纳络酮治疗急性脑梗死的多中心、随机、双盲、对照研究

目的观察盐酸纳络酮对急性脑梗死的临床疗效及安全性。方法将8家医院150例急性脑梗死患者随机分为对照组、纳络酮治疗1组和纳络酮治疗2组,并进行多中心、随机、双盲、对照研究;各组用药前后均进行神经功能缺损评分,治疗30d和3个月分别进行Barthel指数评分,并观察药物副作用。结果对于脑梗死患者急性期神经功能缺损的改善,纳络酮治疗组均优于对照组,尤以治疗2组为明显(P<0.005),而且无明显副作用;3组间治疗30d和3个月的Barthel指数比较均无显著性差异。结论纳络酮有助于脑梗死的急性期治疗,改善临床症状,而且安全性较高。     

A double blind trial of naloxone in the treatment of acute stroke

Naloxone has been reported to have potential benefit in the treatment of stroke. We evaluated the effect of naloxone in a double-blind trial conducted with 15 stroke patients whose deficits ranged from 8 to 60 hours in duration. All but one patient sustained a cerebral infarction. Neurologic function was assessed before and five minutes after each of two injections given to each patient in a double-blind fashion. The injections consisted of naloxone (0.4 mg in 3 patients and 4.0 mg in 12 patients) and saline. Prior to the trial, samples of plasma were obtained for determination of immunoreactive beta-endorphin for each patient. Four patients showed minimal improvement following injection of naloxone, while five patients exhibited a slightly greater improvement following saline injection. There were no significant elevations of plasma beta-endorphin among stroke patients. We conclude that naloxone may not have a significant therapeutic role for stroke in the clinical setting.     

Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial

The aim of the study was to assess the safety and feasibility of a clinical trial on the effect of vinpocetine, a synthetic ethyl ester of apovincamine, in acute ischaemic stroke. Thirty consecutive patients with computed tomography verified diagnosis of acute ischaemic stroke, who could receive drug treatment within 72 h of stroke onset, were enrolled. The patients were randomly allocated to receive either low-molecular weight dextran alone or in combination with vinpocetine. Poor outcome was defined as being dead or having a Barthel index of < 70 or a Rankin score of 3--5. Intention-to-treat analysis was applied. One-tenth of all hospitalized patients with acute ischaemic stroke were eligible for the trial. Thirty eligible patients were treated with either low-molecular weight dextran alone (mean age 57.9 +/- 11.6 years, n = 15) or in combination with vinpocetine (mean age 60.8 +/- 6.6 years, n = 15). The two treatment groups were comparable with respect to major prognostic variables. A relative risk (RR) reduction of poor outcome at 3 months follow-up was 30% (RR = 0.7; 95% confidence interval [CI] 0.1--3.4), as defined by the modified Barthel Index, and 60% as defined by the modified Ranking score (RR = 0.4, 95% CI: 0.1--1.7). The National Institute of Health (NIH--NINDS) Stroke Scale score was marginally significantly better in the vinpocetine treated group at 3 months of follow-up (P = 0.05, ANOVA). No significant adverse effects were seen. This pilot study shows that a full-scale randomized double-blind, placebo-controlled trial of vinpocetine treatment in acute ischaemic stroke is feasible and warranted.     

Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial

Although statins are being used for secondary prevention of ischemic stroke, recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection. We conducted a pilot, double-blind, randomized, multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke. Simvastatin/placebo was given at 3–12 h from symptom onset to 60 patients with cortical strokes. Efficacy on the evolution of several inflammation markers [interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, sApo/Fas, tumor necrosis factor-α, E-selectin, L-selectin and nitrites+nitrates] and neurological outcome was evaluated at baseline, day 1, 3, 5, 7 and 90. No differences were found amongst the biomarkers studied regarding treatment allocation. Although simvastatin patients improved significantly by the third day (46.4% vs. 17.9%, P  =   0.022), a non-significant increase in mortality and greater proportion of infections (odds ratio 2.4, confidence interval 1.06–5.4) in the simvastatin group were the main safety concerns. Therefore, a larger clinical trial is needed to confirm the net benefit of this therapeutic approach.     

