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J Neurol Neurosurg Psychiatry 82:740-746 doi:10.1136/jnnp.2010.235952
  • Research paper

Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study

  1. PARALS study group*
  1. 1ALS Centre, Department of Neuroscience, University of Torino, AOU San Giovanni Battista, Torino, Italy
  2. 2Neuroscience Institute of Torino (NIT), Torino, Italy
  3. 3ALS Centre, Department of Neurology, University of Eastern Piedmont ‘Amedeo Avogadro’, Novara, Italy
  4. 4ALS Centre, Department of Neurological Rehabilitation, Fondazione Salvatore Maugeri, IRCCS, Scientific Institute of Milano, Italy
  1. Correspondence to Professor A Chiò, Department of Neuroscience, University of Torino, AOU San Giovanni Battista, Via Cherasco 15, 10126 Torino, Italy; achio{at}usa.net
  1. Contributors AC, LM and GM had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Received 27 November 2010
  • Revised 27 January 2011
  • Accepted 3 February 2011
  • Published Online First 14 March 2011

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.

Footnotes

  • See Editorial commentary, p 711

  • * The other members of the PARALS study group are: R Mutani, MD (Department of Neuroscience, University of Torino, Advisory Committee); M Balma, MD (Department of Neuroscience, University of Torino, site investigator); S Cammarosano, MD (Department of Neuroscience, University of Torino, site investigator); A Canosa, MD (Department of Neuroscience, University of Torino, site investigator); S Gallo, MD (Department of Neuroscience, University of Torino, site investigator); A Ilardi, MD (Department of Neuroscience, University of Torino, site investigator); L Durelli, MD (Department of Neurology, University of Torino and AOU San Luigi Gonzaga, Orbassano, Advisory Committee); B Ferrero, MD (Department of Neurology, University of Torino and AOU San Luigi Gonzaga, Orbassano, site investigator); S De Mercanti, MD (Department of Neurology, University of Torino and AOU San Luigi Gonzaga, Orbassano, site investigator); A Mauro, MD (Department of Neurorehabilitation, University of Torino, Istituto Auxologico Italiano, IRCCS, Piancavallo, Advisory Committee); M Leone, MD (Department of Neurology, University of Piemonte Orientale ‘Amedeo Avogadro’, and AOU Maggiore, Novara, Advisory Committee); F Monaco, MD (Department of Neurology, University of Piemonte Orientale ‘Amedeo Avogadro’, and AOU Maggiore, Novara, Advisory Committee), N Nasuelli, MD (Department of Neurology, University of Piemonte Orientale Amedeo Avogadro, and AOU Maggiore, Novara, site investigator); L Sosso, MD (Department of Neurology, Ospedale Mauriziano, Torino, site investigator); M Gionco, MD (Department of Neurology, Ospedale Mauriziano, Torino, site investigator); A Marchet, MD (Department of Neurology, Ospedale Martini, Torino, site investigator); C Buffa, MD (Department of Neurology, Ospedale Maria Vittoria, Torino, Advisory Committee); R Cavallo, MD (Department of Neurology, Ospedale S Giovanni Bosco, Torino, site investigator) E Oddenino, MD (Department of Neurology, Ospedale Gradenigo, Torino, site investigator); C Geda, MD (Department of Neurology, Ospedale di Ivrea, and Department of Neurology, Ospedale di Chivasso, site investigator); C Doriguzzi Bozzo, MD (Department of Neurology, Ospedale di Pinerolo, site investigator), U Magliola, MD (Department of Neurology, Ospedale di Pinerolo, site investigator); D Papurello, MD (Department of Neurology, Ospedale di Ciriè, site investigator); P Santimaria, MD (Department of Neurology, Ospedale di Vercelli, site investigator); U Massazza, MD (Department of Neurology, Ospedale di Biella, site investigator); A Villani, MD (Department of Neurology, Ospedale di Domodossola, Advisory Committee) R Conti, MD (Department of Neurology, Ospedale di Domodossola, site investigator); F Pisano, MD (Fondazione Salvatore Maugeri, Clinica del Lavoro e della Riabilitazione, IRCCS, Scientific Institute of Veruno, site investigator); M Palermo, MD (Department of Neurology, Azienda Ospedaliera Santi Antonio e Biagio, Alessandria, site investigator); F Vergnano, MD (Department of Neurology, Ospedale di Casale Monferrato, site investigator); MT Penza, MD (Department of Neurology, Ospedale di Tortona, site investigator); N Di Vito, MD (Department of Neurology, Ospedale di Asti, site investigator); M Aguggia, MD (Department of Neurology, Ospedale di Asti, site investigator); I Pastore, MD (Department of Neurology, Azienda Ospedaliera S Croce e Carle, Cuneo, site investigator); P Meineri, MD (Department of Neurology, Azienda Ospedaliera S Croce e Carle, Cuneo, Advisory Committee); P Ghiglione MD (Department of Neurology, Ospedale di Savigliano, site investigator); D Seliak, MD (Department of Neurology, Ospedale di Savigliano, site investigator); C Cavestro, MD (Department of Neurology, Ospedale di Alba, site investigator); G Astegiano, MD (Department of Neurology, Ospedale di Alba, site investigator); G Corso, MD (Department of Neurology, Ospedale Regionale di Aosta, site investigator); E Bottacchi, MD Department of Neurology, Ospedale Regionale di Aosta, Advisory Committee).

  • Linked article 241513.

  • Funding This paper was supported in part by grants from Regione Piemonte (Ricerca Finalizzata 2002, grant No 12944; Ricerca Scientifica Applicata 2004, grant No A317) and Compagnia di San Paolo (grant No 2003.0078).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Comitato Etico Ospedale Molinette, Torino, Italy.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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