Diagnosis and management of acute ischaemic stroke.
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ABSTRACT:
SUBMITTER: Hurford R
PROVIDER: S-EPMC7577107 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Diagnosis and management of acute ischaemic stroke.
Hurford Robert R Sekhar Alakendu A Hughes Tom A T TAT Muir Keith W KW
Practical neurology 20200607 4
Acute ischaemic stroke is a major public health priority and will become increasingly relevant to neurologists of the future. The cornerstone of effective stroke care continues to be timely reperfusion treatment. This requires early recognition of symptoms by the public and first responders, triage to an appropriate stroke centre and efficient assessment and investigation by the attending stroke team. The aim of treatment is to achieve recanalisation and reperfusion of the ischaemic penumbra wit ...[more]
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Project description:BackgroundCerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries.ObjectivesTo assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke.Search methodsIn May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma).Selection criteriaRandomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke.Data collection and analysisTwo review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data.Main resultsWe identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events: two trials reported on this outcome, with 90% confidence cerebrolysin increased the risks of serious adverse events by at least one third compared to placebo: 62/589 in cerebrolysin group versus 46/600 in placebo group; RR 1.37 90% CI 1.01 to 1.86 (2 trials, 1189 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence).Authors' conclusionsThe findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence suggesting that serious adverse events may be more common with cerebrolysin use in acute ischaemic stroke.
| S-EPMC6463907 | biostudies-literature
Project description:BackgroundCerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries.ObjectivesTo assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke.Search methodsIn May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma).Selection criteriaRandomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke.Data collection and analysisTwo review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data.Main resultsWe identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events (SAEs): there was no significant difference in the total number of SAEs with cerebrolysin (RR 1.16, 95% CI 0.81 to 1.67). This comprised no difference in fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38) and an increase in the number of people with non-fatal SAEs (20/667 with cerebrolysin and 8/668 with placebo: RR 2.47, 95% CI 1.09 to 5.58, P = 0.03) (3 trials, 1335 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence).Authors' conclusionsThe findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence of an increase in non-fatal SAEs with cerebrolysin use but not in total SAEs.
| S-EPMC6478305 | biostudies-literature
Project description: Not available
| S-EPMC8530823 | biostudies-literature
Project description:BackgroundMost ischaemic strokes are caused by a blood clot blocking an artery in the brain. Clot prevention with anticoagulants might improve outcomes if bleeding risks are low. This is an update of a Cochrane review first published in 1995, with recent updates in 2004 and 2008.ObjectivesTo assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) in people with acute presumed or confirmed ischaemic stroke.Search methodsWe searched the Cochrane Stroke Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR), the Database of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA) (The Cochrane Library 2014 Issue 6), MEDLINE (2008 to June 2014) and EMBASE (2008 to June 2014). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies.Selection criteriaRandomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke.Data collection and analysisTwo review authors independently selected trials for inclusion, assessed trial quality, and extracted the data.Main resultsWe included 24 trials involving 23,748 participants. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence relates to the effects of anticoagulant therapy initiated within the first 48 hours of onset. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow-up. Similarly, based on eight trials (22,125 participants), there was no evidence that early anticoagulation reduced the odds of being dead or dependent at the end of follow-up (OR 0.99; 95% CI 0.93 to 1.04). Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99).Authors' conclusionsSince the last version of the review, no new relevant studies have been published and so there is no additional information to change the conclusions. Early anticoagulant therapy is not associated with net short- or long-term benefit in people with acute ischaemic stroke. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any of the currently available anticoagulants in acute ischaemic stroke.
| S-EPMC7065522 | biostudies-literature
Project description:The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke.The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels >180/105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups. There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.
