Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis Presenting as Acute Psychosis and Seizures in a Patient With Multiple Sclerosis: A Diagnostic Challenge.

Autoimmune encephalitis (AE) is a potentially reversible cause of acute neuropsychiatric deterioration; however, diagnosis may be delayed when symptoms overlap with those of pre-existing neurologic disorders. We report the case of a 27-year-old woman with known multiple sclerosis (MS) who presented with acute psychosis and rapidly progressed to focal seizures, encephalopathy, catatonia, dyskinesias, and autonomic instability. Initial neuroimaging demonstrated no evidence of active demyelination or other acute intracranial pathology, raising diagnostic uncertainty regarding atypical MS relapse, infectious encephalitis, and other inflammatory processes. Cerebrospinal fluid (CSF) analysis revealed marked lymphocytic pleocytosis, while extensive infectious studies were negative. Electroencephalography demonstrated focal seizure activity arising from the left frontal region, followed by diffuse slowing with superimposed beta activity suggestive of a delta brush-like pattern. Given the characteristic clinical progression and inflammatory CSF findings, AE was strongly suspected, and immunotherapy with high-dose corticosteroids and plasma exchange was initiated before diagnostic confirmation. The diagnosis was ultimately established by positive anti-N-methyl-D-aspartate (NMDA) receptor antibodies in both CSF and serum. This case highlights the importance of recognizing clinical features atypical for MS relapse, including acute psychosis, seizures, and rapidly progressive encephalopathy, and underscores the risk of diagnostic anchoring in patients with established neurologic disease. Early recognition of anti-NMDA receptor encephalitis and prompt initiation of immunotherapy remain critical to optimizing outcomes in this potentially reversible condition.