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Background: Nearly 40%-50% of the individuals fail to respond to first line antiepileptic drug (AED) monotherapy and 30% are refractory, which calls for the need to recognize predictive markers for treatment failure. This study aims to identify clinical factors predictive of a poor prognosis in patients on AED therapy., Materials and Methods: A prospective follow-up study involving 1056 patients with epilepsy (PWE) aged 5-67 years from North India on phenytoin (PHT, n = 247), carbamazepine (CBZ, n = 369), valproate (VA, n = 271), phenobarbital (PB, n = 50), and multitherapy (MultiT, n = 119) was conducted between 2005 and 2015. Seizure and epilepsy types were diagnosed based on the classifications by the International League Against Epilepsy (ILAE). Patients remaining seizure-free during the past 1 year were assigned to the "no seizure" group and patients experiencing seizure recurrence were assigned to the "recurrent seizures" group., Results: Of the total, 786 (74.4%) patients were successfully followed up with 60% achieving 1-year seizure remission. Seizure recurrence was observed in the remaining 40% of the patients with a high likelihood in patients with the disease onset at ≤5 years of age [55% vs. 38%, P = 0.0016, odds ratio (OR) = 2.02 (95% confidence interval (CI) = 1.31-3.13)], in patients with cryptogenic epilepsy than with idiopathic/symptomatic epilepsy (48% vs. 32%, P = 0.0049, OR = 1.61 [95% CI = 1.16-2.24]), and in patients with pretreatment seizure frequency ≥12/year (46% vs. 27%, P < 0.0001, OR = 2.21 [95% CI = 1.61-3.05]). Logistic regression analysis also revealed a significant association of seizure recurrence (P < 0.05) with the three variables., Conclusion: Our findings suggest that an early disease onset, cryptogenic epilepsy, and a higher pretreatment seizure frequency are related to a poor prognosis or poor remission in people with epilepsy (PWE) on AED therapy., Competing Interests: There are no conflicts of interest

Introduction: "Common epilepsies", merely explored for genetics are the most frequent, nonfamilial, sporadic cases in hospitals. Because of their much debated molecular pathology, there is a need to focus on other neuronal pathways including the existing ion channels., Methods: For this study, a total of 214 epilepsy cases of North Indian ethnicity comprising 59.81% generalized, 40.19% focal seizures, and based on epilepsy types, 17.29% idiopathic, 37.38% cryptogenic, and 45.33% symptomatic were enrolled. Additionally, 170 unrelated healthy individuals were also enrolled. Here, we hypothesize the involvement of epilepsy pathophysiology genes, that is, synaptic vesicle cycle, SVC genes (presynapse), ion channels and their functionally related genes (postsynapse). An interactive analysis was initially performed in SVC genes using multifactor dimensionality reduction (MDR). Further, in order to understand the influence of ion channels and their functionally related genes, their interaction analysis with SVC genes was also performed., Results: A significant interactive two-locus model of STX1A&#95;rs4363087|VAMP2&#95;rs2278637 (presynaptic genes) was observed among SVC variants in all epilepsy cases (P 1000-value = 0.054; CVC = 9/10; OR = 2.86, 95%CI = 1.88-4.35). Further, subgroup analysis revealed stronger interaction for the same model in cryptogenic epilepsy patients only (P 1000-value = 0.012; CVC = 10/10; OR = 4.59, 95%CI = 2.57-8.22). However, interactive analysis of presynaptic and postsynaptic genes did not show any significant association., Conclusions: Significant synergistic interaction of SVC genes revealed the possible functional relatedness of presynapse with pathophysiology of cryptogenic epilepsy. Further, to establish the clinical utility of the results, replication in a large and similar phenotypic group of patients is warranted.

