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Accomando S, Rita Piazza I, Cacciatore F, Notarbartolo V, Corsello G, Giuffrè M. New and old criteria for diagnosing celiac disease: do they really differ? A retrospective observational study. Ital J Pediatr 2024; 50:59. [PMID: 38561850 PMCID: PMC10986084 DOI: 10.1186/s13052-024-01625-w] [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: 11/16/2022] [Accepted: 03/08/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND The aim of this study is to compare two groups of celiac patients: the first one, in which diagnosis was based on a "biopsy sparing" approach according to the 2012 ESPGHAN criteria, and the second one, based on the biopsy approach like the one of the 1991 Revised Criteria, in order to find relevant difference for sex, M/F ratio, age at diagnosis, clinical features at the onset, presence and prevalence of concomitant autoimmune disorders. METHODS Our study involves 61 patients having the Celiac Disease (CD) onset from February 2013 to February 2020. The 32 patients who received diagnosis according "biopsy sparing" criteria were enrolled in group (1) The 29 patients who received diagnosis by duodenal biopsy were enrolled in group (2) Prevalence of comorbidities was analysed through chi-square test. RESULTS In group 1 the prevalence of comorbidities such as Insulin-Dependent Diabetes Mellitus (IDDM) and thyroiditis was of 53%, while in group 2 it was only of 24%. Analysing the IDDM prevalence between the two groups we found a relevant difference. At the same time, the prevalence of thyroiditis was also significantly different. In group 1, male patients, in particular, would seem to have a higher incidence of CD related autoimmune disorders. CONCLUSIONS An increased prevalence of IDDM, thyroiditis and juvenile idiopathic arthritis (JIA) in the first group would show that the "biopsy sparing" approach could expose patients to a greater length of disease activity that might be responsible for the onset of such comorbidities. Further studies should be carried out on more numerous samples of patients in order to confirm or not these data.
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Affiliation(s)
- Salvatore Accomando
- Paediatrics Operative Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, Palermo, Italy.
| | - Ilenia Rita Piazza
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, Palermo, Italy
| | - Francesca Cacciatore
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, Palermo, Italy
| | - Veronica Notarbartolo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, Palermo, Italy
| | - Giovanni Corsello
- Paediatrics Operative Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, Palermo, Italy
| | - Mario Giuffrè
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), School of Medicine, University of Palermo, Palermo, Italy
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Koskinen I, Hervonen K, Huhtala H, Pasternack C, Salmi T, Reunala T, Collin P, Kaukinen K. Mortality and causes of death in different celiac disease phenotypes during long-term follow-up. Dig Liver Dis 2022; 54:1502-1507. [PMID: 35589505 DOI: 10.1016/j.dld.2022.04.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/24/2022] [Accepted: 04/27/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Celiac disease has been associated with increased mortality, but data on long-term mortality are scarce. AIMS To determine long-term mortality in celiac disease. METHODS The study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 - 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time. RESULTS During the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85-1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38-4.24 and HR 2.14, 95% CI 1.05-4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09-1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortality CONCLUSIONS: Overall mortality was not increased in any celiac disease phenotype during a very long-term follow-up.
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Affiliation(s)
- Inka Koskinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland.
| | - Kaisa Hervonen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Camilla Pasternack
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Teea Salmi
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Timo Reunala
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Pekka Collin
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
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Raiteri A, Granito A, Giamperoli A, Catenaro T, Negrini G, Tovoli F. Current guidelines for the management of celiac disease: A systematic review with comparative analysis. World J Gastroenterol 2022; 28:154-175. [PMID: 35125825 PMCID: PMC8793016 DOI: 10.3748/wjg.v28.i1.154] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 08/08/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Wheat and other gluten-containing grains are widely consumed, providing approximately 50% of the caloric intake in both industrialised and developing countries. The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence. This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media. However, in recent years, the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease (CD) from obscurity to global prominence. These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD. Different scientific societies, mainly from Europe and America, have proposed guidelines based on CD's most recent evidence. AIM To identify the most recent scientific guidelines on CD, aiming to find and critically analyse the main differences. METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language. PubMed was lastly accessed on 1 March 2021. RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions. Differences were noted in the possibility of a no-biopsy diagnosis, HLA testing, follow-up protocols, and procedures. CONCLUSION We found a relatively high concordance between the guidelines for CD. Important modifications have occurred in the last years, especially about the possibility of a no-biopsy diagnosis in children. Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.
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Affiliation(s)
- Alberto Raiteri
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Alice Giamperoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Teresa Catenaro
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Giulia Negrini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
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Barnes SE, Zera KA, Ivison GT, Buckwalter MS, Engleman EG. Brain profiling in murine colitis and human epilepsy reveals neutrophils and TNFα as mediators of neuronal hyperexcitability. J Neuroinflammation 2021; 18:199. [PMID: 34511110 PMCID: PMC8436533 DOI: 10.1186/s12974-021-02262-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 08/30/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Patients with chronic inflammatory disorders such as inflammatory bowel disease frequently experience neurological complications including epilepsy, depression, attention deficit disorders, migraines, and dementia. However, the mechanistic basis for these associations is unknown. Given that many patients are unresponsive to existing medications or experience debilitating side effects, novel therapeutics that target the underlying pathophysiology of these conditions are urgently needed. METHODS Because intestinal disorders such as inflammatory bowel disease are robustly associated with neurological symptoms, we used three different mouse models of colitis to investigate the impact of peripheral inflammatory disease on the brain. We assessed neuronal hyperexcitability, which is associated with many neurological symptoms, by measuring seizure threshold in healthy and colitic mice. We profiled the neuroinflammatory phenotype of colitic mice and used depletion and neutralization assays to identify the specific mediators responsible for colitis-induced neuronal hyperexcitability. To determine whether our findings in murine models overlapped with a human phenotype, we performed gene expression profiling, pathway analysis, and deconvolution on microarray data from hyperexcitable human brain tissue from patients with epilepsy. RESULTS We observed that murine colitis induces neuroinflammation characterized by increased pro-inflammatory cytokine production, decreased tight junction protein expression, and infiltration of monocytes and neutrophils into the brain. We also observed sustained neuronal hyperexcitability in colitic mice. Colitis-induced neuronal hyperexcitability was ameliorated by neutrophil depletion or TNFα blockade. Gene expression profiling of hyperexcitable brain tissue resected from patients with epilepsy also revealed a remarkably similar pathology to that seen in the brains of colitic mice, including neutrophil infiltration and high TNFα expression. CONCLUSIONS Our results reveal neutrophils and TNFα as central regulators of neuronal hyperexcitability of diverse etiology. Thus, there is a strong rationale for evaluating anti-inflammatory agents, including clinically approved TNFα inhibitors, for the treatment of neurological and psychiatric symptoms present in, and potentially independent of, a diagnosed inflammatory disorder.
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Affiliation(s)
- Sarah E Barnes
- Department of Pathology, Stanford University, Stanford, CA, USA
| | - Kristy A Zera
- Department of Neurology, Stanford University, Stanford, CA, USA
| | - Geoffrey T Ivison
- Department of Pathology, Stanford University, Stanford, CA, USA
- Department of Infectious Diseases, Stanford University, Stanford, CA, USA
| | | | - Edgar G Engleman
- Department of Pathology, Stanford University, Stanford, CA, USA.
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Di Liberto D, D’Anneo A, Carlisi D, Emanuele S, De Blasio A, Calvaruso G, Giuliano M, Lauricella M. Brain Opioid Activity and Oxidative Injury: Different Molecular Scenarios Connecting Celiac Disease and Autistic Spectrum Disorder. Brain Sci 2020; 10:E437. [PMID: 32659996 PMCID: PMC7407635 DOI: 10.3390/brainsci10070437] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/01/2020] [Accepted: 07/06/2020] [Indexed: 12/11/2022] Open
Abstract
Celiac Disease (CD) is an immune-mediated disease triggered by the ingestion of wheat gliadin and related prolamins from other cereals, such as barley and rye. Immunity against these cereal-derived proteins is mediated by pro-inflammatory cytokines produced by both innate and adaptive system response in individuals unable to adequately digest them. Peptides generated in this condition are absorbed across the gut barrier, which in these patients is characterized by the deregulation of its permeability. Here, we discuss a possible correlation between CD and Autistic Spectrum Disorder (ASD) pathogenesis. ASD can be induced by an excessive and inappropriate brain opioid activity during the neonatal period. Cereal-derived peptides produced in celiac patients cross the blood-brain barrier and bind to endogenous opioid receptors interfering with neurotransmission and generating deleterious effects on brain maturation, learning and social relations. Moreover, an increase in oxidative stress and a decrease in the antioxidant capacity, as well as an extended mitochondrial impairment in the brain, could represent a possible connection between ASD and CD. Therefore, we critically discuss the proposed relationship between ASD and CD and the possible usefulness of a gluten-free diet in ASD patients.
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Affiliation(s)
- Diana Di Liberto
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy;
| | - Antonella D’Anneo
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (A.D.B.); (G.C.); (M.G.)
| | - Daniela Carlisi
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy; (D.C.); (S.E.)
| | - Sonia Emanuele
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy; (D.C.); (S.E.)
| | - Anna De Blasio
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (A.D.B.); (G.C.); (M.G.)
| | - Giuseppe Calvaruso
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (A.D.B.); (G.C.); (M.G.)
| | - Michela Giuliano
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (A.D.B.); (G.C.); (M.G.)
| | - Marianna Lauricella
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy; (D.C.); (S.E.)
