Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Introduction: Multiple microRNAs (miRNAs) participate in the response to hypoxic/ischemic and ischemia-reperfusion events. However, the expression of these miRNAs in circulation from patients with acute ischemic stroke (AIS) receiving recanalization treatment has not been examined, and whether they are associated with the severity and outcome of stroke is still unknown. Materials and methods: In this prospective cohort study, plasma levels of miR-125b-5p, miR-15a-3p, miR-15a-5p, and miR-206 were measured at 24 hours after thrombolysis with or without endovascular treatment in 94 patients with AIS, as determined by qRT-PCR. Stroke severity was assessed based on National Institutes of Health Stroke Scale (NIHSS) score and infarct lesion. Intracranial haemorrhage (ICH) was recorded. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2 at day 90 after stroke. Results: miR-125b-5p and miR-206 levels were correlated with NIHSS scores (P = .014 and P = .002) and cerebral infarction volumes (P = .025 and P = .030). miR-125b-5p levels were significantly higher in patients with an unfavorable outcome than in patients with a favorable outcome (P = .002) and showed good diagnostic accuracy in discriminating the presence of an unfavorable outcome (area under the curve .735, 95% confidence interval .623-.829, P < .001). No association was found between different miRNAs and ICH. Conclusions: In AIS patients after thrombolysis with or without endovascular treatment, miR-125b-5p is a novel prognostic biomarker highly associated with an unfavorable outcome. miR-125b-5p and miR-206 levels are associated with stroke severity.     

Association of hyperdense middle cerebral artery sign with clinical outcome in patients treated with tissue plasminogen activator

BACKGROUND AND PURPOSE: The hyperdense middle cerebral artery sign (HMCAS) is a marker of thrombus in the middle cerebral artery. The aim of our study was to find out the frequency of the HMCAS, its association with initial neurological severity and early parenchymal ischemic changes on CT, its relevance to clinical outcome, and the efficacy of intravenous recombinant tissue plasminogen activator (rtPA) in patients with the HMCAS. METHODS: Secondary analysis of the data from 620 patients who received either rtPA or placebo in the European Cooperative Acute Stroke Study I (ECASS I), a double-blind, randomized, multicenter trial. The baseline CT scans were obtained within 6 hours from the onset of symptoms. Functional and neurological outcomes were assessed using the modified Rankin Scale and the Scandinavian Stroke Scale at day 90. RESULTS: We found an HMCAS in 107 patients(17.7%). The initial neurological deficit was more severe in patients with the HMCAS than in those lacking this sign (P<0.0001). Early cerebral edema and mass effect were also more common in patients with the HMCAS (P<0.0001). The HMCAS was related to the risk of poor functional outcome (grade of 3 to 6 on the modified Rankin Scale) on univariate analysis: 90 patients (84%) with the HMCAS and 310 patients (62%) lacking this sign were dependent or dead at day 90 (P<0.0001). However, this association was no longer significant in a logistic model accounting for the effect of age, sex, treatment with rtPA, initial severity of neurological deficit and early parenchymal ischemic changes on CT. Patients with the HMCAS who were given rtPA had better neurological recovery than those who received placebo (P=0.0297). CONCLUSIONS: The HMCAS is associated with severe brain ischemia and poor functional outcome. However, it has no significant independent prognostic value when accounting for the effect of initial severity of neurological deficit and of early parenchymal ischemic changes on CT. Patients with the HMCAS may benefit from intravenous rtPA.     

Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion

BACKGROUND: Edaravone has potent free radical quenching and antioxidant actions. The agent has been recently in commercial use for acute ischemic stroke patients. In this study, we investigated the therapeutic effect of edaravone on severe carotid-territorial stroke. METHODS: Stroke patients with internal carotid artery occlusion and baseline NIH Stroke Scale Score > or =15 were treated for 14 days with drip intravenous infusion of edaravone (n=30) and were compared with a historical control cohort of similar patients (n=31). Glycerol was also administered to all patients in both groups. RESULTS: Infarct volume (P<0.02) and midline shift (P<0.02) on CT performed on day 2 of the patients treated with edaravone were smaller than those without edaravone. For patients with edaravone, infarct volume (P<0.0001) and midline shift (P<0.0001) on days 5-7 were greater than those on day 2. Hemorrhagic transformation of infarcts on day 2 was less severe in patients with than without edaravone (P<0.03). Within 14 days after the onset of stroke, 6 patients with edaravone (20%) and 14 without edaravone (45%) died directly of stroke (P<0.03). Among all patients, only two treated with edaravone were independent without any assistance 8 weeks after the onset. CONCLUSIONS: Edaravone was associated with delayed evolution of infarcts and edema in patients with severe carotid-territorial stroke and decreased mortality during the acute stage. The agent, however, failed to prevent evolution of infarcts and edema on later days, and did not significantly improve functional outcome among the surviving patients.     

Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups

BACKGROUND AND PURPOSE: Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke. METHODS: To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups. This represents 99% of the worldwide evidence from randomized trials. RESULTS: There was a highly significant reduction of 7 per 1000 (SD 1) in recurrent ischemic stroke (320 [1.6%] aspirin versus 457 [2. 3%] control, 2P<0.000001) and a less clearly significant reduction of 4 (SD 2) per 1000 in death without further stroke (5.0% versus 5. 4%, 2P=0.05). Against these benefits, there was an increase of 2 (SD 1) per 1000 in hemorrhagic stroke or hemorrhagic transformation of the original infarct (1.0% versus 0.8%, 2P=0.07) and no apparent effect on further stroke of unknown cause (0.9% versus 0.9%). In total, therefore, there was a net decrease of 9 (SD 3) per 1000 in the overall risk of further stroke or death in hospital (8.2% versus 9.1%, 2P=0.001). For the reduction of one third in recurrent ischemic stroke, subgroup-specific analyses found no significant heterogeneity of the proportional benefit of aspirin (chi(2)(18)=20. 9, NS), even though the overall treatment effect (chi(2)(1)=24.8, 2P<0.000001) was sufficiently large for such subgroup analyses to be statistically informative. The absolute risk among control patients was similar in all 28 subgroups, so the absolute reduction of approximately 7 per 1000 in recurrent ischemic stroke does not differ substantially with respect to age, sex, level of consciousness, atrial fibrillation, CT findings, blood pressure, stroke subtype, or concomitant heparin use. There was no good evidence that the apparent decrease of approximately 4 per 1000 in death without further stroke was reversed in any subgroup or that in any subgroup the increase in hemorrhagic stroke was much larger than the overall average of approximately 2 per 1000. Finally, there was no significant heterogeneity between the reductions in the composite outcome of any further stroke or death (chi(2)(18)=16.5, NS). Among the 9000 patients (22%) randomized without a prior CT scan, aspirin appeared to be of net benefit with no unusual excess of hemorrhagic stroke; moreover, even among the 800 (2%) who had inadvertently been randomized after a hemorrhagic stroke, there was no evidence of net hazard (further stroke or death, 63 aspirin versus 67 control). CONCLUSIONS: Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence.     

Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.

BACKGROUND AND PURPOSE: The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke. METHODS: We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT. RESULTS: Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13. 4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2. CONCLUSIONS: Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.     

Prolonged hyperglycemia in the early subacute period after cerebral infarction: effects on short term prognosis

Although the adverse effect of admission hyperglycemia in cerebral infarction on prognosis is well known, studies generally have not questioned the effect of hyperglycemia in the early subacute period on prognosis after a stroke. Forty-six patients with acute ischemic stroke were seperated into 3 groups: Group 1) Known diabetes or admission blood glucose (ABG) > or = 140 mg/dl and HbA1c > or = 8,0%); Group 2) ABG > or = 140 mg/dl and HbA1c < 8,0%; and Group 3) ABG < 140 mg/dl and HbA1c < 8,0%. Blood glucose was followed-up 4 times a day for 10 days after the stroke and the mean of these measurements was calculated as the mean of glycemic regulation (MGR). Neurological evaluation was done at presentation and on day 10 and 30 with the National Institute of Health (NIH) scale. Oedema, lesion size and presence of hemorrhagic transformation were evaluated using CT. The MGR was significantly higher in group 1 compared to the other two groups (p < 0,001 and p < 0,01) and in group 2 compared to group 3 (p < 0,001). Patients with clinical worsening had a significantly higher MGR (p < 0,05). Patients with marked cerebral edema had a significantly higher MGR (p < 0,01) compared to patients with lesser edema. No correlation was found between MGR and lesion size or hemorrhagic transformation. Our results show that hyperglycemia in the early subacute period after cerebral infarction is associated with more pronounced cerebral edema and has an adverse effect on short term prognosis. We suggest that studies investigating the effect of insulin infusion on stroke prognosis should also consider infusions for a longer period than 24 hours.     

