To assess the functional decline rate in different body regions according to their time of involvement during the course of amyotrophic lateral sclerosis (ALS).

Functional decline in ALS is likely not to be linear; the analysis of the interplay between the progression rate in different body regions and the time of involvement of each region could help in understanding the anatomical spreading of the pathological lesions.

The study included 1071 ALS patients resident in Piemonte and Valle d’Aosta, Italy, diagnosed between 2007 and 2014. The site of onset was in bulbar region in 384 patients (35.8%), in lower limbs in 364 patients (34.0%), in upper limbs in 304 (28.4%) patients and respiratory muscles in 19 (1.8%). For each patients we calculated the time interval between the symptom onset and the severe impairment of each body region, using medical history (date of onset, site of onset, gastrostomy date, non-invasive ventilation beginning date and tracheostomy date) and ALSFRS-r scores performed at each visit to assess the site-specific progression of the disease. Survival analyses and Cox Proportional Hazard Ratios adjusted for sex and age-classes were performed in order to assess progression profiles and risks.

The progression rate of the disease in the site of onset from the first symptom to severe impairment was significantly slower than that occurred if the same region was involved at later stages of disease (bulbar, upper limbs and lower limbs respectively, HR=0.54, HR=0.54, and HR=0.41, p<0.0001 for all comparisons). The same analysis for respiratory function was not significant (HR 0.91, p=0.690).

Regional progression rate varies according with the different phases of the disease. Our findings suggests that the progression of motor degeneration in ALS is exponential, with an acceleration of neuronal loss in intermediate and later stages of the disease, supporting a prion-like model of disease spreading.