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Falato E, Capone F, Ranieri F, Florio L, Corbetto M, Taffon C, Niolu C, Di Lorenzo G, Di Lazzaro V. Celiac Disease Diagnosed in an Older Adult Patient with a Complex Neuropsychiatric Involvement: A Case Report and Review of the Literature. Brain Sci 2020; 10:brainsci10070426. [PMID: 32635319 PMCID: PMC7408423 DOI: 10.3390/brainsci10070426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/28/2020] [Accepted: 06/30/2020] [Indexed: 11/16/2022] Open
Abstract
We present a case of celiac disease (CD) diagnosis in a 75-year-old woman with a long-term history of chronic delusional jealousy and a complex neurological involvement. The case describes a very unusual clinical picture, provides some clinical clues, and highlights the importance of being aware of CD extraintestinal manifestations in order to get a timely diagnosis.
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Affiliation(s)
- Emma Falato
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 200, 00128 Rome, Italy; (E.F.); (F.C.)
| | - Fioravante Capone
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 200, 00128 Rome, Italy; (E.F.); (F.C.)
| | - Federico Ranieri
- Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy;
| | - Lucia Florio
- Unit of Neurology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy;
| | - Marzia Corbetto
- Department of Neurology, Santa Maria Goretti Hospital, 04100 Latina, Italy;
| | - Chiara Taffon
- Unit of Pathology, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 200, 00128 Rome, Italy;
| | - Cinzia Niolu
- Unit of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy; (C.N.); (G.D.L.)
| | - Giorgio Di Lorenzo
- Unit of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy; (C.N.); (G.D.L.)
| | - Vincenzo Di Lazzaro
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 200, 00128 Rome, Italy; (E.F.); (F.C.)
- Correspondence:
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Trovato CM, Raucci U, Valitutti F, Montuori M, Villa MP, Cucchiara S, Parisi P. Neuropsychiatric manifestations in celiac disease. Epilepsy Behav 2019; 99:106393. [PMID: 31479999 DOI: 10.1016/j.yebeh.2019.06.036] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 06/17/2019] [Accepted: 06/27/2019] [Indexed: 12/12/2022]
Abstract
Celiac disease (CD) is a systemic, chronic immune-mediated disorder elicited by gluten and related prolamines in genetically susceptible subjects. Main manifestations of CD involve the digestive tract; however, a growing body of evidence supports the theory that symptoms may occur in every part of the body. It is known that some patients with CD can be asymptomatic, and additionally, the incidence of "nonclassical" CD with extraintestinal presentation is apparently increasing. We aimed to perform a thorough review of existing evidence for neurological manifestations of CD, providing an up-to-date description of prevalence and examining the pathogenetic mechanisms possibly involved. Neurological presentations are rare in children but as many as 36% of adult patients present with neurological findings. With severe malnutrition after progression of CD, different vitamin deficiencies may develop. Such problems can in turn overlap with previous neurological abnormalities including ataxia, epilepsy, neuropathy, dementia, and cognitive disorders. Here, the most prevalent clinical manifestations in adults and children have been discussed in further detail. Further research is needed to achieve a complete understanding of the nervous system involvement in CD, but clinicians should always remember that neurological and psychiatric symptoms might be part of the CD spectrum of manifestations.
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Affiliation(s)
- Chiara Maria Trovato
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Umberto Raucci
- Pediatric Emergency Department, "Bambino Gesù" Children's Hospital, IRCCS, Rome, Italy
| | - Francesco Valitutti
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Monica Montuori
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Maria Pia Villa
- NESMOS Department, Faculty of Medicine and Psychology, Sapienza University, Sant'Andrea Hospital, Rome, Italy
| | - Salvatore Cucchiara
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Pasquale Parisi
- NESMOS Department, Faculty of Medicine and Psychology, Sapienza University, Sant'Andrea Hospital, Rome, Italy.
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Khan S, AlNajjar A, Alquaydheb A, Nahrir S. Transient Periictal Brain Imaging Abnormality in a Saudi Patient with Probable Celiac Disease Epilepsy and Occipital Calcification Syndrome. Case Rep Neurol Med 2019; 2019:5247961. [PMID: 31080682 PMCID: PMC6475548 DOI: 10.1155/2019/5247961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Revised: 02/08/2019] [Accepted: 03/26/2019] [Indexed: 11/17/2022] Open
Abstract
Celiac disease epilepsy and occipital calcification (CEC) syndrome is a rare, emerging disease first described in 1992. To date, fewer than 200 cases have been reported worldwide. CEC syndrome is generally thought to be a genetic, noninherited, and ethnically and geographically restricted disease in Mediterranean countries. However, we report the first ever case of probable CEC in a Saudi patient. Furthermore, the patient manifested a magnitude of brain magnetic resonance imaging (MRI) signal abnormalities during the periictal period which, to the best of our knowledge, has never been described in CEC. The brain MRI revealed diffusion-weighted imaging (DWI) restriction with a concordant area of apparent diffusion coefficient (ADC) hypointensity around bilateral occipital area of calcification. An imbalance between the heightened energy demand during ictal phase of the seizure and unadjusted blood supply may have caused an electric pump failure and cytotoxic edema, which then led to DWI/ADC signal alteration.
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Affiliation(s)
- Soha Khan
- King Saud Medical City, Riyadh, Saudi Arabia
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Popp A, Mäki M. Gluten-Induced Extra-Intestinal Manifestations in Potential Celiac Disease-Celiac Trait. Nutrients 2019; 11:nu11020320. [PMID: 30717318 PMCID: PMC6412544 DOI: 10.3390/nu11020320] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/28/2019] [Accepted: 01/29/2019] [Indexed: 12/24/2022] Open
Abstract
Celiac disease patients may suffer from a number of extra-intestinal diseases related to long-term gluten ingestion. The diagnosis of celiac disease is based on the presence of a manifest small intestinal mucosal lesion. Individuals with a normal biopsy but an increased risk of developing celiac disease are referred to as potential celiac disease patients. However, these patients are not treated. This review highlights that patients with normal biopsies may suffer from the same extra-intestinal gluten-induced complications before the disease manifests at the intestinal level. We discuss diagnostic markers revealing true potential celiac disease. The evidence-based medical literature shows that these potential patients, who are “excluded” for celiac disease would in fact benefit from gluten-free diets. The question is why wait for an end-stage disease to occur when it can be prevented? We utilize research on dermatitis herpetiformis, which is a model disease in which a gluten-induced entity erupts in the skin irrespective of the state of the small intestinal mucosal morphology. Furthermore, gluten ataxia can be categorized as its own entity. The other extra-intestinal manifestations occurring in celiac disease are also found at the latent disease stage. Consequently, patients with celiac traits should be identified and treated.
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Affiliation(s)
- Alina Popp
- University of Medicine and Pharmacy "Carol Davila" and National Institute for Mother and Child Health "Alessandrescu-Rusescu", Bucharest 020395, Romania.
- Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33520 Tampere, Finland.
| | - Markku Mäki
- Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33520 Tampere, Finland.
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10
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Lin CY, Wang MJ, Tse W, Pinotti R, Alaedini A, Green PHR, Kuo SH. Serum antigliadin antibodies in cerebellar ataxias: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2018; 89:1174-1180. [PMID: 29866704 PMCID: PMC6231948 DOI: 10.1136/jnnp-2018-318215] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 04/24/2018] [Accepted: 04/26/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Gluten sensitivity refers to prominent immunological responses to gluten, usually in conjunction with elevated levels of serum antigliadin antibody (AGA). The association between AGA and cerebellar ataxias has been inconsistently reported. METHODS We performed a systematic literature search and a meta-analysis to study the weighted pooled OR of idiopathic cerebellar ataxia (IDCA) cases to controls or to hereditary ataxia (HA) for AGA seropositivity using fixed effect model. RESULTS Eleven studies were included, with a total of 847 IDCA cases, 1654 controls and 445 HA cases. IDCA cases had fourfold higher odds than controls (OR 4.28, 95% CI 3.10 to 5.90) and twofold higher odds than HA cases (OR 2.23, 95% CI 1.45 to 3.44) of having AGA seropositivity. Sensitivity analysis excluding the most weighted study, which accounted for 69% of the total weight, still showed similar associations (IDCA vs controls, OR 3.18, 95% CI 1.79 to 5.67 and IDCA vs HA, OR 1.72, 95% CI 1.03 to 2.86, respectively). The subgroup analysis showed that, when compared with controls, IDCA cases of both East Asian and Western countries had approximately threefold to fourfold higher odds to have AGA seropositivity (OR 3.41, 95% CI 1.67 to 6.97 and OR 4.53, 95% CI 3.16 to 6.49, respectively), suggesting the lack of ethnic heterogeneity. The odds of AGA seropositivity for HA cases was not significantly higher than controls (OR 1.41, 95% CI 0.82 to 2.44). CONCLUSION Our study indicates the association between AGA and IDCA, across different geographic regions.
