NMDA Receptor Encephalitis: Late Treatment Also Effective

IGURE. Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is a severe form of encephalitis associated with antibodies against NR1-NR2 heteromers of the NMDA receptor.1 Although more common in woman with ovarian teratomas, cases have been reported in males and females without detectable neoplasm.1 Early treatment offers the best outcomes and often includes tumor resection and immunosuppression.2 We describe a tumor-negative, symptomatic girl who went undiagnosed for more than 2 years before immunotherapy was begun. Her symptoms improved despite this late treatment. A 9-year-old otherwise healthy African-American girl presented with headaches and new-onset seizures. She subsequently developed facial and extremity dyskinesias, encephalopathy with visual hallucinations, agitated behavior, and incomprehensible speech (Fig A). The patient continued to decline, ultimately developing autonomic instability with tachycardia and elevated blood pressure leading to respiratory failure and cardiac arrest requiring mechanical ventilation. Serial head magnetic resonance imaging, including fluid-attenuated inversion recovery and spectroscopy, were negative. Cerebrospinal fluid was inflammatory (leukocytes 41 per mm3, predominantly lymphocytes; glucose 69 mg/dL; protein 21 mg/dL) but without viral antigens. Electroencephalography showed bihemispheric slowing, maximal over the right temporal region. Extensive infectious, metabolic, and autoimmune evaluations were negative except for detection of glutamate decarboxylase 65 autoantibody in serum (0.07 nmol/L; normal range 0.00-0.02 nmol/L) but not in cerebrospinal fluid. Serum antiphospholipid antibodies were negative. Total body magnetic resonance imaging and metaiodobenzylguanidine scintigraphy for occult malignancy were negative. Suspicion of autoimmune encephalitis prompted a 5-day course of intravenous immunoglobulin therapy (0.4 g/kg/day) and methylprednisolone (40 mg/kg/ A) Pre-treatment; 9-year-old girl presents with facial and extremity dysinesias, acquired mutism, insomnia, and an inability to walk. (B) Postreatment; 13-year-old girl now 2 years post-treatment is ambulatory with inimal dyskinesias. Cognitive deficits remain. (Videos accompanying hese images may be viewed in the online version of the article at http:// * Communications should be addressed to: Dr. Hole; Stanford University School of Medicine; 108 Pope St.; Menlo Park, CA 94025. E-mail address: mhole@stanford.edu