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.

Keywords: Anti-IgLON5 antibodies; Anti-IgLON5 disease; Autoimmune encephalitis; Neuronal surface antigen.

Fig. 1

Brain magnetic resonance imaging findings. Mesencephalon (A) and pyramidal tracts (A, B) T2/fluid attenuated inversion recovery (FLAIR) hyperintensity, and pontocerebellar atrophy (C; case n. 47). Left medial temporal lobe T2/FLAIR hyperintensity (D; case n. 16). Diffusion-weighted imaging cortical hyperintensity (E, arrows; case n. 6). Mesencephalic atrophy (F; case n. 5). T2/FLAIR hyperintensity of the trigeminal nerves (G, arrows) and lateral pterygoid muscles (H, arrows; case n. 4)

Fig. 2

Total and partial anti-IgLON5 disease composite scores in the French cohort. Distribution of the total and partial composite anti-IgLON5 disease scores at diagnosis in the French cohort. ICS anti-IgLON5 composite score

Fig. 3

Total anti-IgLON5 disease composite score at diagnosis versus last visit. Distribution of the total anti-IgLON5 disease composite score at diagnosis and last visit in 39 patients with available follow-up information, classified according to clinical course (improved, stable, or worsened). ns non-significant; **p < = 0.01. ICS anti-IgLON5 composite score

Fig. 4

Partial anti-IgLON5 disease composite scores at diagnosis versus last visit. Distribution of the partial anti-IgLON5 disease composite (ICS) scores at diagnosis and last visit in 39 patients with available follow-up information, classified according to clinical course (improved, stable, or worsened). ns non-significant; *p < = 0.05; **p < = 0.01. ICS anti-IgLON5 composite score

Fig. 5

Total anti-IgLON5 disease composite score and partial bulbar score at diagnosis and 2-year mortality. Receiver operating characteristic (ROC) curves of total ICS to discriminate 2-year mortality (A). Kaplan–Meier and comparison by log-rank test of the 2-year survival between patients with total ICS at diagnosis ≤ 20 and those with total ICS at diagnosis > 20. Tick marks indicate censored patients (B). ROC curves of partial bulbar ICS to discriminate 2-year mortality (C). Kaplan–Meyer and comparison by log-rank test of the 2-year survival between patients with bulbar ICS at diagnosis ≤ 3 and those with bulbar ICS at diagnosis > 3. Tick marks indicate censored patients (D). AUC area under the curve, ICS anti-IgLON5 composite score, ROC receiver operating characteristic