Awadh Kishor Pandit

High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta‐analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database ‘PubMed’, ‘EMBASE’, and ‘Google Scholar’ as well as from many trial databases. The following search terms were used: ‘Statin therapy’ AND ‘Cardiovascular Disease’, AND ‘Dose’ AND ‘Intracerebral hemorrhage’, AND ‘Randomized Controlled Trials’ AND ‘High Dose Statin’. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed‐effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random‐effect model was used. Beggs funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high‐dose statin and 31,105 subjects receiving placebo were analyzed in our meta‐analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16–2.01; P = 0.002). There was no difference in all‐cause mortality between the two groups (RR = 0.95; 95% CI: 0.86–1.06; P = 0.36). No publication bias was observed through Beggs funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings.

Association between Interleukin-6 (G174C and G572C) promoter gene polymorphisms and risk of ischaemic stroke: A meta-analysis.

Background Interleukin-6 (IL-6), as one of the most typical pro-inflammatory and immunoregulatory cytokines, is believed to be associated with the genesis and maintenance of inflammatory response. Genetic association studies (GAS) that have investigated the association between Interleukin 6 (G174C and G572C) promoter gene polymorphisms and susceptibility to ischemic stroke (IS) which have produced contradictory and unconvincing results. Purpose The aim of this meta-analysis is to provide a relatively comprehensive account of the association of IL-6 (G174C and G572C) polymorphisms with susceptibility to IS. Methods A literature search was conducted using electronic database PubMed, Medline, and Trip database for all case-control studies investigating for association of IL-6 genetic polymorphisms with ischemic stroke published till August 30, 2014. The following combinations of main keywords were used: (‘Interleukin-6’ or ‘IL-6’) and (‘ischaemic stroke or ‘cerebral infarction’ or ‘IS’) and (‘genetic polymorphism’ or ‘single nucleotide polymorphisms’ or ‘SNP’). Pooled Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for IL-6 gene-disease association. Meta-analysis was carried out using Revman 5.3 software. Results 16 case-control studies involving a total of 3,317 IS patients and 3,432 healthy controls for G174C polymorphism and 3 case-control studies with a total of 2,001 IS patients and 2,027 healthy controls for G572C IL-6 gene polymorphisms were included in a meta-analysis. For IL-6 G174C gene polymorphisms, no significant association was observed under dominant [GC + CC vs. GG: OR = 1.01, 95% CI: 0.77–1.34, P = 0. 92], recessive [CC vs. GG + GC: OR = 0.82, 95% CI: 0.40–1.70, P = 0. 59] and allelic model [C vs. G Allele: OR = 0.99, 95% CI: 0.74–1.31, P = 0. 93]. For IL-6 G572C, no significant association was observed under dominant [CC vs. GG + GC: OR = 0.99, 95% CI: 0.57–1.71, P = 0. 97], recessive [CC vs. GG + GC: OR = 0.93, 95% CI: 0.60–1.45, P = 0. 75] and allelic model [C vs. G Allele: OR = 0.95, 95% CI: 0.66–1.36, P = 0. 76]. Conclusion This meta-analysis shows that IL-6 (G174C) and IL-6 (G572C) gene polymorphisms may not be associated with an increased susceptibility to IS. Further studies are required for confirmatory results.

Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR gene) with ischemic stroke: a meta-analysis

