Association of monocyte chemoattractant protein-1 −2518A>G polymorphism with occurrence, severity, and outcome in ischemic stroke

Monocyte chemoattractant protein-1 (MCP-1) is implicated in promoting atherosclerotic diseases, including stroke. Therefore, several studies have investigated the association between variants of the MCP-1 gene and risk of atherosclerotic diseases. We sought to determine the occurrence of MCP-1 ?2518A>G polymorphism in patients with ischemic stroke (IS), and studied its association with the severity of disease and functional outcome after an acute IS. One hundred and forty-five consecutive patients with first ever IS and 145 age- and sex-matched control subjects were recruited. Stroke severity and functional outcome were assessed on admission and at one month post-stroke, respectively. Genotyping for the MCP-1 ?2518A>G polymorphism was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significant difference in the frequency of MCP-1 ?2518A>G genotypes between IS patients and controls was found, with OR = 0.69 (95 % CI 0.46–1.04, P = 0.08). Moreover, carriage of the G allele was not associated with stroke severity (Scandinavian stroke scale score 33.1 vs. 32.5, respectively, P = 0.71), or poor outcome at 1 month post-stroke (63.9 vs. 59.7 %, respectively, P = 0.61). In conclusion, we were unable to demonstrate a significant association of the MCP-1 ?2518A>G gene polymorphism with IS occurrence, severity or functional outcome in a Caucasian population. However, larger studies are necessary to fully elucidate the role of this polymorphism in IS.     

TNFα gene G-308A polymorphism and the risk of ischemic stroke

TNFα, a significant immune mediator, may contribute to the initiation and progression of the ischemic stroke. Genetics of TNFα molecule may have an important role in the risk of ischemic stroke. The most interesting aspects of the G-308A polymorphism remain unexplained; there are many discrepancies between the results. Differences in the ethnicity of the studied cohorts may be taken as one of the possibility. Our study material consisted of 101 patients with ischemic stroke, including 30% classified as lacunar stroke. The diagnosis was based on the presence of rapidly developing neurological signs lasting longer then 24 h and confirmed by neuroimaging matter. All patients were of Polish Caucasian origin. Randomly selected 100 individuals without any sign of the vascular disease of central nervous system were taken as the control material. The frequency of polymorphism G-308A in TNFα gene was determined as described by Rubattu et al. [11]. The genotype distribution in our material was similar and statistically insignificant between patients and controls. The heterozygotic G/A genotype was detected in 9% of patients and in 15% of control materials, homozygotic A/A was found in 5% of patients and only in one of control and G/G in 87% of patients and in 84% of control individuals. Our results are negative with respect to the impact of 308 TNFα polymorphism on the risk of ischemic stroke in Caucasians living in Poland.     

What is the significance of leukoaraiosis in patients with acute ischemic stroke?

BACKGROUND: Leukoaraiosis (LA) may have specific clinical correlates in patients with stroke, but this is not well investigated, so that the significance of LA in patients with stroke remains unclear. METHODS: In a study of 2289 patients with a first-ever acute ischemic stroke, LA was noted in 149 by the use of baseline computed tomography of the brain. These patients were compared with the non-LA group. Statistical tests, including Fisher exact test or a chi(2) test, were used to compare variables, and a multivariate approach using stepwise logistic regression was performed. RESULTS: Patients with LA were significantly older (73.7 vs 62.7 years; P<. 001), and had a higher incidence of hypertension (72.5% vs 47.1%; P<. 001) and subcortical or lacunar infarction (40.3% vs 25.4% and 21.5% vs 8.0%, respectively; P<.001) on neuroimaging studies, compared with the non-LA group. The most common cause of stroke in the LA group was presumed to be small-artery disease associated with hypertension (46% vs 13.5% in the non-LA group). Age and hypertension were very strongly associated with LA (respective odds ratios [95% confidence intervals], 1.06 [1.04-1.08] and 2.33 [1.60-3. 39]). In addition to these risk factors, a close relationship was found between LA and nonsevere stenosis (<50%) of the internal carotid artery (odds ratio, 2.23 [95% confidence interval, 1.32-3. 76]), although the significance of this association remains speculative. The outcome at 1 month after stroke was similar in both groups. CONCLUSION: Our results provide further evidence that LA is related primarily to small-vessel disease.     