Cerebral arterial dissection]

We investigated a total of 98 cases with stroke caused by cerebral arterial dissection recruited in Strategies against Stroke Study for Young Adults in Japan (SASSY-Japan). The most frequent site of dissection was the intracranial vertebrobasilar artery. The stroke subtype was divided into ischemic (TIA and cerebral infarction) and hemorrhagic types (subarachnoid hemorrhage). The ischemic type was predominant (69%) and patients with the ischemic type were younger than those with the hemorrhagic type (P < 0.01). In the intracranial arterial dissection, nearly all cases were of the ischemic type. In contrast, in the extracranial arterial dissection, 60% of cases were ischemic and 40% were hemorrhagic. Cerebral angiography was the most important diagnostic procedure in the hemorrhagic type. In the ischemic type, MRI and MRA were more frequently used to show the findings specific to the dissection such as an intimal flap or double lumen and intramural hematoma. The outcome at discharge is generally good such that the modified Rankin Score was among 0-II in 69% of cases. However, in the hemorrhagic type, recurrence during an acute stage was frequent, and the outcome was poor with a mortalit rate of 19%. The establishment of an effective intervention to prevent the recurrence of subarachnoid hemorrhage is urgently required.     

Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial and uncertain. The aim of this study was to investigate the changes of cerebral microcirculation during cerebral vasospasm and to clarify the roles of microcirculatory disturbances in cerebral ischemia by measuring cerebral circulation time (CCT) and regional cerebral blood flow (rCBF). METHODS: In 24 cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital subtraction angiography (DSA) were performed on the same day between 5 and 7 days after SAH and/or within 4 hours after the onset of delayed ischemic neurological deficits. CCT was obtained by analyzing the time-density curve of the contrast media on DSA images and was divided into proximal CCT, which was the circulation time through the extraparenchymal large arteries, and peripheral CCT, which was the circulation time through the intraparenchymal small vessels. They were analyzed in association with rCBF and angiographic vasospasm. RESULTS: Severe angiographic vasospasm statistically decreased rCBF, and correlation between the degree of angiographic vasospasm and rCBF was seen (r=0.429, P=0.0006). Peripheral CCT showed strong inverse correlation with rCBF (r=-0.767, P<0.0001). Even in none/mild or moderate angiographic vasospasm, prolonged peripheral CCT was clearly associated with decreased rCBF. CONCLUSIONS: In addition to the marked luminal narrowing of large arteries detected as severe angiographic vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected cerebral ischemia during cerebral vasospasm. These results suggested that impaired autoregulatory vasodilation or decreased luminal caliber in intraparenchymal vessels may take part in cerebral ischemia during cerebral vasospasm.     

Combined clinical and radiological prognostic model in acute ischemic stroke

We sought to propose and test the validity ofa comprehensive prognostic model in middle cerebral artery-stroke treated with intravenous thrombolysis. A total of 127 consecutive patients (aged 70 +/- 12 years; 54% males) were included in this retrospective study. Variables included in our prognostic model were: NIHSS on admission (1-3 points), occurrence of hyperdense middle cerebral artery sign and early ischemic signs on baseline CT (1 point each), NIHSS at 24 hours (0-3 points), posttreatment hemorrhage (1 point), and infarct volume (0-4 points). The score range was 1-13, with higher values suggest unfavorable prognosis. Our prognostic score was correlated with the modified Rankin scale (mRS) at 3 months after stroke [correlation coefficient of 0.62, P < 0.001] and can thus help early prediction of the functional outcome. Logistic regression showed that NIHSS at 24 hours and EICs on baseline CT were independent predictor of our prognostic score (adjusted odds ratio of 4.1 and 5). Adopting a cut-off value of prognostic score < or = 3 for favorable prognosis and > or = 7for unfavorable prognosis helped to predict the need for institutionalization and the functional outcome with higher accuracy and predictive values compared with using scores only based on NIHSS.     

