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Ciaccio EJ, Lee AR, Lebovits J, Wolf RL, Lewis SK, Ciacci C, Green PHR. Psychological, Psychiatric, and Organic Brain Manifestations of Celiac Disease. Dig Dis 2024; 42:419-444. [PMID: 38861947 DOI: 10.1159/000534219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 09/07/2023] [Indexed: 06/13/2024]
Abstract
INTRODUCTION Celiac disease is an autoimmune condition that affects approximately 1% of the population worldwide. Although its main impact often concerns the small intestine, resulting in villous atrophy and nutrient malabsorption, it can also cause systemic manifestations, particularly when undiagnosed or left untreated. METHOD Attention is directed to the possible psychological, psychiatric, and organic brain manifestations of celiac disease. Specific topics related to the influence and risk of such manifestations with respect to celiac disease are defined and discussed. Overall, eighteen main topics are considered, sifted from over 500 references. RESULTS The most often studied topics were found to be the effect on quality of life, organic brain dysfunction and ataxia, epilepsy, Down syndrome, generalized psychological disorders, eating dysfunction, depression, and schizophrenia. For most every topic, although many studies report a connection to celiac disease, there are often one or more contrary studies and opinions. A bibliographic analysis of the cited articles was also done. There has been a sharp increase in interest in this research since 1990. Recently published articles tend to receive more referencing, up to as many as 15 citations per year, suggesting an increasing impact of the topics. The number of manuscript pages per article has also tended to increase, up to as many as 12 pages. The impact factor of the publishing journal has remained level over the years. CONCLUSION This compendium may be useful in developing a consensus regarding psychological, psychiatric, and organic brain manifestations that can occur in celiac disease and for determining the best direction for ongoing research focus.
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Affiliation(s)
- Edward J Ciaccio
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Anne R Lee
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Jessica Lebovits
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Randi L Wolf
- Teachers College, Columbia University, New York, New York, USA
| | - Suzanne K Lewis
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Carolina Ciacci
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, Università degli Studi di Salerno, Salerno, Italy
| | - Peter H R Green
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
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Zhu H, Wang W, Li Y. The interplay between microbiota and brain-gut axis in epilepsy treatment. Front Pharmacol 2024; 15:1276551. [PMID: 38344171 PMCID: PMC10853364 DOI: 10.3389/fphar.2024.1276551] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 01/12/2024] [Indexed: 08/12/2024] Open
Abstract
The brain-gut axis plays a vital role in connecting the cognitive and emotional centers of the brain with the intricate workings of the intestines. An imbalance in the microbiota-mediated brain-gut axis extends far beyond conditions like Irritable Bowel Syndrome (IBS) and obesity, playing a critical role in the development and progression of various neurological disorders, including epilepsy, depression, Alzheimer's disease (AD), and Parkinson's disease (PD). Epilepsy, a brain disorder characterized by unprovoked seizures, affects approximately 50 million people worldwide. Accumulating evidence suggests that rebuilding the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and ketogenic diets (KD) can benefit drug-resistant epilepsy. The disturbances in the gut microbiota could contribute to the toxic side effects of antiepileptic drugs and the development of drug resistance in epilepsy patients. These findings imply the potential impact of the gut microbiota on epilepsy and suggest that interventions targeting the microbiota, such as the KD, hold promise for managing and treating epilepsy. However, the full extent of the importance of microbiota in epilepsy treatment is not yet fully understood, and many aspects of this field remain unclear. Therefore, this article aims to provide an overview of the clinical and animal evidence supporting the regulatory role of gut microbiota in epilepsy, and of potential pathways within the brain-gut axis that may be influenced by the gut microbiota in epilepsy. Furthermore, we will discuss the recent advancements in epilepsy treatment, including the KD, fecal microbiota transplantation, and antiseizure drugs, all from the perspective of the gut microbiota.
