Background
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 people with epilepsy suffer from frequent and uncontrolled seizures despite the use of medication, or are unable to tolerate the side effects of those medications. Surgery is an option for some people with uncontrolled seizures, but it is invasive and not suitable for all individuals. As a result, there remains a substantial unmet need for safe, effective therapies for these harder-to-treat epilepsies.
Transcranial magnetic stimulation (TMS) is one of several newer treatments that can potentially offer people with epilepsy a safe and non-invasive alternative to surgery. Long used as a research tool to study brain function, TMS has also been studied as a possible treatment for a number of nervous system conditions, including epilepsy. This non-surgical and painless treatment uses induced magnetic currents to regulate brain function in order to reduce the tendency to have seizures.
Objective
We aimed in this review to evaluate the evidence for the use of repetitive transcranial magnetic stimulation (rTMS) in individuals with epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges (abnormalities on brain electrographic testing that suggest underlying brain disturbance or seizure tendency), antiepileptic medication use, and side effects.
Methods
The latest search for trials was 2 June 2020. We assessed the evidence from eight randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) involving a total of 241 participants comparing rTMS to control treatments (sham treatment, antiepileptic medication, or low‐frequency rTMS).
Results
Some of the included trials showed that rTMS 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 rTMS treatment. One study measured changes in quality of life in seven participants; although not statistically analysed they found that a greater proportion of study participants reported increased quality of life scores with active treatments compared to the sham treatment. One trial reported an increase in antiepileptic medication in a single individual but they had received the control treatment. Side effects were uncommon; the most frequently reported side effect was headache (and the majority of individuals completed the treatment with rTMS). However, one study showed an increase in seizure frequency in two individuals: one during the rTMS treatment (who discontinued the treatment early), and one weeks after the treatment.
Certainty of the evidence
Overall, we judged the certainty of the evidence for the main outcome of reduction in seizure frequency to be low due to unclear information in the published papers about study design and the unclear presentation of results. One included study commented on quality of life, but involved only seven participants.
The evidence is current to June 2020.
Overall, we judged the certainty of evidence for the primary outcomes of this review to be low to very low. We found some evidence to suggest that rTMS is safe but some adverse events were experienced. The variability in technique and outcome reporting prevented meta-analysis, and 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 characterised by repeated unprovoked seizures with various aetiologies. Although antiepileptic medications produce clinical improvement in many individuals, nearly a third of individuals have drug-resistant epilepsy that carries significant morbidity and mortality, and even individuals who have clinical improvement from antiepileptic medications often report iatrogenic symptoms. 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.
This is an updated version of the original Cochrane Review published in 2016.
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.
For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid 1946 to 2 June 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Epilepsy.
We included randomised controlled trials that were double-blinded, single-blinded, or unblinded, and placebo controlled, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, coil, duration or intensity on participants with drug-resistant epilepsy.
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.
The original search revealed 274 records from the databases that after selection provided seven full-text relevant studies for inclusion. The latest search identified 179 new records from the databases that after evaluation against the inclusion and exclusion criteria provided one additional full-text relevant study. The eight included studies (241 participants) were all randomised trials; seven of the studies were blinded. Methodological and design information in the included studies was unclear, particularly relating to randomisation and allocation concealment methods. We were not able to combine the results of the trials in analysis due to differences in the studies' designs.
For the current update, two of the eight studies analysed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively), whilst the other six studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls (low-certainty evidence). One study assessed quality of life and found that more participants showed improvement in quality of life scores with active treatments compared to the sham treatment, but this only involved seven participants (very low-certainty evidence).
Four studies evaluated our secondary endpoint of mean number of epileptic discharges, three of which showed a statistically significant reduction in discharges after active rTMS treatment. Adverse effects were uncommon in the studies and typically involved headache, dizziness, and tinnitus; however increased seizure frequency did occur in a small number of individuals. The included trials reported no significant changes in medication use. Overall the risk of bias was either low or unclear, and the certainty of the evidence was low to very low.