Prevalence of antigliadin antibodies in ataxia patients

We determined antigliadin antibodies in 95 ataxia patients and 73 controls. Antibodies were positive in 8% of the controls, 19% of patients with sporadic ataxia, 8% of patients with recessive ataxia, and 15% of patients with dominant ataxia. Statistical comparison using chi(2) statistics did not reveal significant differences between the groups. Although we found a trend toward a higher prevalence of antigliadin antibodies in patients with sporadic ataxia and dominant ataxia, our data do not support an association of ataxia with antigliadin antibodies.     

Multiple sclerosis and gluten sensitivity

OBJECTIVE: To compare the frequency of gluten sensitivity in patients with multiple sclerosis (MS) and healthy controls. PATIENTS AND METHODS: The patients were 161 clinically definite MS patients who referred to neurology outpatient clinic of Nemazee Hospital, Shiraz, south of Iran from March 2004 to October 2005. IgG and IgA antigliadin antibodies were measured by enzyme immuno assay (EIA) method. The test of IgA antitranstissue glutaminase (tTG) and duodenal biopsy were carried out in patients with either IgA or IgG AGA positive sera. Antigliadin antibodies were also measured for 166 age and sex matched control group. RESULTS: Neither IgG nor IgA antigliadin antibodies showed significant differences between MS patients and controls. Anti-tTG antibody and histopathologic studies were negative in all patients with positive IgG or IgA antigliadin antibodies results. Mean values of IgG and IgA antigliadin antibodies in MS patients with different sex, age, course, and functional systems involvement were not significantly different. CONCLUSION: Gluten sensitivity is not associated with MS in Iran.     

Autoimmunity as a prognostic factor in sporadic adult onset cerebellar ataxia

Cerebellar adult onset ataxia is a heterogeneous condition. The aim of this study was to ascertain if there is a heightened autoimmune background in patients with sporadic cerebellar ataxia of unknown origin, and if autoimmunity correlates with a more rapid evolution of the ataxia. We selected patients with sporadic progressive adult onset cerebellar ataxia with a follow-up of >5 years. As controls we included 43 patients with genetically demonstrated hereditary ataxia. All patients were tested for a panel of neuronal (onconeuronal, glutamate-decarboxylase [GAD], IgG/IgA transglutaminase 6 antibodies) and systemic non-neuronal antibodies (including IgG/IgA gliadin and transglutaminase 2, thyroperoxidase, thyroglobulin, antinuclear, striational, smooth muscle, mitochondrial, liver kidney microsomal, and parietal gastric cells antibodies). Correlation between the antibodies and disease progression was studied with Cox regression models and Kaplan-Meier plots. Forty-four patients were included. All patients were negative for onconeuronal or GAD antibodies. There were no significant differences between patients and controls in the prevalence of transglutaminase 6, 2, gliadin, or thyroid antibodies. However, when we studied the panel of systemic non-neuronal autoantibodies as a group, antibodies were more frequent in patients with sporadic ataxia (p = 0.018). The presence of one or more systemic non-neuronal antibodies correlated with a faster evolution to stage 2 (loss of independent gait) (p = 0.03) and shorter survival (p = 0.03) in patients with sporadic ataxia. We conclude that there is probably a heightened autoimmune background in some patients with sporadic cerebellar ataxia of unknown origin. The presence of systemic non-neuronal autoantibodies is a prognostic marker.     

Is celiac disease associated with Alzheimer's disease?

An increased prevalence of celiac disease has been reported in neurological disorders of unknown etiology. A large proportion of Alzheimer's cases is still of unexplained etiology. Thirty-three Alzheimer's patients and 24 elderly controls were screened for celiac disease. IgA and IgG antigliadin antibodies were assayed in serum samples with enzyme-linked immunoassay. Confirmation of celiac disease in positive subjects was made by assaying IgA anti-endomysium antibodies by indirect immunofluorescence. Two Alzheimer's patients and 2 controls were positive for antigliadin antibodies (6 versus 8%; NS). None was positive for anti-endomysium antibodies. We conclude that the prevalence of celiac disease in Alzheimer's disease is not higher than in cognitively unimpaired elders, suggesting that the immune changes in celiac disease are unlikely to play a role in Alzheimer's disease.     

