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Celiac.com 09/17/2012 - Many aspects of celiac disease simply have not been well studied, so they remain poorly understood. For example, researchers have not done enough study on people with celiac disease to understand if they show any readily available serological markers of neurological disease. To better understand this issue, a research team recently assessed the amount of brain abnormality in patients with celiac disease, along with looking into MR imaging sequences as biomarkers for neurological dysfunction. The study team included S. Currie, M. Hadjivassiliou, M.J. Clark, D.S. Sanders, I.D. Wilkinson, P.D. Griffiths, and N. Hoggard, of the Academic Unit of Radiology at University of Sheffield, Royal Hallamshire Hospital, in Sheffield, UK. For their study, they conducted a retrospective examination of a consecutive group of 33 patients with biopsy proven celiac disease, who had been referred for neurological opinion. The group ranged in age from 19 to 64 years old, with an average of 44±13 years. Researchers divided the group into subgroups based on their main neurological complaints of balance disturbance, headache and sensory loss. They used 3T MR to evaluate variations in brain grey matter density, cerebellar volume, cerebellar neurochemistry and white matter abnormalities (WMAs) between celiac patients and control subjects. The results showed that the celiac patients had a significantly lower cerebellar volume than did control subjects. Celiac patients had 6.9±0.7% of total intracranial volume, compared with 7.4±0.9% for control subjects (p<0.05). Celiac patients also showed significantly less grey matter density in multiple brain regions, both above and below the tentorium cerebelli, compared with the control subjects (p<0.05). The data showed that 12 (36%) patients demonstrated WMAs unexpected for the patient's age, with the highest incidence occurring in the headache subgroup. This group of patients averaged nearly double the number of WMAs per MR imaging session than the subgroup with balance disturbance, and six times more than the subgroup with sensory loss. The MR images of celiac patients who have neurological symptoms show significant brain abnormality on MR imaging, which means that MR imaging may serve as valuable biomarkers of disease in celiac patients. Source: J Neurol Neurosurg Psychiatry. 2012 Aug 20.
Celiac.com 06/06/2014 - Celiac disease guidelines suggest that some patients with high anti-tTG ab levels might be diagnosed without biopsy. A team of Indian researchers recently reviewed their celiac disease database to determine if anti-tissue transglutaminase (tTG) antibody (ab) titers correlate with severity of villous abnormalities in Indian patients, and to find out a cutoff value of anti-tTG ab fold-rise that might best predict celiac disease. The researchers included P. Singh, L. Kurray, A. Agnihotri, P. Das, A.K. Verma, V. Sreenivas, S. Datta Gupta, and G.K. Makharia. The are affiliated with the Departments of Gastroenterology and Human Nutrition, Pathology, and Biostatistics at the All India Institute of Medical Sciences in New Delhi, India. The team reviewed data on 366 anti-tTG ab-positive individuals who received duodenal biopsies. The team conducted anti-tTG ab screens before patients began a gluten-free diet, and they expressed anti-tTG ab results in terms of fold-rise by calculating ratio of observed values with cutoff value. Celiac disease was diagnosed only in patients with positive serology, villous atrophy greater than Marsh grade 2, and clear response to gluten-free diet. Average anti-tTG fold-rise in groups with Marsh grade ≤2 was 2.6 (±2.5), grade 3a was 4.0 (±3.9), 3b was 5.7 (±5.1), and 3c was 11.8 (±8.0). Overall positive likelihood ratio for diagnosing celiac disease was 15.4 and 27.4 at 12- and 14-fold-rise of anti-tTG ab titer, respectively. The positive predictive value of diagnosis of celiac disease was 100% when anti-tTG ab titer was 14-fold higher over the cutoff value. Fifty-seven (43.9%) patients with anti-tTG titer rise less than 2-fold also had celiac disease. Levels of anti-tTG rise directly with severity of villous abnormality. High anti-tTG ab titers indicate likely villous atrophy. Contrary to emerging wisdom, even patients with anti-tTG ab levels less than 2-times baseline should receive mucosal biopsies, because many patients with celiac disease have such low levels. Source: J Clin Gastroenterol. 2014 Feb 27.
Scand J Gastroenterol 1999 Sep;34(9):909-14 AW Morrow Gastroenterology and Liver Centre, Dept of Histopathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. SPECIAL NOTE: European Codex Alimentarius quality wheat starch was used in this study. (Celiac.com 06/25/2000) BACKGROUND: It is expected that in patients with coeliac disease the small bowel mucosal mucosa will return to normal if they adhere to a gluten-free diet (GFD). However, in many this is not the case. This study aims to determine whether this persistent villous atrophy (VA) could be due to continued ingestion of the trace amounts of gluten in gluten-free foods, as defined by the WHO/FAO Codex Alimentarius. METHODS: Duodenal biopsy specimens from 89 adults with long-standing coeliac disease were examined, and the findings correlated with their form of gluten-free diet. RESULTS: In 51 subjects the duodenal specimen was normal, whereas in 38 there was villous atrophy (partial, 28; subtotal, 8; total, 2). There was no relationship between the presence or absence of VA and ingestion of either a GFD as defined by the Codex Alimentarius (Codex-GFD; 39 patients) or a GFD that contained no detectable gluten (NDG diet: 50 patients). Intraepithelial lymphocyte counts were higher, and lactase levels lower, in subjects with an abnormal biopsy specimen than in those in whom it was normal. However, within each of these biopsy groups there was no difference in these variables between patients on a Codex-GFD and those on an NDG-GFD. IgA antigliadin antibody was detected in 4 of 29 patients on a Codex-GFD and in 3 of 13 on a NDG-GFD (NS). CONCLUSION: The persistent mucosal abnormalities seen in patients with coeliac disease on a GFD are not due to the ingestion of trace amounts of gluten. The consequences of these abnormalities have yet to be determined.
Dig Liver Dis. 2004 Aug;36(8):513-8. Celiac.com 12/11/2004 - An Italian study was carried out to determine the incidence of brain perfusion abnormalities in those with celiac disease, and whether gluten intake and associated autoimmune diseases may be considered risk factors in causing cerebral impairment. The researchers used brain single-photon emission computed tomography to examine the brains of 34 adult celiac patients--16 on a gluten-free diet, 18 on a gluten-containing diet, and 18 with other autoimmune diseases--and compared them to 10 age and sex-matched controls with normal jejunal mucosa. The researchers found that 24 out of the 34 in the study--a full 71%--had brain tomography abnormalities. The most significant brain abnormalities were found in the patients with untreated celiac disease (74%), and in those with associated autoimmune disease (69%). The abnormalities mainly affected the frontal region of the brain. The researchers conclude that brain perfusion seems common in celiac disease, but does not appear to be related to associated-autoimmunity, and the condition may be improved by a gluten-free diet.