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Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion.Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes.Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048).In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Background and purposes: Stroke severity scales may expedite prehospital large vessel occlusion (LVO) stroke detection, but few are validated for paramedic use. We evaluated the feasibility of intr...

Background:The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT.Methods:Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0–3 or equal to pre-stroke mRS at 3 months.Results:Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36–0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83–0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32–10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08–0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization.Conclusions:Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Background and Purpose: Standard poststroke treatment monitoring protocols are made problematic during the coronavirus disease 2019 (COVID-19) pandemic by the frequency of patient assessments, requiring repeated donning and doffing procedures in a short interval of time. Methods: A streamlined poststroke treatment protocol was developed to limit frequency of patient encounters while maximizing the yield of each encounter by grouping together different components of poststroke care into single bedside visits. Results: Streamlined order sets were developed late March 2020. During the first 6 weeks following implementation, 70 patients were admitted to a geographically defined designated warm COVID-19 unit with modified poststroke care order sets. Of these, 33 (47.1%) patients received acute reperfusion therapy. All but 3 patients evolved favorably with either stable or improving National Institutes of Health Stroke Scale at 24 hours. In the 3 patients who experienced early neurological deterioration, none were found to be attributable to insufficient patient monitoring. Conclusions: Adapting preexisting poststroke care protocols may be necessary while the risk of COVID-19 infection remains high. We propose a streamlined approach to facilitate poststroke monitoring in patients with stroke with unknown COVID status.

This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019. During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy. Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer. Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.

BackgroundThe benefit of acute carotid stenting compared with no acute stenting on clinical outcomes among patients with tandem lesions (TL) undergoing endovascular thrombectomy (EVT) remains unknown.MethodsWe conducted a a systematic review and meta-analysis of studies comparing acute carotid stenting versus no stenting among TL patients undergoing EVT with regards to 90 day modified Rankin Scale (mRS) score, symptomatic intracerebral hemorrhage (sICH), and mortality. Four reviewers screened citations for eligibility and two assessed retained studies for risk of bias and data extraction. A random effects model was used for the synthesis of aggregated data.Results21 studies (n=1635 patients) were identified for the systematic review; 19 were cohort studies, 1 was a post-hoc analysis of an EVT trial, and 1 was a pilot randomized controlled trial. 16 studies were included in the meta-analysis. Acute stenting was associated with a favorable 90 day mRS score: OR 1.43 (95% CI 1.07, 1.91). No significant heterogeneity between studies was found for this outcome (I2=17.0%; χ2=18.07, p=0.26). There were no statistically significant differences for 3 month mortality (OR 0.80 (95% CI 0.50, 1.28)) or sICH (OR 1.41 (95% CI 0.91, 2.19)).ConclusionsThis meta-analysis suggests that among TL patients undergoing EVT, acute carotid stenting is associated with a greater likelihood of favorable outcome at 90 days compared with no stenting.

BackgroundThe COVID-19 pandemic has disrupted acute stroke care logistics, including delays in hyperacute management and decreased monitoring following endovascular therapy (EVT). We aimed to assess the impact of the pandemic on 90-day functional outcome among patients treated with EVT.MethodsThis is an observational cohort study including all patients evaluated for an acute stroke between March 30, 2020 and September 30, 2020 (pandemic cohort) and 2019 (reference cohort) in a high-volume Canadian academic stroke center. We collected baseline characteristics, acute reperfusion treatment and management metrics. For EVT-treated patients, we assessed the modified Rankin score (mRS) at 90 days. We evaluated the impact of the pandemic on a 90-day favourable functional status (defined as mRS 0–2) and death using multivariable logistic regressions.ResultsAmong 383 and 339 patients included in the pandemic and reference cohorts, baseline characteristics were similar. Delays from symptom onset to evaluation and in-house treatment were longer during the early first wave, but returned to reference values in the subsequent months. Among the 127 and 136 EVT-treated patients in each respective cohort, favourable 90-day outcome occurred in 53/99 (53%) vs 52/109 (48%, p=0.40), whereas 22/99 (22%) and 28/109 (26%, p=0.56) patients died. In multivariable regressions, the pandemic period was not associated with 90-day favourable functional status (aOR 1.27, 95% CI 0.60 to 2.56) or death (aOR 0.74, 95% CI 0.33 to 1.63).ConclusionIn this single-center cohort study conducted in a Canadian pandemic epicenter, the first 6 months of the COVID-19 pandemic did not impact 90-day functional outcomes or death among EVT-treated patients.

Introduction: Several comprehensive stroke centers (CSC) have reported increased delays to reperfusion in acute stroke during the COVID-19 pandemic, but it is unknown whether the pandemic is associated with worse functional outcomes in EVT-treated patients. Methods: We performed an observational cohort study of consecutive adult patients evaluated for suspected stroke at our CSC (located in Montreal, a Canadian pandemic epicenter) between March 30 and May 15 2020 (prospective pandemic cohort) and 2019 (retrospective non-pandemic cohort). We excluded in-hospital strokes. We compared short-term (in-house door-to-puncture and door-to-recanalization delays, TICI 2b/3, complications during EVT) and long-term (90-day mRS ≤2 and death) outcomes with univariate analyses. We assessed the effect of the pandemic on 90-day mRS while controlling for clinical confounders. Results: Overall, 111 and 106 patients were included in the pandemic and non-pandemic cohorts, respectively. The prevalence of COVID-19 in the pandemic cohort was 3% (3/104). Among ischemic stroke patients, 31/77 (40%) and 41/71 (58%) underwent EVT in each respective cohort (p=0.03). Among EVT-treated patients, baseline characteristics and NIHSS scores were similar (median [interquartile range]: 20 [12-25] vs 18 [14-20], p=0.18), but pre-stroke mRS was lower in the exposed cohort (0 [0-1] vs 1 [0-2], p=0.04). Door-to-puncture (87 [65-102] vs 56 [47-74] min, p=0.07) metrics were similar, but door-to-recanalization (122 [99-126] vs 89 [67-97] min, p Conclusion: The COVID-19 pandemic does not appear to have a negative impact on 90-day functional status among EVT-treated patients despite increased delays to recanalization. However, patient selection may have been stricter during the pandemic, as a smaller proportion of evaluated patients underwent EVT and those treated had lower pre-stroke mRS.

