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.

MRI in the Evaluation of Cryptogenic Stroke and Embolic Stroke of Undetermined Source.

Cryptogenic stroke refers to a stroke of undetermined etiology. It accounts for approximately one-fifth of ischemic strokes and has a higher prevalence in younger patients. Embolic stroke of undetermined source (ESUS) refers to a subgroup of patients with nonlacunar cryptogenic strokes in whom embolism is the suspected stroke mechanism. Under the classifications of cryptogenic stroke or ESUS, there is wide heterogeneity in possible stroke mechanisms. In the absence of a confirmed stroke etiology, there is no established treatment for secondary prevention of stroke in patients experiencing cryptogenic stroke or ESUS, despite several clinical trials, leaving physicians with a clinical dilemma. Both conventional and advanced MRI techniques are available in clinical practice to identify differentiating features and stroke patterns and to determine or infer the underlying etiologic cause, such as atherosclerotic plaques and cardiogenic or paradoxical embolism due to occult pelvic venous thrombi. The aim of this review is to highlight the diagnostic utility of various MRI techniques in patients with cryptogenic stroke or ESUS. Future trends in technological advancement for promoting the adoption of MRI in such a special clinical application are also discussed.

Differentiating ischemic stroke patients from healthy subjects using a large-scale, retrospective EEG database and machine learning methods.

OBJECTIVES: We set out to develop a machine learning model capable of distinguishing patients presenting with ischemic stroke from a healthy cohort of subjects. The model relies on a 3-min resting electroencephalogram (EEG) recording from which features can be computed. MATERIALS AND METHODS: Using a large-scale, retrospective database of EEG recordings and matching clinical reports, we were able to construct a dataset of 1385 healthy subjects and 374 stroke patients. With subjects often producing more than one recording per session, the final dataset consisted of 2401 EEG recordings (63% healthy, 37% stroke). RESULTS: Using a rich set of features encompassing both the spectral and temporal domains, our model yielded an AUC of 0.95, with a sensitivity and specificity of 93% and 86%, respectively. Allowing for multiple recordings per subject in the training set boosted sensitivity by 7%, attributable to a more balanced dataset. CONCLUSIONS: Our work demonstrates strong potential for the use of EEG in conjunction with machine learning methods to distinguish stroke patients from healthy subjects. Our approach provides a solution that is not only timely (3-minutes recording time) but also highly precise and accurate (AUC: 0.95).

Modified Rankin Scale Disability Status at Day 4 Poststroke is an Informative Predictor of Long-Term Day 90 Outcome.

BACKGROUND: Long-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated. METHODS: In this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics. RESULTS: Among the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman's rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (kappa=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71. CONCLUSIONS: In this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.

Effect of Magnesium on Deterioration and Symptomatic Hemorrhagic Transformation in Cerebral Ischemia: An Ancillary Analysis of the FAST-MAG Trial.

BACKGROUND: Magnesium (Mg) is a neuroprotectant in preclinical models. Lower serum Mg levels have been associated with symptomatic hemorrhagic transformation (HT) in patients with ischemic stroke. Early treatment of acute ischemic stroke with Mg may reduce rates of symptomatic HT. METHODS: In this post hoc study of the Field Administration of Stroke Therapy Magnesium (FAST-MAG) trial, 1,245 participants with a diagnosis of cerebral ischemia received 20 g of Mg or placebo initiated in the prehospital setting. Posttreatment serum Mg level was measured for 809 participants. Cases of clinical deterioration, defined as worsening by ≥4 points on the National Institute of Health Stroke Scale (NIHSS), were imaged and evaluated for etiology. Symptomatic HT was defined as deterioration with imaging showing new hemorrhage. RESULTS: Clinical deterioration occurred in 187 and symptomatic HT in 46 of 1,245 cases of cerebral ischemia. Rates of deterioration and symptomatic HT were not significantly lower in those who received Mg (15.7% vs. 14.4%, p = 0.591; 2.8% vs. 4.6%, p = 0.281). In cases where serum Mg level was obtained posttreatment, lower serum Mg level (<1.7 mg/dL) was associated with significantly higher rates of deterioration and symptomatic HT (27.5% vs. 15.5%, p = 0.0261; 11.6% vs. 3.65%, p = 0.00819). CONCLUSIONS: Treatment with Mg did not significantly reduce rates of clinical deterioration or symptomatic HT. Future analysis should address whether treatment with Mg could have influenced the subgroup with low serum Mg at baseline.