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Affiliation(s)
- Hanxiao Zhu
- Department of Neurology, The First Affiliated Hospital of Dali University, Dali, China
- Clinical Medical School, Dali University, Dali, China
| | - Wei Wang
- Neurobiology Laboratory, China Agricultural University, Beijing, China
| | - Yun Li
- Department of Neurology, The First Affiliated Hospital of Dali University, Dali, China
- Clinical Medical School, Dali University, Dali, China
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Elwenspoek MM, Thom H, Sheppard AL, Keeney E, O'Donnell R, Jackson J, Roadevin C, Dawson S, Lane D, Stubbs J, Everitt H, Watson JC, Hay AD, Gillett P, Robins G, Jones HE, Mallett S, Whiting PF. Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling. Health Technol Assess 2022; 26:1-310. [PMID: 36321689 PMCID: PMC9638887 DOI: 10.3310/zuce8371] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma. OBJECTIVES The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care. DESIGN (1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives. DATA SOURCES For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used. REVIEW METHODS For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed. RESULTS People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents (n = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research. LIMITATIONS The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet. CONCLUSIONS Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia). FUTURE WORK Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed. STUDY REGISTRATION This study is registered as PROSPERO CRD42019115506 and CRD42020170766. FUNDING This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Martha Mc Elwenspoek
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Howard Thom
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Athena L Sheppard
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Edna Keeney
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Rachel O'Donnell
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Joni Jackson
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Cristina Roadevin
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Sarah Dawson
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | | | | | - Hazel Everitt
- Primary Care Research Centre, Population Sciences and Medical Education, University of Southampton, Southampton, UK
| | - Jessica C Watson
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Alastair D Hay
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Peter Gillett
- Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, UK
| | - Gerry Robins
- Department of Gastroenterology, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Hayley E Jones
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Sue Mallett
- Centre for Medical Imaging, University College London, London, UK
| | - Penny F Whiting
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Al-Beltagi M, Saeed NK. Epilepsy and the gut: Perpetrator or victim? World J Gastrointest Pathophysiol 2022; 13:143-156. [PMID: 36187601 PMCID: PMC9516455 DOI: 10.4291/wjgp.v13.i5.143] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/08/2022] [Accepted: 08/25/2022] [Indexed: 02/07/2023] Open
Abstract
The brain and the gut are linked together with a complex, bi-path link known as the gut-brain axis through the central and enteric nervous systems. So, the brain directly affects and controls the gut through various neurocrine and endocrine processes, and the gut impacts the brain via different mechanisms. Epilepsy is a central nervous system (CNS) disorder with abnormal brain activity, causing repeated seizures due to a transient excessive or synchronous alteration in the brain’s electrical activity. Due to the strong relationship between the enteric and the CNS, gastrointestinal dysfunction may increase the risk of epilepsy. Meanwhile, about 2.5% of patients with epilepsy were misdiagnosed as having gastrointestinal disorders, especially in children below the age of one year. Gut dysbiosis also has a significant role in epileptogenesis. Epilepsy, in turn, affects the gastrointestinal tract in different forms, such as abdominal aura, epilepsy with abdominal pain, and the adverse effects of medications on the gut and the gut microbiota. Epilepsy with abdominal pain, a type of temporal lobe epilepsy, is an uncommon cause of abdominal pain. Epilepsy also can present with postictal states with gastrointestinal manifestations such as postictal hypersalivation, hyperphagia, or compulsive water drinking. At the same time, antiseizure medications have many gastrointestinal side effects. On the other hand, some antiseizure medications may improve some gastrointestinal diseases. Many gut manipulations were used successfully to manage epilepsy. Prebiotics, probiotics, synbiotics, postbiotics, a ketogenic diet, fecal microbiota transplantation, and vagus nerve stimulation were used successfully to treat some patients with epilepsy. Other manipulations, such as omental transposition, still need more studies. This narrative review will discuss the different ways the gut and epilepsy affect each other.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medica City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 26612, Bahrain
