The overwhelming clinical benefit of intra-arterial stroke therapy owes to the major advance in revascularization brought on by the current generation of thrombectomy devices. Nevertheless, there ...remains a sizeable proportion of patients for whom substantial reperfusion cannot be achieved or is achieved too late. This article addresses the persistent challenges that face neurointerventionists and reviews technical refinements that may help to mitigate these obstacles to procedural success. Insights from in vitro modeling and clinical research are organized around a conceptual framework that examines the interaction between the device, the thrombus and the vessel wall.
BACKGROUND AND PURPOSE—Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this ...benefit is exclusive to stent retrievers is unclear.
METHODS—THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System’s Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0–2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany).
RESULTS—Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86–3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT12% versus intravenous23.9%, P=0.18) were observed.
CONCLUSIONS—THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01429350.
BACKGROUND AND PURPOSE—The availability of and expertise to interpret advanced neuroimaging recommended in the guideline-based endovascular stroke therapy (EST) evaluation are limited. Here, we ...develop and validate an automated machine learning-based method that evaluates for large vessel occlusion (LVO) and ischemic core volume in patients using a widely available modality, computed tomography angiogram (CTA).
METHODS—From our prospectively maintained stroke registry and electronic medical record, we identified patients with acute ischemic stroke and stroke mimics with contemporaneous CTA and computed tomography perfusion (CTP) with RAPID (IschemaView) post-processing as a part of the emergent stroke workup. A novel convolutional neural network named DeepSymNet was created and trained to identify LVO as well as infarct core from CTA source images, against CTP-RAPID definitions. Model performance was measured using 10-fold cross validation and receiver-operative curve area under the curve (AUC) statistics.
RESULTS—Among the 297 included patients, 224 (75%) had acute ischemic stroke of which 179 (60%) had LVO. Mean CTP-RAPID ischemic core volume was 23±42 mL. LVO locations included internal carotid artery (13%), M1 (44%), and M2 (21%). The DeepSymNet algorithm autonomously learned to identify the intracerebral vasculature on CTA and detected LVO with AUC 0.88. The method was also able to determine infarct core as defined by CTP-RAPID from the CTA source images with AUC 0.88 and 0.90 (ischemic core ≤30 mL and ≤50 mL). These findings were maintained in patients presenting in early (0–6 hours) and late (6–24 hours) time windows (AUCs 0.90 and 0.91, ischemic core ≤50 mL). DeepSymNet probabilities from CTA images corresponded with CTP-RAPID ischemic core volumes as a continuous variable with r=0.7 (Pearson correlation, P<0.001).
CONCLUSIONS—These results demonstrate that the information needed to perform the neuroimaging evaluation for endovascular therapy with comparable accuracy to advanced imaging modalities may be present in CTA, and the ability of machine learning to automate the analysis.
IMPORTANCE: Endovascular therapy (EVT) is the standard of care for select patients who had a stroke caused by a large vessel occlusion in the anterior circulation, but there is uncertainty regarding ...the optimal anesthetic approach during EVT. Observational studies suggest that general anesthesia (GA) is associated with worse outcomes compared with conscious sedation (CS). OBJECTIVE: To examine the effect of type of anesthesia during EVT on infarct growth and clinical outcome. DESIGN, SETTING, AND PARTICIPANTS: The General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center prospective, randomized, open-label, blinded end-point evaluation that enrolled patients from March 12, 2015, to February 2, 2017. Although the trial screened 1501 patients, it included 128 consecutive patients with acute ischemic stroke caused by large vessel occlusions in the anterior circulation within 6 hours of onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not provide consent were excluded. Primary analysis was unadjusted and according to the intention-to-treat principle. INTERVENTIONS: Patients were randomized to either the GA group or the CS group (1:1 allocation) before EVT. MAIN OUTCOMES AND MEASURES: The primary end point was infarct growth between magnetic resonance imaging scans performed before EVT and 48 to 72 hours after EVT. The hypothesis formulated before data collection was that patients who were under CS would have less infarct growth. RESULTS: Of 128 patients included in the trial, 65 were randomized to GA, and 63 were randomized to CS. For the entire cohort, the mean (SD) age was 71.4 (11.4) years, and 62 (48.4%) were women. Baseline demographic and clinical variables were balanced between the GA and CS treatment arms. The median National Institutes of Health Stroke Scale score was 18 (interquartile range IQR, 14-21). Four patients (6.3%) in the CS group were converted to the GA group. Successful reperfusion was significantly higher in the GA arm than in the CS arm (76.9% vs 60.3%; P = .04). The difference in the volume of infarct growth among patients treated under GA or CS did not reach statistical significance (median IQR growth, 8.2 2.2-38.6 mL vs 19.4 2.4-79.0 mL; P = .10). There were better clinical outcomes in the GA group, with an odds ratio for a shift to a lower modified Rankin Scale score of 1.91 (95% CI, 1.03-3.56). CONCLUSIONS AND RELEVANCE: For patients who underwent thrombectomy for acute ischemic stroke caused by large vessel occlusions in the anterior circulation, GA did not result in worse tissue or clinical outcomes compared with CS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02317237
This trial assessed the value of brain imaging to guide treatment for stroke. Clinical outcomes with embolectomy were not superior to those with standard care in all patients or in the subgroup ...identified by brain imaging as most likely to benefit from embolectomy.
Multiple randomized, controlled trials have shown the efficacy of the use of intravenous tissue plasminogen activator (t-PA), administered up to 4.5 hours after the onset of symptoms of acute ischemic stroke.