金尔伦(盐酸纳洛酮)治疗急性颅脑损伤病人随机双盲多中心前瞻性临床研究

背景：本试验是由中华医学会神经外科学会和中华神经外科杂志部组织,国内18家医院实施,完成金尔伦（盐酸纳洛酮）对受试患者的疗效和用药安全性观察,目的,证明金尔伦在治疗急性中,重型颅脑损伤患者的治疗和安全性,方法：设计并实施了随机双盲前瞻性临床对照试验计划,比较大剂量金尔伦和生理盐水安慰剂的疗效差异,每位受试得接受为期10天随机分组治疗和3个月随访,分析对比治疗前后和治疗过程中患者的病情和重要辅助检查指标的变化,趋势并同时对比随访结束时患者神经功能恢复情况和生活质量状况,全部试验结束后进行揭盲并对结果进行统计学分析,结果,实际完成530例,有效病例511例,其中金尔伦组256例,安慰剂组255例,金尔伦组和安慰剂组死亡率分别为治疗组12．5％,有效病例12．5％,安慰剂组17．3％（P＜0．05）,金尔伦组患者GCS评分在用药后第5天开始明显优于安慰剂组（P＜0．05）,治疗结束后金尔伦组患者GOS评分明显优于安慰剂组（P＜0．05）,金尔伦组患者语言功能评分和生活质量状况评分也明显优于安慰剂组（P＜0．05）,另外,过程中未发现因用药造成的毒副反应,结论：早期应用大剂量金尔伦能明显降低急性颅脑损伤患者死亡率,促进脑神经功能恢复,改善远期生活质量状况,并且具有相当可靠的安全性。     

Extracorporeal rheopheresis in the treatment of acute ischemic stroke: A randomized pilot study

BACKGROUND AND PURPOSE: Extracorporeal rheopheresis is a safe method to optimize hemorheology. Our aim was to determine whether treatment with extracorporeal rheopheresis in patients with acute ischemic hemispheric stroke improves cerebral perfusion as assessed with serial 99mTc-ethyl-cysteinate-dimer single-photon emission CT (99mTc-ECD SPECT). We also investigated how clinical outcome is associated with treatment and imaging results. METHODS: Thirty-three patients (mean age, 64+/-10 years) with acute ischemic hemispheric stroke were included in a prospective, randomized, parallel group pilot study. First treatment with or without extracorporeal rheopheresis took place within 12 hours after the onset of symptoms and was repeated 3 times at intervals of 24 hours. Hemorheological parameters were measured before and after each session. Each patient underwent 99mTc-ECD SPECT immediately before treatment, 6 to 8 hours after treatment, and after 5 days. A semiquantitative SPECT graded scale was used to measure depth and extent of activity deficits and thus to quantify the perfusion deficit. RESULTS: Seventeen patients were actively treated with extracorporeal rheopheresis, and 16 patients did not receive extracorporeal rheopheresis. After 3 months, no differences were found in the functional or neurological outcome. Despite a rapid, sustained decrease of plasma viscosity and erythrocyte aggregation in the rheopheresis group, there was no significant difference in the SPECT graded scale after therapy between the 2 groups. Patients with early reperfusion (decrease in the SPECT graded scale >25% 6 to 8 hours after therapy compared with the baseline examination) experienced a better functional outcome (Modified Rankin Scale) after 3 months compared with patients without reperfusion (P=0.04). CONCLUSIONS: Since quantitative flow mapping and clinical follow-up did not reveal any differences between patients who were treated with extracorporeal rheopheresis and controls, it appears very unlikely that extracorporeal rheopheresis enhances reperfusion after acute cerebral ischemia.     

