Gluten Ataxia

The Gluten File

Excerpts from:
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
Systematic screening of 143 patients with so-called “idiopathic sporadic ataxia” showed that 41% had gluten sensitivity as defined by the presence of circulating antigliadin antibodies(with or without IgA).

”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.


Important - See Diagnostic Testing page for more complete information

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

PubMed Abstracts

RESULTS:The prevalence of TG6 antibodies was 21 of 65 (32%) in idiopathic sporadic ataxia, 35 of 48 (73%) in GA, 16 of 50 (32%) in CD, 4 of 82 (5%) in neurology controls, and 2 of 57 (4%) in healthy controls. Forty-two percent of patients with GA had enteropathy as did 51% of patients with ataxia and TG6 antibodies. Five of 15 consecutive patients with idiopathic sporadic ataxia had immunoglobulin A deposits against TG2, 4 of which subsequently tested positive for TG6 antibodies. After 1 year of gluten-free diet, TG6 antibody titers were significantly reduced or undetectable.
CONCLUSIONS:Antibodies against TG6 are gluten-dependent and appear to be a sensitive and specific marker of GA.
Transglutaminase 6 antibodies in the diagnosis of gluten ataxia.
PMID:23576621  May 2013

Gluten ataxia: an important treatable etiology of sporadic ataxia.
PMID: 22512541 Sept 2012

Case Report of Subacute Cerebellar Ataxia of Adolescence With Long-Term Sequelae.
PMID: 23034974

Immune-mediated acquired ataxias.
PMID:21827889  2012

MR spectroscopy and atrophy in Gluten, Friedreich's and SCA6 ataxias.
PMID 22070551  Nov 2011

Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons.
Transglutaminase 6: a protein associated with central nervous system development and motor function.
PMID:21984379  Oct 2011

Celiac crisis with ataxia in a child.
PMID 21437457  Oct 2011

Results: The incidences of GS in each population were 1% in normal subjects, 2% in hereditary ataxia patients and 9% in sporadic ataxia patients. High serum level of anti-gliadin IgG/IgA and t-transglutaminase IgA were disclosed at the sporadic ataxia patients compared with normal subjects. However, the anti-gliadin IgG is more specific to the disease of sporadic ataxia. Conclusion: Relatively higher incidence of GS was found in the population of sporadic ataxia patients but not in either normal subjects or hereditary ataxia patients in Taiwan. Anti-gliadin IgG still is a very powerful indicator to implicate the immune-related sporadic ataxia and we conclude that GS-related sporadic ataxia exists in Taiwan with linkage to autoimmune events.
Gluten sensitivity: associated sporadic cerebellar ataxia in taiwan.

PMID: 21210327  Dec 2010

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

In recent years, the involvement of the immune system in acquired forms of cerebellar ataxia has been frequently demonstrated. In this study, we describe 6 out of 49 patients with subacute or chronic progressive cerebellar ataxia in whom antibodies against neuronal and non-neuronal antigens were identified. Two women had anti-Yo antibodies; two patients had anti-gliadin antibodies in the presence of celiac disease; one patient had a complex autoimmune disorder associated with anti-Ro-52/SS-A and anti-muscle-specific kinase antibodies, and a patient developed subacute cerebellar syndrome associated with the presence of a prostatic adenocarcinoma and atypical antibodies reacting both with cerebellar tissue and with the prostatic tumor.
Immunological Reactivity against Neuronal and Non-Neuronal Antigens in Sporadic Adult-Onset Cerebellar Ataxia.
PMID: 19786780  Sept 2009

Cerebellar signs in celiac disease.
PMID: 19506229  June 2009

RESULTS: Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement. Such antibodies are absent in ataxia of defined genetic origin or in healthy individuals. Inhibition studies showed that in those patients with ataxia and enteropathy, separate antibody populations react with the two different transglutaminase isozymes. Furthermore, postmortem analysis of brain tissue showed cerebellar IgA deposits that contained transglutaminase 6. INTERPRETATION: Antibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and detection of anti-gliadin and anti-transglutaminase 2 antibodies to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease.
Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase.
PMID: 18825674  Sept 2008

