Neurology of Celiac Disease
September 1, 2002
Abstract & Commentary
Source: Tengah DS, et al. Neurological complications of celiac disease. Postgrad Med J. 2002;78:393-398.
Best recognized as a chronic diarrheal illness with bloating and progressive weight loss, celiac disease has a definite association with a number of conditions including dermatitis herpetiformis, IgA deficiency, IgA nephropathy, Sjogren’s syndrome, autoimmune thyroid disease, Type 1 diabetes, rheumatoid arthritis, and Down’s syndrome. Gastrointestinal carcinoma or lymphoma occurs in up to 15% of refractory or untreated cases. Less commonly associated are several neurological disorders that may occur in up to 10% of patients.
Among 620 patients with celiac disease, 189 (30%) had a neurologic condition, but any causal relationship remained uncertain. Depression (11.5%), epilepsy (4.0%), and migraine (3.2%) were most common, followed by carpal tunnel syndrome and stroke (2.4% each). Spinocerebellar ataxia has been reported in celiac disease but was not seen in this group and an association between celiac disease, antigliadin, antireticulin, or antiendomysial antibodies and cerebellar disorders remains doubtful. Epilepsy is associated with one variant of celiac disease, curiously combined with bilateral occipital calcifications, the latter only in Italians. Folate deficiency may play a role in this syndrome. Peripheral neuropathy was seen in 0.5% (3/620) but does not always respond to a gluten-free diet. Similarly, no definite association exists with multiple sclerosis, Parkinson’s disease, or dementia.
Nutritional deficiency may play a role in the neurologic complications of celiac disease but, again, a causal association remains weak. B6 (pyridoxine) coupled with a gluten-free diet improved depression after 3 years (Scand J Gastroenterol. 1983;18:299-304) and vitamin E replacement reportedly improved ataxia associated with celiac disease (Lancet. 1996;347:446). Deficiency of B12, biopterin, or carnitine and causality for any neurologic condition in celiac disease remains to be proven. Altered autoimmunity and gluten neurotoxicity are etiologic hypotheses in search of evidence.
Commentary
Celiac disease affects 1 in 300 persons of European descent in North America but is rare in blacks and Asians. HLA-DQ2 is expressed in more than 95% of patients with this gluten enteropathy. The disease is induced, in susceptible persons, by food-grain antigens in wheat, barley, and rye. Ingested antigen, toxic amino acid sequences in a-gliadin, induces an inappropriate T-cell mediated immune response when HLA-DQ2 presents the antigen to stimulate intestinal mucosal T cells. Adherence to a gluten-free diet prevents all the disease complications, and early diagnosis is important. Serologic screening for antigliadin antibodies is 90% sensitive but nonspecific, whereas sensitivity and specificity for positive IgA antiendomysial antibodies approaches 98% and 100%, respectively. Small bowel biopsy remains the gold standard. Antibody positivity disappears after 6 months of initiating a gluten-free diet and is useful to monitor compliance. —Michael Rubin
Dr. Rubin, Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.
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