Acute ischemic stroke is a devastating condition that afflicts more than 12 million people every year. Globally, stroke is the 2nd leading cause of death and 3rd leading cause of disability worldwide. While not all patients can avail themselves of existing acute therapies, all patients can benefit from brain optimization measures. This paper details the 12 steps in the management of acute ischemic stroke in the emergency department.

Guipi wan (GPW) is a traditional Chinese medicine commonly used in clinical practice, typically to treat neurological diseases such as neurasthenia and traumatic brain injury. It may have positive effects on cerebral ischemia‒reperfusion injury (cI/R). This study aimed to assess the effects of GPW in a mouse model of cI/R and find its possible targets. C57BL/6J mice were used to establish the cI/R model, and the laser speckle doppler was used to determine the success of the model. GPW was administered intragastrically for 7 days, brain tissue sections were stained with TTC, HE, and TUNEL, Western blot assay was performed to detect the effect of apoptosis-related proteins. Furthermore, we screened active ingredients from the TCM Database and constructed a compound‒target network using the Cytoscape 3.8.0 software. Moreover, we employed protein‒protein interaction and component‒target‒pathway network analyses to determine the potential components of GPW and its target genes, the key target was verified through molecular docking. Finally, we detected the influence of the downstream signaling pathway of the target through Western blot. The results showed that GPW decreased the cerebral infarction area, neurological function scores, and neuronal apoptosis in mice by regulating PI3K/AKT signaling pathway. Network analysis indicated that gamma-aminobutyric acid B receptor 1 (GABBR1) might be a potential target for the treatment of cI/R. Molecular docking indicated that 9 active components in GPW could bind to GABBR1 with desirable binding energy. This study represented the demonstratable effect of GPW in the treatment of cI/R injury and suggested GABBR1 as a potential target using network analysis.

Neurologists are well-versed with acute ischemic stroke, a serious public health concern. Effective acute stroke treatment is built on the rapid application of reperfusion therapy. This calls for prompt symptom recognition by the general population as well as emergency workers, proper referral to specialized stroke centers, and thorough examination and assessment by the on-site stroke team. The main goal of treatment for certain individuals is to restore blood flow to the ischemic penumbra by using intravenous thrombolysis and/or endovascular thrombectomy. Acute stroke patients must be hospitalized and continuously monitored for early neurological decline in order to avoid subsequent problems. After swiftly determining the stroke mechanism, patients can start the proper secondary preventative actions.

Low-molecular-weight heparins (LMWHs) and heparinoids are anticoagulants that may have more powerful antithrombotic effects than standard unfractionated heparin (UFH) but a lower risk of bleeding complications. This is an update of the original Cochrane Review of these agents, first published in 2001 and last updated in 2008.

To determine whether antithrombotic therapy with LMWHs or heparinoids is associated with a reduction in the proportion of people who are dead or dependent for activities in daily living compared with UFH.

We searched the Cochrane Stroke Group Trials Register (last searched February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library Issue 1, 2017), MEDLINE (1966 to February 2017), and Embase (1980 to February 2017). We also searched trials registers to February 2017: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform.

Unconfounded randomised trials comparing LMWH or heparinoids with standard UFH in people with acute ischaemic stroke, in which participants were recruited within 14 days of stroke onset.

Two review authors independently chose studies for inclusion, assessed risk of bias and trial quality, extracted and analysed the data. Differences were resolved by discussion.

We included nine trials involving 3137 participants. We did not identify any new trials for inclusion in this updated review. None of the studies reported data on the primary outcome in sufficient detail to enable analysis for the review. Overall, there was a moderate risk of bias in the included studies. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (96/1616 allocated LMWH/heparinoid versus 78/1486 allocated UFH; odds ratio (OR) 1.06, 95% CI 0.78 to 1.47; 8 trials, 3102 participants, low quality evidence). LMWH or heparinoid were associated with a significant reduction in deep vein thrombosis (DVT) compared with UFH (OR 0.55, 95% CI 0.44 to 0.70, 7 trials, 2585 participants, low quality evidence). However, the number of the major clinical events such as pulmonary embolism (PE) and intracranial haemorrhage was too small to provide a reliable estimate of the effects.

