title: Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study.
abstract: BACKGROUND
  Different amyotrophic lateral sclerosis (ALS) phenotypes have been recognised, 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 the epidemiology and outcome of ALS phenotypes in a population based setting.
  
  
  METHODS
  All ALS cases incident in two Italian regions were prospectively collected from 1995 to 2004 in an epidemiological register. Cases were 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 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 categorisation of ALS patients according to more homogenous clinical groups is relevant in identifying biological markers for ALS and should be considered for the design of clinical trials.
authors.affiliation: Department of Neuroscience, University of Torino, AOU San Giovanni Battista, Via Cherasco 15, 10126 Torino, Italy. achio@usa.net
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000453:epidemiology / Q000503:physiopathology*; D018450:Disease Progression; D004401:Dysarthria / Q000209:etiology; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000294:innervation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000453:epidemiology / Q000209:etiology; D009046:Motor Neurons / Q000502:physiology; D018908:Muscle Weakness / Q000209:etiology; D010641:Phenotype; D012042:Registries; D015656:Respiratory Mechanics; D012737:Sex Factors; D013534:Survival; D014139:Tracheostomy; D034941:Upper Extremity / Q000294:innervation / Q000503:physiopathology