Association Between Hyperacute Blood Pressure Variability and Hematoma Expansion After Intracerebral Hemorrhage: Secondary Analysis of the FAST-MAG Database.

BACKGROUND: Blood pressure variability (BPV) has emerged as a significant factor associated with clinical outcomes after intracerebral hemorrhage (ICH). Although hematoma expansion (HE) is associated with clinical outcomes, the relationship between BPV that encompasses prehospital data and HE is unknown. We hypothesized that BPV was positively associated with HE. METHODS: We analyzed 268 patients with primary ICH enrolled in the National Institutes of Health-funded Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study who received head computed tomography or magnetic resonance imaging on arrival to the emergency department (ED) and repeat imaging within 6-48 h. BPV was calculated by standard deviation (SD) and coefficient of variation (CV) from prehospital data as well as systolic blood pressure (SBP) measurements taken on ED arrival, 15 min post antihypertensive infusion start, 1 h post maintenance infusion start, and 4 h after ED arrival. HE was defined by hematoma volume expansion increase > 6 mL or by 33%. Univariate logistic regression was used for presence of HE in quintiles of SD and CV of SBP for demographics and clinical characteristics. RESULTS: Of the 268 patients analyzed from the FAST-MAG study, 116 (43%) had HE. Proportions of patients with HE were not statistically significant in the higher quintiles of the SD and CV of SBP for either the hyperacute or the acute period. Presence of HE was significantly more common in patients on anticoagulation. CONCLUSIONS: Higher BPV was not found to be associated with occurrence of HE in the hyperacute or the acute period of spontaneous ICH. Further study is needed to determine the relationship.

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.

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.

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.

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

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.

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

Extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 infection.

Coronavirus disease 2019, the infectious disease caused by severe acute respiratory syndrome coronavirus-2, has resulted in a global pandemic with unprecedented health, societal, and economic impact. The disease often manifests with flu-like symptoms and is dominated by pulmonary complications, but widely diverse clinical manifestations involving multiple organ systems can result. We posit that viral tropism and the aberrant host immune response mediate the protean findings and severity in this disease. In general, extrapulmonary manifestations are a harbinger of or contemporaneously associate with disease progression, but in the case of some extrapulmonary findings (gastrointestinal and dermatologic), may track with milder disease. The precise underlying pathophysiological mechanisms remain incompletely elucidated, and additional immune phenotyping studies are warranted to reveal early correlates of disease outcomes and novel therapeutic targets.

Transcranial eddy current damping sensors for detection and imaging of hemorrhagic stroke: feasibility in benchtop experimentation.

OBJECTIVE: Spontaneous intracerebral hemorrhage occurs in an estimated 10% of stroke patients, with high rates of associated mortality. Portable diagnostic technologies that can quickly and noninvasively detect hemorrhagic stroke may prevent unnecessary delay in patient care and help rapidly triage patients with ischemic versus hemorrhagic stroke. As such, the authors aimed to develop a rapid and portable eddy current damping (ECD) hemorrhagic stroke sensor for proposed in-field diagnosis of hemorrhagic stroke. METHODS: A tricoil ECD sensor with microtesla-level magnetic field strengths was constructed. Sixteen gelatin brain models with identical electrical properties to live brain tissue were developed and placed within phantom skull replicas, and saline was diluted to the conductivity of blood and placed within the brain to simulate a hemorrhage. The ECD sensor was used to detect modeled hemorrhages on benchtop models. Data were saved and plotted as a filtered heatmap to represent the lesion location. The individuals performing the scanning were blinded to the bleed location, and sensors were tangentially rotated around the skull models to localize blood. Data were also used to create heatmap images using MATLAB software. RESULTS: The sensor was portable (11.4-cm maximum diameter), compact, and cost roughly $100 to manufacture. Scanning time was 2.43 minutes, and heatmap images of the lesion were produced in near real time. The ECD sensor accurately predicted the location of a modeled hemorrhage in all (n = 16) benchtop experiments with excellent spatial resolution. CONCLUSIONS: Benchtop experiments demonstrated the proof of concept of the ECD sensor for rapid transcranial hemorrhagic stroke diagnosis. Future studies with live human participants are warranted to fully establish the feasibility findings derived from this study.

A systematic review of next-generation point-of-care stroke diagnostic technologies.