Treatment with a LMWH or heparinoid after acute ischaemic stroke appears to decrease the occurrence of DVT compared with standard UFH, but there are too few data to provide reliable information on their effects on other important outcomes, including functional outcome, death and intracranial haemorrhage.

Appropriate acute treatment with plasminogen activators (PAs) can significantly increase the probability of minimal or no disability in selected ischemic stroke patients. There is a great deal of evidence showing that intravenous recombinant tissue PAs (rt-PA) infusion accomplishes this goal, recanalization with other PAs has also been demonstrated in the development of this treatment. Recanalization of symptomatic, documented carotid or vertebrobasilar arterial territory occlusions have also been achieved by local intra-arterial PA delivery, although only a single prospective double-blinded randomized placebo-controlled study has been reported. The increase in intracerebral hemorrhage with these agents by either delivery approach underscores the need for careful patient selection, dose-appropriate safety and efficacy, proper clinical trial design, and an understanding of the evolution of cerebral tissue injury due to focal ischemia. Principles underlying the evolution of focal ischemia have been expanded by experience with acute PA intervention. Several questions remain open that concern the manner in which PAs can be applied acutely in ischemic stroke and how injury development can be limited.

The objectives of this study were to analyze the outcome and hemorrhagic risk of intravenous (IV) argatroban in patients with acute ischemic stroke presenting beyond six hours of ischemic symptom onset.

Eighty patients with acute ischemic stroke who were admitted to the hospital beyond six hours from ischemic symptom onset were retrospectively analyzed. We could not perform IV thrombolysis or intra-arterial thrombolysis because of limited time window. So, IV argatroban was performed to prevent recurrent thrombosis and progression of infarcted area. The outcome was assessed by the National Institute of Health Stroke Scale (NIHSS) score and related hemorrhagic risk was analyzed. Also, each outcome was analyzed according to the initial stroke severity, subtype, and location.

The median NIHSS was 8.0 at admission, 4.1 upon discharge, and 3.3 after three months. A good outcome was achieved in 81% of patients upon discharge and 88% after three months. Symptomatic hemorrhage occurred in only two patients (3%). IV argatroban was effective regardless of initial stroke severity, subtype, and location.

IV argatroban may be an effective and safe treatment modality for acute ischemic stroke presenting beyond six hours of ischemic symptom onset.

Results from apparently conclusive meta-analyses may be false. A limited number of events from a few small trials and the associated random error may be under-recognized sources of spurious findings. The information size (IS, i.e. number of participants) required for a reliable and conclusive meta-analysis should be no less rigorous than the sample size of a single, optimally powered randomized clinical trial. If a meta-analysis is conducted before a sufficient IS is reached, it should be evaluated in a manner that accounts for the increased risk that the result might represent a chance finding (i.e. applying trial sequential monitoring boundaries).

We analysed 33 meta-analyses with a sufficient IS to detect a treatment effect of 15% relative risk reduction (RRR). We successively monitored the results of the meta-analyses by generating interim cumulative meta-analyses after each included trial and evaluated their results using a conventional statistical criterion (alpha = 0.05) and two-sided Lan-DeMets monitoring boundaries. We examined the proportion of false positive results and important inaccuracies in estimates of treatment effects that resulted from the two approaches.

Using the random-effects model and final data, 12 of the meta-analyses yielded P > alpha = 0.05, and 21 yielded P </= alpha = 0.05. False positive interim results were observed in 3 out of 12 meta-analyses with P > alpha = 0.05. The monitoring boundaries eliminated all false positives. Important inaccuracies in estimates were observed in 6 out of 21 meta-analyses using the conventional P </= alpha = 0.05 and 0 out of 21 using the monitoring boundaries.

Evaluating statistical inference with trial sequential monitoring boundaries when meta-analyses fall short of a required IS may reduce the risk of false positive results and important inaccurate effect estimates.

This article summarises the recommendations for the management of managing patients with intracerebral haemorrhage published in 2006 by the European Stroke Initiative (EUSI) on behalf of the European Stroke Council (ESC), the European Neurological Society (ENS), and the European Federation of Neurological Societies (EFNS).

