The spread pattern and survival in sporadic ALS

Abstract

A misfolding pathology has been suggested to spread from onset site to neighbouring areas in a prion-like manner. We examined the pattern of spread and direction of clinical lower motor neuron involvement over time until the appearance of respiratory symptom. A total of 150 patients with sporadic ALS underwent follow-up until respiratory symptoms. Symptom appearances were determined using ALSFRS-R. The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Time from onset to spread to the second site, suggesting propagation speed, is a strong predictor for survival. In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. In most of ALS patients, the spread appears to have a contiguous pattern rather than a random pattern of progression, although the spread to non-contiguous regions was observed in 13%. This finding supports the notion that the ALS pathology gradually spreads to adjacent regions in a longitudinal manner. Although precise mechanism of symptom spread in ALS is not understood, knowledge about the pattern of onset and the anatomical direction of spread may provide valuable prognostic insights.