www.neurologyreviews.com/aug04/nr_aug04_gluten.html

GLUTEN SENSITIVITY IS PREVALENT IN PATIENTS WITH PERIPHERAL
NEUROPATHY

Gluten sensitivity in patients with neuropathy was more frequent than
in a control group and much greater than in the general population,
according to Lieutenant Colonel Eleanor E. Avery, MD. She advised that
a gluten-free diet may be appropriate in patients with antigliadin
antibodies, even in the absence of gastrointestinal symptoms.

"The results of our small pilot study are provocative and consistent
with previous reports showing enhanced prevalence of gluten
sensitivity in neuropathy patients as compared with the general
population," reported Lt. Col. Avery, of the Wilford Hall Medical
Center at Lackland Air Force Base, Texas. She presented her findings
at the 56th Annual Meeting of the American Academy of Neurology.

Peripheral neuropathy is a common diagnosis among patients with
neuropathy, noted Lt. Col. Avery. "Most patients would like an
ideology for their diagnosis as well as a specific treatment and
prognosis," she said. "Too often, the neuropathy is labeled as
cryptogenic or idiopathic when no answer is found." Neurologic
complications generally occur in up to 10% of patients with
established celiac disease; however, gluten sensitivity has been
reported to cause neurologic complications even when enteric disease
is not present. The prevalence of gluten-sensitive enteropathy is
estimated to be between 0.4% and 1% in the United States. "So any
prevalence in the neuropathy population that exceeds that might
indicate an independent cause/effect relationship," theorized Lt. Col.
Avery.

SCREENING FOR NEUROPATHY

Patients who were examined by a neurologist and believed to have
peripheral neuropathy symptoms were sent for standard laboratory
screening. The patients' blood was also sent for an antigliadin
antibody panel and any other special tests that the neurologist deemed
necessary. Serum was obtained from controls, who were patients
hospitalized for other reasons and had no peripheral neuropathy signs
or symptoms. The patients were not matched for age, sex, or race.

A total of 70 patients were screened for antigliadin antibodies. Of 45
patients with neuropathy who were tested, Lt. Col. Avery found that 15
patients (33%) had serum immunoglobulin G (IgG) or IgA antigliadin
positivity or both IgA and IgG positivity. For controls, four of 25
subjects (16%) had antigliadin positivity. The odds ratio for patients
versus controls was 2.58.

GLUTEN SENSITIVITY AND NEUROPATHY

Lt. Col. Avery believes that her findings are important because
peripheral neuropathy can lead to significant morbidity. She
emphasized that the disorder is typically a distal, symmetric axonal
sensory neuropathy and was previously believed to be secondary to fat-
soluble vitamin deficiency. "However," she commented, "recent studies
suggest that the neuropathy can occur in the absence of vitamin
deficiency and in response to a gluten-free diet. This may indicate
that isolated gluten sensitivity can precipitate an autoimmune disease
directed at the peripheral nervous system even in the absence of
celiac sprue.

"It is not known whether these patients have concomitant celiac
disease," Lt. Col. Avery added. "It has been postulated that gliadin
itself is the inciting cause of disease and that neurologic
manifestations occur secondary to direct toxicity of gluten without
concomitant gastrointestinal disease. These observations may offer
alternative treatment modalities, including dietary modification to
the usual symptomatic therapies for idiopathic peripheral neuropathy."

Lt. Col. Avery also said that testing antigliadin antibodies may be a
reasonable addition to a standard neuropathy panel. Further studies
are now under way to determine the prevalence of gluten sensitivity in
a larger population of patients with peripheral neuropathy.

See below link for web page titled "Neurological Manifestations of
Gluten" backed by numerous studies:

http://jccglutenfree.googlepages.com/theneurologicalmanifestationsofgluten

http://www.bmj.com/cgi/content/full/318/7200/1710

Gluten Sensitivity: A Many Headed Hydra
Heightened responsiveness to gluten is not confined to the gut

In a lecture entitled "On the coeliac affection"1 given in London in
1887 Dr Samuel Gee first described the condition we now refer to as
coeliac disease or gluten sensitive enteropathy. With clinical
manifestations confined to the gastrointestinal tract or attributable
to malabsorption, it was logical to assume that the key to the
pathogenesis of this disease resided in the gut. However, focusing
diagnostic criteria on the gut (as most physicians still do) has
delayed the appreciation of the wider spectrum of gluten sensitivity.

