The Gluten File

An Algorithm for the Evaluation of Peripheral Neuropathy


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Our findings suggest that the serological profile of gluten-sensitive ataxia/neuropathy without intestinal involvement lacks the recognition of deamidated gliadin and tissue transglutaminase epitopes.
Serology of celiac disease in gluten-sensitive ataxia or neuropathy: Role of deamidated gliadin antibody.
PMID: 21056914  Nov 2010

Excerpts from: 

Gluten sensitivity as a neurological illness
M Hadjivassiliou, R A Grünewald, G A B Davies-Jones:
Gluten sensitivity is best defined as a
state of heightened immunological responsiveness in genetically susceptible people.15 This definition does not imply bowel involvement. That gluten sensitivity is regarded as principally a disease of the small bowel is a historical misconception.28 Gluten sensitivity can be primarily and at times exclusively a neurological disease.29 The absence of an
enteropathy should not preclude patients from treatment with a gluten-free diet.
Early diagnosis and removal of the
trigger factor by the introduction of
gluten-free diet is a promising therapeutic intervention. IgG antigliadin antibodies should be part of the routine investigation of all patients with neurological  dysfunction of obscure aetiology, particularly patients with ataxia and peripheral neuropathy
Peripheral neuropathy is the second
commonest manifestation of gluten sensitivity. Prospective screening of 101 patients with idiopathic peripheral neuropathy has shown the prevalence of gluten sensitivity to be 40% (unpublished data). The commonest type of peripheral neuropathy we encountered is sensorimotor axonal (26) followed by mononeuropathy multiplex (15), pure motor neuropathy (10), small fibre neuropathy
(four) and mixed axonal and
demyelinating (two). The neuropathy is usually chronic and of gradual progression. Patients with a pure motor neuropathy may progress to involvement of sensory fibres.

”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 the two things which are relevant to CD are nutrition and immunity. People with CD have nutritional deficits because of malabsorption; common causes of neuropathy are B12 deficiency, B1 deficiency, B6 deficiency, and Vitamin E deficiency. Neuropathies are also commonly caused by the immune system through autoimmune mechanisims."..."Latov commented that 20-25% of people with CD might have neuropathy."
Celiac Disease and Peripheral Neuropathy, Norman Latov, MD, PHD 2002

Celiac neuropathy, Chin, et al  2003

Common Food Sensitivity Linked to Painful Peripheral Neuropathy


PubMed Abstracts

Our findings suggest that the serological profile of gluten-sensitive ataxia/neuropathy without intestinal involvement lacks the recognition of deamidated gliadin and tissue transglutaminase epitopes.
Serology of celiac disease in gluten-sensitive ataxia or neuropathy: Role of deamidated gliadin antibody.
PMID: 21056914  Nov 2010

RESULTS: Out of a total of 409 patients with different types of peripheral neuropathies, 53 (13%) had clinical and neurophysiologic evidence of sensory ganglionopathy. Out of these 53 patients, 17 (32%) had serologic evidence of gluten sensitivity. The mean age of those with gluten sensitivity was 67 years and the mean age at onset was 58 years. Seven of those with serologic evidence of gluten sensitivity had enteropathy on biopsy. Fifteen patients went on a gluten-free diet, resulting in stabilization of the neuropathy in 11. The remaining 4 had poor adherence to the diet and progressed, as did the 2 patients who did not opt for dietary treatment. Autopsy tissue from 3 patients demonstrated inflammation in the dorsal root ganglia with degeneration of the posterior columns of the spinal cord.

CONCLUSIONS: Sensory ganglionopathy can be a manifestation of gluten sensitivity and may respond to a strict gluten-free diet. 
Sensory ganglionopathy due to gluten sensitivity.
PMID: 20837968  Sept 2010

Celiac disease is a rare cause of neuropathy that most commonly presents with symmetric distal sensory disturbances. We describe two patients with celiac disease in whom neuropathy presented unusually with progressive weakness of the limbs. In both patients a gluten-free diet induced a significant improvement of muscle strength and neurophysiological abnormalities, suggesting a direct pathogenetic role of sensitivity to gluten. Celiac disease should be considered in patients with idiopathic neuropathy even when gastrointestinal symptoms are absent.
Celiac disease presenting with motor neuropathy: effect of gluten free-diet. 
PMID: 17226827  May 2007

