Acute phase proteins and oxidised low-density lipoprotein in association with ischemic stroke subtype, severity and outcome

Objectives: The goal of our study was to investigate the associations of oxidized LDL (apoB100 aldehyde-modified form) and acute phase proteins (fibrinogen, CRP) with acute ischemic stroke severity and outcome.

Materials and Methods: The study included 61 ischemic stroke patients and 64 controls. Strokes were subtyped according to TOAST criteria, the severity and outcome of stroke (at 1 year) were measured.

Results: The mean triglyceride, fibrinogen, CRP and glucose values were significantly higher among cases. The median oxLDL value for patients with large artery atherosclerosis (LAA) type of stroke was significantly higher than for other subtypes. The oxLDL values did not correlate with age, stroke severity and outcome.

Conclusions: Inflammatory markers (fibrinogen and CRP) predicted the stroke severity and outcome whereas elevation of oxLDL levels did not. Our data refer to possibility that there may exist some links between the LAA subtype of stroke and elevated oxLDL (apoB100 aldehyde-modified form).     

The Role of Tryptophan Catabolism along the Kynurenine Pathway in Acute Ischemic Stroke

Post-stroke inflammation may induce upregulation of the kynurenine (KYN) pathway for tryptophan (TRP) oxidation, resulting in neuroprotective (kynurenic acid, KA) and neurotoxic metabolites (3-hydroxyanthranillic acid, 3-HAA). We investigated whether activity of the kynurenine pathway in acute ischemic stroke is related to initial stroke severity, long-term stroke outcome and the ischemia-induced inflammatory response. Plasma concentrations of TRP and its metabolites were measured in 149 stroke patients at admission, at 24 h, at 72 h and at day 7 after stroke onset. We evaluated the relation between the KYN/TRP ratio, the KA/3-HAA ratio and stroke severity, outcome and inflammatory parameters (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and neutrophil/lymphocyte ratio (NLR)). KYN/TRP but not KA/3-HAA correlated with the NIHSS score and with the infarct volume. Patients with poor outcome had higher mean KYN/TRP ratios than patients with more favourable outcome. The KYN/TRP ratio at admission correlated with CRP levels, ESR and NLR. The activity of the kynurenine pathway for tryptophan degradation in acute ischemic stroke correlates with stroke severity and long-term stroke outcome. Tryptophan oxidation is related to the stroke-induced inflammatory response.     

Admission C – reactive protein after acute ischemic stroke is associated with stroke severity and mortality: The 'Bergen stroke study'

Background

There is growing evidence that inflammation plays an important role in atherogenesis. Previous studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. It is not clear whether this is due a direct dose-response effect or rather an epiphenomenon. We studied the effect of CRP measured within 24 hours after stroke onset on functional outcome, mortality and future vascular events.

Methods

We prospectively studied 498 patients with ischemic stroke who were admitted within 24 hours after the onset of symptoms. CRP and NIH stroke scale (NIHSS) were measured at the time of admission. Short-term functional outcome was measured by modified Rankin scale (mRS) and Barthel ADL index (BI) 7 days after admission. Patients were followed for up to 2.5 years for long-term mortality and future vascular events data.

Results

The median CRP at admission was 3 mg/L. High CRP was associated with high NIHSS (p = 0.01) and high long-term mortality (p < 0.0001). After adjusting for confounding variables, high CRP remained to be associated with high NIHSS (p = 0.02) and high long-term mortality (p = 0.002). High CRP was associated with poor short-term functional outcomes (mRS > 3; BI < 95) (p = 0.01; p = 0.03). However, the association was not significant after adjusting for confounding variables including stroke severity (p = 0.98; p = 0.88). High CRP was not associated with future vascular events (p = 0.98).

Conclusion

Admission CRP is associated with stroke severity and long-term mortality when measured at least 24 hours after onset. There is a crude association between high CRP and short-term functional outcome which is likely secondary to stroke severity. CRP is an independent predictor of long-term mortality after ischemic stroke.     

Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation

Circulating oxidized LDL (oxLDL) levels are strongly correlated to LDL-cholesterol (LDL-c) and apolipoprotein-B100 (apoB100), making it difficult to disentangle their independent contributions to cardiovascular risk. We explored the determinants of oxLDL and the relation between oxLDL and flow-mediated dilation (FMD) of the brachial artery to investigate whether the oxLDL/LDL-c and oxLDL/apoB100 ratios are more informative than the separate variables. FMD of the brachial artery and plasma concentrations of oxLDL, LDL-cholesterol, and apoB100 were measured in 624 men and women (age range 50 to 87 years), participating in a population-based cohort study. OxLDL was strongly correlated with apoB100 (r = 0.82, P < 0.001) and LDL-c (r = 0.67, P < 0.001). Other major independent determinants of oxLDL were sex, HDL-cholesterol, and LDL particle size. LDL-c and apoB100 concentrations were not significantly associated with FMD. After adjustment for age, sex, glucose tolerance status, and Framingham risk score, the oxLDL/apoB100 ratio was negatively related to FMD (P = 0.017). This association was weaker for the oxLDL/ LDL-c ratio (P = 0.062) and absent for oxLDL level (P = 0.27). In contrast to oxLDL, the oxLDL/apoB100 ratio, and to a lesser extent the oxLDL/LDL-c ratio, are related to a functional measure of atherosclerosis. Therefore correction of oxLDL for LDL particle number may improve the clinical usefulness of oxLDL measurement.     

Comparison of Risk Factor between Lacunar Stroke and Large Artery Atherosclerosis Stroke: A Cross-Sectional Study in China

Background

Stroke is the second most common cause of mortality in China. Although most subtypes of ischemic stroke share similar risk factors, they have different etiologies. Our study aimed to evaluate the different risk factor profiles between the stroke subtypes, lacunar infarcts (LI) and large-artery atherosclerosis (LAA), and clarify the characteristics of current acute ischemic stroke in China.

Methods

In this cross-sectional study, we analyzed the clinical characteristics of 1982 patients with acute ischemic stroke who were admitted to the neurology department at the Peking University First Hospital between 2007 and 2014. Ischemic stroke was further classified into LAA, LI, cardioembolism (CE) and undetermined causes of infarction (UDI) according to TOAST classification. Demographic characteristics, risk factors, as well as the findings of laboratory and imaging tests of 1773 patients with LAA and LI, were analyzed by univariate and multivariate logistic analysis.

Results

Of the 1982 ischemic stroke patients included in this study, 1207 were diagnosed with LAA, 566 with LI, 173 with cardioembolism (CE) and 36 with undetermined causes of infarction (UDI). By comparing the risk factors in multivariate logistic regression analysis, hypertension [odds ratio (OR) = 1.832] and white matter leukoaraiosis (WML) (OR = 1.865) were found to be more strongly correlated with LI than LAA. Low density lipoprotein- cholesterol (LDL-c) (OR = 0.774) were more strongly related to LAA than LI.

Conclusions

This study found that hypertension and WML were more strongly correlated with LI than LAA. LDL-c was more strongly related to LAA than LI.     

Association between Statin Use and Short-Term Outcome Based on Severity of Ischemic Stroke: A Cohort Study

Background

Statins reportedly improve clinical outcomes for ischemic stroke patients. However, it is unclear whether the contribution of statin treatment varies depending on the severity of stroke. We sought to investigate the relationship between statin use and the outcome of acute first-ever ischemic stroke patients stratified by stroke severity.

Methods

A total of 7,455 acute first-ever ischemic stroke patients without statin treatment before onset were eligible from the China National Stroke Registry. A National Institutes of Health Stroke Scale (NIHSS) score of 0 to 4 was defined as minor stroke, and a NIHSS score of >4 was defined as non-minor stroke. We analyzed the association between statin use during hospitalization and mortality as well as functional outcome (measured by a modified Rankin Scale score of 0–5) at 3 months after onset using multivariable logistic regression models.

Results

A total of 3,231 (43.3%) patients received statin treatment during hospitalization. Multivariable analysis showed that statin use during hospitalization decreased mortality of ischemic stroke patients (OR, 0.51; 95%CI, 0.38–0.67), but did not improve poor functional outcomes (OR, 0.95; 95CI%, 0.81–1.11) at 3 months. The interaction between statin use and stroke severity was significant both in dependence and death outcome (P = 0.04 for dependence outcome, P = 0.03 for death outcome). After stratification by stroke severity, statin use during hospitalization decreased the mortality of stroke (OR, 0.44; 95%CI, 0.31–0.62) and poor functional outcome (OR, 0.73; 95%CI, 0.57–0.92) at 3 months in the non-minor stroke group.

Conclusions

Statin use during hospitalization may improve the clinical outcome of acute first-ever ischemic stroke depending on the severity of stroke. Non-minor stroke patients may obtain benefit from statin treatment with improvements in poor functional outcomes and mortality.     

