Early reportsDoes cryptic gluten sensitivity play a part in neurological illness?
Abstract
Summary
Background Antigliadin antibodies are a marker of untreated coeliac disease but can also be found in individuals with normal small-bowel mucosa. Because neurological dysfunction is a known complication of coeliac disease we have investigated the frequency of antigliadin antibodies, as a measure of cryptic gluten sensitivity, and coeliac disease in neurological patients.
Methods Using ELISA, we estimated serum IgG and IgA antigliadin antibodies in 147 neurological patients who were divided into two groups. There were 53 patients with neurological dysfunction of unknown cause despite full investigation (25 ataxia, 20 peripheral neuropathy, 5 mononeuritis multiplex, 4 myopathy, 3 motor neuropathy, 2 myelopathy). The remaining 94 patients were found to have a specific neurological diagnosis (16 stroke, 12 multiple sclerosis, 10 Parkinson's disease, 56 other diagnoses) and formed the neurological control group. 50 healthy blood donors formed a third group.
Findings The proportions of individuals with positive titres for antigliadin antibodies in the three groups were 30/53, 5/94, and 6/50 respectively (57, 5, and 12%). The difference in proportion between group 1 and the combined control groups was 0·49 (95% Cl 0·35-0·63). Distal duodenal biopsies in 26 out of 30 antigliadin-positive patients from group 1 revealed histological evidence of coeliac disease in nine (35%), non-specific duodenitis in ten (38%), and no lesion in seven (26%) individuals.
Interpretation Our data suggest that gluten sensitivity is common in patients with neurological disease of unknown cause and may have aetiological significance.
References (12)
- C. Catassi et al.
Coeliac disease in the year 2000: exploring the iceberg
Lancet
(1994) - Wt Cooke
Neurologic manifestations of malabsorption
- E. Grodzinsky et al.
High prevalence of coeliac disease in healthy adults revealed by antigliadin antibodies
Ann Allergy
(1992) - Fd Lee et al.
Biopsy pathology of the small intestine
- Wt Cooke et al.
Neurological and psychiatric complications
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