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

Abstract

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.

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity

“…Of the total 35 male patients with NCWS included in the study, 25 complained of neurological symptoms. This finding agrees with the higher prevalence of male sex observed among the patients analyzed in a recent systematic review, which showed that the majority of gluten-related neurological disorders, proven by histological findings on nervous tissue biopsy or autopsy, affected men [21].…”

Diagnostic Criteria for Primary Autoimmune Cerebellar Ataxia—Guidelines from an International Task Force on Immune-Mediated Cerebellar Ataxias

“…Given that PACA, as proposed in this article, is a new entity and that it is likely to prove to be heterogeneous, it is difficult to put emphasis on any PM pathological findings based on what is available in the literature. Furthermore, most of the literature refers to well-characterized immune-mediated ataxias such as PCD and GA [ 15 , 16 ].…”

“Let Food Be Thy Medicine”: Gluten and Potential Role in Neurodegeneration

“…Not only gluten withdrawal, but probiotics, and some nutraceuticals, such as phyto and synthetic cannabinoids, were suggested to mitigate dietary gluten-induced neurodegeneration [ 20 ]. The clinical basis for gluten associated CNS diseases comes from the numerous neurological, psychiatric and behavioral manifestations, extensively describes in gluten induced conditions in Table 1 [ 16 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”