Approximately 15% of patients undergoing endovascular thrombectomy for anterior circulation acute ischemic stroke have a tandem lesion, defined as a severe stenosis or occlusion of the cervical internal carotid artery ipsilateral to its intracranial occlusion. Patients with tandem lesions have worse outcomes than patients with isolated intracranial occlusions, but the optimal management of their carotid lesions during endovascular thrombectomy remains controversial. The main options commonly used in current practice include acute stent placement in the carotid lesion versus thrombectomy alone without definitive revascularization of the carotid artery. While treatment decisions for these patients are often complex and strategies vary according to clinical, anatomic, and technical considerations, only results from randomized trials comparing these approaches are likely to strengthen current recommendations and optimize patient care.

BackgroundIn A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up of 33·3 months after a prespecified interim analysis showed that medical management alone was superior to the combination of medical management and interventional therapy in preventing symptomatic stroke or death. We aimed to study whether these differences persisted through 5-years' follow-up.MethodsARUBA was a non-blinded, randomised trial done at 39 clinical centres in nine countries. Adults (age ≥18 years) diagnosed with an unruptured brain arteriovenous malformation, who had never undergone interventional therapy, and were considered by participating clinical centres to be suitable for intervention to eradicate the lesion, were eligible for inclusion. Patients were randomly assigned (1:1) by a web-based data collection system, stratified by clinical centre in a random permuted block design with block sizes of two, four, and six, to medical management alone or with interventional therapy (neurosurgery, embolisation, or stereotactic radiotherapy, alone or in any combination, sequence, or number). Although patients and investigators at a given centre were not masked to treatment assignment, investigators at other centres and those in the clinical coordinating centre were not informed of assignment or outcomes at any of the centres. The primary outcome was time to death or symptomatic stroke confirmed by imaging, assessed by a neurologist at each centre not involved in the management of participants' care, and monitored by an independent committee using an adaptive approach with interim analyses. Enrolment began on April 4, 2007, and was halted on April 15, 2013, after which follow-up continued until July 15, 2015. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00389181.FindingsOf 1740 patients screened, 226 were randomly assigned to medical management alone (n=110) or medical management plus interventional therapy (n=116). During a mean follow-up of 50·4 months (SD 22·9), the incidence of death or symptomatic stroke was lower with medical management alone (15 of 110, 3·39 per 100 patient-years) than with medical management with interventional therapy (41 of 116, 12·32 per 100 patient-years; hazard ratio 0·31, 95% CI 0·17 to 0·56). Two patients in the medical management group and four in the interventional therapy group (two attributed to intervention) died during follow-up. Adverse events were observed less often in patients allocated to medical management compared with interventional therapy (283 vs 369; 58·97 vs 78·73 per 100 patient-years; risk difference −19·76, 95% CI −30·33 to −9·19).InterpretationAfter extended follow-up, ARUBA showed that medical management alone remained superior to interventional therapy for the prevention of death or symptomatic stroke in patients with an unruptured brain arteriovenous malformation. The data concerning the disparity in outcomes should affect standard specialist practice and the information presented to patients. The even longer-term risks and differences between the two therapeutic approaches remains uncertain.FundingNational Institute of Neurological Disorders and Stroke for the randomisation phase and Vital Projects Fund for the follow-up phase.

Background Anecdotal cases of exophthalmos after acute mechanical thrombectomy have been described. We sought to estimate the incidence in a large cohort of patients with acute anterior circulation stroke treated with mechanical thrombectomy. Secondarily, we aimed to evaluate the underlying mechanism and to differentiate it on imaging from other pathology with similar clinical orbital features. Methods Between November 2016 and November 2018, we performed a retrospective single-center study of 250 patients who underwent anterior circulation mechanical thrombectomy. Development of exophthalmos was independently evaluated by two readers on preprocedure and 24-h postprocedure non-contrast cerebral CT. Results In the mechanical thrombectomy cohort, six individuals (2.4%) developed interval ipsilateral exophthalmos at 24 h. Of these, at least two patients developed clinical symptoms. There was almost perfect agreement between assessments of the two readers (Cohen’s kappa = 0.907 (95% confidence interval: 0.726, 1.000)). In two patients, there was delayed ophthalmic artery filling on digital subtraction angiography. None of the patients had features of a direct carotid-cavernous fistula. Conclusions Exophthalmos is not uncommon after mechanical thrombectomy (2.4%). The underlying mechanism is difficult to confirm, but it is most likely due to orbital ischemia from hypoperfusion or distal emboli.

Introduction:The benefit of late window endovascular treatment (EVT) for anterior circulation ischemic stroke has been demonstrated using perfusion-based neuroimaging. We evaluated whether non-contrast CT (NCCT) and CT-angiogram (CTA) alone can select late-presenting patients for EVT.Methods:We performed a retrospective comparison of all patients undergoing EVT at a single comprehensive stroke center from January 2016 to April 2017. Patients planned for EVT were divided into early (Results:During the study period, 204 (82%) patients underwent EVT in the early and 44 (18%) in the late window. Median (interquartile range) NIH Stroke Scale Score was similar between groups (early: 18 [15–23] vs. late: 17 [13–21]), as were median ASPECT scores (early: 9 [8–10] vs. late: 9 [7–9]). In the late window, 42 (95%) strokes were of unknown onset. Similar proportions of sHT occurred at 24 hours (early: 12 [6%] vs. late: 4 [9%], p = 0.43). At 3 months, the proportion of patients achieving functional independence (mRS 0–2) were comparable in the early (80/192 [42%]) and late (16/41 [39%]) windows (p = 0.76).Conclusion:NCCT- and CTA-based patient selection led to similar functional independence outcomes and low proportions of sHT in the early and late windows. In centers without access to perfusion-based neuroimaging, this pragmatic approach could be safe, particularly for strokes of unknown onset.

