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Objective: The goal of the present study was to determine the safety and efficacy of intravenous tissue plasminogen activator (IVT) in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT)., Methods: We performed a retrospective analysis of prospectively collected data gathered during a 3-year period for all our patients with AIS and LVO. We analyzed the stroke outcomes and complications between patients who had received a combination of IVT and MT and those who had undergone MT only. Standardized selection criteria, including the uniform use of perfusion imaging, were used for selection for MT, irrespective of IVT administration., Results: Of the patients who had received IVT, 10% had had successful reperfusion found at initial angiography and did not require MT. A door-to-puncture time within 1 hour of presentation was achieved in 19% of both groups. IVT+MT was not associated with an increased incidence of intracranial hemorrhage (IVT+MT, 47.1%; MT, 49%). Of the 73 patients in IVT+MT group, 8 had developed access-site hematomas compared with 9 of the 95 patients in the MT group (28.6% vs. 26.5%; P = 0.85). The IVT+MT group had a lower proportion of patients with a modified Rankin scale score of 5-6 at 90 days compared with the MT group (36% vs. 56%; P = 0.024). Both groups showed statistically similar proportions of patients with a Thrombolysis in Cerebral Infarction scale score of ≥2c (IVT+MT, 50%; MT, 43%; P = 0.58). The IVT+MT group had a greater proportion of patients with Thrombolysis in Cerebral Infarction scale score of 2c (IVT+MT, 29.6%; MT, 16.8%; P = 0.068)., Conclusions: Administration of IVT before MT to patients with AIS with LVO resulted in reperfusion before MT in 10% of patients, reduced the incidence of mortality and severe disability at 90 days, did not affect the door-to-puncture time, and was associated with a similar incidence of systemic and intracranial hemorrhage compared with MT only., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Despite the proven benefit of neurothrombectomy, intracranial hemorrhage (ICH) remains the most serious procedural complication. The aim of this analysis was to identify predictors of different hemorrhage subtypes and evaluate their individual impact on clinical outcome., Methods: Pooled individual patient-level data from three large prospective multicenter studies were analyzed for the incidence of different ICH subtypes, including any ICH, hemorrhagic transformation (HT), parenchymal hematoma (PH), subarachnoid hemorrhage (SAH), and symptomatic intracranial hemorrhage (sICH). All patients (n=389) treated with the Solitaire device were included in the analysis. A multivariate stepwise logistic regression model was used to identify predictors of each hemorrhage subtype., Results: General anesthesia and higher baseline Alberta Stroke Program Early CT score (ASPECTS) were associated with a lower probability of any ICH (OR 0.36, p = 0.003), (OR 0.80, p = 0.032) and HT (OR 0.54, p = 0.023), (OR 0.78, p=0.001), respectively. Longer time from onset to treatment was associated with a higher likelihood of HT (OR 1.08, p = 0.001) and PH (OR 1.11, p = 0.015). Intravenous tissue plasminogen activator (IV-tPA) was also a strong predictor of PH (OR 7.63, p = 0.013). Functional independence at 90 days (modified Rankin Scale (mRS) 0-2) was observed significantly less frequently in all hemorrhage subtypes except SAH. None of the patients who achieved functional independence at 90 days had sICH., Conclusions: General anesthesia and smaller baseline ischemic core are associated with a lower probability of HT whereas IV-tPA and prolonged time to treatment increase the risk of PH after neurothrombectomy., Trial Registration Numbers: SWIFT-NCT01054560; post results, SWIFT PRIME-NCT01657461; post results, STAR-NCT01327989; post results., Competing Interests: Competing interests: All co-authors are consultants for Medtronic Neurovascular., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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 μm 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 imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions., Funding: Medtronic., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Purpose: The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI)., Methods: Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP., Results: MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital ( P =0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group ( P =0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P =0.02; CTP, P =0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups., Conclusions: Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461., (© 2017 American Heart Association, Inc.)

Importance: Mechanical thrombectomy (MT) improves clinical outcomes in patients with acute ischemic stroke (AIS) caused by a large vessel occlusion. However, it is not known whether intravenous thrombolysis (IVT) is of added benefit in patients undergoing MT., Objective: To examine whether treatment with IVT before MT with a stent retriever is beneficial in patients undergoing MT., Design, Setting, and Participants: This post hoc analysis used data from 291 patients treated with MT included in 2 large, multicenter, prospective clinical trials that evaluated MT for AIS (Solitaire With the Intention for Thrombectomy performed from January 1, 2010, through December 31, 2011, and Solitaire Flow Restoration Thrombectomy for Acute Revascularization from January 1, 2010, through December 31, 2012). An independent core laboratory scored the radiologic outcomes in each trial., Interventions: Patients were treated with IVT with tissue plasminogen activator followed by MT (IVT and MT group) with the use of a stent retriever or MT with a stent retriever alone (MT group)., Main Outcomes and Measures: Successful reperfusion, functional independence (modified Rankin Scale score of 0-2) and mortality at 90 days, symptomatic intracranial hemorrhage, emboli to new territory, and vasospasm were compared., Results: Of 291 patients included in the analysis, 160 (55.0%) underwent IVT and MT (mean [SD] age, 67 [13] years; 97 female [60.6%]), and 131 (45.0%) underwent MT alone (mean [SD] age, 69 [12] years; 71 [55.7%] female). Median Alberta Stroke Program Early CT Score at baseline was lower in the IVT and MT group (8 vs 9, P = .04). There was no statistically significant difference in the duration from symptom onset to groin puncture (254 minutes for the IVT and MT group vs 262 minutes for the MT group, P = .10). The number of passes, rate of successful reperfusion, functional independence at 90 days, mortality at 90 days, and emboli to new territory were also similar among groups. Symptomatic intracranial hemorrhage (1% vs 4%) and parenchymal hemorrhages type 1 (1% vs 3%) or type 2 (1% vs 2%) did not differ significantly (P = .25). Vasospasm occurred more often in patients who received IVT and MT vs MT alone (27% vs 14%, P = .006). In multivariate analysis, no statistically significant association was observed between IVT and MT vs MT alone for any of the outcomes., Conclusions and Relevance: The results indicate that treatment of patients experiencing AIS due to a large vessel occlusion with IVT before MT does not appear to provide a clinical benefit over MT alone. A randomized clinical trial seems warranted., Trial Registration: clinicaltrials.gov Identifiers: NCT01054560 and NCT01327989.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Purpose: Imaging findings can predict outcomes in patients with acute stroke. Relationships between imaging findings and clinical and imaging outcomes in patients randomized to intravenous tissue-type plasminogen activator-alone versus tissue-type plasminogen activator plus endovascular therapy (Solitaire device) in the Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) study were assessed., Methods: We evaluated associations between imaging assessments (baseline mismatch profiles/ischemic core volumes and successful reperfusion) with imaging outcomes (27-hour infarct volume/growth) and clinical outcomes (modified Rankin Scale scores at 90 days). Imaging variables that predict favorable clinical outcomes were assessed in both univariate and multivariate models., Results: One hundred and ninety-five patients were included. Successful reperfusion and infarct volume (assessed at 27 hours) were powerful independent predictors of favorable clinical outcomes (modified Rankin Scale score of 0-2 at 90 days). Patients with the target mismatch profile at baseline had a higher rate of reperfusion, lesser infarct growth, smaller infarct volumes, and better clinical outcomes in the Solitaire plus tissue-type plasminogen activator (intervention) group than those in the tissue-type plasminogen activator-alone (control) group. Patients with larger mismatch volumes at baseline had a trend toward better treatment response in the intervention group than patients who had smaller (<50 mL) mismatch volumes., Conclusions: Patients who achieved reperfusion had substantially more favorable clinical and imaging outcomes in both the intervention and the control groups. Infarct volume at 27 hours strongly correlated with clinical outcome at 90 days in both treatment groups. SWIFT PRIME patients with the target mismatch profile had a highly favorable response to endovascular therapy on both clinical and imaging outcomes. Both reperfusion and infarct volumes at 27 hours were powerful and independent predictors of 90-day clinical outcomes., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461., (© 2015 American Heart Association, Inc.)

Rationale: Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator., Aims and Design: This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group., Study Outcomes: This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow., Discussion: This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication., (© 2015 World Stroke Organization.)

Background: Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome., Methods: We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death])., Results: The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12)., Conclusions: In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

Rationale: Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions., Aim: The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke., Design: The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled., Procedures: Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset., Study Outcomes: The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure., Analysis: Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2)., (© 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.)

Background: Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear., Methods: In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead)., Results: Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14)., Conclusions: A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.).

Background and Purpose: Plasmin is a direct-acting thrombolytic with a better safety profile than recombinant tissue-type plasminogen activator (rtPA) in animal models. With the application of retrieval devices for managing acute ischemic stroke, extracted thromboemboli are available for ex vivo examination. We ask whether such thrombi are amenable to plasmin thrombolysis and whether such activity is different with rtPA., Methods: Thromboembolic fragments (total 29) were retrieved from the intracranial carotid artery system of 15 patients with acute ischemic stroke and randomly assigned to ex vivo thrombolysis with plasmin or rtPA. After an initial 2-hour exposure, residual material was exposed to the other agent for an additional 2 hours. Thrombolysis was quantified by change in thrombus area and released d-dimer., Results: Plasmin induced significant ex vivo thrombolysis of cerebral arterial thromboemboli, decreasing area by 45.9% ± 29.4% and 69.2% ± 52.5% and inducing median D-dimer release of 108,180 μg/L (range, 16,780 to 668,050 μg/L) and 16,905 μg/L (range, 240 to 403 085 μg/L) during the first and second 2-hour incubation periods, respectively. These changes were not different from those obtained with rtPA, which decreased area by 34.7% ± 57.8% (P=0.63) and by 68.4% ± 26.9% (P=0.97) and induced median D-dimer release of 151,990 μg/L (range, 9870 to 338,350 μg/L; P=0.51) and 34,520 μg/L (range 3794 to 325,400 μg/L; P=0.19) during the first and second 2-hour incubations., Conclusions: Retrieved human cerebral thromboemboli were amenable to ex vivo lysis by plasmin, the rate and degree of which was not different than that achieved with rtPA.

Background and Purpose: Intra-arterial fibrinolytic therapy is a promising treatment for acute ischemic stroke. Few data are available on its use in elderly patients. The purpose of this study was to compare the baseline characteristics, complications, and outcomes between intra-arterially treated ischemic stroke patients aged > or = 80 years and their younger counterparts., Methods: Patients aged > or = 80 years (n = 33) were compared retrospectively with contemporaneous patients aged < 80 years (n = 81) from a registry of consecutive patients treated with intra-arterial thrombolysis over a 9-year period., Results: The very elderly and younger cohorts were very similar in baseline characteristics, including pretreatment stroke severity (National Institutes of Health Stroke Scale [NIHSS] 17 versus 16), differing only in history of stroke/transient ischemic attack (42% versus 22%, P = .01) and weight (66.8 versus 75.8 kg; P = .02). Significant differences in recanalization (TIMI 2-3) rates could not be detected between the very elderly and younger patients (79% versus 68%, P = .10). Rates of major symptomatic hemorrhage (7% versus 8%) and any intracerebral hemorrhage (39% versus 37%) did not differ. Outcomes at 90 days showed lower rates of excellent functional outcome (mRS < or = 1, 26% versus 40%, P = .02) and survival (57% versus 80%, P = .01) among the very elderly., Conclusions: Intra-arterial fibrinolysis in the elderly can be accomplished with recanalization rates and hemorrhage rates equal to that in younger patients. Although mortality rates are higher and good functional outcomes are lower than in younger persons, nondisabling outcomes may be achieved in a quarter of patients. These findings suggest that the investigation and use of intra-arterial thrombolytic treatment in very elderly patients should not be avoided but pursued judiciously.

Although animal models have demonstrated that late secondary cerebral injury after arterial occlusion and subsequent recanalization may limit the benefit of reperfusion therapy, this phenomenon has not been well characterized in humans. Diffusion-perfusion magnetic resonance imaging studies were performed before treatment, early after treatment, and at day 7 in patients undergoing vessel recanalization with intraarterial thrombolytics. Among 18 patients studied, mean age was 71 (range, 27-94), and median entry National Institutes of Health Stroke Scale score was 13 (range, 6-25). Early after recanalization, partial or complete normalization of diffusion imaging abnormalities occurred in 8 of 18 (44%) patients. Among the eight patients with early diffusion imaging reversal, late secondary injury by day 7 occurred in 5 (63%), and sustained normalization of all reversed tissue occurred in 3 (38%). Pretreatment apparent diffusion coefficient values were lowest in regions experiencing no reversal (mean apparent diffusion coefficient, 608 microm(2)/sec), intermediate in regions with reversal and secondary decline (617 microm(2)/sec), and highest in regions with sustained reversal (663 microm(2)/sec). There was a trend toward less improvement in neurological deficit in patients with secondary injury versus patients with sustained reversal. In the future, late secondary tissue injury may become an important therapeutic target for postreperfusion neuroprotective therapies, with treatment efficacy monitored by serial diffusion magnetic resonance imaging.

Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra-arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion-weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8-38 cm3) and decreased to 10 cm3 (95% CI, 3-17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2-16 cm3) at baseline to 1 cm3 (95% CI, 0.4-2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality.

Background and purposeIntracranial hemorrhage is the most dreaded complication of neurothrombectomy therapy for acute ischemic stroke. The determinants of intracranial hemorrhage and its impact on clinical course remain incompletely delineated. The purpose of this study is to further investigate the clinical and procedural factors leading to intracranial hemorrhage and to define the clinical impact of different hemorrhagic subtypes.Materials and methodsWe analyzed data prospectively collected in the Solitaire FR With Intention for Thrombectomy randomized clinical trial. A multivariable logistic regression model was used to identify independent clinical, imaging, and procedural predictors of any intracranial hemorrhage and of 7 intracranial hemorrhage subtypes. Univariate analysis was used to determine the impact of each of the intracranial hemorrhage subtypes on clinical outcome.ResultsAmong the 144 enrolled patients, any radiologic intracranial hemorrhage (21.3% versus 38.2%, P = .035), symptomatic intracranial hemorrhage (1.1% versus 10.9%, P = .012), and subarachnoid hemorrhage (2.2% versus 12.7%, P = .027) occurred less frequently in the Solitaire FR than in the Merci retriever arms. The most common independent determinant of hemorrhage occurrence was rescue therapy with intra-arterial rtPA, which was associated with any intracranial hemorrhage and 4 subtypes and tended to be used more frequently in the Merci group (10.9% versus 3.4%; P = .09). Among the hemorrhage subtypes, basal ganglionic hemorrhage had the strongest impact on good clinical outcome at 90 days (OR, 0.30; P = .025) and was associated with higher reperfusion, prolonged time to treatment, and rescue therapy with intra-arterial rtPA.ConclusionsIntracranial hemorrhage, especially subarachnoid and symptomatic intracerebral hemorrhage, occurs less frequently with the Solitaire FR than the Merci retriever, in part due to less frequent use of rescue therapy with intra-arterial rtPA. Basal ganglionic hemorrhage strongly affects clinical outcome and is distinctively related to late reperfusion.