Antigliadin antibodies in Huntington's disease

The relevance of gluten sensitivity in sporadic and hereditary ataxia pathogenesis is unclear. The authors found high antigliadin antibody titers in 23 of 52 (44%) patients with Huntington's disease (HD), suggesting a previously unrecognized association between HD and gluten sensitivity. The results further question "gluten ataxia" as a distinct disease entity and raise the possibility that antigliadin antibodies in ataxia and other neurodegenerative diseases may be an epiphenomenon, the mechanisms of which remain to be investigated.     

Chlamydia pneumoniae antibodies in various subtypes of ischemic stroke in Indian patients

BACKGROUND: As infections occur more frequently in developing countries, we carried out this prospective case-control study, to establish the association, if any, between C. pneumoniae antibodies and ischemic stroke particularly in relation to its subtypes. DESIGN: Antibodies (IgG and IgA) to C. pneumoniae in serum were measured by microimmunofluorescence test in 200 consecutive ischemic stroke patients and 200 age and sex matched controls. RESULTS: Seventy two out of 200 ischemic stroke patients (36%) had positive C. pneumoniae antibodies (IgG or IgA), compared to 35 out of 200 controls (17.5%) (p<0.0001). IgG antibody was positive in 64/200 (32%) ischemic stroke patients, compared to 34/200(17%) controls (p<0.0001) and IgA was positive in 20/200(10%) ischemic stroke patients compared to 1/200(0.5%) controls (p<0.0001). Logistic regression analysis showed statistically significant association between C. pneumoniae antibody positivity and ischemic stroke, thereby establishing it as an independent risk factor. Prevalence of C. pneumoniae antibodies was significantly higher in all stroke subtypes (except the stroke of undetermined etiology) compared to controls. CONCLUSION: Significant and independent association was found between C. pneumoniae antibodies and ischemic stroke in this sample of south Indian population. The association was found in all ischemic stroke subtypes, except stroke of undetermined etiology.     

Increased prevalence of silent celiac disease among Greek epileptic children

Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Many reports mention the association between epilepsy and celiac disease and the occasional presence of occipital corticosubcortical calcifications. We investigated 255 children with idiopathic epilepsy. Evaluation included use of routine, easily obtainable studies. Patients were screened for immunoglobulin A (IgA), immunoglobulin G (IgG) antigliadin antibodies and immunoglobulin A antitissue transglutaminase antibodies. Moreover, presence of IgA antiendomysial and antireticulin antibodies was screened. Patients with positive IgA antigliadin antibodies underwent a small intestinal biopsy. Controls consisted of 280 healthy children. Intestinal histopathologic changes, positive IgA antigliadin antibodies or IgG antigliadin antibodies, antireticulin antibodies, and antitissue transglutaminase IgA antibodies were found in five epileptic children but not in control subjects (P = 0.0241). Intracranial calcifications were not found in epileptic children with celiac disease. The findings indicate that prevalence of silent celiac disease is increased among children with idiopathic epilepsy; the type of epilepsy does not appear to play a role. Serum antitissue transglutaminase IgA antibodies could be a good marker for celiac disease screening. Occipital corticosubcortical calcifications are rarer in children with celiac disease and epilepsy.     

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.     

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.     