Risk factors of stroke and −717A > G (rs2794521) CRP gene polymorphism among stroke patients in West Pomerania province of Poland

Background and purposeSome of the risk factors of ischaemic stroke influence the development of atherosclerosis, which is a significant cause of vascular incidents. An inflammatory component plays a role in pathogenesis of both atherosclerosis and atrial fibrillation, the most important risk factor of embolic strokes. C-reactive protein (CRP) concentration in blood reflects the inflammatory process. Concentration of this protein depends on the CRP gene polymorphism. The aim of the study was to assess the relationship between selected risk factors of stroke and variant of −717A > G (rs2794521) CRP gene polymorphism in population of West Pomerania Province of Poland.Materials and methodsThere were 125 consecutive patients with ischaemic stroke analysed, who met the inclusion and exclusion criteria. In all patients, −717A > G CRP gene polymorphism was genotyped and analysed in relation to selected stroke risk factors.ResultsPrevalence of type 2 diabetes was lower in patients with AA genotype of −717A > G CRP gene polymorphism than in patients with other alleles (p = 0.017). Subjects with GG genotype had significantly higher concentration of CRP comparing to AG genotype (p = 0.023). No correlation was found between −717A > G CRP gene polymorphism and the lipid profile and other selected risk factors of stroke.ConclusionsIn patients with ischaemic stroke in West Pomerania Province, the GG genotype of −717A > G CRP gene polymorphism is associated with significantly higher CRP concentration in relation to AG genotype. Patients with AA genotype may be characterised by lower prevalence of type 2 diabetes.     

Does hyperglycaemia play a role on the outcome of acute ischaemic stroke patients?

Summary A consecutive series of 327 patients (188 males, 139 females; mean age 68.4, SEM 1.33) were hospitalized within 12 h of the onset of their first-ever hemispheric infarct. Three groups of patients were identified: diabetics (n = 70), non-diabetic hyperglycaemics (n = 93) and normoglycaemics (n = 164). Case-fatality ratios at 30 days after stroke were 38.6%, 22.6% and 9.2% (P < 0.001) respectively, whereas the causes of death and functional outcome of survivors were not significantly different between the groups. Mean admission serum glucose levels (SGLs) of deceased, impaired/unchanged and improved patients within each one of the three groups, were also not significantly different as opposed to their mean Canadian Neurological Scale (CNS) scores at entry (P < 0.01). Among patients with less severe initial neurological deficit (i.e., CNS score 7.0), 82.6% of non-diabetic hyperglycaemic subjects fared well, in comparison with 56.5% of diabetic and 70.1% of normoglycaemic individuals. The size of the infarcted areas at the second CT correlated with mean CNS scores (P < 0.01) but not with mean SGLs on admission. The site of the ischaemic areas did not correlate with mean SGLs at entry. Therefore the influence of initial SGLs on the clinical course of the present series of patients is questionable or, alternatively, varied probably according to the pattern of residual cerebral blood flow after arterial occlusion.     

Influence of the β-fibrinogen-455G/A polymorphism on development of ischemic stroke and coronary heart disease

Background

Ischemic stroke (IS) and coronary heart disease (CHD) are two vascular disorders that are a common cause of death worldwide. Several studies have assessed the association of the β-fibrinogen-455G/A (FGB-455G/A) polymorphism and risk of IS and CHD, but the results are still inconsistent. Our study aimed to investigate whether the FGB-455G/A polymorphism was associated with susceptibility to IS and CHD by using meta-analysis.

Methods

Relevant studies were identified from PubMed, Embase and four Chinese database up to July 2013.Data were analyzed and processed by Stata 11.2. A pooled OR with 95% CI was calculated to estimate the strength of the genetic association. Cumulative meta-analysis was performed to assess the tendency of pooled OR over time.

Results

45 studies based on a total of 7238 cases and 7395 controls were included in our meta-analysis. The results indicated that the FGB-455G/A polymorphism is associated with the risk of IS when compared with the dominant model (OR = 1.518, 95%CI = 1.279-1.802 for AA + GA vs. GG). In the subgroup analysis by ethnicity, significantly elevated risks were associated with the A allele in Asians (OR = 1.700, 95%CI = 1.417-2.040), but not in Caucasians (OR = 0.942, 95%CI = 0.813-1.091). Both the hypertension and non-hypertension subgroups reached significant results, but no significance was found when stratified according to sex or subtype of IS. Results indicate that the FGB-455G/A polymorphism is associated with CHD (OR = 1.802, 95%CI = 1.445-2.246).

