Abstracts

Rationale: Background: anti-NMDAR encephalitis, first described by Dalmau and colleagues in 20071, is an increasingly recognized autoimmune cause of seizures, autonomic dysregulation, oro-facial dyskinesias, and psychosis sometimes seen in association with teratoma. A unique EEG pattern termed extreme delta brush pattern2 has been described on EEG recordings in several patients identified to have NMDA receptor antibodies, so named because of a similar pattern found in normal neonates termed delta brush. The extreme delta brush pattern is characterized by 18-32 Hz fast frequencies riding on the trough or upslope of a slower 0.5-1.5 Hz delta wave. The clinical manifestations of anti-NMDAR encephalitis are characterized by the laboratory finding of antibodies that bind to an epitope on the NR1 subunit of the NMDA receptor. Ketamine is a non-competitive antagonist inhibiting the NMDA receptor by binding both in the open channel and at an allosteric site, thereby increasing glutamatergic neurotransmission4,5. To the extent that EEG changes in patients receiving ketamine overlap the frequencies of the extreme delta brush pattern, this would support the hypothesis that the underlying pathogenesis in anti-NMDAR encephalitis is a direct effect of irreversible binding of antibodies to an epitope on the NR1 subunit of the NMDA receptor, and the effects of this on synaptic transmission. Methods: Methods: 30 surgical patients with no known psychiatric or neurological disease and without administration of sedatives or other medications were anesthetized with ketamine (2mg/kg intravenous infusion) while recording eight-channel electroencephalography of frontal, parietal, and temporal regions. We analyzed the raw EEG data in these patients at baseline and after ketamine infusion. We compared average spectrograms at baseline and after ketamine injection. We performed phase amplitude coupling analysis for 2 patients at baseline and after ketamine injection. Results: Results: After ketamine injection the raw EEG showed a similar extreme delta brush pattern to that described in severe cases of anti-NMDAR encephalitis reported by Schmitt and colleagues. After ketamine injection the average spectrograms for 30 patients showed a shift from strong alpha power to increased power of faster frequencies over 30 Hz. After ketamine injection we observed for 1 subject there was significant coupling of fast wave (18-32 Hz) and slow wave (0.5-1.5 Hz) (p<0.001) with fast waves distributed on the trough of slow waves. Conclusions: Conclusions: Ketamine and anti-NDMAR antibodies act via similar molecular mechanisms based on the similarity of their respective EEG patterns. This finding supports the hypothesis of extreme delta brush as a unique EEG finding in anti-NMDAR encephalitis that is important for earlier diagnosis and treatment, and strengthens our understanding of ketamine's primary anesthetic effect mediated through the NMDA receptor.