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Affiliation(s)
- Chi-Ying Lin
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - Min-Jung Wang
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Winona Tse
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - Rachel Pinotti
- Levy Library, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - Armin Alaedini
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City, New York, USA
| | - Peter H R Green
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City, New York, USA
| | - Sheng-Han Kuo
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York City, New York, USA
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11
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Bavykina IA, Zvyagin AA, Petrova IV, Nastausheva TL. [Markers of gluten intolerance in children with autism spectrum disorders and Down'syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova 2018; 118:64-68. [PMID: 30141790 DOI: 10.17116/jnevro20181185264] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
AIM To study serological and genetic markers of gluten intolerance in children and teenagers with autism spectrum disorders (ASD) and Down's syndrome (DS). MATERIAL AND METHODS Thirty-three children with ASD (group 1) and 8 with DS (group 2), aged from 2.5 to 15 years, were examined. There were 27 boys and 6 girls in group1, 5 boys and 3 girls in group 2. Most of the children were on a regular diet and only 4 children with ASD kept gluten-free diet (GFD). Using ELI method antibodies to gliadin IgG (AntiGliadin IgG), antibodies to deamidated peptides of gliadin IgA (AntiDGP IgA), immunoglobulin A (IgA) were identified. Haplotypes HLA-DQ2 and DQ8 were determined using PCR. RESULTS AntiGliadin IgG were identified in 12.1% (4) patients of group 1, with the exception of patients on GFD in 13.8%, and in 50% patients of group 2. One child with ASD had selective IgA deficiency. Haplotypes predisposing to celiac disease had 41.9% of patients of group 1 and 37.5% of patients of group 2. In ASD, the distribution of genotypes was as follows: DQ2 (64.3%), DQ8 (28.6%), DQ2/DQ8 (7.1%,). In DS, all patients had haplotype DQ2. AntiDGP IgA were not identified in both groups. CONCLUSION The predominant form of gluten intolerance in children with ASD and DS is sensitivity to gluten, which can be identified in 40-50% of patients. Celiac disease, an autoimmune form of gluten intolerance, can be diagnosed in single cases, although predisposition to it is identified in 41.9% - 37.5% patients with ASD and DS, respectively. Before the start of GFD, laboratory tests should be made to identify forms of gluten intolerance and the use of GFD.
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Affiliation(s)
- I A Bavykina
- Burdenko Voronezh State Medical University, Voronezh, Russia
| | - A A Zvyagin
- Burdenko Voronezh State Medical University, Voronezh, Russia
| | - I V Petrova
- Center of Social Rehabilitation of Children with Disabilities 'Sail of hope', Voronezh, Russia
| | - T L Nastausheva
- Burdenko Voronezh State Medical University, Voronezh, Russia
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12
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Laurikka P, Nurminen S, Kivelä L, Kurppa K. Extraintestinal Manifestations of Celiac Disease: Early Detection for Better Long-Term Outcomes. Nutrients 2018; 10:E1015. [PMID: 30081502 PMCID: PMC6115849 DOI: 10.3390/nu10081015] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 07/25/2018] [Accepted: 07/31/2018] [Indexed: 12/11/2022] Open
Abstract
Population-based screening studies have shown celiac disease to be one of the most common chronic gastrointestinal diseases. Nevertheless, because of the diverse clinical presentation, the great majority of patients remain unrecognized. Particularly difficult to identify are the multifaceted extraintestinal symptoms that may appear at variable ages. Although the pathogenesis and long-term outcome of these manifestations are still poorly established, there is some evidence that unrecognized celiac disease predisposes to severe complications if not diagnosed and prevented with an early-initiated gluten-free diet. Therefore, it is of utmost importance that physicians of different disciplines learn to recognize celiac disease in individuals with non-gastrointestinal symptoms. In the future, more studies are needed to clarify the factors affecting development and prognosis of the extraintestinal manifestations.
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Affiliation(s)
- Pilvi Laurikka
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, 33014 Tampere, Finland.
- Department of Internal Medicine, Hospital District of South Ostrobothnia, 60200 Seinäjoki, Finland.
| | - Samuli Nurminen
- Tampere Center for Child Health Research, Tampere University Hospital and University of Tampere, 33014 Tampere, Finland.
| | - Laura Kivelä
- Tampere Center for Child Health Research, Tampere University Hospital and University of Tampere, 33014 Tampere, Finland.
| | - Kalle Kurppa
- Tampere Center for Child Health Research, Tampere University Hospital and University of Tampere, 33014 Tampere, Finland.
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13
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Abstract
Over the last decade, there have been significant advances in the identification, characterization, and treatment of autoimmune neurologic disorders in children. Many of these diseases include a typical movement disorder that can be a powerful aid to diagnosis. Frequently, movement disorders in autoimmune conditions are the sole or among a few presenting symptoms, allowing for earlier diagnosis of an underlying malignancy or systemic autoimmune disease. Given that early detection and treatment with immunotherapy may confer improved outcomes, recognizing these patterns of abnormal movements is essential for child neurologists. The purpose of this review is to summarize the clinical characteristics, diagnosis, and treatment of movement disorders that occur in pediatric autoimmune disorders.
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Affiliation(s)
- Coral M Stredny
- Department of Neurology, Boston Children's Hospital, Boston, MA.
| | - Jeff L Waugh
- Department of Neurology, Boston Children's Hospital, Boston, MA
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14
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Collin P, Vilppula A, Luostarinen L, Holmes GKT, Kaukinen K. Review article: coeliac disease in later life must not be missed. Aliment Pharmacol Ther 2018; 47:563-572. [PMID: 29322540 DOI: 10.1111/apt.14490] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 08/17/2017] [Accepted: 12/06/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND The presenting symptoms of coeliac disease are often subtle and the diagnosis is frequently delayed or overlooked. Therefore, especially elderly patients may be denied the benefits conferred by gluten free diet which can be dramatically life-changing. AIM To review the occurrence, clinical features, diagnosis and management in coeliac patients detected later in life. METHODS To review manuscripts concerned with coeliac disease in the elderly and to derive subgroups of elderly people from publications on the disorder. RESULTS Approximately a quarter of all diagnoses are now made at the age of 60 years or more and a fifth at 65 years or over. About 4% are diagnosed at 80 years or above. Around 60% remain undetected, since their symptoms are often subtle: tiredness, indigestion, reduced appetite. Good compliance with gluten free diet, resolution of symptoms and improvement in laboratory indices can be achieved in over 90% of patients. CONCLUSIONS Coeliac disease not uncommonly presents for the first time in older patients and is an important diagnosis to make.
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Affiliation(s)
- P Collin
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.,University of Tampere, Tampere, Finland
| | - A Vilppula
- Department of Clinical Neurophysiology, Neuroscience, HUS Medical Imaging Centre, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
| | | | - G K T Holmes
- Department of Gastroenterology, the Royal Derby Hospital, Derby, UK
| | - K Kaukinen
- Department of Medicine, Faculty of Medicine and Life-Sciences, Tampere University Hospital, University of Tampere, Tampere, Finland
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15
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Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet. Acta Neurol Belg 2018; 118:21-27. [PMID: 29247390 DOI: 10.1007/s13760-017-0870-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 12/02/2017] [Indexed: 12/13/2022]
Abstract
Celiac disease (CD) and non celiac gluten sensitivity (NCGS) can be responsible for neurological complications such as ataxia and peripheral neuropathies but also cognitive impairment. This cognitive involvement is variable in its expression, its duration and its prognosis ranging from transient and reversible subtle involvement to dementia itself. Through this article, we tried to achieve a review of the literature to better understand this topic. Several mechanisms were proposed to explain the deleterious influence of gluten-related pathologies on cognitive functions: nutritional deficiencies, elevation of circulating cytokine levels due to systemic inflammation, low brain serotonin levels… Several types of dementia such as Alzheimer dementia, vascular dementia, frontotemporal dementia were reported in association with CD. Memory disorder, acalculia, inattention, visuospatial deficits and executive dysfunction must be sought systematically by a neuropsychological assessment in patients with CD or NCGS. As far as the cognitive impairment is concerned, there is no pathognomonic radiological lesion. Concerning therapeutic management; although its effect is controversial, gluten free diet should be introduced, as early as possible, because of its potentially protective effect.
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16
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Ham H, Lee BI, Oh HJ, Park SH, Kim JS, Park JM, Cho YS, Choi MG. A case of celiac disease with neurologic manifestations misdiagnosed as amyotrophic lateral sclerosis. Intest Res 2017; 15:540-542. [PMID: 29142524 PMCID: PMC5683987 DOI: 10.5217/ir.2017.15.4.540] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/05/2016] [Accepted: 10/14/2016] [Indexed: 12/20/2022] Open
Abstract
Celiac disease (CD) is an immune-mediated enteropathy and is a rare disease in Asia, including in Korea. However, the ingestion of wheat products, which can act as a precipitating factor of CD, has increased rapidly. CD is a common cause of malabsorption, but many patients can present with various atypical manifestations as first presented symptoms, including anemia, osteopenia, infertility, and neurological symptoms. Thus, making a diagnosis is challenging. We report a case of CD that mimicked amyotrophic lateral sclerosis (ALS). The patient was a sexagenary man with a history of progressive motor weakness for 2 years. He was highly suspected as having ALS. During evaluation of his neurological symptoms, esophagogastroduodenoscopy (EGD) was performed because he had experienced loose stools and weight loss for the previous 7 months. On EGD, the duodenal mucosa appeared smooth. A biopsy revealed severe lymphoplasma cell infiltration with flattened villi. His serum endomysial antibody (immunoglobulin A) titer was 1:160 (reference, <1:40). Finally, he was diagnosed as having CD, and a gluten-free diet was immediately begun. At a 4-month follow-up, his weight and the quality of his stool had improved gradually, and the neurological manifestations had not progressed.
