Abstracts

The objectives were to make three key steps toward the development of an advanced, subdural version of the Hybrid Neuroprosthesis (US Patent No. 6,497,699) for the treatment of focal epilepsies both uncontrollable by antiepileptic drugs and unsuitable for surgical intervention. In the first step, we examined whether an antiepileptic drug delivered into the subdural space can alter the course of focal epileptiform EEG activity generated in the underlying neocortical tissue, in the squirrel monkey. The focal epileptiform EEG activity (continuous 1-2 Hz spikes) was induced by the successive, subdural deliveries of 300 microgram dibutyryl cAMP and 6000 units of penicillin-G over the temporal cortex. The examined antiepileptic drug was carbamazepine (1.2 microgram in 20 microliter). In the second step, we tested whether a vector-analysis-based seizure-detection algorithm, specifically tailored for the limited power resources of the future Hybrid Neuroprosthesis, is suitable for recognizing EEG seizures recorded with subdural electrodes in temporal lobe epilepsy patients. The program (SeizureGuard) analyzed Nicolet EEG data files. In the third step, we attempted to construct a miniature, implantable pump able to alternately deliver saline and an antiepileptic drug solution through a catheter. The design aimed to provide a means for regular catheter-flushing with saline to prevent clogging in the drug delivery apparatus. The first study showed that delivering carbamazepine into the temporal cortical subdural space can eliminate focal EEG spikes within 5 minutes. The second study proved that the Seizure Guard program can accurately recognize subclinical temporal lobe EEG seizures, within 1-2 sec after their onset. The third study led to the construction of a 40 mm long, 20 mm diameter peristaltic pump that can reliably alternate the deliveries of two solutions, while offering a simple mechanism for refilling its flexible reservoirs. (1) Delivering an antiepileptic drug solution into the subdural space seemingly capable of profoundly altering the course of epileptiform electrical activity in the underlying neocortical tissue. (2) The SeizureGuard program is suitable for recognizing EEG seizure onsets in patients with focal epilepsy. (3) The miniature, saline/drug peristaltic pump appears to meet the essential criteria of an implantable drug delivery apparatus. These results can be utilized for developing a subdural, seizure-controlling Hybrid Neuroprosthesis that recognizes focal epileptiform EEG activities and, upon the occurrence of such activities, terminates/prevents the clinical seizure by delivering antiepileptic drugs into the very site(s) of seizure genesis. (Supported by NYU/FACES.)