Application of the anti-IgLON5 disease composite score to assess severity, clinical course, and mortality in a French cohort.

Abstract

Anti-IgLON5 disease presents with diverse symptoms, whose severity can be measured by the anti-IgLON5 disease composite score (ICS). This study applied the ICS to a retrospective anti-IgLON5 disease cohort (n = 52; median age 72 years, 63% male) diagnosed in the French Reference Center on Autoimmune Encephalitis (2016-2024), aiming to describe severity and clinical course, and to assess its potential to predict mortality. At diagnosis, the ICS distribution (median 18) aligned with previous publications and correlated with the time to diagnosis (median 19 months); all patients had symptoms in ≥ 2 ICS domains: bulbar (88%), sleep (84%), movement disorders (90%), cognition (64%), and/or other (78%). Of 46 patients with follow-up data, 7 (16%) died shortly after diagnosis; for the others, changes in the ICS mirrored the clinical course: at last visit, it decreased in improving patients (16/46, 35%; median 12 vs 17; p = 0.004), increased in worsening patients (11/39, 24%; median 26 vs 21; p = 0.006) and did not change significantly in stable patients (12/46, 26%; median 16 vs 15; p = 0.222). In the ROC analyses, 2-year mortality was predicted by the total ICS at diagnosis (AUC 69.51, 95% CI [50.19; 88.83]; optimal cut-off > 20, sensitivity 59%, specificity 77%), and by the bulbar score at diagnosis (AUC 74.68, 95% CI [56.17, 93.19]; optimal cut-off > 3, sensitivity 83%, specificity 62%). The ICS is a reproducible tool for assessing anti-IgLON5 disease severity and clinical course. Higher total and bulbar ICS at diagnosis are associated with increased mortality risk, underscoring the need for early and intensive management of bulbar dysfunction.