Screening and diagnosis of anti-N-methyl-D-aspartate receptor encephalitis in encephalitis of unknown origin

Abstract

Objective Anti-N-methyl-D-aspartate receptor (NMDAR) antibodies are pathogenic auto-antibody and diagnostic biomarker of a novel form of autoimmune encephalitis. To determine whether patients previously diagnosed with encephalitis of unknown origin had anti-NMDAR encephalitis, an indirect immunofluorescence antibody assay test was used for the detection of anti-NMDAR IgG in cerebrospinal fluid of the patients. Methods During an one-year period over 3000 cases registered to the Peking Union Medical College Hospital cerebrospinal fluid database. The patient’s data were reviewed for criteria of encephalitis of unknown origin. The criteria of encephalitis of unknown etiology included encephalitic signs with psychiatric symptoms, seizures, cerebrospinal fluid （CSF） inflammation; negative in viral or bacterial testing and no improvement in antiviral medicine. CSF samples of 284 cases fulfilling these criteria were examined for NMDAR antibodies. Results Of the 284 specimens of CSF tested, 46 cases were positive，with a prevalence of 16.2% in our selected cases, including 18 male and 28 female, aged 4—55 years old. The patient typically presented with psychosis, memory deficits, seizures, movement disorders and autonomic instability. The CSF findings included mild to moderate lymphocytic pleocytosis, and normal or mildly increased protein concentration. Thirty-one patients had abnormal electroencephalogram records. Brain magnetic resonance imaging of 12 cases showed fluid-attenuated inversion recovery or T2 mild hyperintensity in a number of non-specific regions. Ovarian teratomas were detected in 6 patients, and patients responded to immunotherapy (corticosteroids, intravenous immunoglobulin). Conclusion A high prevalence for anti-NMDAR antibody encephalitis in our cohort suggests that this novel found encephalitis is not a rare disease in China. NMDAR antibodies should be tested in all patients with encephalitis who fulfilled the criteria of encephalitis of unknown origin. Key words: Receptors; N-methyl-D-aspartate; Encephalitis; Autoantibodies