensus among Canadian epileptologists: Valproate is the drug of choice for generalized epilepsies in the adult (p < 0.05) and elderly population, while lamotrigine is the choice in women of childbearing age (p < 0.05). For the treatment of the focal epilepsies, carbamazepine is the choice (p < 0.05) for all ages and groups. In undetermined epilepsy, carbamazepine and valproate are the choice for adults; carbamazepine, clobazam, and lamotrigine for the elderly; and lamotrigine and carbamazepine for women of childbearing age. Conclusions: The choices of antiepileptic drugs among Canadian epileptologists is similar, with some minor exceptions, with the choices of their American and French counterparts. 1 E. Andermann, 1 F. Andermann, 2 P. Meyvisch, and 2 F. Tonner ( 1 Montreal Neurological Hospital and Institute, McGill University, Quebec, Canada ; and 2 Pharma Sector, UCB SA, Braine‐l’Alleud, Belgium ) Rationale: To evaluate the efficacy and tolerability of levetiracetam (LEV) add‐on therapy in patients with refractory idiopathic generalised epilepsy (IGE) experiencing myoclonic seizures (MCS) or primary generalised tonic‐clonic seizures (PGTCS). Methods: 2 multicentre, placebo (PBO)‐controlled, double‐blind studies were conducted in IGE patients with MCS (Study N166) or PGTCS (Study N01057). N166 recruited patients, age 12–65 years, experiencing ≥8 days with ≥1 MCS during 8 weeks baseline, and receiving 1 standard antiepileptic drug (AED). N01057 recruited patients, age 4–65 years, experiencing ≥3 PGTCS during 8 weeks baseline, and receiving 1–2 AEDs. LEV was uptitrated over 4 weeks to a target dose of 3000 mg/day (60 mg/kg/day for paediatric patients), and evaluated over 12 (N166) or 20 (N01057) weeks. Efficacy was assessed over the entire treatment period (titration+evaluation)), as responder rate (≥50% reduction in seizure days/week (MCS) or seizures/week (PGTCS)), and as seizure freedom rate defined as percentage of seizure‐free study completers in the intention‐to‐treat population over the evaluation period. Tolerability was assessed by evaluating adverse events (AEs). Results: N166 randomised 122 patients (Juvenile Myoclonic Epilepsy (JME) n = 113, Juvenile Absence Epilepsy (JAE) n = 9); 60 LEV and 60 PBO patients provided evaluable data. N01057 randomised 164 patients (JME n = 54, Epilepsy with Grand Mal Seizures on Awakening n = 49, JAE n = 19, Childhood Absence Epilepsy n = 7, other IGE n = 28, unknown syndromes n = 7; 79 LEV and 84 PBO patients provided evaluable data. In N166, responder rates (LEV vs PBO) were 58.3%vs 23.3% (p < 0.001) for MCS and 56.7%vs 21.7% (p < 0.001) for all seizures; seizure freedom rates were 16.7%vs 3.3% (p = 0.029) for MCS and 13.3%vs 0% (p = 0.006) for all seizures. In N01057, responder rates (LEV vs PBO) were 72.2%vs 45.2% (p < = 0.001) for PGTCS, and 59.5%vs 29.8% for all seizure types (p < 0.001); seizure freedom rates were 24.1%vs 7.1% (p = 0.004) for PGTCS and 15.2%vs 6.0% (p = 0.072) for all seizures. In N166, 75.0% LEV vs 66.7% PBO patients reported ≥1 AE during treatment period; 2 LEV and 1 PBO patient withdrew due to AEs. In N01057, 72.2% LEV vs 67.9% PBO patients reported ≥1 AE during treatment period; 1 LEV and 4 PBO patients withdrew due to AEs. Conclusions: These studies provide further evidence that LEV is effective and well tolerated in patients with refractory IGE, significantly reducing the frequency of both MCS and PGTCS and substantially increasing the seizure freedom rates in patients with each of these seizure types. (Supported by Funds from UCB.) 1 Hiba Arif, 2 Richard Buchsbaum, 1 Jennifer Cabot, 1 Jason Sulkowski, 1 Stanley R. Resor Jr., 1 Steven Karceski, 1 Carl W. Bazil, and 1 Lawrence J. Hirsch ( 1 Comprehensive Epilepsy Center, Department of Neurology, Columbia University, New York, NY ; and 2 Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY ) Rationale: Rash is a well known side effect of antiepileptic drug (AED) therapy. Some patients develop rash from multiple AEDs. Very few studies have attempted to determine the frequency of cross‐sensitivity of rashes among all AEDs. Rates of rash cross‐sensitivity with AED use In those with: % (total N) Rash rate (% (total N)) CBZ LTG OXC PB PHT ZNS CBZ Rash 13 (745) 20 (50) 33 (15) 27 (30) 58 (59) 9 (11) CBZ No Rash 87 (745) 8 (366) 3 (76) 3 (120) 18 (268) 4 (174) LTG Rash 10 (864) 26 (38) 20 (15) 8 (13) 39 (36) 12 (17) LTG No Rash 90 (864) 11 (378) 5 (103) 7 (124) 16 (365) 8 (96) OXC Rash 8 (201) 71 (7) 38 (8) 0 (4) 33 (9) 0 (1) OXC No Rash 92 (201) 12 (84) 11 (110) 8 (35) 15 (74) 14 (43) PB Rash 9 (276) 67 (12) 11 (9) 0 (3) 53 (15) 0 (5) PB No Rash 91 (276) 16 (138) 9 (128) 11 (36) 21 (156) 13 (24) PHT Rash 18 (716) 42 (81) 19 (74) 21 (14) 19 (41) 21 (14) PHT No Rash 82 (716) 10 (246) 7 (327) 9 (69) 5 (130) 10 (51) ZNS Rash 8 (174) 25 (4) 0 (10) 0 (6) 0 (3) 37 (8) ZNS No Rash 92 (174) 12 (81) 1 (101) 3 (38) 19 (26) 19 (57) Any Other AED Rash 36 (48/134) 20 (26/131) 19 (43) 15 (73) 43 (114) 14 (42) No Other AED Rash 1 (1/115) 8 (57/733) 4 (158) 7 (203) 14 (602) 6 (132) Bolded%: p < 0.001 compared to those without rash to an AED Our objective was to determine the rates of cross‐sensitivity of rash occurring with use of older and newer AEDs in patients with epilepsy. Methods: As part of the Columbia AED Database, we reviewed the incidence of AED‐related rash for 1875 patients with epilepsy ≥12 years old, including a history of AED rash at any age. We compared the rate of rash when these patients were taking any of the 15 most commonly used AEDs at our center: carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproic acid (VPA) & zonisamide (ZNS). We compared the rates of rash for each AED in patients who had or did not have a rash to: 1) another specific AED; 2) any other AED; & 3) any 2 other AEDs. Data were analyzed with chi‐square or Fisher exact tests, with significance set at p < 0.05. Results: 14.3% (269/1875) of patients had a rash attributed to at least one AED; 2.8% (72/1875) of patients had a rash from ≥2 AEDs. Rates of rash & cross‐sensitivity for the 6 AEDs most commonly causing rash are shown in Table 1. Results of all 15 AEDs will be presented. Conclusions: The cross‐sensitivity rates for rashes involving CBZ & PHT range from 42–58%, those involving CBZ & LTG range from 20–26%, and those involving LTG & PHT range from 19–39%. For most AEDs, the risk of developing a rash increases at least two‐ to threefold if the patient has a rash to one or more other AEDs. (Supported by Elan, GlaxoSmithKline, Novartis, Ortho‐McNeil, Pfizer & UCB Pharma.) 1 Jane Boggs, and 2 Ronald C. Reed ( 1 Neurology, University of Florida, Gainesvilles, FL ; and 2 Neuroscience, Research and Development, Abbott Laboratories, Abbott Park, IL ) Rationale: Drug intoxication after inadvertent substitution of an immediate‐release drug with an extended‐release formulation has been documented (Am J Health‐Syst Pharm 2001;58:402–5). Similarly, it has been speculated that clinical consequences could occur from a lack of recogntion of the differential biopharmaceutic characteristics of the divalproex sodium extended‐release formulation (ER) versus the conventional delayed‐release, enteric‐coated formulation (EC) (Ann Pharmacotherapy 2006; 40:619–25). ER is approved for once daily administration, whereas EC is approved for multiple‐daily dosing. We analyzed prospectively collected cases of adverse effects and breakthrough sizures in patients with epilepsy resulting from the unintentional substitution of EC for multiple‐daily dosing due to medication dispensing errors. Methods: EC vs. ER dispensing errors were tabulated in epilepsy clinics between July 2001 and May 2006. Patients and caregivers were interviewed to determine pharmacy location, circumstances of error, and any seizures or adverse effects that followed the errors. Results: Substitution of clinican prescribed once‐daily ER with EC occurred in six cases, due to lack of availability of ER at the local pharmacy at the time of prescription submission, and in five cases due to mistakes on refills of a previous correctly filled prescription. Two experienced increased tremor of mild but noticeable severity. Three patients had breakthrough seizures. Side effects and seizures abated after discovery of the errors and the correct ER dosing regimens were resumed. One patient was given both ER and EC in one refill, being told by the pharmacy that the two formulations only differed in color. Three other cases documented incorrectly the formulation dispensed, which created confusion for the prescriber, but did not result in problems for the patient. Conclusions: Availability of divalproex‐ER and EC in identical dose strengths has created some confusion among healthcare providers and pharmacies, resulting in patient complications. Prescriptions for EC vs ER require vigilance by all, including the patients receiving the prescriptions. Inadvertent substitution of EC for ER has been documented to have deleterious clinical impact. Additional education of pharmacists may be needed to minimize dispensing errors of this type. (Supported by Abbott Laboratories.) 1 Michael J. Boyd, 1 Robert T. Standring, 1 Patrick L. Alore, 1 Terrence Metz, 2 Michael J. Schneck, and 2 Micheal P. Macken ( 1 Stritch School of Medicine, Loyola University Chicago, Maywood, IL ; and 2 Neurology, Loyola University Chicago, Maywood, IL ) Rationale: Levetiracetam, although currently approved only as adjunctive therapy in the treatment of epilepsy, may be efficacious as a monotherapy across a broad range of seizure disorders. Methods: We retrospectively identified eighty‐five patients (ages 8 months‐98 years; mean 39 years; 51 male, 34 female) with various seizure disorders having been treated with levetiracetam (LEV) monotherapy. While the criteria for inclusion consisted of any length of mono‐ treatment (mean 7.2 months), changes in seizure frequency and seizure freedom were evaluated in three month intervals up to one year. Patients began LEV as either first line therapy (n = 38) or were converted to LEV from other AEDs (n = 47). Medical records were reviewed for seizure type (primary generalized vs. partial), etiology (categorized as tumor (n = 19), trauma (n = 5), stroke (n = 11), idiopathic epilepsy (n = 33) and other (n = 17)), previous number of AEDs, and changes in seizure control or subsequent seizure freedom. Data was evaluated in relation to efficacy across gender, age, seizure etiology, and first‐line vs. conversion therapy. Results: Of the patients immediately available for follow‐up, thirty‐nine remained on LEV for at least 6 months; twenty‐five (64%) became seizure free. Of those continuing to experience refractory seizures, eight (57%) exhibited marked improvement in seizure control, five patients showed no change and one patient demonstrated worse seizure control. Expanding the patient population to at least 3 months on LEV (n = 57), thirty‐eight (67%) were seizure free, and of the breakthrough patients, nine patients (47%) experienced improvement in seizure control while eleven showed no change or reduced control. The pediatric population (<18 years) was found to consist of twenty‐six patients (ages 8 months‐16 years; mean 6.1 years), of which fifteen were available for follow‐up after 6 months on LEV. Eight patients (53%%) became seizure free while two showed >50% reduction in seizures and five (33%) showed no change in control. In comparison across age, this was less than the 63% seizure freedom noted in the age range of 18–65, and 88% in age 65 and older. In a 6 month evaluation across sexes, 87% of males achieved seizure freedom or marked improvement in control, compared to 81% females. We also observed dosing patterns (range: 20mg BID‐1500mg BID, mode: 500mg BID) having direct proportionality to seizure frequency and severity, as well as age. It was noted that although a loading dose of 750mg is recommended, in only seven instances was a higher initial dose used when prescribed below the recommended loading level. Conclusions: Our results indicate that Levetiracetam as a monotherapy can provide an effective and tolerable treatment for a range of seizure disorders. A prospective, double blind study is necessary to confirm our finding. (Supported by UCB Pharmaceuticals.) 1 Thomas Bramley, 1 Brian Meissner, 2 Dilesh Doshi, and 2 Marcia Rupnow ( 1 Outcomes Research, Applied Health Outcomes, Tampa, FL ; and 2 Scientific Affairs, Ortho‐McNeil Janssen Scientific Affairs, LLC, Titusville, NJ ) Rationale: Older antiepileptic drugs (AEDs) are associated with an increased potential for drug interactions when compared with newer AEDs (topiramate, lamotrigine, gabapentin, levetiracetam, etc.). However, the frequency with which patients are susceptible to drug‐drug interactions in clinical practice is not known. This study compared the frequency of potential clinically relevant drug interactions for newer and older AEDs. Methods: In this retrospective, observational study, administrative claims obtained from a state Medicaid program were screened to identify records meeting the following criteria: 1) an AED prescription claim during the enrollment period (September 1, 2003 – September 30, 2004), defined as the index prescription, for either a newer or older agent; 2) an International Classification of Disease, Ninth Revision, Clinical Modification code for epilepsy; 3) continuous enrollment 12 months after the index prescription. The potential for drug‐drug interactions was quantified by the percentage of episodes, regardless of their duration, in which AED exposure coincided with exposure to another non‐AED known to have a clinically relevant interaction with the AED. (1) (1) Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2005;61(3):246–255. Results: A total of 756 patients met the inclusion criteria. The average patient age was 34 (SD ± 22) years; 53% (n = 400) were female. In this patient population, there were 1,444 exposures to AEDs; 34.9% (n = 504) were exposures to new AEDs, and 65.1% (n = 940) were exposures to old AEDs. Of the new AED exposures, 2.6% (n = 13) coincided with another medication known to have a clinically relevant drug interaction as compared with 55.8% (n = 525) of old AED exposures. (1) Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2005;61(3):246–255. Conclusions: This study is the first to document the extent of co‐exposure of AEDs with other drugs known to cause drug interaction. Older AEDs are associated with a greater likelihood of a potential clinically relevant drug interaction than a newer AED in this state Medicaid population. Future research documenting the clinical outcomes of these interactions and analysis adjusting for exposure time of each AED is warranted. (Supported by Ortho‐McNeil Janssen Scientific Affairs, LLC.) 1 John C. DeToledo, 2 Carol A. Westall, and 3 Stephen D. Collins ( 1 International Center for Epilepsy, University of Miami, Miami, FL ; 2 Department of Ophthalmology, University of Toronto, Toronto, ON, Canada ; and 3 Ovation Pharmaceuticals, Deerfield, IL ) Rationale: Multiple reports have estimated the incidence, prevalence, risk factors, and functional outcomes associated with the vigabatrin‐induced visual field defect (VFD). These studies have yielded a range of prevalence estimates. A recent large study of adults and children with complex partial seizures now helps better define incidence and prevalence and a better understanding of the functional impact of retinal injury. Methods: An open‐label, multicenter, longitudinal study with blinded perimetric evaluations. Patients were stratified by age and by exposure to vigabatrin (Group 1: currently treated with vigabatrin at study inclusion; Group 2: previously treated with vigabatrin; Group 3: never treated with vigabatrin, but could initiate vigabatrin if visual fields were normal at baseline. Primary outcome was prevalence of bilateral concentric peripheral constriction (BCPC) via perimetry assessment (at least one static and one kinetic). Prevalence was defined as occurrence of BCPC at study inclusion and on