Gluten ataxia is an immune-mediated disease triggered by the ingestion of gluten in genetically susceptible individuals. It should be considered in the differential diagnosis of all patients with idiopathic sporadic ataxia. Early diagnosis and treatment with a gluten free diet can improve ataxia and prevent its progression. Readily available and sensitive markers of gluten ataxia include antigliadin antibodies. IgA deposits against TG2 in the small bowel and at extraintestinal sites are proving to be additional reliable and perhaps more specific markers of the whole spectrum of gluten sensitivity. They may also hold the key to its pathogenesis.
Gluten ataxia.
PMID: 18787912  Sept 2008

Dermatitis herpetiformis and coeliac disease are gluten-sensitive diseases that share immunopathological mechanisms. Neurological disorders are reported in both diseases, being more frequent in coeliac disease. Dermatitis herpetiformis is rare in paediatric populations and only sporadic cases with neurological dysfunction are reported. Uncertainty exists as to whether early treatment may stop or reverse neurological symptoms. We describe here the case of a child presenting with a rash and ataxia, diagnosed with dermatitis herpetiformis, in whom neurological symptoms and signs regressed after treatment.
Dermatitis herpetiformis presenting as ataxia in a child.
PMID: 17340026 2007

Myoclonus in a context of progressive ataxia suggests one clinical form of the Ramsay-Hunt syndrome (progressive myoclonic ataxia, PMA), whose most frequent causes are: coeliac disease, mitochondriopathies, some spino-cerebellar degenerations, and some late metabolic disorders.
Symptomatic myoclonus.
PMID: 17336775  Sep-Dec 2006

Gluten sensitivity in Japanese patients with adult-onset cerebellar ataxia.
PMID: 16508226  Mar 2006

CONCLUSIONS: Anti-tissue transglutaminase IgA antibodies are present in the gut and brain of patients with gluten ataxia with or without an enteropathy in a similar fashion to patients with celiac disease, latent celiac disease, and dermatitis herpetiformis but not in ataxia control subjects. This finding strengthens the contention that gluten ataxia is immune mediated and belongs to the same spectrum of gluten sensitivity as celiac disease and dermatitis herpetiformis.
Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia.
PMID: 16476935  Feb 2006

CONCLUSION: Screening for AGA presence should be systematically performed at presentation of patients with unknown etiology ataxia; in the event AGA are present without any other etiology, treatment with gluten-free diet must be discussed. ....more 
[Ataxia associated with gluten sensitivity, myth or reality?]
PMID: 16518262 Feb 2006

[Progressive myoclonic ataxia associated with antibodies against Purkinje cells in a celiac patient]
PMID: 16454613 Dec 2005

Cerebellar abnormalities on proton MR spectroscopy in gluten ataxia.
PMID: 15965215 July 2005 

We report an unusual case of celiac disease with cerebellar ataxia. Gastrointestinal signs and malabsorption were not found in this patient. We suggested that celiac disease should be taken into consideration in differential diagnosis of patients with cerebellar ataxia with unknown etiology.
Subclinical celiac disease with cerebellar ataxia.
PMID: 15508272  June 2004

Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy. The diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia.
Dietary treatment of gluten ataxia.
PMID: 12933922  Sept 2003

Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia. Antigliadin antibody testing is essential at first presentation of patients with sporadic ataxia.
Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics
PMID: 12566288  March 2003

Patients with gluten ataxia have antibodies against Purkinje cells. Antigliadin antibodies cross-react with epitopes on Purkinje cells.
The humoral response in the pathogenesis of gluten ataxia.
PMID: 11971090  April 2002

The fact that the disease is strongly associated with the same HLA haplotypes found in coeliac disease not only demonstrates coeliac disease and ataxia with gluten sensitivity to be part of the same disease entity but supports the hypothesis of an immunological pathogenesis of cerebellar degeneration.
Sporadic cerebellar ataxia associated with gluten sensitivity.

PMID: 11335703  May 2001

Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials.

Gluten sensitivity in sporadic and hereditary cerebellar ataxia.
PMID: 11310636  April 2001

Idiopathic cerebellar ataxia associated with celiac disease: lack of distinctive neurological features.
PMID: 9886447  Jan 1999

Cerebellar ataxia associated with subclinical celiac disease responding to gluten-free diet.
PMID 10534283 Oct 1999

Gluten sensitivity is an important cause of apparently idiopathic ataxia and may be progressive. The ataxia is a result of immunological damage to the cerebellum, to the posterior columns of the spinal cord, and to peripheral nerves.
Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia
PMID: 9843103  Nov 1998