Placebo‐Controlled Pilot Study of Centromedian Thalamic Stimulation in Treatment of Intractable Seizures

Abstract

Stimulation of centromedian (CM) thalamic nuclei has been proposed as a treatment for seizures. We implanted programmable subcutaneous (s.c.) stimulators into CM bilaterally in 7 patients with intractable epilepsy to test feasibility and safety. Stimulation was on or off in 3-month blocks, with a 3-month washout period in a double-blind, cross-over protocol. Stimuli were delivered as 90-microseconds pulses at 65 pulses/s, 1 min of each 5 min for 2 h/day, with voltage set to half the sensory threshold. Stimulation was safe and well-tolerated, with a mean reduction of tonic-clonic seizure frequency of 30% with respect to baseline when stimulator was on versus a decrease of 8% when the stimulator was off. There was no improvement in total number of generalized seizures with stimulation, and treatment differences were not statistically significant. Stimulation at low intensity did not alter the EEG acutely, but high-intensity stimulation induced slow waves or 2-3 Hz spike-waves with ipsilateral frontal maximum. In an open-label follow-up segment with stimulator trains continuing for 24 h/day, 3 of 6 patients reported at least a 50% decrease in seizure frequency. There were no side effects. This pilot project demonstrated the feasibility of controlled study of thalamic stimulation in epilepsy, but further study will be needed to demonstrate efficacy.

Invazív neuromoduláció a gyógyszerrezisztens epilepsziák kezelésében

“…Az 1. táblázat azokat a célpontokat foglalja össze, amelyek antiepilepsziás célzattal stimulációra kerültek [11,12,13,14,15,16,17,18,19,20].…”

Possible new avenues in epilepsy treatment: the stimulation techniques deep brain stimulation, vagal nerve stimulation, transcranial magnetic stimulation

“…There is currently an ongoing multicenter study in the US, called the SANTE trial (Medtronic, Minneapolis, MN, USA; Clinicaltrials.gov NCT00101933). The stimulation of the centromedian nucleus of the thalamus, at a stimulation frequency ranging from 4 to 185 Hz, has been tested in 78 patients so far [20,[24][25][26]32] where it leads to a significant reduction in seizure frequency of generalised tonic-clonic seizures and of absences, but not of partial complex seizures [23]. Other studies have indicated no reduction in seizure frequency [20,32].…”

“…The potential beneficial effect of electrical stimulation in various encephalopathies with refractory seizures (e.g. Lennox-Gastaut, Dravet, progressive myoclonic epilepsy) is not yet known, despite encouraging results [26,52,53].…”

Deep brain stimulation for medically refractory epilepsy

“…83 Deep brain stimulation of the CMT may result in hyperpolarization and desynchronization of the ascending reticular and cortical neurons. 83 Fisher et al 23 implanted programmable stimulators into the bilateral CMT in 7 patients with intractable epilepsy (6 with tonic-clonic seizures and 1 with partial complex seizures) to test feasibility and safety. Stimulation was switched on or off in 3-month blocks, with a 3-month washout period in a double-blind, cross-over protocol.…”

“…Multiple epilepsy centers throughout the world have performed trials over the years using DBS for epilepsy, targeting a variety of CNS structures. 11,12,23,33,78,81 These trials have been based around 2 different strategies: 1) targeting of the CNS structures believed to have a "gating" role in the epileptogenic network, such as the STN or thalamus; 34 and 2) targeting of the ictal onset zone with the theory that stimulation may lead to interference with seizure initiation. The latter strategy might ideally be used in patients with MTL epilepsy given the success in reducing seizures in patients after anterior temporal lobectomy.…”