A randomized controlled clinical trial to compare the safety and efficacy of edaravone in acute ischemic stroke

Background and Objective:

Edaravone has potent antioxidant and free radical scavenger properties. Few Japanese studies had demonstrated its neuroprotective role in acute ischemic stroke (AIS). This study aims to evaluate the efficacy of edaravone in terms of functional outcome in a group of Indian patients of AIS.

Materials and Methods:

Fifty patients of AIS were randomly divided into two groups. The study group received 30 mg of edaravone twice daily for 14 days by infusion, while control group received normal saline infusion as placebo. Outcome assessment was done by the Modified Rankin Scale (MRS). MRS score ≤2 at 90 days was considered as a favorable outcome.

Results:

Of 25 patients, 18 (72%) had favorable outcomes (MRS ≤2) at 90 days in edaravone group, while 10 (40%) of 25 patients in placebo group had favorable outcome (P < 0.005). Two patients expired (one in each group) during treatment. The mean Barthel index increased from 41.20 ± 32.70 at baseline to 82.40 ± 18.32 at day 90 in edaravone group as compared with placebo group in which scores were 44.20 ± 22.76 at baseline and 68.20 ± 21.30 at day 90 (P < 0.005).

Conclusions:

We therefore conclude that edaravone effectively improves functional outcome in AIS.     

针刺治疗急性缺血性脑卒中的随机对照预试验

目的 初步探讨针刺能否改善急性缺血性脑卒中患者的日常生活能力,了解其安全性,探索在目前国情下进行与国际标准接轨的关于针刺的大规模多中心随机对照试验的可行性。方法 来自成都市六家市级以上医院的101例急性缺血性脑卒中患者被随机分配到针刺组和非针刺组。针刺组49例,接受针刺(每周5次,共3-4周)和常规治疗(即对症、支持及防治并发症等治疗);非针刺组52例,接受常规治疗。主要疗效判定指标:(1)随访期末死亡/残障率;(2)随访期末死亡/远期住院率。次要疗效判定指标:(1)神经功能缺损评分变化;(2)针刺过程中不良事件发生率。结果 (1)两组病例入选时基线资料可比性好(P>0.05);(2)6个月随访时针刺组死亡/残障率、死亡/远期住院率的相对危险度(RR)及95％可信区间(CI)分别为0.92、0.49-1.73;0.73、0.51-1.05;差异无显著意义;(3)治疗期末神经功能缺损评分针刺组略优于非针刺组,但差异无显著意义(t=1.04.P>0.05);(4)针刺治疗组未出现严重不良反应;(5)失访率低,6个月随访率达95.05％。结论 由于样本量有限,尚不能证明针刺对改善急性缺血性脑卒中患者的日常生活能力及远期住院率是否优于对照组,但显示针刺治疗是安全的。在现有条件下失访率不超过5％,本研究设计及实施方案是可行的。因此,进一步完成主试验以评价     

Neuroprotective treatment with Cerebrolysin in patients with acute stroke: a randomised controlled trial

Summary. Background and purpose. Cerebrolysin is a compound with neurotrophic and neuroprotective activity. It is produced by enzymatic breakdown of purified brain proteins and consists of low molecular weight peptides and amino acids. Cellular and animal models of cerebral ischaemia have shown that it is a potent neuroprotective agent. We explored the safety and preliminary outcome of Cerebrolysin treatment in patients with acute stroke. Methods. Randomised, placebo-controlled, parallel group trial. Patients with acute stroke were randomised within 24h of stroke onset to IV therapy with placebo or Cerebrolysin 50mL/day for 21 days. Both groups received concomitant treatment with ASA 250mg/day PO and pentoxifylline 300mg/day IV. Clinical examinations were performed on days 1, 3, 7, 21 and 90 post baseline. Outcome measures were the Canadian Neurological Scale, the Barthel Index, the Clinical Global Impressions, the Mini-Mental State Examination, and the Syndrome Short Test. Treatment emergent adverse events, lab tests, and vital signs were recorded to assess the safety of Cerebrolysin. Results. 146 patients were enrolled in two groups: 78 Cerebrolysin and 68 placebo. At baseline, no significant group differences were observed. Patients in the Cerebrolysin group had no significant improvement in the CNS score, the Barthel Index and the Clinical Global Impressions when compared to the placebo group. A significant improvement of cognitive function of the patients on Cerebrolysin was observed in the Syndrome Short Test when compared to the placebo group. Cerebrolysin was well tolerated and safe. Adverse events occurred with a similar frequency in both groups. Conclusion. The results demonstrate that neurotrophic treatment with Cerebrolysin is safe and well tolerated by patients with acute stroke. The findings, despite the small sample size, also indicate a potential treatment effect of Cerebrolysin in acute stroke. Larger studies, however, are needed to confirm and extend these findings.     