Conclusion

Our meta-analysis suggests that the FGB-455G/A polymorphism contributes to susceptibility to IS and CHD.     

Association analysis of the −308G > A promoter polymorphism of the tumor necrosis factor alpha (TNF-α) gene in Japanese patients with schizophrenia

Summary. Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (–308G > A) of the gene encoding tumor necrosis factor alpha (TNF-), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the –308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the –308G > A polymorphism of the TNF- gene.     

“Real life” impact of anesthesia strategy for mechanical thrombectomy on the delay,recanalization and outcome in acute ischemic stroke patients

Background and purposeChoice of anesthesia type on outcome for mechanical thrombectomy (MT) in acute ischemic stroke remains controversial. The goal of our research was to study the impact of anesthesia strategy on the delay, angiographic and neurological outcome of MT performed under general anesthesia (GA) vs. conscious sedation (CS).MethodsThis prospective, single-center observational study included patients with anterior circulation large vessel occlusion (ACLVO) strokes treated with MT within 6 hours of symptom onset. All time metrics were evaluated. Angiographic and clinical outcomes were assessed by recanalization rate (mTICI) and 3-month functional independence (mRs). Complications and mortality rate were recorded as safety outcomes.ResultsIn total, 303 consecutive thrombectomies were performed, 86.8% under GA. NIHSS was higher in GA, with median of 19.0 for GA and 16.5 for CS (P = 0.049). Median time from arrival in hospital (door) to groin puncture was 83 min (IQR = 45.0–109.5) for GA compared to 72 min (IQR = 35.0–85.3) for CS, P = 0.170). Median time from arrival in the angiosuite to groin puncture was 20 min (IQR = 15.0–29.0) for GA compared to 15 min (IQR = 10.0–20.0) for CS, P = 0.017). There were no significant differences in recanalization time metrics, successful revascularization rate, functional independence and mortality rate at three months.ConclusionsGA induced a 5 to 10 minutes delay for groin puncture, without impact on recanalization time metrics, or neurological outcome at 3 months. Our results demonstrate that a well-organized workflow is associated with reasonable delay in performing GA for MT, without effect on outcome compared to sedation.     

Functional,cognitive and emotional long–term outcome of patients with ischemic stroke requiring mechanical ventilation

Prognosis of patients with ischemic stroke requiring mechanical ventilation (MV) has been reported to be poor. However, longterm survival and functional outcome have scarcely been studied and nothing is known about the prevalence of cognitive impairment or depression in survivors and their quality of life (QoL).We identified all patients treated for acute ischemic stroke on a Neurological Intensive Care Unit during 3.5 years who required MV for more than 24 hours. Early mortality rate at 2 months and survival rates at 1 and 2 years were determined. Survivors were examined for functional outcome (modified Rankin Scale (mRS), Barthel Index), cognitive impairment (Mini Mental State Examination (MMSE)), depression (Beck Depression Inventory, BDI) and QoL (Short Form–36). Clinical characteristics on admission were analyzed for prognostic significance. Of 101 consecutive patients, 44% died within 60 days. Survival rates at 1 and 2 years were 40% and 33%, respectively.Age > 60 years (p = 0.002) and Glasgow Coma Scale score < 10 on admission (p = 0.002) were independent predictors of early and late mortality. History of myocardial infarction (p = 0.007) independently predicted late mortality at 2 years. Of 33 surviving patients, nine (27%) had a good functional outcome (mRS 0–2). Of 27 survivors who could be interviewed, 17 (63%) had no cognitive impairment (MMSE > 24) and 20 (74%) did not suffer from relevant depression (BDI < 19).In conclusion, longer–term survival of patients with ischemic stroke requiring MV was 33% and every fourth survivor resumed an independent life without dementia or depression. Older patients comatose on admission and with concomitant cardiovascular disease had the lowest probability of a favorable outcome.Drs. Schielke and Busch contributed equally to the study.     

