Celiac Disease - NIH Consensus Development Program - National ...

Neurological/Psychological Presentation of Celiac Disease:Ataxia, Depression, Neuropathy, Seizures, and AutismKhalafalla O. Bushara, M.D.Celiac disease (CD) has long been associated with a wide spectrum of neurological andpsychiatric disorders including cerebellar ataxia, peripheral neuropathy, myositis, epilepsy,dementia, psychosis, and depression. (1–4) Earlier reports have mainly documented the involvementof the nervous system as a complication of prediagnosed CD. However, more recent studiesemphasized that neurological syndromes may be the presenting extra-intestinal manifestation ofgluten sensitivity with or without intestinal pathology. (5,6) These include migraine,encephalopathy, chorea, brain stem dysfunction, myelopathy, mononeuritis multiplex, GuillianBarre-like syndrome, and neuropathy with positive antiganglioside antibodies. (7–10) It has furtherbeen suggested that gluten sensitivity (as evidenced by high antigliadin antibodies) is a commoncause of neurological syndromes (notably cerebellar ataxia) of otherwise unknown etiology. (11)However, further studies showed high prevalence of gluten sensitivity in geneticneurodegenerative disorders such as hereditary spinocerebellar ataxia and Huntington’sdisease. (12,13) It remains unclear whether gluten sensitivity contributes to the pathogenesis of thesedisorders or whether it represents an epiphenomenon.The mechanisms of nervous system pathology in association with gluten sensitivity iscurrently unclear. Nervous system involvement is unlikely to be due to malabsorption-relateddeficiencies. (14) Although few studies suggested immunological mechanisms, most studiesshowed no evidence for a direct immune-mediated insult to the nervous system. (1,11,15)Studies of gluten-free diet in patients with gluten sensitivity and neurological syndromesshowed variable results. In few patients, gluten-free diet was reported to result in improvementof neurological deficits while in the majority of patients reported, gluten-free diet had nosignificant effect. (1,11) Gluten-free diet trials have also been inconclusive in autism andschizophrenia; two diseases in which sensitivity to dietary gluten has been implicated.Further studies are clearly needed to assess the efficacy of gluten-free diet and to addressthe underlying mechanisms of nervous system pathology in gluten sensitivity.References1. Cooke W, Smith W. Neurological disorders associated with adult coeliac disease. Brain.1966; 89(4):683–722.2. Collin P, Pirttila T, Nurmikko T, Somer H, Erila T, Keyrilainen O. Celiac disease, brainatrophy, and dementia. Neurology. 1991;41(3):372–375.3. Finelli PF, McEntee WJ, Ambler M, Kestenbaum D. Adult celiac disease presenting ascerebellar syndrome. Neurology. 1980;30(3):245–249.77