first conclusive perimetry examination. Incidence of BCPC was defined as occurrence of BCPC after first dose of vigabatrin and observed on or after study enrollment. Results: At time of submission, a closed database was available on 432 of 563 patients enrolled. Study completion summer of 2006. Patients in Group 1 (48 children; 150 adults) had received vigabatrin for an average of 4 years. Group 2 patients (55 children; 158 adults) received vigabatrin for an average of 1.8 years (children) and 2.5 years (adults) prior to vigabatrin discontinuation. Prevalence rates of BCPC ranged from 6% to 10% in children and from 20% and 30% in adults. Incidence of BCPC was 31% and 44% of children and adults in Group 1, respectively, and 10% and 26% in Group 2. No patients in Group 3 developed BCPC, however only 7 patients received vigabatrin in this group. One subject in Group 3 had definitive findings of BCPC prior to vigabatrin administration. The earliest finding of a VGB‐VFD was at 11 months. In general, onset was after 2 years of exposure, with the mean times in this study from first vigabatrin dose to BCPC amongst the six cohorts was from 5 to 7 years (at least one BCPC) and 5.5 to 8.5 years (confirmed BCPC). Blinded scoring of fields in subjects with BCPC showed lateral vision averaged 65 degrees and there was little change on average over approximately 2 years from first to last field examination. Conclusions: The VFD associated with vigabatrin therapy for CPS requires many months to years of treatment to appear, is not progressive, is usually asymptomatic, and can be effectively monitored. Because the onset of efficacy in clinical studies is usually within 12 weeks of initiation, and the earliest onset of the VFD was at 11 months, clinicians have the opportunity to assess efficacy before any substantial risk of field defect exists. (Supported by Ovation Pharmaceuticals, Inc.) 1 F. Andermann, 2 M.S. Duh, 3 A. Gosselin, 3 P. Lefebvre, and 3 P.E. Paradis ( 1 Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada ; 2 Analysis Group, Inc., Boston, MA ; and 3 Groupe D’Analyse, Ltée, Montreal, QC, Canada ) Rationale: Compulsory generic substitution may lead to adverse effects in epilepsy patients because of the consequences linked with a single seizure recurrence. This concern is magnified by the widespread use of narrow therapeutic index (NTI) drugs for epilepsy. The objectives of the study are (1) quantify the switch‐back rates from generic to brand‐name AEDs compared to other drugs, and (2) assess the clinical impact of switching from branded Lamictal® (BL) to generic lamotrigine (GL). Methods: We used a public payer database from Ontario, Canada, comprising pharmacy claims from 01/2002 to 03/2006. The Ontario Drug Benefit formulary adopted compulsory conversion to GL in 01/2003, and a steep hurdle was imposed that prevented patients from switching back to BL without documented medical necessity from their doctor. We first calculated the switch‐back rates from generic to brand AEDs (Lamictal®, Frisium®, Depakene®) using a Kaplan‐Meier approach, compared to other chronically used drugs (Zocor®, Prozac®). Secondly, two cohorts of lamotrigine patients were compared with respect to their clinical outcomes: (1) those switching back to BL after being converted to GL (switch‐back group), and (2) those staying on GL after generic entry (generic group). A stratified analysis was conducted on BL patients receiving monotherapy vs polytherapy of AED. The clinical endpoints were proxy for seizure control and tolerability, and included dosages of BL, of GL and number of concomitant AEDs and non‐AED use before and after generic entry. Results: 1452 BL patients (437 monotherapy, 1015 polytherapy) were converted to GL, of which 12.9% switched back to BL (11.7% monotherapy, 13.4% polytherapy). Switch‐back rates of other AEDs were about 20% for Frisium® and Depakene®, both of which were significantly higher than Zocor® (1.5%) or Prozac® (2.9%). In the switch‐back group, the average BL daily dose increased from 229.5 mg at baseline to 279.9 mg GL (p = 0.039) after the generic entry. In the generic group, a similar dose increase was observed from baseline to generic periods (BL 242.8 mg/day versus GL 266.1 mg/day, p < 0.0001). The average number of drug entities dispensed increased for non‐AED co‐dispensings after generic entry compared to baseline (switch‐back group: +12.2%, p = 0.004; generic group: +7.4%, p = 0.03). Conclusions: Switch‐back rates were considerably and significantly higher for Lamictal® and other AEDs than for other chronic disease drugs. Higher generic doses and utilization of other drugs were also found. The extent of switchback differences compared with non AEDs raises concerns. This may be due to loss of seizure control or refusal of epilepsy patients to substitute, despite high cost penalties. Studies to investigate the clinical reasons or resistance to generic switching are required. (Supported by GlaxoSmithKline, RTP, NC, USA.) 1 Charles M. Epstein, 1 Lhys Girard‐Siqueira, and 1 Joshua A. Ehrenberg ( 1 Neurology, Emory University School of Medicine, Atlanta, GA ) Rationale: Several commonly‐used anticonvulsants, including levetiracetam (LEV), are known to have a half‐life in the human bloodstream which is shorter than their typical dosing interval. Their sustained efficacy without intermittent toxicity is not fully understood. Pharmacodynamic changes in the brain are generally suspected to persist longer than blood levels, but the time course of neurological effects has never been measured comprehensively in humans. We used transcranial magnetic stimulation (TMS) to compare LEV blood levels, pharmacodynamic effects, and subjective estimates of toxicity. Methods: Subjects were normal, medication‐free volunteers aged 19–52 who had no history of any renal or CNS disorder, including epileptic seizures in themselves or first‐degree relatives. Following an oral load of LEV 3 gm, blood levels and sequential TMS measures were taken over 48 hours. Subjects used a two‐dimensional visual‐analog scale to estimate the time course of any side effects they observed. Measures of motor threshold (MT) and recruitment at 150% MT were made from the right first dorsal interosseous muscle while stimulating at a fixed point over the left motor cortex. Results: LEV blood levels peaked between 1 and 2 hours after oral administration. MT was maximally elevated beyond 3 hours, and recruitment maximally reduced beyond 5 hours. Changes in recruitment appeared to persist past 24 hours. Subjective toxicity was greatest within an hour of LEV administration, close to the time of peak blood levels. Despite the time lag between toxicity and TMS changes, toxicity estimates correlated significantly with the maximum increase in MT (p < .05, Spearman). Conclusions: There appears to be a substantial time lag between LEV blood levels and TMS measures of neuronal effects, and a similar temporal dissociation between subjective toxicity and maximum neurophysiological change. The time course of TMS changes may help to explain sustained clinical efficacy despite a short peripheral half‐life. (figure 1) (Supported by UCB Pharma.) 1 Sara Eyal, 2 John G. Lamb, 2 Misty Smith‐Yockman, 1 Liat Adar, 3 Boris Yagen, 4 Eitan Fibach, 5 Yoram Altschuler, 2 H. Steve White, and 1 Meir Bialer ( 1 Department of Pharmaceutics, The Hebrew University of Jerusalem, Jerusalem, Israel ; 2 Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT ; 3 Department of Medicinal Chemistry and Natural Products, The Hebrew University of Jerusalem, Jerusalem, Israel ; 4 Department of Hematology, The Hebrew University of Jerusalem, Jerusalem, Israel ; and 5 Department of Pharmacology, The Hebrew University of Jerusalem, Jerusalem, Israel ) Rationale: We assessed whether the antiepileptic and chemotherapeutic drug valproic acid (VPA), an HDAC inhibitor, can induce P‐gp expression in rat liver and brain. Additionally, we determined the effect of multi‐day VPA administration on the anticonvulsant activity of the P‐gp substrate phenytoin (PHT) and on its serum and brain concentrations. Methods: Mdr1a, mdr1b and mdr2 were determined by real‐time polymerase‐chain‐reaction in rats treated for 2 or 7days with 1mmol/kg VPA, valpromide (VPD) or vehicle. The in vitro effect of VPA on P‐gp was analyzed by flow cytometry. PHT anticonvulsant activity was determined in the maximal electroshock (MES) seizure test; results were compared to those obtained in a non‐induced, vehicle‐treated control group. PHT concentrations were assessed by high‐performance‐liquid‐chromatography. Results: Treatment of rats for 2 or 7 days with VPA increased liver expression of mdr1a (2.2‐ and 4.1‐fold, respectively), and mdr2 (2.8‐ and 3.5‐fold, respectively), but not mdr1b. VPA did not significantly alter the expression of either mdr isoform in rat hippocampus or cortex. Similarly, administration of VPD to rats did not increase P‐gp mRNA expression in rat liver or brain. The effect of a series of VPA derivatives on P‐gp expression in SW620, KG1a and MDCK cells correlated with their potency as HDAC inhibitors. Treatment with either VPA or VPD did not alter PHT serum or brain concentrations or compromise its anticonvulsant efficacy against tonic‐extension seizures in the MES Test. Conclusions: VPA induces the expression of P‐gp mRNA in rat livers. However, P‐gp induction by VPA is not sufficient, under the treatment conditions employed, to alter the plasma or brain concentrations and anticonvulsant activity of the P‐gp substrate PHT. Based on the results obtained in the present study, it is not likely that chronic treatment with VPA or VPD will modify the anticonvulsant efficacy of PHT by increasing PgP expression. (Supported by unrestricted funds of Profs. Bialer and NINDS Contract NO1‐NS‐4–2359 (HS White).) 1 Agnes Kowalska, 1 Barbara Fuentes, and 1 Mary Andriola ( 1 Neurology, University Hospital at Stony Brook, Stony Brook, NY ) Rationale: There are approximately over 1 million women of childbearing age in America with epilepsy. More sophisticated diagnostic techniques, effective medications, and improved training of neurologists in epilepsy care have given patients with epilepsy better opportunity for full life and improved seizure control than ever before. There used to be misperception that women with epilepsy should not marry or at least not have children. Most women with epilepsy can and actually do have healthy, normal children. Methods: Retrospective chart review was conducted on 10 pregnant females, with history of epilepsy, who were continued on their antiepileptic drugs during pregnancy. Results: 2 patients were on Trileptal, 3 were on Phenobarbital, 3 were on Topomax, 1 patient was on combination of Lamictal and Tegretol, and 1 patient on combination of Trileptal and Topomax. Three out of ten females had an increase in their AED dosages, in the second trimester, secondary to increase in seizure frequency. One patient had a decrease in the dosage of her AED, and 6 patients had no change in their medication dosages. 5 out of 10 had no reported seizures during the nine months of their pregnancy. All patients had full term, normal vaginal deliveries. 1 out of 10 infants were discharged from the hospital within 48 hours without any complications. 1 infant was admitted to NICU secondary to chorioamnionitis. Conclusions: This limited review showed that there were no physical abnormalities in infants of mothers with epilepsy, on combination or single Antiepileptic Drugs. 1 Karen L. Gilbert, 1 Jenna L. Hott, 1 Barbara C. Jobst, 1 David W. Roberts, and 1 Vijay M. Thadani ( 1 Section of Neurology‐ Epilepsy Program, Dartmouth Hitchcock Medical Center, Lebanon, NH ) Rationale: The precise mechanism of action of levetiracetam (LEV) is unknown; however the mechanism of action distinguishes LEV from most other antiepileptic drugs (AEDs). Anecdotal information suggests that LEV may be an especially useful adjunctive therapy in patients with Vagus Nerve Stimulation (VNS). This study examines the synergistic effects between LEV and VNS, by comparing seizure outcomes in patients with VNS on LEV against groups of patients with VNS on other medications. Methods: This was a retrospective review of outcome after VNS implantation using Engel's classification of seizure outcome following surgery. 132 patients were followed for at least one year following VNS implantation and data pertaining to age, gender, seizure type, AED use and seizure outcome were maintained in a database. Patients had VNS implanted for at least one year. Outcomes of 127 patients, both pediatric and adult patients with partial or generalized seizures were included. The following groups were assessed: patients on LEV and other drugs with VNS; patients on lamotrigine (LTG) and other drugs with VNS; patients on LEV and LTG with VNS; all other patients on other combinations of AEDs with VNS. Results: Out of 127 patients, 17 patients were on LEV and other drugs, 42 patients on LTG and other drugs, 11 patients on a combination of LEV and LTG, and 57 patients were on other combinations of AEDs. Outcomes in terms of Engel's classification were assessed. No group had a statistically significant better outcome (patients in Engel Class I, II, and III, vs. class IV) as compared to the other groups (p = 0.86). When patients on LEV were compared to all other groups (Engel Class I, II and III vs. class IV) there was no significant difference (p = 0.30). When LEV was added on after VNS implantation, it was no more beneficial than the addition of other drugs (p = 0.10). Conclusions: No statistically significant differences in seizure control were found when we compared LEV with other drugs in combination with VNS. Outcomes were about the same for all drug and VNS combinations. Further analysis using other outcome measures will be necessary to demonstrate difference between drugs. The possibility of a Type II error secondary to small numbers of patients in each group is recognized. 1 Varun Goel, 1 James C. Cloyd, 2 Edward E. Patterson, 1 James E. Fisher, 2 Aaron W. Dunn, and 1 Ilo E. Leppik ( 1 Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN ; and 2 Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN ) Rationale: Levetiracetam (LEV) is an antiepileptic drug used for treatment of partial seizures in humans. LEV is available as oral tablets and syrup and an intravenous (IV) formulation (100 mg/mL) is under review at the FDA. The purpose of this pilot study was to obtain data regarding the pharmacokinetics and absolute bioavailability of intramuscular (IM) LEV in dogs to lay the foundation for human studies. Methods: The experiments were done on 6 Hound dogs weighing approximately 22 kg. All dogs received 500 mg (5 mL of IV formulation of LEV) intramuscularly. Three dogs received 500 mg of IV LEV and 3 dogs received 250mg of IV LEV after which the IV catheter was withdrawn and an additional 250 mg was instilled around the vein as an approximation of extravasation. This procedure was done to evaluate the change in pharmacokinetics due to extravasation during IV dosing. A wash out period was allowed between intramuscular and intravenous dosing. Samples were collected starting at 15 min through 24 h at predetermined time intervals. Plasma LEV was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were estimated by non‐compartmental analysis. Results: LEV was completely absorbed after intramuscular administration with a bioavailability of 100%. The median time to achieve maximum plasma concentration (Cmax) after IM dosing was 30 min, and the observed Cmax was 6.13 ± 0.51 μg/mL. After IV injection, LEV showed evidence of mono‐exponential elimination with a half‐life of 174 ± 19 min, a volume of distribution of 2.7 L/kg and a clearance of 258 ± 41 mL/min. Extravasation did not alter LEV pharmacokinetics following IV administration. Conclusions: LEV demonstrated rapid absorption and complete bioavailability in dogs after intramuscular administration. Extravastation around the IV site did not appear to alter LEV pharmacokinetics. These characteristics, in combination with evidence of safety and tolerability, suggest that LEV should be evaluated for Intramuscular administration in humans. (Supported by UCB Pharma.) 