Purpose. - We aimed to assess agreement on intravenous tissue-plasminogen activator (IV tPA) and mechanical thrombectomy (MT) management decisions in acute ischemic stroke (AIS) patients. Secondary objectives were to assess agreement on Diffusion-Weighted-Imaging-Alberta-Stroke-Program-EArly-CT-Score (DWI-ASPECTS), and clinicians' willingness to recruit patients in a randomized controlled trial (RCT) comparing medical management with or without MT. Materials and Methods. - Studies assessing agreement of IV tPA and MT were systematically reviewed. An electronic portfolio of 41 AIS patients was sent to randomly selected providers at French stroke centers. Raters were asked 4 questions for each case: (1) What is the DWI-ASPECTS? (2) Would you perform IV tPA? (3) Would you perform MT? (4) Would you include the patient in a RCT comparing standard medical therapy with or without MT? Twenty responders were randomly selected to study intrarater agreement. Agreement was assessed using Fleiss' Kappa statistics. Results. - The review yielded two single center studies involving 2-5 raters, with various results. The electronic survey was answered by 86 physicians (60 vascular neurologists and 26 interventional neuroradiologists). The interrater agreement was moderate for IV tPA treatment decisions (kappa = 0.565 [0.420-0.680]), but only fair for MT (kappa = 0.383 [0.289-0.491]) and for combined treatment decisions (kappa = 0.399 [0.320-0.486]). The intrarater agreement was at least substantial for the majority of raters. The interrater agreement for DWI-ASPECTS was fair (kappa = 0.325 [0.276-0.387]). Physicians were willing to include a mean of 14 +/- 9 patients (33.1% +/- 21.7%) in a RCT. Conclusion. - Disagreements regarding the use of IVtPA or MT in the management of AIS patients remain frequent. Further trials are needed to resolve the numerous areas of uncertainty. (C) 2019 Elsevier Masson SAS. All rights reserved.

Background and Purpose— Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods— Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel ...

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, p<0.0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1.53, 95% CI 1.14-2.04, p=0.0044). The risk of bias and variability between studies was assessed to be low. Interpretation 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.

The Extending the time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial using Tenecteplase (EXTEND-IA TNK) trial recently showed 2-fold higher early recanalization (ER) rate before mechanical thrombectomy (MT) following intravenous thrombolysis (IVT) with tenecteplase 0.25 mg/kg, as compared to alteplase 0.9 mg/kg. 1 However, most included patients were directly admitted to MT-capable centres ('mothership' paradigm), implying short IVT-to-MT delays.Tenecteplase may therefore be preferred in the mothership setting.Here, we assessed ER rate before MT following tenecteplase or alteplase in patients transferred for MT from a non-MT-capable centre ('drip-and-ship' paradigm), i.e., implying longer IVT-to-MT delays, currently the most frequent situation. 2nclusion criteria for the present retrospective study were (1) acute stroke with large vessel occlusion treated with IVT with tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg; and (2) ER evaluation ≤3 hours from IVT start on pre-MT first angiographic run or non-invasive vascular imaging.Tenecteplase patients were all from one large French non-MT-capable centre, which based on previous trials 3,4 and for practical convenience opted to use tenecteplase off-label before transfer for MT.Alteplase patients were from 23 other French non-MT-capable centres.ER

Background and Purpose—Whether all acute stroke patients with large vessel occlusion need to undergo intravenousthrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis earlyrecanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely,(3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence andpredictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design.Methods—Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership)or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonanceimaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no-ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude ofregression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort.Results—In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498),no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point scorederived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated inthe validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2*or computed tomography–based imaging) also showed good discriminative power and was similarly validated. Highestgrades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER.Conclusions—The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Bothprediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design.

analyses were by intent to treat. Results — We could analyze data for 103 of the 104 included patients (51 control and 52 experimental group; 64 males; median age overall 67 [interquartile range 59–77], 67 right hemispheric lesions, 80 ischemic lesions, National Institutes of Health Stroke Scale score ≥ 8 for 82%). Fugl–Meyer score increased over time ( P <0.0001), with no significant effect of treatment ( P =0.29) or interaction between treatment and time ( P =0.40). The median change in score between D90 and D0 was 27.5 (12–40) and 22.0 (12–56) for control and experimental groups ( P =0.69). Similar results were found for the secondary criteria. Conclusions — Very early after stroke, intensive exercises may not be efficient in improving motor control. This conclusion may apply to mainly severe stroke.

