Predictors in late-stage amyotrophic lateral sclerosis.

Abstract

Aim: Prognostic factors in amyotrophic lateral sclerosis (ALS) are defined by clinical features and progression rate at first observation or over follow-up. The prognostic factors associated with late-stage disease are uncertain. We sought to identify factors predicting survival in advanced ALS. Methods: We analyzed data collected from patients followed at our clinic who progressed to late-stage ALS, defined as ALS Functional Rating Scale Revised (ALSFRS-R) ≤ 24 (group A), patients followed for at least 6 months thereafter constituted group B. We studied demographic and clinical variables, including phenotype, sex, age, diagnostic delay (disease duration at diagnosis), noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), early (from diagnosis to ALSFRS-R ≤ 24) and thereafter late functional progression rates (ΔFS), and survival. Multivariable analysis with Cox regression was performed to ascertain predictive factors for survival in late-stage. Results: Group A included 704 patients and group B 260 patients. For group A, predictors associated with shorter survival were bulbar-onset (p = 0.03), and ΔFS at diagnosis and until late stage (p < 0.001). For group B, predictors associated with shorter survival were older age (p = 0.005), bulbar-onset (p = 0.02), shorter diagnostic delay (p < 0.001), ΔFS until late stage (p < 0.02), and late stage ΔFS (p < 0.001), but not ΔFS at diagnosis. Discussion: Similar to the general ALS population, survival in late-stage patients is predicted by age, region of onset, and diagnostic delay. Although ΔFS in later stages is prognostic, the initial ΔFS at diagnosis is not. Therefore, continuous monitoring of functional decline remains crucial for patients already in advanced stages.