OBJECTIVEThe management of brain arteriovenous malformations (bAVMs) remains controversial. The Treatment of Brain AVMs Study (TOBAS) was designed to manage patients with bAVMs within a clinical research framework. The objective of this study was to study trial feasibility, recruitment rates, patient allocation to the various management groups, and compliance with treatment allocation.METHODSTOBAS combines two randomized care trials (RCTs) and a registry. Designed to be all-inclusive, the study offers randomized allocation of interventional versus conservative management to patients eligible for both options (first RCT), a second RCT testing the role of preembolization as an adjunct to surgery or radiotherapy, and a registry of patients managed using clinical judgment alone. The primary outcome of the first RCT is death from any cause or disabling stroke (modified Rankin Scale score > 2) at 10 years. A pilot phase was initiated at one center to test study feasibility, record the number and characteristics of patients enrolled in the RCTs, and estimate the frequency of crossovers.RESULTSAll patients discussed at the multidisciplinary bAVM committee between June 2014 and June 2016 (n = 107) were recruited into the study; 46 in the randomized trials (23 in the first RCT with 21 unruptured bAVMs, 40 in the second RCT with 17 unruptured bAVMs, and 17 in both RCTs), and 61 patients in the registry. Three patients crossed over from surgery to observation (first RCT).CONCLUSIONSClinical research was successfully integrated with normal practice using TOBAS. Recruitment rates in a single center are encouraging. Whether the trial will provide meaningful results depends on the recruitment of a sufficient number of participating centers.Clinical trial registration no.: NCT02098252 (clinicaltrials.gov)

A 52-year-old right-handed woman presented with acute-onset global aphasia, right hemiparesis, and decreased level of consciousness (NIHSS [National Institutes of Health Stroke Score] 20), developing immediately after elective percutaneous coronary intervention using a 3.0/20-mm cutting balloon ([

Prehospital identification of large vessel occlusion (LVO) stroke may expedite treatment by direct transport to comprehensive stroke centers (CSCs) with endovascular capabilities. The Cincinnati Prehospital Stroke Scale (CPSS) is commonly used for prehospital stroke detection. We aimed to assess whether (1) a high CPSS score can identify LVO and (2) an Emergency Medical Service (EMS) redirection protocol based on high CPSS accelerated endovascular treatment (EVT).A retrospective comparison of patients transported by EMSs for suspected stroke to a high-volume CSC over a 16-month period, before and after implementation of an EMS redirection protocol based on high CPSS score (3/3). Charts were reviewed to determine the presence of LVO. Time to EVT and 3-month outcomes were compared before and after implementation.A prehospital CPSS 3/3 score was found in 223 (59%) patients, demonstrating positive and negative predictive values for LVO of 29% and 94%, respectively. CPSS-based EMS redirection increased the proportion of EVT performed after direct transport to CSC [before: 21 (36%), after: 45 (63%), p0.01] and decreased median first door-to-groin puncture time by 28 minutes [109 (interquartile range (IQR) 64-116) versus 81 (IQR 56-130), p = 0.03]. At 3 months, the proportion of patients achieving functional independence (modified Rankin score 0-2) went from 20/57 (35%) to 29/68 (43%) (p = 0.39) following implementation.CPSS-based EMS redirection accelerated identification of LVO strokes in the out-of-hospital setting and decreased time to EVT. Nevertheless, this protocol was also associated with high rates of non-LVO stroke. Impact on clinical outcomes should be evaluated in a larger cohort.Utilité de l'échelle de Cincinnati pour la redirection des occlusions artérielles cérébrales proximales par les services médicaux d'urgence. Introduction : Dans un contexte pré-hospitalier, le fait de pouvoir identifier l’occlusion de vaisseaux sanguins cérébraux proximaux peut accélérer l’amorce d’un traitement en favorisant un transfert direct vers un centre complet de prise en charge des AVC (comprehensive stroke centers) doté de moyens d’intervention endovasculaire. L’échelle de Cincinnati (Cincinnati Prehospital Stroke Scale ou CPSS) est couramment utilisée afin de détecter les signes d’un AVC dans un contexte pré-hospitalier. Notre intention est double ici : 1) évaluer dans quelle mesure un score élevé à la CPSS peut permettre d’identifier l’occlusion de vaisseaux sanguins cérébraux proximaux ; 2) évaluer dans quelle mesure un protocole des services médicaux d’urgence consistant à rediriger des patients en fonction d’un score élevé à la CPSS a permis d’accélérer l’offre d’un traitement endovasculaire. Méthodes : Au cours d’une période de 16 mois, soit avant et après la mise sur pied de ce protocole en fonction d’un score élevé à la CPSS (3/3), nous avons effectué une comparaison rétrospective des dossiers de patients transportés vers des centres complets de prise en charge des AVC en raison de soupçons d’AVC. Ces dossiers ont été analysés afin de pouvoir identifier les cas d’occlusion proximales. Enfin, les délais permettant d’obtenir un traitement endovasculaire et l’évolution de l’état de santé des patients au bout de 3 mois ont été comparés avant et après la mise sur pied de ce protocole. Résultats : En fonction d'un score de 3/3 à la CPSS obtenu en contexte pré-hospitalier a été observé chez 223 patients (59 %), la valeur prédictive positive et négative pour des cas d’occlusion de vaisseaux sanguins cérébraux proximaux étant respectivement de 29 % et de 94 %. Le fait que les services médicaux d’urgence redirigent des patients en fonction d’un certain score à la CPSS a fini par augmenter le nombre de traitements endovasculaires prodigués à la suite d’un transfert direct vers un centre complet de prise en charge des AVC (avant le protocole : 21 (36 %) ; après le protocole : 45 (63 %) ; p0,01) et par diminuer de 28 minutes les délais entre la prise en charge à l’arrivée et la ponction artérielle (109 [intervalle interquartile de 64-116] contre 81 [intervalle interquartile de 56-130] ; p = 0,03). Au bout de 3 mois, à la suite de la mise sur pied du protocole, la proportion de patients autonomes sur le plan fonctionnel (échelle de Rankin modifiée : 0-2) est passée de 20/57 (35 %) à 29/68 (43 %) (p = 0,39). Conclusion : Le fait de rediriger des patients en fonction d’un certain score à la CPSS a permis d’accélérer la détection de cas d’AVC survenus à la suite de l’occlusion de vaisseaux sanguins cérébraux proximaux et donc de réduire les temps d’intervention. Cela dit, ce protocole a aussi été associé à un taux élevé de détection d’AVC non produits par l’occlusion de vaisseaux sanguins cérébraux proximaux. L’impact de cette constatation en ce qui regarde l’évolution de l’état de santé des patients devrait être évalué dans une plus vaste cohorte.

