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For several years, the only therapy with proven efficacy for acute ischaemic stroke was alteplase, which is approved for use within 4·5 h after stroke onset in many countries, but only within 3 h in the USA. However, the recanalisation rate with alteplase is modest. Several trials have shown substantial clinical benefit of neurothrombectomy within 6 h of ischaemic stroke onset, which has initiated a new era of acute stroke therapy. As neurothrombectomy becomes part of standard practice, additional trials will be needed to determine the best way to organise delivery of this care. Continuing clinical trials with several types of advanced MRI and CT imaging to enhance patient selection are investigating alteplase, other thrombolytic drugs, and novel endovascular devices, for use in later time periods from stroke onset. Consequently, the organisation and implementation of future clinical trials will need to adapt to what has been learned from the present generation of trials. The delivery of care to patients with acute stroke will also need to incorporate newly proven therapies, and much additional work is needed to maximise outcomes in as many patients as possible.

Patients who had had a cryptogenic stroke and had a PFO were randomly assigned to medical therapy or PFO closure. At a median of 5.9 years, the rate of recurrent ischemic strokes was lower in the PFO closure group than in the medical-therapy group.

The Solitaire Flow Restoration Device is a novel, self-expanding stent retriever designed to yield rapid flow restoration in acute cerebral ischaemia. We compared the efficacy and safety of Solitaire with the standard, predicate mechanical thrombectomy device, the Merci Retrieval System. In this randomised, parallel-group, non-inferiority trial, we enrolled patients from 18 sites (17 in the USA and one in France). Patients were eligible for inclusion if they had acute ischaemic stroke with moderate to severe neurological deficits and were treatable by thrombectomy within 8 h of stroke symptom onset. We used a computer-generated randomisation sequence to randomly allocate patients to receive thrombectomy treatment with either Solitaire or Merci (1:1; block sizes of four and stratified by centre and stroke severity). The primary endpoint was Thrombolysis In Myocardial Ischemia (TIMI) scale 2 or 3 flow in all treatable vessels without symptomatic intracranial haemorrhage, after up to three passes of the assigned device, as assessed by an independent core laboratory, which was masked to study assignment. Primary analysis was done by intention to treat. A prespecified efficacy stopping rule triggered an early halt to the trial. The study is registered with ClinicalTrials.gov, number NCT 01054560. Between February, 2010, and February, 2011, we randomly allocated 58 patients to the Solitaire group and 55 patients to the Merci group. The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group (61%vs 24%; difference 37% [95% CI 19–53], odds ratio [OR] 4·87 [95% CI 2·14–11·10]; pnon-inferiority<0·0001, psuperiority=0·0001). More patients had good 3-month neurological outcome with Solitaire than with Merci (58%vs 33%; difference 25% [6–43], OR 2·78 [1·25–6·22]; pnon-inferiority=0·0001, psuperiority=0·02). 90-day mortality was lower in the Solitaire group than it was in the Merci group (17 vs 38; difference −21% [–39 to −3], OR 0·34 [0·14–0·81]; pnon-inferiority=0·0001, psuperiority=0·02). The Solitaire Flow Restoration Device achieved substantially better angiographic, safety, and clinical outcomes than did the Merci Retrieval System. The Solitaire device might be a future treatment of choice for endovascular recanalisation in acute ischaemic stroke. Covidien/ev3.

In this randomized trial involving patients with acute stroke, prehospital administration of magnesium sulfate by paramedics within 2 hours after the onset of stroke symptoms (within 1 hour for 74% of patients) did not improve neurologic outcomes. Stroke is the second leading cause of death and a leading cause of adult disability worldwide. Unfortunately, currently available therapies for acute ischemic stroke, which are all reperfusion-based, are only moderately effective. 1 , 2 Treatment with tissue plasminogen activator (t-PA), the only pharmacologic treatment approved by a regulatory agency for the treatment of acute ischemic stroke, results in early reperfusion in less than half of treated patients, can be started only after neuroimaging has ruled out intracerebral hemorrhage, and is used in only 2 to 7% of patients with acute ischemic stroke in the United States. 1 Mechanical thrombectomy devices improve patient . . .

