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Treatment of Refractory Mesial Temporal Lobe Epilepsy—Reply

Treatment of Refractory Mesial Temporal Lobe Epilepsy—Reply In Reply: We appreciate the concern of Dr Kieling and colleagues regarding the small number of participants in ERSET. Our original plan was to make HRQOL the primary outcome measure, but we changed this to seizure freedom at the request of the National Institutes of Health review panel prior to approval for funding. Nevertheless, we believe our data support a benefit of surgery on HRQOL. Although the effect at 24 months did not reach statistical significance based on the primary intention-to-treat analysis (P = .08), significant differences were found at all earlier time points (P < .009) and at 24 months when postsurgery data from participants in the medical group who received surgery were excluded. The observed effects on secondary outcomes such as driving and socialization further justify a conclusion that early surgery results in psychosocial benefits relative to continued medical management. Dr Gomez-Alonso raised several important issues. Although memory declines were observed over the short-term on some tests in the surgical group and these do tend to persist over time, patients who did not undergo surgery and who continue to have seizures also show decline over a more prolonged period. The study was terminated before sufficient numbers of patients were enrolled to determine definitively whether the immediate cognitive effects of surgery ultimately differed from the longer-term effects of continued seizures. Additional studies are needed. The standardized anteromesial resection rarely causes visual field deficits large enough to impair function. Small superior quadrantic cuts were identified in 3 participants in the surgical group, but these were not clinically significant. We agree that it is unusual that none of the patients in the medical group became seizure-free given that they were cycled through a rigid schedule of AEDs, as described in the Methods section of the article,1 and pharmacotherapy was reviewed by a blinded independent committee. However, the 95% upper confidence bound for the true percentage of seizure-free cases in this group was 12% based on our small sample size. Also, there was 1 participant in this group who was seizure-free for the last 50 weeks of follow-up. Although a few studies have reported the effectiveness of pharmacotherapy following multiple AED trials to be greater than expected, characterization of these patients and the duration of seizure freedom have not been reported. In any event, efficacy of continued pharmacotherapy in patients who fail 2 AED trials would not be expected to approach the seizure freedom rate of 85% and improvement in HRQOL from surgery as suggested by our study. Consequently, we believe that the trial results are sufficient to conclude that surgery is superior to continued medical management early in the course of MTLE. In addition, we agree that a larger prospective study with longer follow-up time is necessary to fully define the advantages and disadvantages of early surgical intervention for pharmacoresistant epilepsy. Such a study might become possible if the ERSET results are an incentive for more patients with early pharmacoresistant epilepsy to be referred to surgery centers in the future than has been the practice in the past. Back to top Article Information Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Engel reported receiving an institutional grant from the National Institutes of Health (NIH); serving as a consultant to Medtronics, Valeant, Acorda, the US Food and Drug Administration, and Best Doctors; receiving fees for expert testimony; receiving fees for serving on lecture/speakers bureaus for Esai, Johnson & Johnson, Novartis, and Lippincott; receiving of patent fees (WO2009/123734A1 and WO2009/123735A1); receiving royalties from Wolters Kluwer, Wiley Blackwell, Elsevier, and MedLink; and receiving reimbursement for travel accommodations/meeting expenses from UCB Pharmaceuticals. Drs McDermott and Langfitt reported receiving an institutional grant from the National Institute of Neurological Disorders and Stroke (NINDS). Dr McDermott also reported receiving reimbursement for travel accommodations/meeting expenses for this study from the NINDS; serving as consultant to Boehringer-Ingelheim, Pfizer, Teva Pharmaceutical Industries, Smith and Nephew, Synosia, and Impax Pharmaceuticals; receiving grant support or having pending grant support from Medivation, NeuroSearch Sweden AB, Boehringer-Ingelheim, and Pfizer. Dr Langfitt also reported receiving reimbursement for travel accommodations/meeting expenses from the NIH; serving as consultant to the NINDS, University of California, San Francisco, Elekta, Northern Illinois University, University of Cincinnati, and the NIH's Center for Scientific Review; receiving grant support or having pending grant support from the NINDS and the Agency for Healthcare Research and Quality; and receiving fees for the development of educational presentations from the NIH. References 1. Engel J Jr, McDermott MP, Wiebe S, et al; Early Randomized Surgical Epilepsy Trial (ERSET) Study Group. Design considerations for a multicenter randomized controlled trial of early surgery for mesial temporal lobe epilepsy. Epilepsia. 2010;51(10):1978-198620550556PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Treatment of Refractory Mesial Temporal Lobe Epilepsy—Reply

