Repetitive transcranial magnetic stimulation for the treatment of drug-resistant epilepsy: A systematic review and individual participant data meta-analysis of real-world evidence

Yonatan A Cooper; Sean T Pianka; Naif M Alotaibi; Diana Babayan; Bahar Salavati; Alexander G Weil; George M Ibrahim; Anthony C Wang; Aria Fallah

doi:10.1002/epi4.12092

Repetitive transcranial magnetic stimulation for the treatment of drug-resistant epilepsy: A systematic review and individual participant data meta-analysis of real-world evidence

Epilepsia Open. 2017 Dec 27;3(1):55-65. doi: 10.1002/epi4.12092. eCollection 2018 Mar.

Authors

Yonatan A Cooper¹, Sean T Pianka¹, Naif M Alotaibi², Diana Babayan³, Bahar Salavati^{4

5}, Alexander G Weil⁶, George M Ibrahim^{2

7}, Anthony C Wang⁷, Aria Fallah^{3

8}

Affiliations

¹ David Geffen School of Medicine University of California Los Angeles Los Angeles California U.S.A.
² Division of Neurosurgery Department of Surgery University of Toronto Toronto Ontario Canada.
³ Department of Neurosurgery David Geffen School of Medicine at University of California Los Angeles UCLA Mattel Children's Hospital Los Angeles California U.S.A.
⁴ Faculty of Medicine Institute of Medical Science University of Toronto Toronto Ontario Canada.
⁵ Temerty Centre for Therapeutic Brain Intervention Centre for Addiction and Mental Health Toronto Ontario Canada.
⁶ Division of Pediatric Neurosurgery Department of Surgery Sainte Justine Hospital University of Montreal Montreal Quebec Canada.
⁷ Division of Neurosurgery Hospital for Sick Children University of Toronto Toronto Ontario Canada.
⁸ Department of Health Policy and Management Jonathan and Karin Fielding School of Public Health University of California Los Angeles Los Angeles California U.S.A.

Abstract

Objective: To perform a systematic review and meta-analysis of real-world evidence for the use of low-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of drug-resistant epilepsy.

Methods: We systematically searched PubMed, Scopus, Medline, and clinicaltrials.gov for all relevant articles. Relevant patient and stimulation predictors as well as seizure outcomes were assessed. For studies with and without individual participant data (IPD), the primary outcomes were the rate of "favorable response" (reduction in seizure frequency ≥50%) and pooled event rate of mean reduction in seizure frequency, respectively. Outcomes were assessed with comparative statistics and random-effects meta-analysis models.

Results: Of 3,477 identified articles, 12 met eligibility and were included in this review. We were able to obtain IPD for 5 articles constituting 34 participants. Univariate analysis on IPD identified greater favorable response event rates between participants with temporal seizure focus versus extratemporal (50% vs. 14%, p = 0.045) and between participants who were stimulated with a figure-8 coil versus other types (47% vs. 0%, p = 0.01). We also performed study-level meta-analysis on the remaining 7 studies without IPD, which included 212 participants. The pooled mean event rate of 50% seizure reduction using low-frequency rTMS was 30% (95% confidence interval [CI] 12-57%). Sensitivity analysis revealed that studies with a mean age ≤21 years and studies using targeted stimulation had the highest seizure reduction rates compared to studies with a mean age >21 years (69% vs. 18%) and not using a targeted stimulation (47% vs. 14-20%). Moreover, we identified high interstudy heterogeneity, moderate study bias, and high publication bias.

Significance: Real-world evidence suggests that low-frequency rTMS using a figure-8 coil may be an effective therapy for the treatment of drug-resistant epilepsy in pediatric patients. This meta-analysis can inform the design and expedite recruitment of a subsequent randomized clinical trial.

Keywords: Epilepsy; Meta‐analysis; Outcome predictors; Repetitive transcranial magnetic stimulation; Treatment.