OBJECTIVE: Stroke is a leading cause of morbidity and mortality. Current diagnostic modalities include CT and MRI. Over the last decade, novel technologies to facilitate stroke diagnosis, with the hope of shortening time to treatment and reducing rates of morbidity and mortality, have been developed. The authors conducted a systematic review to identify studies reporting on next-generation point-of-care stroke diagnostic technologies described within the last decade. METHODS: A systematic review was performed according to PRISMA guidelines to identify studies reporting noninvasive stroke diagnostics. The QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool was utilized to assess risk of bias. PubMed, Web of Science, and Scopus databases were utilized. Primary outcomes assessed included accuracy and timing compared with standard imaging, potential risks or complications, potential limitations, cost of the technology, size/portability, and range/size of detection. RESULTS: Of the 2646 reviewed articles, 19 studies met the inclusion criteria and included the following modalities of noninvasive stoke detection: microwave technology (6 studies, 31.6%), electroencephalography (EEG; 4 studies, 21.1%), ultrasonography (3 studies, 15.8%), near-infrared spectroscopy (NIRS; 2 studies, 10.5%), portable MRI devices (2 studies, 10.5%), volumetric impedance phase-shift spectroscopy (VIPS; 1 study, 5.3%), and eddy current damping (1 study, 5.3%). Notable medical devices that accurately predicted stroke in this review were EEG-based diagnosis, with a maximum sensitivity of 91.7% for predicting a stroke, microwave-based diagnosis, with an area under the receiver operating characteristic curve (AUC) of 0.88 for differentiating ischemic stroke and intracerebral hemorrhage (ICH), ultrasound with an AUC of 0.92, VIPS with an AUC of 0.93, and portable MRI with a diagnostic accuracy similar to that of traditional MRI. NIRS offers significant potential for more superficially located hemorrhage but is limited in detecting deep-seated ICH (2.5-cm scanning depth). CONCLUSIONS: As technology and computational resources have advanced, several novel point-of-care medical devices show promise in facilitating rapid stroke diagnosis, with the potential for improving time to treatment and informing prehospital stroke triage.

Increased Access to and Use of Endovascular Therapy Following Implementation of a 2-Tiered Regional Stroke System.

Background and Purpose- We quantified population access to endovascular-capable centers, timing, and rates of thrombectomy in Los Angeles County before and after implementing 2-tiered routing in a regional stroke system of care. Methods- In 2018, the Los Angeles County Emergency Medical Services Agency implemented transport of patients with suspected large vessel occlusions identified by Los Angeles Motor Scale ≥4 directly to designated endovascular-capable centers. We calculated population access to a designated endovascular-capable center within 30 minutes comparing 2016, before 2-tiered system planning began, to 2018 after implementation. We analyzed data from stroke centers in the region from 1 year before and after implementation to delineate changes in rates and speed of administration of tPA (tissue-type plasminogen activator) and thrombectomy and frequency of interfacility transfer. Results- With implementation of the 2-tier system, certified endovascular-capable hospitals increased from 4 to 19 centers, and within 30-minute access to endovascular care for the public in Los Angeles County, from 40% in 2016 to 93% in 2018. Comparing Emergency Medical Services-transported stroke patients in the first post-implementation year (N=3303) with those transported in the last pre-implementation year (N=3008), age, sex, and presenting deficit severity were similar. The frequency of thrombolytic therapy increased from 23.8% to 26.9% (odds ratio, 1.2 [95% CI, 1.05-1.3]; P=0.006), and median first medical contact by paramedic-to-needle time decreased by 3 minutes ([95% CI, 0-5] P=0.03). The frequency of thrombectomy increased from 6.8% to 15.1% (odds ratio, 2.4 [95% CI, 2.0-2.9]; P<0.0001), although first medical contact-to-puncture time did not change significantly, median decrease of 8 minutes ([95% CI, -4 to 20] P=0.2). The frequency of interfacility transfers declined from 3.2% to 1.0% (odds ratio, 0.3 [95% CI, 0.2-0.5]; P<0.0001). Conclusions- After implementation of 2-tiered stroke routing in the most populous US county, thrombectomy access increased to 93% of the population, and the frequency of thrombectomy more than doubled, whereas interfacility transfers declined.

Derivation and Application of a Tool to Estimate Benefits From Multiple Therapies That Reduce Recurrent Stroke Risk.

