Phenotypic heterogeneity of ALS: a population-based study

Adriano Chiò (1) , Andrea Calvo (1) , Cristina Moglia (1) , Letizia Mazzini (2) , Gabriele Mora (3)

1 UNITO - Università degli studi di Torino = University of Turin
2 University of Novara
3 Fondazione Maugeri

Background. Different ALS phenotypes have been recognized, marked by a varying involvement of spinal and bulbar upper and lower motor neurons. However, the differential characteristics of these phenotypes are still largely unknown. Objective. To define epidemiology and outcome of amyotrophic lateral sclerosis (ALS) phenotypes in a population-based setting. Methods. All ALS cases incident in two Italian regions have been prospectively collected from 1995 through 2004 in an epidemiological register. Cases have been classified according to established ALS phenotypes: classic, bulbar, flail arm, flail leg, pyramidal, respiratory, pure lower motor neuron (PLMN) and pure upper motor neuron (PUMN). Results. ALS phenotype were determined in 1332 out of the 1351 incident patients (98.6%). Classic and bulbar phenotypes had similar mean annual incidence rates. Gender-specific incidence rates showed a male preponderance in respiratory, flail arm, classic and PLMN phenotypes; in all other phenotypes, men and women had similar incidence rates. Age at onset was significantly lower in pyramidal, PLMN and PUMN phenotypes and higher in the bulbar phenotype. The best outcomes were observed in PUMN, pyramidal, PLMN and flail arm phenotypes and the worst in respiratory and bulbar phenotypes. Conclusions. Our epidemiological findings suggest that ALS phenotypes carry distinctive and easily distinguishable clinical and prognostic characteristics, strongly related to a complex interplay between gender and age. The categorization of ALS patients according to more homogenous clinical groups is relevant to identify biological markers for ALS and should be considered for the design of clinical trials.

Mots clés: ALS

Adriano Chiò, Andrea Calvo, Cristina Moglia, Letizia Mazzini, Gabriele Mora. Phenotypic heterogeneity of ALS: a population-based study. Journal of Neurology, Neurosurgery and Psychiatry, 2011, 82 (7), pp.740. ⟨10.1136/jnnp.2010.235952⟩. ⟨hal-00623289⟩