This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.

No abstract

No abstract

Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

No abstract

Background— Clinical studies using ultrasound at diagnostic frequencies in transcranial Doppler devices provided encouraging results in enhancing thrombolysis with tissue plasminogen activator (tPA) in acute stroke. Low-frequency ultrasound does not require complex positioning procedures, penetrates through the skull better, and has been demonstrated to accelerate thrombolysis with tPA in animal experiments in wide cerebrovascular territories without hemorrhagic side effects. We therefore conducted the first multicenter clinical trial to investigate safety of tPA plus low-frequency ultrasound (300 kHz). Methods— Acute stroke patients within a 6-hour time window were included (National Institutes of Health Stroke Scale scores >4). Magnetic resonance imaging (MRI) was used to document vascular occlusion and to rule out cerebral hemorrhage. Patients were allocated to combination therapy alternately; the first patient received tPA only, the second patient received tPA plus ultrasound, etc. Follow-up included serial MRI directly thereafter and 24 hours later to confirm recanalization and tissue imaging. Clinical recovery was measured after treatment and 3 months later. Results— 26 patients (70.4±9.7 years) entered the trial (12 tPA, 14 tPA plus ultrasound). The study was prematurely stopped because 5 of 12 patients from the tPA only group but 13 of 14 patients treated with the tPA plus ultrasound showed signs of bleeding in MRI ( P <0.01). Within 3 days of treatment, 5 symptomatic hemorrhages occurred within the tPA plus ultrasound group. At 3 months, neither morbidity nor treatment-related mortality or recanalization rates differed between both groups. Conclusions— This study demonstrated bioeffects from low-frequency ultrasound that caused an increased rate of cerebral hemorrhages in patients concomitantly treated with intravenous tPA.

No abstract

Background and Purpose-Women experience worse outcomes after stroke compared with men. Prior work has suggested sex-based differences in coagulation and fibrinolysis markers in subjects with acute stroke. We explored whether sex might modify the effect of recombinant tissue plasminogen activator (rtPA) on outcomes in patients with acute ischemic stroke. Methods-Using a combined database including subjects from the National Institute of Neurological Disorders and Stroke (NINDS), Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) A and B, and the Second European Cooperative Acute Stroke Study (ECASS II) trials, we examined 90-day outcomes in patients randomized to rtPA versus placebo by sex. We used logistic regression to control for potential confounders. Results-Among 988 women treated between 0 and 6 hours from symptom onset, patients receiving rtPA were significantly more likely than those receiving placebo to have a modified Rankin Score Յ1 (40.5% versus 30.3%, PϽ0.0008). Among 1190 men, the trend toward benefit in the overall group did not reach statistical significance (38.5% versus 36.7%, Pϭ0.52). An unadjusted analysis showed that women were significantly more likely to benefit from rtPA compared with men (Pϭ0.04). Controlling for age, baseline National Institutes of Health Stroke Scale, diabetes, symptom onset to treatment time, prior stroke, systolic blood pressure, extent of hypoattenuation on baseline computed tomography scan and several significant interaction terms (including onset to treatment time-by-treatment and systolic blood pressure-by treatment) did not substantially change the strength of the interaction between gender and rtPA treatment (Pϭ0.04). Conclusions-In this pooled analysis of rtPA in acute ischemic stroke, women benefited more than men, and the usual gender difference in outcome favoring men was not observed in the thrombolytic therapy group. For patients presenting at later time intervals, when the risks and benefits of rtPA are more finely balanced, sex may be an important variable to consider for patient selection.