To develop a disease-specific outcome scale for autoimmune encephalitis (AIE).

AIE is a severe neurological disease, with long-lasting neurocognitive sequelae. Currently, generic clinical assessment scales are used to evaluate outcome, not capturing the depth of disease-specific sequelae, providing less power in clinical trials. Patient-Reported Outcome Measures (PROMs) assess outcomes most important to patients, ensuring clinical relevance in standard care and clinical trials. We developed a disease-specific Patient-Reported Outcome Scale for Encephalitis (PROSE).

Content validity of individual questions from previously applied PROMs was assessed (235 items) on relevance for the AIE population. We confirmed validity in several AIE focus groups, adding missing items based on key themes identified. AIE patients completed a questionnaire containing all items with content validity (170 items). We conducted a series of validation studies to achieve the most accurate assessment with the fewest items to evaluate levels of disease severity, including item and factor analysis, Rasch modelling and testing of reliability and convergent validity.

Self-reported data was collected for 206 patients with anti-NMDAR (n=87), anti-LGI1 (n=99) and anti-CASPR2 (n=20) encephalitis. Median time from disease onset was 3.5y (range 0-14y). Prospective, repeated assessments were available in 25 patients. Item, factor and Rasch analyses supported the viability of the 40-item PROSE as a unidimensional interval scale of disease severity. PROSE covers six domains assessing cognition, behavior, emotional and physical wellbeing, fatigue and activities of daily living (ADL). There was good overall model fit for the 40-item PROSE, with no evidence of misfitting items or persons (no fit residuals >1.5). Person separation reliability (Cronbach’s alpha 0.92) was acceptable, and total scores were reliable at re-test and in agreement with existing gold standards.

PROSE is a psychometrically robust, disease-specific patient-reported outcome assessment tool for autoimmune encephalitis.