Deep Brain Stimulation for Intractable Epilepsy: Which Target and for Which Seizures?

Abstract

Epilepsia 2004;45(4):346–354 PURPOSE: Animal studies and sporadic case reports in human subjects have suggested that intermittent elec-trical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open-label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thala-mus (ANT), to determine a range of appropriate stimu-lation parameters, and to begin to gather pilot efficacy data. METHODS: We report an open-label pilot study of inter-mittent electrical stimulation of the ANT in five patients (three men, two women; age range, 24–47 years), with follow-up between 6 and 36 months. All patients had in-tractable partial epilepsy. Four of the five patients also had secondarily generalized seizures. Stimulation was delivered by bilateral implantable, programmable de-vices by using an intermittent, relatively high-frequency protocol. Stimulation parameters were 100 cycles per second with charge-balanced alternating current; pulse width, 90 msec; and voltages ranging between 1.0 and 10.0 V. Seizure counts were monitored and compared with preimplantation baseline. RESULTS: Four of the five patients showed clinically and statistically significant improvement with respect to the severity of their seizures, specifically with respect to the frequency of secondarily generalized tonic–clonic seizures and complex partial seizures associated with falls. One patient showed a statistically significant re-duction in total seizure frequency. No adverse events could clearly be attributed to stimulation. None of the patients could determine whether the stimulator was on or off at these parameters. CONCLUSIONS: Electrical stimulation of the ANT ap-pears to be well tolerated. Preliminary evidence sug-gests clinical improvement in seizure control in this small group of intractable patients. Further controlled study of deep brain stimulation of the anterior nucleus is warranted. COMMENTARY D eep brain stimulation has gained a significant therapeu-tic role in the treatment of various neurologic disorders, including movement disorders, chronic pain, and epilepsy. In epilepsy, deep brain stimulation is used to target various neu-roanatomic structures, such as the anterior and centromedian nuclei of the thalamus, the subthalamic nucleus, the cerebellum, and more recently, the hippocampal formation. High-frequency electrical stimulation of the anterior nu-cleus of the thalamus (ANT) and of brain structures that project to the ANT was shown to reduce or inhibit seizure activity in animal models of epilepsy (1,2). Although it is suspected that lesioning of the ANT plays a role in the suppression of seizure activity, a more likely mechanism is the desynchronization of high-voltage synchronized cortical discharges, which renders the cortex less susceptible to seizures (2,3). The first report of a promising therapeutic effect of deep brain stimulation of the ANT was published in 1987 by Upton and Cooper (4), who found a reduction in seizure frequency in four of six patients. In the present study, Kerrigan et al. present the results of an open-label pilot study of intermittent electrical stimulation of the ANT in five patients with refractory epilepsy. The impact of deep brain stimulation of the ANT in the overall seizure frequency was not impressive at all, as no significant de-crease was seen in the total number of seizures after 12 months. A significant reduction in seizure frequency was observed when the analysis was restricted to generalized tonic–clonic seizures or partial seizures. Another open-label study of five patients yielded a better therapeutic response, with a mean reduction of 54% in seizure frequency and with two patients experiencing a 75% decrease in the number of seizures (5). Clearly, no definite conclusions can be derived from small open-label studies of five or six patients, and judgment must be reserved until data from a