Journal of Neurology

, Volume 259, Issue 5, pp 869–878 | Cite as

New findings in the ataxia of Charlevoix–Saguenay

  • José GazullaEmail author
  • Isabel Benavente
  • Ana Carmen Vela
  • Miguel Angel Marín
  • Luis Emilio Pablo
  • Alessandra Tessa
  • María Rosario Barrena
  • Filippo Maria Santorelli
  • Claudia Nesti
  • Pedro Modrego
  • María Tintoré
  • José Berciano
Original Communication


The aim of the study was to enhance our understanding of the pathogenesis of the ataxia of Charlevoix–Saguenay, based on the findings presented herein. Five patients with a molecular diagnosis of this disease underwent clinical, radiological, ophthalmologic and electrophysiological examinations. Five novel mutations, which included nonsense and missense variants, were identified, with these resulting in milder phenotypes. In addition to the usual manifestations, a straight dorsal spine was found in every case, and imaging techniques showed loss of the dorsal kyphosis. Cranial MRI demonstrated hypointense linear striations at the pons. Tensor diffusion MRI sequences revealed that these striations corresponded with hyperplastic pontocerebellar fibres, and tractographic sequences showed interrupted pyramidal tracts at the pons. Ocular coherence tomography demonstrated abnormal thickness of the nerve fibre layer. Electrophysiological studies showed nerve conduction abnormalities compatible with a dysmyelinating neuropathy, with signs of chronic denervation in distal muscles. The authors suggest that the hyperplastic pontocerebellar fibres compress the pyramidal tracts at the pons, and that the amount of retinal fibres traversing the optic discs is enlarged. These facts point to the contribution of an abnormal developmental mechanism in the ataxia of Charlevoix–Saguenay. Accordingly, spasticity would be mediated by compression of the pyramidal tracts, neuromuscular symptoms by secondary axonal degeneration superimposed on the peripheral myelinopathy, while the cause of the progressive ataxia remains speculative. The distinctive aspect of the dorsal spine could be of help in the clinical diagnosis.


ARSACS Peripheral and central myelinopathy Pontocerebellar fibre hyperplasia Retinal nerve fibre hyperplasia Straight dorsal spine 



The authors wish to thank Drs. Jorge Artal, José Luis Capablo, Manuel Gracia-Naya and Pilar Larrodé for referral of patients; Dr. Elena García, for help with the ophthalmological part of this article, and Mr. Juan Luis Fuentes, for the ophthalmologic photographs. We also thank Ms. Stephanie Lyon, for linguistic assessment. This work is dedicated to the memory of Paloma Agüeras (1958–2009).This work was supported by grants of the Italian Ministry of Health (Ricerca Corrente, RC-FSM-02/2010) and of the European Union for EUROSPA (E-RARE grant IT0807), to FMS; and by a grant of the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas and Fondo de Investigaciones Sanitarias (PI07/132E to JB).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • José Gazulla
    • 1
    • 9
    Email author
  • Isabel Benavente
    • 2
  • Ana Carmen Vela
    • 3
  • Miguel Angel Marín
    • 3
  • Luis Emilio Pablo
    • 4
  • Alessandra Tessa
    • 5
  • María Rosario Barrena
    • 6
  • Filippo Maria Santorelli
    • 5
  • Claudia Nesti
    • 5
  • Pedro Modrego
    • 1
  • María Tintoré
    • 7
  • José Berciano
    • 8
  1. 1.Service of NeurologyHospital Universitario Miguel ServetZaragozaSpain
  2. 2.Service of Clinical NeurophysiologyHospital San JorgeHuescaSpain
  3. 3.Service of RadiologyHospital Universitario Miguel ServetZaragozaSpain
  4. 4.Service of OphthalmologyHospital Universitario Miguel ServetZaragozaSpain
  5. 5.Molecular Medicine and NeurogeneticsIRCCS Fondazione Stella Maris. Vial del TirrenoPisaItaly
  6. 6.Service of RadiologyClínica MontecanalZaragozaSpain
  7. 7.Nucleic Acid Chemistry GroupChemistry and Molecular Pharmacology Programme, Institute for Research in Biomedicine of BarcelonaBarcelonaSpain
  8. 8.Department of NeurologyUniversity Hospital Marqués de Valdecilla, University of Cantabria and Centro de Investigación Biomédica en Red de Enfermedades NeurodegenerativasSantanderSpain
  9. 9.ZaragozaSpain

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