Background: Mechanical thrombectomy (MT) has become the cornerstone of acute ischaemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist physicians in their clinical decisions with regard to MT. Methods: These Guidelines were developed based on the standard operating procedure of the European Stroke Organisation and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. Results: We found high quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischaemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6-24h time window in patients meeting the eligibility criteria of published randomized trials. These guidelines further detail

The incidence of subarachnoid haemorrhage (SAH) is 6-8 per 100 000 person years, peaking in the sixth decade. SAH, mostly due to rupture of an intracranial aneurysm, accounts for a quarter of cerebrovascular deaths. Aneurysms increase in frequency with age beyond the third decade, are 1.6 times more common in women and are associated with a number of genetic conditions. Prospective autopsy and angiographic studies indicate that between 3.6 and 6% of the population harbour an intracranial aneurysm. Studies have found an increased rate of SAH in first degree relatives of SAH patients (relative risk 3.7-6.6). In affected families, the most frequent relationship between sufferers is sibling to sibling. The rupture rate of asymptomatic aneurysms was thought to be 1-2% per annum, but the recent International Study of Unruptured Intracranial Aneurysms found that the rupture rate of small aneurysms was only 0.05% per annum in patients with no prior SAH, and 0.5% per annum for large (>10 mm diameter) aneurysms and for all aneurysms in patients with previous SAH. Non-invasive tests such as magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and transcranial Doppler (TCD) have been advocated as alternatives to intra-arterial digital subtraction angiography to screen for aneurysms. Although all are promising techniques, the quality of data testing their accuracy is limited. Overall reported sensitivity for CTA and MRA (TCD is poorer) was 76-98% and specificity was 85-100%, but many subjects had an aneurysm or recent SAH, which could overestimate accuracy. CTA and MRA are much poorer methods for the detection of aneurysms <5 mm diameter, which account for up to one-third of unruptured aneurysms. Elective surgical clipping of asymptomatic aneurysms has a morbidity of 10.9% and mortality of 3. 8%. Treatment of aneurysms by Guglielmi coils, for which there is less long-term follow-up available, has a 4% morbidity and 1% mortality, but only achieves complete aneurysm occlusion in 52-78% of cases. There has been interest in screening for aneurysms, but the indication for, and cost effectiveness of screening are unclear because aneurysm prevalence varies, rupture rate is low, non-invasive imaging tests are not yet accurate enough to exclude small aneurysms and the morbidity and mortality for elective surgical treatment of unruptured aneurysms is high. There may be a limited role for investigation of high risk subgroups. Ideally, screening in such subgroups should be tested in a randomized trial. The avoidance of risk factors for aneurysms such as smoking, hypertension and hypercholesterolaemia should be part of the management of at-risk subjects.

Medtronic.

Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.

The 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.

SummaryBackgroundIdentification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype.MethodsWe identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy.FindingsAmong 110 adults (median age 83 years [IQR 76–87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86–0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ɛ4 possession had 100% sensitivity (95% CI 88–100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ɛ4 possession or finger-like projections had 96% specificity (95% CI 78–100).InterpretationThe CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage.FundingUK Medical Research Council, The Stroke Association, and The Wellcome Trust.

BackgroundMechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist physicians in their clinical decisions with regard to MT.MethodsThese guidelines were developed based on the standard operating procedure of the European Stroke Organisation, and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach.ResultsWe found high quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6–24 hour time window in patients meeting the eligibility criteria of published randomized trials. These guidelines further detail aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities.ConclusionsMT is the standard of care in patients with LVO related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision making with regard to the mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.

ObjectiveThe 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).DesignEligible 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.ResultsTen 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).ConclusionsThe 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 numberNCT01745692; Results.