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Eur J Neurol. 2018 Mar;25(3):592-e38. doi: 10.1111/ene.13564. Epub 2018 Jan 24.

Persistent mucosal damage and risk of epilepsy in people with celiac disease.

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Academic Unit of Gastroenterology, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
Department of Paediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden.
Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Department of Pediatrics, University Hospital, Linköping, Sweden.



Celiac disease (CD) is associated with an increased risk of developing epilepsy, a risk that persists after CD diagnosis. A significant proportion of patients with CD have persistent villous atrophy (VA) on follow-up biopsy. The objective of this study was to determine whether persistent VA on follow-up biopsy affected long-term epilepsy risk and epilepsy-related hospital emergency admissions.


This was a nationwide cohort study. We identified all people in Sweden with histological evidence of CD who underwent a follow-up small intestinal biopsy (1969-2008). We compared those with persistent VA with those who showed histological improvement, assessing the development of epilepsy and related emergency hospital admissions (defined according to relevant International Classification of Diseases codes in the Swedish Patient Register). Cox regression analysis was used to assess outcome measures.


Villous atrophy was present in 43% of 7590 people with CD who had a follow-up biopsy. The presence of persistent VA was significantly associated with a reduced risk of developing newly-diagnosed epilepsy (hazard ratio, 0.61; 95% confidence interval, 0.38-0.98). On stratified analysis, this effect was primarily amongst males (hazard ratio, 0.35; 95% confidence interval, 0.15-0.80). Among the 58 patients with CD with a prior diagnosis of epilepsy, those with persistent VA were less likely to visit an emergency department with epilepsy (hazard ratio, 0.37; 95% confidence interval, 0.09-1.09).


In a population-based study of individuals with CD, persisting VA on follow-up biopsy was associated with reduced future risk of developing epilepsy but did not influence emergency epilepsy-related hospital admissions. The mechanism as to why persistent VA confers this benefit requires further exploration.


celiac; cohort study; epilepsy; villous atrophy

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