A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients.

BACKGROUND: Citicoline may reduce CNS ischemic injury by stabilizing cell membranes and reducing free radical generation. Previous safety and efficacy trials in patients who have had acute strokes suggested that citicoline may improve neurologic outcome with minimal side effects. OBJECTIVE: To determine the safety and efficacy of citicoline treatment in acute stroke patients. METHOD: An 118-center, randomized, double-blind, efficacy trial in 899 patients compared placebo (n = 446) with citicoline (n = 453) (1000 mg PO twice a day) for 6 weeks, with a 6-week post-treatment follow-up period. Patients with acute (< or =24 hours) ischemic strokes clinically thought to be in the middle cerebral artery territory with NIH Stroke Scale (NIHSS) scores > or =8 were enrolled. RESULTS: Mean time to treatment was 13 hours for both groups and mean age was 67 years for those receiving placebo and 68 years for those receiving citicoline. Mean baseline NIHSS scores were 14.5 for placebo and 13.9 for citicoline (p = 0.06); medians were 14 for placebo and 13 for citicoline (p = 0.04). The incidence and type of side effects were similar between the groups. There were no between-group differences on the planned primary analysis, percent of patients with a > or =7-point NIHSS score change at 90 days (placebo 51%, citicoline 52%). There were no between-group differences on the other planned secondary analyses at 90 days, including mortality. However, post hoc analyses using standard "excellent recovery" measures suggested a possible treatment effect on the modified Rankin 0 or 1 (last observation carried forward: placebo 20%, citicoline 26%; p = 0.025) as well as a global outcome statistic. CONCLUSIONS: Citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke as measured by the planned analyses. Post hoc analyses suggest that a modest treatment effect may have been seen if more traditional analyses had been used.     

A randomized trial on the efficacy of intensive rehabilitation in the acute phase of ischemic stroke

Abstract. Sixty patients admitted to hospital for hemispherical ischemic stroke causing severe disabilities were enrolled in the study. The patients were divided in two groups: A and B. The patients in group A were given intensive rehabilitative treatment; those in group B were given ordinary rehabilitative treatment. Both treatments lasted 14 days. At the end of that period, the patients of both groups were sent to the same rehabilitation center to continue treatment, using the same methods for all. The patients were evaluated by means of the modified N. I. H. Stroke Scale and the Barthel-Index on the day of enrolment, on the 14^th and 180^th day. The results obtained from intensive treatment were no better than those obtained from ordinary treatment.This study shows that there is no point in adopting an intensive rehabilitative treatment for an ischemic stroke in its acute phase: a more expensive and time-consuming effort does not in any way lead to a better outcome.     

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.     

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.     

阿替普酶联合胞磷胆碱对急性脑梗死患者凋亡因子及血清miR-124、miR-21的随机对照研究

目的探讨阿替普酶联合胞磷胆碱治疗急性脑梗死(AIS)的临床效果。方法选取2018年3月—2020年5月该院AIS患者124例进行前瞻性随机对照研究,以随机数字表分为观察组(62例)和对照组(62例)。常规治疗基础上,对照组予以阿替普酶,观察组予以阿替普酶联合胞磷胆碱,均治疗2周。对比两组疗效、不良反应与治疗前、治疗2周后美国国立卫生研究院卒中量表(NIHSS)评分、血清细胞凋亡有关因子[可溶性凋亡相关因子配体(sFasL)、可溶性凋亡相关因子(sFas)、B淋巴细胞瘤-2(Bcl-2)]、miR-124、miR-21水平。结果观察组总有效率为91.94%(57/62),对照组为77.42%(48/62),两组比较,差异具有统计学意义(P0.05);两组治疗期间不良反应发生率比较,差异无统计学意义(P0.05)。治疗2周后,两组NIHSS评分均降低,观察组低于对照组(P0.05)。治疗2周后,两组血清sFasL、sFas水平均降低,观察组低于对照组(P0.05);Bcl-2水平均提高,观察组高于对照组(P0.05)。治疗2周后,两组血清miR-124、miR-21水平均降低,观察组降低幅度高于对照组(P0.05)。结论阿替普酶联合胞磷胆碱治疗AIS临床疗效显著,可能通过调控凋亡因子、miR-124、miR-21表达减轻脑损伤,使患者神经功能明显改善。[国际神经病学神经外科学杂志, 2021, 48(2):138-142]     