Effects of low-frequency repetitive transcranial magnetic stimulation on upper extremity motor recovery and functional outcomes in chronic stroke patients: A randomized controlled trial

Background: Repetitive transcranial magnetic stimulation (rTMS) was suggested as a preconditioning method that would increase brain plasticity and that it would be optimal to combine rTMS with intensive rehabilitation.

Objective: To assess the efficacy of inhibitory rTMS on upper extremity motor recovery and functional outcomes in chronic ischemic stroke patients.

Methods: In this randomized controlled trial, experimental group received low-frequency (LF) rTMS to the primary motor cortex of the unaffected side?+?physical therapy (PT), and control group received PT.

Results: No statistically significant difference was found in baseline demographical and clinical characteristics of the subjects including stroke severity or severity of paralysis prior to intervention. There were statistically significant improvements in all clinical outcome measures except for the Brunnstrom Recovery Stages. Fugl–Meyer Assessment, Box and Block test, motor and total scores of Functional Independence Measurement (FIM), and Functional Ambulation Scale (FAS) scores were significantly increased in both groups, however, these changes were significantly greater in the rTMS group except for FAS score. FIM cognitive scores and standardized mini-mental test scores were significantly increased and distal and hand Modified Ashworth Scale scores were significantly decreased only in the rTMS group (p?Conclusions: LF-rTMS can safely facilitate upper extremity motor recovery in patients with chronic ischemic stroke. TMS seems to be a promising treatment for motor, functional, and cognitive deficits in chronic stroke. Further studies with a larger number of patients with longer follow-up periods are needed to establish its effectiveness in stroke rehabilitation.     

Low-density lipoprotein-associated variables and the severity of coronary artery disease: an untreated Chinese cohort study

Abstract

Background and aims: Elevated low-density lipoprotein cholesterol (LDL-C) is causal risk for coronary artery disease (CAD) and LDL-associated variables including LDL-C, apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein a [Lp(a)], small dense LDL (sd-LDL), and oxidized LDL (ox-LDL) have been widely used for predicting the risk of CAD. This study was aimed to compare the values of six LDL-related variables for predicting the severity of CAD using untreated patients undergoing coronary angiography (CAG).

Methods: A group of 1977 individuals were consecutively enrolled and divided into CAD (n?=?1151) and non-CAD groups (n?=?826) according to the results of CAG. LDL-C, apoB, non-HDL-C, Lp(a), sd-LDL and ox-LDL were measured, respectively. The numbers of stenotic arteries and Gensini Scores (GS) were used to calculate the severity of CAD and the associations of six variables with the severity of CAD and predicting value of these parameters were simultaneously examined.

Results: CAD patients had significantly higher concentrations of LDL-related variables than non-CAD ones (all p?<?0.05). Importantly, all variables rose with the increase in the severity of CAD. The predicting value of CAD manifested as sd-LDL?>?ox-LDL?>?apoB?>?non-HDL-C?>?LDL-C?>?Lp(a) [area under curve (AUC): sd-LDL 0.641; ox-LDL 0.640; apoB 0.611; non-HDL-C 0.587; LDL-C 0.583; Lp(a) 0.554; respectively]. In multivariate logistic analysis, all variables showed as independent risk factors for the severity of CAD [odds ratio (OR): ox-LDL?>?sd-LDL?>?apoB?>?non-HDL-C?>?LDL-C?>?Lp(a)].

Conclusions: All of LDL-related variables could be useful marker for predicting the severity of CAD but sd-LDL and ox-LDL appeared to litter better. Further study may be needed to validate our results.     

Left Atrial Appendage Morphology in Patients with Suspected Cardiogenic Stroke without Known Atrial Fibrillation