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Affiliation(s)
- Hyoju Ham
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Bo-In Lee
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyun Jin Oh
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Se Hwan Park
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Su Kim
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Myung Park
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Seok Cho
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myung-Gyu Choi
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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17
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Damulin IV, Degterev DA. [Polyneuropathies in intestinal diseases]. Zh Nevrol Psikhiatr Im S S Korsakova 2017; 117:103-107. [PMID: 28884726 DOI: 10.17116/jnevro201711781103-107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Different aspects of polyneuropathies (PN) developed due to the deficit of group B vitamins in intestinal diseases are considered. Neurological disturbances related to intestinal diseases are caused by malabsorption that leads to the deficit of some compounds extremely important for normal cell metabolism, pathological changes of mucous coat of the stomach and intestine and higher sensitivity to the plant protein gluten. Vitamin B12 deficit can lead to a number of neurological disturbances; patients with pernicious anemia most often develop myelopathy and PN. An increase in serum vitamin B1 concentration is identified in 30-80% of patients with alcoholism. However, vitamin B1 deficit is seen also in ulcer disease, chronic gastritis, acute pancreatitis, esophageal metastatic lesions as well as in primary tumors of the stomach and intestine. Demyelinating as well as axonal PN may develop in patients with enteropathy. Gluten intolerance is the most often cause of PN in pathological changes in the intestine Possibilities of clinical and paraclinical diagnosis of these disorders are analyzed.
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Affiliation(s)
- I V Damulin
- Sechenov First Moscow State Medical University, Moscow, Russia; Moscow Clinical Research Center, Moscow, Russia
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18
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Optic neuritis in a patient with celiac disease. Neurol Neurochir Pol 2017; 51:534-536. [PMID: 28803640 DOI: 10.1016/j.pjnns.2017.07.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 07/12/2017] [Indexed: 11/23/2022]
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19
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Campagna G, Pesce M, Tatangelo R, Rizzuto A, La Fratta I, Grilli A. The progression of coeliac disease: its neurological and psychiatric implications. Nutr Res Rev 2017; 30:25-35. [PMID: 27976606 DOI: 10.1017/s0954422416000214] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The aim of the paper is to show the various neurological and psychiatric symptoms in coeliac disease (CD). CD is a T cell-mediated, tissue-specific autoimmune disease which affects genetically susceptible individuals after dietary exposure to proline- and glutamine-rich proteins contained in certain cereal grains. Genetics, environmental factors and different immune systems, together with the presence of auto-antigens, are taken into account when identifying the pathogenesis of CD. CD pathogenesis is related to immune dysregulation, which involves the gastrointestinal system, and the extra-intestinal systems such as the nervous system, whose neurological symptoms are evidenced in CD patients. A gluten-free diet (GFD) could avoid cerebellar ataxia, epilepsy, neuropathies, migraine and mild cognitive impairment. Furthermore, untreated CD patients have more symptoms and psychiatric co-morbidities than those treated with a GFD. Common psychiatric symptoms in untreated CD adult patients include depression, apathy, anxiety, and irritability and schizophrenia is also common in untreated CD. Several studies show improvement in psychiatric symptoms after the start of a GFD. The present review discusses the state of the art regarding neurological and psychiatric complications in CD and highlights the evidence supporting a role for GFD in reducing neurological and psychiatric complications.
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Affiliation(s)
- Giovanna Campagna
- Medicine and Health Science School,Università "G. d'Annunzio",Via dei Vestini,31,66100 Chieti CH,Italy
| | - Mirko Pesce
- Medicine and Health Science School,Università "G. d'Annunzio",Via dei Vestini,31,66100 Chieti CH,Italy
| | - Raffaella Tatangelo
- Medicine and Health Science School,Università "G. d'Annunzio",Via dei Vestini,31,66100 Chieti CH,Italy
| | - Alessia Rizzuto
- Medicine and Health Science School,Università "G. d'Annunzio",Via dei Vestini,31,66100 Chieti CH,Italy
| | - Irene La Fratta
- Medicine and Health Science School,Università "G. d'Annunzio",Via dei Vestini,31,66100 Chieti CH,Italy
| | - Alfredo Grilli
- Medicine and Health Science School,Università "G. d'Annunzio",Via dei Vestini,31,66100 Chieti CH,Italy
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20
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21
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Abstract
There is a growing interest in the extraintestinal manifestations of common pediatric gastrointestinal diseases, such as inflammatory bowel disease and celiac disease. This article specifically focuses on the neurological symptoms that manifest because of these disorders and their treatments. Many neurological symptoms have been reported in association with these diseases, including neuropathy, myopathy, ataxia, headache, and seizures, among others. It is currently believed that these neurological symptoms are largely overlooked by practitioners and could be a red flag for earlier diagnosis. However, additional research, especially in the pediatric population, is warranted to further elaborate on the causality and pathophysiology of these neurological symptoms.
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Affiliation(s)
- Melissa Shapiro
- From the Section of Gastroenterology, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA
| | - David A Blanco
- From the Section of Gastroenterology, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA.
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22
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Analysis of the concentration of vitamin E in erythrocytes of patients with celiac disease. GASTROENTEROLOGY REVIEW 2017; 11:282-285. [PMID: 28053684 PMCID: PMC5209463 DOI: 10.5114/pg.2016.61354] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 08/11/2015] [Indexed: 11/29/2022]
Abstract
Introduction Consumption of gluten proteins leads to an enteropathy characterised by lymphocytic infiltration of mucous membrane, crypts hypertrophy, and atrophy of villi. Enteropathy leads to disturbances in the immune system as well as secondary deficiency of vitamin E. Aim Analysis of the concentration of vitamin E in erythrocytes of patients with celiac disease. Material and methods Three experimental groups were distinguished among 77 patients with histologically confirmed celiac disease (mean age: 17 years): those who strictly respected gluten-free diet (group I, n = 48), patients breaking dietary recommendations (group II, n = 22), and those with newly diagnosed disease (group III, n = 7). Additionally, a control group consisting of healthy individuals with negative serological markers of celiac disease was formed (group IV, n = 20). Vitamin E concentration was determined by high performance liquid chromatography with ultraviolet detector. Results Significantly lower average concentration of vitamin E was demonstrated in erythrocytes in all examined groups of patients with celiac disease compared to the control group. Among the patients with celiac disease, the highest average concentration of vitamin E in erythrocytes was observed in the group who respected the gluten-free diet, a little lower in patients who violated dietary recommendations, and lowest among patients with newly diagnosed disease. These relationships, however, were not statistically significant. Conclusions Patients with celiac disease are at risk of vitamin E deficiency irrespective of their diet. Vitamin supplementation should be considered in their case, especially immediately after diagnosis of the disease and in case of breaking a gluten-free diet regime.
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23
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Balcı O, Yılmaz D, Sezer T, Hızlı Ş. Is Celiac Disease an Etiological Factor in Children With Migraine? J Child Neurol 2016; 31:929-931. [PMID: 26887413 DOI: 10.1177/0883073816630088] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 01/05/2016] [Indexed: 12/31/2022]
Abstract
To determine the prevalence of celiac disease in children and adolescents with migraine, the authors investigated serum levels of tissue transglutaminase antibody immunoglobulin A and total immunoglobulin A from 81 children with migraine and in a healthy control group of 176 children. Study participants who were positive for tissue transglutaminase immunoglobulin A antibodies underwent a duodenal biopsy. Two patients in the migraine group (2.5%) and 1 in the control group (0.57%) tested positive for serum tissue transglutaminase immunoglobulin A antibodies (P > .05). Duodenal biopsy did not confirm celiac disease in both groups, and these patients were considered "potential celiac" cases. In the present study, children with migraine did not exhibit a higher prevalence rate of celiac disease compared with healthy controls. Therefore, the screening test for celiac disease is not a necessary part of the management of migraine in children.
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Affiliation(s)
- Oya Balcı
- Department of Pediatrics, Division of Pediatric Gastroenterology, Keçiören Training and Research Hospital, Ankara, Turkey
| | - Deniz Yılmaz
- Department of Pediatrics, Division of Pediatric Neurology, Keçiören Training and Research Hospital, Ankara, Turkey
| | - Taner Sezer
- Department of Pediatrics, Division of Pediatric Neurology, Baskent University Medical Faculty, Ankara, Turkey
| | - Şamil Hızlı
- Department of Pediatrics, Division of Pediatric Gastroenterology, Keçiören Training and Research Hospital, Ankara, Turkey
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24
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Sezer T, Balcı O, Özçay F, Bayraktar N, Alehan F. Is Celiac Disease an Etiological Factor in Children with Nonsyndromic Intellectual Disability? J Child Neurol 2016; 31:285-288. [PMID: 26078418 DOI: 10.1177/0883073815589759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Accepted: 05/07/2015] [Indexed: 11/15/2022]
Abstract
To determine the prevalence of celiac disease in children and adolescents with nonsyndromic intellectual disability, we investigated serum levels of tissue transglutaminase antibody and total IgA from 232 children with nonsyndromic intellectual disability and in a healthy control group of 239 children. Study participants who were positive for tissue transglutaminase antibody underwent a duodenal biopsy. A total of 3 patients in the nonsyndromic intellectual disability group (5.45%) and 1 in the control group (0.41%) had positive serum tissue transglutaminase antibody (P > .05). Duodenal biopsy confirmed celiac disease in only 1 patient who had nonsyndromic intellectual disability. In this present study, children with nonsyndromic intellectual disability did not exhibit a higher celiac disease prevalence rate compared with healthy controls. Therefore, we suggest that screening test for celiac disease should not be necessary as a part of the management of mild and moderate nonsyndromic intellectual disability. However, cases of severe nonsyndromic intellectual disability could be examined for celiac disease.