Wide-range C-reactive protein efficacy in acute ischemic stroke patients

OBJECTIVE: To compare the recently introduced wide-range C-reactive protein (wr-CRP) with the widely used high-sensitivity Behring Dade method (hs-CRP) in acute stroke/transient ischemic attack (TIA) patients. MATERIALS AND METHODS: A total of 119 consecutive patients admitted to a tertiary medical center with acute ischemic stroke/TIA were included in the study. Venous blood was obtained for both assays during the first 24 h, 3-5 days, as well as 3-6 months thereafter. RESULTS: A highly significant correlation (r=0.994, P<0.0001) was found between the two methods even when analyzed at three different time points. In addition, a similar correlation was noted between these two assays and other commonly used biomarkers, including white blood cell count, Westergren's sedimentation rate and quantitative fibrinogen. CONCLUSION: Real-time, on-line and low-cost wr-CRP assay is a reasonable alternative to the Behring Dade hs-CRP method in acute stroke/TIA patients.     

A double blind randomized pilot trial of naloxone in the treatment of acute ischemic stroke

Attention has focused on naloxone, an opiate receptor antagonist, because of its potential benefit in reversing neurological damage after acute cerebral ischemia. To evaluate the safety and possible efficacy of high-dose naloxone in ischemic stroke patients we planned a double blind pilot study. Between January 1989 and May 1990 24 patients were randomly assigned to the naloxone or placebo group according to age and neurological deficit. Naloxone was given in a loading dose of 5 mg/kg over 10 minutes followed by a 24-hour infusion at the rate of 3.5mg/kg/h. 10 patients experienced minor side effects but none of them had to discontinue the treatment. 9 patients improved: 6 in the naloxone group and 3 in the placebo group, but no significant difference was found using the non parametric Mann-Whitney test. Our study suggests that naloxone is safe at the dose used, but the results do not support the planning of similar trials on a larger scale.

---

Sommario è stata posta grande attenzione sul Naloxone, un antagonista dei recettori degli oppiacei, e sulla sua potenziale utilità nel far regredire il danno neurologico dopo un'ischemia cerebrale acuta. Per valuatare la sicurezza e la possibile efficacia di alte dosi di naloxone nei pazienti con ictus ischemico, abbiamo programmato uno studio pilota in doppio cieco. Dal gennaio 1989 al maggio 1990 ventiquattro pazienti sono stati assegnati casualmente al gruppo Naloxone o a quello Placebo secondo l'età e il deficit neurologico. Il naloxone venne somministrato in una dose di carico di 5 mg/kg in 10 minuti seguita da un 'infusione di 24 ore (3.5 mg/kg/h). Dieci pazienti ebbero effetti collaterali minori ma nessuno di essi dovette interrompere il trattamento. Nove pazienti migliorarono: sei nel gruppo Naloxone e tre nel gruppo placebo, ma non fu trovata alcuna differenza significativa usando il test non parametrico di Mann-Whitney. Il nostro studio suggerisce che il naloxone è sicuro alla dose usata, ma i risultati non giustificano la pianificazione di trials più grandi con le stesse caratteristiche.

     

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     

Microalbuminuria in patients with acute ischemic stroke

ABSTRACT

Objective: Microalbuminuria could be detected in patients with acute stroke. However, the association between microalbuminuria and the severity of ischemic stroke has not been systematically investigated. This study aimed to systematically explore the prevalence of microalbuminuria in ischemic stroke patients, and the association of microalbuminuria with the severity of ischemic stroke, as well as the prognostic value of microalbuminuria in cerebral infarction patients.

