Neurologic Deficits in Patients With Newly Diagnosed Celiac Disease Are Frequent and Linked With Autoimmunity to Transglutaminase 6

Clin Gastroenterol Hepatol. 2019 Dec;17(13):2678-2686.e2. doi: 10.1016/j.cgh.2019.03.014. Epub 2019 Mar 16.


Background & aims: Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to Transglutaminase 6 (TG6) increases the risk of neurologic defects in patients with a new diagnosis of celiac disease.

Methods: We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging of the brain, magnetic resonance (MR) spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction.

Results: Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from magnetic resonance imaging, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients-these patients had significant atrophy of subcortical brain regions compared with patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later.

Conclusions: In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurologic deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurologic manifestations among clinicians, and reinforcement of adherence to a strict GFD by patients to avoid permanent neurologic disability.

Keywords: Ataxia; Brain Atrophy; Headaches; Peripheral Neuropathy; Wheat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atrophy
  • Autoantibodies / immunology*
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Celiac Disease / diagnostic imaging
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology*
  • Celiac Disease / physiopathology
  • Cerebellum / diagnostic imaging
  • Cohort Studies
  • Diet, Gluten-Free
  • Female
  • GTP-Binding Proteins
  • Gait Ataxia / diagnostic imaging
  • Gait Ataxia / immunology*
  • Gait Ataxia / physiopathology
  • Gliadin / immunology
  • HLA-DQ Antigens
  • Headache / diagnostic imaging
  • Headache / immunology*
  • Headache / physiopathology
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Nystagmus, Pathologic / immunology
  • Nystagmus, Pathologic / physiopathology
  • Peripheral Nervous System Diseases / immunology*
  • Peripheral Nervous System Diseases / physiopathology
  • Prospective Studies
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / immunology*
  • Treatment Outcome
  • White Matter / diagnostic imaging*
  • Young Adult


  • Autoantibodies
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • Immunoglobulin A
  • Immunoglobulin G
  • Gliadin
  • Protein Glutamine gamma Glutamyltransferase 2
  • TGM6 protein, human
  • Transglutaminases
  • GTP-Binding Proteins