Prognostication in Amyotrophic Lateral Sclerosis: A Narrative Review of Pre-Diagnosis and Functional Outcomes

Amyotrophic Lateral Sclerosis (ALS) is a very heterogeneous disease, yet some of the most common questions received by physicians in the ALS clinic are “how much time do I have?” and “what can I expect to happen next?” This line of inquiry is not strictly limited to patients; clinicians also need an idea of prognosis to appropriately plan for treatment decisions and prepare the patient and caregiver for future care needs. This narrative review synthesizes current evidence on prognostic indicators in ALS, organized across three temporal phases: factors preceding diagnosis, factors present at diagnosis, and factors emerging after diagnosis. Pre-diagnosis predictors include age at onset, sex, socioeconomic status, genetic background, premorbid Body Mass Index (BMI) and nutritional status, and comorbid disease. At diagnosis, clinical phenotype and site of onset, diagnostic delay, baseline Amyotrophic Lateral Sclerosis Functional Rating Score-Revised (ALSFRS-R) and forced vital capacity, cognitive involvement, fluid biomarkers, and electrophysiologic measures carry prognostic weight. Post-diagnosis, the trajectory is refined by the rate of ALSFRS-R decline, serial respiratory measures, and weight loss, and is actively modified by clinical interventions including noninvasive ventilation, enteral nutrition, disease-modifying therapy, and multidisciplinary care. Notably, quality of life does not track with physical decline, consistent with the disability paradox described in other severe neurological conditions. For neurorehabilitation, these indicators support a shift from reactive to anticipatory practice: timing equipment provision, communication support, respiratory intervention, and goals-of-care discussions to the predicted trajectory rather than to established deficit. Refinement of prognostic models may also improve stratification in ALS clinical trials.