1 Marcia L. Buck, 2 Matthew J. Gurka, and 3 Howard P. Goodkin ( 1 Pharmacy and Pediatrics, University of Virginia, Charlottesville, VA ; 2 Public Health Sciences, University of Virginia, Charlottesville, VA ; and 3 Neurology and Pediatrics, University of Virginia, Charlottesville, VA ) Rationale: With the current trend toward accelerated approval of drugs in the US, postmarketing reporting of adverse reactions has become an essential tool in establishing the safety profile of new drugs. Between 1993 to 2000, eight new antiepileptic drugs (AEDs) were approved by the Food and Drug Administration (FDA). While premarketing clinical trials suggested a relatively mild adverse effect profile for most of these new drugs, limited information was available at the time of their approval to accurately define their risks. To examine the significance of postmarketing adverse reaction reporting for the new AEDs, we reviewed safety labeling modifications made since their release. Methods: Safety labeling modifications made for the new AEDs from 1993 through December 2005 were identified using prescribing information and a search of the FDA MedWatch database. Results: All the drugs underwent safety labeling changes during this period. In total, there were 38 safety labeling modifications with the median time to the first change being 2 years after introduction (range: 13 months to 12 years). The most common modification in safety labeling (n = 14) involved the adverse reaction section of the prescribing information. Three of the 38 changes involved the addition of a black box warning (2 for felbamate and 1 for lamotrigine). All occurred within 3 years after the introduction to the market place. The remaining labeling modifications consisted of changes in the warnings (n = 10), precautions (n = 10), and clinical pharmacology (n = 1) sections. Although the majority of labeling modifications came within the first 6 years after approval, mean cumulative function (MCF) analysis revealed no identifiable point at which additional changes were unlikely to be made. Conclusions: Over the past 13 years, a significant number of modifications have been made in the safety labeling of the new AEDs, ranging from black box warnings to the addition of new data in the adverse reactions tables. Recurrent data analysis failed to reveal a point at which additional safety information appeared unlikely, suggesting that the adverse effect profiles of the new AEDs may not yet be complete. (Supported by NIH.) 1,2 Keiko Hara, and 1 Minoru Hara ( 1 Neuropsychiatry, Hara Clinic, Yokohama, Japan ; and 2 Neuropsychiatry, National Center of Neurology and Psychiatry, Musashi Hospital, Tokyo, Japan ) Rationale: It is still controversial how to reduce or discontinue antiepileptic drugs (AEDs) without a risk of relapses in patients who have no seizure for years. We present the long‐term prognosis of epilepsy patients who have had relapses while dose reduction of AEDs and evaluate their subsequent long‐term outcome. Methods: 18 patients (10 males, 8 females) who had relapse while they had AED dose reduction were collected. We followed them for 12 ∼ 27 years (mean; 18 years) after relapses. Their age ranged between 26 and 59‐year‐old (mean; 47‐year‐old), seizure onsets ranged between 10 months and 20 years. Idiopathic generalized epilepsy was diagnosed in 5 patients, symptomatic generalized epilepsy in 1 patient, and localization‐related epilepsy in 12 patients. No patient had surgical treatment. Their seizure free period ranged between 21 months and 9 years prior to dose reduction (mean; 5.1 years). We compared the number and dose of AEDs before dose reduction and at present, also examined the clinical course during the follow‐up period. Results: The duration between change in AEDs dose and the relapse was < /= 2 month in 7 patients, 3 ∼ 12 months in 4 patients, 13 ∼ 24 months in 5 patients, and 48 months < in 2 patients. The last two patients relapsed after they delivered, and they had fatigues, sleep deprivations, and change in life styles. On follow up, patients were taking 1∼3 types of AEDs (mean 1.33) compare to 1∼4 types of AEDs (mean 2.16) prior to dose reduction. 13 (72.2%) of 18 patients were still reduced AEDs compared to what they had taken prior to dose reduction. Three patients had same AEDs. Two patients were taking greater doses of AEDs. In all patients, AEDs were increased after relapses. After that, 10 (56%) of 18 patients had no subsequent seizures. 5 (28%) of 18 patients had1∼3 seizures after relapses, but were seizure free for more than 9 years since then. Of the last three patients, two patients had yearly partial seizures. They reduced their medication from 2∼3 kinds of AEDs to one AED, and we did not further change AED because of their requests. The remaining one patient had two seizures in 16 years due to non‐compliance. Conclusions: The results suggest the AEDs necessary to prevent relapses can alter during long‐term follow up in some patients. Lower dose of AEDs become adequate to control seizures compared to the earlier regimen. Thus, AEDs dose reduction should be considered for patients who have no seizure for years. However, the final decision should be decided based on the their clinical and social‐cultural profile. Our data also suggest that reduction of AEDs has a potential of relapses for the patients with no seizure for long period, however the seizure outcomes and dosage of AEDs were still favorable for long term follow‐up, dose reduction did not make their prognosis worse. Further investigations in a larger population and using EEG could be valuable for clinical practice. 1 Dmytro Isaev, 1 Olena Isaeva, 2 Rustem Khazipov, and 1 Gregory L. Holmes ( 1 Medicine, Dartmouth Medical School, Lebanon, NH ; and 2 INMED, INSERM‐U29, Marseille, France ) Rationale: Neuronal surface charge is a key factor determining neuronal excitability. Reduction of the negative surface charge by increasing the level of divalent cations or proton strongly shifts the activation thresholds towards more positive values. However, the physiological mechanisms regulating neuronal surface charge and associated excitability remain largely unknown. Here we studied effect of desialylation on high K/low Mg model of epilepsy. Methods: Patch‐clamp recordings of voltage‐gated sodium currents were made from hippocampal slices at P3–4 rats (n = 7). Extracellular recordings of the effect of neuraminidase (NA) treatment on the probability of evoking seizures were made from CA3 pyramidal cell layer in slices from P8–21 rats using metal electrodes of 50 μm diameter. For in vivo experiments the application cannula with recording electrode was positioned into the CA3 pyramidal cell. 30μl of NA‐contained ACSF or NA blocker‐contained ASCF were applied to the CA3 rat hippocampus, and the animal remained under anesthesia for 2 hours. Application of 10mM (K+)o/low (Mg2+)o (high K) ACSF was made by repetitive injection of 5 μl‐volumes. Results: After two hours of slice incubation with NA peak of current‐voltage relationship of INa recorded from CA3 neurons shifted toward positive potential (∼9mV). Application of high K+ ACSF induced bursting discharges and then recurrent tonic‐like activity in 87% and 38% and clonic‐like activity in 100% and 77% of control and NA‐treated slices, respectively. Subsequently, we tested the effect of NA on the probability of evoking seizures in vivo in rats (postnatal days 8–21). 30 μl NA was applied in to the CA3 region of rat hippocampus. After two hours of incubation with NA, repetitive injection of the high K+ ACSF into hippocampal CA3 pyramidal layer were applied. In the control group, high K+ inevitably induced ictal‐like discharges in all animals tested (n = 10); only two of eight rats treated with NA displayed ictal‐like activity. Seizures in NA‐treated rats were significantly shorter than in the control group. After incubation with a NA blocker in vivo, high K+ ACSF was applied to the same region of the hippocampus. In contrast with a control group of rats where seizures were triggered on the 4th‐6th application, seizures in NA blocker treated rats appeared on the 1st‐30 ml rd application, and were significantly longer. Conclusions: Our results suggest that NA‐mediated control of the level of sialic acids at the neuronal surface serves as a physiological mechanism to control the surface charge and neuronal and network excitability. (figure 1) 1 Pavel Klein, 1 Daniel Herr, 2 Phillip Pearl, 2 JoAnne Natale, 1 Zachary Levine, 1 Claude Nogay, 1 Michelle Mendoza, 1 Jeni Scarito, 1 Bi Tadzong, 2 Tammy Tsuchida, 2 John VandenAnker, 2 Steve Soldin, and 2 Robert McCarer ( 1 Neurology, MedStar Research Institute, Washington, DC ; and 2 Neurology, Children's National Medical Center, Washington, DC ) Rationale: Head injury is the cause of 5% of all epilepsy. Past attempts at preventing epilepsy by treatment with older antiepileptic drugs (AEDs) have been unsuccessful. Levetiracetam is a new generation AED with a favorable side‐effect and pharmacokinetic profile that has potent anti‐epileptogenic effects in animal models of epilepsy. It may thus be useful in preventing the development of epilepsy following traumatic brain injury (TBI). However, there has been no experience in administering levetiracetam rapidly to individuals with acute TBI. In this pilot study, we are evaluating the safety, tolerability, pharmacokinetics and feasibility of acute and chronic administration of levetiracetam to individuals with head injury with a high risk for developing post‐traumatic epilepsy. Here, we report preliminary findings of tolerability. Methods: Male and female subjects aged 6 years and older are enrolled in a fixed dose, open label study with a sample size goal of 60. All have head injury with a high risk for developing post‐traumatic epilepsy (injury with intracranial hemorrhage, penetrating wound injury, depressed skull fracture or early post‐traumatic seizure). Subjects receive levetiracetam 55 mg/kg/day by mouth or via orogastric tube if unable to swallow. Treatment starts within 8 hours of head injury at full dose and continues for 30 days, with one additional month of post‐treatment follow up. In addition, individuals receive phenytoin for one week following head injury as standard clinical care. Results: 30 subjects (24 adult, 6 children) have been enrolled to‐date. 18/30 (60%) subjects (14/24 adult, 4/6 pediatric) have completed the 30 day treatment phase of the study. 3 subjects (1 adult, 2 pediatric) are currently in active treatment follow up. 3 subjects (all adults) have died, all of medication unrelated causes. There have been no medication‐related serious adverse events. 6 subjects (all adults) have discontinued treatment early: 2 because of medication‐ related toxicity (somnolence, n = 1; and combined fatigue, somnolence, irritability, emotional lability, headaches, n = 1) and 4 for medication‐unrelated reasons. Thus, excluding death and subjects still in active follow up, 18/24 (75%) subjects completed treatment as expected. Only 2/24 (8%) of subjects discontinued medication because of poor tolerability. An update of this data and of interim compliance and adverse event data will be presented. Conclusions: Acute and chronic treatment with high dose (55 mg/kg/day) levetiracetam has been well tolerated in 18 subjects with acute head injury with high risk for developing post‐traumatic epilepsy. (Supported by NIH grant 1 R01 NS45656–01A1.) 1 Günter K. Krämer, 2 Bernhard J. Steinhoff, 3 Martha Feucht, 4 Margarethe Pfäfflin, and 4 Theodor May ( 1 Medical Director, Swiss Epilepsy Center, Zürich, Switzerland ; 2 Klinik Für Erwachsene, Epilepsiezentrum Kork, Germany ; 3 Klinik Für Neuropychiatrie Des Kindes‐Und Jugendalters, Universitätsklinikum, Wien, Austria ; and 4 Biochemisches Labor, Gesellschaft Für Epilepsieforschung E.V., Bielefeld, Germany ) Rationale: The economic benefit of generic drugs in several health problems has to be questioned in chronic diseases with the need for a stable medication. In people with successfully treated epilepsy even a single seizure recurrence may have devastating consequences. We addressed the experience of physicians in Germany, Austria, and Switzerland with generic preparations of antiepileptic drugs (G‐AEDs). Methods: Two internet‐based questionnaire studies among members of the German, Austrian, and Swiss sections of the ILAE as well as members of the German Society for Neurology were performed. In the first study about 2.800 E‐mails were sent together with an accompanying letter on December 1, 2005. Some of the 14 questions had already been used for a corresponding survey in the US (Wilner AN. Therapeutic equivalency of generic antiepileptic drugs: results of a survey. Epilepsy Behav 2004;5:995–998). We offered a link to a specially designed website for an easy online response. In the second study another web‐based questionnaire asking for more details will be sent especially to those responders of the first study who had reported problems with G‐AEDs in June 2006. Results: We received 602 responses to the first questionnaire. About 80% of the physicians had experiences with G‐AEDs. About half of them reported problems such as – in decreasing order – additional telephone contacts or visits, hospital admissions, calls for emergency doctors or visits of emergency rooms, disturbances of the physician‐patient relationship, sick certificates, or injuries. In about half of the physicians these experiences had led to changes in their prescription behavior, especially restrictions for substitution. In addition, increased patient counseling and blood level determinations of AEDs were mentioned. The current criteria for approval of G‐AEDs were considered as inappropriate by about 50%, and 90% considered it unacceptable that pharmacists have the possibility of substitution without consultation. The results of the second questionnaire will be available at the end of July. Conclusions: In line with the results of earlier reports from the US, Canada or other countries our studies underline the potential problems with the use of G‐AEDs and justify recommendations to avoid switching different preparations (form branded preparations to generics as well as between generics or from generics to branded preparations) in successfully treated patients. 1 Robert F. Kwarta Jr., 2 Joseph F. Hulihan, 1 Juergen Schmider, and 1 Jeffrey S. Nye ( 1 Pharmaceutical Research & Development, L.L.C., Johnson & Johnson (J&JPRD), Titusville, NJ ; and 2 Ortho‐McNeil Neurologics, Raritan, NJ ) Rationale: The estimated risk of major structural malformations in infants born to women with epilepsy ranges from 2–25% but is generally reported as twice that of the general population (6–10% vs 2–5%). In utero exposure to antiepileptic drugs (AEDs) has been implicated as a factor in this increased risk. Independent pregnancy registries are collecting data on exposure to AEDs, including topiramate (TPM). We report on congenital abnormalities/malformations in newborns exposed in utero to TPM for pregnancies that were prospectively reported to J&JPRD. Methods: The J&JPRD worldwide pharmacovigilance database was searched (18 July 2005) for all reports of TPM exposure during pregnancy in clinical trials, medical literature, spontaneously reported post‐marketing events, and events reported to the company by pregnancy registries. Pregnancies were categorized as prospective if reported to J&JPRD no later than the 16th week of gestation and prior to any information on fetal outcome. A newborn's outcome was classified as a congenital abnormality/malformation if the case report described a structural, genetic or biochemical defect. Results: Cumulative, postmarketing exposure to TPM was more than 3.6 million patient‐years as of 30 June 2005. Information regarding live‐birth outcome was available for 76 prospectively reported pregnancies. Among the 29 pregnancies in which TPM was the only reported AED exposure, reported congenital anomalies were limited to a case of micrognathia and a case of phimosis that was a familial characteristic. Seven other congenital anomalies from prospectively reported pregnancies were associated with AED polytherapy. Most pregnancies with live birth outcomes were retrospective reports (n = 161) associated with both TPM monotherapy and polytherapy. In this group, the most commonly reported abnormalities were cleft lip/palate (8 cases) and hypospadias (7 cases). Neither malformation was uniquely associated with TPM monotherapy. Conclusions: As with other AEDs, TPM should only be used during pregnancy if the benefit to the mother outweighs the risk. Infant outcome data from prospectively reported pregnancies involving TPM exposure are limited, but confirm the higher risk of malformations associated with AED polytherapy. 