Methods: 160 ischemic stroke patients and 54 controls were enrolled and clinical characteristics were recorded. Severity of stroke was assessed by NIHSS score at admission, and outcome was measured using mRS score. The concentration of urinary microalbumin was collected for each participant. Multiple linear regression analysis was performed to evaluate the relationship between microalbuminuria and the severity of ischemic stroke, and logistic regression analysis was employed to identify the prognostic value of microalbuminuria in ischemic stroke patients.

Results: The incidence of microalbuminuria in ischemic stroke patients was 36.88%. The concentration of urinary microalbumin increased with the increasing of cerebral infarction size, and was independently correlated with NIHSS score at admission and mRS score at 3 months after onset. In multivariate logistic regression analyses, microalbuminuria was one of the independent risk factors for poor prognosis of cerebral infarction patients.

Conclusions: MAU?was?found?in?approximately?one-third of patients with acute ischemic stroke. It was correlated with the severity of cerebral infarction at admission and clinical outcomes at 3 months after onset and could be used as a potential indicator of poor prognosis in ischemic stroke patients.     

Chitotriosidase in patients with acute ischemic stroke

BACKGROUND: Following an acute brain ischemia, local endothelia allow monocyte chemoattraction into the lesion site which contributes to brain damage through a group of neurotoxic factors. A relationship exists between the extent of brain damage and the plasma level of monocyte products, including chitotriosidase, though usually strictly related to preexisting infectious-inflammatory diseases. PURPOSE: Since chitotriosidase activity is also elevated in pathogen-free conditions, we tested whether chitotriosidase upregulation might be specifically related to stroke and unrelated to clinically relevant infectious diseases. METHODS: We studied the plasma level of chitotriosidase activity, TNF-alpha and IL-6 in 44 consecutive patients with acute brain ischemia without concomitant symptoms or signs of inflammatory-infectious diseases. Results were compared with stroke severity and outcome as detected by brain CT and NIH scale. Blood samples were collected, on average, 11 h after stroke onset. RESULTS: Chitotriosidase activity positively correlates with stroke severity, as measured by NIH scale (r = 0.69, p < 0.01), to the extent of brain damage as documented by CT (r = 0.75, p < or = 0.001) and the TNF-alpha level (r = 0.76, p < 0.001); it also inversely correlates with the IL-6 level (r = -0.43, p < or = 0.05). CONCLUSION: Our results indicate that chitotriosidase is a specific marker of macrophage activation occurring in stroke which directly correlates with stroke severity independently of preexisting inflammatory or infectious conditions.     

A double-blind study of neurotropin in patients with acute ischemic stroke

Neurotropin was found to reduce brain oedema in an experimental model of brain infarction in the guinea-pig. A randomized double-blind controlled trial with Neurotropin was performed in 220 patients admitted within 24 h after an acute ischemic stroke. 35 of the neurotropin and 41 of the placebo-randomized patients had to be excluded. 10 included patients in the neurotropin and 13 in the placebo-treated group died within the study period of 15 days. A better clinical outcome was observed in the 65 included surviving neurotropin compared with the 56 placebo-treated patients. The size of the infarct and of the oedema zones was significantly more decreased on CTscans from Day 11 compared with Day 3 after stroke in the neurotropin than in the placebo treated group. Neurotropin is helpful in treating brain oedema, related to acute ischemic stroke.     

