10th Anniversary of the Asia Pacific Stroke Organization: State of Stroke Care and Stroke Research in the Asia-Pacific.

The Asia Pacific Stroke Organization is the largest international and professional stroke group in the region. It has worked consistently over the last 10 years to gain visibility and consistency across the Asia-Pacific and beyond. The 10-year journey will be reviewed in the background of many internal and external developments including changes in Asia-Pacific stroke epidemiology, stroke care systems, and stroke service developments as well as major research studies in the Asia-Pacific.

Immediate effects of noxious and innocuous thermal stimulation on brain activation in patients with stroke.

Case-control studies have shown that noxious thermal stimulation (TS) can improve arm function in patients with stroke. However, the neural mechanisms underlying this improvement are largely unknown. We explored functional neural activation due to noxious and innocuous TS intervention applied to the paretic arm of patients with stroke. Sixteen participants with unilateral cortical infarctions were allocated to one of two groups: noxious TS (8 patients; temperature combination: hot pain 46°C to 47°C, cold pain 7°C-8°C) or innocuous TS (n = 8; temperature combination: hot 40°C-41°C, cold 20°C-21°C). All subjects underwent fMRI scanning before and after 30 min TS intervention and performed a finger tapping task with the affected hand. Immediate brain activation effects were assessed according to thermal type (noxious vs. innocuous TS) and time (pre-TS vs post-TS). Regions activated by noxious TS relative to innocuous TS (P < .05, adjusted for multiple comparisons) were related to motor performance and sensory function in the bilateral primary somatosensory cortices, anterior cingulate cortex, insula, thalamus, hippocampus and unilateral primary motor cortex, secondary somatosensory cortex at the contralateral side of lesion, and unilateral supplementary motor area at the ipsilateral side of lesion. Greater activation responses were observed in the side contralateral to the lesion, suggesting a significant intervention effect. Our preliminary findings suggest that noxious TS may induce neuroplastic changes unconstrained to the local area.Trial registration: NCT01418404.

Low-dose versus standard-dose intravenous alteplase for octogenerian acute ischemic stroke patients: A multicenter prospective cohort study.

BACKGROUND AND PURPOSE: The optimal dose of alteplase for acute ischemic stroke among geriatric patients is unclear. We aimed to assess the efficacy and safety of a low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) alteplase for varying severity of Asian geriatric stroke patients. METHODS: The favorable functional outcome on day 90 after stroke onset, and the symptomatic intracranial hemorrhage (SICH) rate following 24-36 h of intravenous alteplase were measured. The baseline NIHSS of 4-8, 9-13, ≥14 were defined as mild, moderate, and high severity, respectively. RESULTS: Totally, 249 geriatric patients treated with low-dose (n = 108) and standard-dose (n = 141) alteplase. Compared to standard-dose alteplase, low-dose alteplase had decrease in favorable functional outcome (22.2% versus 34.8%), and no difference in SICH rates was observed. For mild severity patients, the mortality was significantly increased with standard-dose alteplase (the NNT/NNH = 22.9/8.0 for mild severity, the NNT/ NNH = 15.0/14.7 for moderate severity, and the NNT/NNH = 13.5/19.6 for high severity). CONCLUSIONS: Standard-dose and low-dose alteplase were comparable in reducing major disability, but low-dose alteplase for mild stroke showed much reduced mortality on day 90 for octogenarians.

Statins and the risk of bleeding in patients taking dabigatran.

OBJECTIVES: Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with non-valvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins. MATERIALS AND METHODS: We performed a prospective, multicenter registry study of stroke patients with NVAF who initiated dabigatran therapy within 3 months after a clinically evident ischemic cerebrovascular event between 2013 and 2017. The main outcome measure was symptomatic bleeding after 90, 180, and 360 days. RESULTS: In total, 652 patients (336 statin users, 316 non-users) were followed for 1 year after dabigatran therapy. Cox multivariate analysis demonstrated that male sex, prior use of aspirin, and concurrent use of an antiarrhythmic drug were associated with a higher risk of bleeding at 360 days. After adjusting time-dependent covariates, statin users had a significantly lower bleeding risk (adjusted hazard ratio: 0.11, P < 0.001) than non-users. Kaplan-Meier analysis indicated that patients prescribed with statins had a higher rate of bleeding-free survival (P = 0.028). CONCLUSION: For secondary prevention of stroke in patients with NVAF who are taking dabigatran etexilate, co-prescription with a statin was associated with a lower risk of bleeding complications. Future research is needed to determine the pharmacological mechanism underlying this effect.

