Seizing the Moment: A Randomized Trial of Surgery for Drug-Resistant Pediatric Epilepsy

Seizing the Moment: A Randomized Trial of Surgery for Drug-Resistant Pediatric Epilepsy Childhood-onset drug-resistant epilepsy presents significant short- and long-term medical, psychosocial, and economic challenges. Approximately 10% to 40% of childhood epilepsy is drug resistant, this in the setting of a 1% to 2% lifetime cumulative risk for epilepsy.1 While diverse pathophysiologic entities can lead to epilepsy, various surgical approaches have emerged to enable both precise localization of epileptogenic foci and potentially curative resections or disconnections. To date, 2 randomized trials have examined temporal lobectomy in adults with drug-resistant epilepsy with highly favorable results.2 Although no high-quality studies have explored the benefit of surgery in children with drug-resistant epilepsy, a meta-analysis of the literature found 1 yr seizure freedom rates of 74% and 45% for lesional and non-lesional pediatric epilepsy, respectively.3 Dwivedi et al4 now report in The New England Journal of Medicine the first randomized controlled trial of surgery versus medical therapy for children with drug-resistant epilepsy. The research team at the All India Institute of Medical Sciences designed a single-center randomized trial primarily comparing 1-yr seizure freedom rates in children treated either with surgery or continued best medical therapy. The study encompassed all pediatric epilepsy patients presenting to this tertiary care facility, only excluding patients where consensus could not be reached regarding the location of epileptic focus, or those with a history of status epilepticus, severe metabolic abnormalities, or systemic disease. As a result, the study population included a diversity of structural lesions and semiologies with surgical approach tailored to each. A total of 116 patients were enrolled and randomized with 57 in the surgery group who underwent surgery within 1 mo of randomization and 59 in the medical therapy group who were placed on their current standard of care surgery waiting list which typically lasts 1 yr or more. All seizure localization was accomplished using long-term video EEG and 3-Tesla magnetic resonance imaging scans, with the addition of ictal and interictal SPECT, PET, or magnetoencephalography when appropriate. No patients underwent invasive monitoring with stereoelectroencephalography implantation or subdural grid placement. The primary outcome investigated was seizure freedom at 1 yr based on blinded assessment of seizure diaries with various standardized scores related to seizure severity, behavior, and overall quality of life assessed at baseline and at 1-year follow-up as secondary outcomes. A single patient in the medical therapy group was lost to follow-up and included in intention-to-treat analyses. All other patients were followed for at least 1 yr. In total, the surgical patients underwent 14 temporal lobe resections, 12 non-temporal lobe lesion resections, 15 hemispherotomies, 10 callosotomies, and 6 disconnection or resections of hypothalamic hamartomas, with no crossover from the medical-therapy group. At 1 yr, 77% of patients in the surgery group were completely free of seizures compared to 7% of patients in the medical therapy group. Of the patients who underwent surgery, 