Background and purpose The optimal management of patients with tandem lesions (TL), or cervical internal carotid artery (c-ICA) steno-occlusive pathology and ipsilateral intracranial occlusion, who are undergoing endovascular thrombectomy (EVT) remains unknown. We sought to establish the feasibility of a trial designed to address this question. Materials and methods The Endovascular Acute Stroke Intervention (EASI) study was a single-centre randomized trial comparing EVT to medical therapy for large-vessel occlusion stroke. Patients with TL receiving EVT were randomly allocated to acute c-ICA stenting or no stenting. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0–2 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) at 24 hours and mortality at 90 days. Results Of 301 patients included in EASI between 2013 and 2018, 24 (8.0%) with TL were randomly allocated to acute stenting (n = 13) or no stenting (n = 11). Baseline characteristics were balanced. Eight (61.5%; 95% CI 35.5%–82.3%) and 7 (63.6%; 95% CI 35.4%–84.9%) patients, respectively, had a favorable outcome (mRS 0–2; P = 1.0). One non-stented patient had a symptomatic intracerebral hemorrhage. Conclusions This pilot trial of patients with TL undergoing EVT suggests that a sufficiently powered larger TL trial comparing acute c-ICA stenting to no stenting is feasible. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02157532 .

Background and Purpose— In patients with acute stroke caused by tandem occlusion, the benefit of immediate revascularization (stenting) of the cervical internal carotid artery lesion during endovascular thrombectomy is uncertain. We sought to determine current practice patterns and whether consensus existed among physicians with stroke expertise. Methods— We distributed an online survey to stroke experts affiliated with the Canadian Stroke Consortium, the Canadian Interventional Neuro Group, the Society of Vascular and Interventional Neurology, and international ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) collaborators. Questions were based on clinical scenarios, and multiple choice responses across a Likert-type scale were provided. The survey was sent out in September 2017. After 2 months, data were extracted and then analyzed using descriptive statistics. Results— Responses from 162 stroke experts were analyzed; most were stroke physicians (n=65, 40.1%) and neurointerventionalists (n=74, 45.7%), from Canada (n=95, 58.6%), the United States (n=42, 25.9%), and other countries (n=25, 15.4%). Over half (n=96, 59.3%) of respondents consider acute stenting of the cervical internal carotid artery as a treatment option, whereas 40.7% (n=66) would never use it. Most respondents (n=113, 69.8%) agree that there exists uncertainty about the optimal acute management of patients with tandem occlusion. A majority (n=88, 54.3%) of physicians surveyed would include patients in a randomized trial addressing this question. Conclusions— This survey shows high variability in practice about acute management of tandem occlusion. The existence of community equipoise underscores the importance of a randomized trial evaluating the benefit of acute internal carotid artery stenting in patients with tandem occlusion undergoing endovascular thrombectomy.

Introduction: Accurately balancing risks of interventional treatment and intracranial hemorrhage (ICH) in the untreated course of unruptured brain arteriovenous malformation (uBAVM) patients is critical for optimal management. Observational studies of uBAVM afford an opportunity to address important gaps and previous criticisms of randomized data to help guide treatment decisions and assess long-term risk/benefit ratio. We previously published an individual patient data meta-analysis (IPDMA) in 4 MARS cohorts and identified ICH presentation and increasing age as significant predictors of ICH during follow-up, but was not powered to detect predictors in those with uBAVM. Thus, the goals of this project are to identify risk factors for ICH in uBAVMs, to estimate the risk with precision, and to create personalized, risk-prediction models. Methods: MARS is an international, multi-center study of 11 cohorts with target enrollment of 4,500 uBAVM patients ascertained through population-based or referral-based studies. We are harmonizing both retrospective and prospective data, including clinical, lifestyle, imaging, and angiographic factors. Treatments, complications, and functional outcomes (physician and patient-reported) will be updated annually between 2018-2022. We propose to: 1) identify predictors of outcome in uBAVMs using IPDMA; 2) test whether long-term outcomes differ by treatment using statistical approaches for causal inference and unbiased estimates; 3) compare treatment outcomes in randomized and non-randomized data to address generalizability; and 4) validate models and provide a novel tool for calculating individualized risks. Eligible sites have: a) prior BAVM publications; b) data from a minimum of 100 uBAVM patients; c) agree to random outcome adjudication; and d) agree to MARS data sharing policy. Discussion: The NIH-funded MARS consortium will provide important and comprehensive characterization of the untreated and treated course of uBAVMs, using large observational datasets and sophisticated epidemiological approaches. The data and models generated will be a useful resource for decision-making. We welcome participation from eligible sites with longitudinal data on uBAVM patients

Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Antithrombotic agents increase risks of intracerebral haemorrhage (ICH) and associated adverse outcomes. We determined differential effects of early blood pressure (BP) lowering in patients with/without antithrombotic-associated ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT1 and 2).Post hoc pooled analyses of the INTERACT studies-international, multicentre, prospective, open, blinded end point trials of patients with ICH (6 h) and elevated systolic BP (SBP 150-180 mm Hg) randomly assigned to intensive (target SBP140 mm Hg) or guideline-based (SBP180 mm Hg) BP management. Associations of antithrombotic use and (1) death or dependency (modified Rankin scale scores 3-6) were analysed using logistic regression, and (2) of increased haematoma+intraventricular haemorrhage volume (IVH) with/without intraventricular haemorrhage (IVH) over 24 h were estimated in analyses of covariance.In all, 3184 patients were included in these analyses. Antithrombotic-associated ICH (364 patients, 11%) was not associated with a significantly increased risk of death or dependency (OR 1.38, 95% CI 0.93 to 2.04). There was no heterogeneity in the BP-lowering treatment effect on death or dependency. Among 1309 patients who underwent follow-up CT after 24 h, absolute increase in haematoma±IVH volume was larger (5.2/5.0 mL) in those with compared to those without prior antithrombotics (2.2/0.9 mL; p=0.022/0.031). Intensive BP lowering reduced haematoma±IVH growth by 4.7/7.1 mL in patients on antithrombotics versus 1.3/1.4 mL in those without, although these differences did not reach statistical significance (p homogeneity=0.104/0.059).In patients with ICH, prior antithrombotic therapy is associated with greater haematoma growth, which may be reduced by early intensive BP-lowering treatment.NCT00226096, NCT00716079.

Background Indication and timing of pharmacological venous thromboembolism prophylaxis in intracerebral hemorrhage patients is controversial. Aims To determine whether use of subcutaneous heparin during the first 7 days after spontaneous intracerebral hemorrhage increases risks of death and disability. Methods Data are from the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) study. Patients with acute intracerebral hemorrhage (Results In 2525 patients with available data, there were 465 (22.5%) who received subcutaneous heparin. They had higher death or major disability at 90 days in crude (odds ratio 2.29, 95% confidence interval 1.85–2.84; p Conclusions Use of subcutaneous heparin is associated with poor outcome in acute intracerebral hemorrhage, driven by increased residual disability. Despite the limitations of this study, and no clear relation of heparin with bleeding risk, we recommend careful consideration of the need for venous thromboembolism prophylaxis with heparin in intracerebral hemorrhage patients. Trial registration http://www.clinicaltrials.gov NCT00716079.

Background and Purpose— The significance of structural changes associated with cerebral small-vessel disease (SVD), including white matter lesions (WML), lacunes, and brain atrophy, to outcome from acute intracerebral hemorrhage is uncertain. We determined associations of computed tomographic radiological manifestations of cerebral SVD and outcomes, and in terms of any differential effect of early intensive blood pressure–lowering treatment, in the large-scale Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods— We graded WML (van Swieten scale), the presence of lacunes, and brain atrophy (2 linear measurements and visual rating) for 2069 of 2839 patients with available baseline brain computed tomography ( Results— WML grade and 2 linear measurements of brain atrophy were associated with death or major disability at 90 days: multivariable-adjusted odds ratios for WML (grade 3 and 4 versus 0), frontal ratio, and third ventricle Sylvian fissure distance (most versus least severe atrophy quartile) were 1.42 (95% confidence interval, 1.02–1.98), 1.47 (1.08–1.99), and 1.64 (1.21–2.22), respectively (all P for trend Conclusions— Preexisting cerebral SVD manifestations of WML and brain atrophy predict poor outcome in acute intracerebral hemorrhage. There is no apparent hazard of early intensive lowering of blood pressure according to the INTERACT2 protocol, in patients with underlying cerebral SVD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Background: Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis.Methods: We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis.Findings: Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7–17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2–9·7) and with brainstem CCM location versus other locations (4·4, 2·3–8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1–5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1–15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3–23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3–35·2) for 495 people with brainstem CCM presenting with ICH or FND.Interpretation: Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment.Funding: UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.

Introduction: Endovascular therapy(EVT) is proven effective for patients with acute ischemic stroke with proximal vessel occlusion, treated within 6 hours since symptom onset. However, up to 30% of stroke patients wake up with their symptoms (“wake-up stroke” (WUS)) or have an unknown time of onset. Canadian guidelines suggest that EVT may also be effective up to 12 hours after onset and yet-to-be published data from the DAWN trial also suggest a strong benefit of EVT for these patients if selected by perfusion imaging. We aimed to examine the real-world effectiveness of EVT in late-presenting stroke patients selected for EVT with a simple non-contrast CT (NCCT) and simple phase CT angiogram (CTA). Methods: We analyzed a prospectively collected registry of epidemiological, clinical and imaging data of patients treated for acute ischemic stroke ≥6 hours since symptom onset or WUS in a tertiary stroke center (Hôpital Notre-Dame, Montréal) between 2016 and 2017. Eligibility for EVT was based on a combination of disabling neurological deficit, a NCCT with salvageable brain tissue (ASPECTS >5), and presence of a LVO on CTA. Results: Over a 16-month period, a total of 366 patients were treated with IV thrombolysis and/or EVT. Of these, 46 had WUS or presented ≥ 6 hours since symptom onset and received EVT. Median age was 70, median baseline mRS score 1, median NIHSS at arrival 17 and median ASPECTS 9. Good collaterals on CTA were noted in 63%(29) of patients. 5 patients had posterior circulation stroke with basilar occlusion. Median time from last time seen normal to admission was 9h17(IQR, 6h44-12h46). 31 (67.4%) NCCTs were done at a referent center and not repeated locally to avoid treatment delays. At 3-month follow-up, functional autonomy(mRS ≤ 2) was found in 15 (32.6%) patients while 15 (32,6%) died (mRS=6). Symptomatic hemorrhagic transformation occurred in 3(6.5%) patients. Conclusions: In a real-world setting, EVT is feasible in late-presenting stroke patients selected by NCCT and yields favorable outcomes similar to those seen in the more pragmatic EVT trials.

