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Background: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied., Methods: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage., Results: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group., Conclusions: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.)., (Copyright © 2024 Massachusetts Medical Society.)

Objective: Whether the time from intravenous thrombolysis (IVT) to endovascular treatment (EVT) in patients with acute ischemic stroke has an effect on the functional outcome is unknown., Methods: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, multicenter, observational study that perform EVT in France. Data were analyzed from patients treated by IVT and EVT between October 2013 and December 2018 in 6 comprehensive stroke centers. In the primary analysis, we assessed the association of time from IVT administration to start of EVT with functional outcome (measured with the modified Rankin Scale [mRS]), by means of ordinal logistic regression. Secondary end points included angiographic and safety outcomes., Results: We analyzed 1,986 patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent IVT and EVT. An increased IVT to start of EVT time was associated with a worse functional outcome at 90 days (mRS = 0-2, adjusted odds ratio [OR] per 30 minutes increase in time = 0.91, 95% confidence interval [CI] = 0.86-0.96; mRS = 0-1, adjusted OR per 30 minutes increase in time = 0.89, 95% CI = 0.84-0.94), a lower chance of modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b to 3 reperfusion (adjusted OR per 30 minutes increase in time = 0.93, 95% CI = 0.87-0.98), and an increased probability of symptomatic intracerebral hemorrhage (adjusted OR per 30 minutes increase in time = 1.09, 95% CI = 0.99-1.18)., Interpretation: These findings provide a basis for further studies to determine if the functional outcome of patients with stroke can be greatly improved by optimizing IVT to EVT times. ANN NEUROL 2021;89:511-519., (© 2020 American Neurological Association.)

Background: To date, thrombectomy for large vessel occlusion (LVO) strokes can be performed only in comprehensive stroke centers with thrombectomy capacity. We compared the clinical outcome of patients first referred to a primary stroke center to those admitted directly to a comprehensive stroke center and treated on site in the multicentric observational Endovascular Treatment in Ischemic Stroke (ETIS) registry., Methods: From our perspective, multicenter, observational ETIS registry, we analyzed anterior circulation stroke patients, treated within 8 h, who underwent thrombectomy after thrombolysis and were admitted to a comprehensive stroke center either with drip and ship or mothership. Clinical and safety outcomes were compared between 2 groups., Results: A total of 971 patients were analyzed: 298 were treated with the mothership approach and 673 with drip and ship. Significantly more functional independence (90-day modified Rankin Scale [mRS] 0-2) was achieved in mothership (60.1%) than in drip and ship patients (52.6%; adjusted relative risk [RR] 0.87, 95% CI 0.77-0.98, p = 0.018). Excellent outcome (90-day mRS 0-1) was achieved in 45.3% of the mothership group, compared to 37.9% of the drip and ship group (RR 0.84, 95% CI 0.71-0.98; p = 0.026). According to the distance between the primary stroke center and the comprehensive stroke center, greater functional independence was achieved in mothership than in drip and ship >12.5 miles patients (adjusted RR 0.82; 95% CI 0.71-0.94). Results in the drip-ship group stratified according to time between cerebral imaging and groin puncture (categorized according to the median cut-off: 140 min) were similar. Symptomatic intracerebral hemorrhage rate and mortality within 90 days was similar in both groups (7.5 vs. 5.9%, p = 0.40; 17.4 vs. 16.1%, p = 0.63)., Conclusions: Our study suggests that LVO stroke patients directly admitted to a comprehensive stroke center present a higher chance of functional independence, especially when the distance between the primary stroke center and comprehensive stroke center is >12.5 miles or when the time between cerebral imaging and groin puncture is ≥140 min., (© 2019 S. Karger AG, Basel.)

