title: Variability and prognostic relevance of different phenotypes in amyotrophic lateral sclerosis - data from a population-based registry.
abstract: OBJECTIVE
  The clinical spectrum of amyotrophic lateral sclerosis (ALS) is characterized by a considerable variation. Different phenotypes have been described by previous studies. We assessed clinical variability and prognostic relevance of these phenotypes in a prospective, population-based cohort of ALS patients in Rhineland-Palatinate, Germany.
  
  
  METHODS
  Incident ALS cases, diagnosed between October 2009 and September 2012, were prospectively enrolled and classified according to established ALS phenotype classification (bulbar, classic, flail arm, flail leg, pyramidal, respiratory). Survival probability was described using Kaplan-Meier method. Moreover, the influence of an additional frontotemporal dementia (FTD) was analysed.
  
  
  RESULTS
  Phenotypes of all 200 patients were determined. Bulbar and classic phenotypes accounted for 75% of all cases. Deterioration of functional impairment during disease progression was lowest in flail leg and pyramidal variants, and most pronounced in bulbar and classic phenotypes. A poor survival prognosis was observed for bulbar, classic or respiratory phenotypes. Patients with an additional FTD showed an even worse outcome.
  
  
  CONCLUSIONS
  Results suggest that ALS is a heterogeneous disease, as ALS phenotypes differ in disease progression and survival time. Patients classified as suffering from bulbar, classic and respiratory ALS, as well as those with an additional FTD, show a marked reduction of survival time.
authors.affiliation: Department of Neurology, Klinikum der Stadt Ludwigshafen, Germany. Electronic address: Wolfj@klilu.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Wolf
authors.affiliation: Institute of Public Health, Medical Faculty, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Safer
authors.affiliation: Department of Neurology, Katholisches Klinikum, Brüderhaus, Koblenz, Germany.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Wöhrle
authors.affiliation: Department of Neurology, Klinikum der Stadt Ludwigshafen, Germany.
authors.forename: Frederick
authors.initials: F
authors.lastname: Palm
authors.affiliation: Department of Neurology, Universitätsmedizin, Mainz, Germany.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: Nix
authors.affiliation: Department of Neurology, Krankenhaus der Barmherzigen Brüder, Trier, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Maschke
authors.affiliation: Department of Neurology, Klinikum der Stadt Ludwigshafen, Germany.
authors.forename: Armin J
authors.initials: AJ
authors.lastname: Grau
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification* / Q000453:epidemiology* / Q000503:physiopathology; D018672:Community Health Planning; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012042:Registries; D016019:Survival Analysis
keywords: Amyotrophic lateral sclerosis; Frontotemporal dementia; Phenotype; Population register; Prognosis; Survival