What is TMS?

Transcranial magnetic stimulation (TMS) is a method for focal electrical brain stimulation where small electrical currents are induced in the brain by a powerful magnetic field. Several TMS devices are approved by the FDA for treatment of major depression by repetitive TMS (rTMS) that is most commonly delivered in daily session, over several days to weeks, with hundreds of individual pulses delivered to a predetermined brain region in a half-hour-long session.

In recent years, rTMS, particularly low frequency (0.3 to 1 Hz) rTMS that can induce a lasting reduction in cortical excitability, has emerged as a potential treatment for intractable epilepsy. rTMS risks in epilepsy are modest and include a small possibility (as with any kind of electrical brain stimulation) of triggering a seizure during an rTMS session. The other possible adverse events are discomfort during the session and mild headache and occasional ringing in the ears after a course of rTMS. Overall, however, rTMS is well tolerated by children and adults.

How does it work?

The mechanism by which rTMS may suppress seizures is incompletely understood, but likely relates to the physiologic phenomena of synaptic plasticity where repetitive electrical brain stimulation leads to lasting changes in neuron-to-neuron signaling. Specifically, low frequency electrical stimulation of the cerebral cortex reliably reduces regional cortical excitability. Thus, if it is assumed that excess cortical excitability is a critical abnormality in epilepsy, than it follows that suppression of regional cortical excitability may reduce seizure frequency. 

Does it work?

Numerous open label trials and a few placebo-controlled experiments support an eventual therapeutic role for rTMS when applied over the epileptogenic region, or even when applied in a neutral scalp location, such as over the vertex. Interestingly, the favorable response of some patients with focal epilepsy to rTMS outside of the epileptogenic zone, and in one series a favorable response of patients with primary generalized seizures to rTMS, raises the possibility of wide-spread therapeutic benefit elicited by focal stimulation.

From a scientific perspective, this suggests that the rTMS antiepileptic mechanism may not be as simple as local suppression of intracortical excitability, but rather a network effect of low frequency rTMS. However, the results from placebo controlled trials are mixed, with some showing an appreciable seizure suppression of approximately 90% for several weeks after treatment and others showing little benefit over placebo. These discrepancies likely relate to differences in rTMS methods and in subject selection between trials. The results underscore a need for ongoing studies that will enable clinicians to best match a specific rTMS protocol to a specific epilepsy syndrome.

What roles does TMS play in epilepsy?

Notably, TMS is unique among the neurostimulation technologies that have been applied in epilepsy in its capacity as either a diagnostic or a therapeutic tool. Particularly, navigated TMS (nTMS), where the TMS operator systematically activates multiple brain regions to identify a motor or language response, has become an important part of epilepsy surgery evaluation in some medical centers. nTMS complements fMRI and Wada as an aid to the epilepsy surgery plan and as a means to measure the risk of functional deficit after epilepsy surgery.

What can TMS tell us about the mechanism of epilepsy?

Another interesting TMS protocol, paired-pulse TMS (ppTMS) as a means to assess cortical inhibition or facilitation, is emerging as a potentially practical measure of the excitation-inhibition ratio in patients with epilepsy. ppTMS is more experimental than clinical, but may have a role in patient management in the near future.

In most ppTMS protocols two closely spaced TMS pulses are delivered to the motor cortex to elicit contractions of a hand muscle that is measured as a motor evoked potential (MEP) by electrodes connected to the skin of the hand. The first of the pair of pulses activates an inhibitory cortical response such that when a second TMS pulse is delivered to the same region, the motor response is reduced. The ratio between motor responses to the initial (conditioning) and second (test) pulse reflects the efficiency of inhibitory signaling. Thus in epilepsy syndromes characterized by deficient cortical inhibition, ppTMS may one day help to track disease severity. Similarly, ppTMS may also aid in measuring the effectiveness of other treatments aimed to improve cortical inhibition in epilepsy.

TMS technology and the associated body of scientific knowledge have evolved considerably since TMS was first introduced in the 1980s. Recent medical advances are coinciding with industry interests in identifying TMS roles in specific clinical syndromes. This should translate into greater accessibility to TMS for both patients and clinicians, as well as still further improvement of our knowledge of when and how to use TMS in epilepsy.

Authored By: 
Alexander Rotenberg MD, PhD
Authored Date: 
Reviewed By: 
Mohamad Koubeissi MD
Wednesday, December 2, 2015