Clopidogrel may decrease the risk of post-stroke infection after ischaemic stroke.

BACKGROUND AND PURPOSE: The P2Y12 receptor, a well-known factor in the platelet activation pathway, plays a role in thrombosis as well as systemic inflammation. Clopidogrel, a prototype P2Y12 receptor antagonist, reportedly decreases inflammation and systemic infection. The aim of this study was to evaluate whether clopidogrel use decreases the risk of post-stroke infection following ischaemic stroke. METHODS: A total of 1643 patients with acute ischaemic stroke (within 7 days after onset) were included for analysis between March 2010 and December 2015. Patients were categorized into two groups (clopidogrel users versus clopidogrel non-users), and clinical characteristics and risks of post-stroke infection were compared between the two groups. The inverse probability of treatment weighting using propensity scores for baseline imbalance adjustments was applied. RESULTS: Of the included patients (mean age 67.7 years; men 60.6%), 670 (40.8%) patients were clopidogrel users and 164 (10.0%) patients had post-stroke infection. The proportion of patients with post-stroke infection was significantly lower in clopidogrel users compared to clopidogrel non-users (6.7% vs. 12.2%, P ≤ 0.001). Moreover, clopidogrel users were less likely to be admitted to the intensive care unit (13.3% vs. 35.3%, P = 0.006). A multivariate analysis with inverse probability of treatment weighting revealed that clopidogrel users exhibited a lower risk of post-stroke infection (odds ratio 0.56, 95% confidence interval 0.42-0.75) and intensive care unit admission (odds ratio 0.34, 95% confidence interval 0.22-0.53). CONCLUSIONS: The study suggested that clopidogrel users exhibit a lower risk of infection and develop less severe infections after ischaemic stroke. Further prospective studies are needed.

D-dimer as a predictor of early neurologic deterioration in cryptogenic stroke with active cancer.

BACKGROUND AND PURPOSE: The occurrence of stroke in cancer patients is caused by conventional vascular risk factors and cancer-specific mechanisms. However, cryptogenic stroke in patients with cancer was considered to be more related to cancer-specific hypercoagulability. In this study, we investigated the potential of the D-dimer level to serve as a predictor of early neurologic deterioration (END) in cryptogenic stroke patients with active cancer. METHODS: We recruited 109 cryptogenic stroke patients with active cancer within 72 h of symptom onset. We defined END as an increase of ≥1 point in the motor National Institutes of Health Stroke Scale (NIHSS) score or ≥2 points in the total NIHSS score within 72 h of admission. After adjusting for potential confounding factors in the multivariate analysis, we calculated the odds ratios (ORs) and confidence intervals (CIs) of D-dimer in the prediction of END. RESULTS: Among 109 patients, END events were identified in 34 (31%) patients within 72 h. END was significantly associated with systemic metastasis, multiple vascular territory lesions on the initial magnetic resonance imaging (MRI), initial NIHSS score and D-dimer levels. In the multivariate analysis, the D-dimer level (adjusted OR, 1.11; 95% CI, 1.04-1.17; P < 0.01) and initial NIHSS score (adjusted OR, 1.08; 95% CI, 1.01-1.15; P = 0.03) predicted END after adjusting for potential confounding factors. In the subgroup analysis of 72 follow-up MRIs, D-dimer level was also correlated with new territory lesions on the follow-up MRI in a dose-dependent manner. CONCLUSION: Ischemic stroke patients with active cancer and elevated D-dimer levels appear to be at increased risk for END recurrent thromboembolic stroke.

Prolonged sleep increases the risk of intracerebral haemorrhage: a nationwide case-control study.

