What predicts poor outcome after successful thrombectomy in late time windows?

BACKGROUND: Thrombectomy for acute ischemic stroke treatment leads to improved outcomes, but many patients do not achieve a good outcome despite successful reperfusion. We determined predictors of poor outcome after successful thrombectomy (TICI 2b-3) with an emphasis on modifiable factors. METHODS: Patients from the randomized DEFUSE 3 trial who underwent thrombectomy with TICI 2b-3 revascularization were included. Primary outcome was a poor outcome at 90 days (modified Rankin Scale score 3-6). RESULTS: 70 patients were included. Poor outcome patients were older (73.5 vs 66.5 years; P=0.01), more likely to be female (68% vs 39%; P=0.02), had higher NIHSS scores (20 vs 13; P<0.001), and had poor cerebral perfusion collaterals (hypoperfusion intensity ratio) (median 0.45 vs 0.38; P=0.03). Following thrombectomy, poor outcome patients had larger 24 hour' core infarctions (median 59.5 vs 29.9 mL; P=0.01), more core infarction growth (median 33.6 vs 13.4 mL; P<0.001), and more mild (65% vs 50%; P=0.02) and severe (18% vs 0%; P=0.01) reperfusion hemorrhage. In a logistic regression analysis, the presence of any reperfusion hemorrhage (OR 3.3 [95% CI, 1.67 to 5]; P=0.001), age (OR 1.1 [95% CI, 1.03 to 1.11], P=0.004), higher NIHSS (OR 1.25 [95% CI, 1.07 to 1.41], P=0.002), and time from imaging to femoral artery puncture (OR 5 [95% CI, 1.16 to 16.67], P=0.03) independently predicted poor outcomes. CONCLUSIONS: In late time windows, both mild and severe reperfusion hemorrhage were associated with poor outcomes. Older age, higher NIHSS, and increased time from imaging to arterial puncture were also associated with poor outcomes despite successful revascularization. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02586415.

Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke.

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730.

Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study.

Background and Purpose- Thrombectomy in late time windows leads to improved outcomes in patients with ischemic stroke due to large vessel occlusion. We determined whether patients with rapid neurological improvement (RNI) 24 hours after thrombectomy were more likely to have a favorable clinical outcome in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3). Methods- All patients who underwent thrombectomy in DEFUSE 3 were included. RNI was defined as a reduction of ≥8 on the National Institutes of Health Stroke Scale or National Institutes of Health Stroke Scale zero to one 24 hours after thrombectomy. Clinical outcomes were assessed by an ordinal analysis modified Rankin Scale score and a dichotomous analysis for 90-day independence (modified Rankin Scale score, 0-2). Results- Ninety-one patients in DEFUSE 3 underwent thrombectomy with follow-up data; 31 patients (34%) experienced RNI (RNI+) after thrombectomy and 60 patients (66%) did not (RNI-). Patient demographics and stroke presentation and imaging details were similar between RNI+ and RNI- patients. Reperfusion (Thrombolysis in Cerebral Infarction 2b-3) after thrombectomy was achieved in 26 (84%) RNI+ and 43 (72%) RNI- ( P=0.2). Symptomatic intracranial hemorrhage occurred in no RNI+ and 8% of RNI- patients ( P=0.2). RNI was associated with a favorable modified Rankin Scale shift at day 90 (odds ratio, 3.8; CI, 1.7-8.6; P=0.001) and higher rates of modified Rankin Scale zero to 2 (61% versus 37%; odds ratio, 2.7; CI, 1.1-6.7; P=0.03). Mortality was 3% in RNI+ versus 18% in RNI- ( P=0.05). RNI+ patients had lower median 24-hour National Institutes of Health Stroke Scale (5 [interquartile range (IQR), 1-7] versus 13 [IQR, 7.5-21]; P<0.001), smaller 24-hour infarction volume (21 [IQR, 5-32] versus 65 [IQR, 27-145] mL; P<0.001), and less 24-hour infarct growth (8 [IQR, 1-18] versus 37 [IQR, 16-105] mL; P<0.001) compared with RNI- patients. Hospital stay was shorter in RNI+ (3.7 [IQR, 2.9-7.1] versus 7.4 [IQR, 5.2-12.1] days in RNI-; P<0.001). Conclusions- RNI following thrombectomy correlates with favorable clinical and radiographic outcomes and reduced hospital length of stay. RNI was a favorable prognostic sign following late-window thrombectomy in DEFUSE 3. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials.

BACKGROUND AND PURPOSE: Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians. METHODS: A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform. RESULTS: A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening. CONCLUSIONS: We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields.

Apparent diffusion coefficient threshold for delineation of ischemic core.

BACKGROUND: MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI. Typically used manual methods to delineate restricted diffusion lesions are subjective and time consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require predefined criteria to identify the ischemic core. AIM: The aim of this study is to determine apparent diffusion coefficient-based criteria that can be implemented in a fully automated software solution for identification of the ischemic core. METHODS: Imaging data from patients enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study who had early revascularization following intravenous thrombolysis were included. The patients' baseline restricted diffusion and 30-day T2 -weighted fluid-attenuated inversion recovery lesions were manually delineated after coregistration. Parts of the restricted diffusion lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered noncore. The optimal apparent diffusion coefficient threshold to discriminate core from noncore voxels was determined by voxel-based receiver operating characteristics analysis using the Youden index. RESULTS: 51,045 diffusion positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24 (± 23) ml. Of this, 18 (± 22) ml was ischemic core and 3 (± 5) ml was noncore. The remainder corresponded to preexisting gliosis, cerebrospinal fluid, or was lost to postinfarct atrophy. The apparent diffusion coefficient of core was lower than that of noncore voxels (P < 0.0001). The optimal threshold for identification of ischemic core was an apparent diffusion coefficient ≤ 620 × 10(-6) mm(2) /s (sensitivity 69% and specificity 78%). CONCLUSIONS: Our data suggest that the ischemic core can be identified with an absolute apparent diffusion coefficient threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core.

Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset.

BACKGROUND AND PURPOSE: The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient. METHODS: MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed. RESULTS: A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion. CONCLUSIONS: Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients.

Although the perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch model has been proposed to identify acute stroke patients who benefit from reperfusion therapy, the optimal definition of a mismatch is uncertain. We evaluated the odds ratio for a favorable clinical response in mismatch patients with reperfusion compared with no reperfusion for various mismatch ratio thresholds in patients enrolled in the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. A mismatch ratio of 2.6 provided the highest sensitivity (90%) and specificity (83%) for identifying patients in whom reperfusion was associated with a favorable response. Defining mismatch with a larger PWI/DWI ratio may provide greater power for detecting beneficial effects of reperfusion.