TOAST stroke subtype classification in clinical practice: implications for the Get With The Guidelines-Stroke nationwide registry.

Introduction: The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) is the most commonly used ischemic stroke subtype classification system worldwide and a required field in the US National Get With The Guidelines-Stroke (GWTG-Stroke) registry. However, stroke diagnostics have advanced substantially since the TOAST classification was designed 30 years ago, potentially making it difficult to apply reliably. Methods: In this prospective diagnostic accuracy study, we analyzed consecutive ischemic stroke patients admitted to a Comprehensive Stroke Center between July-October 2021. Clinical practice TOAST classification diagnoses rendered by the stroke team in the electronic medical record (EMR) at discharge were retrieved from GWTG-Stroke registry and compared to a reference ("gold") standard diagnosis derived from agreement between two expert raters after review of the EMR and patient imaging. Results: Among 49 patients; age was 72.3 years (±12.1), 53% female, and presenting NIHSS median 3 (IQR 1-11). Work-up included: brain imaging in 100%; cardiac rhythm assessment in 100%; cervical/cerebral vessel imaging in 98%; TTE ± TEE in 92%; and TCD emboli evaluation in 51%. Reference standard diagnoses were: LAA-6%, SVD-14%, CE-39%, OTH-10%, UND-M (more than one cause)-20%, and UND-C (cryptogenic)-10%. GWTG-Stroke TOAST diagnoses agreed with reference standard diagnoses in 30/49 (61%). Among the 6 subtype diagnoses, specificity was generally high (84.8%-97.7%), but sensitivity suboptimal for LAA (33%), OTH (60%), UND-M (10%), and UND-C (20%). Positive predictive value was suboptimal for 5 of the 6 subtypes: LAA (13%), SVD (58%), OTH (75%), UND-M (50%), and UND-C (50%). Discussion: Clinical practice TOAST classification subtype diagnoses entered into the GWTG-Stroke registry were accurate in only 61% of patients, a performance rate that, if similarly present at other centers, would hamper the ability of the national registry to provide dependable insights into subtype-related care. Development of an updated ischemic stroke subtype classification system, with algorithmic logic embedded in electronic medical records, is desirable.

Magnesium and Hematoma Expansion in Intracerebral Hemorrhage: A FAST-MAG Randomized Trial Analysis.

BACKGROUND: Observational studies suggest that magnesium may have hemostatic effects. FAST-MAG (Field Administration of Stroke Therapy-Magnesium) was a pragmatic clinical trial of magnesium sulfate administered prehospital for acute clinical stroke syndromes and included patients with intracerebral hemorrhage. Exploratory secondary analysis by the treatment group found no reduction in hematoma expansion (HE) associated with magnesium treatment in intracerebral hemorrhage but did not consider serum magnesium levels achieved. We analyzed FAST-MAG intracerebral hemorrhage data for associations between serum magnesium level, HE, and early neurological deterioration, accounting for groupwise biases. METHODS: HE was defined as hematoma volume increase ≥3 mL within 24 hours and early neurological deterioration as ≥1-point Glasgow Coma Scale decline from arrival to hospital day 4. Comparing treatment and placebo groups confirmed biased availability of neuroimaging data. Therefore, HE and neurological deterioration were analyzed and stratified by treatment and placebo groups using univariate tests and adjusted logistic regression. RESULTS: Spontaneous intracerebral hemorrhage was present in 381 patients. Placebo patients had fewer serial neuroimaging studies available (123 [65.4%] versus 145 [75.1%]; P=0.038). Necessary data were available in 104 magnesium- and 85 placebo-treated patients (age, 64.9 [13.0] years; 67.7% male). In the magnesium group, higher magnesium level was associated with less HE (adjusted odds ratio, 0.64 per mg/dL [95% CI, 0.42-0.93]) and less neurological deterioration (adjusted odds ratio, 0.54 per mg/dL [95% CI, 0.33-0.82]). In the placebo group, magnesium level was not associated with either HE or neurological deterioration. CONCLUSIONS: Magnesium may exhibit a hemostatic effect that was only observable in the FAST-MAG magnesium treatment group. Equipoise should be maintained, and specific trials are needed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00059332.