37% were completely seizure free for the entire 1- yr follow-up, while 40% experienced seizures in the postoperative period but subsequently progressed to seizure freedom. Patients in the surgery group demonstrated significant reductions on the Hague seizure severity scale along with significant improvements in behavior and overall quality of life indices, with no significant between-group differences related to intelligence quotient or social quotient on standardized testing. Adverse events in the surgery group included hemiparesis in all patients who underwent hemispherotomy along with monoparesis in 2 patients and language difficulties with hypotonia in 1 patient. All patients who experienced postoperative neurological deficits returned to baseline or near baseline function at 12-mo follow-up. Minor seizure-related adverse events were documented in the medical therapy group along with 1 episode of drug reaction. Despite these postoperative deficits, many of which were predicted based on surgical approach, the surgery group maintained a significant increase in overall quality of life scores. The authors present the first randomized controlled trial of surgery versus medical therapy for pediatric drug-resistant epilepsy, with encouraging results. Despite broad inclusion criteria, including patients with nonlesional epilepsy, the present study resulted in seizure freedom in 77% of patients treated surgically at 1 yr, with only 1 patient with lesional epilepsy not achieving seizure freedom. Additionally, the surgical group included 10 patients who underwent corpus callosotomy which generally results in ∼10% chance of seizure freedom.5 Had these patients been excluded from the present study, rates of seizure freedom may have been even more significant. Invasive seizure monitoring was not employed as part of the author's institutional protocol, though its use may have further improved outcomes, particularly in nonlesional cases. This important study provides class I evidence that epilepsy surgery improves seizure control and quality of life in patients with childhood-onset drug-resistant epilepsy. REFERENCES 1. Baca CB, Vickrey BG, Caplan R, Vassar SD, Berg AT. Psychiatric and medical comorbidity and quality of life outcomes in childhood-onset epilepsy. Pediatrics . 2011; 128( 6): e1532- e1543. Google Scholar CrossRef Search ADS PubMed  2. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med.  2001; 345( 5): 311- 318. Google Scholar CrossRef Search ADS PubMed  3. Tellez-Zenteno JF, Hernandez Ronquillo L, Moien-Afshari F, Wiebe S. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review and meta-analysis. Epilepsy Res.  2010; 89( 2-3): 310- 318. Google Scholar CrossRef Search ADS PubMed  4. Dwivedi R, Ramanujam B, Chandra PS et al.   Surgery for drug-resistant epilepsy in children N Engl J Med.  2017; 377( 17): 1639- 1647. Google Scholar CrossRef Search ADS PubMed  5. Iwasaki M, Uematsu M, Nakayama T et al.   Parental satisfaction and seizure outcome after corpus callosotomy in patients with infantile or early childhood onset epilepsy. Seizure.  2013; 22( 4): 303- 305. Google Scholar CrossRef Search ADS PubMed  Copyright © 2017 by the Congress of Neurological Surgeons http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Seizing the Moment: A Randomized Trial of Surgery for Drug-Resistant Pediatric Epilepsy