In acute stroke management, time is brain. Bringing swift treatment to the patient, instead of the conventional approach of awaiting the patient's arrival at the hospital for treatment, is a potential strategy to improve clinical outcomes after stroke. This strategy is based on the use of an ambulance (mobile stroke unit) equipped with an imaging system, a point-of-care laboratory, a telemedicine connection to the hospital, and appropriate medication. Studies of prehospital stroke treatment consistently report a reduction in delays before thrombolysis and cause-based triage in regard to the appropriate target hospital (eg, primary vs comprehensive stroke centre). Moreover, novel medical options for the treatment of stroke patients are also under investigation, such as prehospital differential blood pressure management, reversal of warfarin effects in haemorrhagic stroke, and management of cerebral emergencies other than stroke. However, crucial concerns regarding safety, clinical efficacy, best setting, and cost-effectiveness remain to be addressed in further studies. In the future, mobile stroke units might allow the investigation of novel diagnostic (eg, biomarkers and automated imaging evaluation) and therapeutic (eg, neuroprotective drugs and treatments for haemorrhagic stroke) options in the prehospital setting, thus functioning as a tool for research on prehospital stroke management.

This trial assessed the value of brain imaging to guide treatment for stroke. Clinical outcomes with embolectomy were not superior to those with standard care in all patients or in the subgroup identified by brain imaging as most likely to benefit from embolectomy. Multiple randomized, controlled trials have shown the efficacy of the use of intravenous tissue plasminogen activator (t-PA), administered up to 4.5 hours after the onset of symptoms of acute ischemic stroke. 1 , 2 However, the global effect of this therapy has been limited, largely because of the narrow time window available for treatment and the risk of symptomatic intracerebral hemorrhage. Although endovascular approaches, including thrombectomy devices, have been shown to achieve greater rates of recanalization than the use of intravenous t-PA, no randomized, controlled trial has been completed comparing clinical outcomes versus standard medical care. Moreover, the potential to benefit from . . .

BackgroundRevascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials.MethodsThe HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography.ResultsAngiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90–99%, 2b67=67–89%, 2b50=50–66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014).ConclusionsThe benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice.

One quarter of ischemic strokes are cryptogenic (no obvious cause). Additional investigation involves assessment for arteriopathies, cardiac sources of embolism (in particular, occult low-burden atrial fibrillation), and disturbances of coagulation. Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. Stage After a gym workout, a 48-year-old man had sudden ataxia, nausea, and diplopia, followed by persistent inability to see the upper left quadrant of space with either the left or right eye. He did not have neck pain. His medical history included hypertension and migraines with aura. Magnetic resonance imaging (MRI) showed a right occipitotemporal and thalamic infarct. Magnetic resonance angiography showed an abrupt cutoff of a distal segment of the right posterior cerebral artery. The complete blood count, prothrombin time, and partial-thromboplastin time were normal. Transthoracic echocardiographic results suggested a possible right-to-left shunt. Cardiac telemetry during the first . . .