JAMA , Volume 307 (23) – Jun 20, 2012

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Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2012.4991
Publisher site
See Article on Publisher Site

Abstract

In Reply: We appreciate the concern of Dr Kieling and colleagues regarding the small number of participants in ERSET. Our original plan was to make HRQOL the primary outcome measure, but we changed this to seizure freedom at the request of the National Institutes of Health review panel prior to approval for funding. Nevertheless, we believe our data support a benefit of surgery on HRQOL. Although the effect at 24 months did not reach statistical significance based on the primary intention-to-treat analysis (P = .08), significant differences were found at all earlier time points (P < .009) and at 24 months when postsurgery data from participants in the medical group who received surgery were excluded. The observed effects on secondary outcomes such as driving and socialization further justify a conclusion that early surgery results in psychosocial benefits relative to continued medical management. Dr Gomez-Alonso raised several important issues. Although memory declines were observed over the short-term on some tests in the surgical group and these do tend to persist over time, patients who did not undergo surgery and who continue to have seizures also show decline over a more prolonged period. The study was terminated before sufficient numbers of patients were enrolled to determine definitively whether the immediate cognitive effects of surgery ultimately differed from the longer-term effects of continued seizures. Additional studies are needed. The standardized anteromesial resection rarely causes visual field deficits large enough to impair function. Small superior quadrantic cuts were identified in 3 participants in the surgical group, but these were not clinically significant. We agree that it is unusual that none of the patients in the medical group became seizure-free given that they were cycled through a rigid schedule of AEDs, as described in the Methods section of the article,1 and pharmacotherapy was reviewed by a blinded independent committee. However, the 95% upper confidence bound for the true percentage of seizure-free cases in this group was 12% based on our small sample size. Also, there was 1 participant in this group who was seizure-free for the last 50 weeks of follow-up. Although a few studies have reported the effectiveness of pharmacotherapy following multiple AED trials to be greater than expected, characterization of these patients and the duration of seizure freedom have not been reported. In any event, efficacy of continued pharmacotherapy in patients who fail 2 AED trials would not be expected to approach the seizure freedom rate of 85% and improvement in HRQOL from surgery as suggested by our study. Consequently, we believe that the trial results are sufficient to conclude that surgery is superior to continued medical management early in the course of MTLE. In addition, we agree that a larger prospective study with longer follow-up time is necessary to fully define the advantages and disadvantages of early surgical intervention for pharmacoresistant epilepsy. Such a study might become possible if the ERSET results are an incentive for more patients with early pharmacoresistant epilepsy to be referred to surgery centers in the future than has been the practice in the past. Back to top Article Information Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Engel reported receiving an institutional grant from the National Institutes of Health (NIH); serving as a consultant to Medtronics, Valeant, Acorda, the US Food and Drug Administration, and Best Doctors; receiving fees for expert testimony; receiving fees for serving on lecture/speakers bureaus for Esai, Johnson & Johnson, Novartis, and Lippincott; receiving of patent fees (WO2009/123734A1 and WO2009/123735A1); receiving royalties from Wolters Kluwer, Wiley Blackwell, Elsevier, and MedLink; and receiving reimbursement for travel accommodations/meeting expenses from UCB Pharmaceuticals. Drs McDermott and Langfitt reported receiving an institutional grant from the National Institute of Neurological Disorders and Stroke (NINDS). Dr McDermott also reported receiving reimbursement for travel accommodations/meeting expenses for this study from the NINDS; serving as consultant to Boehringer-Ingelheim, Pfizer, Teva Pharmaceutical Industries, Smith and Nephew, Synosia, and Impax Pharmaceuticals; receiving grant support or having pending grant support from Medivation, NeuroSearch Sweden AB, Boehringer-Ingelheim, and Pfizer. Dr Langfitt also reported receiving reimbursement for travel accommodations/meeting expenses from the NIH; serving as consultant to the NINDS, University of California, San Francisco, Elekta, Northern Illinois University, University of Cincinnati, and the NIH's Center for Scientific Review; receiving grant support or having pending grant support from the NINDS and the Agency for Healthcare Research and Quality; and receiving fees for the development of educational presentations from the NIH. References 1. Engel J Jr, McDermott MP, Wiebe S, et al; Early Randomized Surgical Epilepsy Trial (ERSET) Study Group. Design considerations for a multicenter randomized controlled trial of early surgery for mesial temporal lobe epilepsy. Epilepsia. 2010;51(10):1978-198620550556PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Jun 20, 2012

References