Brain Abnormalities Common in Celiac Disease Patients

September 10, 2012 — Patients with celiac disease and neurologic symptoms have substantial structural and functional brain deficits as detected on magnetic resonance imaging (MRI), British investigators have observed.

Stuart Currie, PhD, and colleagues from the University of Sheffield, United Kingdom, found that patients with celiac disease and balance disturbances had significantly smaller cerebellar volumes than age- and sex-matched controls.

The same imaging studies showed significantly less grey matter density in multiple regions of the brain, including the cerebellum, among patients with celiac disease than among controls. Similarly, white matter abnormalities (WMAs) were identified in a significant proportion of the celiac disease cohort versus none of the controls.

“We were not surprised by the differences in cerebellar volume because we know that ataxia is one of the commonest neurological manifestations of celiac disease and we were not particularly surprised by the findings of WMAs either because we had previously described this entity of gluten encephalopathy — headache and WMAs — in patients with celiac disease so here, we just demonstrated that these abnormalities are common,” co-investigator Marios Hadjivassiliou, MD, also from the University of Sheffield, told Medscape Medical News.

On the other hand, the fact that other areas of the brain are involved is interesting, he added, “in that they could potentially explain some of the other neurological problems such as sensory disturbances in patients who do not have peripheral neuropathy.”

They might also help explain the anxiety that patients with celiac disease often have as well, he noted.

The study was published online August 20 in the Journal of Neurology, Neurosurgery and Psychiatry.

Neurologic Opinion

As the authors note, 33 eligible patients with celiac disease, mean age 44 years, were referred for neurologic consultation between January 2009 and March 2011.

Patients were referred for imaging for balance disturbances, headache, or sensory loss. The median time from the diagnosis of celiac disease to MRI was 2.1 years.

MRI findings revealed that cerebellar volumes were significantly smaller than those in controls, but only in patients who reported balance disturbances: 6.9% vs 7.4%, respectively (P < .05).

On the other hand, the volume of grey matter in both superior cerebellar hemispheres and in multiple cortical regions was significantly smaller in the patient group overall than in age- and sex-matched controls (P < .05).

Thirty-six percent of patients with celiac disease were also found to harbor WMAs. The prevalence of WMAs was greatest in the headache subgroup, the authors note.

Gluten-Free Diet

As the authors discuss, two thirds of the patient group indicated they followed a gluten-free diet and were compliant with the diet when the imaging took place. The presence of WMAs in patients who appeared to have no known vascular risk factors implies a possible causal link between gluten sensitivity and WMAs, they add.

“What the findings mean is that patients with established celiac disease already on diet appear to have abnormal imaging that could account for some of their ongoing neurological complaints,” Dr. Hadjivassiliou said.

“What it also means is that the gluten-free diet in these cases needs to be strict as exposure to small amounts of gluten may still be enough to continue the neurological insult. This is why close monitoring and demonstration that gluten-related antibodies are eliminated from the blood are essential.”

Anna DePold Hohler, MD, from Boston University School of Medicine in Massachusetts told Medscape Medical News that the findings of decreased brain volume in patients with celiac disease help to solidify the neurologic implications of this disease.

“It also encourages further study in this area to better clarify the connection between the two and to eventually determine if treatment of celiac might also impact the brain,” she added.

The precise pathologic mechanism between brain abnormalities and celiac disease is under investigation but it will probably implicate an immunologic reaction against the TG6 antigen, which is found in the brain.

The TG6 antigen shares 65% homology with TG2, the autoantigen in celiac disease, and TG3, the autoantigen in dermatitis herpetiformis.

The authors and Dr. DePold Hohler have disclosed no relevant financial relationships.

J Neurol Neurosurg Psychiatry. Published online August 20, 2012.