1 Ilo E. Leppik, 2 Luping Zhao, 2 Lynn E. Eberly, 2 Susan L. Harms, and 2 Judith M. Garrard ( 1 Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN ; and 2 School of Public Health, University of Minnesota, Minneapolis, MN ) Rationale: Epilepsy is common in the elderly, and previous studies have shown that upon admission 7.7% are receiving an antiepileptic drug (AED) and 3.3% have an AED added after admission1. This study was done to evaluate the patterns of AED use over a 3‐year period in a large nursing home organization. Methods: Computerized records containing physician's daily medication dosing orders and diagnoses were available for a total of 113,047 unique admissions age 65+ years to Beverly Nursing Homes across the USA January 2000 through December 2002. AED information through the 3rd day of admission was analyzed to avoid errors of omission during the first 48 hours. Results: Overall, 6,200 persons (5.48% of all admissions) had an epilepsy/seizure (EPI/SZ) code. There were 73,853 female admissions of which 3,666 (4.96%) had an EPI/SZ code. There were fewer males admitted (39,193) but 6.47% had an EPI/SZ code (p < 0.0001). A racial disparity was also noted with Blacks, Hispanics and American Indian/Native Alaskans having a higher prevalence of EPI/SZ code than whites and Asians (p < 0.001). 28.5% with an EPI/SZ code were not receiving an AED. The “old‐old” with an EPI/SZ code (85 years+) had lower AED use than the “young old” (65–74) (p < 0.005). Among those with an EPI/SZ code and some AED, use of phenytoin was 66.7%, valproate was 15.3%, Phenobarbital was 9.5%, carbamazepine was 9.7%, gabapentin was 10.3%, and all other new was 4.6% (total > 100% due to polytherapy). Conclusions: The prevalence of AED use at time of admission to a nursing home is much greater than the 1.5% prevalence in community dwelling elderly, suggesting that a marked increase in the incidence of epilepsy occurs prior to admission. There are significant gender and race differences, with males, Blacks, Hispanics and American Indian/Native Alaskan having higher rates of epilepsy. Phenytoin remains by far the most commonly prescribed AED in this population. However, how the assignment of a EPI/SZ code is made cannot be discerned from this database and the high rate of untreated is problematic. Studies conducted in nursing homes are needed to ascertain the appropriateness of the EPI/SZ coding. (Supported by NIH‐NINDS P50 NS16308 1Garrard J, etal. Antiepileptic drug use in nursing home admissions. Annals of Neurology 2003:54:75–85.) 1 Ken G. Makus, and 1 John McCormick ( 1 Neurology, University of Alberta, Edmonton, AB, Canada; and McKesson Phase 4 Solutions, Toronto, ON, Canada ) Rationale: Switching patients from older branded antiepileptic drugs (AEDs) to generic versions can increase the risk of breakthrough seizures and side‐effects.1 Less is known about the consequences of substituting newer AEDs for generic compounds.1 Given the unique challenges in epilepsy treatment and the common concomitant use of narrow therapeutic index epilepsy medications generic substitution for brand‐name AEDs may sacrifice efficacy, tolerability, and safety.2 Though generic drugs are considered bioequivalent to brand names, clinically relevant differences in drug absorption and availability can occur and produce loss of seizure control or toxicity.2 In the current investigation, outcomes associated with substituting one of the first newer AED to become generically available in Canada were assessed for signals warranting further investigation. Methods: The impact of generic lamotrigine in epilepsy patients was assessed using reports of lamotrigine‐linked adverse reactions filed to Health Canada's Adverse Drug Reaction Monitoring Program (CADRMP), a survey of pharmacists, and a physician chart audit. It was hypothesized that utilization of generic lamotrigine may be associated with a change in lamotrigine‐associated adverse reactions. To test this, lamotrigine‐related adverse reactions reported to the CADRMP over identical periods before (baseline period) and after (study period) generic lamotrigine became available were compared. Results: Reports of lamotrigine‐associated adverse reactions to CADRMP rose from 30 during the baseline period to 56 in the study period. Over the latter period 29 of the 56 reports (52%) were linked to generic lamotrigine (versus 23% over the baseline period), 14 of which involved lack of seizure control. Loss of seizure control was the primary reason patients were switched back to Lamictal® in the pharmacists' survey (11/14 patients) and the physicians chart audit (8/9 patients). Seizure control was regained for the majority of patients following a return to branded lamotrigine. Conclusions: These initial reports of loss of seizure control in some patients following brand‐to‐generic Lamotrigine switching, build upon existing similar experiences with older AEDs. The results of this study suggest that (i) seizure control can be compromised when switching from Lamictal® to generic lamotrigine, and (ii) lamotrigine‐associated adverse reactions increased after generic lamotrigine was prescribed. These data stress the vital role physicians play in educating their patients as to the potential risks and benefits of AED generic substitution. Reference 1. Crawford P, Hall WW, Chappell B, et al. Generic prescribing for epilepsy. Is it safe Seizure 1996;5:1–5. 2. Guberman A, Corman C. Generic substitution for brand name antiepileptic drugs: a survey. Can J Neurol Sci 2000; 27 :37–43. (Supported by a grant from GlaxoSmithKline Inc.) 1 Cordula Mauerer, 1 Jan Ricken, 1 Angelika Huettenbrenner, and 1 Soheyl Noachtar ( 1 Department of Neurology, University of Munich, Munich, Germany ) Rationale: This prospective study compared the effects of the new antiepileptic drug (AED) pregabalin (PRE) with the established AED carbamazepine (CBZ) on eye movement and posture control in twelve healthy volunteers who received single doses of 75 mg PRE and 400 mg slow release CBZ in a double‐blind, cross‐over, randomized trial. Methods: The drug effects on electrooculography and postural sway were evaluated for averaged plasma levels, for individual highest to lowest plasma levels and for individual highest to lowest effect. Results: CBZ and PRE both affected eye movements significantly. The strongest impact was seen on saccadic eye movements, with CBZ slowing the peak horizontal saccade by a maximum of 35.6% (PRE 28.5%). The peak vertical saccade was slowed by CBZ (17.6%) and PRE (27.3%). There was no statistically significant difference of the maximum effect between the two substances. CBZ and PRE both also affected body sway. Significant impairment was mostly seen in difficult conditions (reclined head, eyes closed on foam plate showed a 24% increase in body sway for CBZ, 24.7% increase for PRE). Only in selected conditions could a statistically significant difference be seen between the two AEDs. Conclusions: In summary, PRE and CBZ impair eye movement and posture control – as measured by objective electrophysiological methods – similarly. 1 Vladimir Nekrassov, and 1 Maria Sitges ( 1 Basic and Applied Research Division, National Rehabilitation Institute, SSA, Mexico; and Department of Cellular Biology and Physiology, Biomedical Research Institute, UNAM, Mexico ) Rationale: Several studies carried out in epileptic patients treated with common AEDs suggest that the drugs could cause BAEPs alterations. Although, only in a couple of case report studies hearing deficits have been directly linked to the antiepileptic medication. BAEPs are far field‐evoked potentials that consist of several waves that occur within 10 ms post‐stimulus. Determination of BAEPs threshold is an objective measure of the hearing sensitivity. In the guinea pig, changes in the amplitude or the latency of P1, the first wave of BAEPs, reflects cochlear nerve alterations, whereas changes in the parameters of P3 and P4, express alterations in the activity of the medial and the lateral superior olivary nuclei of the brainstem, respectively. Previously we have shown that the BAEPs alterations and the hearing decline induced by amikacin and by the convulsing agents, pentylenetetrazole and 4‐aminopyridine in the guinea pig in vivo are prevented by VPC (ethyl apovincamine‐22‐oate), a nootropic drug with anticonvulsant capabilities. Since the few studies directed to investigate the effects of CBZ, PHT and VPA on BAEP parameters in animals, have only tested their acute effects at extremely high doses, their chronic effects at relevant doses on BAEP parameters and threshold were investigated here in the guinea pig in vivo, and compared with the effects of VPC in parallel. Methods: The latency and amplitude of each BAEP wave elicited by a stimulus of high intensity (100 dB) and the auditory thresholds at two tone frequencies (8 and 4 kHz) before the start of treatment (control recordings), 2 hours after the start of treatment (i.e. first injection of 20 mg/kg CBZ, 6 mg/kg PHT, 30 mg/kg VPA or 2 mg/kg VPC), and 28 days after a daily injection of the above drugs at the indicated doses, were measured following the methods described previously (Epilepsy Res. 2004; 60: 63–71; Clin. Neurophysiol. 2004; 115: 2711–17). Results: P1 and P2 parameters are unchanged by the drugs tested either after the start of treatment or following 28 days of injection. Also, P3 and P4 are unchanged after the start of treatment. However, marked changes are observed after the long term (28 days) treatments; CBZ and PHT increase and VPC reduces P3 and P4 latencies, PHT reduces P3 amplitude, and CBZ and PHT reduce P4 amplitude. Following the 28 days of CBZ, PHT or VPA injection the BAEP thresholds increase, whereas they decrease following the 28 days of VPC injection. Conclusions: The long term treatment with the most commonly used AEDs at therapeutic relevant doses could reduce the hearing sensitivity through physiological changes in specific nuclei of the superior olivary complex. The long term treatment with VPC, in contrast, ameliorates audition. (Supported by: This work was financially supported by Psicofarma S.A. de C.V. and by project P‐48695 from SEP‐CONACYT.) 1 Dakshesh K. Patel, 1 Mary R. Andriola, and 1 Ravindra K. Bhachawat ( 1 Department of Neurology, State University of New York at Stony Brook, Stony Brook, NY ) Rationale: Levetiracetam is an anti‐convulsant approved in 1999 for use as an adjunctive therapy for patients with partial onset seizures in adults. There is significant use of it in patients with generalized epilepsy. The objective of this study was to ascertain the effectiveness of levetiracetam as adjunctive therapy to normalize an EEG in patients who have had a significant decrease in seizure frequency. Methods: A list of patients, who have been on levetiracetam, was generated from past dictations, yielding 105 patients. The dictations of these patients were reviewed to determine the patients diagnosed with primary generalized epilepsy. There were twenty seven patients (n = 27) with ages in the range of 3 years to 55 years that met the criteria. An extensive chart review was conducted to determine whether patient had clinical seizure control and the effect of levetiracetam on the patients EEG. The seizure resolution was tabulated and charted to compare with normalizing of EEG. Results: Of the 27 patients, 11 had resolution (41%) in clinical seizures, 8 had significant reduction (30%) in seizure frequency, 6 patients who failed (22%), and 2 patients were not able to tolerate (7%) the medicine. Of the 11 patients who had resultion, 7 had normalization (64%) of EEG and 2 had an unchanged (18%) EEG. There were 2 other patients with a pending EEG. Conclusions: Levetiracetam is effective as an adjunct therapy in patients with intractable primary generalized epilepsy. It not only improves seizures control, but in those patients with resolution of clinical seizures, there is normalization of EEG in a significant number of patients. (figure 1) 1 Jacqueline French, 2 Grossman Patricia, 3 Barry Gidal, 4 Gwenael Le Teuff, and 5 Celine Bugli ( 1 School of Medicine, University of Pennsylvania, Philadelphia, PA ; 2 Global Outcomes Research, UCB, Atlanta, GA ; 3 School of Pharmacy, University of Wisconsin, Madison, WI ; 4 Keyrus Biopharma, Levallois‐Perret, France ; and 5 LACO, Diegem, Belgium ) Rationale: Over 2 million serious adverse drug reactions occur annually leading to 100,000 deaths in the United States. The objective of this study was to present the results of the investigation conducted in epileptic patients initiating either an enzyme‐inducing AED (EIAED) or a non enzyme‐inducing AED (NEIAED) and their risk of exposure to medications that may incur a potentially adverse PK interaction within a chronologically diverse group of epileptic patients. Specifically, this analysis sought to determine in a group of patients receiving only AED treatment, the risk that a concomitant, potentially interacting drug will be added to a patient medication regimen. Methods: A retrospective cohort study was conducted in epilepsy patients using a US claims Database (1/2001–12/2004). Patients were sub‐grouped: EIAEDs (n = 9296) or NEIAEDs (n = 6573). A non‐AED concomitant medication is defined as a concomitant medication if there exists an overlap with AED treatment of at least 5 days for antibiotics and antifungals and at least 30 days for other classes of drugs. Risk of first addition of a comedication was assessed using a Cox proportional hazard model adjusted to clinical and demographic characteristics including gender, state of the patient during the 6 months prior to AED initiation (based on Charlson comorbidity index, a measure of seriousness of comorbid diseases, Charlson et al., 1987), the type of AED treatment and the age group. Origin time is the date of the first prescription of AED. Results: 2873 patients are censored (18%).The mean time under AED is 395 days (SD = 371). The mean time to addition of first concomitant medication or to end of the follow‐up for censored patient is 67 days (SD = 156). The hazard ratios for the time to first concomitant medication addition are presented in Table 1. Multivariable hazard ratio (HRs) and 95% confidence intervals (CI) of first addition of concomitant medication Covariates HR (95% CI) Male (vs female) 0.8 (0.772;0.828) 18–34 (vs 0–17) 1.112 (1.059;1.169) 35–54 (vs 0–17) 1.379 (1.317;1.443) 55–64 (vs 0–17) 1.636 (1.532;1.746) 65+ (vs 0–17) 1.749 (1.574;1.944) mild state (vs good) 1.434 (1.361;1.512) severe (vs good) 1.536 (1.450;1.629) NEIAED (vs EIAED) 1.126 (1.086;1.167) All p‐values are < 0.001. Conclusions: The risk that a concomitant medication will be added at some time after AED is initiated is significantly higher for females, increases with age and the severity of the state of the patient. This implies that patients with certain characteristics should have their antiepileptic drugs selected to avoid the potential of future drug interactions. This might include avoiding enzyme inducing antiepileptic drugs. (Supported by UCB INC.) 1 Edward E. Patterson, 2 Ilo E. Leppik, 3 Timothy D. O’Brien, 4 Varun Goel, and 2 James C. Cloyd ( 1 Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN ; 2 Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN ; 3 Veterinary Population Medicine, University of Minnesota, St. Paul, MN ; and 4 College of Pharmacy, University of Minnesota, Minneapolis, MN ) Rationale: Levetiracetam (LEV) is a water‐soluble antiepileptic drug and an IV preparation that has received an approval letter from the FDA at the time of the submission of this abstract. However, an IM formulation was not considered during development. The purpose of this pilot study was to obtain data regarding the safety and tolerability of the IV formulation administered intramuscularly to dogs. Methods: Animal experimentation approval was obtained and six dogs weighing approximately 20 kg were purchased. The same IV solution, intended for clinical use, was obtained from UCB Pharma. It contains 100 mg/ml LEV in an aqueous solution with a neutral pH. A standard animal discomfort rating scale was used. Dogs were injected with 5ml (500 mg) of LEV in one longissimus muscle, and 5 ml of saline in the contralateral muscle. Two dogs received IM LEV and control saline on Monday, two on Wednesday and two on Friday. This provided up to five days for reaction to develop. All were sacrificed on Saturday and 4 blocks of tissue of approximately 2 cm3 were removed for standard histopathology. A standard four‐point inflammation scale (0 = no inflammation, 1 = mild, 2 = moderate, 4 = marked) was used as well as examination for tissue damage. Results: Tolerability: Three of the six dogs injected with LEV had slight head turning or a slight squirm; only one had slight vocalization, and 3 had no reaction. Three saline of six controls had slight head turning. Safety: The mean inflammation score for LEV was 0.28, and 0.62 for saline. One of the saline injected dogs had a score of 3 (moderate). Four dogs in each group had no inflammation. Conclusions: The IV preparation of LEV is well tolerated and safe when given as an IM injection to dogs. This suggests that the formulation may be useful in humans, but studies of safety and tolerability will need to be done. (Supported by UCB Pharma.) 