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The Neuropathology of Gluten-Related Neurological Disorders: A Systematic Review.
Rouvroye, MD, Zis, P, Van Dam, AM, Rozemuller, AJM, Bouma, G, Hadjivassiliou, M
Nutrients. 2020;12(3)
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Coeliac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. A wide range of extraintestinal manifestations has been attributed to CD, changing the classic perception of a disease limited to the intestine, to a multisystem disorder. The aim of this study was to analyse the published neuropathology of confirmed cases of gluten-related neurological dysfunction to aid our understanding of the pathogenesis. CD can therefore manifest with dental problems, consequences of malabsorption, skin and neurological disorders. This study is a systematic review of thirty-two neurological disorder focused studies. Results show that: - the neuropathological findings in gluten-related neurological disorders are widespread and not limited to the cerebellum. - the pathology is immune mediated and not related to vitamin or trace elements deficiencies. - the pathophysiology of neurological damage in the context of gluten sensitivity has an immune mediated basis. - more gluten-related neurological disorders affected men (57%), which was even higher in the ataxia group (76%). - transglutaminase 6 antibodies might be helpful in the diagnostic workup of gluten-related neurological disorders. Authors conclude that the current evidence is suggestive of both humoral and cell-mediated immunological responses. Further research is required to investigate the underlying neuropathological mechanism by characterisation of the inflammatory cell infiltrate and identification of target epitopes.
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.
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Psychiatric Manifestations of Coeliac Disease, a Systematic Review and Meta-Analysis.
Clappison, E, Hadjivassiliou, M, Zis, P
Nutrients. 2020;(1)
Abstract
BACKGROUND Coeliac disease (CD) is increasingly prevalent and is associated with both gastrointestinal (GI) and extra-intestinal manifestations. Psychiatric disorders are amongst extra-intestinal manifestations proposed. The relationship between CD and such psychiatric disorders is not well recognised or understood. AIM: The aim of this systematic review and meta-analysis was to provide a greater understanding of the existing evidence and theories surrounding psychiatric manifestations of CD. METHODOLOGY An online literature search using PubMed was conducted, the prevalence data for both CD and psychiatric disorders was extracted from eligible articles. Meta analyses on odds ratios were also performed. RESULTS A total of 37 articles were included in this review. A significant increase in risk was detected for autistic spectrum disorder (OR 1.53, 95% CI 1.24-1.88, p < 0.0001), attention deficit hyperactivity disorder (OR 1.39, 95% CI 1.18-1.63, p < 0.0001), depression (OR 2.17, 95% CI 2.17-11.15, p < 0.0001), anxiety (OR 6.03, 95% CI 2.22-16.35, p < 0.0001), and eating disorders (OR 1.62, 95% CI 1.37-1.91, p < 0.00001) amongst the CD population compared to healthy controls. No significant differences were found for bipolar disorder (OR 2.35, 95% CI 2.29-19.21, p = 0.43) or schizophrenia (OR 0.46, 95% CI 0.02-10.18, p = 0.62). CONCLUSION CD is associated with an increased risk of depression, anxiety, eating disorders as well as ASD and ADHD. More research is required to investigate specific biological explanations as well as any effect of gluten free diet.
3.
Headache Associated with Coeliac Disease: A Systematic Review and Meta-Analysis.
Zis, P, Julian, T, Hadjivassiliou, M
Nutrients. 2018;10(10)
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Coeliac disease (CD) is the best-recognised gluten-related disorder (GRD), and it is characterized by a small bowel enteropathy occurring in genetically susceptible individuals whilst exposed to the protein gliadin. The aim of this study was to systematically review the current literature in order to establish the relationship between headache and CD. This study is a systematic review of 40 articles, studying a total of 42,388 individuals with either headache or GRD. Results show that: - There is an increased prevalence of headache amongst patients with CD. - There is an increased prevalence of CD amongst patients with idiopathic headache. - Headaches associated with CD are mainly migraines. - Gluten-free diet is a very effective treatment for headaches associated with CD. Authors conclude that further studies on the prevalence of gluten sensitivity in patients with idiopathic headache are needed, including further research on the pathogenetic mechanisms.
Abstract
OBJECTIVE The aim of this systematic review was to explore the relationship between coeliac disease (CD) and headache. The objectives were to establish the prevalence of each entity amongst the other, to explore the role of gluten free diet (GFD), and to describe the imaging findings in those affected by headaches associated with CD. METHODOLOGY A systematic computer-based literature search was conducted on the PubMed database. Information regarding study type, population size, the age group included, prevalence of CD amongst those with headache and vice versa, imaging results, the nature of headache, and response to GFD. RESULTS In total, 40 articles published between 1987 and 2017 qualified for inclusion in this review. The mean pooled prevalence of headache amongst those with CD was 26% (95% CI 19.5⁻33.9%) in adult populations and 18.3% (95% CI 10.4⁻30.2%) in paediatric populations. The headaches are most often migraine-like. In children with idiopathic headache, the prevalence of CD is 2.4% (95% CI 1.5⁻3.7%), whereas data for adult populations is presently unavailable. Brain imaging can be normal, although, cerebral calcifications on CT, white matter abnormalities on MRI and deranged regional cerebral blood flow on SPECT can be present. GFD appears to be an effective management for headache in the context of CD, leading to total resolution of headaches in up to 75% of patients. CONCLUSIONS There is an increased prevalence of CD amongst idiopathic headache and vice versa. Therefore, patients with headache of unknown origin should be screened for CD, as such patients may symptomatically benefit from a GFD.