Clinical features and factors associated with outcomes of antibody-negative autoimmune encephalitis in patients requiring intensive care

Background and objectives: Antibody-negative autoimmune encephalitis (AE) is a form of encephalitis characterized by the absence of detectable autoimmune antibodies, despite immunological evidence. However, data on management of patients with antibody-negative AE in the intensive care unit (ICU) are limited. This study aimed to explore the characteristics and subtypes of antibody-negative AE, assess the effects of immunotherapy, and identify factors independently associated with poor functional outcomes in patients requiring intensive care.

Methods: This retrospective, single-center study analyzed consecutive adult patients diagnosed with antibody-negative AE and admitted to the ICU of a large tertiary hospital between 2019 and 2023. Multivariate regression analysis was used to identify factors linked to poor functional outcomes six months after ICU admission, as defined by a modified Rankin Scale score of 3-6. Generalized linear mixed models were applied to evaluate the effect of immunotherapy on longitudinal changes in the Clinical Assessment Scale in Autoimmune Encephalitis and modified Rankin Scale scores.

Results: Of the 1220 patients with severe encephalitis admitted to the ICU, 107 were diagnosed with antibody-negative AE and included in the analysis. Six months after ICU admission, 67 patients (62.6%) had poor functional outcomes, including 28 deaths (26.2%). Factors independently associated with poor outcomes were high-dose corticosteroid therapy (odds ratio [OR] 8.734, 95% confidence interval [CI] 2.483-30.717), older age at onset (OR 1.063, 95% CI 1.028-1.099), acute respiratory failure at ICU admission (OR 10.931, 95% CI 2.062-57.751), and dyskinesia/dystonia (OR 14.109, 95% CI 1.336-148.957). The generalized linear mixed model also indicated that high-dose corticosteroid therapy was associated with poorer longitudinal outcomes.

Conclusions: While high-dose corticosteroids are frequently used to treat AE, their risks may outweigh their benefits in severe antibody-negative AE cases. Older patients and those with dyskinesia/dystonia or respiratory failure, may require more careful monitoring and timely intervention for improved outcomes. However, prospective validation of these findings is necessary to confirm their applicability and guide future treatment strategies.