Electrical Stimulation of the Anterior Nucleus of the Thalamus for the Treatment of Intractable Epilepsy

Abstract

Summary:Purpose: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical 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 thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data. Methods:We report an open-label pilot study of intermittent electrical stimulation of the anterior nucleus of the thalamus in five patients (three men, two women; age range, 24-47 years), with follow-up between 6 and 36 months. All patients had intractable partial epilepsy. Four of the five patients also had secondarily generalized seizures. Stimulation was delivered by bilateral implantable, programmable devices by using an intermittent, relatively high-frequency protocol. Stimulation parameters were 100 cycles per second with charge-balanced alternating current; pulse width, 90 ms; 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 reduction 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 appears to be well tolerated. Preliminary evidence suggests 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. Key Words: Thalamus-Anterior nucleus-Electrical stimulation-Deep brain stimulationIntractable epilepsy.Many patients with epilepsy remain inadequately controlled despite optimal use of antiepileptic medications (AEDs) and also are not candidates for resective brain surgery. The search for alternative therapies for such patients has renewed interest in electrical stimulation of deep brain structures for treating intractable epilepsy.The rationale that electrical stimulation of the nervous system can be effective in treating epileptic seizures is based on both animal data and preliminary human studies. In animal models, electrical stimulation of the thalamus at slow frequencies drives or synchronizes activity in distant brain regions (1,2), whereas stimulation at fast frequencies (>60 cycles/s; cps) can desynchronize intrinsic cortical Accepted January 8, 2004. Address correspondence and reprint requests to Dr. J.F. Kerrigan at Barrow Neurological Institute, 500 West Thomas Road, S-930, Phoenix, AZ 85013, U.S.A. E-mail: jkerrigan@chw.edu activity in distant areas (3). High-f...

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