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Publisher
Congress of Neurological Surgeons
Copyright
Copyright © 2017 by the Congress of Neurological Surgeons
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1093/neuros/nyx600
Publisher site
See Article on Publisher Site

Abstract

Childhood-onset drug-resistant epilepsy presents significant short- and long-term medical, psychosocial, and economic challenges. Approximately 10% to 40% of childhood epilepsy is drug resistant, this in the setting of a 1% to 2% lifetime cumulative risk for epilepsy.1 While diverse pathophysiologic entities can lead to epilepsy, various surgical approaches have emerged to enable both precise localization of epileptogenic foci and potentially curative resections or disconnections. To date, 2 randomized trials have examined temporal lobectomy in adults with drug-resistant epilepsy with highly favorable results.2 Although no high-quality studies have explored the benefit of surgery in children with drug-resistant epilepsy, a meta-analysis of the literature found 1 yr seizure freedom rates of 74% and 45% for lesional and non-lesional pediatric epilepsy, respectively.3 Dwivedi et al4 now report in The New England Journal of Medicine the first randomized controlled trial of surgery versus medical therapy for children with drug-resistant epilepsy. The research team at the All India Institute of Medical Sciences designed a single-center randomized trial primarily comparing 1-yr seizure freedom rates in children treated either with surgery or continued best medical therapy. The study encompassed all pediatric epilepsy patients presenting to this tertiary care facility, only excluding patients where consensus could not be reached regarding the location of epileptic focus, or those with a history of status epilepticus, severe metabolic abnormalities, or systemic disease. As a result, the study population included a diversity of structural lesions and semiologies with surgical approach tailored to each. A total of 116 patients were enrolled and randomized with 57 in the surgery group who underwent surgery within 1 mo of randomization and 59 in the medical therapy group who were placed on their current standard of care surgery waiting list which typically lasts 1 yr or more. All seizure localization was accomplished using long-term video EEG and 3-Tesla magnetic resonance imaging scans, with the addition of ictal and interictal SPECT, PET, or magnetoencephalography when appropriate. No patients underwent invasive monitoring with stereoelectroencephalography implantation or subdural grid placement. The primary outcome investigated was seizure freedom at 1 yr based on blinded assessment of seizure diaries with various standardized scores related to seizure severity, behavior, and overall quality of life assessed at baseline and at 1-year follow-up as secondary outcomes. A single patient in the medical therapy group was lost to follow-up and included in intention-to-treat analyses. All other patients were followed for at least 1 yr. In total, the surgical patients underwent 14 temporal lobe resections, 12 non-temporal lobe lesion resections, 15 hemispherotomies, 10 callosotomies, and 6 disconnection or resections of hypothalamic hamartomas, with no crossover from the medical-therapy group. At 1 yr, 77% of patients in the surgery group were completely free of seizures compared to 7% of patients in the medical therapy group. Of the patients who underwent surgery, 37% were completely seizure free for the entire 1- yr follow-up, while 40% experienced seizures in the postoperative period but subsequently progressed to seizure freedom. Patients in the surgery group demonstrated significant reductions on the Hague seizure severity scale along with significant improvements in behavior and overall quality of life indices, with no significant between-group differences related to intelligence quotient or social quotient on standardized testing. Adverse events in the surgery group included hemiparesis in all patients who underwent hemispherotomy along with monoparesis in 2 patients and language difficulties with hypotonia in 1 patient. All patients who experienced postoperative neurological deficits returned to baseline or near baseline function at 12-mo follow-up. Minor seizure-related adverse events were documented in the medical therapy group along with 1 episode of drug reaction. Despite these postoperative deficits, many of which were predicted based on surgical approach, the surgery group maintained a significant increase in overall quality of life scores. The authors present the first randomized controlled trial of surgery versus medical therapy for pediatric drug-resistant epilepsy, with encouraging results. Despite broad inclusion criteria, including patients with nonlesional epilepsy, the present study resulted in seizure freedom in 77% of patients treated surgically at 1 yr, with only 1 patient with lesional epilepsy not achieving seizure freedom. Additionally, the surgical group included 10 patients who underwent corpus callosotomy which generally results in ∼10% chance of seizure freedom.5 Had these patients been excluded from the present study, rates of seizure freedom may have been even more significant. Invasive seizure monitoring was not employed as part of the author's institutional protocol, though its use may have further improved outcomes, particularly in nonlesional cases. This important study provides class I evidence that epilepsy surgery improves seizure control and quality of life in patients with childhood-onset drug-resistant epilepsy. REFERENCES 1. Baca CB, Vickrey BG, Caplan R, Vassar SD, Berg AT. Psychiatric and medical comorbidity and quality of life outcomes in childhood-onset epilepsy. Pediatrics . 2011; 128( 6): e1532- e1543. Google Scholar CrossRef Search ADS PubMed  2. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med.  2001; 345( 5): 311- 318. Google Scholar CrossRef Search ADS PubMed  3. Tellez-Zenteno JF, Hernandez Ronquillo L, Moien-Afshari F, Wiebe S. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review and meta-analysis. Epilepsy Res.  2010; 89( 2-3): 310- 318. Google Scholar CrossRef Search ADS PubMed  4. Dwivedi R, Ramanujam B, Chandra PS et al.   Surgery for drug-resistant epilepsy in children N Engl J Med.  2017; 377( 17): 1639- 1647. Google Scholar CrossRef Search ADS PubMed  5. Iwasaki M, Uematsu M, Nakayama T et al.   Parental satisfaction and seizure outcome after corpus callosotomy in patients with infantile or early childhood onset epilepsy. Seizure.  2013; 22( 4): 303- 305. Google Scholar CrossRef Search ADS PubMed  Copyright © 2017 by the Congress of Neurological Surgeons

Journal

NeurosurgeryOxford University Press

Published: Mar 1, 2018

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