1 Patricia E. Penovich, 1 Deanna L. Dickens, 1 Jason S. Doescher, 1 Michael D. Frost, 1 El‐Hadi Mouderres, and 1 Frank J. Ritter ( 1 Minnesota Epilepsy Group, PA, Minnesota Epilepsy Group, PA, St. Paul, MN ) Rationale: Conventional use of AEDs in the treatment of epilepsy has utilized serum levels as an indicator of appropriate daily dosage. Pregabalin (PGB), a GABA analog which binds at the α2δ subunit of voltage gated calcium receptors, has a dose response correlation for seizure reduction in phase three human studies at the two doses studied. No serum level to dose correlation has been reported. We have evaluated the effect of daily and weight‐based doses on serum levels in clinical use. Methods: Patients received PGB as adjunctive therapy for refractory partial seizures with or without secondary generalization. Doses were empirically chosen and increased for efficacy or until side effects were experienced. Serum levels were obtained at trough if possible. Serum determinations were sent to MedTox Laboratories (St Paul, MN) for determination by HPLC. Serum levels, age, weight, daily dose, mg/kg/day dose, creatinine, efficacy and reported adverse events were evaluated by retrospective chart review. Results: Thirty‐two patients ages 4–78 (mean 33.6 ± 17.6, median 31) received PGB for two days to over seven years. Weights were 27.5 – 188.5 kg (mean 68.3 ± 30.1, median 67). Total daily doses were 25 – 1050 mg (mean 349 ± 212, median 300) resulting in 0.35–10.9 mg/kg/day (mean 5.1 ± 3.1, median 4.7). Serum levels were 0.99 – 13.4 μg/ml (mean 4.2 ± 3.1, median 4.0). There was a significant correlation p < .01 for the relationship of mg/kg/day to serum concentration. AEs reported in 11 (33%) were tiredness, weight gain, and temporary leg swelling at levels of 1–7 μg/ml. Improved seizure control was reported in 56%; 1 was worse. Efficacy was seen in 7/18 at 2 μg/ml or less and in 11/18 at 4–10 μg/ml. Seven patients had 2 or more levels at different doses and showed linear increase in serum level. Conclusions: PGB is easily utilized as adjunctive therapy in clinical practice. Doses are well tolerated up to 1050 mg/day without serious AEs. Serum levels correlate linearly with increased dosing. 1 Ronald C. Reed, and 1 Sandeep Dutta ( 1 Neuroscience & Anesthesia, Abbott Laboratories Research & Development, Abbott Park, IL ) Rationale: Divalproex extended‐release (ER), administered once‐daily (QD), 1–5g total daily dose, maintains plasma valproic acid concentrations ((VPA)) 24hrs, vs. multiple‐daily dose enteric‐coated, delayed‐release (DR) divalproex (Ped Neurol‘04). Clinically, QD enteric‐coated sodium valproate (EC‐NaVPA, European, ∼ but not identical to DR, USA) reduces seizures (sz) (Acta Neurol Scand‘84). Yet, those treated with QD EC‐NaVPA had 1° generalized sz, responsive to low VPA doses, ∼15.6–19.4 mg/kg/day (Epilepsia‘79). While low EC‐NaVPA or DR doses, given QD, may be therapeutically acceptable and occasionally prescribed, we hypothesize that a QD DR regimen should not be applied to refractory epilepsy (partial ± 2° gen. sz) requiring high total daily doses, e.g. 35.6–56 mg/kg/day (Neurol‘97), due to the potential for excessively high peak (VPA) (>125 mg/L). We examined the impact of QD divalproex dosing, DR vs. ER, on steady‐state (VPA) profiles at commonly used doses in monotherapy (uninduced, UN) and polytherapy (hepatic enzyme‐induced, IND) virtual patients. Methods: Scenarios include adults with epilepsy, UN/IND; QD DR doses from 1125‐ 4000mg vs QD ER (mg dose‐proportional ER, all scenarios) chronically. (VPA)‐time profiles were simulated, each scenario (n = 1000) using a 1‐compartment population (20% inter‐ & 10% intra‐patient variability) kinetic model with nonlinear protein binding (Monte Carlo stochastic simulations, Clinical Trial Simulator software) (Am J Health‐Sys Pharm‘04). Results: Only 1125mg QD DR dose had mean Cmax < 100 mg/L (conventional population upper therapeutic VPA range limit); QD DR ≥2000mg produced mean Cmax > 125 mg/L. Mean DR Cmin was ∼50 mg/L (conventional lower VPA limit) at 2 doses, whereas mean ER Cmin was > 70 mg/L at all doses tested. Excursions well beyond the recommended range of 50–100 mg/L are predicted to commonly occur on QD DR, evidenced by 10th–90th percentile data (considering 80% of patients, DR Cmax is frequently > 100 mg/L & Cmin < 50 mg/L). DR degree of peak‐trough fluctuation (DFL) was 4.4x‐6.2x > ER. Induction Status QD Dose Cmax* Cmin* DFL UN 1125 DR 98 (69–129) 55 (34–78) 0.57 UN 1250 ER 82 (57–112) 73 (49–100) 0.13 UN 2000 DR 126 (91–162) 75 (47–108) 0.52 UN 2250 ER 109 (79–143) 98 (69–129) 0.11 IND 3000 DR 130 (96–169) 54 (29–83) 0.87 IND 3250 ER 101 (70–132) 87 (60–116) 0.14 IND 4000 DR 149 (112–190) 64 (36–98) 0.83 IND 4500 ER 119 (85–156) 104 (72–139) 0.14 *Mean (10th‐90th percentile) Conclusions: QD dosing of ER is appropriate over a large range of total mg/day, but not for QD DR ≥ 2000 mg. QD DR dosing should not be attempted for sz requiring high total daily doses due to potential (VPA) excursions beyond 50–100 mg/L, risking breakthrough sz or toxicity. (Supported by Abbott Labs.) 1 Matthew W. Reynolds, 1 Sheila Crean, 1 Kyle Fahrbach, 1 Congtam Pham, 1 Brian Sercus, 2 Joseph Kerkering, and 3 Kimford J. Meador ( 1 Epidemiology and Risk Management, United BioSource Corporation, Medford, MA ; 2 Medical Affairs, Shire Development Inc., Wayne, PA ; and 3 McKnight Brain Institute, University of Florida, Gainesville, FL ) Rationale: Antiepileptic drugs (AED) have been reported to increase the risk of congenital malformations (CM) in the offspring of mothers who use these drugs. Since there is a significant risk of seizures for the mother during pregnancy, it may be necessary for the mother to continue taking AEDs throughout her pregnancy. Methods: We performed a systematic literature review to identify all published registries and cohort studies of ≥ 1000 births from pregnant epileptic women that reported an incidence of a major congenital malformation. Results: The review included 6 studies (k) that met the inclusion criteria with a total of 16,095 births to epileptic mothers. Three studies reported the incidence of births with CM, three studies reported the incidence of CM as total events, and 4 studies reported the incidence of specific major congenital malformations. The incidence of births with CM was 5.2% (k = 3), and the incidence of CM (as events) was 4.5% (k = 3). The incidence of spina bifida was 0.2% (k = 3), cardiovascular CMs was 0.9% (k = 2), cleft lip or palate was 0.3% (k = 2), urinary malformations was 0.5% (k = 3), and club foot was 0.7% (k = 1). There were three studies that separately reported monotherapy, polytherapy, and/or non‐treated epileptic pregnancies. The incidence of births with CM in women treated with only 1 AED was 6.2% (k = 2), for polytherapy it was 10.2% (k = 2), and for no AED treatment it was 2.8% (k = 1). The incidence of CM events was 3.9% (k = 2) for monotherapy, 6.3% (k = 2) for polytherapy, and 3.2% (k = 2) for no AED treatment. Conclusions: The results of this systematic literature review suggest that the incidence of congenital malformations in the offspring of epileptic mothers is approximately 4% to 5%. The risk of congenital malformations increases from no AED treatment (approximately 3%) to treatment with a single AED (from 4% to 6%), and is highest when the mothers are treated with multiple AEDs (6% to 10%). (Supported by Shire Development Inc.) 1 Jan M. Ricken, 1 Peter Axtner, 1 Katharina Schüler, and 1 Soheyl Noachtar ( 1 Department of Neurology, University of Munich, Munich, Germany ) Rationale: This prospective study compared the effects of the new antiepileptic drugs (AED) oxcarbazepine (OXC) and gabapentin (GBP) on eye movements and posture control in twelve healthy volunteers who received single doses of 900 mg GBP and 600 mg OXC in a double‐blind, cross‐over, randomized trial. Methods: The drug effects on electrooculography and postural sway were evaluated for averaged plasma levels, for individual highest to lowest plasma levels and for individual highest to lowest effect. Results: OXC and GBP both affected eye movements significantly. The strongest impact was seen on vertical eye movements, with GBP slowing the peak vertical saccade by a maximum of 20.4% and OXC by 29.7%. There was no significant difference of the maximum effect between the two substances. GBP affected body sway significantly in most conditions. The maximum impairment was seen in the difficult conditions (reclined head, eyes closed on foam plated showed 25.0% increase in body sway, tandem stance with closed eyes 67.0%). OXC increased body sway in only very few conditions (reclined head, eyes closed on foam plate showed a 6.0% increase, tandem stance with closed eyes 9.4%), and showed significantly less impairment as compared to GBP (p < 0.05). Conclusions: Although OXC and GBP both may cause dizziness, the effects on eye movements and body sway were different. OXC seems to have less CNS side effects as measured by postural control and similar effects as measured by electrooculography at comparable doses. (Supported by Novartis.) 1 Miranda K. Roth, and 2 Nicholas P. Poolos ( 1 Phyisol & Biophys, University of Washington, Seattle, WA ; and 2 Neurol and Physiol & Biophys, University of Washington, Seattle, WA ) Rationale: h‐channels (hyperpolarization‐activated cation channels; Ih; HCN) have been hypothesized to play a role in epileptogenesis due to recent evidence that they are downregulated by seizures, are upregulated by several antiepileptic drugs, and produce epilepsy when genetically deleted in an animal model. Little is known about possible intracellular modulators of h‐channel function apart from the well‐described role of cAMP. Previously we found that inhibition of p38 mitogen‐activated protein kinase (MAPK) downregulated Ih by causing a hyperpolarizing shift in voltage‐dependent activation. We sought to characterize the role of p38 MAPK in the actions of a known upregulator of Ih, the anti‐epileptic drug (AED) lamotrigine (LTG). Methods: We tested the effects of p38 MAPK activation using cell‐attached and whole‐cell recordings of Ih in pyramidal‐like principal (PLP) neurons in the CA1 layer of the hippocampus in rat brain slices. PLPs contain a high somatic density of Ih with biophysical properties similar to Ih in CA1 pyramidal neuron dendrites. Drugs were applied through the pipette and for at least 45 min via bath application before recording. Results: Application of an activator of p38 MAPK and c‐Jun NH2 terminal kinase (JNK), anisomycin (20 μM), produced an ∼11 mV depolarizing shift in Ih voltage‐dependent activation (V1/2 in control =−89 ± 2.4 mV (mean ± SEM), n = 11; V1/2 in anisomycin =−78 ± 2.0 mV, n = 7, p < .001) while a specific inhibitor of JNK, SP600125 (10 μM), caused no change in voltage‐dependent activation (V1/2=−87 ± 3.6 mV, n = 4, p > .05). Thus, the effect of anisomycin is due to the activation of p38 MAPK. In whole cell experiments, pipette‐applied activated p38α MAPK (5 μg/ml) led to a decrease in input resistance (IR) 15 min after the start of recording (p38α=−36.7 ± 7.7%, n = 4; in control =−13.9 ± 3.7%, n = 6, p < .05). Perfusion of p38α MAPK decreased temporal summation (TS) elicited by a train of 20 Hz alpha‐function current injections after 15 min pipette application (−23.6 ± 5.6%, n = 4; in control =−8.6 ± 3.1%, n = 6, p < .05). We then tested whether p38 MAPK is necessary for the action of LTG. A specific p38 MAPK inhibitor, SB203580 (SB, 10 μM), produced an ∼22mV hyperpolarizing shift in voltage‐dependent activation (V1/2 in SB =−111 ± 3.6 mV, n = 6, p < .0001). When SB was applied with LTG (100 μM), the depolarizing effect of LTG was blocked by the hyperpolarizing effect of SB (V1/2 in LTG =−83.6 ± 1.6 mV, n = 5; V1/2 in SB/LTG =−104.2 ± 5.6 mV, n = 5, p < .05). Conclusions: These results show that p38 MAPK plays an important role in the regulation of Ih. Activation of p38 MAPK activity produced a significant upregulation of Ih in hippocampal PLPs which decreased the excitability of PLPs by diminishing IR and TS. These results also suggest that p38 MAPK is necessary for LTG action on Ih. The effects of p38 MAPK on Ih imply that the p38 MAPK pathway is a promising target for novel AEDs. (Supported by NIH Grant NS050229, GlaxoSmithKline.) 1 A. James Rowan, 2 R. Eugene Ramsay, 3 Flavia Macias, and VA Cooperative Study #428 Study Group ( 1 Neurology, Bronx VA Medical Center and Mount Sinai School of Medicine, New York, NY ; 2 Neurology, VA Medical Center and University of Miami School of Medicine, Miami, FL ; 3 Neurology, VA Medical Center, Miami, FL ; and 4 Neurology, 18 VA Medical Centers Across the USA ) Rationale: VA Cooperative Study (VACS) #428 reported on treatment of 593 older individuals (average age 72, range 59–91) with newly diagnosed seizures who were assigned to one of three treatment groups: carbamazepine (CBZ), gabapentin (GBP) or lamotrigine (LTG – Neurology 2005;64:1868–1873). The GBP and LTG groups demonstrated significantly better one year retention in study than CBZ (p = 0.0001), due primarily to superior tolerability. There was little difference among the groups with respect to seizure control. We now consider whether there were age‐related differences in our population with respect to seizure control and AED tolerability. Methods: We divided our population into three groups: ages 60–69, 70–79 and 80+. For each group we determined seizure‐free rates at three, six and 12 months. Likewise, we determined retention in study at 12 months for the three groups. Finally, we considered the incidence of one of the study's principal side effects, sedation, for each age group. Results: For the three age groups, the intent to treat (ITT) seizure free rate at 12 months showed a steady decline from the youngest to the oldest group for all three treatments. The only exception was an improvement for GBP in the 70–79 group followed by a decline for the 80+ group. Overall, LTG was superior to the other two treatments. Breaking down the data into three, six and 12 month observations, we found that seizure free rate for GBP did not decline until after six months for the 60–69 group, whereas it declined steadily for the two older groups. For LTG, decline was arrested after six months for the 80+ group. For CBZ the only steady decline was in the 80+ group. An important side effect, sedation, showed a steady increase in age‐related incidence for the LTG and GBP groups. In particular, two‐thirds (65.6%) of the GBP 80+ group reported sedation comapred with just over half that number (34.4%) for the 60–69 group. There was little change over the ages for CBZ. Conclusions: In elderly patients with newly diagnosed seizures, seizure control appears to decline with increasing age for all three treatments studied in VACS #428. Sedation shows an age‐related increase for LTG and GBP, but little change for CBZ. The most profound increase in sedation occurred with GBP. Age considerations should play an important role in determining AED selection and usage in the elderly. Seizure free rates for three treatments, all ages 60–69 yrs 70–79 yrs 80+ yrs CBZ 27.6 21.4 17.1 GBP 20.3 27.8 17.1 LTG 32.9 27.1 20.7 (Supported by Department of Veterans Affairs.) 