The left atrial appendage (LAA) is the typical origin for intracardiac thrombus formation. Whether LAA morphology is associated with increased stroke/TIA risk is controversial and, if it does, which morphological type most predisposes to thrombus formation. We assessed LAA morphology in stroke patients with cryptogenic or suspected cardiogenic etiology and in age- and gender-matched healthy controls. LAA morphology and volume were analyzed by cardiac computed tomography in 111 patients (74 males; mean age 60 ± 11 years) with acute ischemic stroke of cryptogenic or suspected cardiogenic etiology other than known atrial fibrillation (AF). A subgroup of 40 patients was compared to an age- and gender-matched control group of 40 healthy individuals (21 males in each; mean age 54 ± 9 years). LAA was classified into four morphology types (Cactus, ChickenWing, WindSock, CauliFlower) modified with a quantitative qualifier. The proportions of LAA morphology types in the main stroke group, matched stroke subgroup, and control group were as follows: Cactus (9.0%, 5.0%, 20.0%), ChickenWing (23.4%, 37.5%, 10.0%), WindSock (47.7%, 35.0%, 67.5%), and CauliFlower (19.8%, 22.5%, 2.5%). The distribution of morphology types differed significantly (P<0.001) between the matched stroke subgroup and control group. The proportion of single-lobed LAA was significantly higher (P<0.001) in the matched stroke subgroup (55%) than the control group (6%). LAA volumes were significantly larger (P<0.001) in both stroke study groups compared to controls patients. To conclude, LAA morphology differed significantly between stroke patients and controls, and single-lobed LAAs were overrepresented and LAA volume was larger in patients with acute ischemic stroke of cryptogenic or suspected cardiogenic etiology.     

Haplotype analysis revealed a genetic influence of osteopontin on large artery atherosclerosis

Osteopontin (OPN) is a cytokine that involves in vascular remodeling processes in cerebrovascular diseases. The association of its gene with ischemic stroke was investigated in a Korean population. Representative sequence variants covering the entire OPN gene were genotyped in 455 controls and 271 patients with ischemic stroke including large artery atherosclerosis (LAA), small vessel occlusion, and cardioembolism. Analysis with the individual tagging variants and their haplotypes revealed an evidence of association only with LAA. Significances were shown with the haplotypes, especially with the TCA at the loci C2140T, C5891T, and A7385G conferring a risk of 2.09 for LAA (P < 0.05). The CG at the loci C1013T and A7385G was the most protective haplotype (OR = 0.66, P < 0.05). Our findings suggested that several haplotypes of OPN gene contributed to determining risk factors as well as protective factors of LAA.     

Research on the relationship between fibrinogen level and subtypes of the TOAST criteria in the acute ischemic stroke

Background

Cerebral infarction caused by different reasons seems differ in fibrinogen levels, so the current work intends to explore the relationship between the fibrinogen level and subtypes of the TOAST criteria in the acute stage of ischemic stroke.

Methods

A total of 577 case research objects were treated acute ischemic stroke patients in our hospital from December 2008 to December 2010, and blood samples within 72 hours of the onset were processed with the fibrinogen (PT-der) measurement. Classification of selected patients according to the TOAST Criteria was conducted to study the distribution of fibrinogen levels in the stroke subtypes.

Results

The distribution of fibrinogen levels in the subtypes was observed to be statistically insignificant.

Conclusions

In the acute stage of ischemic stroke, fibrinogen level was not related to the subtypes of the TOAST criteria.

     

Association of ischemic stroke onset time with presenting severity,acute progression,and long-term outcome: A cohort study

BackgroundPreclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.Methods and findingsIn a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules.ConclusionsNight-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Wi-Sun Ryu and colleagues investigate the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in ischemic stroke.     

Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome

Background

Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of stroke severity and outcome.

Methods

Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS) at 3 months and computed tomography (CT) brain infarct volume.

Results

Peak plasma IL-6 concentration correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12 months or stroke severity. Strong associations were also noted between either peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC) count, and all outcome measures.

Conclusions

These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome.     

Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma

Context: C-reactive protein (CRP), a biomarker of inflammation, may correlate with prognosis in several malignancies.

Objective: To investigate the prognostic impact of early postoperative peak serum levels of CRP on tumor-specific outcome in 106 liver transplant patients with hepatocellular carcinoma (HCC).

Methods and results: In multivariate Cox regression analysis, a posttransplant elevated peak CRP level (>versus?≤?3.5?mg/dl) was identified as an independent predictor of poor recurrence-free survival (p?=?0.01; HR?=?4.04; CI?=?1.399–11.640).

Conclusion: Early postoperative serum CRP may serve as a useful inflammation-based biomarker of outcome in liver transplant patients with HCC.     

Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke

Circular RNAs (circRNAs) are highly expressed in the central nervous system and are involved in the regulation of physiological and pathophysiological processes. However, the potential role of circRNAs in stroke remains largely unknown. Here, using a circRNA microarray, we showed that circular RNA Hectd1 (circHectd1) levels were significantly increased in ischemic brain tissues in transient middle cerebral artery occlusion (tMCAO) mouse stroke models and further validated this finding in plasma samples from acute ischemic stroke (AIS) patients. Knockdown of circHectd1 expression significantly decreased infarct areas, attenuated neuronal deficits, and ameliorated astrocyte activation in tMCAO mice. Mechanistically, circHECTD1 functions as an endogenous MIR142 (microRNA 142) sponge to inhibit MIR142 activity, resulting in the inhibition of TIPARP (TCDD inducible poly[ADP-ribose] polymerase) expression with subsequent inhibition of astrocyte activation via macroautophagy/autophagy. Taken together, the results of our study indicate that circHECTD1 and its coupling mechanism are involved in cerebral ischemia, thus providing translational evidence that circHECTD1 can serve as a novel biomarker of and therapeutic target for stroke.

Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AIS: acute ischemic stroke; AS: primary mouse astrocytes; BECN1: beclin 1, autophagy related; BMI: body mass index; circHECTD1: circRNA HECTD1; circRNAs: circular RNAs; CBF: cerebral blood flow; Con: control; DAPI: 4?,6-diamidino-2-phenylindole; ECA: external carotid artery; FISH: fluorescence in situ hybridization; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; Gdna: genomic DNA; GFAP: glial fibrillary acidic protein; GO: gene ontology; HDL: high-density lipoprotein; IOD: integrated optical density; LDL: low-density lipoprotein; LPA: lipoprotein(a); MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MIR142: microRNA 142; mNSS: modified neurological severity scores; MRI: magnetic resonance imaging; NIHSS: National Institute of Health Stoke Scale; OGD-R: oxygen glucose deprivation-reperfusion; PCR: polymerase chain reaction; PFA: paraformaldehyde; SQSTM1: sequestosome 1; TIPARP: TCDD inducible poly(ADP-ribose) polymerase; tMCAO: transient middle cerebral artery occlusion; TTC: 2,3,5-triphenyltetrazolium chloride; UTR: untranslated region; WT: wild type     

GRM7 polymorphisms are not associated with ischemic stroke in Iranian population

Abstract

Objectives: Ischemic stroke is the main neurological cause of acquired incapability in adults and a prominent cause of mortality. Several association studies have been conducted to explore the role of candidate genes in this neurological condition.

Methods: In the present study, we aimed at identification of association between Glutamate Metabotropic Receptor 7 (GRM7) and risk of ischemic stroke in Iranian population. Two intronic variants within this gene (rs6782011 and rs779867) were genotyped in 318 sporadic ischemic stroke cases and 300 unrelated, healthy controls individuals.

Results: No significant difference was found in allele, genotype or haplotype frequencies of these SNPs between cases and controls after correction for multiple comparisons.

Conclusion: Consequently, the assessed GRM7 variants are not implicated in risk of ischemic stroke in Iranian population.     

Stroke outcomes in Malawi, a country with high prevalence of HIV: a prospective follow-up study

Background

Stroke contributes significantly to disability and mortality in developing countries yet little is known about the determinants of stroke outcomes in such countries. 12% of Malawian adults have HIV/AIDS. It is not known whether having HIV-infection alters the outcome of stroke. The aim of this study was to document the functional outcome and mortality at 1 year of first-ever acute stroke in Malawi. Also to find out if the baseline variables, including HIV-infection, affect the outcome of stroke.

Methods and Findings

147 adult patients with first-ever acute stroke were prospectively followed up for 12 months. Conventional risk factors and HIV-infection were assessed at baseline. Stroke severity was evaluated with modified National Institute of Health Stroke Scale (mNIHSS) and functional outcome with modified Rankin scale (mRS). Fifty (34%) of patients were HIV-seropositive. 53.4% of patients had a poor outcome (severe disability or death, mRS 4–6) at 1 year. Poor outcome was related to stroke severity and female gender but not to presence of HIV-infection. HIV-seropositive patients were younger and had less often common risk factors for stroke. They suffer more often ischemic stroke than HIV-seronegative patients.

Conclusions

Mild stroke and male gender were associated with favourable outcome. HIV-infection is common in stroke patients in Malawi but does not worsen the outcome of stroke. However, it may be a risk factor for ischemic stroke for young people, who do not have the common stroke risk factors. Our results are significant, because stroke outcome in HIV-seropositive patients has not been studied before in a setting such as ours, with very limited resources and a high prevalence of HIV.     

