title: Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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%.
  
  
  
  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.
authors.affiliation: Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hadjivassiliou
authors.affiliation: Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
authors.forename: J
authors.initials: J
authors.lastname: Martindale
authors.affiliation: Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: P
authors.initials: P
authors.lastname: Shanmugarajah
authors.affiliation: Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Grünewald
authors.affiliation: Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Sarrigiannis
authors.affiliation: Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
authors.forename: N
authors.initials: N
authors.lastname: Beauchamp
authors.affiliation: Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
authors.forename: K
authors.initials: K
authors.lastname: Garrard
authors.affiliation: Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
authors.forename: R
authors.initials: R
authors.lastname: Warburton
authors.affiliation: Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Sanders
authors.affiliation: Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: D
authors.initials: D
authors.lastname: Friend
authors.affiliation: Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: S
authors.initials: S
authors.lastname: Duty
authors.affiliation: Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Department of Neuroradiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: N
authors.initials: N
authors.lastname: Hoggard
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D003937:Diagnosis, Differential; D004739:England; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D033183:Interdisciplinary Communication; D000070516:Intersectoral Collaboration; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D055815:Young Adult