1 Nicola Specchio, 1 Antonio Gambardella, 1 Anna Teresa Giallonardo, 1 Roberto Michelucci, 1 Carlo Di Bonaventura, 1 Giovanni Boero, 1 Angela La Neve, and 1 Luigi M. Specchio ( 1 Department of Neurological Science, Centre of Epilepsy, Bari, Italy; Clinic of Neurology, Epilepsy Centre, University of Catanzaro; Clinic of Neurology, Epilepsy Centre, University La Sapienza, Roma, Italy; Clinic of Neurology, Ospedale Bellaria, Bologna, Italy; Clinic of Neurology, Epilepsy Centre, University La Sapienza, Roma, Italy; CINEDIV (Centro Interuniversitario Per Lo Studio dell’Epilessia E dei Disturbi Della Vigilanza), Universities of Foggia and Bari, Foggia, Italy; Department of Neurological Science, Centre of Epilepsy, Bari, Italy; and CINEDIV (Centro Interuniversitario Per Lo Studio dell’Epilessia E dei Disturbi Della Vigilanza), University of Foggia, Foggia, Italy ) Rationale: Patients with juvenile myoclonic epilepsy (JME) may be resistant or show adverse effects to valproate. Several reports and open label studies have pointed out the efficacy of levetiracetam in generalised epilepsy (Patsalos, 2004). Moreover, levetiracetam has been shown to be effective in preventing photoparoxismal response in subjects with photosensitive epilepsy (Kasteleijn‐Nolst Trenité et al., 1996). Our previous open‐label study suggested levetiracetam might be effective and well tolerated in resistant cases of JME or may become a reasonable alternative to valproate in newly diagnosed patients. We present a multicentre, prospective, long‐term, open‐label study evaluating the effects of levetiracetam on EEG epileptiform abormalities and on the photoparoxismal response in patients affected by JME. Methods: Ten patients with newly diagnosed and 38 resistant/intolerant to previous AEDs JME were enrolled. After a 8 week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased up to 3000 mg/day according to the patient's response. An EEG evalutation has been performed before starting the treatment and every 3 months. Efficacy parameters were: reduction or sopression of interictal epileptiform abnormalities and photoparoxismal response. Results: The overall mean dose of levetiracetam was 2208 mg/day. The mean study period was 19 (range 0.3–38) months. Four patients had a normal EEG before starting the treatment, 41 had diffuse/generalized spike‐waves and 11 showed a severe phoparoxismal response. After drug administration 27 patients had a normal EEG, 20 showed diffuse/generalized spike‐waves discharges which were judged to be less frequent and wide, and in 4 we had the persistence of phoparoxismal response. The mean monthly frequency of DWM and of GTC seizures in the entire group was significantly reduced after levetiracetam. Conclusions: This open‐label study suggests levetiracetam may be effective in reduction of epileptiform abnormalities, it suppress the photoparoxismal responce and it is well tolerated in resistant cases of JME or may become a reasonable alternative to valproate in newly diagnosed patients. 1 Hermann Stefan, 1 Martina Wangemann, and 1 Bernhard Vens‐Cappell ( 1 Epilepsy Center, Clinic of Neurology, University Hospital, Erlangen, Germany; Clinical Research, Desitin Arzneimittel GmbH, Hamburg, Germany; and Scope International AG, Hamburg, Germany ) Rationale: The aim of the study was to investigate the absorption characteristics of a new modified release dosage form of oxcarbazepine after once daily (OD) or twice daily (bid) application in comparison to an immediate release reference formulation during steady state conditions. Methods: Using an open three‐period crossover design, 3 different treatments were examined after multiple dose administration of oxcarbazepine to 18 healthy male subjects. The test formulations administered were either oxcarbazepine modified release (OXC MR) 600 mg OD or 300 mg bid. The immediate release formulation of oxcarbazepine (OXC IR) 300 mg bid served as the reference formulation. The three treatments were administered during an up‐titration phase of 6 days. Plasma concentration profiles were measured on day 7 during a 24‐hour interval at different time points. A wash‐out period of 14 days elapsed between the periods. Monohydroxycarbamazepine (MHD), the active metabolite of oxcarbazepine as well as the prodrug oxcarbazepine (OXC), were determined in EDTA plasma samples by a validated HPLC method with UV detection. Results: The results of the multiple dose study demonstrated the consistency of the absorption of the primary parameter MHD from the novel OXC MR formulation after OD or bid application. The time concentration profiles following bid administration of 300 mg OXC MR showed that the mean extent parameters for absorption of MHD are equivalent with the OXC IR reference preparation. Results for peak trough fluctuation (PTF) indicate that fluctuation is reduced in the case of the OXC MR formulation (PTF = 39% for OXC MR and 54% for OXC IR). In addition, Cmin concentrations of MHD were 10% higher and Cmax concentrations were 6% lower after OXC MR bid compared to the respective results for OXC IR bid. Furthermore, confidence intervals for the extent of absorption (AUC) demonstrated equivalence between OXC MR 600 mg OD and OXC MR 300 mg bid (AUC: 87–96%) or OXC MR 600 mg OD and OXC IR 300 mg bid (AUC: 88%‐97%). The confidence intervals met the commonly accepted range for bioequivalence of 80–125%. Conclusions: The newly developed OXC MR formulation exhibit appropriate modified release characteristics with similar extent of exposure (AUC), reduced peak plasma concentrations (Cmax) and reduced PTF for the major active metabolite MHD compared to the IR formulation when applied twice daily. From Cmin‐values observed in this study it may be concluded that effective concentrations should be maintained over the entire dosing interval at steady state. Moreover, the OXC MR formulation seems suitable also for once daily dosing in individual cases and therefore improves patient compliance. (Supported by Desitin Arzneimittel GmbH, Hamburg, Germany.) 1 Lise Sofie H. Nissen‐Meyer, 2 Sigrid Svalheim, 2 Erik Taubøll, 3 Tove Lekva, 1 Sjur Reppe, 4 Lene B. Solberg, 4 Gunhild Melhus, 4 Finn P. Reinholt, 2 Leif Gjerstad, and 3 Rune Jemtland ( 1 Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway ; 2 Department of Neurology, Division of Clinical Neuroscience, Rikshospitalet‐Radiumhospitalet, University of Oslo, Oslo, Norway ; 3 Department of Medicine, Endocrine Section, Rikshospitalet‐Radiumhospitalet, University of Oslo, Oslo, Norway ; and 4 Institute of Pathology, Rikshospitalet‐Radiumhospitalet, University of Oslo, Oslo, Norway ) Rationale: A serious complication of long‐term treatment with anti‐epileptic drugs (AEDs) is increased risk for fractures. Phenytoin (PHT) and valproate (VPA) are both known to influence bone health, whereas levetiracetam (LEV) belongs to a new class of drugs with no reported adverse effects on bone. Methods: Female Wistar rats were fed twice daily for 90 days through a gastric tube with either LEV 50 mg/kg (n = 10), 150 mg/kg (n = 12), VPA 300 mg/kg (n = 12), PHT 75 mg/kg (n = 9) or control solution (n = 12). We studied the effect of LEV, VPA and PHT on bone densitometric indices, biomechanical strength and bone turnover serum markers. Results: Mean serum drug concentration 4 hours after last dose was 122, 277, 431 and 74 mol/l in low‐dose LEV, high‐dose LEV, VPA and PHT treated animals, respectively. Whereas PHT and VPA reduced bone mineral density (BMD) and content (BMC) in one or more bone compartments, LEV did not. Only VPA increased bone turnover, whereas treatment with low‐dose LEV caused significant reduction in levels of serum osteocalcin (a bone formation marker) relative to controls. Interestingly, low‐dose LEV also caused reduced biomechanical strength of the femoral neck. Histomorphological analyses showed retention of cartilage remnants at the growth plate metaphysis in low‐dose LEV‐treated vs. control rats (n = 6, each group), suggesting reduced cartilage resorption secondary to impaired local bone mineralization. VPA and PHT promoted cellular differentiation and mineralization of primary rat calvarial osteoblasts in vitro, while LEV was without effect. Conclusions: Our data demonstrate differential effects of PHT, VPA and LEV on bone mass and strength, suggesting a different mechanism of action. Remarkably, the ability of low‐dose LEV to cause decreased biomechanical strength of the femoral neck, without affecting BMD, suggests a primary effect of this drug on bone quality. This should warrant further studies in humans to rule out potential adverse effects of LEV on bone development and growth, especially in children and adolescents. 1 Mutaz Tabbaa, 2 Susan P. Kerls, 2 Anne E. Hammer, 2 Alain Vuong, and 2 John A. Messenheimer ( 1 Neurology, Bay Neurological Institute, Panama City, FL ; and 2 Neurosciences Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC ) Rationale: To assess the efficacy and tolerability of lamotrigine (LAMICTAL, LTG) as adjunctive therapy in the treatment of primary generalized tonic‐clonic (PGTC) seizures in patients with a history of absence seizures. The effect of LTG on PGTC seizures has not been previously evaluated in a placebo‐controlled trial. Therefore, a randomized, blinded, placebo‐controlled study was conducted to assess the efficacy and tolerability of adjunctive therapy with LTG in the treatment of PGTC seizures in patients ≥2 years of age. These results were presented previously. A sub‐analysis of the data was performed for patients with a history of absence seizures and those results are presented here. Methods: Patients with a diagnosis of epilepsy with PGTC seizures who were receiving 1 or 2 antiepileptic drugs (AEDs) at entry were eligible. Patients with partial seizures were excluded based on seizure history and screening electroencephalograms. There were three phases: Baseline; Escalation, during which drug was titrated to a target dose (12 wks if 2–12yrs, 7 wks if > 12yrs); Maintenance, during which doses of drug and concomitant AEDs were maintained for 12 wks. Results: Thirty‐eight (18 LTG, 20 placebo (PBO)) patients with a history of days with absence seizures received drug. Median percent decrease from Baseline in PGTC seizures during the entire treatment period (ETP) was 64% in the LTG group and 30% in the PBO group. This was similar to the efficacy in the overall study population. The median percent change from Baseline in absence seizures during the ETP was a 26% decrease in the LTG group and a 100% increase in the PBO group. The most common treatment‐emergent adverse events (AEs) were headache (22% LTG, 35% PBO) and nausea (22% LTG, 10% PBO). Conclusions: Adjunctive LTG therapy was effective in controlling PGTC seizures and was well tolerated among patients with a history of absence seizures. (Supported by GlaxoSmithKline Research and Development.) 1 Dirk Thomas, 2 Ute Scharfenecker, 1 Brunhild Schiltmeyer, 3 Pam Doty, 1 Willi Cawello, and 1 Rolf Horstmann ( 1 Clinical Development, Schwarz Biosciences GmbH, Monheim, Germany ; 2 Department of ADME, Schwarz Biosciences GmbH, Monheim, Germany ; and 3 Clinical Development, Schwarz Biosciences, Inc., Raleigh, NC ) Rationale: Lacosamide is a new drug being developed for the treatment of epilepsy and neuropathic pain. Preclinical and clinical pharmacological data have been established in a series of trials and phase 3 development is currently ongoing for both indications. Information about the pharmacokinetic drug‐drug‐interaction (DDI) potential of lacosamide is an important part of its safety profile. Methods: Regarding the DDI potential the results of several preclinical studies as well as of 9 Phase 1 trials (n = 184 subjects) and a Phase 2 trial (n = 91 patients) are presented. Results: In vitro lacosamide is not substantially metabolized. In vitro results also show no or low potential to inhibit or to induce CYP isoforms. Since lacosamide has low binding to plasma proteins (<15%), drug displacement interactions are unlikely. In a Phase 1 trial lacosamide was administered to extensive and poor metabolizers of CYP2C19 and the results showed that the activity of CYP2C19 has no clinically relevant effect on the metabolic fate of lacosamide. Further phase 1 DDI trials have been performed with the antiepileptic drugs carbamazepine (inducer of CYP450 system) and valproic acid (inhibitor of CYP450 system) under steady‐state conditions. In these trials, lacosamide had no influence on rate or extent of absorption of carbamazepine or valproic acid and vice versa. DDI trials with digoxin and metformin showed no relevant influence of these drugs on lacosamide and vice versa. Lacosamide did not influence the pharmacokinetics and pharmacodynamics of the oral contraceptive Microgynon® (containing 0.03mg ethinyl estradiol and 0.15mg levonorgestrel). Coadministration of food did not alter the rate or extent of gastrointestinal absorption of lacosamide. A clinical trial in subjects with epilepsy showed no influence of lacosamide on plasma levels of common antiepileptic drugs including phenytoin. Conclusions: No DDI have been observed in these studies. Therefore the data suggest that lacosamide has low potential for DDI in clinical use. 1 Alain Vuong, 1 Susan Kerls, 1 Anne Hammer, and 1 John Messenheimer ( 1 Neurosciences, GlaxoSmithKline, Durham, NC ) Rationale: This abstract reports long term efficacy and tolerability results from the Continuation Phase of a study with lamotrigine (LTG) as adjunctive therapy in patients with primary generalized tonic‐clonic seizures (PGTCS). Methods: LTG‐naïve patients (≥ 2 years, ≥ 13 kg) with inadequately controlled PGTCS, receiving a regimen of 1 or 2 AED(s) and an electroencephalogram (EEG) with evidence of generalized epileptiform discharges or no evidence of interictal expression of partial seizures were enrolled in a randomized, double‐blind, placebo‐controlled trial (results presented at AES 2005). Patients having ≥ 3 PGTCS over an 8‐week Baseline were randomized to receive LTG or placebo (PBO). Subjects, from either group, who completed the Blinded Phase, could enroll into a 1‐year Continuation Phase (subjects on PBO converted to LTG). Results: 89 subjects entered the Continuation Phase. LTG group: n = 42, 50% male, median age = 27 years (n = 9 for 2–12 years, n = 33 for > 12 years, range = 2–53 years),50% with 1 concurrent AED, most common concurrent AEDs were valproate (n = 19, 45%) and phenytoin (n = 15, 36%) median PGTCS during Baseline = 2.0. PBO group: n = 47, 68% male, median age = 23 years (n = 9 for 2–12 years, n = 38 for > 12 years, range = 2–58 years), 68% with 1 concurrent AED, most common concurrent AEDs were valproate (n = 25, 53%) and phenytoin (n = 9, 19%), median PGTCS during Baseline = 2.7. The median percent decrease from Baseline in PGTCS was 90% and 84% during the Continuation Phase for subjects who received LTG and PBO in the Blinded Phase, respectively. For the LTG group, this decrease was similar to that observed in the Blinded Phase (82%). The median PGTCS counts per month were 2.0 and 2.7 during Baseline, and 0.2 and 0.1 during the Continuation Phase for the LTG and PBO groups, respectively. For the LTG group, the median PGTCS count per month was 0.8 in the Blinded Phase. Drug‐related adverse events were 14% (LTG) and 19% (PBO). Conclusions: The results from this study, combined with the efficacy and safety of LTG for partial seizures, demonstrate that LTG is a broad spectrum AED for patients with either partial or generalized seizures. (Supported by GlaxoSmithKline.) 