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Affiliation(s)
- Taner Sezer
- Department of Pediatrics, Division of Child Neurology, Baskent University School of Medicine, Ankara, Turkey
| | - Oya Balcı
- Department of Pediatrics, Division of Child Gastroenterology, Baskent University School of Medicine, Ankara, Turkey
| | - Figen Özçay
- Department of Pediatrics, Division of Child Gastroenterology, Baskent University School of Medicine, Ankara, Turkey
| | - Nilufer Bayraktar
- Hematology laboratory, Baskent University School of Medicine, Ankara, Turkey
| | - Füsun Alehan
- Department of Pediatrics, Division of Child Neurology, Baskent University School of Medicine, Ankara, Turkey
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25
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Abstract
Case finding for celiac disease (CD) is becoming increasingly common practice and is conducted in a wide range of clinical situations ranging from the presence of gastrointestinal symptoms to failure to thrive in children, prolonged fatigue, unexpected weight loss and anemia. Case finding is also performed in associated conditions, such as autoimmune thyroid disease, dermatitis herpetiformis and type 1 diabetes, as well as in patients with irritable bowel syndrome, unexplained neuropsychiatric disorders and first-degree relatives of patients with diagnosed CD. This aggressive active case finding has dramatically changed the clinical characteristics of newly diagnosed patients. For instance, higher numbers of patients who present with extraintestinal symptoms are now being diagnosed with CD. Current recommendations state that due to a high risk for complications if the disease remains undiagnosed, patients with extraintestinal symptoms due to CD require appropriate diagnosis and treatment. Despite criticism regarding the cost-effectiveness of case finding in CD, such an aggressive approach has been considered cost-effective for high-risk patients. The diagnosis of CD among patients with extraintestinal symptoms requires a high degree of awareness of the clinical conditions that carry a high risk for underlying CD. Also, understanding the correct use of specific serology and duodenal histology is key for an appropriate diagnostic approach. Both procedures combined are able to confirm diagnosis in the vast majority of cases. However, in certain circumstances, serology and even duodenal histology cannot confirm or rule out CD. A common cause of negative IgA serology is IgA deficiency. For such eventuality, IgG-based serological tests can help confirm the diagnosis. Importantly, some histologically diagnosed cases still remain seronegative despite exclusion of IgA deficiency. On the other hand, duodenal histology may be normal despite the presence of CD-specific antibodies and active CD. This has been clearly demonstrated in some cases of untreated dermatitis herpetiformis, but may also be due to the patchy condition of CD or lesions that are not adequately recognized by nonexpert endoscopists and/or pathologists. The effectiveness of agluten-free diet depends on the clinical end point addressed. A good example is the outcome of bone loss. While risk for fracture normalizes after the first year of dietary treatment, bone parameters measured by densitometry may not be normalized in the long-term follow-up. Moreover, it is still unclear how far an early gluten-free diet will positively affect associated autoimmune diseases like type 1 diabetes and autoimmune thyroiditis.
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26
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Crespo Pérez L, Tavío Hernández E, Téllez Villajos L, Aicart Ramos M, Cuño Roldán JL, Zarza Sanz B, Cano Ruiz A. [Ataxia and frontal syndrome in a young woman resolved with a gluten-free diet]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 38:545-7. [PMID: 25458545 DOI: 10.1016/j.gastrohep.2014.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2014] [Revised: 08/25/2014] [Accepted: 09/10/2014] [Indexed: 11/19/2022]
Affiliation(s)
- Laura Crespo Pérez
- Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Madrid, España.
| | | | - Luís Téllez Villajos
- Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Madrid, España
| | - Marta Aicart Ramos
- Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Madrid, España
| | | | - Beatriz Zarza Sanz
- Servicio de Neurología, Hospital Universitario Ramón y Cajal, Madrid, España
| | - Ana Cano Ruiz
- Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Madrid, España
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27
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Işıkay S, Kocamaz H. Prevalence of celiac disease in children with idiopathic epilepsy in southeast Turkey. Pediatr Neurol 2014; 50:479-481. [PMID: 24656466 DOI: 10.1016/j.pediatrneurol.2014.01.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/24/2013] [Accepted: 01/05/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND We examined the prevalence of celiac disease in children with idiopathic epilepsy. METHODS Patients were screened for celiac disease using the immunoglobulin A anti-tissue transglutaminase antibody. Upper gastrointestinal endoscopy and small intestinal biopsy were offered to all antibody-positive patients. The control group consisted of 400 healthy children. RESULTS A total of 600 patients (332 boys, 268 girls; 8 months-15 years; 9.40 ± 4.09 years) were studied. In 38 patients, the diagnosis was childhood partial epilepsy with occipital paroxysms. Six of the 38 patients with childhood partial epilepsy with occipital paroxysms (15.7%) had positive immunoglobulin A anti-tissue transglutaminase antibody. The frequency of biopsy-proven celiac disease was 15.7% (6/38) among children with childhood partial epilepsy with occipital paroxysms. None of the control patients had positive immunoglobulin A anti-tissue transglutaminase antibody results. CONCLUSIONS These findings suggest that the prevalence of celiac disease in children with partial epilepsy with occipital paroxysms may be higher than with other types of epilepsies. It may be reasonable to screen individuals with this type of epilepsy for celiac disease.
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Affiliation(s)
- Sedat Işıkay
- Division of Pediatric Neurology, Gaziantep Children's Hospital, Gaziantep, Turkey.
| | - Halil Kocamaz
- Division of Pediatric Gastroenterology, Gaziantep Children's Hospital, Gaziantep, Turkey
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28
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Parisi P, Principessa L, Ferretti A, D'Onofrio D, Del Giudice E, Pacchiarotti C, Villa MP. "EEG abnormalities" may represent a confounding factor in celiac disease: A 4-year follow-up family report. EPILEPSY & BEHAVIOR CASE REPORTS 2014; 2:40-42. [PMID: 25667866 PMCID: PMC4307964 DOI: 10.1016/j.ebcr.2014.01.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 01/20/2014] [Accepted: 01/30/2014] [Indexed: 11/03/2022]
Abstract
OBJECTIVE The occurrence of celiac disease (CD), electroencephalographic (EEG) abnormalities (with "subtle" seizures or even without any clinical seizures), and neurological disorders has been reported since the 1980s, though there has been no definitive consensus about the possible causal relationship. This topic is further complicated by the occurrence in infancy of 'clinical-EEG pictures' called 'benign epilepsy of infancy'. METHODS AND RESULTS Here, we report a 4-year follow-up on two siblings with newly diagnosed biopsy-proven celiac disease showing EEG abnormalities not responsive to a gluten-free diet. CONCLUSIONS This family report indicates that in patients with neurologically asymptomatic CD and EEG abnormalities, it is advisable to make a differential diagnosis between EEG abnormalities associated with CD and an incidental association with cortical hyperexcitability, with "subtle" seizures or even without any clinical seizures. PRACTICE IMPLICATIONS A long follow-up may sometimes be required, as it was in the family described here, to clarify the etiopathogenetic and therapeutic relationships between clinical and EEG features in CD.
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Affiliation(s)
- Pasquale Parisi
- Pediatrics and Child Neurology Unit, NESMOS Dept., Faculty of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa, 1035-1039, 00189 Rome, Italy
| | - Luigi Principessa
- Pediatrics and Child Neurology Unit, NESMOS Dept., Faculty of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa, 1035-1039, 00189 Rome, Italy
| | - Alessandro Ferretti
- Pediatrics and Child Neurology Unit, NESMOS Dept., Faculty of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa, 1035-1039, 00189 Rome, Italy
| | - Danila D'Onofrio
- Pediatrics and Child Neurology Unit, NESMOS Dept., Faculty of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa, 1035-1039, 00189 Rome, Italy
| | - Ennio Del Giudice
- Dept. of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Claudia Pacchiarotti
- Pediatrics and Child Neurology Unit, NESMOS Dept., Faculty of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa, 1035-1039, 00189 Rome, Italy
| | - Maria Pia Villa
- Pediatrics and Child Neurology Unit, NESMOS Dept., Faculty of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa, 1035-1039, 00189 Rome, Italy
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Abstract
BACKGROUND Neuropsychiatric symptoms may represent an atypical manifestation of celiac disease that occur before a gastroenterological diagnosis is made. Some studies suggest that a gluten-free diet is effective in treating the depression, anxiety, and neurological complications associated with celiac disease. METHOD The article describes the case of a patient suffering from chronic, treatment-resistant symptoms of depression and anxiety. The diagnosis of celiac disease and introduction of an elimination diet caused a significant improvement in mental state and everyday functioning in the presenting patient. CONCLUSION The presence of persistent anxiety and depressive symptoms, with a poor reaction to pharmacological treatment, indicates a need to identify somatic reasons for the underlying condition. It is important to remember that celiac disease can occur at any age, not only in childhood. The presence of this somatic cause of persistent depressive and anxiety symptoms should be considered in the diagnostic process in adults.