Background and Purpose- Lowering blood pressure and cholesterol, antiplatelet/antithrombotic use, and smoking cessation reduce risk of recurrent stroke. However, gaps in risk factor control among stroke survivors warrant development and evaluation of alternative care delivery models that aim to simultaneously improve multiple risk factors. Randomized trials of care delivery models are rarely of sufficient duration or size to be powered for low-frequency outcomes such as observed recurrent stroke. This creates a need for tools to estimate how changes across multiple stroke risk factors reduce risk of recurrent stroke. Methods- We reviewed existing evidence of the efficacy of interventions addressing blood pressure reduction, cholesterol lowering, antiplatelet/antithrombotic use, and smoking cessation and extracted relative risks for each intervention. From this, we developed a tool to estimate reductions in recurrent stroke risk, using bootstrapping and simulation methods. We also calculated a modified Global Outcome Score representing the proportion of potential benefit (relative risk reduction) achieved if all 4 individual risk factors were optimally controlled. We applied the tool to estimate stroke risk reduction among 275 participants with complete 12-month follow-up data from a recently published randomized trial of a healthcare delivery model that targeted multiple stroke risk factors. Results- The recurrent stroke risk tool was feasible to apply, yielding an estimated reduction in the relative risk of ischemic stroke of 0.36 in both the experimental and usual care trial arms. Global Outcome Score results suggest that participants in both arms likely averted, on average, 45% of recurrent stroke events that could possibly have been prevented through maximal implementation of interventions for all 4 individual risk factors. Conclusions- A stroke risk reduction tool facilitates estimation of the combined impact on vascular risk of improvements in multiple stroke risk factors and provides a summary outcome for studies testing alternative care models to prevent recurrent stroke. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00861081.

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.

Factors Associated With Participation in the Chronic Disease Self-Management Program: Findings From the SUCCEED Trial.

BACKGROUND AND PURPOSE: Self-management programs may improve quality of life and self-efficacy for stroke survivors, but participation is low. In a randomized controlled trial of a complex, multidisciplinary, team-based secondary stroke prevention intervention, we offered participants Chronic Disease Self-Management Program (CDSMP) workshops in addition to clinic visits and home visits. To enhance participation, workshops were facilitated by community health workers who were culturally and linguistically concordant with most participants and scheduled CDSMP sessions at convenient venues and times. Over time, we implemented additional strategies such as free transportation and financial incentives. In this study, we aimed to determine factors associated with CDSMP participation and attendance. METHODS: From 2014 to 2018, 18 CDSMP workshop series were offered to 241 English and Spanish-speaking individuals (age ≥40 years) with recent stroke or transient ischemic attack. Zero-inflated Poisson regression was used to identify factors associated with participation and attendance (ie, number of sessions attended) in CDSMP. Missing values were imputed using multiple imputation methods. RESULTS: Nearly one-third (29%) of intervention subjects participated in CDSMP. Moderate disability and more clinic/home visits were associated with participation. Participants with higher numbers of clinic and home visits (incidence rate ratio [IRR], 1.06 [95% CI, 1.01-1.12]), severe (IRR, 2.34 [95% CI, 1.65-3.31]), and moderately severe disability (IRR, 1.55 [95% CI, 1.07-2.23]), and who enrolled later in the study (IRR, 1.12 [95% CI, 1.08-1.16]) attended more sessions. Individuals with higher chaos scores attended fewer sessions (IRR, 0.97 [95% CI, 0.95-0.99]). CONCLUSIONS: Less than one-third of subjects enrolled in the SUCCEED (Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities) intervention participated in CDSMP; however, participation improved as transportation and financial barriers were addressed. Strategies to address social determinants of health contributing to chaos and engage individuals in healthcare may facilitate attendance. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01763203.

Neighborhood-level stroke hot spots within major United States cities.

OBJECTIVE: Identifying communities at high risk of stroke is an important step in improving systems of stroke care. Stroke is known to show spatial clustering at the state and county levels, but it is not known if clusters are present within city boundaries. METHODS: We performed a geospatial analysis of the prevalence of stroke within 500 major cities in the United States using the Centers for Disease Control and Prevention 500 Cities Project. For each city, we calculated the Moran's I statistic, which looks for evidence of spatial clustering, and used Monte Carlo simulation to assess for clustering significance. RESULTS: The mean overall crude prevalence of self-reported history of stroke at the city level was 2.8% (IQR 2.4-3.2%). Monte Carlo simulations of spatial patterns of stroke were successfully performed for 497 cities, of which 136 (27.3%) showed significant spatial clustering at the neighborhood level. All nine cities with more than one million inhabitants in 2010 showed significant spatial clustering. CONCLUSIONS: This is the first study to demonstrate that stroke shows clustering at the neighborhood level within many major cities in the United States and within all of the largest cities. Understanding where stroke clusters exist within cities can form the basis of optimizing emergency medical services deployment and improving systems of stroke care.