Antibodies In Epilepsy Research Articles

Antiphospholipid antibodies in epilepsy: A systematic review and meta-analysis.

Autoimmunity is believed to play an important causative role in the pathogenesis of epilepsy. There are evidences for the presence of autoantibodies in patients with epilepsy. To date, many studies have assessed the presence of antiphospholipid antibodies (aPLs) in epilepsy patients, though the relationship has been inconclusive. The aim of this systematic review and meta-analysis was to evaluate the presence of aPLs in epileptic patients as compared to healthy controls. Five electronic databases (PubMed, Web of Science, Embase, Scopus and Google Scholar) were searched systematically. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). L'Abbé plots were generated to visually inspect heterogeneity while publication bias was evaluated via visualization of contour- enhanced funnel plots, and Begg's and Egger's tests. Based on the inclusion criteria, 14 studies were selected involving 1248 epilepsy patients and 800 healthy controls. The majority of epilepsy was categorised as generalised or partial and none had comorbidity with autoimmune diseases. Significant presence of both anticardiolipin (aCL) antibodies (OR: 5.16, 95% CI: 3.21-8.28, p < 0.00001) and anti-β2- glycoprotein I (anti-β2-GPI) antibodies (OR: 2.95, 95% CI: 1.07-8.11, p = 0.04) exhibited comorbid association with epilepsy patients as compared to healthy controls. Subgroup analyses revealed that presence of aCL antibodies was more specifically observed in paediatrics (OR: 4.57, 95% CI: 2.57-8.15, p < 0.00001) than adults (OR: 4.24, 95% CI: 1.80-10.01, p = 0.001). The odds of aCL antibody presence was higher in partial epilepsy patients (OR: 7.88, 95% CI: 3.23-19.24, p < 0.00001) than that of generalised (OR: 3.76, 95% CI: 2.15-6.59, p < 0.00001) and in Asian epileptic patients (OR: 9.56, 95% CI: 2.69-33.95, p = 0.0005) than Europeans (OR: 4.35, 95% CI: 2.74-6.92, p < 0.00001). The presence of anti-β2-GPI antibodies was significant in paediatric (OR: 6.44, 95% CI: 1.39-29.89, p = 0.02) and African population with epilepsies (OR: 10.59, 95% CI: 1.22-92.25, p = 0.03). NOS of the majority of the studies (11/14) indicated a high methodological quality. No substantial heterogeneity was observed either from the quantitative analysis or from the L'Abbé plots while no significant publication bias was detected from funnel plots; Begg's and Egger's tests. Since none of the epilepsy subjects exhibited any comorbid autoimmune disorders, significant presence of aCL and anti-β2-GPI antibodies indicate towards their contribution in immune-mediated general pathogenesis of epilepsy.

Glutamic acid decarboxylase (GAD) antibodies in epilepsy: Diagnostic yield and therapeutic implications

PurposeThe aetiology of adult onset epilepsy remains unascertained in a significant proportion of patients. Antibodies directed against neuronal antigens have been suggested to have a potential pathogenic role in some cases of epilepsy. We describe a series of patients with adult onset epilepsy in whom antibodies to glutamic acid decarboxylase (GAD Abs) have been identified. MethodsAll patients attending a regional epilepsy service with unexplained adult onset epilepsy’ were tested for the presence of GAD Abs. Those with high serum titres underwent CSF analysis, and were offered additional treatment with immunotherapy. Those who underwent immunotherapy were monitored by monthly review. Clinical details and response to treatment was collated by review of notes. ResultsOf 112 patients tested, high serum titres were found in 6 (5.4%) patients. These patients had clinical and electroencephalographic evidence of focal epilepsy. CSF analysis revealed oligoclonal bands and intrathecal GAD Abs in all patients. Five patients received immunotherapy. No improvement in seizures was observed in any. One patient with equivocal MRI evidence of hippocampal sclerosis and concordant video EEG and PET scan, achieved 12 months seizure freedom following temporal lobectomy. ConclusionsThe relevance of GAD Abs to epilepsy remains uncertain. Our experience does not support the routine use of immunotherapy in patients with epilepsy and GAD Abs. Larger studies enrolling greater numbers of patients are required to identify sufficient numbers of patients for controlled treatment trials.

VGKC complex antibodies in epilepsy: Diagnostic yield and therapeutic implications

PurposeIn a significant number of patients developing epilepsy in adult life, the aetiology of their seizures remains unclear. Antibodies directed against the voltage gated potassium channel complex (VGKC Ab) have been identified in various cohorts of patients with epilepsy, although the role of these antibodies in epilepsy pathogenesis is not fully known. MethodWe reviewed the notes of 144 patients with unexplained adult onset epilepsy who had been tested for VGKC Abs. We collected data on their clinical syndrome, investigation results and response to treatment. ResultsWe identified 6 (4.2%) patients who had titres of >400pM. One of the six patients was positive for LGI1 and another for CASPR2 subunit antibodies. All patients were given immunotherapy and experienced improvement in seizure control. No patient had the clinical syndrome of limbic encephalitis. ConclusionPatients with otherwise unexplained epilepsy and positive VGKC Abs are a heterogeneous group. In our cohort there was an overall favourable response to immunotherapy but further prospective studies are needed to determine the significance of these antibodies and the optimum treatment regimen for patients.