BACKGROUND GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available.OBJECTIVES This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1.METHODS During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients' baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics.RESULTS Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA(2)DS(2)-VASc [ Congestive heart failure, Hypertension, Age >= 75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score >= 2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment.CONCLUSIONS The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [ GLORIA-AF]; NCT01468701) (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Background: Advance announcement of forthcoming brain death has developed to enable intensivists and organ procurement organisation coordinators to more appropriately, and separately from each other, explain to relatives brain death and the subsequent post-mortem organ donation opportunity. Research aim: The aim was to assess how potentially involved healthcare professionals perceived ethical issues surrounding the strategy of advance approach. Research design: A multi-centre opinion survey using an anonymous self-administered questionnaire was conducted in the six-member hospitals of the publicly funded East of France regional organ and tissue procurement network called ‘Prélor’. Participants: The study population comprised 460 physicians and nurses in the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Units and the Emergency Departments. Ethical considerations: The project was approved by the board of the Lorraine University Diploma in Medical Ethics and the Prélor Network administrators. Main findings: A slight majority of 53.5% of respondents had previously participated in an advance relatives approach: 83% of the physicians and 42% of the nurses. A majority of healthcare professionals (68%) think that the main justification for advance relatives approach is the comprehensive care of the dying patient and the research of his or her most likely opinion (74%). The misunderstanding of the related issues by relatives is an obstacle for 47% of healthcare professionals and 51% think that the answer given by the relatives regarding the most likely opinion of the person regarding post-mortem organ donation really corresponds to the person opinion in only 50% of the cases or less. Conclusion: Time given by advance approach should be employed to help and enable relatives to authentically bear the values and interests of the potential donor in the post-mortem organ donation discussion. Nurses’ attendance of advance relatives approach seems necessary to enable them to optimally support the families facing death and post-mortem organ donation issues.

Background Intravenous thrombolysis with alteplase alone cannot reperfuse most large-artery strokes. We aimed to determine whether mechanical thrombectomy in addition to intravenous thrombolysis improves clinical outcome in patients with acute ischaemic stroke.Methods THRACE is a randomised controlled trial done in 26 centres in France. Patients aged 18-80 years with acute ischaemic stroke and proximal cerebral artery occlusion were randomly assigned to receive either intravenous thrombolysis alone (IVT group) or intravenous thrombolysis plus mechanical thrombectomy (IVTMT group). Intravenous thrombolysis (alteplase 0.9 mg/kg [maximum 90 mg], with an initial bolus of 10% of the total dose followed by infusion of the remaining dose over 60 min) had to be started within 4 h and thrombectomy within 5 h of symptom onset. Occlusions had to be confirmed by CT or magnetic resonance angiography. Randomisation was done centrally with a computer-generated sequential minimisation method and was stratified by centre. The primary outcome was the proportion of patients achieving functional independence at 3 months, defined by a score of 0-2 on the modified Rankin scale, assessed in the modified intention-to-treat population (ie, patients lost to follow-up and those with missing data were excluded). Safety outcomes were analysed in the per-protocol population (ie, all patients who did not follow the protocol of their randomisation group precisely were excluded from the analysis). THRACE is registered with ClinicalTrials.gov, NCT01062698.Findings Between June 1,2010, and Feb 22,2015,414 patients were randomly assigned to the IVT group (n=208) or the IVTMT group (n=204). Four patients (two in each group) lost to follow-up and six (four in the IVT group and two in the IVTMT group) with missing data were excluded. 85 (42%) of 202 patients in the IVT group and 106 (53%) of 200 patients in the IVTMT group achieved functional independence at 3 months (odds ratio 1.55, 95% CI 1-05-2.30; p=0.028). The two groups had no significant differences in mortality at 3 months (24 [12%] deaths of 202 patients vs 27 [13%] of 206; p=0.70) or symptomatic intracranial haemorrhage at 24 h (four [2%] of 185 vs three [2%] of 192; p=0-71). Common adverse events related to thrombectomy were vasospasm (33 [23%] patients) and embolisation in a new territory (nine [6%]).Interpretation Mechanical thrombectomy combined with standard intravenous thrombolysis improves functional independence in patients with acute cerebral ischaemia, with no evidence of increased mortality. Bridging therapy should be considered for patients with large-vessel occlusions of the anterior circulation.

