Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics.
We previously have described a group of patients with gluten sensitivity presenting with ataxia (gluten ataxia) and suggested that this disease entity may account for a large number of patients with sporadic idiopathic ataxia. We have therefore investigated the prevalence of gluten sensitivity amongst a large cohort of patients with sporadic and familial ataxia and looked at possible genetic predisposition to gluten sensitivity amongst these groups. Two hundred and twenty-four patients with various causes of ataxia from North Trent (59 familial and/or positive testing for spinocerebellar ataxias 1, 2, 3, 6 and 7, and Friedreich's ataxia, 132 sporadic idiopathic and 33 clinically probable cerebellar variant of multiple system atrophy MSA-C) and 44 patients with sporadic idiopathic ataxia from The Institute of Neurology, London, were screened for the presence of antigliadin antibodies. A total of 1200 volunteers were screened as normal controls. The prevalence of antigliadin antibodies in the familial group was eight out of 59 (14%), 54 out of 132 (41%) in the sporadic idiopathic group, five out of 33 (15%) in the MSA-C group and 149 out of 1200 (12%) in the normal controls. The prevalence in the sporadic idiopathic group from London was 14 out of 44 (32%). The difference in prevalence between the idiopathic sporadic groups and the other groups was highly significant (P < 0.0001 and P < 0.003, respectively). The clinical characteristics of 68 patients with gluten ataxia were as follows: the mean age at onset of the ataxia was 48 years (range 14-81 years) with a mean duration of the ataxia of 9.7 years (range 1-40 years). Ocular signs were observed in 84% and dysarthria in 66%. Upper limb ataxia was evident in 75%, lower limb ataxia in 90% and gait ataxia in 100% of patients. Gastrointestinal symptoms were present in only 13%. MRI revealed atrophy of the cerebellum in 79% and white matter hyperintensities in 19%. Forty-five percent of patients had neurophysiological evidence of a sensorimotor axonal neuropathy. Gluten-sensitive enteropathy was found in 24%. HLA DQ2 was present in 72% of patients. Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia. Antigliadin antibody testing is essential at first presentation of patients with sporadic ataxia.
Hadjivassiliou
Marios
M
Department of Neurology, The Royal Hallamshire Hospital, Sheffield, UK. m.hadjivassiliou@sheffield.ac.uk
Grünewald
Richard
R
Sharrack
Basil
B
Sanders
David
D
Lobo
Alan
A
Williamson
Clare
C
Woodroofe
Nicola
N
Wood
Nicholas
N
Davies-Jones
Aelwyn
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis; D001259:Ataxia / Q000150:complications* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002446:Celiac Disease / Q000150:complications* / Q000276:immunology / Q000473:pathology; D002524:Cerebellar Ataxia / Q000150:complications / Q000276:immunology / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D005260:Female; D005621:Friedreich Ataxia / Q000150:complications / Q000276:immunology / Q000473:pathology; D020234:Gait Ataxia / Q000150:complications / Q000276:immunology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005903:Gliadin / Q000276:immunology; D006683:HLA-DQ Antigens / Q000032:analysis; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015995:Prevalence
D000906:Antibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D005903:Gliadin