Anti-NMDA receptor encephalitis masquerading as refractory viral meningitis

Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a rare but increasingly recognized cause of acute encephalopathy, often masquerading as infectious meningoencephalitis. We present a case of a 45-year-old man with prediabetes, psoriasis, and recent-onset seizures, who experienced a rapid two-day decline in mental status. Initial symptoms included headache, aphasia, left facial droop, and confusion, prompting admission and extensive evaluation for acute stroke and infectious etiologies.
Neuroimaging revealed progressive leptomeningeal enhancement and cortical T2 hyperintensities, predominantly in the right cerebral hemisphere. Cerebrospinal fluid (CSF) analyses repeatedly demonstrated lymphocytic pleocytosis and elevated protein, further supporting an inflammatory or infectious process. Despite broad-spectrum antimicrobials and antivirals, the patient’s neurological status deteriorated, requiring intubation and transfer to the medical intensive care unit. Serial imaging continued to show worsening leptomeningeal involvement, and the clinical picture was complicated by recurrent seizures, autonomic instability, and secondary infections.
The diagnostic process was confounded by the overlap of clinical and radiographic features with viral or bacterial meningoencephalitis. Multiple infectious workups—including BioFire, PCR panels for common neurotropic viruses, and cultures—were negative. Initial autoimmune panels were equivocal, with only a weakly positive anti-NMDAR antibody in serum. It was not until a repeat Mayo Clinic panel on day 16 of hospitalization that CSF anti-NMDAR antibodies were definitively detected, confirming the diagnosis of anti-NMDAR encephalitis. Immunomodulatory therapy with high-dose steroids, intravenous immunoglobulin, and plasma exchange was initiated, but neurological improvement remained minimal, with only a gradual rise in Glasgow Coma Scale.
This case underscores the diagnostic challenges posed by anti-NMDAR encephalitis, particularly when neuroimaging and CSF findings mimic infectious etiologies. The delay in diagnosis—attributable to the initial focus on infection and the time required for confirmatory autoimmune testing—may have contributed to the patient’s prolonged encephalopathy and poor neurological recovery. Early consideration of autoimmune encephalitis in patients with unexplained encephalopathy and suggestive imaging is essential, as prompt initiation of immunotherapy is associated with improved outcomes.
Long-term prognosis in anti-NMDAR encephalitis is closely linked to the timing of diagnosis and treatment. This case highlights the need for increased awareness and expedited evaluation for autoimmune causes in patients with atypical or refractory meningoencephalitis, to minimize morbidity and optimize recovery.