IMPORTANCE: Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of ...treatment time with outcomes would help to guide implementation. OBJECTIVE: To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. DESIGN, SETTING, AND PATIENTS: Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. EXPOSURES: Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. RESULTS: Among all 1287 patients (endovascular thrombectomy + medical therapy n = 634; medical therapy alone n = 653) enrolled in the 5 trials (mean age, 66.5 years SD, 13.1; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 95% CI, 0.76 to 0.93; ARD, −6.7%) and less functional independence (OR, 0.81 95% CI, 0.71 to 0.92, ARD, −5.2% 95% CI, −8.3% to −2.1%), but no change in mortality (OR, 1.12 95% CI, 0.93 to 1.34; ARD, 1.5% 95% CI, −0.9% to 4.2%). CONCLUSIONS AND RELEVANCE: In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.
Computed tomography perfusion (CTP) is widely used in the evaluation of acute ischemic stroke patients for endovascular thrombectomy (EVT). The stability of CTP core estimation is suboptimal and ...varies between software packages. We aimed to quantify the volumetric and spatial agreement between the CTP ischemic core and follow-up infarct for four ischemic core estimation approaches using syngo.via.
We included successfully reperfused, EVT-treated patients with baseline CTP and 24h follow-up diffusion weighted magnetic resonance imaging (DWI) (November 2017-September 2020). Data were processed with syngo.via VB40 using four core estimation approaches based on: cerebral blood volume (CBV)<1.2mL/100mL with and without smoothing filter, relative cerebral blood flow (rCBF)<30%, and rCBF<20%. The follow-up infarct was segmented on DWI.
In 59 patients, median estimated CTP core volumes for four core estimation approaches ranged from 12-39 mL. Median 24h follow-up DWI infarct volume was 11 mL. The intraclass correlation coefficient (ICC) showed moderate-good volumetric agreement for all approaches (range 0.61-0.76). Median Dice was low for all approaches (range 0.16-0.21). CTP core overestimation >10mL occurred least frequent (14/59 24% patients) using the CBV-based core estimation approach with smoothing filter.
In successfully reperfused patients who underwent EVT, syngo.via CTP ischemic core estimation showed moderate volumetric and spatial agreement with the follow-up infarct on DWI. In patients with complete reperfusion after EVT, the volumetric agreement was excellent. A CTP core estimation approach based on CBV<1.2 mL/100mL with smoothing filter least often overestimated the follow-up infarct volume and is therefore preferred for clinical decision making using syngo.via.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses ...to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN).
MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status.
We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 95% confidence intervals 1.7-6.2) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 95% confidence intervals 1.0-2.7 for moderate collaterals (grade 2), 1.2 95% confidence intervals 0.7-2.3 for poor collaterals (grade 1), and 1.0 95% confidence intervals 0.1-8.7 for patients with absent collaterals (grade 0).
In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals.
URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.
BACKGROUND AND PURPOSE—Increasing thrombus length (TL) impedes recanalization after intravenous (IV) thrombolysis. We sought to determine whether the clinical benefit of aspiration thrombectomy ...relative to IV r-tPA (recombinant tissue-type plasminogen activator) may be greater at longer TL.
METHODS—THERAPY was a randomized trial of aspiration thrombectomy plus IV r-tPA versus IV r-tPA alone in large-vessel stroke patients with prospective TL measurement ≥8 mm. In this post hoc study, we evaluated the association of TL with trial end points and potential endovascular treatment effect, using univariate, multivariable, and multiplicative interaction analyses.
RESULTS—TL data were available for all 108 patients (28% internal carotid artery, 62% M1, and 10% M2). Median TL was 14.0 mm (interquartile range, 9.7–19.5 mm). Longer TL was associated with worse outcome (90-day modified Rankin Scale scoreodds ratio, 1.24 per 5-mm TL increment; 95% confidence interval, 1.04–1.52; P=0.02), even after adjusting for key outcome predictors (adjusted P=0.004). Longer TL was also associated with more serious adverse events (adjusted P=0.01), more symptomatic hemorrhages (adjusted P=0.03), and increased mortality (adjusted P=0.01). No significant relationship was observed between TL and angiographic reperfusion (modified thrombolysis in cerebral ischemia 2b-3), but greater TL was associated with longer endovascular procedural times (ρ=0.36; P=0.045). Increasing TL was associated with greater aspiration thrombectomy treatment effect (interaction term P=0.03). This might be related to a potentially stronger adverse effect of increasing TL on 90-day modified Rankin Scale for patients treated with IV r-tPA (ρ=0.39; P=0.01) compared with intra-arterial therapy (ρ=0.20; P=0.165).
CONCLUSIONS—Ischemic stroke patients with longer symptomatic thrombi have worse 90-day clinical outcomes but may have a greater relative benefit of aspiration thrombectomy over IV r-tPA alone.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01429350.
Objective To improve the selection of patients with acute ischaemic stroke for intra-arterial treatment using a clinical decision tool to predict individual treatment benefit.Design Multivariable ...regression modelling with data from two randomised controlled clinical trials.Setting 16 hospitals in the Netherlands (derivation cohort) and 58 hospitals in the United States, Canada, Australia, and Europe (validation cohort).Participants 500 patients from the Multicenter Randomised Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands trial (derivation cohort) and 260 patients with intracranial occlusion from the Interventional Management of Stroke III trial (validation cohort).Main outcome measures The primary outcome was the modified Rankin Scale (mRS) score at 90 days after stroke. We constructed an ordinal logistic regression model to predict outcome and treatment benefit, defined as the difference between the predicted probability of good functional outcome (mRS score 0-2) with and without intra-arterial treatment.Results 11 baseline clinical and radiological characteristics were included in the model. The externally validated C statistic was 0.69 (95% confidence interval 0.64 to 0.73) for the ordinal model and 0.73 (0.67 to 0.79) for the prediction of good functional outcome, indicating moderate discriminative ability. The mean predicted treatment benefit varied between patients in the combined derivation and validation cohort from −2.3% to 24.3%. There was benefit of intra-arterial treatment predicted for some individual patients from groups in which no treatment effect was found in previous subgroup analyses, such as those with no or poor collaterals.Conclusion The proposed clinical decision tool combines multiple baseline clinical and radiological characteristics and shows large variations in treatment benefit between patients. The tool is clinically useful as it aids in distinguishing between individual patients who may experience benefit from intra-arterial treatment for acute ischaemic stroke and those who will not.Trial registration clinicaltrials.gov NCT00359424 (IMS III) and isrctn.com ISRCTN10888758 (MR CLEAN).
Purpose To investigate the prevalence of symptomatic carotid web in patients with acute ischemic stroke due to intracranial large vessel occlusion, to determine the clinical and imaging profile of ...patients with carotid web as well as their association with ischemic stroke, and to determine the interobserver agreement in the assessment of carotid webs. Materials and Methods All patients (n = 500) of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) in whom the carotid bifurcation could be assessed (n = 443) were included. The presence of a carotid web at the carotid bifurcations was evaluated at computed tomographic (CT) angiography. Demographics, clinical characteristics, and imaging baseline characteristics were presented by descriptive statistics for patients with an identified carotid web. Interobserver agreement in the detection of carotid webs was examined by using kappa statistics. Results Eleven (2.5%) carotid webs were found at the symptomatic side and two (0.5%) carotid webs were found at the asymptomatic side. Ten (91%) patients with a symptomatic carotid web were female. Nine patients with a symptomatic carotid web did not have major risk factors or other causes for ischemic stroke (82%). Fair to good interobserver agreement (κ, 0.72) was observed for diagnosing carotid webs at CT angiography. Conclusion Carotid webs at the symptomatic carotid bifurcation were observed in 2.5% of the patients with acute ischemic stroke due to large vessel occlusion and were mostly diagnosed in female patients with a fair to good interobserver agreement.
RSNA, 2017 Clinical trial registration nos. NTR1804 and ISRCTN10888758 Online supplemental material is available for this article.
In a follow-up of a trial comparing endovascular thrombectomy with conventional therapy for acute ischemic stroke, the beneficial effect on functional recovery that was observed at 90 days was ...maintained at 2 years. Quality of life was better at 2 years with endovascular treatment.
We reported previously the 90-day outcomes of a trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands MR CLEAN) in which standard treatment was compared with endovascular treatment, administered within 6 hours after the onset of acute ischemic stroke caused by an intracranial arterial occlusion of the anterior circulation.
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Most patients in the intervention group were treated by mechanical thrombectomy with the use of retrievable stents. The trial showed that functional recovery at 90 days was better with the intervention than with standard treatment. Subsequently, the beneficial effect of mechanical thrombectomy on 90-day outcomes . . .
CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions ...misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.
This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.
Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43-1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15-1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.
For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly differed between ischemic lesion agreement and misclassified CTP ischemic core, suggesting that CTP analysis may benefit from revisions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endovascular or intra-arterial treatment (IAT) increases the likelihood of recanalization in patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion. However, a ...beneficial effect of IAT on functional recovery in patients with acute ischemic stroke remains unproven. The aim of this study is to assess the effect of IAT on functional outcome in patients with acute ischemic stroke. Additionally, we aim to assess the safety of IAT, and the effect on recanalization of different mechanical treatment modalities.
A multicenter randomized clinical trial with blinded outcome assessment. The active comparison is IAT versus no IAT. IAT may consist of intra-arterial thrombolysis with alteplase or urokinase, mechanical treatment or both. Mechanical treatment refers to retraction, aspiration, sonolysis, or use of a retrievable stent (stent-retriever). Patients with a relevant intracranial proximal arterial occlusion of the anterior circulation, who can be treated within 6 hours after stroke onset, are eligible. Treatment effect will be estimated with ordinal logistic regression (shift analysis); 500 patients will be included in the trial for a power of 80% to detect a shift leading to a decrease in dependency in 10% of treated patients. The primary outcome is the score on the modified Rankin scale at 90 days. Secondary outcomes are the National Institutes of Health stroke scale score at 24 hours, vessel patency at 24 hours, infarct size on day 5, and the occurrence of major bleeding during the first 5 days.
If IAT leads to a 10% absolute reduction in poor outcome after stroke, careful implementation of the intervention could save approximately 1% of all new stroke cases from death or disability annually.
NTR1804 (7 May 2009)/ISRCTN10888758 (24 July 2012).
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