Coeliac disease and neurological dysfunction: a case-control study

Abstract

BackgroundPrevalence of neurological dysfunction in a prospective cohort of patients newly diagnosed with coeliac disease is yet to be determined. The spectrum of neurological deficit in patients with this disease remains unclear. We aimed to establish the prevalence of neurological deficit in patients newly diagnosed with coeliac disease and to compare the clinicoradiological features of this group with patients presenting with neurological changes that eventually led to diagnosis of the disorder. MethodsPatients with newly diagnosed coeliac disease recruited from a tertiary referral gastrointestinal clinic at the Sheffield Teaching Hospitals NHS Foundation Trust were prospectively reviewed by a neurologist and underwent MRI of the brain. Clinicoradiological features of patients who presented with neurological dysfunction to a tertiary referral neurological clinic and who were subsequently diagnosed with coeliac disease were retrospectively reviewed. MRI biomarkers—cerebellar volume (percentage ratio of cerebellar volume to total intracranial volume [%CV:TIV]); N-acetylaspartate to creatine ratio (NAA/Cr), a marker of neuronal health, measured with cerebellar proton MR spectroscopy; and voxel-based morphometry (VBM)—were analysed. Data were also compared with those of healthy volunteers who underwent the same MRI protocol and who were recruited from the local area. Regional ethics committee approved the study and all participants gave informed consent. Findings30 patients (mean age 47 years, SD 16, range 23–77; 12 men) with newly diagnosed coeliac disease were recruited. 20 patients (61 years, 10, 42–74, nine men) diagnosed with coeliac disease after initially presenting with neurological dysfunction (neurological dysfunction group) were reviewed. MRI data were obtained from a register of 55 healthy volunteers (41 years, 15, 20–77; 32 men). 11 patients (37%) with newly diagnosed coeliac disease had neurological deficits on clinical examination, ten with mild gait ataxia and one with peripheral neuropathy. 16 patients (80%) in the neurological dysfunction group had gait ataxia (nine mild, six moderate, one severe); four patients had peripheral sensory neuropathy. %CV:TIV and NAA/Cr were significantly reduced in the neurological dysfunction group compared with patients with newly diagnosed disease (mean %CV:TIV 7·5 [SD 1·5] vs 8·5 [0·8], 95% CI 0·24–1·76; p=0·01 and NAA/Cr 0·85 [0·13] vs 0·95 [0·07], 0·04–0·17; p=0·004). %CV:TIV and NAA/Cr were also significantly lower in the neurological dysfunction group than in healthy volunteers (mean %CV:TIV 7·5 [SD 1·5] vs 8·4 [1·2], 95% CI 0·05–1·83; p=0·039 and NAA/Cr 0·85 [0·13] vs 0·98 [0·09], 0·05–0·20; p=0·001). There was no significant difference in %CV:TIV or NAA/Cr between patients newly diagnosed with coeliac disease and healthy volunteers. Patients in the neurological dysfunction group showed multiple regions of reduced grey matter density, especially of the cerebellum but also involving supratentorial regions (p<0·05) compared with healthy volunteers. Patients newly diagnosed with coeliac disaese showed only modest reduction in grey matter in the cingulate gyrus (p<0·05). InterpretationOur results might not be generalisable because data were obtained from a tertiary referral centre. Moreover, analysis of the neurological dysfunction subgroup was retrospective. Nonetheless, to our knowledge this is the first study to attempt to provide a prevalence of neurological dysfunction prospectively in patients with coeliac disease while also examining MRI biomarkers of brain dysfunction. This study seems to show that a significant proportion of patients presenting with gastrointestinal symptoms who are diagnosed with coeliac disease already have some neurological dysfunction. The group of patients that present with neurological dysfunction are more severely affected. Serological testing for the disease should be incorporated into the investigation of patients with unexplained neurological symptoms. Increased awareness of the spectrum of neurological dysfunction in coeliac disease and close collaboration between neurologists and gastroenterologists might increase detection and prevent unnecessary delay to dietary treatment, which could lead to permanent neurological disability. FundingCoeliac UK, Bardhan Research & Education Trust.