Off-Hour Effect on 3-Month Functional Outcome after Acute Ischemic Stroke: A Prospective Multicenter Registry

Background and Purpose

The time of hospital arrival may have an effect on prognosis of various vascular diseases. We examined whether off-hour admission would affect the 3-month functional outcome in acute ischemic stroke patients admitted to tertiary hospitals.

Methods

We analyzed the ‘off-hour effect’ in consecutive patients with acute ischemic stroke using multi-center prospective stroke registry. Work-hour admission was defined as when the patient arrived at the emergency department between 8 AM and 6 PM from Monday to Friday and between 8 AM and 1 PM on Saturday. Off-hour admission was defined as the rest of the work-hours and statutory holidays. Multivariable logistic regression was used to analyze the association between off-hour admission and 3-month unfavorable functional outcome defined as modified Rankin Scale (mRS) 3–6. Multivariable model included age, sex, risk factors, prehospital delay time, intravenous thrombolysis, stroke subtypes and severity as covariates.

Results

A total of 7075 patients with acute ischemic stroke were included in this analysis: mean age, 67.5 (±13.0) years; male, 58.6%. In multivariable analysis, off-hour admission was not associated with unfavorable functional outcome (OR, 0.89; 95% CI, 0.72–1.09) and mortality (OR, 1.09; 95% CI, 0.77–1.54) at 3 months. Moreover, off-hour admission did not affect a statistically significant shift of 3-month mRS distributions (OR, 0.90; 95% CI, 0.78–1.05).

Conclusions

‘Off-hour’ admission is not associated with an unfavorable 3-month functional outcome in acute ischemic stroke patients admitted to tertiary hospitals in Korea. This finding indicates that the off-hour effects could be overcome with well-organized stroke management strategies.     

Genetic Variation at the BDNF Locus: Evidence for Association with Long-Term Outcome after Ischemic Stroke

Background and Purpose

Rates and extent of recovery after stroke vary considerably between individuals and genetic factors are thought to contribute to post-stroke outcome. Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair and has been shown to be involved in stroke severity, recovery, and outcome in animal models. Few clinical studies on BDNF genotypes in relation to ischemic stroke have been performed. The aims of the present study are therefore to investigate whether genetic variation at the BDNF locus is associated with initial stroke severity, recovery and/or short-term and long-term functional outcome after ischemic stroke.

Methods

Four BDNF tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS; 600 patients and 600 controls, all aged 18–70 years). Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke recovery was defined as the change in NIHSS over a 3-month period. Short- and long-term functional outcome post-stroke was assessed using the modified Rankin Scale at 3 months and at 2 and 7 years after stroke, respectively.

Results

No SNP was associated with stroke severity or recovery at 3 months and no SNP had an impact on short-term outcome. However, rs11030119 was independently associated with poor functional outcome 7-years after stroke (OR 0.66, 95% CI 0.46–0.92; P =  0.006).

Conclusions

BDNF gene variants were not major contributors to ischemic stroke severity, recovery, or short-term functional outcome. However, this study suggests that variants in the BDNF gene may contribute to poor long-term functional outcome after ischemic stroke.     

Neuron Specific Enolase and C-reactive Protein Levels in Stroke and Its Subtypes: Correlation with Degree of Disability

Stroke is an emergency which threatens life and third leading cause of death and long term disability in developed countries. The use of biomarkers in diagnosing stroke and assessing prognosis is an emerging and rapidly evolving field. The study aimed to investigate the predictive value of biochemical marker of brain damage neuron-specific enolase (NSE) and systemic inflammatory marker C-reactive protein (CRP) with respect to degree of disability at the time of admission and short term in stroke patients. We investigated 120 patients with cerebrovascular stroke who were admitted within 72 h of onset of stroke in the Department of Neurology at Sri Aurobindo Institute of Medical Sciences, Indore, India. NSE and CRP were analyzed by solid enzyme linked immunosorbent assay using analyzer and micro plate reader from Biorad 680. In all patients, the neurological status was evaluated by a standardized neurological examination and the National Institutes of Health Stroke Scale on admission and on day 7. Serum NSE and CRP concentration were found significantly increased in acute stroke cases as compared to control in present study (<0.05 and <0.001 respectively). The maximum serum NSE and CRP levels within 72 h of admission were significantly higher in patients with greater degree of disability at the time of admission. Both biomarkers were found significantly correlated with neurological disability and short term outcome. Our study showed that serum biomarkers NSE and CRP have high predictive value for determining severity and early neurobehavioral outcome after acute stroke.