Aims: It is hypothesized that functionally relevant polymorphisms in genes encoding metabolizing enzymes of sex steroids may influence drug response by directly predisposing women with epilepsy to seizure exacerbation. An alteration in estradiol:progesterone ratio is believed to play a role in seizure occurrence in women. CYP1A1 is a key enzyme involved in the metabolism of estradiol, with variants of the CYP1A1 gene having been reported to play a role in the alteration of sex hormone metabolism in women. The objective of the present study was to test for the association of genetic variants in CYP1A1 with seizure recurrence in patients diagnosed with epilepsy., Materials & Methods: In the study, the association of five variants in CYP1A1 with seizure control in 228 patients with epilepsy on first-line antiepileptic drug therapy for a minimum period of 12 months was investigated., Results: A significant association of an intronic SNP, IVS1 +606C>A (rs2606345), with respect to seizure recurrence (genotypic: p = 3.3 × 10(-4); allelic: p = 7.2 × 10(-4); OR: 2.86; 95% CI: 1.5-5.3) in women with epilepsy from North India was observed., Conclusion: Since CYP1A1 is not involved in the metabolism of any of the first-line antiepileptic drugs, these results imply that variants from genes encoding sex hormone metabolizing enzymes might act as markers for predicting response to antiepileptic drug therapy in women with epilepsy.

Over-expression of efflux transporter P-glycoprotein (PgP) encoded by ABCB1 gene has been implicated in poor responsive epilepsy. Several genetic variants have been shown to influence the expression levels of P-glycoprotein. The aim of the present study was to investigate the role of ABCB1 polymorphisms: C1236T, G2677T/A and C3435T in determining drug response to first line antiepileptic drugs (AEDs) namely phenobarbitone, phenytoin, carbamazepine and valproate in North Indian cohort of epilepsy patients. DNA samples were obtained from 392 consecutive epilepsy patients, out of which 228 had completed follow-up evaluation at 12 months. After attaining steady state of the AEDs in the first two months of study, 133 patients showed complete freedom from seizures (no-seizure group) and 95 patients continued to have seizures (recurrent-seizures group) in the remaining period of study. Comparison of "no-seizure" and "recurrent-seizures" groups revealed no significant differences in allelic, genotypic and haplotypic frequencies for all the studied variants. In conclusion, our finding disproves a general association between ABCB1 polymorphisms and drug response in epilepsy patients., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Background: The first-line antiepileptic drugs, although affordable and effective in the control of seizures, are associated with adverse drug effects, and there is large interindividual variability in the appropriate dose at which patients respond favorably. This variability may partly be explained by functional consequences of genetic polymorphisms in the drug-metabolizing enzymes, such as the CYP450 family, microsomal epoxide hydrolase and UDP-glucuronosyltransferases, drug transporters, mainly ATP-binding cassette transporters, and drug targets, including sodium channels. The purpose of this study was to determine the allele and genotype frequencies of such genetic variants in patients with epilepsy from North India administered first-line antiepileptic drugs, such as phenobarbitone, phenytoin, carbamazepine and valproic acid, and compare them with worldwide epilepsy populations., Materials & Methods: SNP screening of 19 functional variants from 12 genes in 392 patients with epilepsy was carried out, and the patients were classified with respect to the metabolizing rate of their drug-metabolizing enzymes, efflux rate of drug transporters and sensitivity of drug targets., Results: A total of 16 SNPs were found to be polymorphic, and the allelic frequencies for these SNPs were in conformance with Hardy-Weinberg equilibrium. Among all the polymorphisms studied, functional variants from genes encoding CYP2C19, EPHX1, ABCB1 and SCN1A were highly polymorphic in North Indian epilepsy patients, and might account for differential drug response to first-line antiepileptic drugs., Conclusion: Interethnic differences were elucidated for several polymorphisms that might be responsible for differential serum drug levels and optimal dose requirement for efficacious treatment.