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Affiliation(s)
| | - Janusz OEmigielski
- Department of Geriatric Medicine Medical University of ŁódŸ, ŁódŸ, Poland
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Ferretti A, Parisi P, Villa MP. The role of hyperhomocysteinemia in neurological features associated with coeliac disease. Med Hypotheses 2013; 81:524-531. [PMID: 23891042 DOI: 10.1016/j.mehy.2013.06.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2013] [Revised: 06/15/2013] [Accepted: 06/22/2013] [Indexed: 12/14/2022]
Abstract
Although a range of neurological and psychiatric disorders are widely reported to be associated with coeliac patients, their pathogenesis remains unclear. Some such disorders are believed to be secondary to vitamin deficiency due to malabsorption, others to immune mechanisms. We hypothesise that hyperhomocysteinemia might, by damaging the blood-brain barrier, expose neuronal tissue to all neuro-irritative metabolites, such as homocysteine itself, a neurotoxic excitatory and proconvulsant amino acid. Neurons respond to these stimuli through hyperexcitability, thereby predisposing subjects to neurological disorders such as epilepsy and headache. Furthermore, persisting endothelial damage may cause blood extravasation and subsequent deposition of calcium salts. We suggest that this might be the pathogenesis of the CEC syndrome, which is characterized by the association of coeliac disease, epilepsy and cerebral calcifications. Indeed, homocysteine plays a well-known role in cardiovascular endothelial dysfunction, with high serum and cerebrospinal fluid levels often being reported in coeliac patients. Moreover, data in the literature show a strong, growing association of homocysteine with epilepsy and migraine in non-coeliac subjects. Despite these findings, homocysteine has never been held directly responsible for neuronal functional features (neuronal hyperexcitability underlying epilepsy and migraine) and structural brain damage (expressed as cerebral calcification) in coeliac patients. Damage to the blood-brain barrier might also facilitate immune reactions against neuronal tissue to a considerable extent. This hypothesis combines the two afore-mentioned theories (vitamin deficiency due to malabsorption and immune mechanisms). We also wish to point out that no studies have yet investigated the prevalence of neuronal hyperexcitability and subclinical electroencephalic abnormalities in children and adults with newly-diagnosed coeliac disease before the introduction of a gluten-free diet, and in particular any changes following the introduction of the diet. We believe that the onset of clinical symptoms such as migraine and convulsions is preceded by a period in which damage is expressed exclusively by subclinical electroencephalic abnormalities; persisting damage to neuronal tissue subsequently leads to clinical manifestations. We propose two types of investigations: the first is to determine whether newly-diagnosed coeliac patients with hyperhomocysteinemia are a subgroup at risk for neurological features (clinical and subclinical); the second is to determine whether appropriate treatment of hyperhomocysteinemia and vitamin B status deficiency improves neurological abnormalities and reduces the risk of cerebral calcifications. The aim of these investigations is to develop new therapeutic strategies designed to prevent neuronal damage and increase the quality of life in children affected by such disorders.
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Affiliation(s)
- Alessandro Ferretti
- Pediatric Sleep Disease Centre, Child Neurology, NESMOS Department, School of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa 1035-39, 00189 Rome, Italy
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Bhavsar AS, Verma S, Lamba R, Lall CG, Koenigsknecht V, Rajesh A. Abdominal manifestations of neurologic disorders. Radiographics 2013; 33:135-53. [PMID: 23322834 DOI: 10.1148/rg.331125097] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
A variety of disorders-including infectious, inflammatory, hereditary, and metabolic diseases-may affect both the brain and abdominal cavity, and the findings in one region may help establish the diagnosis or limit the differential diagnosis. Establishing an accurate early diagnosis enables clinicians to adequately manage these unusual diseases and potentially avert life-threatening complications. For example, an early diagnosis of Gardner syndrome enables annual sigmoid- or colonoscopy and ultrasonography. In many conditions, abdominal manifestations precede neurologic manifestations and may have prognostic significance. Patients with celiac disease more often present with abdominal manifestations such as duodenitis, slow transit time, reversal of the jejunal-ileal fold pattern, and transient small bowel intussusception than with intracranial manifestations. In other conditions, the neurologic manifestations may be the same as the presenting symptoms. For example, patients with Gardner syndrome may initially present with multiple mandibular or sinonasal osteomas. In addition, sarcoidosis may manifest with multifocal enhancing dural masses. Abdominal and neurologic manifestations may even occur simultaneously, as in several of the phakomatoses such as neurofibromatosis type 1, tuberous sclerosis complex, and von Hippel-Lindau syndrome. Ultimately, familiarity with the appearances of these conditions allows radiologists to pinpoint a diagnosis, even when imaging findings in either location are nonspecific.
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Affiliation(s)
- Anil S Bhavsar
- Department of Radiology, University of Cincinnati Hospitals, 234 Goodman St, ML 0761, PO Box 670761, Cincinnati, OH 45267-0761, USA.
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Ruuskanen A, Kaukinen K, Collin P, Krekelä I, Patrikainen H, Tillonen J, Nyrke T, Laurila K, Haimila K, Partanen J, Valve R, Mäki M, Luostarinen L. Gliadin antibodies in older population and neurological and psychiatric disorders. Acta Neurol Scand 2013; 127:19-25. [PMID: 22494246 DOI: 10.1111/j.1600-0404.2012.01668.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2012] [Indexed: 01/19/2023]
Abstract
OBJECTIVES A variety of neurological and psychiatric disorders have recently been linked to coeliac disease and gluten sensitivity. We here explored whether persistently positive gliadin antibodies (AGA) and coeliac-type HLA increase the risk of gluten sensitivity-related neurological and psychiatric manifestations. The study was carried out in an older population who had consumed gluten for decades but who had no previous coeliac disease diagnosis. MATERIALS AND METHODS The original study population comprised 4272 randomly selected older individuals, of whom 2089 had AGA and transglutaminase 2 antibodies (antiTG2) measured twice within a 3-year interval. Forty-nine persistently AGA-positive but antiTG2-negative subjects with coeliac-type HLA and 52 randomly selected persistently AGA- and antiTG2-negative age- and sex-matched controls were clinically examined for neurological disorders. The Psychological General Well-Being (PGWB) questionnaire, the SF-36 health survey questionnaire and the Depression Scale (DEPS) were employed to evaluate psychological well-being. The medical files of all the study subjects were analysed for previous illnesses. RESULTS Persistently AGA-positive but antiTG2-negative older subjects carrying coeliac disease-type HLA did not evince significantly more neurological symptoms or diseases than AGA-negative control subjects (P = 0.682, P = 0.233). There were no statistically significant differences between AGA-positive and AGA-negative groups in psychological well-being and quality of life when measured by PGWB (P = 0.426), SF-36 questionnaires (P = 0.120) and DEPS (P = 0.683). CONCLUSIONS At population level, persistent AGA positivity did not indicate gluten sensitivity-related neurological and psychiatric disorders.
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Affiliation(s)
- A. Ruuskanen
- Department of Neurology; Päijät-Häme Central Hospital in Lahti; Lahti; Finland
| | - K. Kaukinen
- Department of Gastroenterology and Alimentary Tract Surgery; Tampere University Hospital and Medical School, University of Tampere; Tampere; Finland
| | - P. Collin
- Department of Gastroenterology and Alimentary Tract Surgery; Tampere University Hospital and Medical School, University of Tampere; Tampere; Finland
| | - I. Krekelä
- Department of Gastroenterology; Päijat-Häme Central Hospital in Lahti; Lahti; Finland
| | - H. Patrikainen
- Department of Gastroenterology; Päijat-Häme Central Hospital in Lahti; Lahti; Finland
| | - J. Tillonen
- Department of Gastroenterology; Päijat-Häme Central Hospital in Lahti; Lahti; Finland
| | - T. Nyrke
- Department of Neurophysiology; Päijät-Häme Central Hospital in Lahti; Lahti; Finland
| | - K. Laurila
- Pediatric Research Center, University of Tampere and Tampere University Hospital; Tampere; Finland
| | - K. Haimila
- Finnish Red Cross Blood Service; Helsinki; Finland
| | - J. Partanen
- Finnish Red Cross Blood Service; Helsinki; Finland
| | - R. Valve
- Department of Education and Development in Lahti; University of Helsinki; Helsinki; Finland
| | - M. Mäki
- Pediatric Research Center, University of Tampere and Tampere University Hospital; Tampere; Finland
| | - L. Luostarinen
- Department of Neurology; Päijät-Häme Central Hospital in Lahti; Lahti; Finland
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Abstract
Neurologic complications of celiac disease (CD) include ataxia and peripheral neuropathy, which can be the presenting symptoms and signs. Early diagnosis and intervention could prevent development of further neurologic and systemic complications. Questions remain regarding the prevalence of the neurologic complications, the pathophysiological mechanisms, and the effectiveness of therapy or response to a gluten-free diet.
