Abstracts

Rationale: NMDA Receptor encephalitis is an autoimmune disorder with profound primary CNS manifestations. Typical age of onset ranges in early adulthood (Dalmau et al., 2008). We describe a child who presented with first-time unprovoked seizures and hallmark features of NMDA receptor encephalitis. With acute management of NMDA receptor encephalitis, his seizures resolved, and chronic immune suppressive therapies lead to near-resolution of his dyskinesias and dysautonomia. The patient eventually developed an abrupt onset of clinical seizures with limited cognitive and behavioral neurodevelopment, and was found to have severe inter-ictal abnormalities on EEG and development of multiple seizure types concerning that were reversed with re-introduction of immunosuppressive therapy. To our knowledge, the patient represents the youngest described case of NMDA receptor encephalitis, and first re-reported case progressing into an epileptic encephalopathy. Methods: Chart review, neurophysiology, and MRI Results: Diagnostic workup deonstrated an inflammatory CSF and NMDAR antibodies. Extensive serial investigations for neoplasia remain unrevealing. MRI volumetric mapping analysis revealed a frontotemporal and hippocampal volume loss that correlated with symptomatic progression.At the time of acute diagnosis, his EEG was consistent with a disorganized background with focal slowing and bursts of overriding of fast activity. EEG after immunotherapies demonstrated an improved disorganized background but with multifocal epileptiform discharges. Soon, his EEG suggested the beginnings of an epileptic encephalopathy, including generalized paroxysmal fast activity and a disorganized high-amplitude background. At this time, he demonstrated improved clinical response to immune therapies and was discharged home with close follow-up. Months later, his neurobehavioral development regressed and he developed multiple seizure types, refractory to multiple first-line anti-epileptic drug therapies. His EEG demonstrated runs of continuous spike and slow-wave, tonic seizures, and new spasms with tonic features with a disorganized, high-amplitude background with multifocal spikes and lack of sleep architecture. In the clinical context, these findings were consistent with features of Lennox Gastaut. Given concern for disease progression based his epileptic encephalopathy, immunosuppression was restarted with high-dose steroids resulting in dramatic resolution of his epileptic encephalopathy. He remains clinically stable maintained on chronic steroids and serial rituximab infusions. Conclusions: To our knowledge, this is the youngest described patient with NMDA receptor encephalitis and subsequent epileptic encephalopathy. While his early clinical course was characterized by typical clinical manifestations, his progression into a Lennox Gastaut phenotype was atypical, but also notably, was reversed by high-dose immunosuppressive therapy and treatment of his underlying autoimmune encephalitis suggesting a direct role for pathophysiology of NMDA receptor encephalitis and epileptic encephalopathy. Furthermore, we describe advanced neuroimaging analysis that delineate specific temporal and spatial volumetric changes that track with his clinical course. Our findings based on clinical, electrographic, and neuroanatomic changes raise the question whether NMDA receptor encephalitis alters maturing neuronal networks, which can lead to a potential reversible epileptic encephalopathy. We propose that refractory epilepsy and epileptic encephalopathy in the context of an autoimmune encephalitis should drive consideration aggressive and chronic immunosuppressive therapy.  Funding: None