- Department of Microbiology, Irish Royal College of Surgeon, Busaiteen 15503, Muharraq, Bahrain
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Singh P, Singh AD, Ahuja V, Makharia GK. Who to screen and how to screen for celiac disease. World J Gastroenterol 2022; 28:4493-4507. [PMID: 36157923 PMCID: PMC9476868 DOI: 10.3748/wjg.v28.i32.4493] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 03/03/2022] [Accepted: 06/16/2022] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized, however, many patients have atypical manifestations like iron deficiency anemia, idiopathic short stature, hypertransaminesemia or infertility, etc. These patients often present to the primary care physicians and/or non-gastrointestinal specialties. However, due to a lack of awareness among the healthcare professionals about the various atypical manifestations, many patients are not screened for CeD. In this review, we have summarized the available literature about the prevalence of CeD in various gastrointestinal (chronic diarrhea) and non-gastrointestinal conditions (iron deficiency anemia, short stature, cryptogenic hypertransaminesemia, cryptogenic cirrhosis or idiopathic ataxia etc.) where the diagnosis of CeD should be con-sidered. In addition, we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes, Down's syndrome, and first-degree relatives of patients with CeD. Further, we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies, anti-endomysial antibodies and anti-deamidated gliadin antibodies. Based on the current recommendations, we propose a diagnostic algorithm for patients with suspected CeD.
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Affiliation(s)
- Prashant Singh
- Department of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, United States
| | | | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
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Sharma N, Singh K, Senapati S. Celiac disease poses significant risk in developing depression, anxiety, headache, epilepsy, panic disorder, dysthymia: A meta-analysis. Indian J Gastroenterol 2021; 40:453-462. [PMID: 34839445 DOI: 10.1007/s12664-021-01215-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 06/30/2021] [Indexed: 02/04/2023]
Abstract
Celiac disease (CD) primarily affects the small intestine. Previous studies have identified higher incidences of neuropsychiatric diseases among CD patients compared to non-CD controls. Genome-wide association studies have identified >60 non-human leukocyte antigen (HLA) genes associated with CD, where estimated 15% genes have role in neurological health. We carried out a systematic review and meta-analysis to estimate the potential risk conferred by CD in developing neuropsychiatric diseases. Literature search was performed till June 2019. Incidences of neuropsychiatric diseases were compared among CD and non-CD controls. Funnel plots and Egger's tests were used to evaluate publication bias and estimate study effects. Qualities of the included studies were estimated using Newcastle-Ottawa Scale. Quality of evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Odds of developing neuropsychiatric diseases among CD were evaluated by computing meta-odds ratio (Manten-Haenszel method) and Z test p-value using random and fixed effect models based on the degree of study heterogeneity. Thirteen non-randomized case-control studies were found eligible. Subjects suffering from CD were found to have significantly more risk to develop depression (p<1.00E-05; OR=1.60 [1.37-1.86]), anxiety (p=0.05; OR=1.41 [1.00-1.97]), headache (p<0.1.00E-05; OR=3.27 [2.46-4.34]), epilepsy (p<1.00E-04; OR=11.90 [3.78-37.43]), panic disorder (p<1.00E-04; OR=4.64 [2.22-9.70]), and dysthymia (p=2.00E-03; OR=5.27 [1.83-15.22]). CD is a major predisposing factor in developing array of common neuropsychiatric diseases. Shared biological processes and molecular networks could play a crucial role in disease co-occurrence. Detailed molecular evidences are needed to establish the cause-effect relationship between these diseases.
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Affiliation(s)
- Nidhi Sharma
- Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, School of Life Sciences, Central University of Punjab, Bathinda, 151 401, India
| | - Kavita Singh
- Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Gurugram, 122 002, India
- Centre for Chronic Disease Control, New Delhi, 110 016, India
- Rollins School of Public Health, Emory University, Atlanta, USA
| | - Sabyasachi Senapati
- Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, School of Life Sciences, Central University of Punjab, Bathinda, 151 401, India.