European Cooperative Acute Stroke Study (ECASS): (rt-PA—Thrombolysis in acute stroke) study design and progress report

At present, no therapy for acute ischemic stroke has been established. Vascular occlusions are demonstrated in up to 75–90% of ischemic stroke patients, and it is assumed that rapid lysis of the causal vascular occlusion will improve outcome of ischemic stroke. The purpose of the ECASS study is to evaluate whether thrombolytic therapy with recombinant tissue plasminogen activator, alteplase, improves outcome compared to a placebo-treated control group. Patients with acute ischemic hemispheric stroke in whom intravenous rt-PA (alteplase) could be initiated within 6 h from the onset of symptoms were evaluated by neurological examination and cerebral computed tomographic scans (CT scans) of the brain. Patients fulfilling inclusion criteria and not meeting any exclusion criteria were, after informed consent, treated by 1.1 mg rt-PA per kg body weight (max 100 mg) intravenously or placebo. No angiographic evaluation was included in the trial. In total, 623 patients were randomized in 14 European countries. In addition, 81 patients were treated in an open pilot phase with the active drug. Treatment effect was evaluated using the Barthel Index and the Modified Rankin Scale at 90 ± 7 days in both an intention-to-treat analysis and an explanatory analysis. The clinical course was evaluated by repeated neurological ratings on the Scandinavian Stroke Scale. Adverse events (intracranial hemorrhage or cerebral edema) were evaluated by repeating CT scans at 24 h and at 7 days. Recruitment was terminated in March 1994. Follow-up evaluations were terminated in late June 1994. The first unblinded results are expected in February 1995. Overall mortality was 18.5% in the pilot study and 18.9% in the randomized trial. The incidence of cerebral bleeding complications associated with clinical deterioration was 11.1% (pilot) and 6.5% (randomized trial).     

脑出血患者CT灌注成像的研究

目的 利用CT灌注成像技术(CTP)观察脑出血患者的脑血液动力学变化规律及对临床神经功能缺损评分(SSS)的影响.方法 对41例幕上脑出血患者于发病后5 h～14 d同步行头颅CT平扫和CTP检查,观察时间、血肿体积、水肿范围、发病期间的血糖水平、同步平均动脉压(MBP)对脑出血患者脑血液动力学的影响和这种血液动力学变化与脑出血患者SSS相关性.结果 (1)血肿周围水肿带内、水肿带外(距离水肿边缘1 cm内)、同侧皮层区间不同病理区域脑血流量(分别为CBF1、CBF2、CBF3)差异有统计学意义(P<0.05),且随时间呈波动性变化;CBF1、CBF2呈直线正相关关系(r=0.334,P=0.035),与CBF3无直线相关关系(r=0.027,P=0.870;r=0.142,P=0.383).另外水肿带内CBF1和脑血容量(CBV1)呈直线正相关关系(r=0.803,P=0.000),但与达峰时间(PT1)无相关关系(r=-0.52,P=0.752).(2)CBF1的下降程度与血肿体积、血肿周围水肿范围呈直线负相关关系(r=-0.501,P=0.001;r=-0.589,P=0.000),与发病期间的血糖水平、MBP无相关关系(r=0.141,P=0.386;r=0.014,P=0.930).(3)血肿周围灌注损伤范围(参数图灌注缺损范围-血肿范围,此范围内的CBF<20mL/100 g·min)与血肿体积、血肿周围水肿范围呈直线正相关关系(r=0.449,P=0.003;r=0.645,P=0.000),与发病期间的血糖水平、MBP无相关关系(r=-0.047,P=0.769;r=0.141,P=0.378).(4)脑出血患者同步的SSS与血肿体积、血肿部位、CBF的下降程度、CBV的下降程度呈相关关系(r=-0.418,P=0.007;r=0.542,P=0.000;r=0.376,P=0.017;r=0.312,P=0.051),与血肿最大平面的灌注缺损范围、水肿范围无相关关系(r=-0.283,P=0.073;r=-0.163,P=0.308).结论 (1)脑出血患者血肿周围水肿带内、外及同侧皮层血流减低均降低,但趋势不一致.(2)血肿周围水肿带内存在着缺血性损伤(CBF<20mL/100g·min),其范围和程度均血肿大小、水肿范围有关,随时间波动变化,但未达到统计学差异.(3)出血部位、血肿体积、血肿周围水肿带内脑灌注水平影响脑出血患者的SSS.     