Thrace is a French randomized, multicenter, controlled trial on mechanical thrombectomy for large cerebral arteries acute occlusions. Primary objective was to determine whether a combined IVT/IAMT is superior to standard IV rTpa alone when initiated within 4h of acute ischemic stroke onset in adult patients with moderate-to-severe strokes (NIHSS>10) due to large artery occlusion. The primary outcome measure was the good clinical outcome (mRs 0-2) at 3 months. Complete data were analyzed for the 2 nd intermediate analysis using O’Brien and Fleming stopping rules. Results: 412 patients were included. For the second intermediate analysis, 395 patients were considered. Data were complete and monitored for 385 patients (195 IV/ 190 IV+IAMT). The mean age of our population was 62.5 years and the median NIHSS= 18. Occlusions were located on C1 in 57 (14,8%) and M1 in 326 cases (84,6%) At 3 months, the difference of good outcome between the two arms was significant according to the O’Brien-Fleming boundaries. Conclusion: After this intermediate analysis, THRACE was considered as positive and the Scientific Committee, following the DSMB advice, decided to stop the study. The final results will be presented.

Practitioners are faced with a substantial challenge when considering recombinant tissue plasminogen activator (rt‐PA) therapy for older patients with ischemic stroke. Patients aged over 80 years suffer from the most severe cerebral infarcts. The benefit of rt‐PA treatment compared with single standard care only in stroke units remains to be clearly assessed.

BACKGROUND AND PURPOSE:Providing non-therapeutic intensive care for some patients in hopeless condition after cerebrovascular stroke in order to protect their organs for possible post-mortem organ donation after brain death is an effective but ethically tricky strategy to increase organ grafting. Finding out the feelings and opinion of the involved healthcare professionals and assessing the training needs before implementing such a strategy is critical to avoid backlash even in a presumed consent system.PARTICIPANTS AND METHODS:A single-centre opinion survey of healthcare professionals was conducted in 2013 in the potentially involved wards of a French University Hospital: the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Unit and the Emergency Department. A questionnaire with multiple-choice questions and one open-ended question was made available in the different wards between February and May 2013.ETHICAL CONSIDERATIONS:The project was approved by the board of the Lorraine University Diploma in Medical Ethics.RESULTS:Of a total of 340 healthcare professionals, 51% filled the form. Only 21.8% received a specific education on brain death, and only 18% on potential donor's family approach and support. Most healthcare professionals (93%) think that non-therapeutic intensive care is the continuity of patient's care. But more than 75% of respondents think that the advance patient's consent and the consent of the family must be obtained despite the presumed consent rule regarding post-mortem organ donation in France.CONCLUSION:The acceptance by healthcare professionals of non-therapeutic intensive care for brain death organ donation seems fairly good, despite a suboptimal education regarding brain death, non-therapeutic intensive care and families' support. But they ask to require previously expressed patient's consent and family's approval. So, it seems that non-therapeutic intensive care should only remain an ethically sound mean of empowerment of organ donors and their families to make post-mortem donation happen as a full respect of individual autonomy.

