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Little is known about the prognostic role of fasting glucose after mechanical thrombectomy (MT).We investigated whether fasting glucose on the next day after MT was associated with long-term outcome in acute ischemic stroke patients according to diabetes.We retrospectively analyzed 181 consecutive patients with acute anterior circulation ischemic stroke who underwent MT in 2 comprehensive stroke centers in Poland. Glucose levels were evaluated on admission and on the next day after MT. Fasting hyperglycemia (FHG) was defined as the glucose level above 5.5 mmol/L. Unfavorable outcome was defined as modified Rankin scale (mRS) of 3-6 at day 90 from stroke onset.Patients with FHG had higher mRS at 3-month follow-up compared with those without FHG (3.71 ± 2.56 versus 1.87 ± 2.22, P.001). In the subgroup analyses, FHG was associated with poor neurological outcome in the group without diabetes (3.74 ± 2.52 versus 1.81 ± 3.74, P.001) but not with diabetes (3.64 ± 2.67 versus 2.30 ± 3.74, P= .11). Patients without diabetes who had FHG were older, had higher glucose on admission, higher prevalence of atrial fibrillation, cardioembolic stroke etiology and bleeding brain complications compared with the group with normal fasting glucose. After adjustment for potential confounders, fasting glucose (odds ratio [OR] 1.46; 95% CI 1.19-1.79, P.001), age (OR 1.06; 95% CI 1.02-1.10, P = .001), successful reperfusion (OR 0.09; 95% CI 0.04-0.22, P.001) and baseline NIHSS score (OR 1.18; 95% CI 1.08-1.29, P.001) were predictors of mRS 3-6 at 3-month follow-up in the whole group. In the subgroup without diabetes, fasting glucose (OR 1.57; 95% CI 1.17-2.11, P = .002), age (OR 1.05; 95% CI 1.01-1.08, P = .008), successful reperfusion (OR 0.11; 95% CI 0.04-0.30, P.001) and baseline NIHSS score (OR 1.14; 95% CI 1.04-1.26, P = .011) were independent predictors of unfavorable 3-month outcome.Fasting glucose on the next day after MT in patients with acute ischemic stroke is an independent risk factor for worse 3-month outcome.

Background: Oxidative stress plays an important role in vascular pathology and contributes to the pathophysiology of primary intracerebral hemorrhage (PICH). Glutathione peroxidase 1 (GPX1) is a key enzyme of the antioxidant system. Here, we investigated whether a functional C593T polymorphism of GPX1 gene is associated with PICH in a Polish population. Methods: Genotyping was performed in 192 PICH patients and 197 unrelated controls matched for age and sex. All were of Caucasian origin. The C593T GPX1 polymorphism was investigated using the polymerase chain reaction/restriction fragment length polymorphism method. Results: Multivariable logistic regression analysis revealed a significant association between genotypes containing the T allele and the entire PICH group (OR = 1.53; 95% CI = 1.02–2.29) and lobar PICH (OR = 2.36; 95% CI = 1.31–4.26) but not nonlobar PICH (OR = 1.19; 95% CI = 0.75–1.89). Conclusions: We found a positive association between the studied GPX1 polymorphism and lobar PICH in a Polish population.

Background – Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (−844 G/A, −675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. Methods – We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. Results – A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. Conclusions – Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of −844 G/A, −675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke.

Summary Background The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. Methods To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis. Findings We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13–1·30, p=4·50 × 10 −8 ; joint OR 1·19, 1·12–1·26, p=1·30 × 10 −9 ). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29–1·49, p=3·26 × 10 −19 ; joint OR 1·37, 1·30–1·45, p=2·79 × 10 −32 ) and ZFHX3 (first stage OR 1·19, 1·11–1·27, p=2·93 × 10 −7 ; joint OR 1·17, 1·11–1·23, p=2·29 × 10 −10 ) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18–1·42, p=3·50 × 10 −8 ; joint OR 1·24, 1·15–1·33, p=4·52 × 10 −9 ) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2 , which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12–1·28, p=6·82 × 10 −8 ; joint OR 1·17, 1·11–1·23, p=2·92 × 10 −9 ). Other loci associated with stroke in previous studies, including NINJ2 , were not confirmed. Interpretation Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke. Funding US National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Objectives – Data concerning an association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and ischemic stroke (IS) remain inconsistent. Results of some studies suggest that DD genotype may be a risk factor for small vessel disease (SVD) stroke. Here, we investigated whether this polymorphism is associated with IS of different etiologies in a Polish population. Subjects and methods – Ischemic stroke etiology was established according to the TOAST criteria. We studied 92 stroke patients with large vessel disease and their 184 matched controls; 96 stroke patients with SVD and 192 controls; 180 patients with cardioembolic stroke (CE) and 180 controls. ACE I/D polymorphism was determined using the polymerase chain reaction method. Results – The distribution of ACE genotypes and alleles was essentially the same in all analyzed IS subtypes and their matched controls. Conclusions – We failed to find an association between ACE polymorphism and etiological subtypes of IS in a Polish population.

Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

Production of the proinflammatory cytokine interleukin 1β (IL1β) increases in several acute or chronic diseases.1 The IL1β gene is a member of the IL1 gene family clustered on chromosome 2.1 A C/T polymorphism in the promoter region of the IL1β gene at position −511 influences the protein production, with the highest levels in T allele carriers.2 Data suggest that inflammation plays a role in the pathogenesis of subarachnoid haemorrhage (SAH) from ruptured aneurysm.3 We hypothesise that individuals genetically predisposed to an exaggerated cytokine production may be at risk of aneurysmal SAH. We studied the significance of IL1β –511 C/T polymorphism in patients with aneurysmal SAH and in healthy controls. We included 231 unrelated patients with aneurysmal SAH, of a total of 401 patients with SAH admitted to the Institute of Neurology, Krakow, Poland between 2003 and 2005. Patients with dissecting and fusiform aneurysms (n = 10), arteriovenous malformations (n = 30), SAH of unknown origin (n = 39), those who were comatose …