Serum Antibodies To Campylobacter Jejuni In Multifocal Motor Neuropathy

Multifocal motor neuropathy (MMN) has been frequently associated with high titers of anti-ganglioside antibodies but the cause of this immune response is not known. Recently a possible association with an antecedent Campylobacter jejuni (CJ) infection has been reported in three patients who developed MMN and high titers of anti-GM1 antibodies after CJ enteritis. Furthermore reactivity with the lipopolysaccharides (LPS) of CJ have been reported in some patients with chronic motor neuropathies and high anti-ganglioside antibodies. To determine whether CJ may be involved in the pathogenesis of MMN we examined 22 patients with MMN, including 6 with anti-ganglioside reactivity (2 GM1, 2 GD1a, 1 GM1+GD1a, 1 GM1+GM2), for the presence of anti-CJ antibodies by Covalink ELISA and immunoblot, and correlated their presence with that of anti-ganglioside antibodies. As controls we examined 17 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 23 with amyotrophic lateral sclerosis (ALS), 43 with other neurological diseases (OND) and 23 normal subjects (NS). By ELISA we found high titers (1/640) of anti-CJ in 8 patients (36%) with MMN (4 IgM, 2 IgA, 1 IgM+IgA, 1 IgM+IgG+IgA), 2 each with CIDP (12%; 1 IgA and 1 IgM) and ALS (9%; 1 IgM and 1 IgG), one with OND (2%; IgG) and none in NS (MMN vs. neurological controls p < 0.0005; MMN vs. NS p < 0.005). By immunoblot, 5 patients with MMN (23%), one of whom was also positive by ELISA, had a very intense reactivity (3 IgG, 1 IgA, 1 IgG+IgA) with a 14 kD band corresponding to the lipopolysaccharides (LPS) of CJ, as compared to two patients with ALS (9%; 1 IgG and 1 IgM), one each with CIDP (6%; IgG) and NS (4%), while no reactivity was found in OND (MMN vs. neurological controls p < 0.01). Overall anti-CJ antibodies were detected by at least one method in 12 MMN patients (55%), 3 CIDP (18%), 4 SLA (17%), 1 OND (2%) and 1 NS (4%) (MMN vs. neurological controls p < 0.0005; MMN vs. NS p < 0.0005). Anti-ganglioside antibodies were similarly frequent in patients with (33%) or without (20%) anti-CJ reactivity. The high frequency of anti-CJ antibodies in MMN patients supports the hypothesis of an association between MMN and CJ even if it is still unclear whether this reflects a concurrent or previous CJ infection possibly involved in the pathogenesis of MMN. If this is the case, the lack of association with anti-ganglioside antibodies suggests that these antibodies might not be the only anti-neuronal antigens induced by CJ.     

Dietary treatment of gluten ataxia

BACKGROUND: Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. No systematic study of the effect of gluten-free diet on gluten ataxia has ever been undertaken. OBJECTIVE: To study the effect of gluten-free diet on patients presenting with ataxia caused by gluten sensitivity. METHODS: 43 patients with gluten ataxia were studied. All were offered a gluten-free diet and monitored every six months. All patients underwent a battery of tests to assess their ataxia at baseline and after one year on diet. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. Fourteen patients refused the diet (control group). Three patients had persistently raised antigliadin antibodies despite adherence to the diet and were therefore excluded from the analysis. RESULTS: After one year there was improvement in ataxia reflected in all of the ataxia tests in the treatment group. This was significant when compared with the control group. The diet associated improvement was apparent irrespective of the presence of an enteropathy. CONCLUSIONS: 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.     

Gluten ataxia

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 sensitivity in sporadic and hereditary cerebellar ataxia

Gluten sensitivity, with or without classical celiac disease symptoms and intestinal pathology, has been suggested as a potentially treatable cause of sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally high serum immunoglobulin A (IgA) and IgG anti-gliadin antibody titers and typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with cerebellar ataxia who were tested for molecularly characterized hereditary ataxias. A high prevalence of gluten sensitivity was found in patients with sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including patients with known ataxia genotypes indicating a hitherto unrecognized association between hereditary ataxias and gluten sensitivity. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials.     

