Neurological evaluation of patients with newly-diagnosed coeliac disease presenting to gastroenterologists: A 7-year follow-up study

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Coeliac disease (CD) is part of a spectrum of gluten-related disorders that encompass diverse manifestations including dermatitis herpetiformis (DH) and neurological dysfunction (gluten ataxia, gluten neuropathy, gluten encephalopathy).

The extent patients with classic CD presentation suffer from neurological problems is still unknown and is an ongoing area of research interest. Research has found evidence of cognitive deficits, which may recover to some degree after starting a gluten-free diet (GFD), which patients with CD carry an increased risk of developing including vascular dementia, some reports of brain atrophy and white matter lesions alongside neurological problems mirroring those found in patients presenting neurologically with gluten ataxia/gluten encephalopathy. A recent validation study based on the UK national population data bank has replicated some of these findings including evidence of cognitive problems and brain white matter changes compared to controls.


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A number of antibodies have been associated with neurological complications in these patients including anti-gliadin antibodies as well as tissue transglutaminase 6 (TG6) which have been implicated as potentially diagnostic/pathogenic in the development of gluten ataxia. Transglutaminase 2 antibodies (TG2), a major diagnostic indicator for CD, have also been found deposited around brain vessel walls in patients with gluten ataxia.

This research group has previously shown that 67% of 100 patients newly-diagnosed with CD, presenting to gastroenterologists, have evidence of neurological dysfunction. Headache and loss of coordination were the main manifestations. Furthermore, 60% had abnormal brain imaging. In this follow-up study, we reviewed 30 of the original participating patients, 7 years after their baseline assessment. The aim of this investigation was to characterise any change in the clinical (neurological) phenotype of these patients and also to investigate relationships between antibody status and rate of brain atrophy.


The mean age of subjects at baseline (on presentation and diagnosis of CD) was 47.8 years and 55 years at follow up. Results demonstrated a significant reduction in the prevalence of headaches (47% to 20%) but an increase in the prevalence of incoordination (27% to 47%). Whilst those patients who had coordination problems at baseline reported improvement on a GFD, there were 7 patients reporting incoordination not present at baseline. All 7 patients had positive serology for one or more of gluten sensitivity-related antibodies at follow-up. As strict adherence to a GFD is thought to lead to elimination of gluten-related antibodies, this suggests suboptimal adherence to a GFD. However, the fact that these patients had very mild coordination problems compared with the typical severe problems often observed in these patients suggests that even a GFD which is not 100% strict may still offer some protection. In total, 50% of the follow-up cohort were positive for one or more gluten-related antibody. A comparison of brain imaging from baseline and follow-up showed a greater rate of cerebellar grey matter atrophy in the antibody positive group compared to the antibody negative group, although the level was significantly lower than baseline measurements.


This research group has previously demonstrated that patients with gluten ataxia who adhere to a strict GFD, as shown by the absence of gluten-related antibodies, improve. Those who do not go onto the diet, worsen and for those who follow the diet but are still serologically positive, also worsen, but at a slower pace. This may indicate a role for antibodies as a marker for gluten-sensitive patients who are at continued risk of neurological injury. In fact, as CD is autoimmune, the presence of these antibodies in the blood may be the actual driver of neurological problems as they react and promote a chronic inflammatory state. This current study further supports the relevance of serological markers in the assessment of CD patients by gastroenterologists.

In conclusion, patients with CD who do not strictly adhere to a GFD and are serologically positive are at risk of developing ataxia and have a significantly higher rate of cerebellar atrophy when compared to patients with negative serology. Regular review and close monitoring is important.


Hadjivassiliou M, Croall I.D., Grunewald R.A. et al. Nutrients. 2021, 13, 1846.