BACKGROUND AND PURPOSE: Although abnormal sleep duration is positively associated with increased risk for cardiovascular disease and mortality, the specific impact on intracerebral haemorrhage (ICH) risk remains unclear. The relationship between sleep duration and the risk of ICH was investigated in our study. METHODS: A nationwide, multicentre matched case-control study was performed to investigate the risk factors for haemorrhagic stroke, using patients from 33 hospitals in Korea. In all, 490 patients with ICH and 980 age- and sex-matched controls were enrolled. Detailed information regarding sleep, sociodemographic factors, lifestyle and medical history before ICH onset was obtained using qualified structured questionnaires. Sleep duration was categorized and the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression with 7 h as the reference duration. RESULTS: The number of subjects with long sleep duration, more than 8 h, was significantly greater in the ICH group than in the control group (≥8 h, 30.4% vs. 22.6%, P = 0.002). After controlling for relevant confounding factors, longer sleep duration was found to be independently associated with the risk of ICH in a dose-response manner (8 h, OR 1.57, 95% CI 1.00-2.47; ≥9 h, OR 5.00, 95% CI 2.18-11.47). CONCLUSIONS: Our study suggested that long sleep duration is positively associated with an increased ICH risk in a dose-dependent manner. Further studies on the relationship linking long sleep duration with increased risk of ICH are required.

Clinical utility of arterial spin-labeling as a confirmatory test for suspected brain death.

Diagnosis of brain death is made on the basis of 3 essential findings: coma, absence of brain stem reflexes, and apnea. Although confirmatory tests are not mandatory in most situations, additional testing may be necessary to declare brain death in patients in whom results of specific components of clinical testing cannot be reliably evaluated. Recently, arterial spin-labeling has been incorporated as part of MR imaging to evaluate cerebral perfusion. Advantages of arterial spin-labeling include being completely noninvasive and providing information about absolute CBF. We retrospectively reviewed arterial spin-labeling findings according to the following modified criteria based on previously established confirmatory tests to determine brain death: 1) extremely decreased perfusion in the whole brain, 2) bright vessel signal intensity around the entry of the carotid artery to the skull, 3) patent external carotid circulation, and 4) "hollow skull sign" in a series of 5 patients. Arterial spin-labeling findings satisfied the criteria for brain death in all patients. Arterial spin-labeling imaging has the potential to be a completely noninvasive confirmatory test to provide additional information to assist in the diagnosis of brain death.

Association between metabolic syndrome and functional outcome in patients with acute ischaemic stroke.

BACKGROUND AND PURPOSE: There is a paucity of information on the role of metabolic syndrome (MetS) as a prognosticator after ischaemic stroke. We investigated the association between MetS and functional outcome in patients with acute ischaemic stroke. METHODS: We evaluated 691 consecutive patients with acute stroke who were admitted to a tertiary medical center between January 2007 and June 2011. We defined MetS as having three or more of the five cardinal cardiovascular risk factors. Unfavorable functional outcome was determined using responder analysis, in which the outcome was adjusted by the initial severity of the stroke. Multivariable logistic regression analysis was used to evaluate the relationship between MetS and unfavorable outcomes (UnFO). RESULTS: Among 691 patients, 277 patients were classified as having an UnFO. The association between MetS and UnFO remained significant after adjusting for possible confounders; the adjusted odds ratio (95% confidence interval) was 1.57 (1.13-2.19). The risk for UnFO was positively associated with the number of MetS components. CONCLUSIONS: MetS may be a potent predictor of functional outcome after ischaemic stroke.

Lithium pretreatment reduces brain injury after intracerebral hemorrhage in rats.

OBJECTIVE: In addition to the mood-stabilizing effects of lithium in patients with bipolar disorder, recent in vitro and in vivo studies in rodents increasingly implicate that lithium may be useful for treating acute cerebral ischemia, neuroinflammatory conditions, and chronic neurodegenerative diseases. However, whether lithium has a protective effect against hemorrhagic stroke is yet unknown. To test this possibility, we attempted to determine lithium's effect on experimental intracerebral hemorrhage (ICH). METHODS: We treated adult rats with either lithium (2 mEq/kg) or saline for 3 days before inducing ICH via a stereotaxic infusion of collagenase into the left basal ganglia. Hematoma volumes, hemispheric swelling, long-term hemispheric atrophy, microglial activation, cell death, cyclooxygenase-2 expression, and behavioral outcomes were assessed. RESULTS: Per behavioral tests 2 days after ICH, the lithium-treated group recovered better than did the saline-treated group. Three days after ICH, the hematoma volumes did not differ between the groups, but hemispheric swelling was less in the lithium-treated group. Forty-two days after ICH, hemispheric atrophy was less in the lithium-treated group. Lithium reduced cell death, cyclooxygenase-2 expression, and reactive microglia in the perihematomal regions. CONCLUSION: The present study shows that lithium, via anti-inflammation, reduces the perihematomal cell death, which is associated with sensorimotor recovery after experimental ICH.

