Capturing what matters: patient-reported LGI1-ANTibody encephalitis outcome RatiNg scale (LANTERN)

Background LGI1-antibody encephalitis (LGI1-Ab-E) is a common form of autoimmune encephalitis where most patients demonstrate ‘good’ clinician-rated outcomes. However, more targeted questionnaires reveal numerous debilitating symptoms for many years. To better quantify these persistent features, we designed the LGI1-Antibody Encephalitis Rating (LANTERN) scale, a quantified, disease-specific patient-reported outcome measure (PROM), adhering to FDA guidelines. Methods A participant-driven mixed-methods approach to develop a clinically valid questionnaire over three stages: (1) Item generation through semi-structured interviews; (2) Repeated cognitive debriefing rounds to advance comprehensibility, relevance and comprehensiveness; (3) Psychometric survey to condense the most sensitive and valid questions. Analyses incorporated sensitivity testing with multiple internal and external validations. Results From 73 items across six domains (Stage 1; n = 18), a questionnaire assessing the frequency and severity of 43 symptoms (80 questions), plus nine activities of daily living (ADL), was developed through cognitive debriefing (Stage 2; n = 15). This 89-question survey was completed (Stage 3; n = 66 patients and 32 relatives) and distilled, using exploratory factor analyses, to a three-factor symptom-burden questionnaire comprising 41 questions (19 symptoms and 6 ADL), separated into physical, cognitive/behavioural and ADL domains. These factors demonstrated strong internal reliability (Cronbach alpha: 0.85–0.91), correlations with relative-completed questionnaires (R = 0.73–0.85; p < 0.001), good-to-excellent intraclass re-testing correlations (0.81–0.98; n = 19) and strong associations with numerous predefined external measures. Discussion LANTERN represents a PROM for LGI1-Ab-E, with initial content, structural and construct validity and test–retest reliability. It can be used as a reliable, tailored, efficient and sensitive method to establish symptom burden in people with LGI1-Ab-E, both in clinical practice and trials.