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Julian T, Hadjivassiliou M, Zis P. Gluten sensitivity and epilepsy: a systematic review. J Neurol 2019; 266:1557-1565. [PMID: 30167878 PMCID: PMC6586915 DOI: 10.1007/s00415-018-9025-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 08/14/2018] [Accepted: 08/17/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The aim of this systematic review was to establish the prevalence of epilepsy in patients with coeliac disease (CD) or gluten sensitivity (GS) and vice versa and to characterise the phenomenology of the epileptic syndromes that these patients present with. METHODOLOGY A systematic computer-based literature search was conducted on the PubMed database. Information regarding prevalence, demographics and epilepsy phenomenology was extracted. RESULTS Epilepsy is 1.8 times more prevalent in patients with CD, compared to the general population. CD is over 2 times more prevalent in patients with epilepsy compared to the general population. Further studies are necessary to assess the prevalence of GS in epilepsy. The data indicate that the prevalence of CD or GS is higher amongst particular epileptic presentations including in childhood partial epilepsy with occipital paroxysms, in adult patients with fixation off sensitivity (FOS) and in those with temporal lobe epilepsy (TLE) with hippocampal sclerosis. A particularly interesting presentation of epilepsy in the context of gluten-related disorders is a syndrome of coeliac disease, epilepsy and cerebral calcification (CEC syndrome) which is frequently described in the literature. Gluten-free diet (GFD) is effective in the management of epilepsy in 53% of cases, either reducing seizure frequency, enabling reduced doses of antiepileptic drugs or even stopping antiepileptic drugs. CONCLUSION Patients with epilepsy of unknown aetiology should be investigated for serological markers of gluten sensitivity as such patients may benefit from a GFD.
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Affiliation(s)
- Thomas Julian
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Rd, Sheffield, S10 2HQ, UK.
| | - Marios Hadjivassiliou
- Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
| | - Panagiotis Zis
- Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
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Amanat M, Thijs RD, Salehi M, Sander JW. Seizures as a clinical manifestation in somatic autoimmune disorders. Seizure 2019; 64:59-64. [DOI: 10.1016/j.seizure.2018.11.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 11/10/2018] [Accepted: 11/22/2018] [Indexed: 02/07/2023] Open
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Aziz DA, Kahlid M, Memon F, Sadiq K. Spectrum of Celiac disease in Paediatric population: Experience of Tertiary Care Center from Pakistan. Pak J Med Sci 2017; 33:1301-1306. [PMID: 29492048 PMCID: PMC5768814 DOI: 10.12669/pjms.336.13489] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective: To determine clinical features and relevant laboratory investigations of patient with celiac disease (CD) and comparing classical celiac disease (CCD) with Non-diarrheal celiac disease (NDCD). Methods: This is a five years retrospective study conducted at The Aga Khan University Hospital Karachi, Pakistan from January 2010 to December 2015, enrolling children from one year to 15 years of either gender diagnosed as celiac disease in accordance with revised ESPGHAN criteria. Biopsy samples with grade 2 or more on Modified Marsh Classification were considered as consistent with celiac disease. Celiac patients were categorized into Classical celiac disease (with Chronic Diarrhea) and non-diarrheal celiac disease (Atypical celiac) and their clinical features and relevant laboratory investigations were documented. Results: Total 66 patients were selected with celiac disease according to inclusion criteria, 39 (59.09%) patients were labeled as CCD and 27 (40.91%) patients were labeled as NDCD. Marsh grading 3a and above were more marked in CCD as compared to NDCD. Mean titer for Tissue transglutaminase antibodies (TTG) were higher in CCD group in comparison to NDCD group. In CCD, the most common clinical presentations were abdominal distension whereas in NDCD, the most remarkable features were recurrent abdominal pain (62.9%). Frequency of failure to thrive is significantly high in CCD (82.05%) but patients merely with short stature were more common in NDCD (33.3%). Refractory anemia was present in 66.6% patients in NDCD group and 41.1% patients in CCD group. 74.3% patients in CCD group were vitamin D deficient whereas 85% patient had vitamin D deficiency in NDCD group (p= 0.03). Conclusion: NDCD is not uncommon in our population. Recurrent abdominal pain, failure to thrive or patients only with short stature and refractory anemia are prominent features in NCDC group whereas abdominal distension, failure to thrive and recurrent abdominal pain were noticeable features in CCD. High grade histopathology and raised antibodies titer is hallmark of CCD. Vitamin D deficiency is almost equally present in both groups.
