Neurological Dysfunction in Coeliac Disease and Non-coeliac Gluten Sensitivity

Marios Hadjivassiliou, MD; Dasappaiah G. Rao, MD; Richard A. Grünewald, DPhil; Daniel P. Aeschlimann, PhD; Ptolemaios G. Sarrigiannis, MD; Nigel Hoggard, MD; Pascale Aeschlimann, BSc; Peter D. Mooney, MD; David S. Sanders, MD

Disclosures

Am J Gastroenterol. 2016;111(4):561-567. 

In This Article

Methods

We undertook a retrospective analysis of all consecutive patients presenting with neurological dysfunction related to gluten sensitivity, to a neurology clinic (Neuroscience Department, Royal Hallamshire Hospital, Sheffield, UK), with an interest in neurological manifestations of GRD for 20 years between 1994 and 2014. No alternative etiology for their neurological dysfunction was found despite extensive investigations. All patients had been clinically assessed on several occasions and almost all remained under active follow-up on a six-monthly or yearly basis. All patients included had detectable circulating AGA (IgG and or IgA) at baseline as this was the only serum marker for gluten sensitivity available in 1994. Additional immunological markers (anti-endomysium antibodies and TG2 IgA antibodies) were assessed after they became locally available. All the serological testing was carried out at the regional clinical immunology lab. TG6 antibody testing was undertaken as previously described in some but not all patients as this test became available in 2008[12] TG6 testing is not as yet readily available and such testing was undertaken in the investigators lab. All patients underwent duodenal biopsy, HLA typing, and were offered GFD (irrespective of the presence or absence of enteropathy). All patients were reassessed clinically and with repeat brain imaging including magnetic resonance spectroscopy of the cerebellum (for patients with gluten ataxia) and magnetic resonance imaging of the brain in gluten encephalopathy or neurophysiology for patients with gluten neuropathy. All patients included had evidence of clinical and/or imaging and/or neurophysiological improvement on repeat assessments. Details of the methodology for such assessments (neurophysiology, magnetic resonance spectroscopy, and clinical assessment of the ataxia) has been described in detail elsewhere.[6,13,14] The above investigations and follow-up represent our normal clinical practice in caring for such patients.

The patients were separated into two groups based on the presence or absence of enteropathy. Group 1 consisted of all patients with enteropathy (triad of villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes) on biopsy (CD). Group 2 consisted of patients without enteropathy (NCGS). Group 2 was further subdivided into those patients with the HLA-DQ2 or -DQ8 (Group 2a) and those patients with HLA other than DQ2 or DQ8 (Group 2b). We also compared those patients in Group 2 with circulating TG2 antibodies with those without circulating TG2 antibodies.

Planned comparisons included the age of onset of symptoms, the prevalence of HLA subtypes and antibodies in the comparator groups. The frequency of dichotomous variables was compared using the χ 2 test. Means of interval data were compared using Student's t-test, Fisher's exact test, or analysis of variance where parametric or Kruskal–Wallis analysis of variance if non-parametric.

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