Paradoxical longevity in obese patients with intracerebral hemorrhage.

BACKGROUND: The paradoxical phenomenon of relative longevity among obese patients with established diseases has been reported for various disease conditions. The authors sought to investigate whether the obesity paradox also applies to intracerebral hemorrhage (ICH) survivors. METHODS: A total of 1,604 patients with ICH from 33 centers with nationwide coverage were prospectively enrolled to this cohort between October 2002 and March 2004. Baseline information including body mass index (BMI) was collected at admission, and mortality status was ascertained from the governmental mortality archive on December 2006. Associations between obesity and 30-day mortality or long-term risk of death were analyzed. RESULTS: Among the 1,356 patients with ICH included, the 30-day mortality rate was 7.2% and the long-term mortality rate was 26.9% after a mean follow-up of 33.6 ± 15.5 months. Neither BMI nor obesity status were associated with 30-day mortality after ICH. However, BMI was independently associated with a lower risk of long-term mortality (hazard ratio [HR] 0.91 per 1-kg/m(2) increase; 95% confidence interval [CI] 0.87-0.95). As compared with patients of normal weight, underweight subjects had a higher risk of death (HR 1.64; 95% CI 1.11-2.40), and conversely, overweight (HR 0.69; 95% CI 0.49-0.96) or obese (HR 0.61; 95% CI 0.43-0.88) subjects showed a lower risk of post-ICH death. CONCLUSION: In our study, obesity was associated with a lower risk of long-term death but not with 30-day mortality after ICH. Thus, it may be considered that an obesity status in a patient with ICH be treated as an indication of metabolic reservoir capacity and an increased likelihood of survival.

Reduced severity of strokes in patients with silent brain infarctions.

BACKGROUND: Silent brain infarctions (SBIs), leukoaraiosis (LA), and microbleeds (MBs) are ischaemic silent radiologic abnormalities that act as predictors of subsequent strokes. This study investigated the independent effect of silent radiologic abnormalities on initial stroke severity and short-term outcome. METHODS: A consecutive series of patients who had their first ischaemic stroke within 72 h of symptom onset were included. Demographic and clinical characteristics were collected on admission, and magnetic resonance imaging was performed to evaluate the ischaemic lesion, SBI, LA, and MB. Factors potentially associated with lower initial stroke severity (admission NIH Stroke Scale 0-5) and good short-term outcome (discharge NIH Stroke Scale 0-5, modified Rankin Scale 0-1) were validated by multivariate analysis. RESULTS: Silent brain infarctions were noted in 82 (45%) of the 182 patients. Although there were no statistically significant differences in stroke subtypes and lesion location, univariate analysis revealed that patients with SBI had reduced stroke severity (P = 0.005) and infarction volume (P = 0.001). After adjusting for covariates, the presence of SBI was independently associated with lower stroke severity and good short-term outcome when the NIH Stroke Scale was used as dependent variable (OR 3.368, 95% CI 1.361-8.332, P = 0.009; OR 3.459, 95% CI 1.227-9.755, P = 0.019, respectively). However, the presence of SBI lost significance when the discharge-modified Rankin Scale was used as dependent variable (P = 0.058). CONCLUSION: Amongst silent radiologic abnormalities, SBI was the only predictor of reduced stroke severity and infarct volume. Silent brain infarction deserves more attention in evaluating stroke severity.

Increased serum alkaline phosphatase as a predictor of long-term mortality after stroke.

BACKGROUND: Although the critical role of alkaline phosphatase in bone mineralization is clearly understood, the potentially adverse effect of high alkaline phosphatase levels on the cardiovascular system was only recently suggested. In this study, we hypothesized that increased levels of serum alkaline phosphatase may be associated with poor outcome after stroke in terms of mortality. METHODS: We prospectively included patients with acute stroke admitted consecutively to our hospital, from October 2002 to September 2008. A total of 2,029 patients were selected for the analyses. In the analyses of mortality, the patients were divided by baseline measurements into quintiles of alkaline phosphatase levels (<57, 57-69, 70-81, 82-97, >97 IU/L). RESULTS: In the Cox proportional hazard models, compared with the first alkaline phosphatase quintile, adjusted hazard ratios of the third, fourth, and fifth quintiles for all-cause death were 1.67 (95% confidence interval 1.12-2.49), 1.79 (1.20-2.67), and 2.83 (1.95-4.10). When we divided the patients into ischemic and hemorrhagic stroke, the association was also significant for both subtypes of stroke. In terms of vascular death, compared to the first alkaline phosphatase quintile, the adjusted hazard ratios of the fourth and fifth quintiles of alkaline phosphatase were 1.81 (95% confidence interval 1.14-2.86) and 2.78 (1.87-4.15). CONCLUSION: Our study demonstrated that increased serum levels of alkaline phosphatase are an independent predictor of all-cause and vascular death after either ischemic or hemorrhagic stroke.