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Affiliation(s)
- Danish Abdul Aziz
- Dr. Danish Abdul Aziz, MBBS, MRCPCH, FCPS. Senior Instructor, Department of Paediatrics, Aga Khan University Hospital, Karachi, Pakistan
| | - Misha Kahlid
- Misha Khalid, Final Year of MBBS Medical Student, Aga Khan University Hospital, Karachi, Pakistan
| | - Fozia Memon
- Dr. Fozia Memon, MBBS, FCPS, Chief Resident, Department of Paediatrics, Aga Khan University Hospital, Karachi, Pakistan
| | - Kamran Sadiq
- Dr. Kamran Sadiq, MBBS, FCPS. Assistant Professor and Paediatric Gastroenterologist, Department of Paediatrics, Aga Khan University Hospital, Karachi, Pakistan
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Lin Z, Si Q, Xiaoyi Z. Association between epilepsy and systemic autoimmune diseases: A meta-analysis. Seizure 2016; 41:160-6. [PMID: 27592469 DOI: 10.1016/j.seizure.2016.08.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Revised: 07/29/2016] [Accepted: 08/12/2016] [Indexed: 02/05/2023] Open
Abstract
PURPOSE To investigate the association between systemic autoimmune diseases (SAD) and epilepsy and to determine whether the strength of this association is increased in the young. METHODS A meta-analysis was done, analyzing the association between epilepsy and SAD using the available data in Medline and Embase through February 2016. We followed the recommendations of the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement and the MOOSE (meta-analysis of observational studies in epidemiology) guidelines. RESULTS A total of twenty-five studies met the inclusion criteria for this meta-analysis, which included 10,972 patients with epilepsy (PWE) and 2,618,637 patients with SAD. The PWE cohort was shown to have more than a 2.5-fold increased risk of SAD. The patients with SAD were also shown to have a more than 2.5-fold increased risk of epilepsy. The results indicated that patients <20 years of age had a 3-fold increased risk of SAD and epilepsy (OR=3.04 [95% CI 1.27-7.27], P=0.01; OR=3.15 [95% CI 1.92-5.15], P<0.01; respectively), and these risks were shown to be higher than patients >20 years of age. The PWE cohort had a 2.6-fold increased risk of celiac disease (OR=2.65 [95% CI 1.41-4.97], P<0.01). The patients with systemic lupus erythematosus had a 4.5-fold increased risk of epilepsy (OR=4.57 [95% CI 2.40-8.67], P<0.01). CONCLUSIONS There is an association between epilepsy and SAD, which was shown to be stronger at a young age.
