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.
BACKGROUND AND PURPOSE—To assess the effect of inter-hospital transfer on time to treatment and functional outcome after endovascular treatment (EVT) for acute ischemic stroke, we compared patients ...transferred from a primary stroke center to patients directly admitted to an intervention center in a large nationwide registry.
METHODS—MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry is an ongoing, prospective, observational study in all centers that perform EVT in the Netherlands. We included adult patients with an acute anterior circulation stroke who received EVT between March 2014 to June 2016. Primary outcome was time from arrival at the first hospital to arterial groin puncture. Secondary outcomes included the 90-day modified Rankin Scale score and functional independence (modified Rankin Scale score of 0–2).
RESULTS—In total 821/1526 patients, (54%) were transferred from a primary stroke center. Transferred patients less often had prestroke disability (227/800 28% versus 255/699 36%; P=0.02) and more often received intravenous thrombolytics (659/819 81% versus 511/704 73%; P<0.01). Time from first presentation to groin puncture was longer for transferred patients (164 versus 104 minutes; P<0.01, adjusted delay 57 minutes 95% CI, 51–62). Transferred patients had worse functional outcome (adjusted common OR, 0.75 95% CI, 0.62–0.90) and less often achieved functional independence (244/720 34% versus 289/681 42%, absolute risk difference −8.5% 95% CI, −8.7 to −8.3).
CONCLUSIONS—Interhospital transfer of patients with acute ischemic stroke is associated with delay of EVT and worse outcomes in routine clinical practice, even in a country where between-center distances are short. Direct transportation of patients potentially eligible for EVT to an intervention center may improve functional outcome.
BACKGROUND AND PURPOSE—Thrombus imaging characteristics have been reported to be useful to predict functional outcome and reperfusion in acute ischemic stroke. However, conflicting data about this ...subject exist in patients undergoing endovascular treatment. Therefore, we aimed to evaluate whether thrombus imaging characteristics assessed on computed tomography are associated with outcomes in patients with acute ischemic stroke treated by endovascular treatment.
METHODS—The MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry is an ongoing, prospective, and observational study in all centers performing endovascular treatment in the Netherlands. We evaluated associations of thrombus imaging characteristics with the functional outcome (modified Rankin Scale at 90 days), mortality, reperfusion, duration of endovascular treatment, and symptomatic intracranial hemorrhage using univariable and multivariable regression models. Thrombus characteristics included location, clot burden score (CBS), length, relative and absolute attenuation, perviousness, and distance from the internal carotid artery terminus to the thrombus. All characteristics were assessed on thin-slice (≤2.5 mm) noncontrast computed tomography and computed tomography angiography, acquired within 30 minutes from each other.
RESULTS—In total, 408 patients were analyzed. Thrombus with distal location, higher CBS, and shorter length were associated with better functional outcome (adjusted common odds ratio, 3.3; 95% CI, 2.0–5.3 for distal M1 occlusion compared with internal carotid artery occlusion; adjusted common odds ratio, 1.15; 95% CI, 1.07–1.24 per CBS point; and adjusted common odds ratio, 0.96; 95% CI, 0.94–0.99 per mm, respectively) and reduced duration of endovascular procedure (adjusted coefficient B, −14.7; 95% CI, −24.2 to −5.1 for distal M1 occlusion compared with internal carotid artery occlusion; adjusted coefficient B, −8.5; 95% CI, −14.5 to −2.4 per CBS point; and adjusted coefficient B, 7.3; 95% CI, 2.9–11.8 per mm, respectively). Thrombus perviousness was associated with better functional outcome (adjusted common odds ratio, 1.01; 95% CI, 1.00–1.02 per Hounsfield units increase). Distal thrombi were associated with successful reperfusion (adjusted odds ratio, 2.6; 95% CI, 1.4–4.9 for proximal M1 occlusion compared with internal carotid artery occlusion).
