Glycine receptor antibodies and coeliac disease-related neurological dysfunction

AbstractGluten sensitivity can manifest with a spectrum of neurological dysfunction including ataxia, encephalopathy and neuropathy with or without associated coeliac disease (CD). Gluten sensitivity can also present with central nervous system (CNS) hyperexcitability and cortical myoclonus which is often accompanied with refractory CD. CNS hyperexcitability can also be associated with Glutamic Acid Decarboxylase (GAD) antibodies or much less commonly with Glycine Receptor Antibodies (GlyR-Abs) but the direct pathogenic roles of these antibodies remain debatable. We have previously reported a link between gluten sensitivity and anti-GAD associated ataxia which improves with the adoption of gluten-free diet. It is unclear if a similar link exists between gluten driven CNS hyperexcitability and the presence of GlyR-Abs. We report two cases of CD presenting with CNS hyperexcitability and associated GlyR-Abs. Apart from ataxia and cortical myoclonus, one patient had refractory CD and died from enteropathy-associated T-cell lymphoma. The other patient not only improved with strict gluten-free diet but also showed serological elimination of circulating GlyR-Abs. We conclude that there is an interaction between gluten sensitivity and GlyR-Abs-associated CNS hyperexcitability and in such patients gluten-free diet is an important therapeutic intervention. The elimination of GlyR-Abs by the adoption of gluten free diet suggests that these antibodies may represent an epiphenomenon rather than being directly implicated in the pathogenesis.

Download Full-text

A Gluten Free Diet in the Management of Epilepsy in People with Coeliac Disease or Gluten Sensitivity

Gastrointestinal Disorders ◽

10.3390/gidisord2030026 ◽

2020 ◽

Vol 2 (3) ◽

pp. 281-299

Author(s):

Zoë Gilbey ◽

Justine Bold

Keyword(s):

Coeliac Disease ◽

Small Sample ◽

Gluten Free Diet ◽

Gluten Sensitivity ◽

Gluten Free ◽

Exclusion Criteria ◽

Search Terms ◽

Small Sample Sizes ◽

Eeg Pattern

The aim of this review was to assess the effects of a gluten free diet (GFD) in the management of epilepsy in people with coeliac disease (CD) or gluten sensitivity (GS). A systematic approach was used to undertake a literature review. Five electronic databases (PubMed; Scopus; Google Scholar; Cochrane Epilepsy Group specialised register; Cochrane Register of Controlled Trails (CENTRAL) via the Cochrane Register of Online Trials) were searched using predetermined relevant search terms. In total, 668 articles were identified. Duplicates were removed and predefined inclusion and exclusion criteria were applied, and a PRISMA flow chart was produced. Data was extracted using Covidence software. Twelve studies on Epilepsy and CD involving a total of 70 participants were selected for analysis; narrative synthesis was used owing to the small sample sizes in the selected studies. None of the 12 studies meeting inclusion criteria investigated gluten sensitivity and epilepsy. All the included studies support a link between epilepsy and CD. GFD was effective in 44 out of 70 participants across the studies in terms of a reduction of seizures, reduction of antiepileptic drugs (AEDs) or normalisation of EEG pattern. A total of 44 participants showed a reduction in seizures (across eight studies) and complete cessation of seizures was reported in 22 participants. In general, the earlier the GFD is implemented after the onset of seizures, the better the likelihood of the GFD being successful in supporting control of seizures. Mechanisms linking gluten with epilepsy are not fully understood; possible hypotheses include gluten mediated toxicity, immune-induced cortical damage and malabsorption. Evidence suggests the effectiveness of a GFD in supporting the management of epilepsy in patients with CD, although the quality of evidence is low. There appears to be a growing number of neurologists who are prepared to advocate the use of a GFD. A multidisciplinary approaches and further research are recommended. It could be argued that when balancing potential treatments such as AEDs or surgery, a GFD has a low likelihood of harm.