| S-EPMC8370078 | biostudies-literature
Project description:Neurological worsening in acute ischaemic stroke patients is common with significant morbidity and mortality.To determine the factors associated with early neurological worsening within the first 9 h after onset of acute ischaemic stroke.The National Institute of Health Stroke Scale (NIHSS) was used to assess stroke severity. Early neurological worsening was defined as NIHSS score increase ≥4 NIHSS points within 9 h of symptom onset compared to NIHSS score within 3 h of symptom onset. Patients with early neurological worsening were compared to patients with unchanged or improved NIHSS scores.Of the 2484 patients admitted with ischaemic stroke, 552 patients had NIHSS score within 3 h of symptom onset, and 44 (8.0%) experienced early neurological worsening. The median NIHSS on admission was 8.4 in both groups. Early neurological worsening was associated with low body temperature on admission (P = 0.01), proximal compared to distal MCA occlusion (P = 0.007) and with ipsilateral internal carotid artery stenosis >50% or occlusion (P = 0.04). Early neurological worsening was associated with higher NIHSS day 7 (P < 0.001) and higher mortality within 7 days of stroke onset (P = 0.005).Early neurological worsening has serious consequences for the short-term outcome for patients with acute ischaemic stroke and is associated with low body temperature on admission, and with extracranially and intracranially large-vessel stenosis or occlusion.
| S-EPMC4744656 | biostudies-other
Project description:OBJECTIVE:The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). DESIGN:Eligible patients had IVT started within 4.5?hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90?min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0-2 at day 90. RESULTS:Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13-21). Median stroke onset to IVT start was 120?min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0-1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0-2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021). CONCLUSIONS:The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival. TRIAL REGISTRATION NUMBER:NCT01745692; Results.
| S-EPMC5256149 | biostudies-literature
Project description:BackgroundPeople with hyperglycaemia concomitant with an acute stroke have greater mortality, stroke severity, and functional impairment when compared with those with normoglycaemia at stroke presentation. This is an update of a Cochrane Review first published in 2011.ObjectivesTo determine whether intensively monitoring insulin therapy aimed at maintaining serum glucose within a specific normal range (4 to 7.5 mmol/L) in the first 24 hours of acute ischaemic stroke influences outcome.Search methodsWe searched the Cochrane Stroke Group Trials Register (September 2013), CENTRAL (The Cochrane Library 2013, Issue 8), MEDLINE (1950 to September 2013), EMBASE (1980 to September 2013), CINAHL (1982 to September 2013), Science Citation Index (1900 to September 2013), and Web of Science (ISI Web of Knowledge) (1993 to September 2013). We also searched ongoing trials registers and SCOPUS.Selection criteriaRandomised controlled trials (RCTs) comparing intensively monitored insulin therapy versus usual care in adults with acute ischaemic stroke.Data collection and analysisWe obtained a total of 1565 titles through the literature search. Two review authors independently selected the included articles and extracted the study characteristics, study quality, and data to estimate the odds ratio (OR) and 95% confidence interval (CI), mean difference (MD) and standardised mean difference (SMD) of outcome measures. We resolved disagreements by discussion.Main resultsWe included 11 RCTs involving 1583 participants (791 participants in the intervention group and 792 in the control group). We found that there was no difference between the treatment and control groups in the outcomes of death or dependency (OR 0.99, 95% CI 0.79 to 1.23) or final neurological deficit (SMD -0.09, 95% CI -0.19 to 0.01). The rate of symptomatic hypoglycaemia was higher in the intervention group (OR 14.6, 95% CI 6.6 to 32.2). In the subgroup analyses of diabetes mellitus (DM) versus non-DM, we found no difference for the outcomes of death and disability or neurological deficit. The number needed to treat was not significant for the outcomes of death and final neurological deficit. The number needed to harm was nine for symptomatic hypoglycaemia.Authors' conclusionsAfter updating the results of our previous review, we found that the administration of intravenous insulin with the objective of maintaining serum glucose within a specific range in the first hours of acute ischaemic stroke does not provide benefit in terms of functional outcome, death, or improvement in final neurological deficit and significantly increased the number of hypoglycaemic episodes. Specifically, those people whose glucose levels were maintained within a tighter range with intravenous insulin experienced a greater risk of symptomatic and asymptomatic hypoglycaemia than those people in the control group.
| S-EPMC10770823 | biostudies-literature