Aspirin resistance in patients with acute ischemic stroke

Aspirin is used in ischemic stroke therapy. However, some patients are not responsive to the antithrombotic action of aspirin. The aim of this study was to assess the prevalence of aspirin resistance in stroke patients and its association with mortality. One-hundred and six patients (mean age 64.9 ± 14.6 years, 53 male) with acute ischemic stroke were consecutively recruited. All subjects were taking aspirin regularly. Aspirin responsiveness was determined by Ultegra Rapid Platelet Function Assay-ASA (VerifyNow Aspirin). Aspirin resistance was defined as aspirin reaction unit (ARU) ≥ 550. Aspirin resistance was detected in 35 patients. There were not any significant differences in age, gender and comorbidities between aspirin-resistant and aspirin-sensitive patients. The mean National Institute of Health Stroke Scale (NIHSS) scores of the aspirin-resistant and aspirin-sensitive patients were 15 ± 3 and 12 ± 5, respectively (p = 0.006). Twenty-seven patients had a history of prior ischemic stroke and eight of them had aspirin resistance. Eleven patients died in-hospital and a total of 43 patients died during 2 years. Both the in-hospital and 2-year mortality rates were significantly higher in patients with aspirin resistance (20 vs. 5.6%, p = 0.038 and 60.0 vs. 31.0%, p = 0.004, respectively). Regression analysis revealed aspirin resistance [odds ratio (OR) 3.097, 95% confidence interval (CI) 1.070–8.959, p = 0.037] as an independent predictor of 2-year mortality, as well as age (OR 1.051, 95% CI 1.003–1.102, p = 0.038) and NIHSS scores (OR 1.208, 95% CI 1.016–1.437, p = 0.033). Aspirin resistance is not uncommon in patients with acute ischemic stroke and is associated with short and long term mortality in these patients.     

Homocysteine testing in patients with acute ischemic stroke

OBJECTIVE: To determine pretesting factors associated with elevated total homocysteine (tHcy) levels in a cohort of patients with acute ischemic stroke and to identify patient characteristics associated with physicians' decisions to obtain tHcy levels in routine clinical practice. METHODS: Patient demographics, traditional stroke risk factors, and the results of tHcy tests were recorded for a consecutive series of adult patients with ischemic stroke admitted to an academic medical center from January 1997 to December 1999 (n = 674). Stroke subtype was classified using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Univariate analyses were used to identify patient characteristics associated with elevated tHcy levels and factors associated with tHcy testing. Multivariable stepwise logistic regression analyses were then used to identify the independent associations of univariately significant variables with tHcy testing. RESULTS: Of 674 patients, 131 (19.4%) were tested for tHcy. There were no associations between age, sex, stroke subtype, or the presence of other stroke risk factors and tHcy levels. Younger age (odds ratio [OR] = 0.54/decade, 95% CI = 0.46 to 0.62), the presence of hyperlipidemia (OR = 1.9, 95% CI = 1.2 to 2.9), diabetes (OR = 0.47, 95% CI = 0.29 to 0.78), and cardioembolic (OR = 0.47, 95% CI = 0.23 to 0.95) and small-vessel (OR = 0.43, 95% CI = 0.22 to 0.83) stroke subtypes were independently associated with tHcy testing. CONCLUSIONS: Elevated tHcy levels were not associated with any of the studied characteristics of ischemic stroke patients. More research is needed to determine factors that aid in selecting patients for tHcy testing and improving diagnostic yield.     

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.     

动静脉联合溶栓治疗大脑中动脉闭塞引起的急性缺血性脑卒中

目的研究动静脉联合溶栓治疗大脑中动脉闭塞引起的急性缺血性脑卒中的安全性和有效性。方法回顾分析我院采用静脉溶栓或动静脉联合溶栓病例23例。卒中严重程度采用NIHSS评分评估,CTA,MRA或全脑血管造影评估再通情况,溶栓治疗后72 h内观察溶栓后非症状性和症状性出血,临床预后通过改良RS评分进行评估。结果静脉溶栓组14例,动静脉联合溶栓组9例,两组患者入院后NISS评分无统计学差异,动静脉联合溶栓后大脑中动脉再通率明显高于静脉溶栓组(77.8 vs.28.6%,P=0.036),而术后出现症状性及非症状性颅内出血与静脉溶栓比较无明显差异,90 d达到mRS 0-2分患者比例与静脉组比较无统计学差异,联合溶栓组高于静脉组。结论与静脉溶栓比较,应用动静脉联合溶栓治疗大脑中动脉闭塞引起的急性缺血性脑卒中是一种安全、有效的方法。