Antibodies in Epilepsy

Antibody mediated limbic encephalitis is an increasingly recognized cause of seizures in cryptogenic epilepsy. Autoimmune encephalitis and epilepsy have been linked to both neuronal intracellular antibodies (GAD65, ANNA-1, and Ma) and neuronal cell surface antibodies (VGKC complex, NMDAR, AMPA, GABA-B, and GluR5). This article outlines the latest data on these various antibodies with a focus on their association with acute seizures in limbic encephalitis and likely increased risk for chronic epilepsy. There is mounting evidence that these antibodies may play a role in acute onset and chronic seizures in the general epilepsy population without manifesting typical limbic encephalitis symptoms. This review will discuss the data supporting early recognition and treatment options, beyond typical antiepileptic medications, necessary to improve outcomes in this epilepsy subgroup.

Antibodies to voltage-gated potassium and calcium channels in epilepsy

Objective To determine the prevalence of antibodies to ion channels in patients with long standing epilepsy. Background Although the CNS is thought to be protected from circulating antibodies by the blood brain barrier, glutamate receptor antibodies have been reported in Rasmussen's encephalitis, glutamic acid decarboxylase (GAD) antibodies have been found in a few patients with epilepsy, and antibodies to voltage-gated potassium channels (VGKC) have been found in a non-paraneoplastic form of limbic encephalitis (with amnesia and seizures) that responds to immunosuppressive therapy. Methods We retrospectively screened sera from female epilepsy patients ( n = 106) for autoantibodies to VGKC (Kv 1.1, 1.2 or 1.6), voltage-gated calcium channels (VGCC) (P/Q-type), and GAD. All positive results, based on the values of control data [McKnight, K., Jiang, Y., et al. (2005). Serum antibodies in epilepsy and seizure-associated disorders. Neurology 65, 1730–1735], were retested at lower serum concentrations, and results compared with previously published control data. Demographics, medical history, and epilepsy related information was gathered. Results The studied group consisted predominantly of patients with long standing drug resistant epilepsy. VGKC antibodies were raised (>100 pM) in six patients. VGCC antibodies (>45 pM) were slightly raised in only one patient. GAD antibodies were <3 U/ml in all patients. The clinical features of the patients with VGKC antibodies differed from previously described patients with limbic encephalitis-like syndrome, and were not different with respect to seizure type, age at first seizure, duration of epilepsy, or use of anti-epileptic drugs from the VGKC antibody negative patients. Conclusion The results demonstrate that antibodies to VGKC are present in 6% of patients with typical long-standing epilepsy, but whether these antibodies are pathogenic or secondary to the primary disease process needs to be determined.

Serum antibodies in epilepsy and seizure-associated disorders

To investigate whether autoantibodies to ion channels and other neural antigens are present in the sera of patients with epilepsy and seizure-related diseases. Sera were obtained from 139 patients, including 26 with preexisting autoimmune disease, 46 in whom an autoimmune basis was suspected, and 67 with drug-resistant epilepsy. The sera were assayed for antibodies to voltage-gated potassium (VGKC) and calcium (VGCC) channels, glutamic acid decarboxylase (GAD), gangliosides, glutamate receptor type 3, cardiolipins, DNA, and nuclear antigens; the results were compared with results from a large cohort of healthy and disease controls. Increased titers of VGKC antibodies (>100 pM) were detected in 16 of 139 (11%) patients with seizures but only 1 control (0.5%). Eight VGKC-positive patients presented with an acute/subacute illness, and 5 of these had the highest VGKC antibodies; 3 patients improved spontaneously, another 5 patients responded well to immunomodulatory therapy. The other VGKC-positive patients had longer disease duration (>6 years) and intermediate levels of antibodies; immunotherapies have not been tested in this group. Very high levels of GAD antibodies (>1,000 U) were found in an additional 3 patients (2.1%) with long-standing drug-resistant epilepsy. The presence of autoantibodies to voltage-gated potassium channels and glutamic acid decarboxylase suggests that the immune system may contribute to certain forms of epilepsy or seizure-associated disorders. Further studies are needed to determine whether the antibodies are pathogenic.

Anticardiolipin and antinuclear antibodies in epilepsy—a population-based cross-sectional study

Increased prevalence of autoantibodies has been suggested in patients with epilepsy. This study determined the presence of autoantibodies in a representative cohort of 960 patients with epilepsy. The frequency of antinuclear antibodies (ANA), immunoglobulin G class anticardiolipin antibodies (aCL) and anti-B2-glycoprotein I antibodies were studied in 960 consenting adult patients with epilepsy and in 580 population-based reference subjects identified from the Finnish Population Registry. Overall the frequencies of the autoantibodies studied did not differ between patients with epilepsy and reference subjects. aCL were present in 4.5% of the patients and in 5.0% of the reference subjects and 17% of both the patients and the reference subjects had antinuclear antibodies. However, patients with partial epilepsy for ≥30 years were three times more likely to have aCL than patients with partial epilepsy for <10 years. Patients with partial epilepsy and ≥1 seizure per month were 2.2 times more likely to have aCL than patients with partial epilepsy with <1 seizure per month. Moreover, ANA tended to be more frequent among patients with ≥1 seizure per month. No association was found between the major antiepileptic drugs and autoantibodies. Overall the frequencies of the autoantobodies studied were similar in the large epilepsy cohort and in matched reference subjects from the general population. However, a long duration of epilepsy and poor seizure control were associated with an increased presence of aCL in patients with partial epilepsy.