White matter lesions and poor outcome after intracerebral hemorrhage: a nationwide cohort study.

BACKGROUND: The ability to predict poor outcome is important for patient care and treatment decision-making in cases of intracerebral hemorrhage (ICH). Previous studies have included relatively brief follow-up periods and small numbers of patients, and are limited in terms of considerations regarding individual brain vulnerabilities. METHODS: The authors prospectively enrolled 1,321 ICH patients nationwide from 33 hospitals. Clinical, laboratory, and imaging variables, including white matter lesions (WMLs), were collected at admission. Immediate outcome after ICH was measured using total Glasgow Coma Scale (GCS) score at admission, early outcome using 30-day mortality, and long-term outcome using relative risk for mortality. The vital status of included patients was ascertained on December 31, 2006, using Korean National Death Certificates (mean follow-up, 32.6 months). RESULTS: Of the 1,321 ICH patients included, 352 (27.8%) presented with a moderate GCS score (8.5-12.4) and 249 (19.7%) with a severe GCS score (

Effects of glucose level on early and long-term mortality after intracerebral haemorrhage: the Acute Brain Bleeding Analysis Study.

AIMS/HYPOTHESIS: Admission hyperglycaemia is associated with a poor outcome in patients with ischaemic stroke. However, its prognostic effects after intracerebral haemorrhage (ICH) are still unclear. METHODS: We prospectively enrolled patients with ICH at 33 centres in Korea between October 2002 and March 2004. A total of 1,387 patients who had ICH and underwent brain computed tomography within 48 h of symptom onset were included in the study (n = 1,387). Clinical information and radiological findings were collected at admission. Glucose levels were examined in relation to early (up to 30 days after ictus) and long-term (after 30 days) mortality rates using Cox regression analysis. To eliminate short-term effects, long-term mortality rate analysis was performed on surviving patients for more than 30 days. RESULTS: The long-term mortality rate was 21.1% after a mean follow-up of 434.3 +/- 223.2 days and was found to increase significantly with glucose quartile (p < 0.001). Admission glucose level was an independent risk factor for early mortality (per mmol/l; adjusted HR 1.10 [95% CI 1.01-1.19]), but not for long-term mortality. Moreover, when analysis was restricted to patients without diabetes, glucose level was found to be an independent risk factor for post-ICH mortality (n = 1,119; adjusted HR 1.10 [95% CI 1.03-1.17]) and had marginal significance for early (p = 0.053) and long-term mortality (p = 0.09). CONCLUSIONS/INTERPRETATION: We found that admission glucose levels were associated with early mortality after ICH. In patients without diabetes, admission glucose levels were associated with long-term mortality. We therefore suggest that intensive lowering of glucose level should be further investigated in ICH patients.

Ischemic preconditioning enhances neurogenesis in the subventricular zone.

