Objective:

Background:

LGI1-Ab-E is a common form of autoimmune encephalitis where most patients demonstrate ‘good’ clinician-rated outcomes. However, more targeted questionnaires reveal numerous experience-debilitating symptoms for many years. To better quantify these persistent features, we designed LGI1-ANTibody-Encephalitis RatiNg (LANTERN), a quantified, disease-specific PROM.

Design/Methods:

A participant-driven mixed-methods approach, advocated by FDA guidelines, 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) A psychometric survey to condense the most sensitive and valid questions. Analyses incorporated sensitivity-testing and multiple internal and external validations.

Results:

From 73 items across six domains (Stage 1; n=18), a questionnaire assessing frequency and severity of 43 symptoms (80 questions), plus nine activities of daily living (ADL), was developed through cognitive debriefing (Stage 2, n=15). In Stage 3, this 89-question survey was completed (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 intra-class re-testing correlations (0.81-0.98; N=19) and strong associations with numerous predefined external measures.

Conclusions:

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 tailored and sensitive method to estimate symptom burden over time in people with LGI1-Ab-E, both in clinical practice and trials.