Download Full-text

Stiff Person Syndrome and Gluten Sensitivity

Nutrients ◽

10.3390/nu13041373 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1373

Author(s):

Marios Hadjivassiliou ◽

Panagiotis Zis ◽

David S. Sanders ◽

Nigel Hoggard ◽

Ptolemaios G. Sarrigiannis

Keyword(s):

Autoimmune Diseases ◽

Axial Stiffness ◽

Acid Decarboxylase ◽

Gluten Sensitivity ◽

Stiff Person Syndrome ◽

Gluten Free ◽

Serological Evidence ◽

Gad Antibodies ◽

The Mean

Stiff person syndrome (SPS) is a rare autoimmune disease characterised by axial stiffness and episodic painful spasms. It is associated with additional autoimmune diseases and cerebellar ataxia. Most patients with SPS have high levels of glutamic acid decarboxylase (GAD) antibodies. The aetiology of SPS remains unclear but autoimmunity is thought to play a major part. We have previously demonstrated overlap between anti-GAD ataxia and gluten sensitivity. We have also demonstrated the beneficial effect of a gluten-free diet (GFD) in patients with anti-GAD ataxia. Here, we describe our experience in the management of 20 patients with SPS. The mean age at symptom onset was 52 years. Additional autoimmune diseases were seen in 15/20. Nineteen of the 20 patients had serological evidence of gluten sensitivity and 6 had coeliac disease. Fourteen of the 15 patients who had brain imaging had evidence of cerebellar involvement. Twelve patients improved on GFD and in seven GFD alone was the only treatment required long term. Twelve patients had immunosuppression but only three remained on such medication. Gluten sensitivity plays an important part in the pathogenesis of SPS and GFD is an effective therapeutic intervention.

Download Full-text

Food label usage and reported difficulty with following a gluten-free diet among individuals in the USA with coeliac disease and those with noncoeliac gluten sensitivity

Journal of Human Nutrition and Dietetics ◽

10.1111/jhn.12032 ◽

2013 ◽

Vol 26 (5) ◽

pp. 479-487 ◽

Cited By ~ 17

Author(s):

L. Verrill ◽

Y. Zhang ◽

R. Kane

Keyword(s):

Coeliac Disease ◽

Gluten Free Diet ◽

Gluten Sensitivity ◽

Gluten Free ◽

Food Label ◽

The Usa

Download Full-text

The rise and fall of gluten!

Proceedings of The Nutrition Society ◽

10.1017/s0029665115000038 ◽

2015 ◽

Vol 74 (3) ◽

pp. 221-226 ◽

Cited By ~ 8

Author(s):

Imran Aziz ◽

Federica Branchi ◽

David S. Sanders

Keyword(s):

Coeliac Disease ◽

Agricultural Production ◽

Clinical Symptoms ◽

Gluten Free Diet ◽

Gluten Sensitivity ◽

Gluten Free ◽

Western Asia ◽

Fertile Crescent ◽

Gluten Sensitive Enteropathy ◽

The Relationship

Mankind has existed for 2·5 million years but only in the last 10 000 years have we been exposed to wheat. Wheat was first cultivated in the Fertile Crescent (South Western Asia) with a farming expansion that lasted from about 9000BC to 4000BC. Thus it could be considered that wheat (and gluten) is a novel introduction to man's diet! Prior to 1939 the rationing system had already been devised. This led to an imperative to try to increase agricultural production. Thus it was agreed in 1941 that there was a need to establish a Nutrition Society. The very roots of the society were geared towards necessarily increasing the production of wheat. This goal was achieved and by the end of the 20th century, global wheat output had expanded 5-fold. Perhaps as a result the epidemiology of coeliac disease (CD) or gluten sensitive enteropathy has changed. CD is a state of heightened immunological responsiveness to ingested gluten in genetically susceptible individuals. CD now affects 1 % or more of all adults, for which the treatment is a strict lifelong gluten-free diet. However, there is a growing body of evidence to show that a far greater proportion of individuals without coeliac disease are taking a gluten-free diet of their own volition. This clinical entity has been termed non-coeliac gluten sensitivity (NCGS), although the condition is fraught with complexities due to overlap with other gluten-based constituents that can also trigger similar clinical symptoms. This review will explore the relationship between gluten, the rising prevalence of modern coeliac disease, and the new entity of NCGS along with its associated uncertainties.

Download Full-text

Pilot study on non-celiac gluten sensitivity: effects of Bifidobacterium longum ES1 co-administered with a gluten-free diet

Minerva Gastroenterologica e Dietologica ◽

10.23736/s1121-421x.20.02673-2 ◽

2020 ◽

Vol 66 (3) ◽

Author(s):

Francesco Di Pierro ◽

Francesca Bergomas ◽

Paolo Marraccini ◽

Maria R. Ingenito ◽

Lorena Ferrari ◽

...

