Understanding Long-Term Survival in ALS: A Cohort Study on Subject Characteristics and Prognostic Factors

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with variable clinical progression. While median survival is 2–4 years, 5–15% of individuals survive for longer. Methods: We conducted a retrospective, observational study using a population-based ALS register in Lombardy, Italy, to identify the clinical characteristics of long-term ALS survivors (≥10 years). Incident cases included in two periods (1998–2002 and 2008–2012) were considered. Results: A total of 828 ALS cases were included. Median survival for the entire cohort was 2.2 years (IQR 1.1–4.4). However, long-term survival was observed in 7% of individuals at 10 years, and 3% at 15 years. Long-survivors had a median survival of 13.4 years, significantly longer than the 1.9 years of non-long-survivors (IQR 1.0–3.6). Long-survivors were younger at disease onset and diagnosis, had longer diagnostic delay, and were more likely to have had a spinal onset. The cohort also showed a higher proportion of males among long-term survivors (75% vs. 59%). No significant difference in survival was observed between the two examined periods. Conclusions: Our findings suggest that long-term ALS survival is likely influenced by a complex interplay of clinical, genetic, and environmental factors, along with the intrinsic rate of motor neuron degeneration.