Phenotypic heterogeneity of amyotrophic lateral sclerosis: A population based study

Adriano Chiò, Andrea Calvo, Cristina Moglia, Letizia Mazzini, Gabriele Mora, R. Mutani, M. Balma, S. Cammarosano, A. Canosa, S. Gallo, A. Ilardi, L. Durelli, B. Ferrero, S. De Mercanti, A. Mauro, M. Leone, F. Monaco, N. Nasuelli, L. Sosso, M. GioncoA. Marchet, C. Buffa, R. Cavallo, E. Oddenino, C. Geda, C. Doriguzzi Bozzo, U. Magliola, D. Papurello, P. Santimaria, U. Massazza, A. Villani, R. Conti, F. Pisano, M. Palermo, F. Vergnano, M. T. Penza, N. Di Vito, M. Aguggia, I. Pastore, P. Meineri, P. Ghiglione, D. Seliak, C. Cavestro, G. Astegiano, G. Corso, E. Bottacchi

Research output: Contribution to journalArticle

202 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)740-746
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume82
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Amyotrophic Lateral Sclerosis
Phenotype
Motor Neurons
Population
Arm
Incidence
Age of Onset
Leg
Epidemiology
Biomarkers
Clinical Trials

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery

Cite this

Phenotypic heterogeneity of amyotrophic lateral sclerosis : A population based study. / Chiò, Adriano; Calvo, Andrea; Moglia, Cristina; Mazzini, Letizia; Mora, Gabriele; Mutani, R.; Balma, M.; Cammarosano, S.; Canosa, A.; Gallo, S.; Ilardi, A.; Durelli, L.; Ferrero, B.; De Mercanti, S.; Mauro, A.; Leone, M.; Monaco, F.; Nasuelli, N.; Sosso, L.; Gionco, M.; Marchet, A.; Buffa, C.; Cavallo, R.; Oddenino, E.; Geda, C.; Doriguzzi Bozzo, C.; Magliola, U.; Papurello, D.; Santimaria, P.; Massazza, U.; Villani, A.; Conti, R.; Pisano, F.; Palermo, M.; Vergnano, F.; Penza, M. T.; Di Vito, N.; Aguggia, M.; Pastore, I.; Meineri, P.; Ghiglione, P.; Seliak, D.; Cavestro, C.; Astegiano, G.; Corso, G.; Bottacchi, E.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 82, No. 7, 07.2011, p. 740-746.

Research output: Contribution to journalArticle

Chiò, A, Calvo, A, Moglia, C, Mazzini, L, Mora, G, Mutani, R, Balma, M, Cammarosano, S, Canosa, A, Gallo, S, Ilardi, A, Durelli, L, Ferrero, B, De Mercanti, S, Mauro, A, Leone, M, Monaco, F, Nasuelli, N, Sosso, L, Gionco, M, Marchet, A, Buffa, C, Cavallo, R, Oddenino, E, Geda, C, Doriguzzi Bozzo, C, Magliola, U, Papurello, D, Santimaria, P, Massazza, U, Villani, A, Conti, R, Pisano, F, Palermo, M, Vergnano, F, Penza, MT, Di Vito, N, Aguggia, M, Pastore, I, Meineri, P, Ghiglione, P, Seliak, D, Cavestro, C, Astegiano, G, Corso, G & Bottacchi, E 2011, 'Phenotypic heterogeneity of amyotrophic lateral sclerosis: A population based study', Journal of Neurology, Neurosurgery and Psychiatry, vol. 82, no. 7, pp. 740-746. https://doi.org/10.1136/jnnp.2010.235952
Chiò, Adriano ; Calvo, Andrea ; Moglia, Cristina ; Mazzini, Letizia ; Mora, Gabriele ; Mutani, R. ; Balma, M. ; Cammarosano, S. ; Canosa, A. ; Gallo, S. ; Ilardi, A. ; Durelli, L. ; Ferrero, B. ; De Mercanti, S. ; Mauro, A. ; Leone, M. ; Monaco, F. ; Nasuelli, N. ; Sosso, L. ; Gionco, M. ; Marchet, A. ; Buffa, C. ; Cavallo, R. ; Oddenino, E. ; Geda, C. ; Doriguzzi Bozzo, C. ; Magliola, U. ; Papurello, D. ; Santimaria, P. ; Massazza, U. ; Villani, A. ; Conti, R. ; Pisano, F. ; Palermo, M. ; Vergnano, F. ; Penza, M. T. ; Di Vito, N. ; Aguggia, M. ; Pastore, I. ; Meineri, P. ; Ghiglione, P. ; Seliak, D. ; Cavestro, C. ; Astegiano, G. ; Corso, G. ; Bottacchi, E. / Phenotypic heterogeneity of amyotrophic lateral sclerosis : A population based study. In: Journal of Neurology, Neurosurgery and Psychiatry. 2011 ; Vol. 82, No. 7. pp. 740-746.
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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.",
author = "Adriano Chi{\`o} and Andrea Calvo and Cristina Moglia and Letizia Mazzini and Gabriele Mora and R. Mutani and M. Balma and S. Cammarosano and A. Canosa and S. Gallo and A. Ilardi and L. Durelli and B. Ferrero and {De Mercanti}, S. and A. Mauro and M. Leone and F. Monaco and N. Nasuelli and L. Sosso and M. Gionco and A. Marchet and C. Buffa and R. Cavallo and E. Oddenino and C. Geda and {Doriguzzi Bozzo}, C. and U. Magliola and D. Papurello and P. Santimaria and U. Massazza and A. Villani and R. Conti and F. Pisano and M. Palermo and F. Vergnano and Penza, {M. T.} and {Di Vito}, N. and M. Aguggia and I. Pastore and P. Meineri and P. Ghiglione and D. Seliak and C. Cavestro and G. Astegiano and G. Corso and E. Bottacchi",
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T1 - Phenotypic heterogeneity of amyotrophic lateral sclerosis

T2 - A population based study

AU - Chiò, Adriano

AU - Calvo, Andrea

AU - Moglia, Cristina

AU - Mazzini, Letizia

AU - Mora, Gabriele

AU - Mutani, R.

AU - Balma, M.

AU - Cammarosano, S.

AU - Canosa, A.

AU - Gallo, S.

AU - Ilardi, A.

AU - Durelli, L.

AU - Ferrero, B.

AU - De Mercanti, S.

AU - Mauro, A.

AU - Leone, M.

AU - Monaco, F.

AU - Nasuelli, N.

AU - Sosso, L.

AU - Gionco, M.

AU - Marchet, A.

AU - Buffa, C.

AU - Cavallo, R.

AU - Oddenino, E.

AU - Geda, C.

AU - Doriguzzi Bozzo, C.

AU - Magliola, U.

AU - Papurello, D.

AU - Santimaria, P.

AU - Massazza, U.

AU - Villani, A.

AU - Conti, R.

AU - Pisano, F.

AU - Palermo, M.

AU - Vergnano, F.

AU - Penza, M. T.

AU - Di Vito, N.

AU - Aguggia, M.

AU - Pastore, I.

AU - Meineri, P.

AU - Ghiglione, P.

AU - Seliak, D.

AU - Cavestro, C.

AU - Astegiano, G.

AU - Corso, G.

AU - Bottacchi, E.

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

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