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Journal of Neurology

, Volume 264, Issue 6, pp 1118–1126 | Cite as

Deciphering the causes of sporadic late-onset cerebellar ataxias: a prospective study with implications for diagnostic work

  • O. Gebus
  • S. Montaut
  • B. Monga
  • T. Wirth
  • C. Cheraud
  • C. Alves Do Rego
  • I. Zinchenko
  • G. Carré
  • M. Hamdaoui
  • G. Hautecloque
  • L. Nguyen-Them
  • B. Lannes
  • J. B. Chanson
  • O. Lagha-Boukbiza
  • M. C. Fleury
  • D. Devys
  • G. Nicolas
  • G. Rudolf
  • M. Bereau
  • M. Mallaret
  • M. Renaud
  • C. Acquaviva
  • M. Koenig
  • M. Koob
  • S. Kremer
  • I. J. Namer
  • C. Cazeneuve
  • A. Echaniz-Laguna
  • C. Tranchant
  • Mathieu AnheimEmail author
Original Communication

Abstract

The management of sporadic late-onset cerebellar ataxias represents a very heterogeneous group of patients and remains a challenge for neurologist in clinical practice. We aimed at describing the different causes of sporadic late-onset cerebellar ataxias that were diagnosed following standardized, exhaustive investigations and the population characteristics according to the aetiologies as well as at evaluating the relevance of these investigations. All patients consecutively referred to our centre due to sporadic, progressive cerebellar ataxia occurring after 40 years of age were included in the prospective, observational study. 80 patients were included over a 2 year period. A diagnosis was established for 52 patients (65%) corresponding to 18 distinct causes, the most frequent being cerebellar variant of multiple system atrophy (n = 29). The second most frequent cause was inherited diseases (including spinocerebellar ataxias, late-onset Friedreich’s disease, SLC20A2 mutations, FXTAS, MELAS, and other mitochondrial diseases) (n = 9), followed by immune-mediated or other acquired causes. The group of patient without diagnosis showed a slower worsening of ataxia (p < 0.05) than patients with multiple system atrophy. Patients with later age at onset experienced faster progression of ataxia (p = 0.001) and more frequently parkinsonism (p < 0.05) than patients with earlier onset. Brain MRI, DaT scan, genetic analysis and to some extent muscle biopsy, thoracic-abdominal-pelvic tomodensitometry, and cerebrospinal fluid analysis were the most relevant investigations to explore sporadic late-onset cerebellar ataxia. Sporadic late-onset cerebellar ataxias should be exhaustively investigated to identify the underlying causes that are numerous, including inherited causes, but dominated by multiple system atrophy.

Keywords

Cerebellar ataxia Multiple system atrophy Genetics Dat-scan Imaging 

Notes

Compliance with ethical standards

Conflicts of interest

The authors have no conflict of interest to declare except MA and MM. MA declares honoraria and travel grants from Actelion Pharmaceuticals, UCB, Teva, and AbbVie. MM declares congress fee registration from LFB Biomedicaments.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • O. Gebus
    • 1
  • S. Montaut
    • 1
  • B. Monga
    • 2
  • T. Wirth
    • 1
  • C. Cheraud
    • 1
  • C. Alves Do Rego
    • 1
  • I. Zinchenko
    • 1
  • G. Carré
    • 1
  • M. Hamdaoui
    • 1
  • G. Hautecloque
    • 1
  • L. Nguyen-Them
    • 3
  • B. Lannes
    • 4
  • J. B. Chanson
    • 1
    • 5
  • O. Lagha-Boukbiza
    • 1
    • 5
  • M. C. Fleury
    • 1
    • 5
  • D. Devys
    • 6
  • G. Nicolas
    • 7
    • 8
    • 9
  • G. Rudolf
    • 1
    • 5
    • 10
  • M. Bereau
    • 11
  • M. Mallaret
    • 12
  • M. Renaud
    • 1
    • 5
  • C. Acquaviva
    • 13
  • M. Koenig
    • 14
  • M. Koob
    • 15
  • S. Kremer
    • 15
  • I. J. Namer
    • 16
  • C. Cazeneuve
    • 17
  • A. Echaniz-Laguna
    • 1
    • 5
  • C. Tranchant
    • 1
    • 5
    • 10
  • Mathieu Anheim
    • 1
    • 5
    • 10
    Email author
  1. 1.Service de NeurologieHôpitaux Universitaires de Strasbourg, Hôpital de HautepierreStrasbourgFrance
  2. 2.Faculté de MédecineUniversité de Lubumbashi, Faculté de Médecine et Ecole de Santé Publique, Département de Santé PubliqueLubumbashiDemocratic Republic of the Congo
  3. 3.Service de Neurologie 2Hôpital Pitié-Salpêtrière, AP-HPParisFrance
  4. 4.Service d’Anatomo-pathologieHôpitaux Universitaires de Strasbourg, Hôpital de HautepierreStrasbourgFrance
  5. 5.Fédération de Médecine Translationnelle de Strasbourg (FMTS)Université de StrasbourgStrasbourgFrance
  6. 6.Laboratoire de Diagnostic GénétiqueHôpitaux Universitaire de Strasbourg, Nouvel Hôpital CivilStrasbourgFrance
  7. 7.Inserm U1079, University of Rouen, IRIB, Normandy UniversityRouenFrance
  8. 8.Normandy Centre for Genomic Medicine and Personalized MedicineRouenFrance
  9. 9.Department of Genetics and CNR-MAJRouen University HospitalRouenFrance
  10. 10.Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)INSERM-U964/CNRS-UMR7104/Université de StrasbourgIllkirchFrance
  11. 11.Service de Neurologie 1Centre Hospitalier Régional Universitaire de BesançonBesançonFrance
  12. 12.Service de NeurologieCentre Hospitalier Universitaire de GrenobleGrenobleFrance
  13. 13.Service Maladie Héréditaire du MétabolismeCentre de Biologie et Pathologie Est, CHULyonFrance
  14. 14.Laboratoire de Génétique MoléculaireEA7402, Institut Universitaire de Recherche Clinique, CHU et Université de MontpellierMontpellierFrance
  15. 15.Service d’imagerie 2-CHU de Strasbourg, Université de Strasbourg, Laboratoire I CubeStrasbourgFrance
  16. 16.Service de Médecine NucléaireHôpitaux Universitaires de Strasbourg, Hôpital de HautepierreStrasbourgFrance
  17. 17.Département de GénétiqueHôpitaux Universitaires Pitié-Salpêtrière Charles Foix, AP-HPParisFrance

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