To compare clinical features of autoimmune brainstem encephalitis (BE) with brainstem disorders of alternative etiology.

Autoimmune BE is an immune-mediated brainstem disorder associated with neural antibodies. Distinct clinical features have been described, and diagnostic criteria proposed, but their performance in clinical practice remains uncertain.

Medical records of patients with suspected BE at our institution between January 1, 2005, and December 31, 2024, were retrospectively reviewed. Patients with brainstem-predominant CNS disorder and an attributed final diagnosis were included. Patients were classified as definite autoimmune (neural antibody positive), seronegative autoimmune BE (clinical diagnosis), other inflammatory disorders or non-autoimmune. Diagnostic criteria (Gilligan et al., 2024) were applied to autoimmune BE cohorts to assess performance.

Of 756 patients screened, 214 (28%) met inclusion criteria: 102 (48%) definite autoimmune BE, 43 (20%) probable antibody-negative autoimmune BE, 23 (11%) other inflammatory disorders, and 46 non-autoimmune etiologies (15 infectious [7%], 7 vascular [3%], and 24 neoplastic disorders [11%]). Altered mental status was less frequent in definite autoimmune BE than non-autoimmune group (13% vs 52%, p<0.001). Diplopia, vestibulocochlear involvement, and coexisting ataxia were more common in definite autoimmune BE than in non-autoimmune brainstem disorders (84% vs 50%; 69% vs 35%; 82% vs 57%, respectively; all p<0.001). MRI brainstem and cerebellar abnormalities were more common in non-autoimmune disorders (78% and 67%, respectively) than definite autoimmune BE (33% and 17%, respectively; all p<0.001). Inflammatory CSF abnormalities (≥1 pleocytosis, elevated IgG index or CSF-exclusive OCBs) did not differ significantly between groups (78% definite, 79% probable, 73% other inflammatory, 57% non-autoimmune; p=0.070). Diagnostic criteria for probable antibody-negative autoimmune BE had 42% sensitivity and 100% specificity.

Autoimmune BE has distinct clinical features but fewer MRI abnormalities than non-autoimmune mimics. In this context, antibody testing becomes critical for diagnosis. Low sensitivity of current criteria highlights the need for BE-specific diagnostic biomarkers.