Coeliac disease and neurological complications

Coeliac disease is associated with various neurological complications - the two most common being cerebellar ataxia and peripheral neuropathy. However the evidence suggests that these neurological complications are not the result of vitamin or trace element deficiencies - but instead seem to be the result of neurotoxic effects of gluten sensitivity and particularly the pathophysiologic role of antigliadin antibodies.

• Hyperexcitable brain and refractory coeliac disease is the proposed term to encompass a spectrum of immune mediated diseases triggered by gluten ingestion (1)
  
  • a syndrome associated with Gluten related disorders (GRD)
    • whilst coeliac disease (gluten sensitive enteropathy) remains one of the best characterised GRD, neurological dysfunction is one of the commonest extraintestinal manifestations with a range of presentations such as:
      • cerebellar ataxia,
      • peripheral neuropathy,
      • sensory ganglionopathy
      • and encephalopathy (headaches and white matter abnormalities)
        
        
      • neurological manifestations can occur with or without enteropathy
      • neurological manifestations occur with normal vitamin levels e.g. B12 levels
        
        
• several neurological disorders have been described in association with coeliac disease, including epilepsy, myoclonus, ataxia, myelopathy and peripheral neuropathy (2)
  • gluten neuropathy is defined as apparently sporadic idiopathic neuropathy in the absence of an alternative aetiology and in the presence of serological evidence of gluten sensitivity
    • most common type is symmetrical sensorimotor axonal peripheral neuropathy, but other types of neuropathies have also been reported (4)
• the pathogenesis of neurological complications in coeliac disease remains unknown. Dietary and immune-mediated mechanisms have been suggested, but conclusive evidence is lacking
  • has been suggested that there is a potential pathophysiologic role of antigliadin antibodies in a neurotoxic autoimmune process (3)
  • current evidence suggests that neurological manifestations are immune mediated. Vitamin and trace element deficiencies rarely play a part, particularly as most patients with neurological manifestations have no enteropathy and are thus not prone to malabsorption and vitamin deficiencies (4)
    
    
• most patients who present with neurological manifestations of gluten sensitivity have no gastrointestinal symptoms. Patients with coeliac disease might not have gastrointestinal symptoms either. Therefore, gluten sensitivity cannot be diagnosed on a clinical basis alone
  • untreated patients typically have circulating antibodies to gliadin and to one or more type of transglutaminase
    • transglutaminase 6 in patients with neurological manifestations (4)

Reference:

• Hadjivassiliou M et al. Hyperexcitable brain and refractory coeliac disease: a new syndrome.J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):e2.
• Ryan AM et al.Vacuolar leucoencephalopathy and pulvinar sign in association with coeliac disease. BMJ Case Rep. 2009;2009.
• Hadjivassiliou M, Gibson A, Davies-Jones CA, et al . Does cryptic gluten sensitivity play a part in neurological illness? Lancet 1996;347:369-71
• Hadjivassiliou M et al. Gluten sensitivity: from gut to brain. Lancet Neurol. 2010 Mar;9(3):318-30.