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Cognitive performance is impaired in coeliac patients on gluten free diet: a case-control study in patients older than 65 years of age. Dig Liver Dis 2012; 44:729-35. [PMID: 22484003 DOI: 10.1016/j.dld.2012.03.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2011] [Revised: 02/17/2012] [Accepted: 03/04/2012] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Retrospective studies and case reports suggest an association between coeliac disease and impaired cognitive function. AIM To evaluate functional and cognitive performances in coeliac disease vs. control patients older than 65 years. METHOD Eighteen coeliac disease patients (75±4 years, group A) on gluten free diet since 5.5±3 years and 18 age-sex matched controls (76±4 years, group B) were studied using a battery of neuropsychological tests. Results of functional and cognitive tests are expressed as "row scores" and as "equivalent scores" by relating "raw scores" to reference rank categories. RESULTS Barthel Index of functional performance was similar in the 2 groups. "Raw score" was significantly lower in coeliac disease than controls for Mini Mental Test Examination (p=0.02), Trail Making Test (p=0.001), Semantic Fluency (p=0.03), Digit Symbol Test (p=0.007), Ideo-motor apraxia (p<0.001) and Bucco-facial apraxia (p<0.002). "Equivalent score" was also lower in coeliac disease than controls for Semantic memory (p<0.01) and for Ideo-motor apraxia (p=0.007). CONCLUSION Cognitive performance is worse in elderly coeliac disease than control patients, despite prolonged gluten avoidance in coeliacs. Awareness on the increasing phenomenon of late-onset coeliac disease is important to minimize diagnostic delay and prolonged exposure to gluten that may adversely and irreversibly affect cognitive function.
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Fabbri E, Rustignoli L, Muscari A, Puddu GM, Guarino M, Rinaldi R, Minguzzi E, Caio G, Zoli M, Volta U. Recurrent ischemic strokes in a young celiac woman with MTHFR gene mutation. World J Gastroenterol 2012; 18:3472-6. [PMID: 22807619 PMCID: PMC3396202 DOI: 10.3748/wjg.v18.i26.3472] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2011] [Revised: 10/12/2011] [Accepted: 05/12/2012] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is frequently associated with neurological disorders, but very few reports concern the association with ischemic stroke. A 26-year-old woman affected by CD with secondary amenorrhea, carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia, was affected by two occipital ischemic strokes within a period of 5 mo. At the time of the second stroke, while she was being treated with folic acid, acetylsalicylic acid and a gluten-free diet, she had left hemianopsia, left hemiparesthesias, and gait imbalance. Brain magnetic resonance imaging showed a subacute right occipital ischemic lesion, which was extended to the dorsal region of the right thalamus and the ipsilateral thalamo-capsular junction. Antitransglutaminase and deamidated gliadin peptide antibodies were no longer present, while antinuclear antibodies, antineuronal antibodies and immune circulating complexes were only slightly elevated. Since the patient was taking folic acid, her homocysteine levels were almost normal and apparently not sufficient alone to explain the clinical event. A conventional cerebral angiography showed no signs of vasculitis. Finally, rare causes of occipital stroke in young patients, such as Fabry’s disease and mitochondrial myopathy, encephalomyopathy, lactic acidosis and stroke-like symptoms, were also excluded by appropriate tests. Thus, the most probable cause for the recurrent strokes in this young woman remained CD, although the mechanisms involved are still unknown. The two main hypotheses concern malabsorption (with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immune-mediated mechanisms. CD should be kept in mind in the differential diagnosis of ischemic stroke in young patients.
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Sidhom O, Laadhar L, Zitouni M, Ben Alaya N, Rafrafi R, Kallel-Sellami M, Lahmar H, El Hechmi Z, Makni S. Spectrum of Autoantibodies in Tunisian Psychiatric Inpatients. Immunol Invest 2012; 41:538-49. [DOI: 10.3109/08820139.2012.685537] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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IgA-class autoantibodies against neuronal transglutaminase, TG6 in celiac disease: No evidence for gluten dependency. Clin Chim Acta 2011; 412:1187-90. [DOI: 10.1016/j.cca.2010.09.042] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Revised: 09/10/2010] [Accepted: 09/10/2010] [Indexed: 01/09/2023]
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Abstract
OBJECTIVE To describe the prevalence of Coeliac disease (CD) and its clinical management. METHODS Narrative review. RESULTS Coeliac disease (CD) is an immune-mediated disorder that primarily affects the gastrointestinal (GI) tract. Recent data suggest a prevalence of about 1% in most Western countries, a figure that likely represents an increase in the prevalence of CD. Risk groups include those who are members of families with individuals who have CD as well as those with Type I diabetes and a variety of autoimmune diseases. Whereas biopsy is the gold standard in diagnosis, serological tests are crucial in determining who should undergo endoscopy and biopsy. HLA testing should be used only to rule out CD. Currently, a gluten-free diet is the only available therapy. CONCLUSION In conclusion, CD is one of the most common immune-mediated disorders in the Western world. It should be considered in patients with a number of varying GI and non-GI symptoms, as well as in high-risk groups that include first-degree relatives.
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Affiliation(s)
- J F Ludvigsson
- Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
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Volta U, Villanacci V. Celiac disease: diagnostic criteria in progress. Cell Mol Immunol 2011; 8:96-102. [PMID: 21278763 PMCID: PMC4003134 DOI: 10.1038/cmi.2010.64] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2010] [Accepted: 12/09/2010] [Indexed: 12/12/2022] Open
Abstract
Until a few years ago, celiac disease (CD) was thought to be a rare food intolerance that was confined to childhood and characterized by severe malabsorption and flat intestinal mucosa. Currently, CD is regarded as an autoimmune disorder that is common in the general population (affecting 1 in 100 individuals), with possible onset at any age and with many possible presentations. The identification of CD is challenging because it can begin not only with diarrhea and weight loss but also with atypical gastrointestinal (constipation and recurrent abdominal pain) and extra-intestinal symptoms (anemia, raised transaminases, osteoporosis, recurrent miscarriages, aphthous stomatitis and associated autoimmune disorders), or it could be completely symptomless. Over the last 20 years, the diagnostic accuracy of serology for CD has progressively increased with the development of highly reliable tests, such as the detection of IgA tissue transglutaminase and antiendomysial and IgG antideamidated gliadin peptide antibodies. The routine use of antibody markers has allowed researchers to discover a very high number of 'borderline' cases, characterized by positive serology and mild intestinal lesions or normal small intestine architecture, which can be classified as potential CD. Therefore, it is evident that the 'old celiac disease' with flat mucosa is only a part of the spectrum of CD. It is possible that serology could identify CD in its early stages, before the appearance of severe intestinal damage. In cases with a positive serology but with mild or absent intestinal lesions, the detection of HLA-DQ2 and HLA-DQ8 can help reinforce or exclude the diagnosis of gluten sensitivity.
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Affiliation(s)
- U Volta
- Department of Clinical Medicine, St Orsola-Malpighi University Hospital, Bologna, Italy.
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Abstract
Gluten-restricted diets have become increasingly popular among parents seeking treatment for children diagnosed with autism. Some of the reported response to celiac diets in children with autism may be related to amelioration of nutritional deficiency resulting from undiagnosed gluten sensitivity and consequent malabsorption. A case is presented of a 5-year-old boy diagnosed with severe autism at a specialty clinic for autistic spectrum disorders. After initial investigation suggested underlying celiac disease and varied nutrient deficiencies, a gluten-free diet was instituted along with dietary and supplemental measures to secure nutritional sufficiency. The patient's gastrointestinal symptoms rapidly resolved, and signs and symptoms suggestive of autism progressively abated. This case is an example of a common malabsorption syndrome associated with central nervous system dysfunction and suggests that in some contexts, nutritional deficiency may be a determinant of developmental delay. It is recommended that all children with neurodevelopmental problems be assessed for nutritional deficiency and malabsorption syndromes.
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Freeman HJ, Gillett HR, Gillett PM, Oger J. Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis. World J Gastroenterol 2009; 15:4741-4. [PMID: 19824105 PMCID: PMC2761549 DOI: 10.3748/wjg.15.4741] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a gluten-free diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 (or, about 4.3%) was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.
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Sensorineural hearing loss and celiac disease: a coincidental finding. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2009; 23:531-5. [PMID: 19668795 DOI: 10.1155/2009/540675] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Celiac disease (CD) can be associated with a variety of extraintestinal manifestations, including neurological diseases. A new neurological correlation has been found between CD and sensorineural hearing loss (SNHL). OBJECTIVE To verify the association between SNHL and CD, and to establish whether the neurological hearing impairment in CD is related to nonorgan-specific and antineuronal antibodies, as well as the presence of autoimmune disorders. METHODS A sample of 59 consecutive biopsy- and serologically proven CD patients were studied. Among CD patients, 11 were newly diagnosed and 48 were on a gluten-free diet. Hearing function was assessed by audiometric analysis in all CD patients as well as in 59 age- and sex-matched controls. Patients were tested for a panel of immune markers including nonorgan-specific autoantibodies and antineuronal antibodies. RESULTS SNHL was detected in five CD patients (8.5%) and in two controls (3.4%). In one patient, the SNHL was bilateral, whereas the remaining four had a monolateral impairment. The prevalence of SNHL was not significantly different between CD patients and controls. At least one of the antibodies tested for was positive in two of the five CD patients with SNHL and in 12 of the 54 CD patients without SNHL. Antineuronal antibodies to central nervous system antigens were consistently negative in the five CD patients with SNHL. Only one of the five CD patients with SNHL had Hashimoto thyroiditis. CONCLUSIONS SNHL and CD occur coincidentally. Hearing function should be assessed only in CD patients with clinical signs of hearing deficiency.
