Double‐blind, Randomized Controlled Pilot Study of Bilateral Cerebellar Stimulation for Treatment of Intractable Motor Seizures

Abstract

Summary: Purpose:The efficacy and safety of cerebellar stimulation (CS) was reevaluated in a double-blind, randomized controlled pilot study on five patients with medically refractory motor seizures, and especially generalized tonic-clonic seizures.Methods: Bilateral modified four-contact plate electrodes were placed on the cerebellar superomedial surface through two suboccipital burr holes. The implanted programmable, batteryoperated stimulator was adjusted to 2.0 µC/cm 2 /phase with the stimulator case as the anode; at this level, no patient experienced the stimulation. Patients served as their own controls, comparing their seizure frequency in preimplant basal phase (BL) of 3 months with the postimplant phases from 10 months to 4 years (average, eight epochs of 3 months each). During the month after implantation, the stimulators were not activated. The patient and the evaluator were blinded as to the next 3-month epoch, as to whether stimulation was used. The patients were randomized into two groups: three with the stimulator ON and two with the stimulator OFF. After a 4-month postimplantation period, all patients had their stimulator ON until the end of the study and beyond. Medication was maintained unchanged throughout the study. EEG paroxysmal discharges also were measured.Results: Generalized tonic-clonic seizures: in the initial 3-month double-blind phase, two patients were monitored with the stimulation OFF; no change was found in the mean seizure rate (patient 1, 100%, and patient 5, 85%; mean, 93%), whereas the three patients with the stimulation initially ON had a reduction of seizures to 33% (patient 2, 21%; patient 3, 46%; patient 4, 32%) with a statistically significant difference between OFF and ON phase of p = 0.023. All five patients then were stimulated and monitored. At the end of the next 6 months of stimulation, the five patients had a mean seizure rate of 41% (14-75%) of the BL. The second patient developed an infection in the implanted system, which had to be removed after 11 months of stimulation; the seizures were being reduced with stimulation to a mean of one per month from a mean of 4.7 per month (BL level) before stimulation. At the end of 24 months, three patients were monitored with stimulation, resulting in a further reduction of seizures to 24% (11-38%). Tonic seizures: four patients had these seizures, which at 24 months were reduced to 43% (10-76%). Follow-up surgery was necessary in four patients because of infection in one patient and lead/electrode displacement needing repositioning in three patients. The statistical analysis showed a significant reduction in tonic-clonic seizures (p < 0.001) and tonic seizures (p < 0.05).Conclusions: The superomedial cerebellar cortex appears to be a significantly effective and safe target for electrical stimulation for decreasing motor seizures over the long term. The effect shows generalized tonic-clonic seizure reduction after 1-2 months and continues to decrease over the first 6 months and then maintains this effectiveness over the st...

Cerebellar output controls generalized spike‐and‐wave discharge occurrence

“…So far, only 3 clinical studies applying electrical DBS to the CN have been reported, which is in contrast to the dozens of studies performed to investigate the therapeutic use of cerebellar surface stimulation (as reviewed by Krauss and Koubeissi66). Although initially promising, the clinical studies on the effects of cerebellar surface stimulation reported inconsistent results,12, 13, 14, 15, 16, 17, 18, 19, 20, 21 which may partially be due to suboptimal placement of electrodes. Unlike the current results, which show a regional preference for the effect of lateral CN stimulation on GSWD occurrence, it was recently shown that manipulating Purkinje cells in the medial cerebellum is most effective in controlling kainate‐induced temporal lobe epilepsy 67.…”

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…”

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].…”