Circadian variation in stroke onset: Differences between ischemic and hemorrhagic stroke and weekdays versus weekends.

OBJECTIVES: To delineate diurnal variation onset distinguishing ischemic from hemorrhagic stroke, wake from sleep onset, and weekdays from weekends/holidays. MATERIALS AND METHODS: We analyzed patients enrolled in the FAST-MAG trial of field-initiated neuroprotective agent in patients with hyperacute stroke within 2h of symptoms onset. Stroke onset times were analyzed in 1h, 4h, and 12h time blocks throughout the 24h day-night cycle. Patient demographic, clinical features, stroke severity, and prehospital workflow were evaluated for association with onset times. RESULTS: Among 1615 acute cerebrovascular disease patients, final diagnoses were acute cerebral ischemia in 76.5% and Intracerebral hemorrhage in 23.5%. Considering all acute cerebrovascular disease patients, frequency of wake onset times showed a bimodal pattern, with peaks on onsets at 09:00-13:59 and 17:00-18:59 and early morning (00:00-05:59) onset in only 3.8%. Circadian rhythmicity differed among stroke subtypes: in acute cerebral ischemia, a single broad plateau of elevated incidences was seen from 10:00-21:59; in Intracerebral hemorrhage, bimodal peaks occurred at 09:00 and 19:00. The ratio of Intracerebral hemorrhage to acute cerebral ischemia occurrence was highest in early morning, 02:00-06:59. Marked weekday vs weekends pattern variation was noted for acute cerebral ischemia, with a broad plateau between 09:00 and 21:59 on weekdays but a unimodal peak at 14:00-15:59 on weekends. CONCLUSIONS: Wake onset of acute cerebrovascular disease showed a marked circadian variation, with distinctive patterns of a broad elevated plateau among acute cerebral ischemia patients; a bimodal peak among intracerebral hemorrhage patients; and a weekend change in acute cerebral ischemia pattern to a unimodal peak.

Neurologic Improvement in Acute Cerebral Ischemia: Frequency, Magnitude, Predictors, and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: Investigations of rapid neurologic improvement (RNI) in patients with acute cerebral ischemia (ACI) have focused on RNI occurring after hospital arrival. However, with stroke routing decisions and interventions increasingly migrating to the prehospital setting, there is a need to delineate the frequency, magnitude, predictors, and clinical outcomes of patients with ACI with ultra-early RNI (U-RNI) in the prehospital and early postarrival period. METHODS: We analyzed prospectively collected data of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized clinical trial. Any U-RNI was defined as improvement by 2 or more points on the Los Angeles Motor Scale (LAMS) score between the prehospital and early post-emergency department (ED) arrival examinations and classified as moderate (2-3 point) or dramatic (4-5 point) improvement. Outcome measures included excellent recovery (modified Rankin Scale [mRS] score 0-1) and death by 90 days. RESULTS: Among the 1,245 patients with ACI, the mean age was 70.9 years (SD 13.2); 45% were women; the median prehospital LAMS was 4 (interquartile range [IQR] 3-5); the median last known well to ED-LAMS time was 59 minutes (IQR 46-80 minutes), and the median prehospital LAMS to ED-LAMS time was 33 minutes (IQR 28-39 minutes). Overall, any U-RNI occurred in 31%, moderate U-RNI in 23%, and dramatic U-RNI in 8%. Any U-RNI was associated with improved outcomes, including excellent recovery (mRS score 0-1) at 90 days 65.1% (246/378) vs 35.4% (302/852), p < 0.0001; decreased mortality by 90 days 3.7% (14/378) vs 16.4% (140/852), p < 0.0001; decreased symptomatic intracranial hemorrhage 1.6% (6/384) vs 4.6% (40/861), p = 0.0112; and increased likelihood of being discharged home 56.8% (218/384) vs 30.2% (260/861), p < 0.0001. DISCUSSION: U-RNI occurs in nearly 1 in 3 ambulance-transported patients with ACI and is associated with excellent recovery and decreased mortality at 90 days. Accounting for U-RNI may be useful for routing decisions and future prehospital interventions. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov. Unique identifier: NCT00059332.

Quantifying the amount of greater brain ischemia protection time with pre-hospital vs. in-hospital neuroprotective agent start.

The objective of this study is to quantify the increase in brain-under-protection time that may be achieved with pre-hospital compared with the post-arrival start of neuroprotective therapy among patients undergoing endovascular thrombectomy. In order to do this, a comparative analysis was performed of two randomized trials of neuroprotective agents: (1) pre-hospital strategy: Field administration of stroke therapy-magnesium (FAST-MAG) Trial; (2) in-hospital strategy: Efficacy and safety of nerinetide for the treatment of acute ischemic stroke (ESCAPE-NA1) Trial. In the FAST-MAG trial, among 1,041 acute ischemic stroke patients, 44 were treated with endovascular reperfusion therapy (ERT), including 32 treated with both intravenous thrombolysis and ERT and 12 treated with ERT alone. In the ESCAPE-NA1 trial, among 1,105 acute ischemic stroke patients, 659 were treated with both intravenous thrombolysis and ERT, and 446 were treated with ERT alone. The start of the neuroprotective agent was sooner after onset with pre-hospital vs. in-hospital start: 45 m (IQR 38-56) vs. 122 m. The neuroprotective agent in FAST-MAG was started 8 min prior to ED arrival compared with 64 min after arrival in ESCAPE-NA1. Projecting modern endovascular workflows to FAST-MAG, the total time of "brain under protection" (neuroprotective agent start to reperfusion) was greater with pre-hospital than in-hospital start: 94 m (IQR 90-98) vs. 22 m. Initiating a neuroprotective agent in the pre-hospital setting enables a faster treatment start, yielding 72 min additional brain protection time for patients with acute ischemic stroke. These findings provide support for the increased performance of ambulance-based, pre-hospital treatment trials in the development of neuroprotective stroke therapies.

Beyond the Golden Hour: Treating Acute Stroke in the Platinum 30 Minutes.

BACKGROUND: To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized. METHODS: In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy-Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients. RESULTS: Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25-30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57-79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3-5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3-18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0-1) in 35.5%, functional independence (modified Rankin Scale score, 0-2) in 53.2%, and mortality in 17.7%. CONCLUSIONS: Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.

Magnesium Sulfate and Hematoma Expansion: An Ancillary Analysis of the FAST-MAG Randomized Trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is the deadliest form of stroke. In observational studies, lower serum magnesium has been linked to more hematoma expansion (HE) and intracranial hemorrhage, implying that supplemental magnesium sulfate is a potential acute treatment for patients with ICH and could reduce HE. FAST-MAG (Field Administration of Stroke Therapy - Magnesium) was a clinical trial of magnesium sulfate started prehospital in patients with acute stroke within 2 hours of last known well enrolled. CT was not required prior to enrollment, and several hundred patients with acute ICH were enrolled. In this ancillary analysis, we assessed the effect of magnesium sulfate treatment upon HE in patients with acute ICH. METHODS: We retrospectively analyzed data that were prospectively collected in the FAST-MAG study. Patients received intravenous magnesium sulfate or matched placebo within 2 hours of onset. We compared HE among patients allocated to intravenous magnesium sulfate or placebo with a Mann-Whitney U. We used the same method to compare neurological deficit severity (National Institutes of Health Stroke Scale) and global disability (modified Rankin Scale) at 3 months. RESULTS: Among 268 patients with ICH meeting study entry criteria, mean 65.4±13/4 years, 33% were female, and 211 (79%) had a history of hypertension. Initial deficit severities were median (interquartile range) of 4 (3-5) on the Los Angeles Motor Scale in the field and National Institutes of Health Stroke Scale score of 16 (9.5-25.5) early after hospital arrival. Follow-up brain imaging was performed a median of 17.1 (11.3-22.7) hours after first scan. The magnesium and placebo groups did not statistically differ in hematoma volume on arrival, 10.1 (5.6-28.7) versus 12.4 (5.6-28.7) mL (P=0.6), or HE, 2.0 (0.1-7.4) versus 1.5 (-0.2 to 8) mL (P=0.5). There was no difference in functional outcomes (modified Rankin Scale score of 3-6), 59% versus 50% (P=0.5). CONCLUSIONS: Magnesium sulfate did not reduce HE or improve functional outcomes at 90 days. A benefit for patients with initial hypomagnesemia was not addressed. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00059332.

National Institutes of Health Stroke Scale Correlates Well with Initial Intracerebral Hemorrhage Volume.

OBJECTIVES: The US Centers for Medicare and Medicaid Services (CMS) currently publicly reports hospital-quality, risk-adjusted mortality measure for ischemic stroke but not intracerebral hemorrhage (ICH). The NIHSS, which is captured in CMS administrative claims data, is a candidate metric for use in ICH risk adjustment and has been shown to predict clinical outcome with accuracy similar to the ICH Score. Correlation between early NIHSS and initial ICH volume would further support use of the NIHSS for ICH risk adjustment. MATERIALS AND METHODS: Among 372 ICH patients enrolled in a large multicenter trial (FAST-MAG), the relation between early NIHSS and early ICH volume was assessed with correlation and linear trend analysis. RESULTS: Overall, there was strong correlation between NIHSS and ICH volume, r = 0.77 (p < 0.001), and for every 10cc increase in ICH the NIHSS increased by 4.5 points. Correlation coefficients were comparable in all subgroups, but magnitude of NIHSS increase with ICH unit volume increase was greater with left than right hemispheric ICH, with presence rather than absence of IVH, with imaging done within the first hour than second hour after last known well, with men than women, and with younger than older patients. CONCLUSION: Early NIHSS neurologic deficit severity values correlate strongly with initial ICH hematoma volume. As with ischemic stroke, lesion volume increases produce greater NIHSS change in the left than right hemisphere, reflecting greater NIHSS sensitivity to left hemisphere function. These findings provide further support for the use of NIHSS in risk-adjusted mortality measures for intracerebral hemorrhage.

Heterogeneity between proximal and distal aspects of occlusive thrombi on pretreatment imaging in acute ischemic stroke.

BACKGROUND: The potential heterogeneity in occlusive thrombi caused by in situ propagation by secondary thrombosis after embolic occlusion could obscure the characteristics of original thrombi, preventing the clarification of a specific thrombus signature for the etiology of ischemic stroke. We aimed to investigate the heterogeneity of occlusive thrombi by pretreatment imaging. METHODS: Among consecutive stroke patients with acute embolic anterior circulation large vessel occlusion treated with thrombectomy, we retrospectively reviewed 104 patients with visible occlusive thrombi on pretreatment non-contrast computed tomography admitted from January 2015 to December 2018. A region of interest was set on the whole thrombus on non-contrast computed tomography under the guidance of computed tomography angiography. The region of interest was divided equally into the proximal and distal segments and the difference in Hounsfield unit densities between the two segments was calculated. RESULTS: Hounsfield unit density in the proximal segment was higher than that in the distal segment (mean difference 4.45; p < 0.001), regardless of stroke subtypes. On multivariate analysis, thrombus length was positively correlated (ß = 0.25; p < 0.001) and time from last-known-well to imaging was inversely correlated (ß = -0.0041; p = 0.002) with the difference in Hounsfield unit densities between the proximal and distal segments. CONCLUSIONS: The difference in density between the proximal and distal segments increased as thrombi became longer and decreased as thrombi became older after embolic occlusion. This time/length-dependent thrombus heterogeneity between the two segments is suggestive of secondary thrombosis initially occurring on the proximal side of the occlusion.

COVID-19 Impact on Acute Ischemic Stroke Treatment at 9 Comprehensive Stroke Centers across Los Angeles.

OBJECTIVE: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC). METHODS: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution. RESULTS: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p < 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008). CONCLUSION: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019.

Frequency, Determinants, and Outcomes of Emboli to Distal and New Territories Related to Mechanical Thrombectomy for Acute Ischemic Stroke.

Background and Purpose: Clot fragmentation and distal embolization during endovascular thrombectomy for acute ischemic stroke may produce emboli downstream of the target occlusion or in previously uninvolved territories. Susceptibility-weighted magnetic resonance imaging can identify both emboli to distal territories (EDT) and new territories (ENT) as new susceptibility vessel signs (SVS). Diffusion-weighted imaging (DWI) can identify infarcts in new territories (INT). Methods: We studied consecutive acute ischemic stroke patients undergoing magnetic resonance imaging before and after thrombectomy. Frequency, predictors, and outcomes of EDT and ENT detected on gradient-recalled echo imaging (EDT-SVS and ENT-SVS) and INT detected on DWI (INT-DWI) were analyzed. Results: Among 50 thrombectomy-treated acute ischemic stroke patients meeting study criteria, mean age was 70 (±16) years, 44% were women, and presenting National Institutes of Health Stroke Scale score 15 (interquartile range, 8­19). Overall, 21 of 50 (42%) patients showed periprocedural embolic events, including 10 of 50 (20%) with new EDT-SVS, 10 of 50 (20%) with INT-DWI, and 1 of 50 (2%) with both. No patient showed ENT-SVS. On multivariate analysis, model-selected predictors of EDT-SVS were lower initial diastolic blood pressure (odds ratio, 1.09 [95% CI, 1.02­1.16]), alteplase pretreatment (odds ratio, 5.54 [95% CI, 0.94­32.49]), and atrial fibrillation (odds ratio, 7.38 [95% CI, 1.02­53.32]). Classification tree analysis identified pretreatment target occlusion SVS as an additional predictor. On univariate analysis, INT-DWI was less common with internal carotid artery (5%), intermediate with middle cerebral artery (25%), and highest with vertebrobasilar (57%) target occlusions (P=0.02). EDT-SVS was not associated with imaging/functional outcomes, but INT-DWI was associated with reduced radiological hemorrhagic transformation (0% versus 54%; P<0.01). Conclusions: Among acute ischemic stroke patients treated with thrombectomy, imaging evidence of distal emboli, including EDT-SVS beyond the target occlusion and INT-DWI in novel territories, occur in about 2 in every 5 cases. Predictors of EDT-SVS are pretreatment intravenous fibrinolysis, potentially disrupting thrombus structural integrity; atrial fibrillation, possibly reflecting larger target thrombus burden; lower diastolic blood pressure, suggestive of impaired embolic washout; and pretreatment target occlusion SVS sign, indicating erythrocyte-rich, friable target thrombus.

Intracranial atherosclerotic disease mechanistic subtypes drive hypoperfusion patterns.

BACKGROUND AND PURPOSE: In symptomatic intracranial atherosclerotic stenosis (ICAS), borderzone infarct pattern and perfusion mismatch are associated with increased risk of recurrent strokes, which may reflect the shared underlying mechanism of hypoperfusion distal to the intracranial atherosclerosis. Accordingly, we hypothesized a correlation between hypoperfusion volumes and ICAS infarct patterns based on the respective underlying mechanistic subtypes. METHODS: We conducted a retrospective analysis of consecutive symptomatic ICAS cases, acute strokes due to subocclusive (50%-99%) intracranial stenosis. The following mechanistic subtypes were assigned based on the infarct pattern on the diffusion-weighted imaging: Branch occlusive disease (BOD), internal borderzone (IBZ), and thromboembolic (TE). Perfusion parameters, obtained concurrently with the MRI, were studied in each group. RESULTS: A total of 42 patients (57% women, mean age 71 ± 13 years old) with symptomatic ICAS received MRI within 24 h of acute presentation. Fourteen IBZ, 11 BOD, and 17 TE patterns were identified. IBZ pattern yielded higher total Tmax > 4 s and Tmax > 6 s perfusion delay volumes, as well as corresponding Tmax  > 4 s and Tmax  > 6 s mismatch volume, compared to BOD. TE pattern exhibited greater median Tmax  > 6 s hypoperfusion delay in volume compared to BOD. In IBZ versus TE, the volume difference between Tmax > 4 s and Tmax > 6 s (Δ Tmax  > 4 s - Tmax  > 6 s) was substantially greater. CONCLUSION: ICAS infarct patterns, in keeping with their respective underlying mechanisms, may correlate with distinct perfusion profiles.

Impaired Distal Perfusion Predicts Length of Hospital Stay in Patients with Symptomatic Middle Cerebral Artery Stenosis.

BACKGROUND AND PURPOSE: Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients. METHODS: This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max > 6 second delay, T max 4-6 second delay, and <4 second delay. The outcome was LOS, both as a continuous variable and categorical (≥7 days [prolonged LOS] vs. <7 days). We used adjusted regression analyses to determine the association between perfusion categories and LOS. RESULTS: One hundred and seventy eight of 194 patients met the inclusion criteria. After adjusting for age and NIHSS, T max >6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max > 6 second (ß coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (ß coefficient = 1.24, 95% CI -.85 to 3.34, P = .244). CONCLUSION: In patients with symptomatic MCA stenosis, T max > 6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings.

Adiposity and Outcome After Ischemic Stroke: Obesity Paradox for Mortality and Obesity Parabola for Favorable Functional Outcomes.

BACKGROUND AND PURPOSE: A survival advantage among individuals with higher body mass index (BMI) has been observed for diverse acute illnesses, including stroke, and termed the obesity paradox. However, prior ischemic stroke studies have generally tested only for linear rather than nonlinear relations between body mass and outcome, and few studies have investigated poststroke functional outcomes in addition to mortality. METHODS: We analyzed consecutive patients with acute ischemic stroke enrolled in a 60-center acute treatment trial, the NIH FAST-MAG acute stroke trial. Outcomes at 3 months analyzed were (1) death; (2) disability or death (modified Rankin Scale score, 2-6); and (3) low stroke-related quality of life (Stroke Impact Scale

Decision-Making Visual Aids for Late, Imaging-Guided Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Speedy decision-making is important for optimal outcomes from endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Figural decision aids facilitate rapid review of treatment benefits and harms, but have not yet been developed for late-presenting patients selected for EVT based on multimodal computed tomography or magnetic resonance imaging. METHODS: For combined pooled study-level randomized trial (DAWN and DEFUSE 3) data, as well as each trial singly, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of EVT for patients with AIS and large vessel occlusion using automated (algorithmic) and expert-guided joint outcome table specification. RESULTS: Among imaging-selected patients 6 to 24 hours from last known well, for the full 7-category modified Rankin Scale (mRS), EVT had number needed to treat to benefit 1.9 (interquartile range [IQR], 1.9 to 2.1) and number needed to harm 40.0 (IQR, 29.2 to 58.3). Visual displays of treatment effects among 100 patients showed that, with EVT: 52 patients have better disability outcome, including 32 more achieving functional independence (mRS 0 to 2); three patients have worse disability outcome, including one more experiencing severe disability or death (mRS 5 to 6), mediated by symptomatic intracranial hemorrhage and infarct in new territory. Similar features were present in person-icon figures based on a 6-level mRS (levels 5 and 6 combined) rather than 7-level mRS, and based on the DAWN trial alone and DEFUSE 3 trial alone. CONCLUSIONS: Personograph visual decision aids are now available to rapidly educate patients, family, and healthcare providers regarding benefits and risks of EVT for late-presenting, imaging-selected AIS patients.

A Prehospital Acute Stroke Trial has Only Modest Impact on Enrollment in Concurrent, Post-arrival-Recruiting Stroke Trials.

BACKGROUND: Because "time is brain," acute stroke trials are migrating to the prehospital setting. The impact upon enrollment in post-arrival trials of earlier recruitment in a prehospital trial requires delineation. METHODS: We analyzed all patients recruited into acute and prevention stroke trials during an 8-year period when an academic medical center (AMC) was participating in a prehospital treatment trial - the NIH Field Administration of Stroke Treatment - Magnesium (FAST-MAG) study. RESULTS: During the study period, in addition to FAST-MAG, the AMC participated in 33 post-arrival stroke trials: 27 for acute cerebral ischemia, one for intracerebral hemorrhage, and 5 secondary prevention trials. Throughout the study period, the AMC was recruiting for at least 3 concurrent post-arrival acute trials. Among 199 patients enrolled in acute stroke trials, 98 (49%) were in FAST-MAG and 101 (51%) in concurrent, post-arrival acute trials. Among FAST-MAG patients, 67% were not eligible for any concurrent acute, post-arrival trial. Of 134 patients eligible for post-arrival acute trials, 101 (76%) were enrolled in post-arrival trials and 32 (24%) in FAST-MAG. Leading reasons FAST-MAG patients were ineligible for post-arrival acute trials were: NIHSS too low (23.4%), intracranial hemorrhage (17.9%), IV tPA used in standard management (9.0%), NIHSS too high (7.1%), and age too high (5.2%). CONCLUSIONS: A prehospital hyperacute stroke trial with wide entry criteria reduced only modestly, by one-fourth, enrollment into concurrently active, post-arrival stroke trials. Simultaneous performance of prehospital and post-arrival acute and secondary prevention stroke trials in research networks is feasible.

Efficient Multimodal MRI Evaluation for Endovascular Thrombectomy of Anterior Circulation Large Vessel Occlusion.

BACKGROUND: MRI and CT modalities are both current standard-of-care options for initial imaging in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). MR provides greater lesion conspicuity and spatial resolution, but few series have demonstrated multimodal MR may be performed efficiently. METHODS: In a prospective comprehensive stroke center registry, we analyzed all anterior circulation LVO thrombectomy patients between 2012-2017 who: (1) arrived directly by EMS from the field, and (2) had initial NIHSS ≥6. Center imaging policy was multimodal MRI (including DWI/GRE/MRA w/wo PWI) as the initial evaluation in all patients without contraindications, and multimodal CT (including CT with CTA, w/wo CTP) in the remainder. RESULTS: Among 106 EMS-arriving endovascular thrombectomy patients, initial imaging was MRI 62.3%, CT in 37.7%. MRI and CT patients were similar in age (72.5 vs 71.3), severity (NIHSS 16.4 v 18.2), and medical history, though MRI patients had longer onset-to-door times. Overall, door-to-needle (DTN) and door-to-puncture (DTP) times did not differ among MR and CT patients, and were faster for both modalities in 2015-2017 versus 2012-2014. In the 2015-2017 period, for MR-imaged patients, the median DTN 42m (IQR 34-55) surpassed standard (60m) and advanced (45m) national targets and the median DTP 86m (IQR 71-106) surpassed the standard national target (90m). CONCLUSIONS: AIS-LVO patients can be evaluated by multimodal MR imaging with care speeds faster than national recommendations for door-to-needle and door-to-puncture times. With its more sensitive lesion identification and spatial resolution, MRI remains a highly viable primary imaging strategy in acute ischemic stroke patients, though further workflow efficiency improvements are desirable.

Predictors and Functional Outcomes of Fast, Intermediate, and Slow Progression Among Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: We aimed to delineate the determinants of the initial speed of infarct progression and the association of speed of infarct progression (SIP) with procedural and functional outcomes. METHODS: From a prospectively maintained stroke center registry, consecutive anterior circulation ischemic stroke patients with large artery occlusion, National Institutes of Health Stroke Scale score ≥4, and multimodal vessel, ischemic core, and tissue-at-risk imaging within 24 hours of onset were included. Initial SIP was calculated as ischemic core volume at first imaging divided by the time from stroke onset to imaging. RESULTS: Among the 88 patients, SIP was median 2.2 cc/h (interquartile range, 0-8.7), ranging most widely within the first 6 hours after onset. Faster SIP was positively independently associated with a low collateral score (odds ratio [OR], 3.30 [95% CI, 1.25-10.49]) and arrival by emergency medical services (OR, 3.34 [95% CI, 1.06-10.49]) and negatively associated with prior ischemic stroke (OR, 0.12 [95% CI, 0.03-0.50]) and coronary artery disease (OR, 0.32 [95% CI, 0.10-1.00]). Among the 67 patients who underwent endovascular thrombectomy, slower SIP was associated with a shift to reduced levels of disability at discharge (OR, 3.26 [95% CI, 1.02-10.45]), increased substantial reperfusion by thrombectomy (OR, 8.30 [95% CI, 0.97-70.87]), and reduced radiological hemorrhagic transformation (OR, 0.34 [95% CI, 0.12-0.94]). CONCLUSIONS: Slower SIP is associated with a high collateral score, prior ischemic stroke, and coronary artery disease, supporting roles for both collateral robustness and ischemic preconditioning in fostering tissue resilience to ischemia. Among patients undergoing endovascular thrombectomy, the speed of infarct progression is a major determinant of clinical outcome.

