Causes of Neurologic Dysfunction in Celiac Disease and Gluten Sensitivity

Jaime Toro, MD

An analysis of neurologic phenotypes and etiologies in patients with celiac disease and gliadin antibody–positive patients without celiac disease

Celiac disease (CD) is an autoimmune disease triggered by gluten, a protein in wheat, rye, or barley. CD affects about 1% of the population and typically is characterized by gastrointestinal complaints. Gluten sensitivity (GS) is an illness distinct from CD with a prevalence of about 6%. Patients with GS lack villous atrophy or second-generation antibodies (Tg2-IgA or -IgG, or deamidated gliadin IgA or IgG) but can test positive for antibodies to gliadin. Both CD and GS may present with various neurologic and psychiatric comorbidities such as ataxia, epilepsy, peripheral neuropathies, inflammatory myopathies, myelopathies, headache, and gluten encephalopathy (Psychiatr Q 2012; 83:91).

To identify the causes of neurologic dysfunction in patients with CD or GS, researchers reviewed the medical records of 68 patients with either CD or gliadin-positive CS, divided into three groups according to CD-prerequisite human leukocyte antigen (HLA) haplotype and CD serologic findings. Group 1 patients had the HLA-DQ2 or DQ8 haplotype and had second-generation CD serologic testing positivity (Tg2-IgA or -IgG, or deamidated gliadin IgA or IgG) during neurologic evaluation or had a duodenal biopsy-proven diagnosis of CD before the evaluation. Group 2 patients did not have HLA-DQ2 or DQ8 haplotype but had first-generation CD serologic testing positivity (gliadin IgA or IgG). Group 3 patients had the HLA-DQ2 or DQ8 haplotype and had gliadin IgA or IgG testing positivity.

In group 1, 42 of 44 patients had CD. Neurologic conditions in this group included cerebellar ataxia (13), neuropathy (11), dementia (8), and myeloneuropathy (5). Causes of neurologic dysfunction were autoimmune; deficiency of vitamin E, folate, or copper; genetic; toxic; metabolic; tardive akathisia; superficial CNS siderosis; or unknown. In groups 2 and 3, none had CD; 21 of 24 patients had cerebellar ataxia. Causes of neurologic dysfunction in groups 2 and 3 were autoimmune, multiple system atrophy, toxic, nutritional deficiency, other, or unknown.

Citation(s):

McKeon A et al. The neurologic significance of celiac disease biomarkers. Neurology 2014 Nov 11; 83:1789.