Subiah Vivekanandhan

Serum prolactin levels for differentiation of nonepileptic versus true seizures: limited utility

Frequently occurring nonepileptic psychogenic seizures (PNES) are a cause of substantial morbidity. Differentiation of these from true seizures may sometimes be very difficult. Serum prolactin level estimation following the event has been described as a useful test for this purpose. We conducted this study to assess the role of this test in diagnosis of PNES. Serum prolactin was estimated from venous blood samples of 19 patients (13 females, 6 males) with PNES and 17 patients (5 females, 12 males) with true complex partial seizures with or without secondary generalization. The age range was 12-39 years in the PNES group and 9-42 years in the true seizure group. Five patients (all females) in the PNES group (26.3%) had raised prolactin levels, all of them having greater than twice normal levels. In the true seizure group, 10 of 17 (58.8%) patients had raised levels; only 3 (17.6%) of these had greater than twice normal levels. The difference in percentage of patients with abnormal prolactin levels between these groups was not found to be significant. We demonstrate that serum prolactin level estimation is not a useful method for differentiation of psychogenic nonepileptic from true epileptic seizures.

Association of Angiotensin-Converting Enzyme Insertion(I)/Deletion (D) Genotype in Alzheimer's Disease Patients of North Indian Population

ABSTRACT Several lines of evidence support for the role of angiotensin-converting enzyme (ACE) in Alzheimers disease (AD) patients. Most human genetic studies have focussed on ACE insertion (I)/deletion (D) polymorphism and have yielded conflicting results. We have evaluated the association of ACE polymorphism with serum ACE activity in 95 AD patients and 110 healthy controls from north Indian population. In Alzheimers patients a higher frequency of D allele was detected (I/D ratio 0.53:0.47) compared with the control group (I/D ratio 0.54:0.45), the difference being not statistically significant (p > .05). AD patients were found to be more homozygous for the D allele (26.3%) compared with controls (20.8%). The observed genotype distribution was in agreement with Hardy- Weinberg equilibrium. We observed that the D/D genotype is more in patients with a higher serum ACE activity. The D allele and the D/D genotype in AD patients may influence increased risk of cognitive impairment.

Association between Interleukin-10 -1082G/A Gene Polymorphism and Risk of Stroke in the North Indian Population: A Case-Control Study.

BACKGROUND Anti-inflammatory interleukin-10 (IL-10) cytokine and its genetic variations may play an important role in the pathogenesis of various human diseases including stroke. OBJECTIVE The aim of this present case-control study was to determine the association between IL-10 -1082G/A (rs1800896) gene polymorphism and risk of stroke in the North Indian population. METHODS Genotyping was carried out by using SNaPshot method (Applied Biosystems, Foster City, California, United States) for 250 ischemic stroke (IS) patients, 250 age- and sex-matched IS free controls, 100 intracerebral hemorrhage (ICH) patients, and 100 age- and sex-matched ICH free controls. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis with adjustment for multiple demographic and risk factor variables was used to calculate the strength of association between IL-10 (-1082G/A) polymorphism and risk of stroke. RESULTS Conditional logistic regression analysis showed an independent association between IL-10 -1082G/A and risk of IS under a dominant model (odds ratio [OR] = 2.39, 95% confidence interval [CI] = 1.34-4.27, P = .003) and an allelic model (OR = 2.49, 95% CI 1.71-3.63, P < .001). An independent association between IL-10 -1082G/A, under the dominant model (OR = 6.8, 95% CI 2.2-20.7, P < .001) and the allelic model (OR = 3.4, 95% CI 1.8-6.3, P < .001), and the risk of ICH was also observed. CONCLUSION Our results suggest that IL-10 -1082G/A gene polymorphism is an independent risk factor for the risk of IS and ICH in the North Indian population. Our findings indicate that IL-10 -1082G/A polymorphism may be used as a genetic marker for identifying individuals at increased risk of developing stroke.

Tumor necrosis factor-alpha (- 308G/A, + 488G/A, - 857C/T and -1031 T/C) gene polymorphisms and risk of ischemic stroke in north Indian population: A hospital based case-control study.