CONCLUSIONS—Distal location, higher CBS, and shorter length are associated with better functional outcome and faster endovascular procedure. Distal thrombus is strongly associated with successful reperfusion, and a pervious thrombus is associated with better functional outcome.
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 . . .
Endovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. ...Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO.
MR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included.
IVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT.
www.isrctn.com : ISRCTN80619088 . Registered on 31 October 2017.
The Society of Neurointerventional Surgery revised its operational definition of emergent large vessel occlusion (ELVO) recently to include proximal M2 segment middle cerebral artery (MCA) ...occlusions. We sought to assess the benefit of endovascular thrombectomy (EVT) over best medical care for M2 segment MCA occlusion.
Patient level data from trials in the HERMES Collaboration were included. The HERMES core laboratory identified patients with M2 segment MCA occlusions and further classified them as proximal versus distal, anterior versus posterior division, and dominant versus co-dominant versus non-dominant. Primary outcome was modified Rankin Scale (mRS) score 0-2 at 90 days. Secondary outcomes were modified Thrombolysis in Cerebral Infarction (mTICI) rates at end of procedure, 90-day mRS shift, 90-day mRS 0-1, 24 hours National Institute of Health Stroke Scale (NIHSS) score 0-2, symptomatic intracerebral hemorrhage (ICH), and death.
130 patients with M2 MCA (proximal location n=116 vs distal n=14, anterior division n=72 vs posterior n=58, dominant n=73 vs co-dominant n=50 vs non-dominant n=7) were included. Successful reperfusion (mTICI 2b or 3) among those undergoing EVT was seen in 59.2% of patients. Treatment effect favored EVT (adjusted OR 2.39, 95% CI 1.08 to 5.28, p=0.03) for 90-day mRS 0-2 (58.2% EVT vs 39.7% control). Direction of benefit favored EVT for other outcomes. Treatment effect favoring EVT was maximal in patients with proximal M2 segment MCA occlusions (n=116, adjusted OR 2.68, 95% CI 1.13 to 6.37) and in dominant M2 segment MCA occlusions (n=73, adjusted OR 4.08, 95% CI 1.08 to 15.48). No sICH (0%) was observed in patients treated with EVT compared with five (7.9%) in the control arm.
Patients with proximal M2 segment MCA occlusions eligible for EVT trial protocols benefited from EVT.
Patients with aneurysmal subarachnoid hemorrhage (SAH) who experience delayed cerebral ischemia (DCI) have an increased risk of poor outcome. Delayed cerebral ischemia is considered to be caused by ...vasospasm. However, not all patients with DCI have vasospasm. Inversely, not all patients with vasospasm develop clinical symptoms and signs of DCI. In the past, treatments aiming at vasospasm were not successful in preventing ischemia. The purpose of this review is to give an overview of clinical data showing that DCI cannot always be attributed to vasospasm, and to present an in-depth analysis of clinical and autopsy studies on the role of microthrombosis in the pathogenesis of DCI. Clinical studies show that DCI is associated with an activation of the coagulation cascade within a few days after SAH, preceding the time window during which vasospasm occurs. Furthermore, impaired fibrinolytic activity, and inflammatory and endothelium-related processes, lead to the formation of microthrombi, which ultimately result in DCI. The presence of microthrombi is confirmed by autopsy studies. Insight in the pathophysiology of DCI is crucial for the development of effective therapies against this complication. Because multiple pathways are involved, future research should focus on drugs with pleiotropic effects.
•Prediction of the final infarct volume in acute ischemic stroke patients.•Takes into account the baseline CTP images and the time and treatment parameters.•Convolutional neural network trained and ...validated on a multicenter dataset.•Operates on the native CTP measurements without explicit deconvolution.•Improved performance over classical approach.
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CT Perfusion (CTP) imaging has gained importance in the diagnosis of acute stroke. Conventional perfusion analysis performs a deconvolution of the measurements and thresholds the perfusion parameters to determine the tissue status. We pursue a data-driven and deconvolution-free approach, where a deep neural network learns to predict the final infarct volume directly from the native CTP images and metadata such as the time parameters and treatment. This would allow clinicians to simulate various treatments and gain insight into predicted tissue status over time. We demonstrate on a multicenter dataset that our approach is able to predict the final infarct and effectively uses the metadata. An ablation study shows that using the native CTP measurements instead of the deconvolved measurements improves the prediction.
