To identify autoimmune encephalitis (AE) mimics and clinical features reported in the literature.

Recent evidence suggesting that AE is as frequent as infectious encephalitis has increased awareness and testing for immune-mediated causes of neurological impairment. Consistent with this theme, several publications have focused on patients in whom a diagnosis of AE was initially overlooked. On the contrary, AE remains a rare diagnosis in clinical practice, opening up the possibility for symptoms, signs, and test findings associated with other etiologies to be misattributed to AE.

Case reports published in PubMed in English language before 04/2022 were reviewed. Cases in whom AE was clearly suspected during the diagnostic work-up or misdiagnosed were included.

A total of forty-five patients with a final diagnosis different from AE were included from 40 reports. Median age was 52 (range 5-86) years; 30/45 (67%) were male. Twenty-eight patients fulfilled the criteria for possible AE (62%), five for definite AE (11%), and twelve neither (27%). Features suggestive of AE were acute/subacute altered mental status (ranging from abnormal behavior to coma), (82%); new-onset refractory status epilepticus, (7%); CSF pleocytosis (42%) or oligoclonal bands (9%), and apparent response to immunotherapy (38%). In 26 cases, imaging corresponded to the anatomical classification of limbic encephalitis, 15 had one or more cortical/subcortical T2-abnormalities, one meningeal involvement, one brainstem involvement, and two had normal MRI. In 12 patients, clinically not relevant neural autoantibodies were detected in serum and/or CSF, including GAD, Anti-Zic4, CASPR2, VGKC, anti-N-type calcium channel antibody, anti-LGI1, and GQ1B. We identified four common AE mimic categories: neoplasms (15 patients), infectious diseases (9 patients), genetic diseases (9 patients), and neurodegenerative diseases (7 patients). Five patients had other etiologies.

Despite well-defined clinical diagnostic criteria, the misdiagnosis of AE encompasses atypical presentation of common disorders and less likely rare diagnoses.