Abstracts

Nonlinear dynamical analysis of EEG has provided useful insights into the progressive preictal entrainment, and the subsequent postictal disentrainment of the epileptic brain[rsquo]s spatio-temporal EEG activity (IEEE TBME 2003; :616-627). This transition at seizures is described as dynamical resetting of the epileptic brain (IEEE TBME 2004; :493-506). We used nonlinear dynamical analysis of EEG data in a human status epilepticus (SE) patient and cobalt/homocysteine (Co/HCT) induced experimental SE in rats treated with antiepileptic drugs (AEDs) to test the hypothesis of dynamical resetting by AEDs. Following the Co/HCT procedure described in (Epilepsy Res 1988; :79-86), four male Sprague-Dawley rats (240-280 g) were induced into SE. EEG was continuously recorded and rats were AED treated with intraperitoneal diazepam (10 mg/kg) and phenobarbital (25 mg/kg) at SE stage I, III, or V (Epilepsy Res 1990; :49-60). EEG data from an episode of SE (stage III and IV) was recorded from a 6 year old patient treated unsuccessfully with rectal diazepam (10 mg) 18 minutes into the episode. He was subsequently treated successfully with intravenous lorazepam (0.1 mg/kg) 54 minutes into the episode. The rat and patient EEG data were analyzed using nonlinear dynamical techniques that use the convergence of the largest short-term Lyapunov exponent over time at each electrode site to statistically quantify the brain[rsquo]s dynamical entrainment ([alpha] = 0.01). The brain of all four rats was dynamically entrained before AED treatment. Two of the four rats were successfully treated (one at stage I and one at stage V). The successful AED treatment resulted in immediate brain dynamical disentrainment, whereas dynamical entrainment at focal electrode pairs (pairs including a focal electrode) remained in unsuccessful treatments. Similar results were found in the patient data. Focal electrode pairs remained entrained following the unsuccessful treatment of diazepam, whereas the successful treatment of lorazepam resulted in disentrainment at both focal and non-focal electrode pair sites within 10 minutes of the treatment and sustained for the remainder of the recording. These results support the hypothesis of dynamical resetting of the epileptic brain following successful treatments with AEDs in both SE-induced rats and a human case. We have shown for the first time, a very good correspondence between measures defined from nonlinear analysis and clinical morphology of EEG with the treatment efficacy of AEDs in stopping status epilepticus. These results indicate that our measures may provide useful information about the state of the patient, as well as the evaluation and development of AEDs with maximum efficacy in dynamical resetting of the brain. (Supported by Barrow Neurological Foundation and NIH EB002089 BRP grant on Brain Dynamics.)