Deep vein thrombosis (DVT) is perceived as uncommon among Asian stroke patients. However, there is a paucity of published data, and thus, we studied the frequency, characteristics and prognosis of DVT following ischemic stroke in Asian patients with lower limb paresis.

Doppler ultrasound scans of the lower limbs were performed at days 7-10 and 25-30 after stroke onset. The functional status of patients was assessed at 6 months using the modified Rankin scale.

DVT was detected in 30% of patients at days 7-10 and in 45% of patients at days 25-30. Most thromboses were distal. There were significant associations of age and degree of weakness with the presence of DVT at days 25-30, but not at days 7-10. DVT in the first month after stroke was associated with poorer outcome at 6 months.

DVT following ischemic stroke among Asians is common and associated with poor functional outcome.

To assess the use of evidence-based investigations and treatments in patients with acute stroke in selected Australian hospitals and to compare management and outcomes between stroke and other types of hospital specialty unit.

Retrospective, multicentre audit of hospital case files.

Eight metropolitan tertiary-care hospitals from five Australian States.

300 consecutive patients from each hospital admitted between 17 September 1999 and 23 May 2001 and having a discharge diagnosis of stroke or transient ischaemic attack.

Use of investigations and treatments supported by best available evidence; comparison of management and outcomes between stroke, neurology, general medical and geriatric units.

2383 patients were audited (median age, 72.7 years; 52% men); 72% had ischaemic events, and 28% haemorrhagic events. Use of investigations and treatments varied between hospitals and types of unit. Stroke units or teams cared directly for 23% of patients (range across hospitals, 0-100%). Although 47% of patients with ischaemic events presented within 3 hours of symptom onset (when thrombolysis might provide benefit), only nine (2%) received thrombolysis. Angiotensin-converting enzyme (ACE) inhibitors were given to 28% of survivors at discharge (range, 14%-38%). Stroke units were more likely to use diagnostic tests, while neurology units were more likely to prescribe heparin acutely for patients with ischaemic stroke (not recommended for patients in general), and geriatric units were less likely to discharge patients with atrial fibrillation on anticoagulation therapy. Outcomes also varied significantly between types of unit. In-hospital survival rates were 90% (stroke units), 91% (neurological units), 82% (general medical units) and 79% (geriatric units) (P < 0.001). Stroke units and neurological units sent more patients home than the other units. Stroke units also sent fewer patients to rehabilitation and had longer mean length of stay.

Acute stroke care varies between Australian tertiary-care hospitals and types of specialty unit, with suboptimal use of many evidence-based interventions.

The purpose of this study was to examine the association between hemostatic activation and stroke severity, and to provide data on hemostatic variables in acute ischemic stroke.

The patient material comprised 76 consecutive patients with acute ischemic stroke (median 16 h, interquartile range 3-48). Levels of hemostatic variables were determined in blood samples collected on the day of hospitalization. Stroke severity was assessed on admission by the Oxfordshire Community Stroke Project (OCSP) classification, and on discharge (median 9 days, interquartile range 6-14) by Barthel Index (BI, scores 0-50, 55-90, or 95-100) and modified Rankin Scale (mRS, scores 0-1 or 2-6). Associations were assessed by multiple linear regression analyses.

Levels of the fibrin degradation product D-Dimer and the activation peptide prothrombin fragment 1 + 2 (F1 + 2) were linearly related to stroke severity, whether assessed on admission (P = .001 and.03, respectively, for the OCSP classification), or on discharge (P = .009 and.43, respectively, for BI; and.001 and.05, respectively, for mRS). High levels of D-Dimer and F(1 + 2), as well as low levels of antithrombin and protein C were also present in patients with a presumed embolic source, and low antithrombin or protein C was borderline significantly associated with atrial fibrillation (P = .072 and.058, respectively). Low levels of protein C or protein S, and the presence of antiphospholipid antibodies, including lupus anticoagulant (LA), was detected in 13/73 (18%) and 15/70 (21%) of the patients, respectively.