Chlamydia pneumoniae in elderly patients with stroke (C-PEPS): a case-control study on the seroprevalence of Chlamydia pneumoniae in elderly patients with acute cerebrovascular disease

BACKGROUND AND PURPOSE: Multiple studies have suggested an association between Chlamydia pneumoniae infection and atherosclerotic vascular disease. We investigated whether serological markers of C. pneumoniae infection were associated with acute stroke or transient ischaemic attack (TIA), exclusively in elderly patients. METHODS: One-hundred white patients aged over 65 years admitted with acute stroke or TIA, and 87 control patients admitted with acute non-cardiopulmonary, non-infective disorders were recruited prospectively. Using an enzyme-linked immunosorbent assay kit, the presence of C. pneumoniae immunoglobulins IgA, IgG, IgM in patients' sera was determined. RESULTS: The seroprevalence of C. pneumoniae-specific IgA, IgG, IgM were 63, 71, and 14% in the stroke/TIA group (median age = 80), and 62, 65, and 17% in the control group (median age = 80), respectively. Using a logistic regression statistical model, adjusting for age and sex, history of hypertension, smoking, diabetes, ischaemic heart disease (IHD), ischaemic electrocardiogram (ECG), the odds ratios (ORs) of having a stroke/TIA in relation to C. pneumoniae-specific IgA, IgG, IgM were 1.04, 1.24, 0.79 (p = NS). Further analysis identified 43 acute stroke/TIA cases and 44 controls without history of IHD or ischaemic ECG or both. After adjusting for history of hypertension, smoking, diabetes, age and sex, the ORs in this subgroup were 1.40 for IgA [95% confidence interval (CI) 0.53-3.65; p = 0.49], 2.41 for IgG (95% CI 0.90-6.46; p = 0.08) and 1.55 for IgM (95% CI 0.45-5.40; p = 0.49). CONCLUSIONS: Although a high seroprevalence of C. pneumoniae in elderly patients was confirmed, no significant association between serological markers of C. pneumoniae infection and acute cerebrovascular events was found. There was, however, a weak trend towards increased ORs for acute cerebrovascular disease in a subgroup of C. pneumoniae seropositive elderly patients without any history of IHD or ischaemic ECG.     

The humoral response in the pathogenesis of gluten ataxia

OBJECTIVE: To characterize humoral response to cerebellum in patients with gluten ataxia. BACKGROUND: Gluten ataxia is a common neurologic manifestation of gluten sensitivity. METHODS: The authors assessed the reactivity of sera from patients with gluten ataxia (13), newly diagnosed patients with celiac disease without neurologic dysfunction (24), patients with other causes of cerebellar degeneration (11), and healthy control subjects (17) using indirect immunocytochemistry on human cerebellar and rat CNS tissue. Cross-reactivity of a commercial IgG antigliadin antibody with human cerebellar tissue also was studied. RESULTS: Sera from 12 of 13 patients with gluten ataxia stained Purkinje cells strongly. Less intense staining was seen in some but not all sera from patients with newly diagnosed celiac disease without neurologic dysfunction. At high dilutions (1:800) staining was seen only with sera from patients with gluten ataxia but not in control subjects. Sera from patients with gluten ataxia also stained some brainstem and cortical neurons in rat CNS tissue. Commercial anti-gliadin antibody stained human Purkinje cells in a similar manner. Adsorption of the antigliadin antibodies using crude gliadin abolished the staining in patients with celiac disease without neurologic dysfunction, but not in those with gluten ataxia. CONCLUSIONS: Patients with gluten ataxia have antibodies against Purkinje cells. Antigliadin antibodies cross-react with epitopes on Purkinje cells.     