Ischemic preconditioning (IPC) before subsequent prolonged ischemia is considered an emerging endogenous means of ischemic brain protection. We tested whether IPC induces endogenous neurogenesis in the subventricular zone (SVZ) and angiogenesis in the peri-ischemic area. Middle cerebral artery occlusion was administered to rats by filament insertion for 10 min (IPC) and/or 2 h (prolonged focal ischemia [PFI]). IPC alone increased 5'-bromo-2'-deoxyuridine (BrdU) (+) cells 2.5-fold in the SVZ compared with controls at 7 days. The numbers of BrdU/doublecortin (Dcx) or BrdU/neuronal nuclei (NeuN) double-labeled cells also increased, but extents of BrdU/glial fibrillary acidic protein (GFAP) double-labeling in the SVZ were not different. The IPC+PFI group showed about a 40% reduction in infarct volume. PFI increased BrdU (+) cells in the SVZ, and this was greatly enhanced by IPC treatment. The number of BrdU/Dcx double-labeled cells was strongly increased in ischemic brains administered IPC. Differentiation into mature neurons was also enhanced at 14 and 28 days. In addition, IPC significantly promoted angiogenesis in the ischemic penumbra as indicated by von Willebrand factor (vWF) staining. Our results indicate that IPC enhances neurogenesis in the SVZ even without subsequent PFI, and also enhances neurogenesis and angiogenesis after subsequent PFI. We conclude that IPC confers neuroprotection, and also promotes endogenous neurogenesis and angiogenesis.

Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke.

In this study, we sought to elucidate whether phenylpropanolamine (PPA) in cold remedies (small and divided doses) increases the risk of hemorrhagic stroke (HS). PPA exposure significantly increased the risk, and the risk was much higher in women. In women, linear trends were also found in recency, duration, and dosage of PPA exposure. PPA contained in cold remedies increases the risk of HS, particularly in women.

APOE epsilon2/epsilon4 polymorphism and cerebral microbleeds on gradient-echo MRI.

The association of APOE genotypes with cerebral microbleeds (CMBs) was examined on the basis of the location of CMBs in 414 patients who were admitted primarily because of stroke. With respect to possession of the epsilon2 or epsilon4 allele, the adjusted odds ratio was 1.94 (1.05 to 3.58) for lobar CMBs but 1.21 (0.69 to 2.11) for nonlobar CMBs. This suggests that the pathogenesis of CMBs may differ depending on their location.

Rotational vertebral artery syndrome: oculographic analysis of nystagmus.

In four patients with rotational vertebral artery syndrome (RVAS), the initial nystagmus was mostly downbeat, with the horizontal and torsional components beating toward the compressed vertebral artery side (n = 3) or directed away (n = 1). Three patients showed spontaneous reversal of the nystagmus and two exhibited no or markedly diminished responses on immediate retrial of head rotation (habituation). The patterns of nystagmus suggest that RVAS may result from differing mechanisms.

Medial medullary infarction: abnormal ocular motor findings.

In 20 consecutive patients with isolated medial medullary infarction, abnormal ocular motor findings included nystagmus (n = 8), ocular contrapulsion (n = 5), and contralesional ocular tilt reaction (n = 2). The nystagmus was ipsilesional (n = 4), gaze-evoked (n = 5), upbeating (n = 4), and hemiseesaw (n = 1). The ocular motor abnormalities may be explained by involvements of the nucleus prepositus hypoglossi, medial longitudinal fasciculus or efferent fibers from the vestibular nuclei, climbing fibers, and cells of the paramedian tracts.

Left ventricular hypertrophy is associated with cerebral microbleeds in hypertensive patients.

BACKGROUND: Cerebral microbleeds (CMBs) are indicative of hemorrhage-prone microangiopathy and known to be closely associated with chronic hypertension. However, no studies have been undertaken on the association between left ventricular (LV) hypertrophy and the severity of CMB. METHODS: One hundred two consecutive stroke patients with hypertension were examined. CMBs were counted using T2*-weighted gradient echo MRI data. With use of ordinal logistic regression analysis, the associations between LV mass index and other vascular risk factors and CMBs were analyzed. RESULTS: Hypertensive patients with CMBs showed a higher LV mass index than patients without. The grades of LV mass index were significantly correlated with the grades of CMB in the whole brain (p = 0.02), in the central gray matter (p < 0.01), and in the infratentorial area (p < 0.01), but not with those in the subcortical white matter. Ordinal regression analysis revealed that the LV mass index was independently associated with increased CMB severity (p = 0.01), regionally in the central gray matter (p < 0.01) and in the infratentorial area (p < 0.01), but not in the subcortical white matter (p = 0.63). After excluding patients with cerebral amyloid angiopathy, the association between the LV mass index and the CMB severity in the subcortical white matter became significant (p < 0.01). CONCLUSIONS: There is a close relationship between CMBs and LV hypertrophy in hypertensive patients with stroke. Thus, CMBs should be understood as one type of cerebral target organ damage by chronic hypertension.