Cerebellar stimulation in the management of medically intractable epilepsy: a systematic and critical review

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>The wide application of deep brain stimulation in the management of movement as well as other degenerative neurological and psychiatric disorders has renewed the interest in using deep brain stimulation in the management of medically intractable epilepsy. Various stimulation targets have been used with significantly varying results in aborting seizure activity. Electrical cerebellar stimulation (CS) has been used for more than 50 years in the management of epilepsy, with conflicting results. In the current study, the authors review the pertinent literature to outline the role of CS in the management of medically refractory epilepsy.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The PubMed medical database was systematically searched for the following terms: “cerebellar,” “epilepsy,” “stimulation,” and “treatment,” and all their combinations. Case reports were excluded from this study.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The pertinent articles were categorized into 2 large groups: animal experimental and human clinical studies. Particular emphasis on the following aspects was given when reviewing the human clinical studies: their methodological characteristics, the number of participants, their seizure types, the implantation technique and its associated complications, the exact stimulation target, the stimulation technique, the seizure outcome, and the patients' psychological and social poststimulation status. Three clinical double-blind studies were found, with similar implantation surgical technique, stimulation target, and stimulation parameters, but quite contradictory results. Two of these studies failed to demonstrate any significant seizure reduction, whereas the third one showed a significant poststimulation decrease in seizure frequency. All possible factors responsible for these differences in the findings are analyzed in the present study.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Cerebellar stimulation seems to remain a stimulation target worth exploring for defining its potential in the treatment of medically intractable epilepsy, although the data from the double-blind clinical studies that were performed failed to establish a clear benefit in regard to seizure frequency. A large-scale, double-blind clinical study is required for accurately defining the efficacy of CS in epilepsy treatment.</jats:p></jats:sec>

Deep Brain Stimulation for the Treatment of Epilepsy: Circuits, Targets, and Trials

“…The mechanism of action was originally thought to be thalamic inhibition via stimulation-induced Purkinje cell output, but this remains somewhat unclear [32]. In the 1970s, Cooper and colleagues were the first to report human cerebellar stimulation for epilepsy.…”

“…More rigorously controlled studies across 17 patients found none seizure free and 5/17 with reduced seizures. A detailed review on the patient has also recently been published [32].…”

“…In a nonhuman primate model of chronic focal motor seizures, thalamotomy restricted to the anterior part of the ventro-postero-lateral nucleus was able to produce longlasting benefit and in most cases led to nearly complete seizure suppression [29]. Thalamic relays are also thought to mediate the benefits from lesions and electrical stimulation of the cerebellum for epilepsy, but this circuit and its influence is less clearly defined [30][31][32]. More precise work identifying and manipulating neural signaling within the thalamocortical network is currently being performed [33].…”

Brain stimulation for the treatment of epilepsy

“…However, these initial studies yielded mixed results, with seizure termination not achieved in several studies. 19 The results from these early studies, including the absence of significant adverse effects, led to additional research into cerebellar stimulation in patients with medically refractory epilepsy.…”

“…After numerous small clinical studies that produced promising results, 19 Van Buren et al 45 performed the first double-blind crossover study of 5 patients with medically intractable seizures in whom electrodes were placed on the superior surface of the cerebellum. The patients had a variety of partial and generalized seizures, with focal and/or bilaterally synchronous epileptiform discharges on EEG.…”