抗GD3 IgG抗体阳性的急性共济失调神经病的临床特点(附1例报告)

目的 探讨抗GD3 IgG抗体阳性的不完全Miller Fisher综合征(MFS)的亚型急性共济失调神经病的发病机制和临床特点.方法 回顾性分析1例抗GD3 IgG抗体阳性的不完全MFS的亚型急性共济失调神经病患者的临床资料并文献复习.结果 本例患者为69岁女性,急性起病.发病前有上呼吸道感染史.因"行走不稳20 d...     

Should coeliac disease be considered in the work up of patients with chronic peripheral neuropathy?

OBJECTIVE: To investigate whether there is an association between chronic peripheral neuropathy and coeliac disease. METHODS: The cause of chronic peripheral neuropathy was first investigated in a group of 478 patients. Published reports were then examined systematically for an association between chronic peripheral neuropathy and coeliac disease. Cases were divided into two groups: group A, polyneuropathy preceding duodenal biopsy and controls undergoing duodenal biopsies; group B, coeliac disease preceding polyneuropathy. Patients with cerebellar ataxia, small fibre neuropathy, or a cause for their neuropathy were excluded. RESULTS: In 425 of the 478 patients, a cause other than coeliac disease was established. In the patients with no determined cause for neuropathy, one had abnormally increased IgA antigliadin antibodies but duodenal biopsy was normal. Ten previous studies of patients with chronic peripheral neuropathies were reviewed. The incidence of biopsy proven coeliac disease in patients with polyneuropathy did not differ from the controls (group A). In patients with a proven coeliac disease (group B), polyneuropathy could not be diagnosed more often than in the general population. CONCLUSIONS: The results of both the clinical study and the literature review suggest that it is unlikely that chronic peripheral neuropathy without other neurological signs is associated with coeliac disease.     

GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia

Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain–Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.     

Antineuronal antibodies in sporadic late-onset cerebellar ataxia

Sporadic late-onset cerebellar ataxia of unknown cause is considered a neurodegenerative disorder whose underlying mechanisms are still unknown. To identify antineuronal autoantibodies, immunohistochemical and immunoblotting techniques were performed in 67 patients with sporadic cerebellar degeneration of unknown cause. Elevated P/Q-type voltage-gated calcium channel (VGCC)-specific antibodies were found in eight patients (11.9%). There was no hint of a paraneoplastic disorder in any of the patients. The present findings suggest an autoimmune contribution to the pathophysiology of a subgroup of sporadic late-onset cerebellar ataxia.     

The clinical significance of anti-prothrombin antibodies for risk assessment of thromboembolism in patients with lupus anticoagulant

INTRODUCTION: Thromboembolism is a common manifestation of lupus anticoagulant (LA), however only a subgroup of LA-patients is affected by thrombosis. Study objective was to investigate whether anti-prothrombin antibodies can identify LA-patients at increased risk for thrombosis. MATERIALS AND METHODS: In total 79 patients, 50 with (42 men/8 women) and 29 without thrombosis (21 men/8 women), were investigated for their presence of anti-prothrombin IgG and IgM antibodies using assays from two different manufacturers (Aeskulisa=assay I, CoaChrom=assay II). RESULTS: The prevalence of elevated levels of anti-prothrombin IgG, IgM as well as IgG and/or IgM antibodies was 66% [assayI] (36% [assayII]), 38% (24%) and 72% (50%) in patients with thrombosis and 55% (24%), 28% (28%) and 66% (41%) in patients without thrombosis, respectively. Neither anti-prothrombin IgG or IgM nor IgG and/or IgM antibodies were found to indicate an increased risk for thrombosis. In the subgroup of patients with arterial or venous thrombosis there was also no association between anti-prothrombin antibodies and thrombosis. The comparison of median levels of IgG and IgM anti-prothrombin antibodies between patients with and without thrombosis yielded a borderline statistically significant difference only for anti-prothrombin IgG antibodies by using assay II (p=0.033), all other comparisons were not statistically significant. CONCLUSIONS: In conclusion, presence of anti-prothrombin antibodies was not associated with thromboembolism in LA-patients.