Abstracts

Rationale: Ketamine, a noncompetitive NMDA receptor antagonist and anesthetic used for veterinary care, has been reported to induce seizures in humans and baboons. As the baboon offers a natural model of genetic generalized epilepsy with myoclonic (MS) and generalized tonic-clonic seizures (GTCS), we evaluated the electroclinical response, including ictal and interictal epileptiform activity (IED), induced by ketamine on scalp and intracranial (Ic) EEG. Methods: Six baboons (all adults, four females) had scalp EEG recordings and were implanted with subdural grid, strip and depth electrodes for invasive video-EEG monitoring for 2 to 21 days. Ketamine was administered intramuscularly to all baboons in doses ranging from 50-70 mg (5-6 mg/kg) for transfer from primate chair to their cages. Scalp and Ic video-EEG recordings were reviewed for ictal and interictal changes within 10 minutes of ketamine administration. The baboons were unresponsive within 30 seconds of the ketamine administration. Results: Scalp EEG Analysis: IEDs occurred within 2-3 minutes of ketamine administration, with a frequency of 0.2-1 Hz before onset of generalized slowing. Ictal EEG was characterized by generalized polyspike-wave discharges associated with myoclonic seizures, or a rhythmical discharge preceding GTCS lasting at most 30 seconds. After 1-2 minutes, background suppression was noted in association with tonic activity, alternating with generalized IEDs that correlated with brief muscle relaxation with myoclonus. Ic-EEG Analysis: Initial change was predominantly noted in the occipital regions and consisted of 4-6 Hz occipital slowing lasting for 30-45 seconds followed by repetitive spikes in left, right or bi-occipital regions. Paroxysmal fast activity, IEDs or slowing occurred simultaneously in the sensorimotor regions. Generalized slowing with bi-occipital burst suppression (BS) pattern was characteristic to all Ic-recordings. The BS eventually spread to the central regions before becoming generalized, which was correlated to the tonic activity and release myoclonus observed on scalp recordings. Majority of Ic-EEG seizures were subclinical, originating focally from occipital, central, or frontal regions, or at times generalized in onset. Conclusions: While scalp EEG showed activation of generalized IEDs only, Ic-EEG demonstrated focal seizures or central polyspikes during the occipital burst suppression pattern, reflecting ketamine's proconvulsant effect. Subsequently, onset of the tonic activity alternating with release myoclonus, was correlated with the BS pattern spreading to the central regions, representing ketamine's anesthetic effect and not an ictal phenomenon. The early proconvulsant and anesthetic effects in the occipital lobe are surprising as NMDA receptors are less concentrated as compared to other brain regions, suggesting additional mechanisms for IED or seizure activation. Funding: NIH Funding : R21 NS065431