Exploring the diagnosis delay and ALS functional impairment at diagnosis as relevant criteria for clinical trial enrolment

Objectives were: i) to describe the phenotypic heterogeneity of incident amyotrophic lateral sclerosis (ALS) patients diagnosed in 2012 in French ALS centres; ii) to look at the associations between ALSFRS-R score and ALSFRS-R slope (Delta FS) at time of diagnosis with diagnosis delay, Delta LS phenotypes and Airlie House diagnosis criteria (AHDC); iii) to describe the rate of progression on FS, according to diagnosis delay. Methods: Incident ALS cases diagnosed in French ALS centres were included. The rate of progression was evaluated as follows: Delta FS=(48 - ALSFRS-R at time of diagnosis)/duration from onset to diagnosis (months). Fast and slow progressors were defined by FS >1 and <0.5, respectively. Results: At time of diagnosis, 476 patients were classified into eight phenotypes: bulbar (33.0%), spinal lumbar (28.2%), spinal cervical (23.1%), flail leg (4.4%), ALS/FTD (4.2%), possible flail arm (4.0%), respiratory (2.1%), dropped-head (1.0%). Median FS (n=358/476) was 1.0 [0.5-2.0]. FS was associated with AHDC (p=0.009), but not with clinical phenotype (p=0.902). Stratification on diagnosis delay (<12 months or 18 months) allowed to differentiate fast progressors from slow progressors. Conclusion: At time of inclusion in therapeutic trial closed to diagnosis, FS or diagnosis delay may discriminate the rate of progression.