Introduction One of the aims of the European Stroke Organisation (ESO) is to facilitate academic, multinational clinical stroke research. However, despite examples of successful regional and national stroke research networks and collaborative groups, there is no organisational structure at a European level that can facilitate multinational clinical stroke research. Materials and methods In a project including a survey and a workshop and involving stroke researchers in the ESO, we sought to identify the challenges faced by existing clinical stroke research networks, to define the purpose and roles of any future European stroke research collaboration, and to propose an organisational structure. Results The survey and workshop gave strong support for an alliance model with independent network members, with the purpose of facilitating clinical stroke research through improved coordination and communication, provision of support, education, and advocacy and communication with other stakeholders. The focus of a proposed European clinical stroke research alliance should be multinational randomised-controlled trials in acute care, prevention and rehabilitation, but the alliance could also support other forms of multi-national clinical stroke research. Conclusion There is an interest for increased collaboration on multinational clinical stroke research in Europe, in the form of an alliance of independent research networks and collaborative groups. The ESO Trials Network Committee will continue consultation with existing stroke research networks and collaborative groups, and other key stakeholders, to assess the feasibility and support for development of an ESO Trials Alliance.

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.

Background and Purpose— Mannitol is often used to reduce cerebral edema in acute intracerebral hemorrhage but without strong supporting evidence of benefit. We aimed to determine the impact of mannitol on outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods— INTERACT2 was an international, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage ( Results— There was no significant difference in poor outcome between mannitol (n=1533) and nonmannitol (n=993) groups: propensity score–matched odds ratio of 0.90 (95% confidence interval, 0.75–1.09; P =0.30) and multivariable odds ratio of 0.87 (95% confidence interval, 0.71–1.07; P =0.18). Although a better outcome was suggested in patients with larger (≥15 mL) than those with smaller (P homogeneity Conclusions— Mannitol seems safe but might not improve outcome in patients with acute intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Background Several simple clinical grading scores have been developed for intracerebral hemorrhage, primarily to predict 30-day mortality. Aims We aimed to determine the accuracy of three popular scores (original intracerebral hemorrhage, modified intracerebral hemorrhage, and intracerebral hemorrhage grading scale) on 30-day mortality and 90-day death or major disability, and whether the magnitude of benefit varies according to prognosis graded by the three predictive scores. Methods Data from the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial which included 2839 intracerebral hemorrhage patients (Results Among 2556 (90%) participants with available data, the modified intracerebral hemorrhage had the highest discrimination (receiver operator characteristic 0·75) for 90-day poor outcome compared with the original intracerebral hemorrhage (receiver operator characteristic 0·68) and intracerebral hemorrhage grading scale (receiver operator characteristic 0·69). All scores had good positive predictive value (approximately 80–90%) for poor outcome but poor sensitivity and positive predictive value for death. The scores do not clearly discriminate a patient group most likely to benefit from blood pressure lowering. Conclusions Intracerebral hemorrhage prognostic scores are not useful in defining patients at high probability of early death, but they are reliable for predicting poor outcome, defined by death or major disability. Potential benefits of early intensive blood pressure lowering are broadly applicable across grades of severity defined by such scores.

Background and Purpose— We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) to better inform clinicians and researchers in their efforts to improve outcomes for patients. Methods— We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and 2, respectively). The study group was divided into a derivation cohort (INTERACT2, n=964) and a validation cohort (INTERACT1, n=346). Multivariable logistic regression was used to identify factors associated with clinically significant (≥6 mL) increase in hematoma volume at 24 hours after symptom onset. A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model. Results— A 24-point BRAIN score was derived from INTERACT2 (C-statistic, 0.73) based on baseline ICH volume (mL per score, ≤10=0, 10–20=5, >20=7), recurrent ICH (yes=4), anticoagulation with warfarin at symptom onset (yes=6), intraventricular extension (yes=2), and number of hours to baseline computed tomography from symptom onset (≤1=5, 1–2=4, 2–3=3, 3–4=2, 4–5=1, >5=0) predicted the probability of ICH growth (ranging from 3.4% for 0 point to 85.8% for 24 points) with good discrimination (C-statistic, 0.73) and calibration (Hosmer–Lemeshow P =0.82) in INTERACT1. Conclusions— The simple BRAIN score predicts the probability of hematoma growth in ICH. This could be used to improve risk stratification for research and clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00226096 and NCT00716079.

Item does not contain fulltext OBJECTIVES: To investigate the effects of intensive blood pressure (BP) lowering according to baseline BP levels and optimal achieved BP levels in patients with acute intracerebral hemorrhage (ICH). METHODS: INTERACT2 was an open, blinded endpoint, randomized controlled trial in 2,839 patients with ICH within 6 hours of onset and elevated systolic BP (SBP) (150-220 mm Hg) who were allocated to receive intensive (target SBP /=190 mm Hg (p homogeneity = 0.790). Analyses of achieved BP showed linear increases in the risk of physical dysfunction for achieved SBP above 130 mm Hg for both hyperacute (1-24 hours) and acute (2-7 days) phases while modest increases were also observed for achieved SBP below 130 mm Hg. CONCLUSIONS: Intensive BP lowering appears beneficial across a wide range of baseline SBP levels, and target SBP level of 130-139 mm Hg is likely to provide maximum benefit in acute ICH. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the effect of intensive BP lowering on physical function is not influenced by baseline BP.