Background Genetic factors may play a role in the susceptibility of Ischemic stroke (IS). Previous studies have shown that Tumour necrosis factor-α (TNF-α) gene polymorphisms were associated with the risk of IS in multiple ethnicities. The present case–control study tested the hypothesis that genetic polymorphisms of the TNF-α gene may affect the risk of IS in North Indian population. We investigated the association of four single nucleotide polymorphisms (− 308G/A, + 488G/A, − 857C/T and -1031 T/C) within TNF-α gene promoter and their haplotypes with the risk of IS. Methods IS was classified using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification. Genotyping was performed for 250 IS patients and 250 age- and sex-matched IS free controls by using SNaPshot technique. Multivariate logistic regression was used to control the confounding effects of demographic and risk factor variables. Haplotype analyses were done by using PHASE software and Linkage disequilibrium (LD) analyses were done by using Haploview version 4.2 software. Results An independent association between TNF-α + 488G/A (OR = 2.59; 95%CI 1.46 to 4.60; p = 0.001) and -857C/T (OR = 1.77; 95%CI 1.01 to 3.11; p < 0.04) and risk of IS was observed under dominant model. However, no significant association between -308G/A and -1031 T/C gene polymorphisms and risk of IS was observed. Haplotype analysis showed that A308-G488-C857-T1031 haplotypes were significantly associated with the increased risk of IS [OR = 1.66; 95%CI 1.02 to 2.71; p = 0.003]. Strong linkage disequilibrium (LD) was observed for + 488G/A and -857C/T (D’ = 0.41, r2 = 0.004). Conclusions Two SNPs (+ 488G/A and -857C/T) of TNF-α gene and their haplotypes are significantly associated with the risk of IS in the population enrolled from North India. Our findings indicate that polymorphisms and haplotypes of TNF-α gene may be used as a genetic marker for identifying individuals at increased risk for developing IS.

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.

Biomarkers to enhance accuracy and precision of prediction of short-term and long-term outcome after spontaneous intracerebral haemorrhage: a study protocol for a prospective cohort study

BackgroundSeveral studies reported prognostic value of biomarker in intracerebral hemorrhagic (ICH) but they are either preliminary observation or inadequately powered to analyse independent contribution of biomarkers over and above clinical and neuroimaging data.ObjectiveTo examine whether the biomarker can significantly add to the predictive accuracy of prognosis of ICH.Method/designIn a multi-centric prospective cohort study, 1020 patients with ICH within 72 hours of onset are being recruited. After obtaining written informed consent from patients/proxy, venous blood sample (10 ml) is being collected and analysed for C-reactive protein (CRP) level, S100B, Glial fibrillary acidic protein (GFAP), Troponin, change in leukocyte count and Copeptin levels. The patients are telephonically followed using stroke scales (Barthel Index and modified Rankin Scale) at 3, 6, 12 months and 2 years after the recruitment.DiscussionThis protocol will aim at predicting the short term or long term prognosis with the use of clinical, neuroimaging and biomarkers in order to help clinician to stratify patients for early referral or intervention.

Association between Interleukin-6 (-174 G/C and -572 C/G) Promoter Gene Polymorphisms and Risk of Intracerebral Hemorrhage in North Indian Population: A Case Control Study

Background: Interleukin-6 (IL-6), a pro-inflammatory cytokine is involved in various vascular pathologies including stroke. Till date, no studies have been reported for the association between IL-6 gene polymorphisms with the risk of Intracerebral hemorrhage (ICH). Objective: The aim of this present case-control study was to investigate the association between IL-6 (-174 G/C and -572 C/G) gene polymorphisms and risk of ICH in North Indian population. Methods: Genotyping was carried out by using SNaPshot method for ICH patients and 100 age-sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between IL-6 (-174 G/C and -572 C/G) polymorphisms and risk of ICH. Results: Hypertension, diabetes, dyslipidemia, smoking and low socioeconomic status were found to be associated with the risk of ICH. The distribution of -174 G/C and -572 C/G genotypes was consistent with Hardy Weinberg Equilibrium (HWE) in the ICH and control subjects. Conditional logistic regression analysis showed a significant association between IL-6 -572 C/G gene polymorphism and the risk of ICH under dominant model (OR=3.7; 95%CI 1.05 to 13.1; p=0.004) and allelic model (OR=2.6; 95%CI 1.1 to 6.2; p=0.01). No significant association was observed for the association between IL-6 -174 G/C gene polymorphism and risk of ICH. Conclusion: Our results suggest that IL-6 (-572 C/G) polymorphism is significantly associated with the risk of ICH in North Indian population. Further prospective studies with large sample size are needed for independent validation.