1 H. Steve White, 1 Ajay Srivastava, 2 Brian Klein, 2 Boyu Zhao, 3 Yong Moon Choi, 3 Robert Gordon, and 3 S. James Lee ( 1 Pharmacology and Toxicology, University of Utah, Salt Lake City, UT ; 2 Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Springhouse, PA ; and 3 SK Bio‐Pharmaceuticals, Fairfield, NJ ) Rationale: RWJ 333369, S‐2‐O‐carbamoyl‐1‐O‐chlorophenyl‐ethanol, is in clinical development for the treatment of focal epilepsy. The present investigation describes the results obtained from the extensive preclinical anticonvulsant studies that have been conducted to date. Methods: RWJ 333369 was tested in several mouse (MES, pentylenetetrazol (PTZ), bicuculline, and picrotoxin) and rat (MES and PTZ) acute seizure models following oral (p.o.) and intraperitoneal (i.p.) administration. It was also tested for its ability to: block audiogenic seizures in the Frings mouse, block behavioral and electrographic seizures in the corneal and hippocampal kindled rat, the lamotrigine (LTG)‐resistant amygdala kindled rat; and refractory seizures in the 6 Hz seizure model. Lastly, RWJ 333369 was tested for its ability to prevent and interrupt Li‐pilocarpine (Li‐Pilo)‐induced status epilepticus in rats. Results: In mice, i.p. RWJ 333369 was found to be active in the MES, PTZ, bicuculline, picrotoxin and audiogenic seizure tests. In rats, it was active in the acute MES test following p.o. administration. RWJ 333369 reduced seizure severity in the corneal kindled rat and seizure severity and afterdischarge duration (ADD) in the hippocampal kindled rat models of partial epilepsy. RWJ 333369 was also active in two models of refractory epilepsy at doses devoid of motor impairment. In the LTG‐resistant amygdala kindled rat, RWJ 333369 produced a dose‐dependent reduction in the behavioral seizure score and ADD. In the 6 Hz seizure model, the antiseizure activity of RWJ 333369 was maintained as the stimulus intensity was increased from 22 to 44 mAmp. When administered prior to Li‐Pilo, RWJ 333369 (i.p.) prevented the onset of status epilepticus. Following i.v. administration, it was able to interrupt fully established Li‐Pilo‐induced status epilepticus. Conclusions: In animal models, RWJ 333369 was active at non‐toxic doses and found to possess a broad‐spectrum anticonvulsant profile in rodent models of generalized and partial epilepsy. When administered prior to, or after, the onset of Li‐Pilo‐induced status epilepticus, it was able to either prevent, or halt, Li‐Pilo‐induced status epilepticus, respectively. In contrast to CBZ, PHT, LTG, and TPM, RWJ 333369 possesses activity in the LTG‐resistant amygdala kindled rat and the 6 Hz seizure models. These latter findings suggest that RWJ 333369 possesses a unique profile relative to these well‐established AEDs and support the continued development of this investigational AED. (Supported by NINDS Contract 1‐NO1‐NS‐4–2311 and a contract from Johnson and Johnson Pharmaceutical Research and Development, L.L.C.) 1 Xiao‐Feng Yang and 1 Steven M. Rothman ( 1 Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO ) Rationale: Although levetiracetam (LEV) has established antiepileptic utility, there is still no convincing mechanistic data that account for its therapeutic success. Based upon recent binding experiments that show high affinity for SV2A, a synaptic vesicle protein, we decided to investigate the possibility that LEV inhibits neurotransmitter release. Methods: Imaging and electrophysiology experiments were carried out on 500 μm thick rat hippocampal slices cut on a vibratome and maintined in a submerged perfusion chamber. A bipolar stimulating electrode was placed in the Schaffer collateral layer and evoked potentials were recorded in the dendritic layer of CA1. The synaptic vesicle label FM1–43 was imaged with a 2‐photon microscope. Results: When slices were exposed to LEV (100 μM) for 30 minutes, we found no alteration of baseline evoked synaptic potentials nor any change in paired pulse potentiation (PPP). However, when slices were preincuabated in LEV for 3 hours, there was a significant, frequency and concentration dependent, reduction in both PPP and synaptic facilitation. At 40 and 80 Hz stimulation, 30 μM LEV reduced PPP from 160% to 139% of control and 155% to 120% of control, respectively (n = 8 slices). With 100 μM LEV, stimulation frequencies as low as 5 Hz, reduced PPP from 125% to 110% of control (n = 8 slices). With repetitive stimulation from 5–80 Hz, there was a progressive decrease in successive responses in LEV‐treated (100 μM) slices that was not seen in control slices. The figure below shows the effect of a series of pulses at 80 Hz, control slices are on top, LEV below. (figure 1)When slices were incubated in ucb L060 (100 μM), a LEV enantiomer lacking antiepileptic and SV2A binding activity, there was no effect on synaptic physiology. When slices were preincubed in FM1–43 and electrically stimulated to destain, there was a significant reduction in destaining rate in LEV (100 μM) exposed slices, compared to control and enantiomer‐exposed slices, suggesting that LEV inhibited some phase of vesicle release. Conclusions: Our data are most economically explained by a presynaptic effect of LEV on neurotransmitter release. It is possible that LEV directly blocks vesicle docking and that this effect is amplified at higher rates of stimulation. Alternatively, LEV could alter calcium buffering in presynaptic terminals or the actual flux of calcium into the terminals. Any of these mechanisms would be compatible with the known affinity of LEV for SV2A. LEV may require access to some intracellular compartment, explaining the necessity for a prolonged slice exposure. (Supported by the Alafi Family Foundation and the NIH (R01 NS042936 to SMR).) 1 Qian Zhao, 1 Junli Zhou, and 1 Gregory Holmes ( 1 Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH ) Rationale: Status epilepticus (SE) is often followed by severe cognitive impairment, including memory impairment. We have shown that SE is associated with impairment of single cells in the hippocampus that fire action potentials when the animal is in a specific location in space, the so‐called place cells, and that place cell function correlates well with performance in tasks of visual‐spatial memory. Place cell patterns therefore appear to be an excellent measure of spatial memory and may serve as a tool to assess seizure‐induced impairment in memory. Here we determined the relationship between spatial memory and place cell function following SE. In addition, we determined if levetiracetam (LEV), an antiepileptic drug with a novel mechanism of action, can improve cognitive function and place cell firing patterns when administered following SE. Methods: The study was designed to i) assess to relationship between learning and memory as measured in the Morris water maze with place cell firing patterns and histopathology in rats with and without a prior history of SE; and ii) determine whether LEV administered after SE alters subsequent outcome as measured by performance in the water maze, place cell function, and histopathology. Adult male rats were subjected to lithium‐pilocarpine (Li‐Pilo) SE at postnatal (P) day 70 (n = 30) and then treated with LEV or normal saline (NS) for 14 days. Following discontinuation of the drug animals were studied in the water maze and then had electrodes placed and single units recorded starting at P120. Following the testing, brains were examined for cell loss using and mossy fiber sprouting. Results: SE was associated with severely impaired performance in the water maze with SE rats demonstrating no learning over four days of testing. Paralleling this memory deficit was a marked disturbance in firing patterns of pyramidal neurons in CA1. Non‐SE rats learned quickly over four days of water maze testing and had normal pyramidal cell firing patterns. LEV had no major effects on water maze performance or place cell function. Histopathological examination of the brains showed severe cell loss in CA1 in all of the SE rats with lesser degrees of injury in CA3 and the hilus. LEV treatment resulted in less histological damage in the hippocampus but had no effect on spatial memorty function or place cell physiology in either control or SE rats. Conclusions: This study demonstrates that abnormalities in place cell firing patterns can be associated with adverse behavioral consequences. The profound deficit in pyramidal cell function in this study parallels the deficiencies in spatial memory seen in our rats. While LEV did not alter water maze performance, less cell loss was seen in animals receiving LEV than animals receiving NS. Because of the severity of the SE‐induced it is quite likely that any subtle beneficial effect of LEV on cognition would not be apparent. (Supported by NINDS (Grants: NS27984 and NS44295) and a grant from UCB.) 1 Syed Nizamuddin Ahmed, 1 Carly Mann, 1 D. Barry Sinclair, 1 Daphne Quigley, 2 Blayne Iskew, and 3 Arto Ohinmaa ( 1 Medicine (Neurology), University of Alberta, Edmonton, AB, Canada ; 2 Regional Telemedicine Program, Capital Health, Edmonton, AB, Canada ; and 3 Public Health, University of Alberta, Edmonton, AB, Canada ) Rationale: Most epilepsy patients require regular follow‐up care ideally done by a neurologist. In Canada, most specialist care is confined to the major cities, and long distances incur significant costs for both patients and health care system. In Alberta, Canada there are more than 280 videoconferencing sites that can be used for telemedicine in clinical consultations. In disciplines where clinical history and focused examination is sufficient for decision making, telemedicine is expected to substitute a proportion of conventional visits. The aim of the study was to estimate cost savings and patient satisfaction of the telemedicine compared to the conventional clinic visit. Methods: This prospective randomized controlled study includes all out‐of‐town epilepsy patients coming to follow‐up at the epilepsy clinic. After an informed consent, patients were randomized to either conventional (n = 20) or telemedicine (n = 20) clinics. Patients or caregivers filled patient satisfaction and travel cost questionnaires in both alternatives. Cost analysis included costs of traveling, lodging and lost productivity. Results: Average age of the population was 40 years (range 19–73; 45% females). 83% of patients preferred their next visit through telemedicine. About 90% of patients indicated a need for companion travel (mainly by car) to conventional clinic. Average lost working time for conventional clinic was 5.6 hours and 4.7 hours for caregivers and patients respectively. The value of lost productivity ($16.40/hour) was $169, hotel cost (12%; $85/night) $10.20 and the value of car mileage (2 × 280 km; $0.33/km) $185, totaling about $364. Patient costs for telehealth were minor. Conclusions: Telemedicine can play a major role in the follow‐up care of epilepsy patients, reduce patient costs and improve patient satisfaction. This is the first full time epilepsy telemedicine clinic in Western Canada. (Supported by: Project was funded by Capital Health Regional Telehealth in Edmonton and the Department of Medicine Alternative Relationship Plan.) 1 Hajo M. Hamer, 2 Annika Spottke, 1 Christiane Aletsee, 1 Susanne Knake, 1 Janine Reis, 1 Wolfgang H. Oertel, 1 Felix Rosenow, and 1 Richard Dodel ( 1 Neurology, University of Marburg, Marburg, Germany ; and 2 Neurology, University of Bonn, Bonn, Germany ) Rationale: There are no recent studies on the direct and indirect costs of epilepsy in Germany. Therefore, we performed a pilot study to estimate these costs of epilepsy in a German epilepsy center. Methods: A prevalence‐based, cross‐sectional convenience cohort of adults attending the outpatient clinic of our tertiary epilepsy center was evaluated. Seizure‐free patients and patients presenting with their first seizure were excluded. Direct and indirect costs were prospectively recorded over a three months period using questionnaires and a patient diary. Cost driving factors were identified. Results: 101 patients were included (40.7 ± 15.2 years; disease duration: 18.1 ± 15.3 years; 6 patients had focal epilepsy with simple partial seizures only, 28 with complex partial seizures, 43 with secondarily generalized tonic‐clonic seizures; 20 had idiopathic generalized epilepsy). The total costs of epilepsy per patient were in average € 2550 ± 4200 over the three months period. Direct cost contributed 41% to the total costs. Costs of anticonvulsant medication were the main contributor to the direct costs while indirect costs were caused mainly by losses due to early retirement. Cost driving factors included higher seizure frequency, longer disease duration, ictal falls and inadequate behavior. Conclusions: Indirect costs were higher than direct costs in adult patients with active epilepsy attending a German epilepsy center. Medication contributed the most to the direct costs and early retirement was the main factor for the indirect costs. The costs of epilepsy in this German study were above average of the European costs of epilepsy. 1 Mark Rusch, and 2 W. Curt LaFrance Jr. ( 1 Psychology, Medical College of Wisconsin, Milwaukee, WI ; and 2 Neurology and Psychiatry, Rhode Island Hospital/Brown Medical School, Providence, RI ) Rationale: Psychological nonepileptic seizures (NES) are sudden paroxysmal alterations in consciousness, behavior, sensory‐motor function or autonomic activity without epileptiform correlates that are often misdiagnosed as epileptic seizures. Definitive diagnosis occurs with video EEG long term monitoring (LTM), usually conducted during admission to comprehensive epilepsy centers. Although many newly diagnosed NES patients are referred for psychiatric or psychological treatment of a presumed underlying emotional disorder, others are simply discharged without clear direction or recommendations. A recent NINDS/NIMH/American Epilepsy Society (AES) sponsored international NES Treatment Workshop (Washington, DC, May 2005) identified a lack of knowledge in the field regarding standard of care in the management of patients with NES. Methods: We administered a preliminary survey to AES members via web and on paper to determine actual post‐diagnostic instructions given to patients and referral practices, or NES “treatment as usual” (TAU). Results: Half of the 90 respondents were neurologists, 12% were neuropsychologists/psychologists, and 9% were psychiatrists, from 12 countries and 25 states. Video EEGs were done at 80% of the sites, and LTM is used in one‐third of the sites to confirm NES diagnosis. Provocative testing was used at half of the sites. All respondents reported discussing the diagnosis of NES with the patients, and 91% discuss with the family. The term most often used for the events was “nonepileptic seizures,” and stress, anxiety/depression, and past trauma were the three etiologies most commonly given to the patient. Treatment was recommended by 95% of the respondents, and 69% of neurologists continued to follow the patient after NES diagnosis. Referrals were most commonly made to psychiatrists and clinical psychologists for treatment. The respondents thought that NES education, psychotherapy, and psychopharmacologic interventions were the most effective treatments. AEDs were tapered by 77% of the respondents, and 37% prescribed psychotropics if comorbid diagnoses were made. Conclusions: The preliminary survey results are intended to inform clinicians and researchers about the range of standard practices among physicians and allied health professional members of AES regarding their responses to NES patients. The survey addresses what neurologists and clinicians discussed with patients about the diagnosis of NES, the terms used to describe the episodes, and the recommendations for treatment. The final survey will summarize national practices, and the range of care, or TAU, offered to patients with NES. (Supported by American Epilepsy Society Research and Training Workshop Award.) 