A retrospective study was conducted to assess the appropriateness of the utilization of therapeutic drug monitoring (TDM) services with regards to antiepileptic drugs (AEDs) at a tertiary care hospital, and analysis of 5094 samples of the carbamazepine (CBZ), phenytoin (PHT), valproic acid (VAP), and phenobarbitone (PB) was undertaken. Maximum requisitions were received for CBZ (54.92%) followed by PHT (27.05%), VAP (14.40%), and PB (3.61%). About 2.12% requisitions were received for patients taking unlabeled AEDs. Reasons for TDM were routine monitoring (36.3%), adverse drug reactions (ADRs) (17.2%), relapse (30.7%), no response (3.35%), and irregular treatment (2.24%) and not mentioned (10.5%). Majority of the samples (69%) were drawn for measuring trough levels; however, in 22% time of last dose was not mentioned and 9.64% were for peak or random levels. In all, 6.9% requisitions for TDM were sent before steady-state levels, and in 15.5% duration of therapy was not mentioned. Blood levels within therapeutic range were found with CBZ (63%) followed by PB (56.52%), VAP (45.99%), and PHT (42.52%). Blood levels were above therapeutic range in 45.69%, 29%, and 21.73% patients taking VAP, PHT, and PB, respectively. Unsuspected poor compliance was uncovered in 11.8%, 41.2%, and 29.3% requisitions sent with ADR, relapse, and routine monitoring as reason for drug levels, respectively. Only half of all AED measurement requisitions were complete and met the criteria for appropriate AED-level determination. Incomplete requisitions lead to difficulty in uniform interpretation of results and thus add to unnecessary costs.

Aim: The aim of this article is to describe the hippocampal characteristics among children with calcified neurocysticercosis (cNCC). Materials and Methods: This cross-sectional study was conducted among children with epilepsy aged 3-14 years diagnosed with cNCC. Patients showing evidence of cNCC, with prior serial imaging evidence of active NCC, were enrolled. Eligible participants were subjected to magnetic resonance imaging (MRI)-based protocol and sleep-deprived electroencephalography. Hippocampal characteristics on the MRI were described. Results: A total of 31 children with mean (SD) age of 10.3 (3.2) years with cNCC were enrolled in the study. We observed that 42% (13/31) of children with cNCC had borderline (10-20% difference in the volumes of right and left hippocampi) (n = 8) or clear (>20% difference) (n = 5) hippocampal atrophy. Among 31 children with cNCC, 27 (87.1%) had nidus within the lesion and 21 (67.7%) had perilesional gliosis. Conclusion: Children with cNCC are at risk of seizure recurrence on tapering anti-seizure medications. Our study with limited sample size revealed that hippocampal atrophy and perilesional gliosis are prevalent among children with cNCC, predisposing them to the risk of epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of oral dexamethasone and prednisolone in the treatment of newly diagnosed children aged 3–36 months of West syndrome. Methods: An open-labeled, randomized controlled clinical trial with parallel group assignment was conducted among children aged 3–36 months with newly diagnosed West syndrome. They were randomized to receive either oral dexamethasone (0.6 mg/kg/day QID) (n = 20) or oral prednisolone (4 mg/kg/day BD) (n = 20). Proportion of children who achieved spasm freedom at 2 weeks was the primary outcome. Secondary outcome measures were proportion of children who achieved electroclinical resolution, greater than 50% reduction in spasms frequency, time to cessation of spasms, and adverse effects at 2 weeks. Results: The efficacy of oral dexamethasone was comparable to oral prednisolone in terms of proportion of children who achieved spasms cessation (13 [65%] vs. 8 [40%]; P = 0.21), electroclinical remission (13 [65%] vs. 8 [40%] P = 0.21), greater than 50% reduction of spasms (3 [15%] vs. 7 [35%] P = 0.65), and time to cessation of spasms (5.31 [2.81] vs. 4.37 [1.41] P = 0.39). Adverse effect profile was also comparable with irritability (18 [90%] vs. 12 [60%] P = 0.06] being most common. Conclusion: There was no difference in electroclinical remission at 2 weeks between oral dexamethasone and prednisolone in children with infantile spasms in this small pilot trial. Further evaluation is suggested with an adequately powered study and long-term follow-up. [ABSTRACT FROM AUTHOR]

The article reports on the study that patients with epilepsy use complementary and alternative medicine (CAM) as first-line treatment because of superstitious beliefs attached to the disease. It is stated that blood samples were taken from a total of 108 patients taking unlabeled pills from a CAM provider specializing in the treatment of epilepsy contained prescription antiepileptic drugs (AED). Most of the patients had serum levels of these drug in the subtherapeutic or supratherapeutic range.