Background and Purpose- Intravenous thrombolysis (IVT) within 4.5 hours of symptom onset is currently recommended before mechanical thrombectomy (MT). We compared functional outcome, neurological recovery, reperfusion, and adverse events according to the use or not of IVT before MT. Methods- This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was favorable 90-day functional outcome defined as a modified Rankin Scale of ≤2. Secondary outcomes were successful reperfusion following all procedures and after the first-line procedure, number of device passes, and change in National Institutes of Health Stroke Scale score at 24 hours. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage. Results- Three hundred eighty-one patients were included, 250 of whom received IVT before MT (IVT+MT group). There were no significant differences between IVT+MT and MT-alone groups in 90-day favorable functional outcome, in successful reperfusion rate (modified Thrombolysis In Cerebral Infarction 2b or 3), in National Institutes of Health Stroke Scale score improvement at 24 hours, or in hemorrhagic complication rate. The 90-day mortality rate in the IVT+MT group was lower than after MT alone (fully-adjusted risk ratio, 0.59; 95% CI, 0.39-0.88). In a subgroup of patients without anticoagulant medication before stroke onset, we observed in the IVT+MT group a better functional outcome (fully-adjusted risk ratio, 1.38; 95% CI, 1.02-1.89), a higher successful recanalization rate after first-line strategy (fully-adjusted risk ratio, 1.26; 95% CI, 1.05-1.50), and a lower mortality rate (fully-adjusted risk ratio, 0.58; 95% CI, 0.36-0.93). Conclusions- Our results show that IVT+MT patients in the ASTER trial have lower 90-day mortality compared with those receiving MT alone. In a selected population of patients without prestroke anticoagulation, we demonstrated that IVT associated with MT might improve functional outcome and recanalization while reducing mortality rates.

Background and Purpose: Tandem anterior circulation lesions in the setting of acute ischemic stroke (AIS) are a complex endovascular situation that has not been specifically addressed in trials. We determined the predictors of successful reperfusion and good clinical outcome at 90 days after mechanical thrombectomy (MT) in patients with AIS with tandem lesions in a pooled collaborative study., Methods: This was a retrospective analysis of consecutive patients presenting to 18 comprehensive stroke centers with AIS due to tandem lesion of the anterior circulation who underwent MT., Results: A total of 395 patients were included. Successful reperfusion (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 76.7%. At 90 days, 52.2% achieved a good outcome (modified Rankin Scale score 0-2), 13.8% suffered a parenchymal hematoma and 13.2% were dead. Lower National Institutes of Health Stroke Scale score [odds ratio (OR), 1.26; 95% confidence intervals (CI), 1.07-1.48, P = 0.004], Alberta Stroke Program Early CT Score ≥7 (OR, 2.00; 95% CI, 1.07-3.43, P = 0.011), intravenous thrombolysis (OR, 1.47; 95% CI, 1.01-2.12, P = 0.042) and stenting of the extracranial carotid lesion (OR, 1.63; 95% CI, 1.04-2;53, P = 0.030) were independently associated with successful reperfusion. Lower age (OR, 1.58; 95% CI, 1.26-1.97, P < 0.001), absence of hypercholesterolemia (OR, 1.77; 95% CI, 1.10-2.84, P = 0.018), lower National Institutes of Health Stroke Scale scores (OR, 2.04; 95% CI, 1.53-2.72, P < 0.001), Alberta Stroke Program Early CT Score ≥7 (OR, 2.75; 95% CI, 1.24-6.10, P = 0.013) and proximal middle cerebral artery occlusion (OR, 1.59; 95% CI, 1.03-2.44, P = 0.035) independently predicted a good 90-day outcome., Conclusions: Intravenous thrombolysis and emergent stenting of the extracranial carotid lesion were predictors of a successful reperfusion after MT of patients with AIS with tandem lesion of the anterior circulation., (© 2018 EAN.)

Background: Modern endovascular thrombectomy (MET), using stent retrievers or large-bore distal aspiration catheters in stroke patients with acute basilar artery occlusion (BAO), is routinely performed to date. However, more than 35% of BAO patients treated with MET die within 90 days despite high recanalization rates. The purpose of this study is to investigate the parameters associated with 90-day mortality in patients with BAO after MET., Methods: We analyzed 117 consecutive BAO patients included in the Endovascular Treatment in Ischemic Stroke prospective clinical registry of consecutive acute ischemic stroke patients treated with MET (60 patients [51.3%] treated with a stent retriever as first-line technique) between March 2010 and April 2017. Successful recanalization was defined as modified thrombolysis In cerebral infarction scores 2b-3 at the end of MET, and mortality was defined as modified Rankin Scale 6 at 90 days. Associations of baseline characteristics (patient and treatment characteristics) and intermediate outcomes (recanalization, complications) with 90-day mortality were investigated in univariate and multivariate analyses., Results: Overall successful recanalization rate was 79.5, and 41.9% (95% CI 32.8-51.0%) of patients died within 90 days after MET. Patients with successful recanalization had a lower mortality rate (32.9 vs. 74.4%; p < 0.001). Failure of successful recanalization was an independent predictor of mortality (OR 5.1; 95% CI 1.34-19.33). In multivariate analysis, age ≥60 years (OR 6.37; 95% CI 1.74-23.31), admission National Institute of Health Stroke Scale (NIHSS) ≥13 (OR 4.62; 95% CI 1.42-15.03), lower posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS; OR 1.71; 95% CI 1.19-2.44), use of antithrombotic medication prior to stroke onset (OR 3.38; 95% CI 1.03-11.08), absence of intravenous thrombolysis (OR 3.36; 95% CI 1.12-10.03), and angioplasty/stenting of the basilar artery (OR 4.71; 95% CI 1.34-16.54) were independent predictors for mortality after MET., Conclusions: Failure of successful recanalization was a strong predictor for mortality. In the setting of recanalization, age, admission NIHSS, pc-ASPECTS, absence of intravenous thrombolysis, and angioplasty/stenting of the basilar artery were also independent predictors for mortality after MET of BAO patients., (© 2018 S. Karger AG, Basel.)

Background and Purpose: The impact of intravenous recombinant tissue plasminogen activator (IV-rtPA) in patients with acute ischaemic stroke (AIS) but no arterial occlusion is currently a matter of debate. This study aimed to assess functional outcome of such patients with respect to IV-rtPA use., Methods: A retrospective case-control analysis was performed comparing the outcome of AIS patients without arterial occlusion with or without IV-rtPA use. Patients were selected from prospective consecutive observational registries of five European university hospitals. The primary study outcome was excellent outcome at 3 months after stroke, as defined by a modified Rankin Scale (mRS) 0-1., Results: A total of 488 patients without arterial occlusion documented by angiography were included in the present study; 300 received IV-rtPA and 188 did not. No between-group difference was found for excellent outcome before and after adjustment for baseline characteristics (adjusted odds ratio for no IV-rtPA use 0.79, 95% confidence interval 0.51-1.24, P = 0.31). Similar results were found for favourable outcome (defined as a 90-day mRS of 0-2) whereas a higher rate of early neurological improvement was found in IV-rtPA-treated patients (adjusted odds ratio 1.99; 95% confidence interval 1.29-3.07, P = 0.002). Sensitivity analyses yielded similar results., Conclusions: Our study suggests that AIS patients without visible arterial occlusion treated with IV-rtPA may have no better outcome at 3 months than those untreated. However, only a randomized controlled trial would provide a definitive answer about the impact of rtPA in acute stroke patients without occlusion. Until then, these patients should be treated by rtPA as recommended., (© 2016 EAN.)

Background: Thirty percent of ischemic stroke (IS) patients suffering from acute stroke are under antiplatelet therapy., Aims: We evaluated whether prior antiplatelet use before intravenous (IV), intra-arterial (IA) or combined IV/IA therapy may be associated with worse outcomes and an increased intracerebral hemorrhage (ICH) risk after reperfusion therapies., Methods: We analyzed data from our patient registry (n = 874) and conducted a systematic review of previous observational studies. The primary outcome was the percentage of patients who developed symptomatic ICH (sICH), defined in our registry per ECASS-II definition., Results: We identified 43 previous reports that evaluated the impact of prior antiplatelet use on outcomes after reperfusion therapy in AIS patients. Prior antiplatelet use was found in 35% of AIS patients, eligible for reperfusion therapies and was associated with a worse vascular profile. In an unadjusted meta-analysis that included our registry data, prior antiplatelet use was associated with more sICH per ECASS-II definition (OR, 1.78 (95% CI, 1.48-2.13), and less favorable outcome (OR, 0.86; 95% CI, 0.77-0.98). However, in multivariate analyses conducted in our registry showed that prior antiplatelet use was not associated with worse outcome (P > 0.23); and in the systematic review, only 3 studies reported a slight, but significant adjusted increase in sICH risk, of whom one had conflicting results according to sICH definition., Conclusions: These results suggest no significant detrimental effect of prior antiplatelet use in AIS patients treated by IV, IA or combined IV/IA therapy. Further studies are needed to assess the specific impact of different and cumulative antiplatelet agents., (© 2014 World Stroke Organization.)

Background and Purpose: In acute ischemic stroke patients treated by intravenous thrombolysis, a diffusion-weighted imaging (DWI) Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is an independent factor of functional outcomes. Our aim was to assess the impact of pretreatment DWI-ASPECTS on outcomes after endovascular therapy, with a specific emphasis on recanalization., Methods: We analyzed data collected between April 2007 and March 2013 in a prospective clinical registry of acute ischemic stroke patients treated by endovascular approach. Every patient with a documented internal carotid artery or middle cerebral artery occlusion who underwent an acute DWI-MRI before treatment was eligible for this study. The primary outcome was a favorable outcome defined by modified Rankin Scale of 0 to 2 at 90 days., Results: Two hundred ten patients were included and median DWI-ASPECTS was 7 (interquartile range, 4-8). DWI-ASPECTS≥5 was the optimal threshold to predict a favorable outcome (area under the curve=0.69; sensitivity, 90%; specificity, 38%). In a multivariate analysis including confounding variables, the adjusted odds ratio for favorable outcomes associated with a DWI-ASPECTS of ≥5 was 5.06 (95% confidence interval, 1.86-13.77; P=0.002). Nonetheless, the occurrence of a complete recanalization was associated with an increased rate of favorable outcomes in patients with DWI-ASPECTS under 5 (50% versus 3%, P<0.001)., Conclusions: DWI-ASPECTS≥5 seems to be the optimal threshold to predict favorable outcomes among patients undergoing endovascular reperfusion within 6 hours. Selected patients with a DWI-ASPECTS of <5 may still benefit when a complete reperfusion is achieved., (© 2014 American Heart Association, Inc.)

Background and Purpose: Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization., Methods: We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days., Results: A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5-43) after a median onset time to imaging of 110 minutes (interquartile range, 77-178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31-0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206-285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90-13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (P<0.005)., Conclusions: Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.

Background and Purpose: The potential detrimental effect of diabetes mellitus and admission glucose level (AGL) on outcomes after stroke thrombolysis is unclear. We evaluated outcomes of patients treated by intravenous and/or intra-arterial therapy, according to diabetes mellitus and AGL., Methods: We analyzed data from a patient registry (n=704) and conducted a systematic review of previous observational studies. The primary study outcome was the percentage of patients who achieved a favorable outcome (modified Rankin score ≤2 at 3 months)., Results: We identified 54 previous reports that evaluated the effect of diabetes mellitus or AGL on outcomes after thrombolysis. In an unadjusted meta-analysis that included our registry data and previous available observational data, diabetes mellitus was associated with less favorable outcome (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.73-0.79) and more symptomatic intracranial hemorrhage (OR, 1.38; 95% CI, 1.21-1.56). However, in multivariable analysis, diabetes mellitus remained associated with less favorable outcome (OR, 0.77; 95% CI, 0.69-0.87) but not with symptomatic intracranial hemorrhage (OR, 1.11; 95% CI, 0.83-1.48). In unadjusted and in adjusted meta-analysis, higher AGL was associated with less favorable outcome and more symptomatic intracranial hemorrhage; the adjusted OR (95% CI) per 1 mmol/L increase in AGL was 0.92 (0.90-0.94) for favorable outcome, and 1.09 (1.04-1.14) for symptomatic intracranial hemorrhage., Conclusions: These results confirm that AGL and history of diabetes mellitus are associated with poor clinical outcome after thrombolysis. AGL may be a surrogate marker of brain infarction severity rather than a causal factor. However, randomized controlled evidences are needed to address the significance of a tight glucose control during thrombolysis on clinical outcome.

Background and Purpose: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy., Methods: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2., Results: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33)., Conclusions: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset.

Objective: To evaluate the incidence, baseline characteristics, and clinical prognosis of blood-brain barrier (BBB) disruption after endovascular therapy in acute ischemic stroke patients., Methods: A total of 220 patients treated with endovascular therapy between April 2007 and October 2011 were identified from a prospective, clinical, thrombolysis registry. All patients underwent a nonenhanced CT scan immediately after treatment. CT scan or MRI was systematically realized at 24 hours to assess intracranial hemorrhage complications. BBB disruption was defined as a hyperdense lesion on the posttreatment CT scan., Results: BBB disruption was found in 128 patients (58.2%; 95% confidence interval [CI], 51.4%-64.9%). Cardioembolic etiology, high admission NIH Stroke Scale score, high blood glucose level, internal carotid artery occlusion, and use of combined endovascular therapy (chemical and mechanical revascularization) were independently associated with BBB disruption. Patients with BBB disruption had lower rates of early major neurologic improvement (8.6% vs 31.5%, p < 0.001), favorable outcome (39.8% vs 61.8%, p = 0.002), and higher rates of 90-day mortality (34.4% vs 14.6%, p = 0.001) and hemorrhagic complications (42.2% vs 8.7%, p < 0.001) than those without BBB disruption. By multivariable analysis, patients with BBB disruption remained with a lower rate of early neurologic improvement (adjusted odds ratio [OR], 0.28; 95% CI, 0.11-0.70) and with a higher rate of mortality (adjusted OR, 2.37; 95% CI, 1.06-5.32) and hemorrhagic complications (adjusted OR, 6.38; 95% CI, 2.66-15.28)., Conclusion: BBB disruption has a detrimental effect on outcome and is independently associated with mortality after endovascular therapy. BBB disruption assessment may have a role in prognosis staging in these patients.

Background and Purpose: Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular)., Methods: We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale≤3 at 24 hours or a decrease of ≥10 points within 24 hours., Results: DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P<0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P<0.001) and increased with tertiles of time to recanalization (Ptrend=0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61-10.77) for complete recanalization and 1.24 (95% CI, 1.04-1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale≤1 (67.6% versus 9.0%; P<0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P=0.024)., Conclusions: DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.

Background: The impact of prior statin use on outcomes after thrombolysis is unclear. We evaluated outcomes of patients treated by IV, intra-arterial (IA) thrombolysis, or combined therapy, according to prior statin use., Methods: We analyzed data from a patient registry (606 patients) and conducted a systematic review., Results: We identified 11 previous studies (6,438 patients) that evaluated the effect of statin use on outcomes after IV thrombolysis (8 studies), IA thrombolysis (2 studies), or a single/combined approach (1 study). In our registry and in most of the retrieved studies, statin users had more risk factors and concomitant antiplatelet treatment than nonstatin users. Regardless of treatment strategy, prior statin use was not associated with favorable outcome (adjusted odds ratio [OR] 1.36; 95 confidence interval [CI] 0.86-2.16), symptomatic intracranial hemorrhage (sICH) (OR 0.57; 95% CI 0.22-1.49), or recanalization (OR 1.87; 95% CI 0.69-5.03). In meta-analysis, prior statin use was not associated with favorable outcome (crude OR 0.99; 95% CI 0.88-1.12), but was associated with an increased risk of sICH (crude OR 1.55; 95% CI 1.23-1.95). However, when the available multivariable associations were combined (5 studies), the effect of prior statin use on risk of sICH was not significant (OR 1.31; 95% CI 0.97-1.76)., Conclusions: These results suggest no beneficial or detrimental effect of prior statin use in acute stroke patients treated by IV thrombolysis, IA thrombolysis, or combined therapy, although the numbers of patients treated by IA thrombolysis or combined therapy are too small to exclude an effect.

Background and Purpose: Pending the results of randomized controlled trials, the benefit and safety of bridging therapy (combined intravenous and intra-arterial thrombolysis) remain to be determined. The aim of this analysis was to give reliable estimates of efficacy and safety outcomes of bridging therapy., Methods: We conducted a systematic review of all studies using bridging therapy published between January 1966 and March 2011., Results: The literature search identified 15 studies. The pooled estimate for recanalization rate was 69.6% (95% CI, 63.9%-75.0%). Meta-analysis on clinical outcomes showed a pooled estimate of 48.9% (95% CI, 42.9%-54.9%) for favorable outcome, 17.9% (95% CI, 12.7%-23.7%) for mortality, and 8.6% (95% CI, 6.8%-10.6%) for symptomatic intracranial hemorrhage. In meta-regression analysis, the shorter mean time to intravenous treatment, the greater the recanalization rate (per 10-minute decrease: OR, 1.24; 95% CI, 1.02-1.51) and the lower mortality rate (per 10-minute decrease: OR, 0.75; 95% CI, 0.60-0.94). By using the control groups of intravenous alteplase-treated patients in 8 studies, bridging therapy was associated with a favorable outcome (OR, 2.26; 95% CI, 1.16-4.40), but no differences in mortality or symptomatic intracranial hemorrhage outcomes were found., Conclusions: Bridging therapy is associated with acceptable safety and efficacy in stroke patients. Time to intravenous treatment is critical to improve recanalization rates and favorable outcomes.

Background: Intravenous (IV) alteplase is not currently recommended in octogenarian patients, and the benefit/risk ratio of endovascular (intra-arterial, IA) therapy remains to be determined. The aim of this study was to determine the impact of a combined IV-IA approach in octogenarians., Methods: From a single-centre interventional study, we report age-specific outcomes of patients treated by a combined IV-IA thrombolytic approach. Patients ≥80 years with documented arterial occlusion treated by conventional IV thrombolysis constituted the control group., Results: Among 84 patients treated by the IV-IA approach, those ≥80 years (n = 25) had a similar rate of early neurological improvement to that of patients <80 years, whereas the 90-day favourable outcome rate was lower in octogenarians (adjusted odds ratio, OR, 0.21; 95% confidence interval, CI, 0.06-0.75). No difference in symptomatic intracranial haemorrhage was observed whereas a higher rate of 90-day mortality (adjusted OR, 3.27; 95% CI, 0.76-14.14) and asymptomatic intracranial haemorrhage (adjusted OR, 6.39; 95% CI, 1.54-26.63) were found in patients ≥80 years old. Among octogenarians, and compared to IV-thrombolysis-treated patients (n = 24), patients treated by the IV-IA approach had a higher rate of recanalization (76 vs. 33%, p = 0.003) associated with increased early neurological improvement (32 vs. 8%, p = 0.07). Although there was a higher rate of asymptomatic intracranial haemorrhage (44 vs. 8%, p = 0.005) observed in the IV-IA group, no difference existed in symptomatic intracranial haemorrhage rates and 90-day favourable outcome., Conclusion: The IV-IA approach in octogenarians was associated with lower efficacy at 3 months and higher mortality and asymptomatic haemorrhagic complications than in patients <80 years old. Definite recommendations cannot be given, but an endovascular approach may cause more harm than positive effects in patients over 80 years and should not be considered outside an approved protocol., (Copyright © 2011 S. Karger AG, Basel.)

Background: The efficacy of intravenous (IV) alteplase is restricted by the speed of recanalisation and the site of the occlusion. The aim of this study was to ascertain the effect of a combined IV-endovascular approach (intra-arterial alteplase and, if required, additional thrombectomy) in patients with stroke due to arterial occlusion., Methods: We compared recanalisation rates, neurological improvement at 24 h, and functional outcome at 3 months between two periods (February, 2002, to March, 2007, vs April, 2007, to October, 2008) in patients in a prospective registry who were treated with different regimens of alteplase within 3 h of symptom onset. Patients with confirmed occlusion who were treated before April, 2007, were treated with IV alteplase; after April, 2007, patients were treated with a systematic IV-endovascular approach. Analysis was by intention to treat., Findings: 46 (87%) of 53 patients treated with the IV-endovascular approach achieved recanalisation versus 56 (52%) of 107 patients in the IV group (adjusted relative risk [RR] 1.49, 95% CI 1.21-1.84; p=0.0002). Early neurological improvement (NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h) occurred in 32 (60%) patients in the IV-endovascular group and 42 (39%) patients in the IV group (adjusted RR 1.36, 0.97-1.91; p=0.07). Favourable outcome (mRS of 0-2 at 90 days) occurred in 30 (57%) patients in the IV-endovascular group and 47 (44%) patients in the IV group (adjusted RR 1.16, 0.85-1.58; p=0.35). The mortality rate at 90 days was 17% in both groups, and symptomatic intracranial haemorrhage was reported in five (9%) patients in the IV-endovascular group and in 12 (11%) patients in the IV group. Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV-endovascular group., Interpretation: An IV-endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion. In patients treated with an IV-endovascular approach, a shorter time from symptom onset to recanalisation is associated with better clinical outcomes.

Background and purpose: Tandem anterior circulation lesions in the setting of acute ischemic stroke (AIS) are a complex endovascular situation that has not been specifically addressed in trials. We determined the predictors of successful reperfusion and good clinical outcome at 90 days after mechanical thrombectomy (MT) in patients with AIS with tandem lesions in a pooled collaborative study. Methods: This was a retrospective analysis of consecutive patients presenting to 18 comprehensive stroke centers with AIS due to tandem lesion of the anterior circulation who underwent MT. Results: A total of 395 patients were included. Successful reperfusion (modified thrombolysis in cerebral infarction score 2b–3) was achieved in 76.7%. At 90 days, 52.2% achieved a good outcome (modified Rankin Scale score 0–2), 13.8% suffered a parenchymal hematoma and 13.2% were dead. Lower National Institutes of Health Stroke Scale score [odds ratio (OR), 1.26; 95% confidence intervals (CI), 1.07–1.48, P = 0.004], Alberta Stroke Program Early CT Score ≥7 (OR, 2.00; 95% CI, 1.07–3.43, P = 0.011), intravenous thrombolysis (OR, 1.47; 95% CI, 1.01–2.12, P = 0.042) and stenting of the extracranial carotid lesion (OR, 1.63; 95% CI, 1.04–2;53, P = 0.030) were independently associated with successful reperfusion. Lower age (OR, 1.58; 95% CI, 1.26–1.97, P < 0.001), absence of hypercholesterolemia (OR, 1.77; 95% CI, 1.10–2.84, P = 0.018), lower National Institutes of Health Stroke Scale scores (OR, 2.04; 95% CI, 1.53–2.72, P < 0.001), Alberta Stroke Program Early CT Score ≥7 (OR, 2.75; 95% CI, 1.24–6.10, P = 0.013) and proximal middle cerebral artery occlusion (OR, 1.59; 95% CI, 1.03–2.44, P = 0.035) independently predicted a good 90‐day outcome. Conclusions: Intravenous thrombolysis and emergent stenting of the extracranial carotid lesion were predictors of a successful reperfusion after MT of patients with AIS with tandem lesion of the anterior circulation. [ABSTRACT FROM AUTHOR]

Background and purpose: The DAWN trial recently showed compelling evidence in treating late window and wake‐up stroke patients with thrombectomy using a clinical‐imaging mismatch. The aim was to evaluate the results of thrombectomy for unknown‐onset strokes (UOS) treated in our centres after a diffusion weighted imaging/fluid attenuated inversion recovery (DWI‐FLAIR) mismatch based selection. Methods: A multicentre, cohort study was performed of consecutive UOS treated by thrombectomy between 2012 and 2016. UOS with proximal anterior circulation occlusion discovered beyond 6 h from ‘last seen normal’ were compared with known‐onset strokes (KOS) for whom thrombectomy was started within 6 h from onset. Time intervals were recorded from first time found abnormal. Results were adjusted for age, diabetes, hypertension, National Institutes of Health Stroke Scale, site of occlusion, DWI Alberta Stroke Programme Early CT Score, intravenous thrombolysis and use of general anaesthesia. Results: Amongst 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a ‘last time seen well’ beyond 6 h and DWI‐FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 h. Favourable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, P = 0.022). After pre‐specified adjustment, this difference was not significant (adjusted relative risk 0.91; 95% confidence interval 0.80–1.04; P = 0.17). No differences were found in secondary outcomes. Time intervals from first found abnormal were significantly longer in UOS. Conclusion: Thrombectomy of UOS with anterior circulation occlusion and DWI‐FLAIR mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h from onset. This pattern of imaging could be used for patient selection when time of onset is unknown. [ABSTRACT FROM AUTHOR]

Background and purpose The endothelium is crucial in maintaining the haemostatic balance between pro- and anti-thrombotic factors. In this pilot study, the association of endothelial biomarkers with arterial recanalization and clinical outcome in the setting of acute ischaemic stroke ( AIS) was evaluated amongst patients treated with recombinant tissue plasminogen activator (rt- PA). Methods Sixty-four AIS patients treated with rt-PA were prospectively recruited. Blood was collected before thrombolysis and analysed for von Willebrand factor ( vWF), soluble thrombomodulin ( sTM) and soluble endothelial protein C receptor ( sEPCR). Complete recanalization was defined by a Thrombolysis in Myocardial Infarction Score of 3. Favourable clinical outcome was defined by a modified Rankin Score of 0-2 at 90 days. Results Amongst the 64 patients, 31 had no documented occlusion, 19 had persistent occlusion and 14 had complete recanalization. After adjustment for confounding factors, these patients presented lower sTM and sEPCR levels than patients with persistent occlusion (median sTM, 21 vs. 48 ng/ml, P = 0.008; median sEPCR, 78 vs. 114 ng/ml, P = 0.018), but similar levels compared with patients without occlusion. vWF levels did not differ between groups. None of these biomarkers was significantly associated with favourable outcome. Conclusions Recanalization after thrombolytic therapy is associated with low sTM and sEPCR levels but not with vWF levels. If corroborated in further larger studies, these findings could be helpful in the identification of patients resistant to rt-PA thrombolysis who could benefit from a modified recanalization therapy. [ABSTRACT FROM AUTHOR]