Impact of the PDE4D gene polymorphism and additional SNP–SNP and gene–smoking interaction on ischemic stroke risk in Chinese Han population

Aims: To investigate the association between phosphodiesterase 4D gene (PDE4D) gene single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) risk, and impact of additional SNP- SNP and gene- smoking interaction on IS risk in Chinese population.

Methods: A total of 1228 subjects (666 males, 562 females) were selected, including 610 IS patients and 618 control subjects. Logistic regression model was used to examine the association between SNPs in PDE4D gene and IS risk. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the SNP- SNP and gene- smoking interaction.

Results: IS risks were significantly higher in carriers of A allele of rs12188950 polymorphism than those with GG genotype (GA + AA vs. GG), adjusted OR (95%CI) = 1.61 (1.26–2.19), and also significantly higher in carriers of T allele of rs966221 polymorphism than those with CC (CT + TT vs. CC), adjusted OR (95%CI) = 1.82 (1.39–2.23). We found that there was a significant SNP- SNP interaction between rs966221 and rs12188950. Subjects with CT or TT of rs966221 and GA or AA of rs12188950 genotype have the highest IS risk, compared to subjects with CC of rs966221 and GG of rs12188950 genotype, OR (95%CI) was 3.52 (2.68–4.69). We also found a significant gene–environment interaction between rs966221 and smoking. Smokers with CT or TT of rs966221 genotype have the highest IS risk, compared to never smokers with CC of rs966221 genotype, OR (95%CI) was 3.97 (2.25–5.71).

Conclusions: Our results support an important association of rs966221 and rs12188950 minor allele and its interaction with increased risk of IS risk, and additional interaction between rs966221 and smoking.     

Microembolic signals and clinical outcome in patients with acute stroke – a prospective study

The occurrence of microembolic signals (MES) in patients with transient ischemic attack (TIA) or stroke has already been described; the influence of the time interval between onset of symptoms and transcranial Doppler monitoring (TCD) on the MES rate or MES prevalence and the possible prognostic value of the early detected MES rate on the outcome of TIA or stroke symptoms in a 3 month interval are discussed. In a prospective study we evaluated 61 patients consecutively admitted to our stroke unit after their first ischemic neurological deficit involving the vascular territory of MCA and/or ACA. All of the patients underwent a 30-minute bilateral transcranial Doppler monitoring of their MCAs for the identification of MES. Monitoring was performed within 12.3 + -9.3 (average mean + -SD) hours of stroke onset for the first time, the second time 48 hours after first TCD monitoring. Prognosis for the recovery of neurological deficits was evaluated by using the Barthel index (BI) and Scandinavian Stroke Scale (SSS) at the time of admission of the patient to the stroke unit, and with Barthel indices after one month and after 3 months. As a result, 56% of all patients showed MES in at least one of the two registrations. MES were recorded not only on the symptomatic side. The MES prevalence between both TCD monitorings was significantly different (total MES prevalence: 1st TCD: 26 patients: 2nd TCD: 13 patients; p < 0.04; ipsilateral MES prevalence: 1st TCD: 19 patients; 2nd TCD: 9 patients; p < 0.01). The regression analysis showed a significant influence of the total MES rate on both neurological scores at admission (SSS: 0.03; Barthel index: 0.04), but not for the Barthel scores after one and three months. In conclusion, we found an influence of the time interval between onset of neurological symptoms of TIA or stroke on the MES rate and the prevalence of MES. The prevalence of MES or the MES rate, found after a short time interval to the onset of symptoms, did not have a prognostic value on the outcome of neurological deficits up to a three month follow-up.     

What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke?