Endovascular therapy (EVT) for acute ischemic stroke due to proximal occlusion of the anterior intracranial circulation, started within 6 h from symptom onset, has been proven safe and effective. ...Recently, EVT has been proven effective beyond the 6-h time window in a highly selected population using CT perfusion or MR diffusion. Unfortunately, these imaging modalities are not available in every hospital, and strict selection criteria might exclude patients who could still benefit from EVT. The presence of collaterals on CT angiography (CTA) may offer a more pragmatic imaging criterion that predicts possible benefit from EVT beyond 6 h from time last known well. The aim of this study is to assess the safety and efficacy of EVT for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow.
The MR CLEAN-LATE trial is a multicenter, randomized, open-label, blinded endpoint trial, aiming to enroll 500 patients. We will investigate the efficacy of EVT between 6 and 24 h from time last known well in acute ischemic stroke due to a proximal intracranial anterior circulation occlusion confirmed by CTA or MRA. Patients with any collateral flow (poor, moderate, or good collaterals) on CTA will be included. The inclusion of poor collateral status will be restricted to a maximum of 100 patients. In line with the current Dutch guidelines, patients who fulfill the characteristics of included patients in DAWN and DEFUSE 3 will be excluded as they are eligible for EVT as standard care. The primary endpoint is functional outcome at 90 days, assessed with the modified Rankin Scale (mRS) score. Treatment effect will be estimated with ordinal logistic regression (shift analysis) on the mRS at 90 days. Secondary endpoints include clinical stroke severity at 24 h and 5-7 days assessed by the NIHSS, symptomatic intracranial hemorrhage, recanalization at 24 h, follow-up infarct size, and mortality at 90 days, DISCUSSION: This study will provide insight into whether EVT is safe and effective for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow on CTA.
NL58246.078.17 , ISRCTN19922220 , Registered on 11 December 2017.
BACKGROUND AND PURPOSE—A score of ≥2B on the modified Thrombolysis in Cerebral Infarction scale is generally regarded as successful reperfusion after endovascular treatment for ischemic stroke. The ...extended Thrombolysis in Cerebral Infarction (eTICI) includes a 2C grade, which indicates near-perfect reperfusion. We investigated how well the respective eTICI scores of 2B, 2C, and 3 correlate with clinical outcome after endovascular treatment.
METHODS—We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, nationwide registry of endovascular treatment in the Netherlands. We included patients with a proximal intracranial occlusion of the anterior circulation for whom final antero-posterior and lateral digital subtraction angiography imaging was available. Our primary outcome was the distribution on the modified Rankin Scale at 90 days per eTICI grade. We performed (ordinal) logistic regression analyses, using eTICI 2B as reference group, and adjusted for potential confounders.
RESULTS—In total, 2807/3637 (77%) patients met the inclusion criteria. Of these, 17% achieved reperfusion grade eTICI 0 to 1, 14% eTICI 2A, 25% eTICI 2B, 12% eTICI 2C, and 32% eTICI 3. Groups differed in terms of age (P<0.001) and occlusion location (P<0.01). Procedure times decreased with increasing reperfusion grades. We found a positive association between reperfusion grade and functional outcome, which continued to increase after eTICI 2B (adjusted common odds ratio, 1.22 95% CI, 0.96–1.57 for eTICI 2C versus 2B; adjusted common odds ratio, 1.33 95% CI, 1.09–1.62 for eTICI 3 versus 2B).
CONCLUSIONS—Our results indicate a continuous relationship between reperfusion grade and functional outcome, with eTICI 3 leading to the best outcomes. Although this implies that interventionists should aim for the highest possible reperfusion grade, further research on the optimal strategy is necessary.
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