Effect of Repetitive Transcranial Magnetic Stimulation on Seizure Frequency and Epileptiform Discharges in Drug-Resistant Epilepsy: A Meta-Analysis

Archana Mishra, Rituparna Maiti, Biswa Ranjan Mishra, Monalisa Jena, Anand Srinivasan, Archana Mishra, Rituparna Maiti, Biswa Ranjan Mishra, Monalisa Jena, Anand Srinivasan

Abstract

Background and purpose: The role of low-frequency repetitive transcranial stimulation (rTMS) in drug-resistant epilepsy (DRE) has been conflicting and inconclusive in previous clinical trials. This meta-analysis evaluated the efficacy of rTMS on seizure frequency and epileptiform discharges in DRE.

Methods: A standard meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO: CRD42018088544). After performing a comprehensive literature search using specific keywords in MEDLINE, the Cochrane database, and the International Clinical Trial Registry Platform (ICTRP), reviewers assessed the eligibility and extracted data from seven relevant clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate the effect size as the mean difference in seizure frequency and interictal epileptiform discharges between the groups. Quality assessment was performed using a risk-of-bias assessment tool, and a meta-regression was used to identify the variables that probably influenced the effect size.

Results: The random-effects model analysis revealed a pooled effect size of -5.96 (95% CI= -8.98 to -2.94), significantly favoring rTMS stimulation (p=0.0001) over the control group with regard to seizure frequency. The overall effect size for interictal epileptiform discharges also significantly favored rTMS stimulation (p<0.0001), with an overall effect size of -9.36 (95% CI=-13.24 to -5.47). In the meta-regression, the seizure frequency worsened by 2.00±0.98 (mean±SD, p=0.042) for each week-long lengthening of the posttreatment follow-up period, suggesting that rTMS exerts only a short-term effect.

Conclusions: This meta-analysis shows that rTMS exerts a significant beneficial effect on DRE by reducing both the seizure frequency and interictal epileptiform discharges. However, the meta-regression revealed only an ephemeral effect of rTMS.

Keywords: medication resistant epilepsy; seizure episode; transcranial magnetic stimulations.

Conflict of interest statement

The authors have no potential conflicts of interest to disclose.

Copyright © 2020 Korean Neurological Association.

Figures

Fig. 1. PRISMA flow diagram for the…
Fig. 1. PRISMA flow diagram for the study selection process. USG: ultrasonography.
Fig. 2. Forest plot of the included…
Fig. 2. Forest plot of the included studies pooled together using a random-effects model for assessing the change in seizure frequency (A). Randomized controlled trials are indicated by the first author and year of publication. The size of each box is proportional to the weight of the corresponding study in the analysis, and the lines represent its 95% CI. Each open diamond represents the pooled relative risk, and its width represents the corresponding 95% CI. The sensitivity analysis excluded the study of Seynaeve et al.20 (B). *Sham vs. round coil, †Sham vs. figure of 8 coil, ‡1 Hz vs. placebo, §0.33 Hz vs. placebo. rTMS: repetitive transcranial magnetic stimulation.
Fig. 3. Forest plot of the included…
Fig. 3. Forest plot of the included studies pooled together using a random-effects model for assessing the change in interictal epileptiform discharges. Randomized controlled trials are indicated by the first author and year of publication. The size of each box is proportional to the weight of the corresponding study in the analysis, and the lines represent its 95% CI. Each open diamond represents the pooled relative risk, and its width represents the corresponding 95% CI. rTMS: repetitive transcranial magnetic stimulation.
Fig. 4. Bubble plot of the effect…
Fig. 4. Bubble plot of the effect of the duration of the follow-up period (adjusted for type of coil, duration of active treatment, and stimulation frequency) on the mean difference in seizure frequency. The studies/units of analysis are depicted by circles along the line of the meta-regression. The Y-axis represents the treatment effect and the X-axis represents the covariates used in the meta-regression analysis. The size of each symbol is inversely proportional to the variance of the estimated treatment effect.

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