Activation of the hemostatic system is independently related to acute stroke severity and short-term outcome. Low levels of coagulation inhibitors or presence of antiphospholipid antibodies is a relatively frequent finding in unselected patients with acute ischemic stroke, but a causative role cannot be inferred from our study.

Postacute rehabilitation stroke services represent a large component of stroke care. In the United States and elsewhere, major changes in the organization and funding of these services are limiting patient access to organized inpatient multidisciplinary care. We conducted a systematic review to evaluate the effectiveness of such services.

We defined our intervention as organized inpatient multidisciplinary rehabilitation commencing at least 1 week after stroke and sought randomized trials that compared this model of care with an alternative. The analysis was stratified by the particular service characteristics. We identified a heterogeneous group of 9 trials (6 of stroke rehabilitation units; 3 of general rehabilitation wards) recruiting 1437 patients. Organized inpatient multidisciplinary rehabilitation was associated with a reduced odds of death (odds ratio, 0.66; 95% CI, 0.49 to 0.88; P:<0.01), death or institutionalization (odds ratio, 0.70; 95% CI, 0.56 to 0.88; P:<0.001), and death or dependency (odds ratio, 0.65; 95% CI, 0.50 to 0.85; P:<0.001), which was consistent across a variety of trial subgroups. For every 100 patients receiving organized inpatient multidisciplinary rehabilitation, an extra 5 returned home in an independent state.

The results indicate that there can be substantial benefit from organized inpatient multidisciplinary rehabilitation in the postacute period, which is both statistically significant and clinically important.

Treatment for venous thromboembolism (VTE) is highly effective in preventing morbidity and mortality, yet pulmonary embolism (PE) accounts for up to 25% of early deaths after stroke. This is because the current diagnostic paradigm is reactive rather than proactive: the clinician responds to VTE when it becomes symptomatic, in the expectation that initiation of treatment will prevent progression to more serious manifestations. This approach is flawed, because sudden death from PE is frequently unheralded and nonfatal symptomatic pulmonary emboli are often unrecognized or misdiagnosed.

Morbidity and mortality from PE could be reduced either by more effective thromboprophylaxis or earlier diagnosis and treatment of established VTE. The fact that early use of short-term, low-dose, unfractionated heparin (UFH) is not associated with sustained, clinically meaningful benefit suggests that a fundamental change in the diagnostic approach to VTE is needed, one which requires a greater appreciation that clinically apparent events are merely the tip of the thromboembolism iceberg.

Research into a strategy of screening for subclinical VTE in these patients is needed, with a view to identifying a subgroup at risk of progression to symptomatic and life-threatening events, in whom outcome might be improved by anticoagulation.

Anticoagulation with intravenous unfractionated heparin (IVUH) while awaiting therapeutic oral anticoagulant levels is a common practice in patients with acute and subacute cerebral ischemia. A promising alternative strategy is to use bridging subcutaneous low-molecular-weight heparin (LMWH), which may have a favorable risk-benefit profile compared with IVUH and may permit earlier discharge with completion of transition to warfarin therapy as an outpatient.

A LMWH, enoxaparin 1 mg/kg BID, was used as bridging anticoagulation therapy in 24 consecutive patients admitted to a university stroke center in whom the treatment plan included transition from acute to chronic anticoagulation. The LMWH group was contrasted with the preceding 24 patients transitioned to warfarin with IVUH at the same center.

Fewer patients in the LMWH bridging therapy group experienced neurological worsening than in the IVUH bridging therapy group (2/24 versus 8/24; P:=0.033). Fewer total adverse events were noted in the LMWH group than in the IVUH cohort (3 versus 20; P:=0. 002). Fifteen of the 24 LMWH patients (62.5%) were discharged while still receiving LMWH and completed transition to warfarin as outpatients, receiving an average of 3.6 days of outpatient transitional therapy. In these 15 patients, use of LMWH was associated with a net savings of $2197 per patient.

In this pilot cohort with subacute cerebral ischemia, bridging LMWH appeared to be safer than bridging IVUH and was associated with reduced hospital stay and reduced total cost of care.