The ATP-binding cassette (ABC) superfamily of transporters is known to efflux antiepileptic drugs (AEDs) primarily in the brain, gastrointestinal tract, liver, and kidneys. In addition, they are also known to be involved in estrogen disposition and may modulate seizure susceptibility and drug response. The objective of the present study was to investigate the role of genetic variants from ABC transporters in seizure control in epilepsy patients treated with monotherapy of first-line AEDs for 12 months.On the basis of gene coverage and functional significance, a total of 98 single nucleotide polymorphisms from ABCB1, ABCC1, and ABCC2 were genotyped in 400 patients from North India. Of these, 216 patients were eligible for therapeutic assessment. Genetic variants were compared between the ‘no-seizures’ and the ‘recurrent-seizures’ groups. Bonferroni corrections for multiple comparisons and adjustment for covariates were performed before assessment of associations.Functionally relevant promoter polymorphisms from ABCC2: c.-1549G>A and c.-1019A>G either considered alone or in haplotype and diplotype combinations were observed for a significant association with seizure control in women (odds ratio>3.5, P<10-3, power>95%). Further, low protein-expressing CGT and TGT (c.-24C>T, c.1249G>A, c.3972C>T) haplotypes were always observed to be present in combination with the AG (c.-1549G>A, c.-1019A>G) haplotype that was over-represented in women with ‘no seizures’.The distribution of the associated variants supports the involvement of ABCC2 in controlling seizures in women possibly by lowering of its expression. The biological basis of this finding could be an altered interaction of ABCC2 with AEDs and estrogens. These results necessitate replication in a larger pool of patients. [ABSTRACT FROM AUTHOR]

Stigmatized psychosocial perception poses a serious challenge and source of discrimination which impedes epilepsy patients from attaining a satisfactory quality of life. The present study was aimed to obtain information on knowledge, attitudes and practices (KAP) of epilepsy patients in Delhi and compare with the published data from India. We included 120 people with epilepsy (PWE) attending the Neurology outpatient services of the Institute of Human Behavior and Allied Sciences (IHBAS), Delhi. Demographic details and responses to a questionnaire assessing the knowledge, attitude and practices were recorded. Although majority of the patients belonged to low socioeconomic strata, the literacy rate was reasonably high (70%). A large majority (94%) of PWE had heard about epilepsy and 91% knew that epilepsy can be treated with modern drugs. Positive attitude was observed with respect to allowing a child with epilepsy to study (80%), not objecting children to play with a child with epilepsy (95%), marriage (89%) and having children (92%). Negative attitude was refl ected in the belief that epilepsy is due to supernatural powers (16%) and sins committed by patient or ancestors (21%). Analysis of Indian data revealed regional differences in KAP which could be attributed to local factors, such as literacy, awareness about epilepsy, and practice of different systems of medicine. Some of the differences can also be attributed to category of study population whether it included patients or non epilepsy individuals, since the former are likely to have less negative attitudes than the public. There is a need to create awareness about epilepsy on a nation-wide basis to dispel the misconceptions and stigma through effective and robust programs with the aim to lessen the disease burden. [ABSTRACT FROM AUTHOR]

Background & Objectives: Depression, anxiety and suicide are the main psychiatric comorbidities which are more prevalent among persons with epilepsy (PWE). This study aims to determine the prevalence of depression, anxiety and suicidal ideation/behaviour in PWE and to correlate their clinical profile with psychiatric comorbidities in a population in North India. Methods: This study was conducted at Pt. BD Sharma PGIMS, Rohtak Haryana among PWE attending outpatient clinic at the Department of Neurology. A total of 100 eligible PWE were included in this study. The demographic and clinical history was documented. All patients filled up the Hospital anxiety and depression scale (HADS) and Columbia-suicide severity rating scale (C-SSRS) questionnaire. Results: The prevalence of depression and anxiety among PWE was found to be 60% and 70% respectively and the prevalence of suicidal ideation and suicidal behaviour was 42% and 3% respectively among PWE. Female gender, longer duration of epilepsy, higher seizure frequency, temporal lobe epilepsy, polytherapy, uncontrolled epilepsy and drug resistant epilepsy were found to be positively correlated with these psychiatric comorbidities. Conclusion: This study shows that the prevalence of depression, anxiety and suicidal ideation/behaviour is high among PWE in Haryana, North India. PWE should be screened for these psychiatric comorbidities to improve their quality of life. [ABSTRACT FROM AUTHOR]