Electrical Brain Stimulation and Epilepsy—Fighting Fire with Fire

abstract & Commentary

Source: Velasco M, et al. Subacute electrical stimulation of the hippocampus blocks intractable temporal lobe seizures and paroxysmal EEG activities. Epilepsia 2000;41(2): 158-169.

Deep brain stimulation has improved selected movement disorders, and vagal nerve stimulation has been found to ameliorate refractory epilepsy. These favorable results have now encouraged a growing interest in using direct brain stimulation to prevent the onset and spread of seizures. Although preliminary investigations in animal models are going on, Velasco and colleagues have investigated the effect of subacute temporal lobe electrical stimulation in 10 patients. Four men and six women between 11-35 years old underwent intracranial monitoring with depth and subdural electrodes to determine the location of epilepic foci prior to temporal lobectomy. After tapering off antiepileptic medications, patients were monitored over two to three weeks to characterize seizures and determine the outcome of subacute stimulation. All patients had complex-partial seizures and seven suffered from secondary general attacks as well. Velasco et al applied electrical stimulation consisting of biphasic current pulses at a rate of 130 per second to contiguous pairs of depth and subdural contacts nearest to the region of seizure onset.

Stimulation intensities used were 5-10% of the intensity typically required to evoke an epileptiform afterdischarge. Stimulation continued for 23 hours each day. The remaining hour was used to record EEG. Following the monitoring period, patients underwent temporal lobectomy. The resected tissue did not show any pathological changes related to stimulation when compared to unstimulated tissue.

Subacute stimulation produced a marked response in seven patients. In every such patient, no seizures occurred after the first week of stimulation. Interictal discharges also decreased over the course of stimulation and the frequency of interictal spikes declined 10-fold after two weeks. Patients who best responded to subacute stimulation had electrode contacts located in or on the hippocampal formation. In the five patients with the fastest and most complete antiepileptic response, contacts were located in either the anterior hippocampus or the anterior parahippocampal gyrus. Over the course of stimulation, Velasco et al noted that the background surface EEG of responders progressively normalized. Two patients with electrode contacts either in the medial hippocampus or the anterior perforate space had an initial improvement in seizure frequency that reversed when stimulation was interrupted. After stimulation restarted, both patients became seizure free. One patient had electrode contacts in the white matter and did not respond to stimulation.

Commentary

The results of the study by Velasco et al provide compelling evidence that direct brain stimulation may become an effective treatment for patients with refractory epilepsy. Nevertheless, many questions remain before the clinical use of direct brain stimulation can be fully assessed. At present, its capacity for long-term success remains unknown, nor do we know whether any reduction of antiepileptic drugs can be taken safely. Furthermore, the behavioral effects of chronic direct hippocampal stimulation remain unknown. With growing interest in the anticonvulsant effects, neurologists can expect to hear more of direct brain stimulation in the treatment of epilepsy. —fal

Which of the following answers is false?

a. Electrodes were best placed in the anterior parahippocampal gyrus.

b. Stimulation lasted 23 hours a day.

c. Patients remained off anticonvulsants.

d. Stimulation intensity was 50% of that required to induce seizures.