The treatment of coeliac disease remained empirical until 1940-50,
when the Dutch paediatrician Willem Dicke noted the deleterious effect
of wheat flour on individuals with coeliac disease.2 Removal of all
dietary products containing wheat resulted in complete resolution of
the gastrointestinal symptoms and a resumption of normal health. The
introduction of the small bowel biopsy in 1950-60 confirmed the gut as
the target organ in coeliac disease. The characteristic features of
villous flattening, crypt hyperplasia, and increase in intraepithelial
lymphocytes with improvement on gluten free diet became the mainstays
of the diagnosis of coeliac disease.

However, in 1966 Marks et al showed an enteropathy with a striking
similarity to coeliac disease in 9 out of 12 patients with dermatitis
herpetiformis.3 The enteropathy and the rash were gluten dependent and
the skin disease could occur even without histological evidence of gut
involvement. This discovery started to shift the emphasis from the gut
as the sole protagonist in this disease. With dermatitis herpetiformis
too came the concept of "latent" gluten sensitivity. The term is now
used to describe people with a histologically normal small bowel while
on a normal diet who at some stage of their lives have had or will
have an abnormal small bowel that responds to a gluten free diet.4

Also in 1966 Cooke and Thomas-Smith published a paper on neurological
disorders associated with adult coeliac disease.5 Further case reports
have since been published, but most are based on patients with coeliac
disease who later develop neurological dysfunction, implying that gut
disease is a prerequisite. We have, however, shown that neurological
dysfunction can not only precede coeliac disease but can also be its
only manifestation.6 Of even more interest is the demonstration of a
high prevalence of circulating antigliadin antibodies (IgG, IgA, or
both) in patients with neurological dysfunction of obscure aetiology
(57% v 5% in neurological controls and 12% in normal controls).7 Only
35% of these patients had histological evidence of coeliac disease.
The remaining 65% have gluten sensitivity where the target organ is
the cerebellum or the peripheral nerves, a situation analogous to that
of the skin in dermatitis herpetiformis.

In the light of these findings the specificity of antigliadin
antibodies has been questioned yet again. When the histological
criteria for coeliac disease are used as the gold standard, IgG
antigliadin antibody has low specificity. Nevertheless, IgG
antigliadin antibodies have a high sensitivity not only for patients
with coeliac disease but also for those with minimal or no bowel
damage where the principal target organ is the cerebellum or
peripheral nervous system. Supportive evidence for this contention
comes from the HLA genotype of patients with neurological disorders
associated with gluten sensitivity. As coeliac disease has one of the
strongest HLA associations of any immune disease (HLA DQ2 in more than
90% of patients) one would expect that patients positive for
antigliadin antibodies and with normal duodenal mucosa should have a
similar HLA genotype if they are truly gluten sensitive. In fact 85%
of our patients with neurological disorders associated with gluten
sensitivity have an HLA genotype in keeping with coeliac disease
compared with 25% of the normal population.8

Unlike antiendomysium or antireticulin antibodies, antigliadin
antibodies are antibodies against the extrinsic causal factor for
gluten sensitivity. Antiendomysium antibodies may be more specific for
coeliac disease, but no large scale data are available as yet on their
specificity or sensitivity in patients with gluten sensitivity where
the immunological target organ may be other than the gut.

The typical clinical expression of a patient with gluten sensitivity
where the sole manifestation is neurological is cerebellar ataxia,
often with a peripheral neuropathy.9 Most of these patients will have
histologically normal mucosa on biopsy and few or no gastrointestinal
symptoms. Both the ataxia and the neuropathy may be reversible with
adherence to a gluten free diet.9

Marsh's "modern" definition of gluten sensitivity is to be
recommended: "a state of heightened immunological responsiveness to
ingested gluten in genetically susceptible individuals."10 Such
responsiveness may find expression in organs other than the gut.
Gastroenterologists, dermatologists, neurologists, and other
physicians need to be aware of these developments if the diagnosis and
treatment of the diverse manifestations of gluten sensitivity are to
be advanced. The aetiology of such diverse manifestations presents the
next challenge.

What brought this on?

(By the way, Thunderbird underlines that "suspectible" word, and when
counting things, "many" is more appropriate than "high."  Also, "villi"
has two l's.)

Who's "we"?

Most of the stuff you've posted here is simple common sense, such as
diseases leading to morbidity, and neuropathy frequently involving
peripheral neuropathy.

But unless one has some sort of GI problem, how would gluten or gliadin
get into circulation, much less to the peripheral nerves?  Shouldn't you
have mentioned something like "leaky gut syndrome" first?  If gliadin is
getting into the bloodstream, that's where I'd begin the discussion.
After all, that's why they call this stuff "gluten enteropathy"!