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The Neuropathology of Gluten-Related Neurological Disorders: A Systematic Review

1
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AG&M research institute, 1081HZ Amsterdam, The Netherlands
2
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, 1081HZ Amsterdam, The Netherlands
3
Medical School, University of Cyprus, 2408 Nicosia, Cyprus
4
Amsterdam UMC, Vrije Universiteit, Department of Pathology, Amsterdam Neuroscience, 1081HZ Amsterdam, The Netherlands
5
Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF South Yorkshire, UK
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(3), 822; https://doi.org/10.3390/nu12030822
Received: 17 February 2020 / Revised: 10 March 2020 / Accepted: 18 March 2020 / Published: 20 March 2020
(This article belongs to the Special Issue Gluten-Related Disorders: Time to Move from Gut to Brain)
Gluten-related neurological disorders (GRND) represent a spectrum of neurological manifestations that are triggered by gluten. In coeliac disease, a T-cell mediated enteropathy is triggered by gluten in genetically predisposed individuals. The underlying pathological mechanism of the neurological dysfunction is not yet clear. The aim of this review is to collate existing neuropathological findings in GRND as a means of aiding the understanding of the pathophysiology. A systematic search of the Pubmed Database yielded 188 articles, of which 32 were included, containing 98 eligible cases with a description of pathological findings in GRND. In gluten ataxia, loss of Purkinje cells, atrophy, gliosis and astrocytosis were apparent, as well as diffuse lymphocytic infiltration and perivascular cuffing with lymphocytes. In patients with large-fiber neuropathy, nerve biopsies revealed axonopathy, loss of myelinated fibers and focal and perivascular infiltration by inflammatory cells. Inflammatory infiltrate was also observed in muscle in myopathy and in cerebrum of patients with encephalopathy and patients with epilepsy. Such changes were not seen in skin biopsies from patients with small fiber neuropathies. The findings from this systematic review suggest an immune mediated pathogenesis for GRND. Future research should focus on the characterization of the inflammatory cell infiltrates and identifying target epitopes. View Full-Text
Keywords: gluten; coeliac disease; neurological disorders; gliadin; ataxia; neuropathy; myopathy; encephalopathy gluten; coeliac disease; neurological disorders; gliadin; ataxia; neuropathy; myopathy; encephalopathy
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Rouvroye, M.D.; Zis, P.; Van Dam, A.-M.; Rozemuller, A.J.; Bouma, G.; Hadjivassiliou, M. The Neuropathology of Gluten-Related Neurological Disorders: A Systematic Review. Nutrients 2020, 12, 822.

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