Prognostic Determinants of Presentation and Outcome in Anti-IgLON5 Disease

BACKGROUND AND OBJECTIVES: Anti-IgLON5 disease is characterized by substantial clinical heterogeneity and variable outcomes. We investigated the associations of clinical features as well as serum neurofilament light chain (NfL), phosphorylated tau (p-tau), IgG4 levels, and the HLA-DRB110:01∼DQB105:01 haplotype with disease presentation and outcome. METHODS: This is a retrospective observational study of patients with anti-IgLON5 disease diagnosed in our laboratory with adequate clinical information and follow-up. Neurologic disability was evaluated with the modified Rankin Scale (mRS) and the anti-IgLON5 composite score (ICS). Serum NfL and p-tau181 levels were measured using a commercial single-molecule array (Simoa) assay and IgG4 levels by flow cytometry. Associations between biomarkers and baseline clinical features were assessed using Spearman rank correlation and linear regression analyses. Prognostic variables were evaluated using binary logistic and Cox proportional hazards regression models. DISCUSSION: Serum NfL levels correlate with neurologic disability, whereas the bulbar phenotype was the main risk factor of mortality, indicating that these patients should be closely monitored and considered for early interventions (i.e., tracheostomy) that may modify an otherwise poor prognosis.