Clinical implication of hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator

To determine the clinical implications of hemorrhagic transformation (HT) after thrombolysis, 241 eligible patients receiving alteplase for acute ischemic stroke were studied. HT was classified, according to the European Cooperative Acute Stroke Study criteria, as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH). Symptomatic intracranial hemorrhage (SICH) was defined according to the National Institute of Neurological Disorders and Stroke study. A novel classification, clinically significant intracranial hemorrhage (CSICH) was defined as HTs associated with an unfavorable clinical outcome (modified Rankin Scale 5–6) at 3 months. For all subtypes of HT, we found that patients receiving alteplase were more often in the standard-dose group (0.90 ± 0.02 mg/kg) than in the lower dose group (0.72 ± 0.07 mg/kg). PH and SICH were related to an unfavorable clinical outcome, while HI was not. There was a positive trend between age and CSICH in patients receiving the standard dose (P = 0.0101), and between alteplase dose and CSICH in patients ≥70 years old (P = 0.0228). All PHs (including asymptomatic PHs) and symptomatic HIs have been found to be associated with unfavorable outcome, and for this reason defined as CSICH. Independent predictors of CSICH were age ≥70 years and the standard dose of alteplase. Further studies of thrombolysis for ischemic stroke with different doses of alteplase are warranted.     

Long-term prognosis of cerebral ischemia in young adults. National Research Council Study Group on Stroke in the Young.

BACKGROUND AND PURPOSE: Prognosis of ischemic stroke in young adults is reported as favorable, and transient ischemic attack (TIA) is commonly considered a benign event. We investigated long-term outcome and prognostic predictors of cerebral ischemia in patients under 45 years of age. METHODS: Three hundred thirty-three patients aged 15 to 44 years who suffered from a first-ever TIA or ischemic stroke were prospectively followed up with annual clinical evaluation or complete phone interview. End points were the composite outcome event of stroke, myocardial infarction, and vascular or nonvascular death and death from all causes. The probability of event-free survival was estimated by the Kaplan-Meier method. Univariate and multivariate estimates of hazard ratios were calculated according to the Cox proportional hazards analysis. RESULTS: An average follow-up of 96 months was available in 330 patients (99.1%). Survival was worse in patients with stroke at entry (86.5%) than in those with TIA (97.1%). Mortality in both groups was significantly higher than in the general population (standardized mortality ratio [SMR] 14.5, P<0.0001, Poisson distribution test, and SMR 7.9, P=0.002). The average annual mortality rate was higher during the first (3.94%, 95% CI 1.84 to 6. 04) than in the subsequent years. The average annual incidence rate of new stroke was higher in patients with stroke than in those with TIA at entry, and it declined from 1.56% (95% CI 0.21 to 2.91) during the first year to 0.06% (95% CI 0.04 to 0.08) at the end of the follow-up. Myocardial infarction occurred later, after the first year, with similar rates in patients with stroke and TIA at entry. The average annual rates of new stroke (2.36%), myocardial infarction (1.68%), and death (3.05%) were higher in patients with the mixed atherothrombotic and cardioembolic etiology than in the remaining patients. Male gender, age >35 years, stroke at entry, and cardiac diseases were independent predictors of the composite outcome event at the Cox regression analysis, whereas only stroke at entry and cardiac diseases predicted death from all causes. CONCLUSIONS: Stroke and TIA in young adults have severe prognostic implications, because the mortality risk was highly increased with respect to the general population. Preventive measures are strongly recommended in the presence of any unfavorable prognostic profile.     