BACKGROUND: Pulmonary embolism after acute ischemic stroke (AIS) is associated with a high in-hospital mortality. The benefit from pharmacological prophylaxis for venous thromboembolism (VTE) is uncertain probably due to doubts about the optimal agent and dose. We evaluated the benefit/risk ratio of different anticoagulant regimens in the prevention of VTE in patients with AIS. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched up to January 2005. Randomized controlled trials (RCT) comparing early administration of either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) with control were included. Endpoints were objectively diagnosed deep-vein thrombosis (DVT), pulmonary embolism, intracranial hemorrhage (ICH), and extracranial hemorrhage (ECH). Low-dose UFH was arbitrarily defined as < or =15,000 IU/day, low-dose LMWH as < or =6000 IU/day or weight-adjusted dose of < or =86 IU/kg/day. RESULTS: Sixteen trials involving 23,043 patients with AIS met the inclusion criteria. The number of events was small and different doses of anticoagulant treatment were used. Compared to control, high-dose UFH was associated with a reduction in pulmonary embolism (OR=0.49, 95% confidence interval (CI)=0.29-0.83), but also with an increased risk of ICH (OR=3.86, 95% CI=2.41-6.19) and ECH (OR=4.74, 95% CI=2.88-7.78). Low-dose UFH decreased the thrombosis risk (OR=0.17, 95% CI=0.11-0.26), but had no influence on pulmonary embolism (OR=0.83, 95% CI=0.53-1.31); the risk of ICH or ECH was not statistically significant increased (OR=1.67, 95% CI=0.97-2.87 for ICH; and OR=1.58, 95% CI=0.89-2.81 for ECH, respectively). High-dose LMWH decreased both DVT (OR=0.07, 95% CI=0.02-0.29) and pulmonary embolism (0.44, 95% CI=0.18-1.11), but this benefit was offset by an increased risk for ICH (OR=2.01, 95% CI=1.02-3.96) and ECH (OR=1.78, 95% CI=0.99-3.17). Low-dose LMWH reduced the incidence of both DVT (OR=0.34, 95% CI=0.19-0.59) and pulmonary embolism (OR=0.36, 95% CI=0.15-0.87), without an increased risk of ICH (OR=1.39, 95% CI=0.53-3.67) or ECH (OR=1.44, 95% CI=0.13-16). For low-dose LMWH, the numbers needed to treat were 7 and 38 for DVT and pulmonary embolism, respectively. CONCLUSIONS: Indirect comparison of low and high doses of UFH and LMWH suggests that low-dose LMWH have the best benefit/risk ratio in patients with acute ischemic stroke by decreasing the risk of both DVT and pulmonary embolism, without a clear increase in ICH or ECH.     

IL6-174G > C genetic polymorphism influences antidepressant treatment outcome

Background: Major depressive disorder is a condition associated with dysregulated cytokine levels; among these, IL6. Furthermore, genetic variations within cytokine genes have been proposed to predict antidepressant treatment outcome.

Objectives: This study aims to evaluate the role of IL6-174G?>?C and IL6R D358A A?>?C functional polymorphisms in antidepressant treatment phenotypes, specifically remission, relapse, and treatment resistant depression (TRD).

Methods: The referred polymorphisms were genotyped in 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months.

Results: It was found that patients carrying IL6-174 GC genotype present a protection towards the development of TRD (OR?=?0.242; 95% CI?=?0.068–0.869; p?=?.038), when compared with GG genotype. Additionally, carriers of IL6-174?CC genotype remit earlier than patients with IL6-174 GG/GC genotypes, with a median time to remission of 6 weeks for CC carriers and 15 weeks for GG or GC carriers (p?=?.030, Log-rank test). No association was found between IL6R D358A genetic polymorphism and any of the treatment phenotypes evaluated.

Conclusions: The IL6-174G?>?C polymorphism influences antidepressant treatment outcome in this sub-set of MDD patients, providing a putative mechanistic link for the dysregulated IL-6 levels described in the literature in patients with TRD.     

Is CT perfusion helpful in the treatment allocation of patients with acute ischemic stroke? An expert-opinion analysis

Background

Intravenous tPA is the standard treatment for acute ischemic stroke within 4.5 hours of symptom onset. Neuroradiological selection is currently based upon non-contrast- brain CT scan (NCCT).

Aims

To verify, in an “expert-opinion setting”, the possible usefulness of CT perfusion (CTP) in decision-making toward i.v. thrombolysis.

Patients and method

One hundred and three consecutive patients with acute ischemic stroke who underwent NCCT and CTP were re-evaluated by an expert in cerebrovascular disease, to verify if adding CTP information would have changed expert’s opinion.

Results

After CTP, a definitive decision was made for 20 more patients, changing the proportion of patients candidate to i.v. tPA from 44% to 51%, and reducing uncertainty from 29% to 10%. CTP results were useful inmilder stroke (p = 0.01).

Conclusions

In a “real world” setting, CT perfusion could be useful for clinical decision, in particular for milder stroke.