Performance of Diagnostic Criteria for Autoimmune Encephalitis in Patients With Suspected Rapidly Progressive Dementia.

Abstract (English)

BACKGROUND AND OBJECTIVES: The Graus criteria for possible autoimmune encephalitis (AE) are increasingly used to identify patients most likely to benefit from autoantibody testing and empiric immunotherapy. However, the performance of Graus criteria in patients with suspected rapidly progressive dementia (RPD) is unknown. We aimed to determine the diagnostic performance of the Graus criteria for possible AE in patients with suspected RPD and to identify the factors associated with progression to autoimmune dementia (AiD). METHODS: In this observational cohort study, patients ≥18 years with suspected RPD were enrolled and evaluated at 2 tertiary care centers (Washington University in St. Louis, MO, and Mayo Clinic Jacksonville, FL) from 2016 to 2024. Clinical data, brain imaging, electroencephalograms, and biofluid measures were reviewed, and consensus diagnoses were assigned by independent reviewers. We evaluated the diagnostic performance of the Graus criteria for possible AE against the consensus diagnosis. Among patients with AE, multivariable logistic regression models were used to identify factors independently associated with progression to AiD. RESULTS: Two hundred sixty-one patients with suspected RPD were enrolled (mean age 61.1 years, 46% female, 83% non-Hispanic White), including 74 patients (28%) with AE. The Graus criteria for possible AE demonstrated 89% sensitivity, 96% specificity, and 94% accuracy for the diagnosis of AE in patients with suspected RPD. Two patients with AE died within 3 months of symptom onset. Cognitive impairment persisted beyond 3 months in 47 of 72 surviving patients with AE (65%), meeting proposed criteria for AiD. In multivariable analysis, older age (odds ratio [OR] 1.4 per decade, 95% CI 1.0-1.9), longer time to initiation of immunomodulatory treatments (OR 1.4 per month, 95% CI 1.1-1.9), and treatment with rituximab (OR 4.3, 95% CI 1.2-15.1) were independently associated with AiD. DISCUSSION: The Graus criteria for possible AE reliably identified patients with suspected RPD due to AE. In patients with AE, older age, delays in the initiation of immunomodulatory therapies, and rituximab use (a proxy for severe/refractory AE) were independently associated with progression to AiD. These findings apply to patients evaluated at specialized referral centers and warrant confirmation in broader settings. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the Graus criteria accurately distinguish AE from other causes of RPD.