Results of initial randomised trials of endovascular treatment for ischaemic stroke, published in 2013, were neutral but limited by the selection criteria used, early-generation devices with modest efficacy, non-consecutive enrolment, and treatment delays. In the past year, six positive trials of endovascular thrombectomy for ischaemic stroke have provided level 1 evidence for improved patient outcome compared with standard care. In most patients, thrombectomy was performed in addition to thrombolysis with intravenous alteplase, but benefits were also reported in patients ineligible for alteplase treatment. Despite differences in the details of eligibility requirements, all these trials required proof of major vessel occlusion on non-invasive imaging and most used some imaging technique to exclude patients with a large area of irreversibly injured brain tissue. The results indicate that modern thrombectomy devices achieve faster and more complete reperfusion than do older devices, leading to improved clinical outcomes compared with intravenous alteplase alone. The number needed to treat to achieve one additional patient with independent functional outcome was in the range of 3·2–7·1 and, in most patients, was in addition to the substantial efficacy of intravenous alteplase. No major safety concerns were noted, with low rates of procedural complications and no increase in symptomatic intracerebral haemorrhage. Thrombectomy benefits patients across a range of ages and levels of clinical severity. A planned meta-analysis of individual patient data might clarify effects in under-represented subgroups, such as those with mild initial stroke severity or elderly patients. Imaging-based selection, used in some of the recent trials to exclude patients with large areas of irreversible brain injury, probably contributed to the proportion of patients with favourable outcomes. The challenge is how best to implement imaging in clinical practice to maximise benefit for the entire population and to avoid exclusion of patients with smaller yet clinically important potential to benefit. Although favourable imaging identifies patients who might benefit despite long delays from symptom onset to treatment, the proportion of patients with favourable imaging decreases with time. Health systems therefore need to be reorganised to deliver treatment as quickly as possible to maximise benefits. On the basis of available trial data, intravenous alteplase remains the initial treatment for all eligible patients within 4·5 h of stroke symptom onset. Those patients with major vessel occlusion should, in parallel, proceed to endovascular thrombectomy immediately rather than waiting for an assessment of response to alteplase, because minimising time to reperfusion is the ultimate aim of treatment.

Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke due to internal carotid artery (ICA) or middle cerebral artery (MCA) M1 occlusion with a small ischemic core. However, the effect of EVT on acute stroke with a large ischemic core remains unclear. This study aimed to evaluate the association of EVT plus medical care versus medical care alone with outcomes in patients with acute stroke and a large ischemic core due to ICA or MCA M1 occlusion. PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 2000 to September 25, 2024. There were no language restrictions. Randomized controlled trials (RCTs) of patients with acute stroke and a large ischemic core that compared EVT plus medical care versus medical care alone were evaluated. We computed the random-effects estimate based on the inverse variance method. Risk ratio (RR) with 95% confidence interval (CI) was used to measure outcomes of EVT plus medical care versus medical care alone. The primary outcome was functional independence, defined as modified Rankin Scale (mRS) of 0-2 at 90 days post-stroke; and the lead secondary outcome was reduced disability, defined as ordinal shift of mRS. Safety outcomes were requiring constant care or death (mRS 5-6), death, and early symptomatic intracranial hemorrhage (sICH). Grading of Recommendations Assessment, Development and Evaluations (GRADE) was used to evaluate summaries of evidence for the outcomes. We included six RCTs comprising 1870 patients (826 females [44.2%]) with acute stroke and a larger moderate or large ischemic core due to ICA or MCA M1 occlusion. All patients were nondisabled before stroke. Pooled results showed that at 90 days post-stroke, EVT plus medical care, compared with medical care alone, was associated with greater functional independence (RR 2.53, 95% CI [1.95, 3.29]; p  < 0.001; number needed to treat [NNT], 9, 95% CI [6,15]) and reduced disability (common odds ratio 1.63, 95% CI [1.38, 1.93]; p < 0.001; NNT, 4 [minimum possible NNT, 2; maximum possible NNT, 6]). EVT plus medical care, compared with medical care alone, was associated with a lower risk of requiring constant care or death (RR 0.74, 95% CI [0.66, 0.84]; p  <  0.001; NNT, 7, 95% CI [6,11]). EVT plus medical care, compared with medical care alone, was associated with a nonsignificantly higher proportion of patients with early symptomatic intracranial hemorrhage (RR 1.65, 95% CI [1.00, 2.70]; p  =  0.05). The rates of death were not significantly different between the EVT plus medical care and medical care alone groups (RR 0.86, 95% CI [0.72, 1.02]; p  =  0.08). Main limitations include variability in imaging definitions of large core and inclusion of both larger moderate and large cores in the analysis. Among patients with acute stroke and a larger moderate or large ischemic core due to ICA or MCA M1 occlusion who were nondisabled before stroke, EVT plus medical care, compared with medical care alone, may be associated with improved functional independence, reduced disability, and reduced rates of severe disability or death at 90 days post-stroke. PROSPERO registration number: CRD42024514605.