BACKGROUND:Recommended treatments for spontaneous intracranial hypotension (SIH) range from bed rest only to neurosurgery. However, the serious form of SIH is poorly defined. A better description of patient characteristics and their outcome may help define therapeutic options.METHODS:We reviewed 24 cases of patients with SIH and separated them into 2 groups according to whether or not they presented with signs of severity at admission: disturbance of consciousness, subdural hematomas (SDHs), and cerebral venous thrombosis.RESULTS:Nine patients (37%) were classified as having a serious form of SIH: six (25%) presented SDHs; three (12%) disturbance of consciousness; and one (4%) cerebral venous thrombosis. Bed rest and epidural blood patches (EBPs) were sufficient to treat all patients in the nonserious form group and 4 patients in the serious form group. Two patients (8%) had to undergo cerebrospinal fluid leak repair, and 3 others (12%) evacuation of SDHs. Outcome was good in both groups, with only one (4%) death due to extensive SDHs. Times to diagnosis in the serious form group (63 vs. 35 days, P = 0.052) and to recovery (9 months vs. 5 months, P = 0.088) tended to be higher without reaching difference.CONCLUSIONS:The presence of SDHs, disturbance of consciousness, and a trend toward a longer time to diagnosis and recovery seem to define the serious form of SIH. These patients may require exploration and surgical repair of cerebrospinal fluid leak, only after failure of conservative measures--bed rest and time--and EBP, with good outcome.

Background and Purpose— We aimed at comparing the long-term benefit–risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis. Methods— Long-term follow-up study of patients included in Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S), a randomized, controlled trial of carotid stenting versus endarterectomy in 527 patients with recently symptomatic severe carotid stenosis, conducted in 30 centers in France. The main end point was a composite of any ipsilateral stroke after randomization or any procedural stroke or death. Results— During a median follow-up of 7.1 years (interquartile range, 5.1–8.8 years; maximum 12.4 years), the primary end point occurred in 30 patients in the stenting group compared with 18 patients in the endarterectomy group. Cumulative probabilities of this outcome were 11.0% (95% confidence interval, 7.9–15.2) versus 6.3% (4.0–9.8) in the endarterectomy group at the 5-year follow-up (hazard ratio, 1.85; 1.00–3.40; P =0.04) and 11.5% (8.2–15.9) versus 7.6% (4.9–11.8; hazard ratio, 1.70; 0.95–3.06; P =0.07) at the 10-year follow-up. No difference was observed between treatment groups in the rates of ipsilateral stroke beyond the procedural period, severe carotid restenosis (≥70%) or occlusion, death, myocardial infarction, and revascularization procedures. Conclusions— The long-term benefit–risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis favored endarterectomy, a difference driven by a lower risk of procedural stroke after endarterectomy. Both techniques were associated with low and similar long-term risks of recurrent ipsilateral stroke beyond the procedural period. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00190398.

Background: Cerebrovascular events in neuroborreliosis are a rare condition described only in isolated or small case series. No specific clinical or radiological features have been identified, and diagnosis is based on very different criteria. Methods: We retrospectively describe cases diagnosed in the Stroke Unit of Nancy Hospital, located in the endemic area of the northeast of France. We also reviewed other cases found in the literature. Results: We identified 5 cases in our center and 57 other reported cases. Mean age was 39 years (range 5 to 77). Possible previous contact with Borrelia burgdorferi (B burgdorferi) was found in about half of cases. Additional neurologic symptoms (headache, cognitive impairment, and/or gait disturbance) were found in 44% of cases. Cerebral imaging revealed both ischemic (87%) and hemorrhagic lesions (13%) with a multiterritorial aspect in 22% of strokes, and signs of vasculitis in 71%. Analysis of cerebrospinal fluid (CSF) revealed lymphocytic meningitis in 90% of cases and elevated protein level in 86%. CSF/serum anti-B burgdorferi antibody index (AI) was positive in 91% of cases. Outcome was favorable after appropriate antibiotic treatment. Our 5 patients presented a modified Rankin scale score 0-1, without any stroke recurrence, after a median follow-up of 2.8 years. Conclusions: The diagnosis of Lyme neuroborreliosis should be considered for patients with cerebrovascular events without obvious cause living in an endemic area, in the presence of repeat multiterritorial strokes at short intervals, other neurologic symptoms, a history of B burgdorferi infection, and radiological signs of vasculitis. Diagnosis can be confirmed by CSF analysis with AI but with an incomplete sensitivity. (C) 2015 by National Stroke Association