Association between interleukin-6 (G174C and C572G) promoter gene polymorphisms and risk of ischemic stroke in North Indian population: a case-control study

Background: Polymorphisms of G174C and C572G in the interleukin-6 (IL-6) promoter gene can affect both transcription and secretion of IL-6 and may be involved in inflammation related to and pathogenesis of ischemic stroke (IS). Whether these IL-6 gene polymorphisms are risk factors for IS or not, remains controversial. Objective: The aim of this study was to determine the association between IL-6 G174C and C572G gene polymorphisms and susceptibility to ischemic stroke in North Indian Population. Methods: Two hundred and fifty IS patients and 250 age- and sex-matched controls were studied. Genotyping was performed using SNaPshot method. Stroke was classified using Trial of Org 10172 in acute stroke treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between IL-6 (G174C and C572G) polymorphisms and risk of IS. Results: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary life style and low socioeconomic status were found to be associated with the risk of IS. Conditional logistic regression analysis showed a significant association of IL-6 G174C with the risk of IS under dominant model (OR, 1.61; 95%CI, 1.0–2.4; P value 0.02) and allelic model (OR, 1.5; 95%CI, 1.0–2.1; P value 0.02). For IL-6 C572G, multivariate adjusted analysis showed a significant association with the risk of IS under dominant model for overall IS (OR, 1.81; 95%CI, 1.04–3.15; P value 0.03) and small vessel disease subtype of IS (OR, 2.8; 95%CI, 1.3–6.0; P value 0.006). Conclusion: Our results suggest that IL-6 (G174C) polymorphism is significantly associated with the risk of IS in North Indian population. However, IL-6 (C572G) polymorphism is found significantly associated with the risk of IS after adjusting the demographic and risk factors variables. Prospective studies with large sample size are required for independent validation. Our findings could be helpful in identifying individuals at increased risk for developing IS.

Association between lymphotoxin alpha (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke in North Indian population: a hospital-based case-control study

Purpose: Lymphotoxin alpha (LTA), a proinflammatory cytokine, plays an important role in promoting atherosclerosis which is an independent risk factor for stroke. Recent genetic studies have suggested that polymorphisms in the LTA gene, which affect its expression and biological function, may contribute to the development of stroke. The aim of this case-control study was to determine the association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. Methods: Genotyping was determined by using SNaPshot method for 250 ischemic stroke (IS) patients, 250 age and sex matched IS free controls, 100 intracerebral hemorrhage (ICH) patients and 100 age and sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. The linkage disequilibrium (LD) was analyzed by using HaploView 4.2 software. Results: The distribution of LTA (-252 A/G and -804 C/A) genotypes was consistent with Hardy–Weinberg equilibrium. Adjusted conditional logistic regression analysis showed no significant association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of both IS and ICH. Based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, a significant association between LTA -252 A/G gene polymorphism and small vessel disease subtype of IS under dominant model (OR, 2.06; 95% CI, 1.03–4.12; p value 0.04) with the risk of IS was observed. No LD was observed for both single nucleotide polymorphisms (SNPs) in north Indian population. Conclusion: Neither -252 G/A nor -804 C/A polymorphism of the LTA gene was found to be associated with overall stroke as well as any subtype of IS excluding SVD in North Indian population.

Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection

OBJECTIVES The objective of our study was to describe the clinical characteristics, electrophysiology, MRI features and conduct viral assays in patients with Monomelic Amyotrophy (MMA) and follow them up over one year. METHODS Consecutive patients with MMA who attended the Neurology services from April 2013 to March 2014 were included. Age and sex matched controls were taken for the purpose of viral assay analysis. The clinical evaluation was repeated at six months and one year. RESULTS 109 cases and 109 controls were included in the study. The patients were predominantly males (98.2%; n=107/109) and had involvement of upper limbs (83.5%; n=91/109). 26 (23.8%) patients with clinically unilateral involvement had bilateral neurogenic changes in the electromyography. Serological assays of Japanese E, West Nile Virus, and Poliovirus 1, 2 and 3, HIV 1 and 2 were negative in all the cases and controls. CONCLUSIONS Patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA.