Background and Purpose: The relative contribution of each Alberta Stroke Program Early CT Score (ASPECTS) region to poststroke disability likely varies across regions. Determining the relative weights of each ASPECTS region may improve patient selection for endovascular stroke therapy (EST). Methods: In the combined Solitaire Flow Restoration with the Intention for Thrombectomy (SWIFT), Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), and Solitaire Flow Restoration with the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) databases, we identified patients treated with the Solitaire stent retriever. Using 24-h CT scan, a multivariate ordinal regression was used to determine the relative contribution of each ASPECTS region to clinical outcome separately in each hemisphere. The coefficients from the regression were used to create a weighted ASPECTS (wASPECTS), which was compared with the original ASPECTS to predict 90-day modified Rankin Scale disability outcomes in an independent validation cohort. Results: Among 342 patients treated with EST, the average age was 67 years, 57% were female, and the median National Institutes of Health Stroke Scale (NIHSS) score was 17 (IQR 13–20). The median ASPECTS at presentation was 8 (IQR 7–10). The most commonly involved ASPECTS regions on 24-h CT were the lentiform nuclei (70%), insula (55%), and caudate (52%). In multivariate analysis, preservation of M6 (β = 9.7) and M4 (β = 4.4) regions in the right hemisphere was most strongly predictive of good outcome. For the left hemisphere, M6 (β = 5.5), M5 (β = 4.1), and M3 (β = 3.1) generated the greatest parameter estimates, though they did not reach statistical significance. A wASPECTS incorporating all 20 parameter estimates resulted in improved discrimination against the original ASPECTS in the independent cohort (C-statistic 0.78 vs. 0.67, right hemisphere). Conclusions: For both right and left hemisphere, preservation of the high cortical regions was more strongly associated with improved outcomes compared to the deep regions. Our findings support taking into consideration the location and relative weightings of the involved ASPECTS regions when evaluating a patient for EST.

Background: Apparent diffusion coefficient (ADC) imaging is a biomarker of cytotoxic injury that predicts edema formation and outcome after ischemic stroke. It therefore has the potential to serve as a “tissue clock” to describe the extent of ischemic injury and potentially predict response to therapy. The goal of this study was to determine the relationship between baseline ADC signal intensity, revascularization, and edema formation. Methods: We examined the ADC signal intensity ratio (ADCr) of the stroke lesion (defined as the baseline DWI hyperintense region) compared to the contralateral normal hemisphere in 65 subjects from the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy trial. The associations between ADCr, neurologic outcome, and cerebral edema were examined. Finally, we explored the interaction between baseline ADCr and vessel recanalization at day 7 on post-stroke edema. Results: We found that lower initial ADCr was associated with a worse outcome on the modified Rankin Scale (mRS) at 90 days (52.2% of those with ADCr <64% were mRS 5–6 vs. 19.1% with ADCr ≥64%, p = 0.006). Those subjects with reconstitution of flow distal to the initial vessel occlusion showed greater normalization of ADCr on follow-up scan (increase in ADCr of 16.4 ± 2.07 vs. 1.99 ± 4.33%, p = 0.0039). In those patients with low baseline ADCr, successful revascularization was associated with reduced edema (median swelling volume 164 mL [interquartile range (IQR) 53.3–190 mL] vs. 20.7 mL [IQR 3.20–55.1 mL], p = 0.024). Conclusions: This study reaffirms the association of ADCr with outcome after stroke, supports the idea that reperfusion may attenuate rather than enhance post-stroke edema, and indicates that the degree of edema with and without revascularization may be predicted by ADCr.

Background: Apparent diffusion coefficient (ADC) imaging is a biomarker of cytotoxic injury that predicts edema formation and outcome after ischemic stroke. It therefore has the potential to serve as a “tissue clock” to describe the extent of ischemic injury and potentially predict response to therapy. The goal of this study was to determine the relationship between baseline ADC signal intensity, revascularization, and edema formation. Methods: We examined the ADC signal intensity ratio (ADCr) of the stroke lesion (defined as the baseline DWI hyperintense region) compared to the contralateral normal hemisphere in 65 subjects from the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy trial. The associations between ADCr, neurologic outcome, and cerebral edema were examined. Finally, we explored the interaction between baseline ADCr and vessel recanalization at day 7 on post-stroke edema. Results: We found that lower initial ADCr was associated with a worse outcome on the modified Rankin Scale (mRS) at 90 days (52.2% of those with ADCr <64% were mRS 5–6 vs. 19.1% with ADCr ≥64%, p = 0.006). Those subjects with reconstitution of flow distal to the initial vessel occlusion showed greater normalization of ADCr on follow-up scan (increase in ADCr of 16.4 ± 2.07 vs. 1.99 ± 4.33%, p = 0.0039). In those patients with low baseline ADCr, successful revascularization was associated with reduced edema (median swelling volume 164 mL [interquartile range (IQR) 53.3–190 mL] vs. 20.7 mL [IQR 3.20–55.1 mL], p = 0.024). Conclusions: This study reaffirms the association of ADCr with outcome after stroke, supports the idea that reperfusion may attenuate rather than enhance post-stroke edema, and indicates that the degree of edema with and without revascularization may be predicted by ADCr.

Background and Purpose: The relative contribution of each Alberta Stroke Program Early CT Score (ASPECTS) region to poststroke disability likely varies across regions. Determining the relative weights of each ASPECTS region may improve patient selection for endovascular stroke therapy (EST). Methods: In the combined Solitaire Flow Restoration with the Intention for Thrombectomy (SWIFT), Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), and Solitaire Flow Restoration with the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) databases, we identified patients treated with the Solitaire stent retriever. Using 24-h CT scan, a multivariate ordinal regression was used to determine the relative contribution of each ASPECTS region to clinical outcome separately in each hemisphere. The coefficients from the regression were used to create a weighted ASPECTS (wASPECTS), which was compared with the original ASPECTS to predict 90-day modified Rankin Scale disability outcomes in an independent validation cohort. Results: Among 342 patients treated with EST, the average age was 67 years, 57% were female, and the median National Institutes of Health Stroke Scale (NIHSS) score was 17 (IQR 13–20). The median ASPECTS at presentation was 8 (IQR 7–10). The most commonly involved ASPECTS regions on 24-h CT were the lentiform nuclei (70%), insula (55%), and caudate (52%). In multivariate analysis, preservation of M6 (β = 9.7) and M4 (β = 4.4) regions in the right hemisphere was most strongly predictive of good outcome. For the left hemisphere, M6 (β = 5.5), M5 (β = 4.1), and M3 (β = 3.1) generated the greatest parameter estimates, though they did not reach statistical significance. A wASPECTS incorporating all 20 parameter estimates resulted in improved discrimination against the original ASPECTS in the independent cohort (C-statistic 0.78 vs. 0.67, right hemisphere). Conclusions: For both right and left hemisphere, preservation of the high cortical regions was more strongly associated with improved outcomes compared to the deep regions. Our findings support taking into consideration the location and relative weightings of the involved ASPECTS regions when evaluating a patient for EST.

Background: Cellular phone conversations between on-scene patients or their legally authorized representatives (LARs) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials. Methods: The NIH Field Administration of Stroke Therapy – Magnesium (FAST-MAG) Trial implemented a voice-over-internet protocol (VOIP) simultaneous ring system (multiple investigator cell phones called simultaneously and first responder connected to call) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial. For 1 month, the number, origin, duration, and yield of enrolling line calls were monitored prospectively. Results: Six investigators were connected to 106 enrolling line calls, with no identified unanswered calls. Thirty-five percent of new patient calls yielded an enrollment. The most common reasons for non-enrollment were last known well >2 h (n = 7) and uncon sentable patient without LAR available (n = 7). No non-enrollments were directly attributable to the VOIP system. In enrollments, consent was provided by the patient in 67% and a LAR in 33%. The duration of enrollment calls (mean ± SD: 8.4 ± 2.5 min, range 6–14) was longer than non-enrollment calls (5.5 ± 3.5, range 2–13; p < 0.001). The median interval from last known well to study agent start was 46 min, and 70% were enrolled within 60 min of onset. Conclusions: The simultaneous ring system was reliable and effective, permitting enrollment of a substantial number of patients within the first hour after stroke onset. VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials.

Background: Cellular phone conversations between on-scene patients or their legally authorized representatives (LARs) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials. Methods: The NIH Field Administration of Stroke Therapy – Magnesium (FAST-MAG) Trial implemented a voice-over-internet protocol (VOIP) simultaneous ring system (multiple investigator cell phones called simultaneously and first responder connected to call) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial. For 1 month, the number, origin, duration, and yield of enrolling line calls were monitored prospectively. Results: Six investigators were connected to 106 enrolling line calls, with no identified unanswered calls. Thirty-five percent of new patient calls yielded an enrollment. The most common reasons for non-enrollment were last known well >2 h (n = 7) and uncon sentable patient without LAR available (n = 7). No non-enrollments were directly attributable to the VOIP system. In enrollments, consent was provided by the patient in 67% and a LAR in 33%. The duration of enrollment calls (mean ± SD: 8.4 ± 2.5 min, range 6–14) was longer than non-enrollment calls (5.5 ± 3.5, range 2–13; p < 0.001). The median interval from last known well to study agent start was 46 min, and 70% were enrolled within 60 min of onset. Conclusions: The simultaneous ring system was reliable and effective, permitting enrollment of a substantial number of patients within the first hour after stroke onset. VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials.

Background: Little is known about whether vascular risk factors predispose to atherosclerotic stroke depending on age. We evaluated predictors of large vessel atherosclerotic stroke (LVAS) stratified by age in two geographically and racially distinct study populations. Methods: Data collected over a 4-year period in prospectively maintained registries on 3,053 subjects with ischemic cerebrovascular events were analyzed: 1,982 patients from a hospital in South Korea and 1,071 patients admitted to a hospital in Los Angeles, Calif., USA. Independent vascular risk factor associations with LVAS mechanism were evaluated in three groups stratified by age (years) at symptom onset: young (≤50 years), older (51–75 years), and oldest (>75 years). Results: Altogether at both study sites, 972 (31.8%) patients had LVAS mechanism, of whom 391 (40.2%) were female. Risk factor profiles were not significantly different between LVAS versus other stroke mechanisms. Among young patients, after adjusting for covariates, current smoking was the only predictor of atherosclerotic stroke at both Korean (OR 2.04; 95% CI: 1.13–3.69) and Californian sites (OR 4.78, 95% CI 1.54–14.89), while the metabolic syndrome was the only predictor of atherosclerotic stroke among the older patients (OR 1.58, 95% CI 1.17–2.12 for Korean; OR 1.75, 95% CI 1.07–2.84 for Californian), but not in the young or oldest groups. Conclusions: Across race and region, the estimated impact of vascular risk factors for LVAS varies by age, and this is most prominently seen among persons of less than 76 years of age. Some risk factors have an early effect (smoking) and others an effect that plays out over time.

Background: Little is known about whether vascular risk factors predispose to atherosclerotic stroke depending on age. We evaluated predictors of large vessel atherosclerotic stroke (LVAS) stratified by age in two geographically and racially distinct study populations. Methods: Data collected over a 4-year period in prospectively maintained registries on 3,053 subjects with ischemic cerebrovascular events were analyzed: 1,982 patients from a hospital in South Korea and 1,071 patients admitted to a hospital in Los Angeles, Calif., USA. Independent vascular risk factor associations with LVAS mechanism were evaluated in three groups stratified by age (years) at symptom onset: young (≤50 years), older (51–75 years), and oldest (>75 years). Results: Altogether at both study sites, 972 (31.8%) patients had LVAS mechanism, of whom 391 (40.2%) were female. Risk factor profiles were not significantly different between LVAS versus other stroke mechanisms. Among young patients, after adjusting for covariates, current smoking was the only predictor of atherosclerotic stroke at both Korean (OR 2.04; 95% CI: 1.13–3.69) and Californian sites (OR 4.78, 95% CI 1.54–14.89), while the metabolic syndrome was the only predictor of atherosclerotic stroke among the older patients (OR 1.58, 95% CI 1.17–2.12 for Korean; OR 1.75, 95% CI 1.07–2.84 for Californian), but not in the young or oldest groups. Conclusions: Across race and region, the estimated impact of vascular risk factors for LVAS varies by age, and this is most prominently seen among persons of less than 76 years of age. Some risk factors have an early effect (smoking) and others an effect that plays out over time.