Low Cholesterol Levels Increase Symptomatic Intracranial Hemorrhage Rates After Intravenous Thrombolysis: A Multicenter Cohort Validation Study.

AIM: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis. METHODS: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24-36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings. RESULTS: For enrolled 1845 patients, SICH rates were ≥2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 [0.281-0.846], p=0.0106), the ECASS II (adjusted RR: 0.318 [0.130-0.776], p=0.0119), and SITS-MOST standards (adjusted RR: 0.214 [0.048-0.957], p=0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of ＜130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24-36 h. CONCLUSIONS: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of ＜130 mg/dL is supposed to a candidate marker for predicting SICH within 24-36 h.

Early functional improvement after stroke correlates with cardiovascular fitness.

Cardiovascular fitness exerts directly beneficial effects on functional and cognitive outcomes in patients of chronic stroke. However, the effect of early rehabilitation on cardiovascular function has not yet been thoroughly examined. We tested whether complementary rehabilitation program could influence cardiovascular fitness in an early stage of stroke patients. The associations for post-acute stroke functional recovery with cardiovascular fitness were explored. Thirty-seven patients with mean poststroke interval of 8.6 ± 3.8 days underwent inpatient rehabilitation of 22.8 ± 3.8 days. Functional outcomes of 15.3 points (17.2%) in functional independence measure improved after rehabilitation program. The therapeutic cardiovascular fitness was determined in ramp exercise test on a cycling ergometer. Peak oxygen uptake (V˙O2peak) significantly increased by 24.8% after early stroke rehabilitation. Multivariate regression analysis was performed to assess for associations of functional improvement with respect to change in V˙O2peak and extremities motor impairment. V˙O2peak gain accounted for more functional recovery than extremities motor improvement (R2 = 0.42). In conclusion, these results suggest that cardiovascular fitness appears to increase after complementary program in early stroke rehabilitation, and better cardiovascular fitness may be associated with greater functional improvement.

Effect of the Interaction Between Hypertension and Cerebral White Matter Changes on the Progression of Alzheimer Disease.

BACKGROUND: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. OBJECTIVE: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. METHOD: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). RESULTS: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. CONCLUSION: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

Hyperglycemia predicts unfavorable outcomes in acute ischemic stroke patients treated with intravenous thrombolysis among a Chinese population: A prospective cohort study.

BACKGROUND AND PURPOSE: Poorly controlled blood glucose was reported to cause deterioration of acute ischemic stroke. In this study, we investigated whether an elevated admission serum glucose level in the 3-h time window of intravenous thrombolysis for acute ischemic stroke determined poor functional outcomes among Chinese population. METHODS: This was a prospective cohort study. From December 1, 2004 to December 31, 2016, a total of 2370 patients were enrolled and categorized into two cohorts by blood glucose levels of ≥200 and <200 mg/dl in the 3 h after stroke onset. The primary objective was to determine whether admission hyperglycemia increased major disability and death at 30 and 90 days, which was defined by a modified Rankin Scale of 3-6. The secondary objective was to determine whether admission hyperglycemia increased the symptomatic intracranial hemorrhage (SICH) at 90 days. The number needed to harm (NNH) and patient expected event rate (PEER) were evaluated for both the primary and secondary objectives. RESULTS: The primary outcome occurred in 216 of 305 patients (70.8%) in the blood glucose ≥200 mg/dl cohort and in 951 of 1587 patients (59.9%) in the blood glucose <200 mg/dl cohort at 30 days, and in 191 of 287 patients (66.6%) in the blood glucose ≥200 mg/dl cohort and in 827 of 1517 patients (54.5%) in the blood glucose <200 mg/dl cohort at 90 days. Patients with admission hyperglycemia had significantly increased major disability and death at 30 (adjusted relative risk (RR): 1.194 [1.073-1.329], p = 0.0012) and 90 days (adjusted RR: 1.203 [1.079-1.340], p = 0.0008). Admission hyperglycemia increased the risk of the occurrence of SICH by nearly 2-fold (adjusted RR: 1.891 [0.977-3.657], p = 0.0585 with the SITS-MOST criteria and adjusted RR: 1.884 [1.138-3.121], p = 0.0139 with the NINDS criteria). NNH values of admission hyperglycemia in major disability and death at 30 and 90 days were 9 and 10, and NNH values of SICH by the SITS-MOST NINDS criteria were 44 and 34, respectively. CONCLUSIONS: The study evidenced the association and temporal relationship of admission hyperglycemia causing deterioration of functional outcomes and increased SICH among Chinese population with acute ischemic stroke treated with intravenous thrombolysis.

MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism.

Endothelial senescence leads to cell dysfunction, which in turn eventually results in cardiovascular disease. Identifying factors that regulate endothelial senescence may provide insight into the pathogenesis of aging. Insulin-like growth factor (IGF) signaling has a significant role in the physiology of endothelial cells (ECs). Overactivation of IGF signaling has been implicated in promoting the aging process. Lectin­like oxidized low­density lipoprotein (oxLDL) receptor­1 (LOX­1) is a scavenger receptor that mediates the internalization of oxLDL into cells. Previous studies by our group have indicated that microRNA let­7g exerts an anti­aging effect on ECs and also suppresses LOX-1 expression. Since LOX­1 also induces the aging process, the present study we explored whether let­7g still exerts an anti­aging effect on ECs when LOX­1 is suppressed. Angiotensin II (Ang II) was used to induce senescence in ECs. It was revealed that Ang II significantly increased the expression of aging markers, including ß­galactosidase, LOX­1, IGF1 and its receptor IGF1R. On the contrary, Ang II decreased the expression of the anti­aging gene sirtuin 1 (SIRT1). When LOX­1 was knocked down by small interfering RNA, let­7g still dose­dependently decreased the expression of ß­galactosidase (ß­gal), LOX­1, IGF1 and IGF1R, and SIRT1 was still upregulated. Using senescence­associated ß­gal staining, it was confirmed that let­7g exerts a LOX­1­independent anti­aging effect on ECs. In conclusion, the present study demonstrated that let­7g has an anti­aging effect regardless of the presence or absence of LOX-1.

Three years of the nationwide post-acute stroke care program in Taiwan.

Prolonged hospital stay and readmission are prevalent problems for stroke patients in Taiwan after the acute stage, partly due to the unmet need of post-acute care. In March 2014, Taiwan's National Health Insurance Administration launched a nationwide Post-Acute Care-CerebroVascular Disease (PAC-CVD) program. The Taiwan Stroke Society, coordinating 11 allied disciplines, took responsibility for the preparation and implementation of the program. As of June 2016, 6839 consecutive stroke patients were enrolled. On discharge from the PAC program, the functional status had improved in 87.5% of patients, with a significant decrease in the mean modified Rankin Scale score from 3.7 to 3.0. The rates of readmission and mortality in the PAC group were also lower than in the control group. In conclusion, the Taiwan's PAC-CVD program is an innovative and essentially effective national program of post-acute stroke care. We believe such experience should be helpful for policy makers of stroke care worldwide.

TRPV4 Activation Contributes Functional Recovery from Ischemic Stroke via Angiogenesis and Neurogenesis.

The endothelial transient receptor potential cation channel subfamily V member 4 (TRPV4) plays a crucial role in vascular remodeling; however, TRPV4-mediated angiogenesis after ischemic neuronal death as a neurorestorative strategy has not yet been thoroughly examined. In this study, we first tested whether TRPV4 activation can improve functional recovery in rats subjected to transient brain ischemia. The possible mechanisms for TRPV4 activation-promoted functional recovery were explored. A TRPV4 agonist, 4α-phorbol 12,13-didecanoate (4α-PDD), was intravenously injected via the tail vein at 6 h and 1, 2, 3, 4 days after ischemic stroke. The treatment reduced infarct volume by almost 50% (14.7 ± 3.7 vs. 29.2 ± 6.2%; p < 0.0001) and improved functional outcomes (p = 0.03) on day 5. To explore the therapeutic mechanism, we measured endothelial nitric oxide synthase (eNOS) expression and phosphorylation, vascular endothelial growth factor A (VEGFA) signaling, and neural stem/progenitor cells (NPCs). TRPV4 activation significantly increased eNOS expression and phosphorylation (serine 1177) by more than 2-fold in the ischemic region. The expressions of VEGFA and VEGF receptor-2 were significantly higher in the treated animals, especially an increase of the proangiogenic VEGFA164a isoform while a decrease of the antiangiogenic VEGFA165b isoform. We evaluated angiogenesis by detecting microvessel density in ischemic region. Using the immunohistochemistry staining, we found that 4α-PDD treatment caused a 3.4-fold increase of microvessel density (p < 0.0001). In addition, NPC proliferation and migration in the ischemic hemisphere were increased by 3-fold and 5-fold, respectively. In conclusion, our data suggest that TRPV4 activation by 4α-PDD may improve poststroke functional improvement through angiogenesis and neurogenesis.

