Gluten-sensitive idiopathic neuropathies
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Diagnosis of gluten-sensitive neuropathies without a clear cause is on the rise. These idiopathic neuropathies were first identified by screening for anti-gliadin IgG (AGA). The criteria have been critiqued because of the large misdiagnosis rate of coeliac disease (CD), and because AGA exists in the normal population at over 12%, far more abundant than cases of neuropathy. The problem in diagnosis arises because there are precursor states prior to coeliac disease. These are called subclinical coeliac disease and early gluten-sensitive enteropathy and are defined as Marsh grade 1 and 2 coeliac disease. Coeliac disease was diagnosed by duodenal biopsy, often misinterpreted as negative as high as grade 3 on the Marsh scale. Anti-gliadin antibodies may precede or lag the appearance of coeliac disease. Studies in Scandinavia found an increase of pathologies as much as 10 years before coeliac disease. These included gastrointestinal symptoms, anemia or other autoimmune disease. In addition IgG and IgA responses sometimes accompany allergic responses to proteins. Gliadin is exceptional in that it has several proteins which remain peptides of considerable length after digestion, and migrate into systemic circulation.
A subset of people with idiopathic neuropathies have only anti-gliadin antibodies but none of the other enteropathic criteria. About 1/3 have no DQ2 or DQ8 and an apparent abundance of HLA-DQ1. One percent of coeliacs in Europe have no DQ2 and DQ8 but have DQ1. The DQ1 serotype is very common in the normal population, over 65% of Americans have one copy, therefore the linkage is speculative.
At least one study suggests that gluten neuropathy can be effectively treated with a gluten-free diet. In the study, 35 patients with gluten neuropathy adhered to a gluten-free diet, where adherence was monitored serologically. After one year, the treatment group had improved significantly compared to the control group. The indicators of improvements were improvements of sural sensory action potential and subjective improvement of neuropathic symptoms. Subgroup analysis suggested that severe neuropathy might imply reduced capacity for recovery of the peripheral nerves or longer recovery.
Other neurological manifestations associated with gluten-sensitivity
Gluten involvement in idiopathic neuropathies was first defined as neurological dysfunction of an unknown cause associated with increased anti-gliadin antibodies. Early studies primarily focused on "gluten ataxia" and peripheral neuropathies.
A 2008 review concluded "From a purely evidence-based analysis of methodology, it can only be said that it is possible there is an association between coeliac disease or AGA and ataxia, but this association would need to be confirmed by a wide range of investigators doing better designed studies." See also Ataxia (Gluten)
A 2008 literature review concluded that, "based on principles of evidence-based medicine and evaluations of methodology, there is only a 'possible' association [of celiac disease and peripheral neuropathy], due to lower levels of evidence and conflicting evidence. There is not yet convincing evidence of causality."
A 2008 literature review concluded that, "From the evidence-based perspective, there is conflicting evidence whether there is or is not an association between coeliac disease or auto-antibodies and epilepsy. As yet there is no compelling evidence that there is a causal relation. There probably is a specific syndrome—coeliac disease with epilepsy and calcifications—which is rare and perhaps geographically specific."
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- Marsh M (1992). "Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue')". Gastroenterology 102 (1): 330–54. PMID 1727768.
- Grossman G (April 2008). "Neurological complications of coeliac disease: what is the evidence?". Pract Neurol 8 (2): 77–89. doi:10.1136/jnnp.2007.139717. PMID 18344378.