It's going to take a long time...

[annelb]

Today I had the chance to chat with a neurologist. He mentioned something about staying up with what is new. Of course I asked him about celiac disease. His response to my question was that there is too much "hype" about celiac disease and that antibodies are found in a large percent of "normals". Obviously he has not read anything that Dr. Hadjivassiliou had written. :(

It is going to take a long time to raise awareness about CD. It is going to take forever to raise awareness of gluten sensitivity.

I am hoping that he will be curious enough to check out a few articles.

Anne

[jcc]

Pick some good ones!

Cara

[Leslieand]

Dr. Hadjivassiliou is so credible with such great research to back his hypothesis (Dr. Fine please submit your research) in neurological symptoms that I would think him very convincing.
But antigliadin antibodies lack specificity"
IgG anti-gliadin antibodies have been the best diagnostic marker in the neurological population we have studied. IgG anti-gliadin antibodies have a very high sensitivity for CD but they are said to lack specificity. In the context of a range of mucosal abnormalities and the concept of potential CD, they may be the only available immunological marker for the whole range of gluten sensitivity of which CD is only a part. Further support for our contention comes from our HLA studies. Within the group of patients with neurological disease and gluten sensitivity (defined by the presence of anti-gliadin antibodies) we have found a similar HLA association to that seen in patients with CD: 70% of patients have the HLA DQ2 (30% in the general population), 9% have the HLA DQ8, and the remainder have HLA DQ1. The finding of an additional HLA marker (DQ1) seen in the remaining 20% of our patients may represent an important difference between the genetic susceptibility of patients with neurological presentation to those with gastrointestinal presentation within the range of gluten sensitivity.

"But antigliadin antibodies have been superseded by anti-endomysial and transglutaminase antibodies"
The introduction of more CD specific serological markers such as anti-endomysium and more recently transglutaminase antibodies may have helped in diagnosing CD but their sensitivity as markers of other manifestations of gluten sensitivity (where the bowel is not affected) is low. This certainly reflects our experience with patients with gluten sensitivity who present with neurological dysfunction. Endomysium and transglutaminase antibodies are only positive in the majority but not in all patients who have an enteropathy. Patients with an enteropathy represent only a third of patients with neurological manifestations and gluten sensitivity. Antigliadin antibodies unlike endomysium and transglutaminase antibodies are not autoantibodies. They are antibodies against the protein responsible for gluten sensitivity.

"What do I do with a patient with positive anti-gliadin antibody test but normal duodenal biopsy"
Only one third of the patients with neurological disorders associated with gluten sensitivity have villous atrophy on duodenal biopsy. Even some with biochemical markers of malabsorption such as low serum vitamin B12, low red cell folate, or vitamin D concentrations had normal conventional duodenal histology.17 These cases may illustrate the patchy nature of bowel involvement in coeliac disease and the inaccurate interpretation of duodenal biopsies by inexperienced histopathologists. Preliminary data based on staining of the subpopulation of T cells in the small bowel epithelium suggests that these patients have potential CD.24 There are, however, patients where the immunological disorder is primarily directed at the nervous system with little or no damage to the gut. Our practice is to offer a gluten-free diet to these patients unless the HLA genotype is not consistent with susceptibility to gluten intolerance (that is, other than HLA DQ2, DQ8, or DQ1). All patients are followed up and any clinical response is documented.

"But my patient has not responded to a gluten free diet"
Reports in the literature of the effect of the gluten-free diet on neurological dysfunction are conflicting. Almost all patients reported in the literature have the diagnosis of CD before the development of neurological dysfunction. They may represent a different group of patients from those presenting with neurological dysfunction without bowel involvement. Additionally, improvement of gastrointestinal symptoms and improvement of the histological abnormalities on repeat small bowel biopsy often were the measures used to assess the response to the diet. Serological evidence of response (for example, sustained elimination of antigliadin antibodies) has rarely been used as confirmation of strict adherence to the gluten-free diet. Incomplete elimination of gluten from the diet may be enough to abolish gastrointestinal symptoms with recovery of the small bowel mucosa but is insufficient to arrest the state of heightened immunological responsiveness resulting in neuronal injury. There is a group of patients with CD "resistant" to gluten-free diet. This may reflect hypersensitivity to the minute amounts of gluten present in most "gluten-free" products. An analogous situation may exist in cases of gluten ataxia or gluten related neuropathy. The monitoring of neurological improvement in such cases is made difficult by the slow and sometimes incomplete regeneration of the nervous system. In cases of gluten ataxia where the underlying pathology is loss of Purkinje cells, one may only expect the stabilisation of the disease without any definite clinical improvement. This is in marked contrast to the response seen in patients with florid gastrointestinal symptoms who notice almost immediate improvement after the introduction of a gluten-free diet.

"Isn't the neurological damage nutritional?"
Nutrient deficiencies (B12, folate, vitamin D, vitamin E) are rare in this neurological population. Given that two thirds of these patients have no enteropathy this is hardly surprising. The concept of the neurological manifestations being nutritional in origin is now outmoded. Intestinal mucosal damage in coeliac disease is the result of both humoral and T cell mediated inflammation. Such inflammation is not, however, confined to the gut, as activated HLA restricted gliadin specific T cells25 and antigliadin antibodies are found systemically. Antigliadin antibodies are also found in the CSF.26 Postmortem findings from two of our patients with gluten ataxia has shown perivascular cuffing with both CD4 and CD8 cells. This inflammation was primarily seen in the white matter of the cerebellum. There was also marked but patchy Purkinje cell loss. We have also found antibodies against Purkinje cells in patients with gluten ataxia. Our research suggests that IgG antigliadin antibodies cross react with epitopes on Purkinje cells from human cerebellum.27 Characterisation of the anti-Purkinje cell antibodies by immunoblotting may provide a useful marker for the diagnosis of gluten ataxia in a manner analogous to the use of antiendomysium antibodies as a marker for coeliac disease or the anti-Yo antibody in paraneoplastic cerebellar degeneration.

http://jnnp.bmjjournals.com/cgi/content/full/72/5/560
Good luck,
Leslie

[annelb]

That is one of my favorite articles Leslie :D It is a good one to print out for him.

Thanks,
Anne