A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy

Abstract

Objective: To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double-blind, sham-controlled trial. Methods: Twenty-one patients with malformations of cortical development and refractory epilepsy underwent five consecutive sessions of low-frequency rTMS, either sham or active (1Hz, 1,200 pulses), focally targeting the malformations of cortical development. The number of epileptiform discharges in the electroencephalogram and the number of clinical seizures were measured before (baseline), immediately after, as well as 30 and 60 days after rTMS treatment. Results: rTMS significantly decreased the number of seizures in the active compared with sham rTMS group ( p Ͻ 0.0001), and this effect lasted for at least 2 months. Furthermore, there was a significant decrease in the number of epileptiform discharges immediately after ( p ϭ 0.01) and at week 4 ( p ϭ 0.03) in the active rTMS group only. There were few mild adverse effects equally distributed in both groups. The preliminary cognitive evaluation suggests improvement in some aspects of cognition in the active rTMS group only. Interpretation: Noninvasive brain stimulation for epilepsy may be an alternative treatment for pharmaco-resistant patients with clearly identifiable seizure foci in the cortical convexity and who are not eligible for surgical treatment.

Noninvasive Brain Stimulation Protocols in the Treatment of Epilepsy: Current State and Perspectives

“…37 Definitive reasons for these heterogeneous results are difficult to state because the studies differ in more than one aspect (Table 1). In the studies conducted by Fregni et al 35 and Theodore et al, 36 rTMS intensity was stronger than in the study conducted by Cantello et al, 37 and more stimuli were applied. Moreover, in the former studies, the epileptogenic zone was stimulated, whereas in the latter study, stimulation over the vertex was performed.…”

“…For the three randomized, double-blinded and sham-controlled studies, only one resulted in a significant reduction of seizure frequency and interictal discharges, 35 whereas in another study a trend for a reduction of epileptic seizures was found, 36 and in a third study only significantly reduced epileptiform discharges were documented. 37 Definitive reasons for these heterogeneous results are difficult to state because the studies differ in more than one aspect (Table 1).…”

“…Thus it could be argued that more intense rTMS and rTMS over the epileptogenic zone might be preferable. However, Fregni et al 35 and Theodore et al 36 included only patients with focal epilepsy, whereas patients with primarily generalized epilepsies also participated in the study conducted by Cantello et al 37 Thus, it cannot be excluded that the type of epilepsy has an impact on the proneness to profit from rTMS. From a pathophysiological perspective, it would make sense that focal epilepsies with a cortical origin, which will be more easily influenced by rTMS, might profit more from rTMS than primary generalized epilepsies with a subcortical origin much more distant to the electrical current flow induced by TMS.…”

Not all that glitters is gold: A guide to surgical trials in epilepsy

“…Several RCTs (5/12) evaluated VNS (whether implanted9, 14, 17, 31, 32 or transcutaneous6). Two evaluated HS (implanted34 or transcranial12), and the rest individually evaluated CS,35 TNS,11 rTMS,13 thalamic stimulation,33 and RNS 10, 16, 18. All pivotal RCTs were followed by open‐label extensions that allowed long‐term data collection 7, 8, 10, 16, 36…”

“…Resective epilepsy surgery, in appropriately selected patients, is the accepted treatment of choice for DRE as supported by two randomized clinical trials,3, 4 multiple retrospective cohort series, and a practice parameter issued by the American Academy of Neurology recommending a surgical evaluation for any patient with uncontrolled disabling complex partial seizures 5. Similarly, a plethora of nonresective yet surgical DRE treatments have flourished recently, including various neuromodulation procedures6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and thermal‐based19 and radiation‐based neurosurgeries 20. A position statement by the Practice Management Committee Health Care Reform Workgroup of the American Epilepsy Society called for access and insurance coverage for all patients with epilepsy for more aggressive therapeutic strategies, including neurosurgery and implanted electronic devices, when medications fail to yield optimal seizure control 21.…”