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Affiliation(s)
- Zhang Lin
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Qi Si
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zou Xiaoyi
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
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Işıkay S, Kocamaz H, Sezer S, Özkars MY, Işıkay N, Filik B, Şan M, Kanmaz A. The Frequency of Epileptiform Discharges in Celiac Disease. Pediatr Neurol 2015; 53:78-82. [PMID: 26092417 DOI: 10.1016/j.pediatrneurol.2015.02.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Revised: 02/04/2015] [Accepted: 02/09/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND We studied patients with celiac disease to define the frequency of epileptiform discharges on electroencephalography. METHODS A total of 307 children with a diagnosis of celiac disease (study group) and 197 age- and sex-matched healthy children as controls (control group) were included in this study. The study group was further divided into newly diagnosed celiac disease patients (n = 216) and patients who were on a gluten-free diet (n = 91) for at least 6 months. Medical histories of all children including age, sex, symptoms, weight, height, physical examination findings, and laboratory data were recorded. All patients underwent an electroencephalograph in a pediatric neurology electroencephalograph laboratory with a 32-channel electroencephalograph for 30 minutes. RESULTS Twenty-five patients were defined to have epileptiform discharges (spike/sharp-wave discharges); 24 (7.8%) of those patients were in the celiac disease group and 1 (0.5%) was in the control group (P = 0.001). Among those 24 patients, 21 (9.7%) were in newly diagnosed celiac disease group and 3 (3.3%) were in the gluten-free diet group (P = 0.03). CONCLUSIONS Patients diagnosed with celiac disease are prone to epileptiform activities on electroencephalography and should be evaluated carefully. Moreover, strict adherence to a gluten-free diet early should be advised in those patients with epileptiform activities because it may effectively decrease the occurrence of epileptiform activities.
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Affiliation(s)
- Sedat Işıkay
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey.
| | - Halil Kocamaz
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey
| | - Sadettin Sezer
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey
| | - Mehmet Yaşar Özkars
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey
| | - Nurgül Işıkay
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey
| | - Bülent Filik
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey
| | - Murat Şan
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey
| | - Alper Kanmaz
- Department of Pediatric Neurology, Gaziantep Children's Hospital, Şehitkamil, Gaziantep, Turkey
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Işikay S, Kocamaz H. THE NEUROLOGICAL FACE OF CELIAC DISEASE. ARQUIVOS DE GASTROENTEROLOGIA 2015; 52:167-170. [PMID: 26486280 DOI: 10.1590/s0004-28032015000300002] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Accepted: 11/05/2014] [Indexed: 11/22/2022]
Abstract
BACKGROUND Several neurological disorders have also been widely described in celiac disease patients. OBJECTIVE The aim of this study was to determine the incidence of accompanying different neurologic manifestations in children with celiac disease at the time of diagnosis and to discuss these manifestations in the light of the recent literature. METHODS This prospective cross sectional study included 297 children diagnosed with celiac disease. The medical records of all patients were reviewed. RESULTS In neurological evaluation, totally 40 (13. 5%) of the 297 celiac patients had a neurological finding including headache, epilepsy, migraine, mental retardation, breath holding spells, ataxia, cerebral palsy, attention deficit hyperactivity disorder, Down syndrome and Turner syndrome in order of frequency. There was not any significant difference between the laboratory data of the patients with and without neurological manifestations. However; type 3a biopsy was statistically significantly more common among patients without neurological manifestations, while type 3b biopsy was statistically significantly more common among patients with neurological manifestations. CONCLUSION It is important to keep in mind that in clinical course of celiac disease different neurological manifestations may be reported.
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Affiliation(s)
- Sedat Işikay
- Department of Pediatric Neurology, Faculty of Medicine, Sutcu Imam University, Kahramanmaras, Turkey, BR
| | - Halil Kocamaz
- Department of Pediatric Gastroenterology, Gaziantep Children's Hospital, Gaziantep, Turkey, BR
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Abstract
Autoimmunity and inflammation have been implicated as causative factors of seizures and epilepsy. Autoimmune disorders can affect the central nervous system as an isolated syndrome or be part of a systemic disease. Examples of systemic autoimmune disorders include systemic lupus erythematosus, antiphospholipid syndrome, rheumatic arthritis, and Sjögren syndrome. Overall, there is a 5-fold increased risk of seizures and epilepsy in children with systemic autoimmune disorders. Various etiologic factors have been implicated in causing the seizures in these patients, including direct inflammation, effect on blood vessels (vasculitis), and production of autoantibodies. Potential treatments for this autoimmune injury include steroids, immunoglobulins, and other immune-modulatory therapies. A better understanding of the mechanisms of epileptogenesis in patients with systemic autoimmune diseases could lead to targeted treatments and better outcomes.
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