Background and Purpose— Degree and timing of blood pressure (BP) lowering treatment in relation to hematoma growth were investigated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 (INTERACT2). Methods— INTERACT2 was an international clinical trial of intensive (target systolic BP [SBP], Results— Greater SBP reduction was associated with reduced hematoma growth (13.3, 5.0, and 3.0 mL for P trend6 hours (5.4 mL). The smallest mean absolute hematoma growth (2.0 mL) was in those achieving target SBP 5 to 8 times versus 3 to 4 (3.1 mL) and 0 to 2 times (5.2 mL). Conclusions— Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

We read with great interest the Controversies in Stroke article, “Emergent Carotid Stenting After Thrombectomy in Patients With Tandem Lesions,” about emergent stenting after thrombectomy in patients with tandem lesions by Behme et al.1 Drs Behme and Ribo provide very cogent and well-defended arguments supporting, respectively, an emergent stenting approach and a delayed carotid intervention strategy. In our view, the optimal treatment in patients with tandem lesions remains unknown and is largely driven by individual physician preference and local institutional routine rather than by evidence from high-quality clinical data. It should be noted that in the HERMES meta-analysis (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials), only 122 patients (about 10% of the total study population) had tandem lesions (such patients were excluded from SWIFT-PRIME [Solitaire™ With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke] and EXTEND-IA …

Objective:To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA).Methods:We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ≥2. ARUBA closed recruitment on April 15, 2013.Results:After a median of 33.3 months of follow-up (interquartile range 16.3–49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ≥2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11–0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04–0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT (p < 0.001).Conclusion:Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades.ClinicalTrials.gov identifier:NCT00389181.Classification of evidence:This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ≈3 years.

Objective: To clarify associations between intracerebral hemorrhage (ICH) location and clinical outcomes among participants of the main phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). \ud Methods: Associations between ICH sites and poor outcomes (death [6] or major disability [3–5] of modified Rankin Scale) and European Quality of Life Scale (EQ-5D) utility scores at 90 days were assessed in logistic regression models. \ud Results: Of 2,066 patients included in the analyses, associations were identified between ICH sites and poor outcomes: involvement of posterior limb of internal capsule increased risks of death or major disability (odds ratio [OR] 2.10) and disability (OR 1.81); thalamic involvement increased risks of death or major disability (OR 2.24) and death (OR 1.97). Involvement of the posterior limb of the internal capsule, thalamus, and infratentorial sites were each associated with poor EQ-5D utility score (≤0.7 [median]; OR 1.87, 2.14, and 2.81, respectively). Posterior limb of internal capsule involvement was strongly associated with low scores across all health-related quality of life domains. ICH encompassing the thalamus and posterior limb of internal capsule were associated with death or major disability, major disability, and poor EQ-5D utility score (OR 1.72, 2.26, and 1.71, respectively). \ud Conclusion: Poor clinical outcomes are related to ICH affecting the posterior limb of internal capsule, thalamus, and infratentorial sites. The highest association with death or major disability and poor EQ-5D utility score was seen in ICH encompassing the thalamus and posterior limb of internal capsule. \ud ClinicalTrials.gov registration: NCT00716079.

Stroke is a major burden to patients and society, and resources spent on stroke research must be used efficiently and produce good value in terms of improvements in human health. However, many instances of poor value from stroke research funding have resulted from the way in which stroke research topics have been chosen and how studies have been designed, conducted, analysed, regulated, managed, disseminated, or reported. A cooperative effort of European stroke researchers aimed to identify sources of inefficiency and waste, recommend approaches to increase value, and highlight examples of best practice in stroke research. Evidence suggests that progress has been made, but there is room for much improvement; researchers, funders, regulators, and other stakeholders in stroke research might consider these recommendations when planning new research.

Background: Stroke affects one in six people throughout their lifetimes and is the most frequent cause of disability in adults. Several recanalization therapies have emerged and the management of patients in stroke units has improved over the last decades. Summary: This article examines the current treatment options for stroke patients, summarizing the key clinical evidence, as well as listing the complications and practical issues related to each of these main treatment options. Key Messages: Recent advances in the treatment of acute stroke include developments in intravenous thrombolysis (IVT), intra-arterial treatment and bridging therapies. Clinical Implications: Treatment within a stroke unit reduces mortality and disability regardless of age, sex and stroke severity. IVT is widely available and reduces disability when initiated within 4.5 h after the onset of symptoms. The major limitations of IVT are the low recanalization rates and the narrow time frame. Intra-arterial treatment, especially when using newly developed stent-retrievers, achieves very high recanalization rates. It is restricted by its limited availability and by the longer time span required to initiate therapy. Bridging both therapies is a promising approach that combines the advantages of both therapies, but the superiority of this approach remains to be proven. Future strategies to reduce the burden of acute stroke in Europe should focus on immediate access to acute stroke care and dedicated stroke units for all patients. i 2014 S. Karger AG, Basel

RESUME Parmi les differents types d’accidents vasculaires cerebraux, l’hemorragie cerebrale constitue l’une des formes les plus graves. Pourtant, la prise en charge des patients en phase aigue de l’hemorragie se heurte toujours a plusieurs obstacles : (1) Il n’existe actuellement aucune classification systematique des hemorragies cerebrales. (2) La strategie du bilan diagnostique en phase aigue de l’hemorragie n’a pas encore ete standardisee. (3) Nos moyens d’intervention therapeutique restent limites. (4) Pour certaines pathologies neurovasculaires a risque hemorragique (anevrismes, malformations arterioveineuses, cavernomes cerebraux), le benefice d’une intervention preventive prealablement a tout signe de rupture reste parfois incertain. L’evolution recente vers une classification etiologique, la mise en place d’un bilan etiologique standardise, ainsi que les grandes lignes des nouvelles strategies therapeutiques — dont l’abaissement rapide de la pression arterielle en phase aigue de l’hemorragie cerebrale — seront illustres dans le cadre de cette presentation.

