Abstracts

Rationale: Low frequency rTMS has emerged as a promising potential therapeutic for treating epileptic patients who fail medical therapy and are not surgical candidates. However, despite several clinical studies, it is still unclear whether rTMS therapy is truly effective. We therefore performed a systematic review and meta-analysis focused on synthesizing both individual patient data (IPD) and study-level summary statistics to provide the strongest evidence to-date for the use of rTMS, and inform clinical decision-making for the management of pharmacoresistant epilepsy. Methods: We queried PubMed, SCOPUS, and MEDLINE for all relevant studies using a predetermined search algorithm and inclusion criteria. We then extracted data using pre-determined forms including relevant demographic and treatment parameters as possible outcome predictors. For studies with obtainable IPD, the primary outcome was the “favorable response rate” (defined as 50% reduction in seizure frequency). For studies with only study-level statistics, primary outcome was the pooled mean event rate of seizure frequency reduction. A random-effect model was used for analysis, and outcomes were described using comparative statistics. Results: Of 3477 articles identified citations, 12 met eligibility criteria for this analysis. We obtained IPD for 5/12 articles constituting 34 total participants. Univariate analysis of IPD to identify outcome predictors revealed an increased “favourable response rate” between participants with temporal seizure focus vs. extra-temporal focus (50% vs. 14%, p = 0.045) and between participants who were stimulated with a figure-8 coil vs. any other coil type (47% vs. 0%, p = 0.01). We also performed analysis of study-level summary statistics on the remaining 7 studies without IPD constituting 212 total participants. The pooled mean event rate of 50% seizure reduction using low frequency rTMS was 30% (95% CI 12%-57%). Sensitivity analysis revealed that studies with a mean age =21 years had higher seizure reduction rates than studies with mean age > 21  (69% vs. 18%), and studies that used a figure-8 coil also reduced seizure rates more than studies that did not use a figure-8 coil (47% vs. 14-20%). Additionally, we further identified high interstudy heterogeneity, moderate study bias (using an internal assessment tool), and high publication bias. Conclusions: Our analysis suggests that low frequency rTMS using a figure-8 coil may be an effective palliative therapeutic option for the treatment of drug-resistant epilepsy, particularly in pediatric patients and those that harbor a temporal lobe focus.  This meta-analysis can inform the design and expedite recruitment of a subsequent randomized clinical trial. Funding: No Funding was received.