Abstract Objective: Studies on association between methylenetetrahydrofolate reductase gene (MTHFR) C677T gene polymorphism and ischemic stroke have shown conflicting results. We have conducted a meta-analysis to determine the precise association of the C677T polymorphism of MTHFR gene with risk of ischemic stroke. Materials and methods: We searched electronic databases Medline, EMBASE, and Google Scholar (last search dated till August 2014). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from random or fixed-effects models were calculated. The methodological quality of included studies was determined by the quality assessment scale. Results: Thirty eight case–control studies fulfilled our inclusion criteria comprising 6310 patients and 8297 controls. The significant associations between MTHFR C677T genetic polymorphism and risk of ischemic stroke were observed in dominant (OR, 1·09; 95% CI, 1·06–1·12, P-value < 0·001) and recessive (OR, 1·31; 95% CI, 1·19–1·44, P-value < 0·001) inheritance models. In an Asian population, significant association between the MTHFR polymorphism and ischemic stroke was observed (dominant model: OR 1·36, 95% CI 1·23–1·49 and under recessive model OR, 1·29; 95% CI, 1·15–1·45). In the Caucasian population borderline, non-significant association was observed under dominant model of inheritance (OR, 1·05; 95% CI, 0·99–1·10) but significant association was observed under the recessive model of inheritance (OR, 1·33; 95% CI, 1·13–1·58). Conclusion: The present study results suggest that MTHFR C677T genetic polymorphism is a probable risk of ischemic stroke.

Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline.

Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctors information) were noted. Results: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis.

Acute pancreatitis: Rare complication of chicken pox in an immunocompetent host

Chicken pox is a highly contagious infection, caused by the varicella zoster virus. Although generally a benign, self-limited disease, varicella may be associated with serious complications especially in adults. We present acute pancreatitis- a rare complication, in otherwise healthy patients suffering from chicken pox. The presence of pancreatitis in association with chickenpox in immunocompetent patients can influence the outcome of the latter. This interesting case will hopefully increase awareness about this complication and its fatality in chicken pox.

Association between beta-1 adrenergic receptor gene polymorphism and ischemic stroke in North Indian population: A case control study

Stroke is a multi-factorial disease caused by a combination of genetic and environmental factors. The purpose of this case control study was to determine the relationship of beta-1 adrenergic receptor polymorphism with ischemic stroke in North Indian population. In this study, 224 patients and 224 age- and sex-matched controls were recruited from the outpatient department and neurology ward of All India Institute of Medical Sciences, New Delhi. Genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. PCR results were confirmed by DNA sequencing. Frequency distributions of genotypes and alleles were compared between cases and controls using logistic regression. Mean age of cases and controls was 53.9 ± 13.4 and 53.6 ± 12.9 years respectively. Multivariate logistic regression analysis showed an independent association between Ser49Gly polymorphism and ischemic stroke under a dominant model of inheritance (OR, 2.5; 95% CI, 1.2 to 5) and large vessel disease (LVD) under a recessive model of inheritance (OR, 6.5; 95% CI, 1.7 to 23; P=0.005). Independent association of Arg389Gly polymorphism with small vessel disease (SVD) (OR, 7.09; 95% CI, 1.9 to 25; P=0.003) under recessive model of inheritance. The findings of the present study Ser49Gly polymorphism of the ADRB1 gene confer higher risk of ischemic stroke in a North Indian population and especially in patients with LVD. Our findings also show that Arg389Gly polymorphism of ADRB1 confers higher risk of SVD in North Indian population.

Autologous hematopoietic stem cell transplantation in progressive severe multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS), which is disabling and majorly involves younger population. Various available treatments in forms of immunomodulation are not very effective; however, stem cell transplantation seems to be promising in recent literature. The current case report is a novel evidence for autologous hematopoietic stem cell transplantation (HSCT) in progressive MS. Case Summary: A 33 year old male with secondary progressive MS (SPMS), after being failed and/or intolerance to standard approved interferon (IFN) and mitoxantrone therapy, autologous HSCT was administered. At 2years of post-stem cell transplantation follow-up, he has remained stable with some improvement in functional status (Expanded Disability Status Scale (EDSS) reduced by 1.5), with no relapse, no treatment related complications, and no fresh magnetic resonance imaging (MRI) lesions. Conclusion: Autologous stem cell transplantation may be beneficial in progressive forms of MS, but needs to be tested in well-designed randomized trial.

Association between Endothelial nitric oxide synthase G894T gene polymorphism and risk of ischemic stroke in North Indian population: a case-control study.