移动卒中单元在院前救治急性缺血性脑卒中的应用

急性缺血性脑卒中是严重威胁人类健康的疾病,时间窗内的治疗对该病至关重要。传统模式往往由于院前时间的延误以及入院后头颅CT检查时间的延误,使患者错过了最佳的治疗时间。移动卒中单元的出现使救治时间大大缩短,患者在配备头颅CT的急救车上即可进行诊治,为院内的下一步治疗节约了时间,提高了急性脑卒中患者的救治率,降低了致残率。     

A randomized controlled trial of hemodilution therapy in acute ischemic stroke

Rapid hemodilution in the early phase of ischemic stroke by the combination of venesection (250-650 ml during the first 2 days) and administration of low-molecular weight dextran was evaluated in a prospective controlled trial. Fifty-two patients were randomized to hemodilution therapy and 50 to a control group; the two groups were comparable in important prognostic variables. Mean hemoglobin was reduced from 147 to 127 g/l, hematocrit from 43 to 37% and, in a subsample of patients, whole-blood viscosity at a shear rate of 23 sec-1 from 7.0 to 4.3 cps over the first 2 days. Hemodilution was then maintained by repeated dextran infusions. Of the hemodiluted patients, 85% improved in neurological scoring over the first 10 days as compared to 64% of the control patients (p less than 0.025). The case fatality rate during the first 3 months was little affected by hemodilution. Among the survivors, 8% of the hemodiluted and 31% of the non-hemodiluted patients were unable to walk at 3 months. The proportion of surviving patients still hospitalized at the 3-month follow-up was 13% in the hemodilution group and 39% in the control group (p less than 0.01). The combination of venesection and dextran 40 administration is thus an unsophisticated but effective way to achieve rapid hemodilution in patients with acute cerebral infarction, and it improves the overall clinical outcome over the first 3 months.     

Ginsenoside-Rd improves outcome of acute ischaemic stroke - a randomized, double-blind, placebo-controlled, multicenter trial

Background and purpose: Ginsenoside‐Rd is a receptor‐operated calcium channel antagonist and has shown promise as a neuroprotectant in our phase II study. As an extended work, we sought to confirm its efficacy and safety of Ginsenoside‐Rd in patients with acute ischaemic stroke. Methods: We conducted a randomized, double‐blind, placebo‐controlled trial involving 390 patients with acute ischaemic stroke in a 3:1 ratio to receive a 14‐day intravenous infusion of Ginsenoside‐Rd or placebo within 72 h after the onset of stroke. Our primary end‐point was the distribution of disability scores on the modified Rankin scale (mRs) at 90 days. Results: The efficacy analysis was based on 386 patients (Ginsenoside‐Rd group: 290; placebo group: 96). Ginsenoside‐Rd significantly improved the overall distribution of scores on the mRs, as compared with the placebo (P = 0.02; odds ratios [OR], 1.74; 95% confidence interval [CI], 1.08–2.78). There were significant differences between the two groups when we categorized the scores into 0–1 vs. 2–5 (P = 0.01; OR, 2.32; 95% CI, 1.23–4.38; 66.8% vs. 53.1%). It also improved the National Institutes of Health Stroke Scale (NIHSS) at 15 days [P < 0.01; least squares mean (LSM), ?0.77; 95% CI, ?1.31 to ?0.24]. Mortality and rates of adverse events were similar in the two groups. Conclusions: Ginsenoside‐Rd improved the primary outcome of acute ischaemic stroke and had an acceptable adverse‐event profile.     

