Anti-neuronal antibodies, epilepsy and white matter lesions are all increased in celiac disease, and studies of subclinical disease finds some extra-intestinal inflammatory conditions can precede coeliac disease.
In addition to an increase in anti-gliadin antibodies a HLA-DQ association has been suggested. Since there is a component of latent or subclinical coeliac disease within the idiopathic population it is not surprising an association with DQ2 was found. Also suggested was a link to DQ1.
Cerebellar ataxia
In gluten ataxia, early studies of disease identified a number patients with idiopathic cerebellar ataxia that had coeliac disease or signs of enteropathy. The ataxia, which involved gait and often limbs, was often associated with higher anti-gliadin antibodies. Gluten sensitivity was also suggested as a rare but possible cause of cerebral ataxia in small children Each of these studies uncovered a higher than expected number of coeliacs relative to the general population, but a subset of ataxia remained with elevated anti-gliadin antibodies. This idiopathic gluten ataxia may have anti-purkinje antibodies that are not adsorbed by gliadin. A gluten-free diet may improve gluten ataxia in the idiopathic subset, however a percentage did not respond to the diet. Other studies find no association between anti-gliadin antibodies and idiopathic cerebral ataxia. Still other studies suggest that a gluten-free diet has no impact on the course of disease. Both the proponents and critics of gluten ataxia have produced studies that lacked the proper sample size or controls to be considered objective.Peripheral neuropathies
The link of peripheral neuropathies with gluten-sensitive enteropathy is considerably stronger than with gluten ataxia. Coeliacs complain of burning, tingling or numbness in the hands or feet with some sensory loss. In addition axonopathy, nultifocal axonal polynephropathy, small-fiber neuropathy, motor neuropathy and anti-ganglioside antibody are found in coeliac disease. A few studies report idiopathic neuropathies which were not defined as enteropathic and fewer studies report the presence of anti-gliadin antibodies. Other studies found a normal occurrence of AGA in idiopathic peripheral neuropathies. Even among those that advocate gluten-sensitive neuropathies, the effective treatment rate on gluten-free diet is low. In instances where vitamin or mineral deficiencies are involved the recovery rate is substantially higher, however within the coeliac subset of neuropathies and within the idiopathic gluten-sensitive subset the response rate to gluten abstinence is low. One possibility is that enteropathy or gluten sensitivity is causing an autoimmune condition that once triggered becomes irreversible, the other possibility is that transient malnutrition causes damage that is irreversible, and a final possibility is that atypical anti-gliadin antibodies are damaging the nervous system; however such damage should quickly abate on a gluten-free diet.Epilepsy
As early as the 1960s it had been noticed that individuals with coeliac disease have neurological problems sometimes resembling epilepsy Subsequently epilepsy, particularly temporal lobe epilepsy, was found in coeliac disease patients. In the mid 1980s, studies conducted in Southern Europe noticed an association between epilepsy, occipital calcifications, and folic acid deficiency. Such calcifications are also seen in dementia. There is a growing body of evidence suggesting that subclinical cases in older adults will typically progress toward dementia, a large number of studies in Italy and Spain have documented earlier onset cases. Though the autoimmune condition is not known, folic acid malabsorption may be the cause.A number of studies have shown a link between gluten and brain calcifications that are either linked to epileptic disease such as Sturge-Weber syndrome, to a risk of epilepsy, or to visual or auditory problems caused by rare forms of epilepsy. Some of the studies have found celiac disease, while others have found increased anti-gliadin IgA, and still others have found remission or more easily treated disease with the removal of gluten. In the case of epileptic diseases the role of avitaminosis appears to be the key to restoring gastrointestinal function and folic acid and vitamin B12 metabolism. However, there is a gap in the literature as to the extent to which neuropathology is either caused by enteropathy or is the result of anti-gliadin IgA. The involvement of gluten in epilepsy is minor: Aside from the normal risk, the increase of coeliac disease incidence in epilepsy is small, and the idiopathic gluten-sensitive component is smaller still. The increased risk of epilepsy in coeliac disease is also small, but there appear to be substantive differences in the types of epilepsy coeliacs have, and this may extend to people who have idiopathic gluten-sensitivity.
Autism
In the early 1990s it was hypothesized that autism can be caused or aggravated by opioid peptides that are metabolic products of gluten. Several treatments based on this hypothesis are widely promoted. Popular diets eliminate foods containing gluten, often in combination with casein; studies supporting these diets have had significant flaws, so the data are inadequate to guide autism treatment recommendations.A recent review of the benefit of gluten-elimination diets indicates studies lack large scale, good quality randomised controlled trials
Other possible associations
Reductions and remissions of schizophrenic symptoms on a gluten-free diet have been noted in a subset of schizophrenic patients.. Many of these definitions were developed when the ability to define Marsh 1 and 2 grades CD was poor; and given the "brain calcification" association with GSE, it is likely that some cases of schizophrenia can be explained by GSE. The associations that remain, in terms of treatment results, appearto be weak.
Anti-gliadin antibodies are often elevated in Chronic fatigue syndrome; however, the study was conducted at a time when it was difficult to diagnose all grades of enteropathy. Significantly increased levels of IgA and IgG antibodies against gliadin and gluten were found in multiple sclerosis compared with controls. IgA antibodies against casein were significantly increased. Anti-endomycium and anti-transglutaminase antibodies were negative. Recent studies indicate that GSE is not associated with multiple sclerosis. And other studies question the association with idiopathic disease.
A recent study of children with severe cerebral palsy suggest a high percentage have anti-gliadin antibodies A study of patients with neurological myopathies demonstrated large percent were 'gluten sensitive' and many responded favorably with no other treatment.
Single studies with no corroborating studies or approaches are often difficult to use as evidence of association. Coeliac disease can cause a broad spectrum of problems, but associating non-enteropathic sensitivity is considerably less certain.
Adapted from the Wikipedia article Gluten-sensitive idiopathic neuropathies, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki
