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Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Goyal Mayank,Menon Bijoy K,van Zwam Wim H,Dippel Diederik W J,Mitchell Peter J,Demchuk Andrew M,Dávalos Antoni,Majoie Charles B L M,van der Lugt Aad,de Miquel Maria A,Donnan Geoffrey A,Roos Yvo B W E M,Bonafe Alain,Jahan Reza,Diener Hans-Christoph,van den Berg Lucie A,Levy Elad I,Berkhemer Olvert A,Pereira Vitor M,Rempel Jeremy,Millán Mònica,Davis Stephen M,Roy Daniel,Thornton John,Román Luis San,Ribó Marc,Beumer Debbie,Stouch Bruce,Brown Scott,Campbell Bruce C V,van Oostenbrugge Robert J,Saver Jeffrey L,Hill Michael D,Jovin Tudor G, Lancet (London, England) BACKGROUND:In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. METHODS:We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. FINDINGS:We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. INTERPRETATION:Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. FUNDING:Medtronic. 10.1016/S0140-6736(16)00163-X
Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. Albers Gregory W,Marks Michael P,Kemp Stephanie,Christensen Soren,Tsai Jenny P,Ortega-Gutierrez Santiago,McTaggart Ryan A,Torbey Michel T,Kim-Tenser May,Leslie-Mazwi Thabele,Sarraj Amrou,Kasner Scott E,Ansari Sameer A,Yeatts Sharon D,Hamilton Scott,Mlynash Michael,Heit Jeremy J,Zaharchuk Greg,Kim Sun,Carrozzella Janice,Palesch Yuko Y,Demchuk Andrew M,Bammer Roland,Lavori Philip W,Broderick Joseph P,Lansberg Maarten G, The New England journal of medicine BACKGROUND:Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. METHODS:We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. RESULTS:The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18). CONCLUSIONS:Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .). 10.1056/NEJMoa1713973
Risk Factors for Acute Ischemic Stroke Caused by Anterior Large Vessel Occlusion. Hendrix Philipp,Sofoluke Nelson,Adams Matthew D,Kunaprayoon Saran,Zand Ramin,Kolinovsky Amy N,Person Thomas N,Gupta Mudit,Goren Oded,Schirmer Clemens M,Rost Natalia S,Faber James E,Griessenauer Christoph J Stroke Background and Purpose- Accurate prediction of acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) that is amendable to mechanical thrombectomy remains a challenge. We developed and validated a prediction model for anterior circulation LVO stroke using past medical history elements present on admission and neurological examination. Methods- We retrospectively reviewed AIS patients admitted between 2009 and 2017 to 3 hospitals within a large healthcare system in the United States. Patients with occlusions of the internal carotid artery or M1 or M2 segments of the middle cerebral artery were randomly split into 2/3 derivation and 1/3 validation cohorts for development of an anterior circulation LVO prediction model and score that was further curtailed for potential use in the prehospital setting. Results- A total of 1654 AIS were reviewed, including 248 (15%) with proximal anterior circulation LVO AIS. In the derivation cohort, National Institutes of Health Stroke Scale score at the time of cerebrovascular imaging, current smoking status, type 2 diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis was significantly associated with anterior circulation LVO stroke. The prehospital score was curtailed to National Institutes of Health Stroke Scale score, current smoking status, and type 2 diabetes mellitus. The areas under the curve for the prediction model, prehospital score, and National Institutes of Health Stroke Scale score alone were 0.796, 0.757, and 0.725 for the derivation cohort and 0.770, 0.689, and 0.665 for the validation cohort, respectively. The Youden index J was 0.46 for a score of >6 with 84.7% sensitivity and 62.0% specificity for the prediction model. Conclusions- Previously reported LVO stroke prediction scores focus solely on elements of the neurological examination. In addition to stroke severity, smoking, diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis were associated with anterior circulation LVO AIS. Although atherosclerotic stenosis may not be known until imaging is obtained, smoking and diabetes mellitus history can be readily obtained in the field and represent important elements of the prehospital score supplementing National Institutes of Health Stroke Scale score. 10.1161/STROKEAHA.118.023917
Mechanical Thrombectomy for Acute Ischemic Stroke: A Meta-Analysis of Randomized Trials. Elgendy Islam Y,Kumbhani Dharam J,Mahmoud Ahmed,Bhatt Deepak L,Bavry Anthony A Journal of the American College of Cardiology BACKGROUND:Acute ischemic stroke is a leading cause of serious disability and death worldwide. Individual randomized trials have shown possible benefits of mechanical thrombectomy after usual care compared with usual care alone (i.e., intravenous thrombolysis) in the management of acute ischemic stroke patients. OBJECTIVES:This study systematically determined if mechanical thrombectomy after usual care would be associated with better outcomes in patients with acute ischemic stroke caused by large artery occlusion. METHODS:The authors included randomized trials that compared mechanical thrombectomy after usual care versus usual care alone for acute ischemic stroke. Random effects summary risk ratios (RR) were constructed using a DerSimonian and Laird model. RESULTS:Nine trials with 2,410 patients were available for analysis. Compared with usual care alone, mechanical thrombectomy was associated with a higher incidence of achieving good functional outcome, defined as a modified Rankin scale (mRS) of 0 to 2 (RR: 1.45; 95% confidence interval [CI]: 1.22 to 1.72; p < 0.0001) and excellent functional outcome defined as mRS 0 to 1 (RR: 1.67; 95% CI: 1.27 to 2.19; p < 0.0001) at 90 days. There was a trend toward reduced all-cause mortality with mechanical thrombectomy (RR: 0.86; 95% CI: 0.72 to 1.02; p = 0.09). The risk of symptomatic intracranial hemorrhage was similar with either treatment modality (RR 1.06: 95% CI: 0.73 to 1.55; p = 0.76). CONCLUSIONS:In acute ischemic stroke due to large artery occlusion, mechanical thrombectomy after usual care was associated with improved functional outcomes compared with usual care alone, and was found to be relatively safe, with no excess in intracranial hemorrhage. There was a trend for reduction in all-cause mortality with mechanical thrombectomy. 10.1016/j.jacc.2015.09.070
Cerebral Hyperperfusion Syndrome After Carotid Revascularization and Acute Ischemic Stroke. Kirchoff-Torres Kathryn F,Bakradze Ekaterina Current pain and headache reports PURPOSE OF REVIEW:Cerebral hyperperfusion syndrome (CHS) is a rare but significant complication after carotid revascularization and is increasingly recognized after acute stroke treatments. In this review, we discuss the epidemiology and pathophysiology of CHS, clinical presentation including ipsilateral headache, seizures, and focal neurological deficits, and radiographic presentation. We propose preventive therapies with emphasis on acute stroke post-thrombectomy hyperperfusion. RECENT FINDINGS:CHS was first described after carotid revascularization but is now also reported in patients with acute ischemic stroke. Proposed criteria involve a combination of new clinical symptoms, radiographic evidence of hyperperfusion, and/or presence of intracerebral hemorrhage occurring within 30 days after the carotid or intracranial vessel manipulation. Strongest risk factors include reduced cerebral vasoreactivity, contralateral stenosis of ≥ 70%, post-procedure hypertension, and recent ipsilateral stroke. Pathophysiology is incompletely understood but is likely due to increase in cerebral blood flow and impaired cerebral autoregulation, particularly in the areas of disrupted blood-brain barrier, as well as baroreceptor dysfunction during carotid surgery. Strict blood pressure control pre-, during, and post-procedure is recommended, depending on the recanalization status of the vessel. However, there is no randomized data regarding the goal blood pressure to prevent cerebral hyperperfusion syndrome. With technical advances, carotid or intracranial vessel manipulation is increasingly common. CHS is a likely under-recognized and serious complication of carotid revascularization and intracranial thrombectomy. Awareness of and surveillance for CHS is important to reduce morbidity and mortality. Future research should focus on validation of proposed diagnostic criteria and determining optimal post-procedure hemodynamic management to prevent CHS. 10.1007/s11916-018-0678-4
Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Hyperacute changes in cerebral blood flow during cerebral ischaemia and reperfusion are important determinants of injury. Cerebral blood flow is regulated by neurovascular coupling, and disruption of neurovascular coupling contributes to brain plasticity and repair problems. However, it is unknown how neurovascular coupling is affected hyperacutely during cerebral ischaemia and reperfusion. We have developed a remote middle cerebral artery occlusion model in the rat, which enables multi-modal assessment of neurovascular coupling immediately prior to, during and immediately following reperfusion. Male Wistar rats were subjected to remote middle cerebral artery occlusion, where a long filament was advanced intraluminally through a guide cannula in the common carotid artery. Transcallosal stimulation evoked increases in blood flow, tissue oxygenation and neuronal activity, which were diminished by middle cerebral artery occlusion and partially restored during reperfusion. These evoked responses were not affected by administration of the thrombolytic alteplase at clinically used doses. Evoked cerebral blood flow responses were fully restored at 24 h post-middle cerebral artery occlusion indicating that neurovascular dysfunction was not sustained. These data show for the first time that the rat remote middle cerebral artery occlusion model coupled with transcallosal stimulation provides a novel method for continuous assessment of hyperacute neurovascular coupling changes during ischaemia and reperfusion, and offers unique insight into hyperacute ischaemic pathophysiology. 10.1177/0271678X16669512
Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery. Gupta Rishi,Sun Chung-Huan Johnny,Rochestie Dustin,Owada Kumiko,Khaldi Ahmad,Johnson Andrew K,Horn Christopher M Journal of neurointerventional surgery BACKGROUND:Mechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood-brain barrier and reperfusion injury. OBJECTIVE:To examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy. METHODS:We retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 points at 24 hours. RESULTS:The 35 patients studied had an average age of 64±14 years of age with a median NIHSS score of 15 (IQR 9-20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a ≥8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67). CONCLUSIONS:This preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment. 10.1136/neurintsurg-2016-012498
[Application of transcranial Doppler in prognosis assessment of nerve function in patients with acute cerebral infarction after intracranial mechanical thrombectomy]. Pan Luping,Jin Jiaolei,Huang Rui,Wang Wanping,Chen Qiuyue Zhonghua wei zhong bing ji jiu yi xue OBJECTIVE:To investigate the application value of transcranial Doppler (TCD) in the prognosis assessment of nerve function in patients with acute cerebral infarction (ACI) after intracranial mechanical thrombectomy. METHODS:A retrospective analysis was conducted. The clinical data of 43 patients with acute anterior circulation cerebral infarction who received intra-arterial mechanical thrombotomy for recanalization admitted to Taizhou Central Hospital from January 2018 to December 2019 were analyzed. The modified Rankin scale (mRS) score of patients were followed up by telephone at 3 months after surgery to evaluate the prognosis of neurologic outcome. Patients with mRS score 0-2 were enrolled in the good prognosis group, while those with a score of 3-6 were enrolled in the poor prognosis group. The gender, age, past history, underlying diseases, occluded arteries, atherosclerotic stenosis and bridging treatment, time from onset to reperfusion, blood flow dynamics under TCD at 1 day after thrombectomy, and National Institutes of Health stroke scale (NIHSS) scores before and 1, 7, and 14 days after thrombectomy were compared between the two groups. Multivariate Logistic regression analysis was used to screen the prognostic factors of nerve function at 3 months after mechanical thrombectomy in patients with ACI. The receiver operating characteristic (ROC) curve was drawn to evaluate the prognostic value for neurological function assessed by TCD. RESULTS:Forty-three patients were enrolled in the final analysis, with 23 patients in the good prognosis group and 20 in the poor prognosis group. The recanalization was successfully achieved in both groups without complications. However, the hemodynamics of intracranial arteries evaluated by TCD 1 day after operation in both groups still showed partial or complete occlusion, and the hemodynamics of patients in the poor prognosis group was worse than that in the good prognosis group (poor blood flow: 40.0% vs. 0%, inadequate blood flow: 30.0% vs. 17.4%, good blood flow: 30.0% vs. 82.6%), and the differences were statistically significant (all P < 0.01). Before thrombotomy, there was no significant difference in NIHSS score between the two groups. After thrombotomy, the NIHSS score of the two groups gradually decreased with the extension of time, but the NIHSS score at 14 days after operation of the poor prognosis group was still significantly higher than that of the good prognosis group (10.55±2.93 vs. 4.65±1.70, P < 0.01). Univariate analysis showed that compared with the good prognosis group, the proportion of patients with diabetes and arteriosclerosis stenosis in the poor prognosis group were significantly increased (30.0% vs. 4.3%, 45.0% vs. 17.4%, both P < 0.05), and the time from onset to reperfusion was prolonged (minutes: 385.9±96.2 vs. 294.5±95.1, P < 0.01). Multivariable Logistic regression analysis showed that the therosclerosis stenosis [odds ratio (OR) = 9.334, 95% confidence interval (95%CI) was 1.092-79.775, P = 0.041] and the reperfusion time (OR = 1.016, 95%CI was 1.006-1.027, P = 0.002) were associated with prognosis of nerve function at 3 months after mechanical thrombectomy in patients with ACI. ROC curve analysis suggested that the evaluation of intracranial hemodynamics by TCD might be able to predict the prognosis of neurological function in patients with ACI after 3 months of intracranial mechanical thrombectomy, the area under ROC curve (AUC) was 0.768 (95%CI was 0.620-0.917), the sensitivity was 65.0%, the specificity was 87.0%, the positive predictive value was 82.6%, and the negative predictive value was 70.0%. CONCLUSIONS:The evaluation of intracranial hemodynamics assessed by TCD is helpful in early judging the prognosis of neurological function in patients with ACI after intracranial mechanical thrombectomy. 10.3760/cma.j.cn121430-20200410-00281
Endovascular Treatment for Patients With Acute Stroke Who Have a Large Ischemic Core and Large Mismatch Imaging Profile. Rebello Leticia C,Bouslama Mehdi,Haussen Diogo C,Dehkharghani Seena,Grossberg Jonathan A,Belagaje Samir,Frankel Michael R,Nogueira Raul G JAMA neurology IMPORTANCE:Endovascular therapy (ET) is typically not considered for patients with large baseline ischemic cores (irreversibly injured tissue). Computed tomographic perfusion (CTP) imaging may identify a subset of patients with large ischemic cores who remain at risk for significant infarct expansion and thus could still benefit from reperfusion to reduce their degree of disability. OBJECTIVE:To compare the outcomes of patients with large baseline ischemic cores on CTP undergoing ET with the outcomes of matched controls who had medical care alone. DESIGN, SETTING, AND PARTICIPANTS:A matched case-control study of patients with proximal occlusion after stroke (intracranial internal carotid artery and/or middle cerebral artery M1 and/or M2) on computed tomographic angiography and baseline ischemic core greater than 50 mL on CTP at a tertiary care center from May 1, 2011, through October 31, 2015. Patients receiving ET and controls receiving medical treatment alone were matched for age, baseline ischemic core volume on CTP, and glucose levels. Baseline characteristics and outcomes were compared. MAIN OUTCOMES AND MEASURES:The primary outcome measure was the shift in the degree of disability among the treatment and control groups as measured by the modified Rankin Scale (mRS) (with scores ranging from 0 [fully independent] to 6 [dead]) at 90 days. RESULTS:Fifty-six patients were matched across 2 equally distributed groups (mean [SD] age, 62.25 [13.92] years for cases and 58.32 [14.79] years for controls; male, 13 cases [46%] and 14 controls [50%]). Endovascular therapy was significantly associated with a favorable shift in the overall distribution of 90-day mRS scores (odds ratio, 2.56; 95% CI, 2.50-8.47; P = .04), higher rates of independent outcomes (90-day mRS scores of 0-2, 25% vs 0%; P = .04), and smaller final infarct volumes (mean [SD], 87 [77] vs 242 [120] mL; P < .001). One control (4%) and 2 treatment patients (7%) developed a parenchymal hematoma type 2 (P > .99). The rates of hemicraniectomy (2 [7%] vs 6 [21%]; P = .10) and 90-day mortality (7 [29%] vs 11 [48%]; P = .75) were numerically lower in the intervention arm. Sensitivity analysis for patients with a baseline ischemic core greater than 70 mL (12 pairs) revealed a significant reduction in final infarct volumes (mean [SD], 110 [65] vs 319 [147] mL; P < .001) but only a nonsignificant improvement in the overall distribution of mRS scores favoring the treatment group (P = .18). All 11 patients older than 75 years had poor outcomes (mRS score >3) at 90 days. CONCLUSIONS AND RELEVANCE:In properly selected patients, ET appears to benefit patients with large core and large mismatch profiles. Future prospective studies are warranted. 10.1001/jamaneurol.2016.3954
Abnormal Blood Flow on Transcranial Duplex Sonography Predicts Poor Outcome After Stroke Thrombectomy. Kneihsl Markus,Niederkorn Kurt,Deutschmann Hannes,Enzinger Christian,Poltrum Birgit,Horner Susanna,Thaler Daniela,Kraner Julia,Fandler Simon,Colonna Isabella,Fazekas Franz,Gattringer Thomas Stroke Background and Purpose- Hemodynamic changes following mechanical thrombectomy for large vessel occlusion stroke could be associated with complications and might affect prognosis. We investigated postinterventional middle cerebral artery blood flow on transcranial duplex sonography (TCD) and its prognostic value for anterior large vessel occlusion stroke patients. Methods- We identified all ischemic stroke patients who had undergone mechanical thrombectomy for anterior circulation large vessel occlusion from 2010 onwards. Postinterventional middle cerebral artery flow was graded according to the sonographic Thrombolysis in Brain Ischemia score and related to patient outcome stratified by the angiographic Thrombolysis in Cerebral Infarction reperfusion status. Results- Of 215 large vessel occlusion stroke patients, 193 patients (90%) showed successful angiographic recanalization (Thrombolysis in Cerebral Infarction grade 2b-3). Of those, 69 (36%) patients had abnormal sonographic middle cerebral artery blood flow (Thrombolysis in Brain Ischemia grade 0-4) within 72 hours after mechanical thrombectomy, which was an independent predictor for poor 90-day outcome. Conclusions- TCD indicates abnormal middle cerebral artery hemodynamics in a substantial proportion of patients with angiographically defined successful mechanical thrombectomy of the anterior cerebral circulation. Such changes are associated with poor short-term outcome. 10.1161/STROKEAHA.118.023213
Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke. Lansberg Maarten G,Christensen Soren,Kemp Stephanie,Mlynash Michael,Mishra Nishant,Federau Christian,Tsai Jenny P,Kim Sun,Nogueria Raul G,Jovin Tudor,Devlin Thomas G,Akhtar Naveed,Yavagal Dileep R,Haussen Diogo,Dehkharghani Seena,Bammer Roland,Straka Matus,Zaharchuk Greg,Marks Michael P,Albers Gregory W, Annals of neurology OBJECTIVE:To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset. METHODS:We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging. RESULTS:Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140). INTERPRETATION:The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856. 10.1002/ana.24953
Leukocytes, Collateral Circulation, and Reperfusion in Ischemic Stroke Patients Treated With Mechanical Thrombectomy. Semerano Aurora,Laredo Carlos,Zhao Yashu,Rudilosso Salvatore,Renú Arturo,Llull Laura,Amaro Sergi,Obach Victor,Planas Anna M,Urra Xabier,Chamorro Ángel Stroke Background and Purpose- Peripheral immune cells are activated after stroke and may in turn influence the fate of ischemic brain tissue, thus exerting a dual role in ischemic stroke. We evaluated the contribution of neutrophil and lymphocyte counts to hemorrhagic complications and functional outcome in stroke patients treated with mechanical thrombectomy (MT) with varying degrees of collateral circulation and reperfusion. Methods- We retrospectively analyzed 433 consecutive ischemic stroke patients treated with MT. Neutrophil and lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) were collected before MT and 1 day after symptom onset. Outcome measures included categories of hemorrhagic transformation, symptomatic intracerebral hemorrhage, 3-month functional dependence (modified Rankin Scale, 3-6), and mortality. Patients were categorized according to their baseline collateral status and the degree of reperfusion after MT. Results- Neutrophil counts and NLR increased, whereas lymphocyte counts decreased after MT (<0.001), and changes in neutrophils and NLR at day 1 were significantly greater in patients with poor reperfusion. Neutrophil counts and NLR were significantly higher already at admission in patients with poor 3-month outcome. In adjusted analysis, the impact of neutrophilia on poor functional outcome was more substantial in patients with good collaterals achieving successful reperfusion (aOR, 3.09 per quartile; 95% CI, 1.95-4.90), whereas admission lymphopenia (aOR, 4.08 per decreasing quartile; 95% CI, 1.56-10.64) and higher NLR (aOR, 3.76 per quartile; 95% CI, 1.44-9.79) predicted subsequent symptomatic intracerebral hemorrhage in patients with poor collaterals and successful reperfusion. Conclusions- In patients treated with MT, neutrophil and lymphocyte counts are dynamic parameters associated with hemorrhagic complications and long-term outcome. The extent of collateral circulation and the success of brain reperfusion influence the strength of these associations and highlight the dual role of leukocytes in acute stroke. 10.1161/STROKEAHA.119.026743
Increased middle cerebral artery mean blood flow velocity index after stroke thrombectomy indicates increased risk for intracranial hemorrhage. Kneihsl Markus,Niederkorn Kurt,Deutschmann Hannes,Enzinger Christian,Poltrum Birgit,Fischer Renate,Thaler Daniela,Hermetter Christina,Wünsch Gerit,Fazekas Franz,Gattringer Thomas Journal of neurointerventional surgery BACKGROUND AND PURPOSE:Cerebral hyperperfusion has been related to the risk of intracranial hemorrhage (ICH) in stroke patients after vessel recanalization therapy. We hypothesized that after successful mechanical thrombectomy for acute anterior circulation stroke, hemodynamics detectable by transcranial Duplex (TCD) sonography would vary, and that increased blood flow velocities would be associated with ICH. METHODS:We retrospectively identified all ischemic stroke patients with successful endovascular recanalization for anterior circulation vessel occlusion (Thrombolysis in Cerebral Infarction 2b-3) between 2010 and 2017. We reviewed their postinterventional TCD examinations for mean blood flow (MBF) velocities of the recanalized and contralateral middle cerebral artery (MCA) and searched for an association with postinterventional ICH and clinical outcome. RESULTS:123 stroke patients (mean age 63±14 years, 40% women) with successful anterior circulation thrombectomy were analyzed. Of those, 18 patients had postinterventional ICH. ICH patients had an increased MCA MBF velocity index (=MBF velocity of the recanalized divided by the contralateral MCA) compared with non-ICH patients (1.32±0.39 vs 1.02±0.32, P<0.001). In multivariate analysis, a higher MCA MBF velocity index was associated with postinterventional ICH and poor 90 day outcome. CONCLUSIONS:A high MCA MBF velocity index on TCD after successful recanalization therapy for anterior circulation stroke indicates a risk for postinterventional ICH and worse prognosis. 10.1136/neurintsurg-2017-013617
Update on cerebral hyperperfusion syndrome. Lin Yen-Heng,Liu Hon-Man Journal of neurointerventional surgery Cerebral hyperperfusion syndrome (CHS) is a clinical syndrome following a revascularization procedure. In the past decade, neurointerventional surgery has become a standard procedure to treat stenotic or occluded cerebral vessels in both acute and chronic settings, as well as endovascular thrombectomy in acute ischemic stroke. This review aims to summarize relevant recent studies regarding the epidemiology, diagnosis, and management of CHS as well as to highlight areas of uncertainty. Extracranial and intracranial cerebrovascular diseases in acute and chronic conditions are considered. The definition and diagnostic criteria of CHS are diverse. Although impaired cerebrovascular autoregulation plays a major role in the pathophysiology of CHS, the underlying mechanism is still not fully understood. Its clinical characteristics vary in different patients. The current findings on clinical and radiological presentation, pathophysiology, incidence, and risk factors are based predominantly on carotid angioplasty and stenting studies. Hemodynamic assessment using imaging modalities is the main form of diagnosis although the criteria are distinct, but it is helpful for patient selection before an elective revascularization procedure is conducted. After endovascular thrombectomy, a diagnosis of CHS is even more complex, and physicians should consider concomitant reperfusion injury. Management and preventative measures, including intensive blood pressure control before, during, and after revascularization procedures and staged angioplasty, are discussed in detail. 10.1136/neurintsurg-2019-015621
Endovascular Stroke Treatment Outcomes After Patient Selection Based on Magnetic Resonance Imaging and Clinical Criteria. Leslie-Mazwi Thabele M,Hirsch Joshua A,Falcone Guido J,Schaefer Pamela W,Lev Michael H,Rabinov James D,Rost Natalia S,Schwamm Lee,González R Gilberto JAMA neurology IMPORTANCE:Which imaging modality is optimal to select patients for endovascular stroke treatment remains unclear. OBJECTIVE:To evaluate the effectiveness of specific magnetic resonance imaging (MRI) and clinical criteria in the selection of patients with acute ischemic stroke for thrombectomy. DESIGN, SETTING, AND PARTICIPANTS:In this observational, single-center, prospective cohort study, we studied 72 patients with middle cerebral artery or terminal internal carotid artery occlusion using computed tomographic angiography, followed by core infarct volume determination by diffusion weighted MRI, who underwent thrombectomy after meeting institutional criteria from January 1, 2012, through December 31, 2014. In this period, 31 patients with similar ischemic strokes underwent endovascular treatment without MRI and are categorized as computed tomography only and considered in a secondary analysis. INTERVENTIONS:Patients were prospectively classified as likely to benefit (LTB) or uncertain to benefit (UTB) using diffusion-weighted imaging lesion volume and clinical criteria (age, National Institutes of Health Stroke Scale score, time from onset, baseline modified Rankin Scale [mRS] score, life expectancy). MAIN OUTCOMES AND MEASURES:The 90-day mRS score, with favorable defined as a 90-day mRS score of 2 or less. RESULTS:Forty patients were prospectively classified as LTB and 32 as UTB. Reperfusion (71 of 103 patients) and prospective categorization as LTB (40 of 103 patients) were associated with favorable outcomes (P < .001 and P < .005, respectively). Successful reperfusion positively affected the distribution of mRS scores of the LTB cohort (P < .001). Reperfusion was achieved in 27 LTB patients (67.5%) and 24 UTB patients (75.0%) (P = .86). Favorable outcomes were obtained in 21 (52.5%) and 8 (25.0%) of LTB and UTB patients who were treated, respectively (P = .02). Favorable outcomes were observed in 20 of the 27 LTB patients (74.1%) who had successful reperfusion compared with 8 of the 24 UTB patients (33.3%) who had successful reperfusion (P = .004). The ratio of treated to screened patients was 1:3. CONCLUSIONS AND RELEVANCE:Prospective classification as LTB by MRI and clinical criteria is associated with likelihood of favorable outcome after thrombectomy, particularly if reperfusion is successful. Selection of patients using MRI compares favorably with selection using computed tomographic techniques with the distinction that a higher proportion of screened patients were treated. 10.1001/jamaneurol.2015.3000
Endovascular therapy for ischemic stroke with perfusion-imaging selection. Campbell Bruce C V,Mitchell Peter J,Kleinig Timothy J,Dewey Helen M,Churilov Leonid,Yassi Nawaf,Yan Bernard,Dowling Richard J,Parsons Mark W,Oxley Thomas J,Wu Teddy Y,Brooks Mark,Simpson Marion A,Miteff Ferdinand,Levi Christopher R,Krause Martin,Harrington Timothy J,Faulder Kenneth C,Steinfort Brendan S,Priglinger Miriam,Ang Timothy,Scroop Rebecca,Barber P Alan,McGuinness Ben,Wijeratne Tissa,Phan Thanh G,Chong Winston,Chandra Ronil V,Bladin Christopher F,Badve Monica,Rice Henry,de Villiers Laetitia,Ma Henry,Desmond Patricia M,Donnan Geoffrey A,Davis Stephen M, The New England journal of medicine BACKGROUND:Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. METHODS:We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. RESULTS:The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. CONCLUSIONS:In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.). 10.1056/NEJMoa1414792
Effect of endovascular reperfusion in relation to site of arterial occlusion. Lemmens Robin,Hamilton Scott A,Liebeskind David S,Tomsick Tom A,Demchuk Andrew M,Nogueira Raul G,Marks Michael P,Jahan Reza,Gralla Jan,Yoo Albert J,Yeatts Sharon D,Palesch Yuko Y,Saver Jeffrey L,Pereira Vitor M,Broderick Joseph P,Albers Gregory W,Lansberg Maarten G, , Neurology OBJECTIVE:To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL). METHODS:We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions. RESULTS:Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7). CONCLUSIONS:The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials. 10.1212/WNL.0000000000002399
Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. Nogueira Raul G,Jadhav Ashutosh P,Haussen Diogo C,Bonafe Alain,Budzik Ronald F,Bhuva Parita,Yavagal Dileep R,Ribo Marc,Cognard Christophe,Hanel Ricardo A,Sila Cathy A,Hassan Ameer E,Millan Monica,Levy Elad I,Mitchell Peter,Chen Michael,English Joey D,Shah Qaisar A,Silver Frank L,Pereira Vitor M,Mehta Brijesh P,Baxter Blaise W,Abraham Michael G,Cardona Pedro,Veznedaroglu Erol,Hellinger Frank R,Feng Lei,Kirmani Jawad F,Lopes Demetrius K,Jankowitz Brian T,Frankel Michael R,Costalat Vincent,Vora Nirav A,Yoo Albert J,Malik Amer M,Furlan Anthony J,Rubiera Marta,Aghaebrahim Amin,Olivot Jean-Marc,Tekle Wondwossen G,Shields Ryan,Graves Todd,Lewis Roger J,Smith Wade S,Liebeskind David S,Saver Jeffrey L,Jovin Tudor G, The New England journal of medicine BACKGROUND:The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. METHODS:We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. RESULTS:A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). CONCLUSIONS:Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .). 10.1056/NEJMoa1706442
Association of Time From Stroke Onset to Groin Puncture With Quality of Reperfusion After Mechanical Thrombectomy: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials. Bourcier Romain,Goyal Mayank,Liebeskind David S,Muir Keith W,Desal Hubert,Siddiqui Adnan H,Dippel Diederik W J,Majoie Charles B,van Zwam Wim H,Jovin Tudor G,Levy Elad I,Mitchell Peter J,Berkhemer Olvert A,Davis Stephen M,Derraz Imad,Donnan Geoffrey A,Demchuk Andrew M,van Oostenbrugge Robert J,Kelly Michael,Roos Yvo B,Jahan Reza,van der Lugt Aad,Sprengers Marieke,Velasco Stephane,Lycklama À Nijeholt Geert J,Ben Hassen Wagih,Burns Paul,Brown Scott,Chabert Emmanuel,Krings Timo,Choe Hana,Weimar Christian,Campbell Bruce C V,Ford Gary A,Ribo Marc,White Phil,Cloud Geoffrey C,San Roman Luis,Davalos Antoni,Naggara Olivier,Hill Michael D,Bracard Serge, JAMA neurology Importance:Reperfusion is a key factor for clinical outcome in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) for large-vessel intracranial occlusion. However, data are scarce on the association between the time from onset and reperfusion results. Objective:To analyze the rate of reperfusion after EVT started at different intervals after symptom onset in patients with AIS. Design, Setting, and Participants:We conducted a meta-analysis of individual patient data from 7 randomized trials of the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) group. This is a multicenter cohort study of the intervention arm of randomized clinical trials included in the HERMES group. Patients with anterior circulation AIS who underwent EVT for M1/M2 or intracranial carotid artery occlusion were included. Each trial enrolled patients according to its specific inclusion and exclusion criteria. Data on patients eligible but not enrolled (eg, refusals or exclusions) were not available. All analyses were performed by the HERMES biostatistical core laboratory using the pooled database. Data were analyzed between December 2010 and April 2015. Main Outcomes and Measures:Successful reperfusion was defined as a modified thrombolysis in cerebral infarction score of 2b/3 at the end of the EVT procedure adjusted for age, occlusion location, pretreatment intravenous thrombolysis, and clot burden score and was analyzed in relation to different intervals (onset, emergency department arrival, imaging, and puncture) using mixed-methods logistic regression. Results:Among the 728 included patients, with a mean (SD) age of 65.4 (13.5) years and of whom 345 were female (47.4%), decreases in rates of successful reperfusion defined as a thrombolysis in cerebral infarction score of 2b/3 were observed with increasing time from admission or first imaging to groin puncture. The magnitude of effect was a 22% relative reduction (odds ratio, 0.78; 95% CI, 0.64-0.95) per additional hour between admission and puncture and a 26% relative reduction (odds ratio, 0.74; 95% CI, 0.59-0.93) per additional hour between imaging and puncture. Conclusions and Relevance:Because the probability of reperfusion declined significantly with time between hospital arrival and groin puncture, we provide additional arguments for minimizing the intervals after symptom onset in anterior circulation acute ischemic stroke. 10.1001/jamaneurol.2018.4510