代谢综合征对急性脑梗死早期预后的影响

目的 探讨急性脑梗死早期预后的影响因素，分析代谢综合征（metabolic syndrome，MS）是否为急性脑梗死早期预后的独立影响因素。方法 采用前瞻性研究设计，纳入连续性急性脑梗死163例，发病1个月时进行改良Rankin量表（mRS）评分作为结局变量，0=mRS 0～2，1=mRS 3～5；急诊入院时进行美国国立卫生研究院卒中量表(NIHSS)评分、格拉斯哥昏迷量表（GCS）评分；依据病史及辅助检查确定TOAST分型。以性别、年龄、吸烟、饮酒、NIHSS评分、GCS评分、TOAST分型、合并症[感染、心肌梗死（MI）、心衰（HF）]、是否合并MS为自变量作单因素分析。多因素分析采用两分类logistic回归，自变量为多分类时采用变量哑化技术。结果 单因素分析结果发现，性别（P <0.05）、吸烟史（P＜0.05）、NIHSS评分（P <0.01）、GCS评分（P <0.01）、TOAST分型（P <0.01）、感染（P <0.01）、HF（P <0.05）、MS（P <0.01）对早期预后（mRS评分）的影响有统计学差异。多因素分析结果发现，MS（OR 3.869，95%CI 1.542～9.711，P <0.01）、NIHSS评分（OR 19.699，95%CI 2.107～184.134，P <0.01）、TOAST分型（OR 0.188，95%CI 0.067～0.525，P <0.01）、感染（OR 2.950，95%CI 1.202～7.238，P＜0.05）对mRS有统计学差异。结论 MS、NIHSS评分、TOAST分型、感染是预后差的独立危险因素。这对急性脑梗死的预后评价、对MS高危人群实施干预提供了可靠的依据。     

Identification of major ischemic change. Diffusion-weighted imaging versus computed tomography.

BACKGROUND AND PURPOSE: Thrombolytic therapy is not recommended in patients with CT changes of recent major infarction, which has been defined as reduced attenuation or cerebral edema involving >33% of the middle cerebral artery territory (European Cooperative Acute Stroke Study [ECASS] criteria). Diffusion-weighted imaging (DWI) is more sensitive than CT in detecting acute ischemia, and the combination of DWI, MR perfusion imaging, and MR angiography provides additional information from a single examination. We sought to determine whether DWI could identify the presence and extent of major ischemia as well as CT in hyperacute stroke patients. METHODS: Seventeen suspected hemispheric stroke patients were studied with both CT and DWI within 6 hours of symptom onset. None received thrombolytic therapy. The scans were examined separately by 2 neuroradiologists in a blinded fashion for ischemic change and cerebral edema, graded as normal, <33%, or >33% of the MCA territory. Final diagnosis of stroke was determined with the use of standard clinical criteria and T2-weighted imaging at day 90. RESULTS: Sixteen of 17 patients had a final diagnosis of stroke. Acute ischemic changes were seen in all 16 on DWI (100% sensitivity) and in 12 of 16 on CT (75% sensitivity). DWI identified all 6 patients with major ischemia on CT, with excellent agreement between the 2 imaging techniques (kappa=0.88). One patient eligible for thrombolysis on the ECASS CT criteria had major ischemia on DWI. CONCLUSIONS: DWI is more sensitive than CT in the identification of acute ischemia and can visualize major ischemia more easily than CT.     

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.     

Intracerebral hemorrhage survival: French register data

Cerebral hemorrhages are subject to a heavy short- and long-term case fatality. A study of prognostic factors and of relative survival based on the data of a population registry is of great value to study patients having a hematoma of all ages, irrespective of the method of care. We have listed 183 patients having a cerebral hemorrhage between 1 January 1985 and 31 December 1996 and living in the city of Dijon, France. Eighteen clinical and CT-scanning variables have been studied. We have found four predictive factors of death at one month from cerebral hemorrhages. These are, in decreasing order: the existence of consciousness disorders at the initial clinical examination (OR = 5.80, p < 0.0001); an intraventricular hemorrhage (OR = 5.60, p < 0.0001); a hematoma volume over 11 cubic centimeters (OR = 3.53, p = 0.027); lastly, in male patients an age over 70 years (OR = 4.90, p = 0.039). With regard to long-term survival, the existence of consciousness disorders remains the principal predictive factor of case fatality in both crude and relative survival (OR = 5.52, p < 0.0001, in crude survival versus OR = 22.2 in relative survival, p < 0.0001), followed by age over 70 years (OR = 3.71, p < 0.0001 in crude survival and OR = 2.41 in relative survival, p = 0.086). The existence of consciousness disorders at the initial examination following a cerebral hemorrhage would seem to be the principal worst prognostic factor of short- and long-term survival and of relative survival, age and sex having less importance. Moreover, intraventricular hemorrhage and hematoma volume are short-term, pejorative factors. These data, based on a population-based registry, are an important consideration in the acute management of hemorrhagic therapy, and for the design of further therapeutic trials on this severe pathology.     

Migraine history and migraine-induced stroke in the Dijon stroke registry

Two thousand three hundred and eighty-nine patients with first-ever stroke were registered in the population-based Dijon Stroke Registry over an 11-year period. There was a history of migraine in 49 cases (2%), with a majority of women (2.8% versus 1.1% men) with the following distribution: 27 cases among 1,380 large-artery cerebral infarctions (1.9%), 6 cases among 358 small-artery cerebral infarctions (1.6%), 6 cases among 412 cerebral infarctions due to cardiac embolism (1.4%), 7 cases among 191 cerebral hemorrhages (3. 6%) and 3 cases among 47 subarachnoid hemorrhages (6.3%). The male/female ratio was 0.58 for the 49 strokes with a history of migraine versus 1.27 for the 2,340 strokes with no history of migraine. Twelve migraine-induced ischemic strokes occurred with an infarction of the posterior area of the brain in young patients. The annual incidence was 0.80/100,000/year (confidence interval, CI = 0. 37-1.57) with a predominance of women (1.02/100,000/year, CI = 0. 52-1.25; men: 0.57/100,000/year; CI = 0.28-1.04). We conclude that a history of migraine is more frequent in women, in particular in those with hemorrhagic strokes, and that the incidence of migraine-induced stroke in our population-based study is higher in women, although it remains low.     

Human Cytomegalovirus Linked to Stroke in a Chinese Population

Aim: Human cytomegalovirus (HCMV) is implicated in several cardiovascular disorders, including atherosclerosis, coronary heart disease, and cardiac transplant arteriopathy. We aimed to evaluate the relationship between HCMV and stroke. Methods: Real‐time polymerase chain reaction (PCR) and ELISA were performed on plasma samples isolated from 200 patients diagnosed with stroke and 200 controls. All participants belonged to the Stroke Hypertension Investigation in Genetics (SHINING) study. Results: HCMV seropositivity was higher in the stroke group than in controls (55.0% vs. 23.5%; P < 0.0001). The presence of HCMV DNA increased the risk of stroke (unadjusted odds ratio [OR], 3.98; 95% confidence interval [CI], 2.59 to 6.11; P < 0.0001). Risks were also increased for the subtypes ischemic stroke (unadjusted OR, 4.01; 95% CI, 2.57–6.24; P < 0.0001) and hemorrhagic stroke (unadjusted OR, 3.80; 95% CI, 1.64–8.78; P= 0.0018). Increased risk with HCMV remained significant after adjustment for age, sex, body mass index, hypertension, and smoking (ischemic stroke: adjusted OR, 4.07; 95% CI, 2.52–6.32; P < 0.0001; hemorrhagic stroke: adjusted OR, 3.88; 95% CI, 1.61–9.36; P= 0.0026). Conclusions: We demonstrate a novel link between HCMV infection and stroke. These findings may provide important insights into the pathogenesis of stroke.     

Vascular protection in brain ischemia

Vascular damage occurring after cerebral ischemia may lead to a worse outcome in patients with ischemic stroke, as it facilitates edema formation and hemorrhagic transformation. There are several phases in the development of vascular injury (acute, subacute and chronic) and different mediators act in each one. Therapeutic options to avoid vascular injury must be focused on acting in each phase. However, even though experimental studies have demonstrated the benefit of therapeutic interventions both in the acute and chronic phases of cerebral ischemia, only the chronic phase offers a therapeutic window sufficiently wide enough to provide vascular protection in clinical practice. Several drugs including erythropoietin and HMG-CoA reductase inhibitors (statins), antihypertensive (angiotensin modulators), antibiotics (minocycline) and antihyperglycemic drugs (thiazolidinediones) have been proved to provide vascular protection in patients with ischemic stroke. Anti-inflammatory, antioxidant, and antiapoptotic actions are responsible for the vascular protective effect related to these drugs.