Diagnostic Yield of Anti‐Neuronal Antibody Testing in Patients Suspected of an Infectious Encephalitis

Background and Objectives Recognition of autoimmune encephalitis (AIE) can be difficult as typical radiological or cerebrospinal fluid abnormalities may be lacking. We investigated the yield of comprehensive diagnostic testing for anti‐neuronal antibodies in patients suspected of encephalitis in an acute setting. Methods In a prospective multicenter cohort, we included patients suspected of encephalitis in whom a lumbar puncture was performed. We retrospectively selected patients from this cohort in whom no infectious cause was identified and an autoimmune CNS disease was considered. Immunohistochemistry was performed on the CSF samples as an index test to screen for anti‐neuronal antibodies, and confirmatory cell‐based assays were performed. Results Between 2017 and 2021, 723 episodes were included in 707 patients. The median age was 55 years, and 347 (48%) of the episodes occurred in women. In 59 of 723 episodes (8%), a clinical diagnosis of autoimmune CNS disease was made. Twenty‐three (3%) of them fulfilled the diagnostic criteria for possible AIE, and 9 (1%) had antibody‐positive AIE (five anti‐NMDAR encephalitis, two anti‐LGi1 encephalitis, one anti‐Ma2 encephalitis and anti‐CV2 encephalitis). Extensive antibody testing identified no additional anti‐neuronal antibodies in the remaining 47 episodes. Discussion In a cohort of patients with a suspected encephalitis presenting in an acute setting, the incidence of possible AIE was low, and in only one‐third of possible AIE episodes an anti‐neuronal antibody was detected. Anti‐neuronal antibody testing beyond what was done in the clinical setting did not yield additional cases of antibody‐positive AIE.