Contexte et objectifs Des cas anecdotiques d’exophtalmie apres thrombectomie mecanique aigue (MT) ont ete decrits. Avec cette etude, nous avons cherche a estimer l’incidence dans une large cohorte de patients ayant subi un AVC aigu de la circulation anterieure traite par MT. Deuxiemement, nous avons cherche a evaluer le mecanisme sous-jacent a ce phenomene. Methodes Nous avons effectue une etude retrospective monocentrique de 250 patients ayant eu une MT en circulation anterieure, compares a 250 patients avec enroulement anevrismal ayant servi de temoins. Le developpement de la proptose et du diametre du muscle extra-oculaire a ete evalue de maniere independante sur une tomodensitometrie cerebrale sans contraste effectuee avant et apres 24 heures. Resultats Dans la cohorte MT, six individus (2,4%) ont developpe une proptose ipsilaterale a 24 heures d’intervalle associee a un epaississement associe a la MOE. Parmi ceux-ci, au moins deux patients ont developpe des symptomes cliniques. Dans le groupe temoin enroule d’anevrisme, il n’y avait pas d’individus positifs [difference de risque = 2,4% (intervalle de confiance a 95%: 0,5, 4,3); p = 0,0303. Conclusions L’exophtalmie n’est pas rare apres la MT et n’a pas ete retrouvee apres l’enroulement de l’anevrisme (2,4% vs 0%). Outre l’ischemie orbitale et la CCF directe, d’autres mecanismes, tels que la toxicite, restent a definir.

A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), the first randomized clinical trial for brain arteriovenous malformations (bAVMs), was planned as a straightforward simple attempt to learn whether deferring intervention for a bAVM that had not bled would prove superior to

Background and Purpose— To compare potential risk factors, clinical symptoms, diagnostic delay, and 3-month outcome between spontaneous internal carotid artery dissection (sICAD) and spontaneous vertebral artery dissection (sVAD). Methods— We compared patients with sICAD (n=668) and sVAD (n=302) treated in 3 university hospitals. Results— Patients with sICAD were older (46.3±9.6 versus 42.0±10.2 years; P P =0.004), and presented more frequently with tinnitus (10.9% versus 3.4%; P s of Health Stroke Scale, 10±7.1 versus 5±5.9; P P P =0.007). Thunderclap headache (9.2% versus 3.6%; P =0.001) and neck pain were more common (65.8% versus 33.5%; P P P P =0.21), and all other variables remained significant. Time to diagnosis was similar in sICAD and sVAD and improved between 2001 and 2012 compared with the previous 10-year period (8.0±10.5 days versus 10.7±13.2 days; P =0.004). In sVAD, favorable outcome 3 months after ischemic stroke (modified Rankin Scale, 0–2: 88.8% versus 58.4%; P P =0.001), and recurrent ischemic stroke (2.8% versus 0.7%; P =0.02) within 3 months were more frequent. Conclusions— sICAD and sVAD patients differ in many aspects. Future studies should perform separate analyses of these 2 entities.

Resume Le centre de reference CERVCO est implique dans la prise en charge de differentes maladies vasculaires rares du cerveau et de la retine. Les progres observes au cours des dernieres annees sont variables en fonction des pathologies concernees. Le centre de reference est largement implique dans de multiples activites de recherche qui ont permis au cours des 5 dernieres annees d’ameliorer le diagnostic et la prise en charge de ces affections. Les enjeux pour l’avenir varient pour chacune d’entre elles. Le centre de reference aura besoin d’outils d’evaluation simplifies, d’une reconnaissance officielle d’un reseau de medecins « experts » et d’une adaptation des moyens techniques et humains pour atteindre les objectifs fixes.

BACKGROUND: in the second Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2), a minority of patients received withdrawal of active treatment (WAT). We wished to determine the characteristics of these patients, and the relation of this decision-making to subsequent management and final outcome. METHODS: the INTERACT2 cohort of acute intracerebral haemorrhage (ICH) patients had a decision of WAT within 7 days after hospital admission recorded. Multivariable logistic regression was used to identify the determinants of WAT and poor outcome at 90 days, defined by modified Rankin scale (mRS) scores 3–6. RESULTS: of 2,779 participants with available data, WAT occurred in 121 (4%) and this was significantly associated with increasing age, greater neurological severity, larger haematoma volume, intraventricular extension and randomisation to intensive BP lowering. Compared to other patients, those with WAT had greater mortality (81/121 [67%] versus 205/2624 [8%]; P < 0.001) and survivors were more likely to be severely disabled (mRS score 4–5, 19/39 [49%] versus 695/2419 [29%]; P = 0.006). CONCLUSIONS: WAT was undertaken in patients with recognised predictors of poor prognosis, who subsequently were more likely to die or be left with severe disability. Improved understanding of specific factors determining WAT in ICH patients might improve care delivery and outcomes. CLINICAL TRIAL REGISTRATION: the INTERACT2 study is registered with ClinicalTrials.gov (NCT00716079).

Background and purpose: Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). Methods: The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (Results: 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were: age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension, and use of proxy-responders. High (≥14) NIHSS score, larger ICH and proxy-responders were associated with low scores in all five dimensions of the EQ-5D. NIHSS score had a strong association with poor HRQoL (pConclusions: Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity, and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score.