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Published on: November 26, 2018
Prognostic Determinants of Presentation and Outcome in Anti-IgLON5 Disease
Lidia Sabater1,2, Mar Guasp1,3, Raquel Ruiz García4
1Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-CaixaResearch Institute, Barcelona, Spain.
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.
Results:
We included 78 patients (median age 66 years, 55% male). Higher serum NfL levels correlated with clinical severity at diagnosis, as measured with the mRS (r = 0.438; p = 0.002) and ICS (r = 0.30; p = 0.029). Patients with the HLA-DRB1*10:01∼DQB1*05:01 haplotype more frequently presented with the bulbar or sleep phenotypes (24/41; 58%) compared with those without the haplotype (4/28; 14%; p = <0.001). Sixty-six patients received immunotherapy, and 14 (21%) showed clinical improvement at the last follow-up. In the multivariate Cox regression model, the neuromuscular phenotype was the only independent predictor of good outcome (mRS: 0-3; HR: 10.8; 95% CI 2.48-47.1; p = 0.002). Among the 30 patients who died (42%), the strongest independent predictor of mortality was the bulbar phenotype (HR: 2.59; 95% CI 1.08-6.21; p = 0.033), while serum NfL levels showed a significant but limited association (HR: 1.02; 95% CI 1.00-1.04; p = 0.02).
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.