Paramedic Global Impression of Change During Prehospital Evaluation and Transport for Acute Stroke.

Background and Purpose- The prehospital setting is a promising site for therapeutic intervention in stroke, but current stroke screening tools do not account for the evolution of neurological symptoms in this early period. We developed and validated the Paramedic Global Impression of Change (PGIC) Scale in a large, prospective, randomized trial. Methods- In the prehospital FAST-MAG (Field Administration of Stroke Therapy-Magnesium) randomized trial conducted from 2005 to 2013, EMS providers were asked to complete the PGIC Scale (5-point Likert scale values: 1-much improved, 2-mildly improved, 3-unchanged, 4-mildly worsened, 5-much worsened) for neurological symptom change during transport for consecutive patients transported by ambulance within 2 hours of onset. We analyzed PGIC concurrent validity (compared with change in Glasgow Coma Scale, Los Angeles Motor Scale), convergent validity (compared with National Institutes of Health Stroke Scale severity measure performed in the emergency department), and predictive validity (of neurological deterioration after hospital arrival and of final 90-day functional outcome). We used PGIC to characterize differential prehospital course among stroke subtypes. Results- Paramedics completed the PGIC in 1691 of 1700 subjects (99.5%), among whom 635 (37.5%) had neurological deficit evolution (32% improvement, 5.5% worsening) during a median prehospital care period of 33 (IQR, 27-39) minutes. Improvement was associated with diagnosis of cerebral ischemia rather than intracranial hemorrhage, milder stroke deficits on emergency department arrival, and more frequent nondisabled and independent 3-month outcomes. Conversely, worsening on the PGIC was associated with intracranial hemorrhage, more severe neurological deficits on emergency department arrival, more frequent treatment with thrombolytic therapy, and poor disability outcome at 3 months. Conclusions- The PGIC scale is a simple, validated measure of prehospital patient course that has the potential to provide information useful to emergency department decision-making. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00059332.

Subject Retention in Prehospital Stroke Research Using a Telephone-Based Physician-Investigator Driven Enrollment Method.

BACKGROUND AND PURPOSE: Subject retention into clinical trials is vital, and prehospital enrollment may be associated with higher rates of subject withdrawal than more traditional methods of enrollment. We describe rates of subject retention in a prehospital trial of acute stroke therapy. METHODS: All subjects were enrolled into the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial. Paramedics screened eligible subjects and contacted the physician-investigator using a dedicated in-ambulance cellular phone. Physician-investigators obtained explicit informed consent from the subject or on-scene legally authorized representative (LAR) who reviewed and signed a consent form. Exception from informed consent (EFIC) was utilized in later stages of the study. RESULTS: There were 1,700 subjects enrolled; 1,017 provided consent (60%), 662 were enrolled via LAR (39%), and 21 were enrolled via EFIC (1%). Of the 1,700 patients, 1,413 (83%) completed the 90-day visit, 265 (16%) died prior to the 90-day visit, and 22 (1.3%) withdrew from the study before completion. There were no differences in rates of withdrawal by method of study enrolment, i.e., self-consent (n = 14), 1.4%; LAR (n = 8), 1.2%; EFIC (n = 0) 0%. CONCLUSION: There was a high rate of retention when subjects were enrolled into prehospital stroke research using a phone-based method to obtain explicit consent.