Neurostimulation for epilepsy: do we know the best stimulation parameters?

Commentary Under ideal circumstances, basic science research precedes clinical adoption of a technology. The reverse path has tended to prevail with deep brain stimulation (DBS) for epilepsy. After pioneering work in use of DBS for psychiatric conditions by Heath and Delgado, the New York neurosurgeon Irving Cooper was the first to use the technology to treat clinical epilepsy (1). Two recent multicenter clinical trials provided Class I evidence of efficacy for direct brain stimulation of anterior thalamus (2) and at the seizure focus (3). Having been involved in discussions to establish the clinical parameters of stimulation in one of these trials, I can lament the lack of guidance from basic science as to the best stimulation parameters. Variables to be considered are prodigious , including anatomic site of stimulation, pulse width, pulse frequency, delivery as constant current or constant voltage, intensity of stimulation, whether to ramp intensity up over time and if so what time intervals, bipolar local stimulation versus stimulation to a distant reference, initial polarity negative or positive, and cycling of stimulation by a clock setting (how long on and off?) versus continuous stimulation or responsive stimulation (responsive to what?). The combi-natorial possibilities are overwhelming, amounting to many thousands of possible choices. For the clinical trials, educated and rather arbitrary guesses were made, locking the protocol into parameters that might be far from optimal. The anterior thalamic DBS study stimulated at 5V, 0.9 ms pulses, at 145 pulses per second, on for 1 minute and off for 5 minutes. Some of the parameters imitated those of pilot trials from Cooper and the Velascos (4). Upper limits to the amount of current per pulse can be derived from studies of stimulation-induced tissue damage (5). Experience with movement disorders, where tremor can be assayed rapidly upon changes of stimulation settings, generated the concept that low-frequency stimulation was less effective than high-frequency. Although stimulation for movement disorders is usually done continuously, experience with intermittent vagus nerve stimulation and the desire to preserve battery life persuaded investigators in the thalamic DBS study to use intermittent stimulation. Respon-Preliminary results from animal and clinical studies demonstrate that electrical stimulation of brain structures can reduce seizure frequency in patients with refractory epilepsy. Since most researchers derive stimulation parameters by trial and error, it is unclear what stimulation frequency, amplitude and duration constitutes a set of optimal stimulation parameters for aborting seizure activity in a given …