Epilepsy is one of the most prevalent and disabling disorders across all age groups. Nearly 1% of adults and up to 5% of children are diagnosed as having epilepsy; more than 30% of cases are refractory to treatment. A study in the early 1970s by Cooper et al88
demonstrated significant seizure reduction in more than 50% of their patients with intractable epilepsy who had undergone cerebellar electrical stimulation; improvements in visual, verbal, and memory function were noted. Salcman et al89
described 5 patients who underwent cerebellar cortical stimulation for intractable epilepsy. Histopathologic analysis performed at the time of electrode implantation revealed marked degeneration of the Purkinje cell layer in all patients; the authors concluded that neuronal damage in patients with epilepsy may be related to the cumulative effects of the frequency and chronicity of the disease. Davis and Emmonds90
reported that most of their patients who had undergone cerebellar stimulation were either seizure-free or had significant reduction in seizure frequency during an average stimulation time frame of 8 years; in 65% of the patients, anticonvulsant medication requirements were reduced. However, a double-blind prospective clinical trial of cerebellar stimulation in 12 patients with various types of medically refractory epilepsy found no decrease in the severity or frequency of seizures.91
In a double-blind trial of cerebellar stimulation in 5 patients with generalized seizures, Velasco et al92
reported a 33% reduction in seizure frequency.
Most investigators studying cerebellar stimulation for seizure control place the electrodes via a bur hole approach. Despite postoperative imaging to confirm location, such placement may lead to variability of the exact structures being stimulated, and this may partially explain the variability in some of the reports. Larger double-blind trials with defined cohorts are necessary to fully evaluate the potential benefits of cerebellar stimulation for epilepsy.
The CM and the anterior nucleus (AN) of the thalamus have been proposed as targets for DBS treatment of epilepsy.93-96
Andrade et al96
described 8 patients with intractable seizures who underwent bilateral DBS of the AN (6 patients) or of the CM (2 patients) of the thalamus; 3 patients had a generalized seizure disorder, and 5 had partial complex seizures. During a follow-up period of 2 to 7 years, all patients experienced a reduction in seizures; however, the 2 patients who underwent CM DBS did not have a clear benefit in overall control of their seizures. Of the 6 patients who underwent AN DBS, 5 had a greater than 50% reduction in seizure frequency, although not with initial stimulator activation. These findings led the authors to postulate that seizure reduction may initially be due to the postsurgical microthalamotomy effect and that longer term improvement may be due to long-term stimulation. Placebo effect cannot be completely excluded when interpreting these findings. McIntrye et al97
noted improvement in seizure frequency after discontinuation of stimulation.
The Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy (SANTE) trial, a double-blind trial of AN DBS for refractory seizures, has suggested that targeting the AN of the thalamus is effective for refractory epilepsy. On the basis of the recently published results of the SANTE trial, the European Union has approved this strategy for treating epilepsy; however, the US Food and Drug Administration has not granted approval in the United States.98
The AN is a relatively large area, and the precise target within that subnucleus has yet to be clarified. Chkhenkeli et al99
demonstrated improvement in seizure activity with low frequency stimulation of the inferior caudate nucleus. Although their study consisted of 57 patients, the severity of seizures and the evaluation protocols varied substantially, and several patients had undergone previous resective surgeries. A study of a small number of patients with refractory seizures reported benefit with STN stimulation.100
The hippocampus has also been a target; its appeal is the potential for being a treatment for patients who have bilateral seizure activity for which bilateral temporal lobectomy is rarely an option. Initial results from Velasco et al101
showed variable but consistent reductions in seizures in 85% of patients (N=15) undergoing hippocampal stimulation. In a long-term follow-up study, Boon et al102
reported that their 10 patients did not experience significant improvement after unilateral hippocampal stimulation ipsilateral to the seizure focus.
A randomized, double-blind multicenter sham stimulation trial of the responsive neurostimulator is currently under way in the United States. The responsive neurostimulator system is an implanted device designed to detect abnormal activity in the brain and respond, similar to an implantable cardiac defibrillator, by delivering electrical stimulation to suppress development of seizure activity. Electrodes rest on the surface of the brain connected to the programmable neurostimulator, which is implanted in the skull. More randomized, double-blind, controlled multicenter trials are necessary to establish the future role of DBS in patients with epilepsy. However, this renewed interest will undoubtedly spawn further investigations into the potential of this treatment option.