Intake of potassium- and magnesium-enriched salt improves functional outcome after stroke: a randomized, multicenter, double-blind controlled trial.

Background: Stroke is one of the leading causes of mortality and neurologic deficits. Management measures to improve neurologic outcomes are in great need. Our previous intervention trial in elderly subjects successfully used salt as a carrier for potassium, demonstrating a 41% reduction in cardiovascular mortality by switching to potassium-enriched salt. Dietary magnesium has been associated with lowered diabetes and/or stroke risk in humans and with neuroprotection in animals.Objective: Because a large proportion of Taiwanese individuals are in marginal deficiency states for potassium and for magnesium and salt is a good carrier for minerals, it is justifiable to study whether further enriching salt with magnesium at an amount near the Dietary Reference Intake (DRI) amount may provide additional benefit for stroke recovery.Design: This was a double-blind, randomized controlled trial comprising 291 discharged stroke patients with modified Rankin scale (mRS) ≤4. There were 3 arms: 1) regular salt (Na salt) (n = 99), 2) potassium-enriched salt (K salt) (n = 97), and 3) potassium- and magnesium-enriched salt (K/Mg salt) (n = 95). The NIH Stroke Scale (NIHSS), Barthel Index (BI), and mRS were evaluated at discharge, at 3 mo, and at 6 mo. A good neurologic performance was defined by NIHSS = 0, BI = 100, and mRS ≤1.Results: After the 6-mo intervention, the proportion of patients with good neurologic performance increased in a greater magnitude in the K/Mg salt group than in the K salt group and the Na salt group, in that order. The K/Mg salt group had a significantly increased OR (2.25; 95% CI: 1.09, 4.67) of achieving good neurologic performance compared with the Na salt group. But the effect of K salt alone (OR: 1.58; 95% CI: 0.77, 3.22) was not significant.Conclusions: This study suggests that providing the DRI amount of magnesium and potassium together long term is beneficial for stroke patient recovery from neurologic deficits. This trial was registered at clinicaltrials.gov as NCT02910427.

A multiparameter model predicting in-hospital mortality in malignant cerebral infarction.

The early identification of patients with large hemisphere infarctions (LHIs) at risk of fatal brain edema may result in better outcomes. A quantitative model using parameters obtained at admission may be a predictor of in-hospital mortality from LHI.This prospective study enrolled all patients with LHI involving >50% of the middle cerebral artery (MCA) admitted to our neurological intensive care unit within 48 hours of symptom onset. Early clinical and radiographic parameters and the baseline CHADS2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke [double weight]) were analyzed regarding their ability to predict patient outcomes.Seventy-seven patients with LHIs were identified, 33 (42.9%) with complete MCA infarction (CMCA), and 44 (57.1%) with incomplete MCA infarction (IMCA). The predictors of CMCA score included: >1/3 early hypodensity in computed tomography findings, hyperdense MCA sign, brain edema, initial National Institutes of Health Stroke Scale (NIHSS) score ≥17, and stroke in progression during the 1st 5 days of admission. The cutoff CMCA score was 2, with a sensitivity of 81.8% and specificity of 70.5%. Mortality score 1, used for predicting in-hospital mortality from LHI, included CMCA and CHADS2 scores ≥4 (sensitivity 100.0%, specificity 57.4%), and mortality score 2 included CMCA and CHADS2 scores ≥4, and NIHSS score ≥26, during the 1st 5 days (sensitivity 100.0%, specificity 91.7%).Patients qualifying for a mortality score of 2 were at high-risk of in-hospital mortality from LHI. These findings may aid in identifying patients who may benefit from invasive therapeutic strategies, and in better describing the characteristics of those at risk of mortality.