1 Louise Mc Quaid, 1 Maire White, 2 Colin Doherty, 1 Kevin Murphy, 1 Tony Kenny, 1 Norman Delanty, and 1 Mary Fitzsimons ( 1 Department of Neurology and IT Department, Beaumont Hospital, Dublin, Ireland ; and 2 Department of Neurology, St James's Hospital, Dublin, Ireland ) Rationale: Clinical research is an information intensive business involving the integration of different types of data including unstructured and structured text, alphanumeric, diagnostic image data, sound and video. Data collection and management in research proves cumbersome due to limitations posed by incomplete, inaccessible, unreadable paper charts or data stored on disparate electronic databases, compromising quality, integrity and integration of data. For example, identification of patients who meet inclusion criteria for clinical research studies is arduous. Reliability of phenotyping for genetic research can be similarly compromised. A secure, standardised EPR can overcome data management limitations by allowing multiple users simultaneous access to information at different locations. It facilitates ease of updating, interrogation, auditing and detailed analysis of complex data. The aim is to develop an epilepsy EPR to support epilepsy clinical and research services. Methods: A review of various research projects in the epilepsy programme was conducted including: imaging research, SUDEP, pharmacogenetics, and epilepsy and pregnancy. Interviews with researchers were carried out to understand information requirements. Strands of information common to all projects and project specific information was recorded. The feedback was used to build and tailor system screens more appropriate to user needs. Reports were constructed to understand how researchers interrogate the system and identify trend data required for statistical reporting. Results: The epilepsy EPR is at an advanced stage with the development of five core components including: clinic‐administration, demographics, social history, medications and epilepsy history. Technical development is based on international healthcare standards to facilitate exchange of data between different systems. It has two components: one manages generic patient information and one that manages epilepsy specific information based on the International League Against Epilepsy (ILAE). The system architecture can therefore be applied to develop EPR's for the management of other diseases. Conclusions: Better data management is critical to advance the quality of research activites. An EPR can facilitate this by providing researchers with information where and when needed. Benefits include standardised data entry using international code sets to ensure efficient exchange of information, allowing for interrogation of large data populations. Capturing data at the point of care will improve quality and integrity. Improving efficiency of clinical research is highly dependable on quality clinical information. An EPR can contribute by acting as an interface between clinical care and research. A demonstration of the epilepsy EPR will be available in the exhibition area at the AES. (Supported by Irish Health Research Board.) 1 John McDermott, 1 Chalres Deacon, and 1 Cecile Walti ( 1 Neurology, Sherbrooke University Hospital – Centre Hospitalier Universitaire De Sherbrooke, Sherbrooke, QC, Canada ) Rationale: CSE is a medical emergency with significant risk of mortality and neurologic sequellae. Prompt treatment may reduce this risk. Methods: We designed a protocol for the treatment of CSE according to the recommendations found in the literature and the pharmacological agents that are locally available. CSE was defined as generalized tonic‐clonic (or tonic in children) seizure activity beyond 5 minutes or repeated seizures without return of normal level of consciousness. The protocol was presented to the emergency, neurology and pediatrics departments with the goal of optimizing treatment of CSE at the Sherbrooke University Hospital. The major recommendations include optimal support therapy at onset, lorazepam at minute 1, phenytoin at minute 5 and a choice of propofol, phenobarbital or midazolam for refractory seizures. A retrospective review of 19 episodes of CSE from January 2005 to May 2006 was then performed. The initial management, investigation and use of antiepileptic agents were evaluated. Where possible the doses and the timing of administration were also evaluated and compared to the recommendations proposed in the protocol. Results: 13 cases of CSE were identified in adults (12 patients) and 6 in children (4 patients). A clear etiology was found in 18 cases. Supportive treatment and initial investigations were generally appropriate. In all cases, patients received lorazepam. 9 received less than 50% of the recommended dose and significant delays (>5 min since management began) occurred in 4 cases. In 11 cases, lorazepam was administered in a stepwise, incremental manner. Phenytoin was indicated in all 19 episodes and administered in 15. Five adult patients received 1 gram IV without titration to weight, contributing to a low dose. It was administered at a rate < 30 mg/min in 4 adult cases. Perfusion was initiated only after significant delay (>15 min since management began) in 8 cases. Patients were intubated in 10 cases. Two patients who were intubated had received sub‐optimal initial treatment. In both, seizure activity stopped when provided intubation induction agents. CSE persisted from < 10 minutes to 45 minutes from onset of management. EEG monitoring was performed in 7 patients, none had residual seizure activity. One patient had continued seizure activity subsequent to administration of initial agents; it was controlled with intubation induction agents. Conclusions: We found a tendency to administer medications below the recommended doses. In some, significant delays occurred prior to treatment. A tendency to administer lorazepam in an incremental manner contributed to delays in optimal treatment in some cases. Closer adherence to recommendations is suggested to minimize duration of seizure activity. 1 Blagovest Nikolov, 1 Douglas Labar, 1 Kenneth Perrine, 2 Joyce Cramer, and 1 Cynthia Harden ( 1 Neurology, Weill Medical College of Cornell University, New York, NY ; and 2 Psychiatry, Yale School of Medicine ) Rationale: Mood disorders are a frequent comorbidity in persons with epilepsy. As part of the Epilepsy Foundation's initiative on mood disorders, a survey was developed to assess knowledge of and attitudes and practices towards mood disorders in epilepsy. After this survey was piloted at the American Epilepsy Society Meeting in 2004, it was thought that information was needed from a more representative sample of US neurologists; therefore the survey was distributed to members of the American Academy of Neurology (AAN). Methods: The survey entitled “Mood in Epilepsy Neurology Practice Questionnaire”consists of 14 questions including three demographic items. A 5‐degree Likert scale was developed for most answer choices. We used an internet survey provider to send the questions via e‐mail to 900 randomly selected AAN members. Results: 156 responses (17%) were obtained and the percentages of the answers to selected questions follow: 1) How often do you ask epilepsy patients about their mood? Never 1/Rarely 7/Sometimes 26/Often 46/Always 20 2) How much do you think that symptoms of a mood disorder are important factors in determining an epilepsy patient's quality of life? Very little 1/To a mild degree 1/Somewhat 10/Quite a bit 52/A lot 36 3) When you diagnose a mood disorder in an epilepsy patient, how often do you initiate a medication to treat it (medication for depression, anxiety, etc)? Never 6/Rarely 12/Sometimes 38/Often 38/Always 6 4) When you diagnose a mood disorder in an epilepsy patient with a mood disorder, how often do you refer the patient to a psychiatrist for initiation of treatment? Never 3/Rarely 21/Sometimes 44/Often 24/Always 8 5) How frequently do you limit your prescribing of antidepressants because of concern about exacerbating seizures? Always 1/Often 5/Sometimes 30/Rarely 50/Never 14 6) In your practice, how much of an obstacle is the patient's insurance coverage when referring epilepsy patients with depression for psychiatric treatment? Overwhelming obstacle 7/Often an obstacle 26/Sometimes an obstacle 31/Usually not an obstacle 13/Rarely an obstacle 13/Don't know 10 7) Your age in years 25–35 = 17; 35–45 = 29; 45–55 = 27; 55–65 = 22; 65 and older = 5 8) Type of Practice Adult Neurology –Academic = 33 Adult Neurology – Private = 39 Adult Epileptology –Academic = 11 Adult Epileptology – Private = 4 Pediatric Neurology –Academic = 9 Pediatric Neurology – Private = 4 Pediatric Epileptology –Academic = 4 Pediatric Epileptology – Private = 0 Conclusions: A random survey of AAN members finds that practitioners are aware of the importance of mood problems in patients with epilepsy. Further, the respondents often ask these patients about their mood and initiate a plan of treatment. However, since completing this survey was voluntary, the sample may have been biased in favor of such responses. Difficulty with insurance issues when trying to obtain psychiatric care is consistently reported. (Supported by Epilepsy Foundation.) 1 Cheryl P. Shore, 1 Janice M. Buelow, and 2 Jingwei Wu ( 1 Indiana University School of Nursing, Indiana University/Purdue University, Indianapolis, IN ; and 2 Division of Biostatistics, Indiana University School of Medicine, Indiana University/Purdue University, Indianapolis, IN ) Rationale: In a sample of caregivers of children with epilepsy and significant learning problems, we noted that some caregivers gave accounts of a prompt diagnosis of epilepsy, while others described a delay. The purpose of this pilot study was to answer the research question: What factors are associated with a delay to a diagnosis of epilepsy in children with both a seizure disorder and learning problems? Methods: Qualitative data from twenty retrospective, open ended interviews with primary caregivers of children who had both a diagnosis of epilepsy and significant learning problems were examined for presence or absence of factors. Interviews were dichotomized into two categories: those that described a timely diagnostic process, and those that told of a delay. The qualitative data were then coded as to the presence or absence of factors. These included: annual income greater than $30,000, both parents actively involved with the child, parental college education, generalized tonic/clonic seizures as the presenting seizure type, caregiver mention of child fever or febrile seizures, and a diagnosis of developmental delay prior to diagnosis of epilepsy. Child age at diagnosis was also noted. SPSS was used to describe the data and conduct logistic regression analysis to explore for associations between presence/absence of factors and age of child with delay to diagnosis. Results: Of the twenty caregivers, 11 described the diagnostic process as prompt, while 9 regarded it as delayed. Older child age at diagnosis was found to associate with the delayed group, (p = .05). Three of the dichotomous factors described above were significantly associated with group membership (delay to diagnosis versus prompt diagnosis): some college education of at least one parent/caregiver (p = .02), generalized tonic/clonic seizure as the presenting seizure type (p = .04), and a diagnosis of developmental delay prior to diagnosis of epilepsy (p = .04). Conclusions: While our pilot study utilized a small sample, our findings suggest that delay to diagnosis might be associated with child, parent and seizure factors. Our sample was too small to conduct multifactor logistic regression analyses which would allow us to explore the influence of factors in combination. Our goal is to conduct a larger study with a more diverse sample in order to explore combinations of factors that are associated with an increased risk for delay to a diagnosis of epilepsy. (Supported by the Center for Enhancing Quality of Life in Chronic Illness at Indiana University School of Nursing and by R01 NR04536 and a supplement from the Office of Rare Diseases to Joan. K. Austin.) 1 Tricia Y. Ting, 1 Olukemi Ajayi, 2 Krauss Gregory, 1 Krumholz Allan, 1 Hopp Jennifer, and 1 Joseph Martinez ( 1 Neurology, University of Maryland SOM, Baltimore, MD ; and 2 Neurology, Johns Hopkins University SOM, Baltimore, MD ) Rationale: Acute repetitive seizures (ARS), multiple seizures within 24 hours with recovery between seizures, are common. It has been thought that ARS requires urgent treatment in the Emergency Department (ED), but the management of ARS is not as well‐defined as other acute seizure presentations such as status epilepticus or alcohol withdrawal seizures. ARS is commonly treated with benzodiazepines (BZD) sometimes with a longer‐acting antiepileptic drug (AED), such as intravenous phenytoin (PHT), valproic acid (VPA), or leviteracitam (LEV). A better understanding of the characteristics of ARS and its response to therapy may help to optimize treatment of ARS in an ED setting. Methods: Patients who presented to the UMMC ED (Baltimore, MD) with ARS between 11/01/05 through 2/1/06 were identified. Initial search criteria included all patients at least 18 years of age with discharge diagnosis code(s) for seizure(s). ARS characteristics, ED treatment course including length of stay, and outcome were extracted. Patients who presented with status epilepticus or alcohol withdrawal seizures were excluded from this analysis. Results: Over a 3‐month period, 88 patients presented to the ED with seizures. Of these, 20 (23%) met criteria for ARS (median 3 seizures). Eight patients received either no treatments or only a single dose of BZD. Nine patients received some combination of BZD with a longer acting AED (PHT or VPA). Three patients received only a longer acting AED (PHT or LEV). No patients had recurrent seizures after treatment (or lack of treatment). Patients who received a combination of BZD and longer acting AED or a longer acting AED alone had an average length of stay greater than 10 hours and were more likely to be admitted, while patients who received no treatment or BZD only stayed in the ED for less than 10 hours on average and were less likely to be admitted. Conclusions: The majority of patients with ARS do well, even when not treated or given only a single dose of BZD. While all patients in this study had an excellent outcome, patients who were treated with a longer acting AED or a combination of longer acting AED and BZD tended to have longer ED stays and were more likely to be admitted. Based on these findings, perhaps the urgent use of longer acting AEDs to treat ARS in the ED setting should be reconsidered.
TI - Sunday, December 3, 2006 Poster Session II 7:30 a.m.–4:30 p.m.
JF - Epilepsia
DO - 10.1111/j.1528-1167.2006.00001_6.x
DA - 2006-10-01
UR - https://www.deepdyve.com/lp/wiley/sunday-december-3-2006-poster-session-ii-7-30-a-m-4-30-p-m-Ubz3LTFpO0
SP - 119
VL - 47
IS - 
DP - DeepDyve
ER -