Epilepsy is a common neurological disorder that appears in various forms. Many individuals with epilepsy have satisfactory seizure control with the use of antiepileptic medications. Yet, nearly a third of individuals suffer from frequent and uncontrolled seizures despite taking medications, or find that they cannot tolerate the side-effects of those medications. Surgery is an option for some individuals with uncontrolled seizures, but it is invasive and not suitable for all individuals. Therefore, there remains a substantial unmet need for safe, effective therapies for these harder-to-treat epilepsies.
Transcranial magnetic stimulation (TMS) is one of several emerging treatments that can potentially offer individuals a safe and non-invasive alternative to epilepsy surgery. Long used as a research tool to study brain function, TMS has also been studied as a possible treatment for a number of neurological conditions, including epilepsy. This non-surgical and painless treatment uses induced magnetic currents to modulate brain function in order to reduce the tendency to have seizures.
This review aims to assess the evidence for the use of TMS in individuals with epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges (sharp or spiking abnormalities on brain electrographic testing that suggest underlying brain disturbance or seizure tendency that can be focal, multifocal, or diffuse), antiepileptic medication use, and side-effects.
The last search for trials for this review was 10 March 2016. We assessed the evidence from seven randomized controlled trials (230 participants) comparing TMS to control treatments ('sham' (placebo)) TMS, antiepileptic medication, and low-frequency TMS). We were not able to combine the results of the trials in analysis due to differences in the designs of the studies; therefore, we have summarized the results of the seven studies narratively.
Some of the trials show that TMS reduces the number of seizures individuals had compared to before the therapy, but other trials did not show any significant differences in seizure frequency. Four trials showed a reduction in epileptiform discharges following TMS treatment. None of the studies measured changes in quality of life, and only one trial reported an increase in antiepileptic medication in a single person. Side-effects were not commonly reported; the most frequent side-effect reported was headache (and the majority of individuals completed the treatment with TMS).
Quality of the evidence
Overall, we judged the quality of the evidence in this review for the main outcome of reduction in seizure frequency to be low due to unclear information in the published papers about how the studies were designed and unclear presentation of results. This review provides no information about the effect of TMS on quality of life. It is important that future studies are larger and measure important outcomes, such as the effect of TMS on reducing seizure frequency, improving quality of life, and any side-effects associated with TMS compared with other available treatments.
Overall, we judged the quality of evidence for the primary outcomes of this review to be low. There is evidence that rTMS is safe and not associated with any adverse events, but given the variability in technique and outcome reporting that prevented meta-analysis, the evidence for efficacy of rTMS for seizure reduction is still lacking despite reasonable evidence that it is effective at reducing epileptiform discharges.
Epilepsy is a highly prevalent neurological condition characterized by repeated unprovoked seizures with various etiologies. Although antiepileptic medications produce clinical improvement in most individuals, nearly a third of individuals have drug-resistant epilepsy that carries significant morbidity and mortality. There remains a need for non-invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low-frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy.
To assess the evidence for the use of TMS in individuals with drug-resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side-effects.
We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 10 March 2016), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) up to March 2016. We also searched SCOPUS (1823 to June 2014) as a substitute for Embase (but it is no longer necessary to search SCOPUS, because randomized controlled trials (RCTs) and quasi-RCTs in EMBASE are now included in CENTRAL).
Eligible studies were RCTs that were double-blinded, single-blinded or unblinded, and placebo, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, duration, intensity, or setup (focal or vertex treatment) on patients with drug-resistant epilepsy. The search revealed 274 records from the databases, that after selection provided seven full-text relevant studies for inclusion. Of the seven studies included, five were completed studies with published data and included randomized, blinded trials. The total number of participants in the seven trials was 230.
We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use.
Two of the seven studies analyzed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively). The other five studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls. We were not able to combine the results of the trials in analysis due to differences in the designs of the studies. Four studies evaluated our secondary endpoint of mean number of epileptic discharges, and three of the four showed a statistically significant reduction in discharges. Quality of life was not assessed in any of the studies. Adverse effects were uncommon among the studies and typically involved headache, dizziness, and tinnitus. No significant changes in medication use were found in the trials.