High-dose intravenous naloxone for the treatment of acute ischemic stroke

To evaluate the safety and possible efficacy of high-dose naloxone for the treatment of acute cerebral ischemia, 38 patients received a loading dose of 160 mg/m2 over 15 minutes followed by a 24-hour infusion at the rate of 80 mg/m2/hr. Nausea and/or vomiting were common side effects. Naloxone was discontinued in seven patients (because of hypotension in one, bradycardia and hypotension in two, myoclonus in one, focal seizures in two, and hypertension in one); all seven patients responded to treatment and no permanent sequelae to naloxone were noted. Twelve of the 38 patients showed early neurologic improvement (by completion of the naloxone loading dose). However, there was no correlation between such a loading dose response and clinical outcome at 3 months. Our experience suggests that naloxone is safe at the dose used, but data for efficacy are inconclusive.     

Normobaric oxygen therapy in acute ischemic stroke: A pilot study in Indian patients

Purpose:

Clinical and radiological assessment of effects of normobaric high-flow oxygen therapy in patients with acute ischemic stroke (AIS).

Materials and Methods:

Patients with anterior circulation ischemic strokes presenting within 12 h of onset, ineligible for intravenous thrombolysis, an National Institute of Health Stroke Scale (NIHSS) score of >4, a mean transit time (MTT) lesion larger than diffusion-weighted image (DWI) (perfusiondiffusion mismatch), and an evidence of cortical hypoperfusion on magnetic resonance imaging (MRI) were included into the trial. Active chronic obstructive pulmonary disease (COPD), requirement of >3/L min oxygen delivery to maintain SaO2 > 95%, rapidly improving neurological deficits, pregnancy, contraindications to MRI, or unstable medical conditions were excluded. The experimental group received humidified oxygen at flow rates of 10 L/min for 12 h. The NIHSS, modified Rankin Score (mRS), Barthel Index (BI) were measured at 0, 1, 7 day of admission and at 3 months follow-up. MRI with DWI/PWI was performed at admission, 24 h later and at 3 months follow-up.

Results:

Of 40 patients (mean age = 55.8 years ± 13.2) (range, 26–82), 20 patients were randomized to normobaric oxygen (NBO). The mean NIHSS in NBO and control groups were 14.25 and 12.7 at admission which decreased to 11.6 and 9.5 on the seventh day, and 9.4 and 9.05 at 3 months, respectively. The mean mRS (3.7/3.7) and BI (58.2/53.9) in NBO and control groups improved to 2/2.2 and 73.05/73.8 at the end of 3 months, respectively.

Conclusions:

NBO did not improve the clinical scores of stroke outcome in Indian patients with AIS.     

A randomized efficacy trial of citicoline in patients with acute ischemic stroke

BACKGROUND AND PURPOSE: Citicoline (cytidine-5'-diphosphocholine; CDP-choline) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation. A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects. METHODS: The current trial was a 33-center, randomized, double-blind, efficacy trial in 394 patients comparing placebo (n=127) with citicoline (n=267) (500 mg po daily) for 6 weeks, with a 6-week posttreatment follow-up period. Patients with acute (24 hours) ischemic strokes clinically assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale (NIHSS) > or = 5 were enrolled. RESULTS: Mean time to treatment was 12 hours, and mean age was 71 for placebo and 70 for citicoline. Although mean baseline NIHSS were similar for both groups, there was a higher percentage of placebo patients with NIHSS <8 (34% vs 22%; P<0.01). The incidence and type of side effects were similar between the groups. The planned primary analysis (logistic regression: 5 categories Barthel) failed the proportional odds assumption and was rendered unreliable. There were no between-group differences seen on the planned secondary assessment analyses at 90 days, including the Barthel Index > or = 95 at 12 weeks (last observation carried forward: placebo 40%; citicoline 40%) or mortality rate (placebo 18%; citicoline 17%). However, post hoc analyses in a subgroup of patients with baseline NIHSS > or = 8 found that citicoline-treated patients were more likely to have a full recovery (Barthel > or = 95): placebo 21%; citicoline 33%; P=0.05; whereas no difference was seen in patients with baseline NIHSS<8 (placebo 77%; citicoline 69%; P>0.1. CONCLUSIONS: The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial. Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit.     

Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial

Background and purpose:  Ginsenoside-Rd is a selective competitive Ca²⁺ receptor antagonist. A phase II randomized, double-blind, placebo-controlled, multicenter study was conducted to examine the efficacy and safety of ginsenoside-Rd in patients with acute ischaemic stroke.
Methods:  A total of 199 patients were randomized equally to receive a 14-day infusion of placebo (group B), ginsenoside-Rd 10 mg (group A) or ginsenoside-Rd 20 mg (group C). Primary end-points were National Institutes of Health Stroke Scale (NIHSS) scores at 15 days. Secondary end-points were NIHSS scores and the Barthel Index at 8 days, the Barthel Index and the modified Rankin scale at 15 days and 90 days. The safety end-points included serious and non-serious adverse events, laboratory values and vital signs. Analysis was by intention to treat.
Results:  For the primary study outcome, there is significant difference amongst the three groups at 15 days in NIHSS scores ( P  = 0.0003). Comparing group A with B and group B with C, the difference in the mean for NIHSS was significant in statistics ( P  = 0.0004, P  = 0.0009 respectively). This is no significant difference between group A and C ( P  = 0.9640). For the secondary study outcome, ginsenoside-Rd did not improve neurological functioning. Incidence of serious and non-serious adverse events was similar amongst the three groups.
Conclusions:  Ginsenoside-Rd may be of some benefit in acute ischaemic stroke.     

Nimodipine in acute ischemic stroke: a double-blind controlled study

Nimodipine (BAY e 9736), a new dihydropyridine derivative, has been shown to reduce neurological deficits and mortality induced by acute cerebral ischemia in experimental studies. We investigated the effects of this calcium antagonist in patients with acute ischemic stroke through a randomized, double-blind, parallel-designed trial in which nimodipine was compared with placebo. Forty-one of 54 screened cases were found to fulfil the inclusion criteria (sudden occurrence of a focal neurological deficit secondary to an acute ischemic event in the carotid area diagnosed after a complete neurological work-up) and entered the study. Nineteen of them were treated with nimodipine (40 mg t.i.d. administered for 28 days) and the remaining 22 with placebo, given in identical tablets. In all patients the treatment started within 12 h after the onset of the symptoms. Course and intensity of the neurological deficit were evaluated by the Mathew Scale (slightly modified). Forty patients concluded the trial. Nimodipine was withdrawn in one case following the occurrence of a skin rash whose causative relation with the test drug could not be clarified. Altogether, however, nimodipine was well tolerated and no severe cardiovascular adverse reactions were observed. In terms of efficacy, the scores obtained by the Mathew Scale showed a higher rate of improvement on nimodipine than on placebo, thus indicating that patients receiving the latter drug did not fare as well as those receiving the test medication. Our data suggest that nimodipine may be beneficial in the treatment of acute stroke.     

低温治疗急性缺血性卒中的研究进展

脑血管病作为神经系统的常见病及多发病,是目前导致人类死亡的三大主要疾病之一,也是第一大致残性疾病.缺血性卒中是脑血管病最常见的类型,约占脑血管病的70％.在现有的诸多治疗手段中,低温是有效的神经保护措施.自20世纪50年代低温的神经保护作用被发现以来,其已被提出用于外伤性脑损伤、卒中、心脏停搏性脑病、新生儿缺血缺氧性脑病、肝性脑病、脊髓损伤及动脉瘤手术等多个领域.本文根据近年来文献报道,就低温在急性缺血性卒中治疗中的研究进展进行综述,以期为开展低温的临床应用提供依据.