No Difference Between Noxious and Innocuous Thermal Stimulation on Motor Recovery of Upper Extremity in Patients With Acute Stroke: A Randomized Controlled Trial With 6-Month Follow-up.

BACKGROUND: Thermal stimulation (TS) has been developed and incorporated into stroke rehabilitation. However, whether noxious and innocuous TS induce the same effects on motor function recovery after stroke is still unknown. A comparative study of different temperature combination regimens is needed. OBJECTIVE: To compare the short- and long-term effectiveness between noxious and innocuous TS on motor recovery of upper extremity in patients with acute stroke. DESIGN: Randomized, controlled trial with concealed allocation, intention-to-treat analysis and blinded outcome assessors. SETTING: A university hospital rehabilitation department in Taiwan. PARTICIPANTS: A total of 79 patients with acute ischemic stroke were recruited. The majority had moderate to severe motor impairment of the upper extremity (UE). INTERVENTION: In addition to traditional rehabilitation, the experimental group (n = 39) underwent noxious TS (heat pain 46-47°C/cold pain 7-8°C), and the control group (n = 40) received innocuous TS (heat 40-41°C/cold 20-21°C). TS intervention was applied for 30 minutes once per day and for a total of 20-24 times during hospital stay. A custom-made TS instrument, comprising 2 thermal stimulators and their respective thermal pads constructed in a closed-loop system, was used. OUTCOMES: The Fugl-Meyer upper extremity score (the primary outcome), Action Research Arm Test, Motricity Index, Barthel Index, and modified Ashworth scale (the secondary outcomes) were administered by a blinded assessor at baseline, post-12th TS, post-intervention, 1-month, and 6-month follow-ups. RESULTS: No significant differences between groups were found on the primary outcome at postintervention and follow-up assessments. At 1-month follow-up, the innocuous group showed a small effect (partial η2 = 0.02) that was greater than that of the noxious group, but that effect was eliminated at 6 months. Both groups presented significant within-group improvements over time (both P < .001). CONCLUSIONS: Combining noxious TS with traditional rehabilitation did not yield better short-term or long-term results than combining innocuous TS with traditional rehabilitation on UE functional recovery for individuals with acute stroke. LEVEL OF EVIDENCE: II.

Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke.

BACKGROUND: The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS: In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS: The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P<0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P=0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P=0.83). There were no significant between-group differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS: Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours. (Funded by the National Health and Medical Research Council of Australia; HeadPoST ClinicalTrials.gov number, NCT02162017 .).

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients.

BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.

Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients.

BACKGROUND: We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. METHODS: From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. RESULTS: Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. CONCLUSIONS: Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Methylation in the matrix metalloproteinase-2 gene is associated with cerebral ischemic stroke.

Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke. This study included 298 patients with ischemic stroke and 258 age-matched and sex-matched controls. MMP-2 promoter methylation levels were measured by pyrosequencing at eight potential cytosine-guanine (CpG) sites. Multivariate regression analysis was used to adjust for general stroke risk factors, and the specific effects of sex and stroke subtype were analysed. The methylation levels of MMP-2 in the peripheral blood of the patients with stroke were lower than controls in all eight CpG sites, especially at site 1, site 5, site 7, and site 8 (adjusted p=0.036, 0.002, 0.021, and 0.041, respectively). In subgroup analysis by sex, a significant association was found only in men but not in women. When the stroke subtype was considered, men with small-vessel stroke had significantly lower methylation levels at all MMP-2 CpG sites than the controls (3.01% vs 3.65%, adjusted p=0.018). Although men with large-artery atherosclerosis stroke also had lower MMP-2 methylation levels, no significant difference was found (3.25% vs 3.65%, adjusted p=0.253). Demethylation of the MMP-2 promoter in patients with ischemic stroke was in a sex and stroke subtype-specific manners. These findings may add to the understanding of epigenetic modification of MMP-2 on ischemic stroke.