Abstracts

Rationale: Preliminary results from animal and clinical studies have shown that stimulation of deep brain structures can reduce seizure frequency and severity in patients with refractory partial and secondary generalized seizures. However, there still remain some fundamental questions that need to be answered. The most important of them being what is the exact mechanism of action of the stimulation and what type of stimulation parameters would be most effective to suppress a seizure? Many current seizure suppression methodologies rely on continual stimulation of a seizure focus or seizure-gating networks. Continual focal stimulation is undesirable for several reasons, namely, the damage induced by it, which appears more severe than that induced by timely stimulation with equal or even longer total exposure time, and an increased neuronal excitation threshold, which increases the necessary amount of delivered charge to achieve the same response. The purpose of our research is to evaluate the therapeutic effects of multiple responsive stimulation modalities which could be used to develop an efficient closed-loop prosthesis that can intervene before the clinical onset of a seizure. Methods: Long-Evans rats were bilaterally implanted with stainless steel electrodes and seizures were chemically induced using kainate treatments. A custom-built constant current programmable biphasic stimulator system was used to deliver the stimulation on demand. When a seizure was detected, both implanted sites were stimulated with a 5 sec train of rectangular constant current biphasic pulses. The frequency and amplitude of the stimulation was selected as one of the six protocols, specifically altering frequency (5Hz, 60 Hz, and 130 Hz) and amplitude (low amplitude and high amplitude) within each protocol. Histological analysis of the explanted brains were performed after data collection to evaluate electrode placement and any adverse reactions. Results: Preliminary data suggests that the efficacy of seizure suppression strongly depends on simulation parameters and the degree of seizure spread from the focus. While stimulus frequency seems to be the key parameter for disinhibition of seizure activity, stimulus intensity and charge density also seemed critical as to whether the given stimulus will successfully terminate epilpetiform afterdischarges. Conclusions: For patients with refractory epilepsy, responsive focal neuro-stimulation prior to a seizure will be a less invasive option and may lead to greater efficacy as compared with other treatments such as resection or callosotomy. Stimulation of the epileptogenic focus allows for spatial specificity, targeting only regions of the brain involved in the seizure, while responsive stimulation allows for temporal specificity and aims to suppress the epileptoform activity by stimulating the target neuron population only when a seizure is predicted or detected. Thus, an efficient responsive focal stimulation protocol could reduce the possible side effects of systemic administration of pharmacotherapy and the neural damage caused due to excessive exposure of the tissue to stimulation.