Gluten Ataxia: Fact or Fiction?
Gluten Ataxia: Fact or Fiction?
Abstract & Commentary
Source: Hadjivassiliou M, et al. Gluten ataxia in perspective: Epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003;126:685-691.
This population report investigated the prevalence of gluten sensitivity amongst a large cohort of patients with both sporadic and familial ataxia. Hadjivassiliou and associates studied 224 patients with various causes of ataxia from North Trent in England. Fifty-nine of the patients had known genetic causes, including either spino cerebellar ataxias or Friedreich’s ataxia. A total of 132 of the patients had sporadic idiopathic cerebellar degeneration, and 33 had a clinically probable cerebellar variant of multiple system atrophy. An additional 44 patients with sporadic idiopathic ataxia from the Institute of Neurology in 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 normal controls was 12%. In the patients with familial ataxia, it was 14%. It was 41% in the sporadic idiopathic group and 15% in the multiple system atrophy group. In the patients from London, antigliadin antibodies were present in 14 out of 44. The clinical onset in patients with presumed gluten ataxia occurred at a mean age of 48 years, and the mean duration of ataxia was 9.7 years. Gait ataxia occurred in all patients. The patients had ocular signs in 84% and dysarthria in 66%; upper limb ataxia was evident in 75% and lower limb ataxia in 90%. Gastrointestinal symptoms were present only in 13%. The MRI scans showed atrophy of the cerebellum in approximately 80%. Nerve conduction studies showed a sensorimotor axonal neuropathy in 45% of the patients. Gluten-sensitive enteropathy was present in 24% of the patients, and the HLA DQ2 genotype was present in 72% of patients. Hadjivassiliou et al concluded that gluten ataxia is the most single common cause of sporadic idiopathic ataxia.
Commentary
This paper contributes to an increasing body of evidence that suggests that gluten sensitivity may contribute to a number of neurologic syndromes. Gluten sensitivity is most commonly recognized as a chronic diarrheal illness with bloating and progressive weight loss, known as coeliac disease. It is also associated with a number of other conditions, including dermatitis herpetiformis, IgA deficiency, IgA nephropathy, Sjogren syndrome, autoimmune thyroid disease, type 1 diabetes, rheumatoid arthritis, and Down’s syndrome.
Most prior studies of gluten-associated ataxia have been small with limited numbers of patients. Two studies were published in 2001. In 1 American study, the prevalence of antigliadin antibody positivity in both sporadic and familial ataxias was 27% and 37%, respectively.
In a larger study from Germany, the prevalence of gluten ataxia among sporadic idiopathic ataxias was found to be 12 out of 104 (11.5%).1 In this population, the prevalence of IgG antigliadin antibodies amongst normal controls was 5%. Of the 12 patients, 2 had typical changes of gluten sensitive enteropathy, and 5 had an elevated interepithelial lymphocyte count. Five patients had no evidence of any abnormal biopsied gastrointestinal abnormalities. In this study from Germany, the link with HLA DQ2 hepatype was 70%. The symptoms were noted not to be related to low blood concentrations of vitamins, particularly vitamin E. Previously, ataxia associated with coeliac disease had been suggested as a consequence of vitamin E deficiency, and some patients responded to vitamin E supplementation. This is plausible, since patients with mutations in the alpha-tocopherol binding protein are known to have low vitamin E levels and to develop progressive cerebellar ataxia. In the German study, the clinical syndrome was dominated by progressive cerebellar ataxia of stance and gait, as well as dysarthria and limb ataxia. The symptoms, however, were relatively mild. One feature that has been found both in the present study as well as in the German one is frequent loss of posterior column sensation, as well as bladder dysfunction and reduced ankle reflexes. In the German study, a prominent axonal neuropathy with reduced amplitudes and abnormal evoked potentials affected about 50% of the patients. All patients showed cerebellar atrophy on MRI. CSF studies were normal.
A critical issue is the nature of antibodies and screening for sporadic ataxia in patients. Some patients with putative gluten ataxia have IgG antigliadin antibodies, whereas most commonly IgA antibodies are found during routine screening. More specific antibodies are those against antiendomysium, which correlate well with coeliac disease but lack sensitivity and specificity when used in screening patients with ataxia. In the present study, the IgG antigliadin antibody was the best marker of gluten sensitivity. The clinical findings of ataxia in these groups of patients do not allow one to separate these patients from other patients with sporadic ataxia. There is a paucity of neuropathologic reports from patients with gluten ataxia. Only 2 patients have been studied who showed some perivascular cuffing with CD4 and CD8 cells, as well as patchy loss of Purkinje cells.
The finding of a strong association with certain HLA and inflammatory changes makes it likely that these patients are suffering from an immune-mediated cerebellar degeneration. This may be similar to the antibodies that occur in paraneoplastic cerebellar degeneration, such as the anti-Yo antibody. The major difficulty with identifying gluten ataxia is the high prevalence of antigliadin antibodies in the normal population.
It is unclear whether a gluten-free diet has efficacy in these patients. Most of them identified and have had disease of long duration, making it too late to intervene. It has been reported that resolution of symptoms with a gluten-free diet might be in patients diagnosed early. It is worthwhile to screen antigliadin antibodies in patients with sporadic ataxia at their initial presentation. If positive, consider a gluten-free diet since at present, there are no other effective treatments for sporadic cerebellar ataxias. At present, the entity of gluten ataxia warrants further investigation to establish its pathophysiology, more reliable screening tools, and the efficacy of gluten-free diets. — M. Flint Beal
Dr. Beal is Professor and Chairman; Department of Neurology; Cornell University Medical College New York, NY.
References
1. Burk K, et al. Brain. 2001;124:1013-1019.
This population report investigated the prevalence of gluten sensitivity amongst a large cohort of patients with both sporadic and familial ataxia.Subscribe Now for Access
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