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Research paper
Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients
  1. M Hadjivassiliou1,
  2. J Martindale2,
  3. P Shanmugarajah1,
  4. R A Grünewald1,
  5. P G Sarrigiannis1,
  6. N Beauchamp2,
  7. K Garrard2,
  8. R Warburton2,
  9. D S Sanders3,
  10. D Friend1,
  11. S Duty1,
  12. J Taylor1,
  13. N Hoggard4
  1. 1Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
  2. 2Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK
  3. 3Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
  4. 4Department of Neuroradiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
  1. Correspondence to Dr M Hadjivassiliou, m.hadjivassiliou{at}


Background Cerebellar ataxias are the result of diverse disease processes that can be genetic or acquired. Establishing a diagnosis requires a methodical approach with expert clinical evaluation and investigations. We describe the causes of ataxia in 1500 patients with cerebellar ataxia.

Methods All patients were referred to the Sheffield Ataxia Centre, UK, and underwent extensive investigations, including, where appropriate genetic testing using next-generation sequencing (NGS). Patients were followed up on a 6-monthly basis for reassessment and further investigations if indicated.

Results A total of 1500 patients were assessed over 20 years. Twenty per cent had a family history, the remaining having sporadic ataxia. The commonest cause of sporadic ataxia was gluten ataxia (25%). A genetic cause was identified in 156 (13%) of sporadic cases with other causes being alcohol excess (12%) and cerebellar variant of multiple system atrophy (11%). Using NGS, positive results were obtained in 32% of 146 patients tested. The commonest ataxia identified was EA2. A genetic diagnosis was achieved in 57% of all familial ataxias. The commonest genetic ataxias were Friedreich's ataxia (22%), SCA6 (14%), EA2 (13%), SPG7 (10%) and mitochondrial disease (10%). The diagnostic yield following attendance at the Sheffield Ataxia Centre was 63%.

Conclusions Immune-mediated ataxias are common. Advances in genetic testing have significantly improved the diagnostic yield of patients suspected of having a genetic ataxia. Making a diagnosis of the cause of ataxia is essential due to potential therapeutic interventions for immune and some genetic ataxias.

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  • Contributors MH runs the Sheffield Ataxia Centre. All patients were assessed by MH, PS, DF, SD and JT. JM, NB, RW and KG have been responsible for the genetic testing and putting together the NGS panel of ataxia tests. DSS was involved with the assessment of patients with gluten ataxia. PS was involved in the assessment of patients with myoclonic ataxia. RAG was involved with the assessment of some of the patients and the critical review of the manuscript. NH was responsible for all the imaging. MH produced the first draft of the paper. All authors read, provided input and approved the final manuscript.

  • Competing interests None declared.

  • Ethics approval This type of report does not require ethical approval according to the Regional Ethics Committee.

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

  • Data sharing statement The list of the ataxia NCG panel tests.