Keyword(s):

Pilot Study ◽

Bifidobacterium Longum ◽

Gluten Free Diet ◽

Gluten Sensitivity ◽

Gluten Free

Download Full-text

Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet

Clinical Nutrition ◽

10.1016/j.clnu.2021.03.006 ◽

2021 ◽

Author(s):

Lorcan McGrogan ◽

Mary Mackinder ◽

Fiona Stefanowicz ◽

Maria Aroutiounova ◽

Anthony Catchpole ◽

...

Keyword(s):

Coeliac Disease ◽

Gluten Free Diet ◽

Gluten Free ◽

Micronutrient Deficiencies

Download Full-text

Wait-and-See Approach or Gluten-Free Diet Administration—The Rational Management of Potential Coeliac Disease

Nutrients ◽

10.3390/nu13030947 ◽

2021 ◽

Vol 13 (3) ◽

pp. 947

Author(s):

Anna Szaflarska-Popławska

Keyword(s):

Small Intestine ◽

Celiac Disease ◽

Prognostic Factors ◽

Coeliac Disease ◽

Gluten Free Diet ◽

Gluten Free ◽

Individual Basis ◽

Therapeutic Decisions ◽

Rational Management ◽

Wait And See

Potential celiac disease (PCD) is a heterogeneous disease; only some patients develop full celiac disease (CD), characterised by advanced atrophic changes in the small intestine. Few accurate prognostic factors exist for the progression of PCD; therefore, therapeutic decisions should be made on an individual basis in each case. Patients with clinical gastroenterological or parenteral symptoms often benefit from a gluten-free diet, and those left on a diet containing gluten should receive clinical, serological and histopathological supervision.

Download Full-text

The impact of symptoms on quality of life before and after diagnosis of coeliac disease: the results from a Polish population survey and comparison with the results from the United Kingdom

BMC Gastroenterology ◽

10.1186/s12876-021-01673-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Emilia Majsiak ◽

Magdalena Choina ◽

Dominik Golicki ◽

Alastair M. Gray ◽

Bożena Cukrowska

Keyword(s):

Quality Of Life ◽

United Kingdom ◽

Coeliac Disease ◽

Gluten Free Diet ◽

Gluten Free ◽

The United Kingdom ◽

Before And After ◽

The Mean ◽

The Uk

Abstract Background Coeliac disease (CD) is characterised by diverse clinical symptoms, which may cause diagnostic problems and reduce the patients’ quality of life. A study conducted in the United Kingdom (UK) revealed that the mean time between the onset of coeliac symptoms and being diagnosed was above 13 years. This study aimed to analyse the diagnostic process of CD in Poland and evaluate the quality of life of patients before and after CD diagnosis. In addition, results were compared to the results of the original study conducted in the UK. Methods The study included 2500 members of the Polish Coeliac Society. The patients were asked to complete a questionnaire containing questions on socio-demographic factors, clinical aspects and quality of life, using the EQ-5D questionnaire. Questionnaires received from 796 respondents were included in the final analysis. Results The most common symptoms reported by respondents were bloating (75%), abdominal pain (72%), chronic fatigue (63%) and anaemia (58%). Anaemia was the most persistent symptom, with mean duration prior to CD diagnosis of 9.2 years, whereas diarrhoea was observed for the shortest period (4.7 years). The mean duration of any symptom before CD diagnosis was 7.3 years, compared to 13.2 years in the UK. CD diagnosis and the introduction of a gluten-free diet substantially improved the quality of life in each of the five EQ-5D-5L health dimensions: pain and discomfort, anxiety and depression, usual activities, self-care and mobility (p < 0.001), the EQ-Index by 0.149 (SD 0.23) and the EQ-VAS by 30.4 (SD 28.3) points. Conclusions Duration of symptoms prior to the diagnosis of CD in Poland, although shorter than in the UK, was long with an average of 7.3 years from first CD symptoms. Faster CD diagnosis after the onset of symptoms in Polish respondents may be related to a higher percentage of children in the Polish sample. Introduction of a gluten-free diet improves coeliac patients’ quality of life. These results suggest that doctors should be made more aware of CD and its symptoms across all age groups.

Download Full-text