Three months after the initiation of gluten-free diet, his ankle edema disappeared, electromyoneurographic signs of polyneuropathy improved and liver aminotransferases normalized. Good knowledge of CD extraintestinal signs and serologic screening are essential for early CD recognition and therapy.
Celiac disease manifested by polyneuropathy and swollen ankles.
PMID: 17552018  May 2007

A total of 35 patients participated in the study, with 25 patients going on the diet and 10 not doing so. There was a significant difference in the change of sural sensory action potentials (pre-defined primary endpoint), with evidence of improvement in the intention-to-treat group and deterioration in the control group. Subjective change in neuropathy symptoms also showed significant differences, with patients in the intention-to-treat group reporting improvement and those in the control group reporting deterioration. Gluten-free diet may thus be a useful therapeutic intervention for patients with gluten neuropathy
Dietary treatment of gluten neuropathy. PMID: 17013890  Sept 2006

Positive immunoglobulin (Ig)G with or without IgA antigliadin antibodies was found in 34% (47/140) of the patients with idiopathic neuropathy. This compares with 12% prevalence of these antibodies in the healthy controls. The prevalence of coeliac disease as shown by biopsy in the idiopathic group was at least 9% as compared with 1% in the controls. The clinical features of 100 patients (47 from the prevalence study and 53 referred from elsewhere) with gluten neuropathy included a mean age at onset of 55 (range 24-77) years and a mean duration of neuropathy of 9 (range 1-33) years. Gluten-sensitive enteropathy was present in 29% of patients. The human leucocyte antigen types associated with coeliac disease were found in 80% of patients.
Neuropathy associated with gluten sensitivity.
PMID: 16835287 Jul 2006

Anti-tissue transglutaminase IgA antibodies in peripheral neuropathy and motor neuronopathy.
PMID: 16774628 July 2006

Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside.
PMID: 16766047  Jun 2006

CONCLUSION: There was a high frequency of additional sources of DSP in patients with DM. These patients more often had sensory symptoms and findings in the hands. Tests that may be useful in the evaluation of DSP in diabetic patients include measures of vitamins B1, B6, B12, serum triglycerides, and immunofixation.
Additional causes for distal sensory polyneuropathy in diabetic patients.
PMID: 16484643  Mar 2006

CONCLUSIONS: Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study. 
Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings.
PMID: 16216941  Oct 2005

Gluten sensitivity and neuromyelitis optica: two case reports.
PMID: 15965221 Jul 2005

Cobalamine deficiency associated with neuropathy and oral mucosal melanosis in untreated gluten-sensitive enteropathy.
PMID: 16041109  June 2005

Coeliac disease is associated with numerous neurological manifestations including cerebellar ataxia, myelopathy, myopathy, and peripheral neuropathy. This report describes four patients who presented subacutely with presyncope and postural nausea. All four patients had biopsy proven coeliac disease with dysautonomia present on autonomic evaluation.
Autonomic neuropathy and coeliac disease.
PMID: 15774451  April 2005

Peripheral Neuropathy and Celiac Disease.
PMID: 15610706 Jan 2005

Neurologic complications are estimated to occur in 10% of affected patients, with ataxia and peripheral neuropathy being the most common problems
Celiac neuropathy.
May 2003   Full Text

Although previously considered rare, neurologic manifestations of gastrointestinal diseases are increasingly recognized
Neurologic manifestations of gastrointestinal disease Feb 2002

Our data suggest that gluten sensitivity is common in patients with neurological disease of unknown cause and may have aetiological significance.
Does cryptic gluten sensitivity play a part in neurological illness?
Feb 1996

Both vitamin depletion and immunological mechanisms may cause neurological disorder. Neurological manifestations may occur before the gastrointestinal symptoms.
Neurological diseases associated with celiac disease Feb 2000

It is well known that coeliac disease may be associated with various neurological manifestations. The most common neurological manifestations were neuropathy, memory impairment and cerebellar ataxia.
Coeliac disease presenting with neurological disorders

Peripheral neuropathies, of axonal and demyelinating types, have also been reported and may respond to elimination of gluten from the diet.
The neurology and neuropathology of coeliac disease Dec 2000

The neuropathy of celiac disease may be autoimmune and associated with anti-ganglioside antibodies.
Ganglioside reactive antibodies in the neuropathy associated with celiac disease June 2002


Please Note

While many of these references discuss peripheral neuropathy within the context of Celiac Disease, the research of Dr. Marios Hadjivassiliou and others is showing us that gluten sensitivity can manifest solely as neurological disease without meeting the strict diagnostic criteria (villous atrophy) for Celiac Disease. 

Gluten Sensitivity as a Neurological Illness