Background and purpose: Stroke is a multi-factorial disease influenced by both genetic and environmental factors. The aim of this case-control study was to determine the association between Endothelial Nitric Oxide Synthase G894T (rs1799983) gene polymorphism and susceptibility to ischemic stroke (IS) in North Indian population. Methods: In this present case-control study, genotyping was performed by using Polymerase chain reaction – Restriction fragment length polymorphism (PCR-RFLP) method for 250 IS patients and 250 age and sex matched controls. PCR results were confirmed by DNA sequencing. Frequency distribution of genotypes and alleles were compared between cases and controls using conditional logistic regression. Results: Hypertension, Diabetes, Dyslipidemia, Low Socioeconomic Status and Family History of Stroke were found to be independent risk factors for IS. Mean age of cases and controls were 52.83 ± 12.59 and 50.97 ± 12.70 years. Multivariate logistic regression analysis showed a significant association between eNOS G894T (rs1799983) polymorphism and risk of IS [OR = 1.57; 95%CI 1.05–2.37; p = 0.028] under dominant model. Based on Trial of Org 10172 in Acute Stroke Treatment classification, an independent association of large vessel disease (LVD) was observed with the risk of IS under the dominant [OR = 2.09; 95% CI 1.17–3.75; p = 0.01] and recessive [4.09 95% CI 1.06–15.68; p = 0.04] models. All the observed genotype frequencies were in accordance with the Hardy–Weinberg equilibrium (HWE) in both cases and controls. Conclusion: The findings of the present study suggest that polymorphism in G894T position of eNOS gene might be a risk factor for IS mainly for LVD stroke subtype in North Indian population. Further large prospective studies are required to confirm these findings.

Low Socioeconomic Status Is an Independent Risk Factor for Ischemic Stroke: A Case-Control Study in North Indian Population

Background: Stroke is a multifactorial disease and is influenced by complex environmental interactions. The contribution of various risk factors to the burden of stroke worldwide is not well known, particularly in developing countries. The present case-control study is aimed at exploring the association between a low socioeconomic status and the risk of ischemic stroke among the North Indian population. Methods: The study design was a hospital-based, case-control study. Age- and sex-matched controls were included. The demographic characteristics and risk factor variables were documented by means of a personal interview through a standardized case record form. The household asset index for determining the socioeconomic status (HAISS) was used for the assessment of the socioeconomic status of the population. HAISS was validated with the widely used Kuppuswamy scale for measurement of socioeconomic status. The multivariable logistic regression model was used to estimate the odds ratio associated with stroke. Results: In all, 224 ischemic stroke patients and 224 controls were recruited between February 2009 and February 2012. The mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The low economic status was independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.8; 95% CI 1.2-6.3). Conclusion: Our findings suggest that there is a significant association between a low socioeconomic status and the risk of ischemic stroke risk in North Indian population. Well-designed studies embedded with long-term prospective cohorts are required for confirming the results.

Association between Beta Adrenergic Receptor Polymorphism and Ischemic Stroke: A Meta-Analysis

Background and Purpose The purpose of this meta-analysis was to determine the precise association between beta-2 adrenergic receptor (β2AR) polymorphism and Ischemic stroke. Methods Published case control studies on association between β2AR and ischemic stroke were searched from electronic databases. Pooled Odds ratio and 95% Confidence interval were calculated by using software RevMan version 5.2. Results A total of three studies involving 1,642 cases and 1,673 controls, which were published from 2007 to 2014, were subjected to meta-analysis for allelic association and 518 cases and 510 controls for genotypic association. Pooled analysis of two studies for genotypic association suggested that subjects carrying Gln27Glu polymorphism of β2AR had an increased risk for Ischemic stroke under recessive model (OR 2.09; 95% CI; 1.20 to 3.64) and under dominant model (OR 1.47; 95% CI 1.14 to 1.90). Pooled analysis of three studies for allelic association showed a significantly higher Glu27 allele of β2AR in the patients with ischemic stroke (OR 1.58; 95% CI; 1.38 to 1.81). Conclusions The present meta-analysis suggests that Gln27Glu polymorphism of β2AR gene is associated with increased risk for ischemic stroke.