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Lionetti E, Francavilla R, Maiuri L, Ruggieri M, Spina M, Pavone P, Francavilla T, Magistà AM, Pavone L. Headache in pediatric patients with celiac disease and its prevalence as a diagnostic clue. J Pediatr Gastroenterol Nutr 2009; 49:202-207. [PMID: 19543115 DOI: 10.1097/mpg.0b013e31818f6389] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVES To establish the prevalence of headache in children with celiac disease (CD), the response to a gluten-free diet, and the prevalence of CD in children affected by headache. METHODS This hospital-based study included 2 steps. In the retrospective part, 354 children with CD answered a questionnaire investigating the presence of headache before and after the gluten-free diet. The same questionnaire was administered to 200 healthy children matched for sex and age. In the prospective part, 79 children affected by headache were screened for CD by antitransglutaminase IgA. Diagnosis of CD was confirmed by duodenal biopsy; before starting a gluten-free diet patients underwent a brain positron emission tomography study. After 6 months of follow-up children were reevaluated for the presence of headache. RESULTS Overall, 88 patients with CD complained of headaches before the diagnosis of CD as compared with 16 in the control group (24.8% vs 8%, P < 0.001). After the institution of a gluten-free diet, the headaches significantly improved in 68 children (77.3%), of whom 24 (27.3%) were headache-free during the study period. Four of 79 (5%) headache patients were found to have CD compared with 0.6% of the general population (P = 0.005). The brain positron emission tomography studies did not show any anomalies. During the follow-up, headaches improved in all 4 children with CD. CONCLUSIONS We recorded -- in our geographical area -- a high frequency of headaches in patients with CD and vice versa with a beneficial effect of a gluten-free diet. Screening for CD could be advised in the diagnostic work-up of patients with headache.
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Affiliation(s)
- Elena Lionetti
- Department of Paediatrics, University of Catania, Catania, Italy.
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Symposium 1: Joint BAPEN and British Society of Gastroenterology Symposium on ‘Coeliac disease: basics and controversies’ Coeliac disease in the twenty-first century. Proc Nutr Soc 2009; 68:234-41. [DOI: 10.1017/s0029665109001414] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Coeliac disease (CD), traditionally perceived as a rare childhood condition presenting with malabsorption, is instead an autoimmune multisystem disorder usually presenting in adulthood, affecting ⩾1% of the population and linked to the genetic expression of human leucocyte antigens (HLA) DQ2 and DQ8. Presentation occurs most often in the 40–60 years age-group, but potentially at any age. Symptoms attributable to the gut or to malabsorption may be mild, non-specific or absent; under one-third of patients have diarrhoea and almost half are overweight. Histological diagnosis no longer requires small intestine villous atrophy. The Marsh classification recognizes increased intraepithelial lymphocytes and crypt hyperplasia with intact villi as part of the gluten enteropathy spectrum, while some individuals have more subtle abnormalities identified only on electron microscopy. Serological testing for CD autoantibodies (to endomysium and tissue transglutaminase) has revolutionized diagnosis, shifting the process towards primary care. However, a substantial number of patients with CD are seronegative, particularly those without villous atrophy. The autoantibody to endomysium may be produced before histological change. The immune response to transglutaminase is crucial to the disease process. An exciting new development is the link between antibodies to organ-specific transglutaminases and clinical presentation; transglutaminases 2 (gut), 3 (skin) and 6 (nervous system). Negative testing for CD does not preclude its development later and HLA testing may allow ‘once and for all’ exclusion. In conclusion, an increasing proportion of patients with CD do not meet the ‘classic’ picture of malabsorption, positive serological testing and villous atrophy. Insisting on all these criteria for diagnosis will result in under diagnosis.
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Neurological disorders in adult celiac disease. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2009; 22:909-11. [PMID: 19018335 DOI: 10.1155/2008/824631] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Celiac disease may initially present as a neurological disorder. Alternatively, celiac disease may be complicated by neurological changes. With impaired nutrient absorption, different deficiency syndromes may occur and these may be manifested clinically with neurological changes. However, in patients with deficiency syndromes, extensive involvement of the small intestine with celiac disease is often evident. There are a number of reports of celiac disease associated with neuropathy, ataxia, dementia and seizure disorder. In these reports, there is no clear relationship with nutrient deficiency and a precise mechanism for the neurological changes has not been defined. A small number of patients have been reported to have responded to vitamin E administration, but most do not. In some, gluten antibodies have also been described, especially in those with ataxia, but a consistent response to a gluten-free diet has not been defined. Screening for celiac disease should be considered in patients with unexplained neurological disorders, including ataxia and dementia. Further studies are needed, however, to determine if a gluten-free diet will lead to improvement in the associated neurological disorder.
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El Moutawakil B, Chourkani N, Sibai M, Moutaouakil F, Rafai M, Bourezgui M, Slassi I. [Celiac disease and ischemic stroke]. Rev Neurol (Paris) 2009; 165:962-6. [PMID: 19144365 DOI: 10.1016/j.neurol.2008.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2008] [Revised: 07/25/2008] [Accepted: 09/29/2008] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Neurological manifestations of celiac disease are various. An association with ischemic stroke is not common and has not been well documented. We report two cases. OBSERVATIONS The first patient had experienced several transient ischemic strokes in the past 2 years and then had an acute ischemic stroke involving the territory of the right posterior cerebral artery. Investigations revealed celiac disease with no other recognizable etiology. The clinical course was marked by persistent visual aftereffects, but no new vascular event. The second patient had been followed since 1998 for celiac disease confirmed by pathology and serology tests. She was on a gluten-free diet. The patient had an ischemic stroke involving the territory of the left middle cerebral artery. Apart from a positive serology for celiac disease and iron deficiency anemia, the etiological work-up was negative. DISCUSSION The mechanisms of vascular involvement in celiac disease are controversial. The most widely incriminated factor is autoimmune central nervous system vasculitis, in which tissue transglutaminase, the main auto-antigen contributing to maintaining the integrity of endothelium tissue, plays a major role. Other mechanisms are still debated, mainly vitamin deficiency. CONCLUSION Being a potentially treatable cause of ischemic stroke, celiac disease must be considered as a potential etiology of stroke of unknown cause, particularly in young patients, and even without gastrointestinal manifestations.
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Affiliation(s)
- B El Moutawakil
- Service de neurologie et d'explorations fonctionnelles, CHU Ibn Rochd, quartier des hôpitaux, Casablanca, Maroc.
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Alehan F, Ozçay F, Erol I, Canan O, Cemil T. Increased risk for coeliac disease in paediatric patients with migraine. Cephalalgia 2008; 28:945-9. [PMID: 18624809 DOI: 10.1111/j.1468-2982.2008.01630.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The aim was to determine the prevalence of coeliac disease (CD) in paediatric patients with migraine. Serum tissue transglutaminase IgA (tTGA) antibodies and IgA concentrations were measured in 73 patients with migraine (age range 6-17 years) and the control group (n = 147). Patients having positive tTGA antibodies underwent duodenal biopsy. Four patients (5.5%) from the study group and one (0.6%) from the control group had positive tTGA antibody titres (P < 0.05). Three patients with migraine had normal duodenal histology and were considered as potential CD. One patient from the study group and one from the control group declined to have biopsy. tTGA antibody is considered as a reliable indicator for the presence of CD. However, some patients with positive antibodies may have normal biopsy initially and are classified as having potential CD. Our finding of a higher prevalance of tTGA antibodies in paediatric migraine patients suggests that an association between migraine and CD might exist.
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Affiliation(s)
- F Alehan
- Divisions of Child Neurology, Baskent University of Medicine, Ankara, Turkey.
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Anandacoomaraswamy D, Ullal J, Vinik AI. A 70-year-old male with peripheral neuropathy, ataxia and antigliadin antibodies shows improvement in neuropathy, but not ataxia, after intravenous immunoglobulin and gluten-free diet. J Multidiscip Healthc 2008; 1:93-6. [PMID: 21197340 PMCID: PMC3004541 DOI: 10.2147/jmdh.s3018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
This is a case of a 70-year-old man with severe peripheral neuropathy, type 2 diabetes and progressively worsening cerebellar ataxia. He was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology. The peripheral neuropathy improved with a gluten-free diet, antioxidants and intravenous immunoglobulin, whereas the ataxia did not. This case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia.
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A role for anti-transglutaminase 2 autoantibodies in the pathogenesis of coeliac disease? Amino Acids 2008; 36:685-91. [DOI: 10.1007/s00726-008-0127-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2008] [Accepted: 05/12/2008] [Indexed: 12/20/2022]
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