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However, the global effect of this therapy has been limited, largely because of the narrow time window available for treatment and the risk of symptomatic intracerebral hemorrhage. Although endovascular approaches, including thrombectomy devices, have been shown to achieve greater rates of recanalization than the use of intravenous t-PA, no randomized, controlled trial has been completed comparing clinical outcomes versus standard medical care. Moreover, the potential to benefit from . . .
Stent retrievers and large-bore aspiration catheters have doubled substantial reperfusion rates compared to first-generation devices. This has been accompanied by a 3-fold reduction in procedural ...time to revascularization. To measure future thrombectomy improvements, new benchmarks for technical efficacy are needed. This review summarizes the recent literature concerning biomarkers of procedural success and harm and highlights future directions.
Expanded Treatment in Cerebral Ischemia (eTICI), which incorporates scores for greater levels of reperfusion, improves outcome prediction. Core laboratory-adjudicated studies show that outcomes following eTICI 2c (90%-99% reperfusion) are superior to eTICI 2b50 and nearly equivalent to eTICI 3. Moreover, eTICI 2c improves scale reliability. Studies also confirm the importance of rapid revascularization, whether measured as first pass effect or procedural duration under 30 minutes. Distal embolization is a complication that impedes the extent and speed of revascularization, but few studies have reported its per-pass occurrence. Distal embolization and emboli to new territory should be measured after each thrombectomy maneuver. Collaterals have been shown to be an important modifier of thrombectomy benefit. A drawback of the currently accepted collateral grading scale is that it does not discriminate among the broad spectrum of partial collateralization. Important questions that require investigation include reasons for failed revascularization, the utility of a global Treatment in Cerebral Ischemia scale, and the optimal grading system for vertebrobasilar occlusions.
Emerging data support a lead technical efficacy endpoint that combines the extent and speed of reperfusion. Efforts are needed to better characterize angiographic measures of treatment harm and of collateralization.
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.
Objective
Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid‐attenuated inversion ...recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion‐weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline‐recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open‐label, phase 2a, prospective study (NCT01282242).
Methods
Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90‐day modified Rankin Scale (mRS).
Results
Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5–13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0–1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions.
Interpretation
Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980–993
BACKGROUND AND PURPOSE—In acute ischemic stroke, fast and complete recanalization of the occluded vessel is associated with improved outcomes. We describe a novel measure for newer generation ...devicesthe first pass effect (FPE). FPE is defined as achieving a complete recanalization with a single thrombectomy device pass.
METHODS—The North American Solitaire Acute Stroke Registry database was used to identify a FPE subgroup. Their baseline features and clinical outcomes were compared with non-FPE patients. Clinical outcome measures included 90-days modified Rankin Scale score, National Institutes of Health Stroke Scale score, mortality, and symptomatic intracranial hemorrhage. Multivariate analyses were performed to determine whether FPE independently resulted in improved outcomes and to identify predictors of FPE.
RESULTS—A total of 354 acute ischemic stroke patients underwent thrombectomy in the North American Solitaire Acute Stroke registry. FPE was achieved in 89 out of 354 (25.1%). More middle cerebral artery occlusions (64% versus 52.5%) and fewer internal carotid artery occlusions (10.1% versus 27.7%) were present in the FPE group. Balloon guide catheters were used more frequently with FPE (64.0% versus 34.7%). Median time to revascularization was significantly faster in the FPE group (median 34 versus 60 minutes; P=0.0003). FPE was an independent predictor of good clinical outcome (modified Rankin Scale score ≤2 was seen in 61.3% in FPE versus 35.3% in non-FPE cohort; P=0.013; odds ratio, 1.7; 95% confidence interval, 1.1–2.7). The independent predictors of achieving FPE were use of balloon guide catheters and non-internal carotid artery terminus occlusion.
CONCLUSIONS—The achievement of complete revascularization from a single Solitaire thrombectomy device pass (FPE) is associated with significantly higher rates of good clinical outcome. The FPE is more frequently associated with the use of balloon guide catheters and less likely to be achieved with internal carotid artery terminus occlusion.
To evaluate the efficacy of dual-energy computed tomography (CT) in the differentiation of intracerebral hemorrhage (ICH) from iodinated contrast material in patients who received contrast material ...via intraarterial or intravenous delivery.
This retrospective study was approved by the local institutional review board, which waived the informed consent requirement for the analysis. Sixteen patients with acute stroke and two with head trauma who had undergone intraarterial or intravenous administration of iodinated contrast material were evaluated by using dual-energy CT to differentiate areas of hyperattenuation secondary to contrast material staining from those representing ICH. A dual-energy CT scanner was used for imaging at 80 and 140 kV, and a three-material decomposition algorithm was used to obtain virtual unenhanced images and iodine overlay images. The sensitivity, specificity, and accuracy of dual-energy CT in the prospective differentiation of intraparenchymal contrast material from hemorrhage were obtained. Follow-up images were used as the standard of reference.
There were 28 intraparenchymal areas of hyperattenuation classified at dual-energy CT as iodinated contrast material staining (n = 20, 71%), hemorrhage (n = 5, 18%), or both (n = 3, 11%). Two of the three areas of hyperattenuation seen on both virtual unenhanced and iodine overlay images were related to mineralization. The sensitivity, specificity, and accuracy of dual-energy CT in the identification of hemorrhage were 100% (six of six areas), 91% (20 of 22 areas), and 93% (26 of 28 areas), respectively.
Dual-energy CT can help differentiate ICH from iodinated contrast material staining with high sensitivity and specificity in patients who have recently received intraarterial or intravenous iodinated contrast material.
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