A meta-analysis of the global impact of the COVID-19 pandemic on stroke care & the Houston Experience.

OBJECTIVE: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston. METHODS: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. RESULTS: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. INTERPRETATION: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics.

Routine surveillance of pelvic and lower extremity deep vein thrombosis in stroke patients with patent foramen ovale.

Patent foramen ovale (PFO) is a potential conduit for paradoxical embolization to the systemic atrial circulation of a thrombus originating in the venous system. In a selected group of subjects, the prevalence of deep vein thrombosis (DVT) was assessed. Subjects were identified if they underwent magnetic resonance venography (MRV) pelvis and lower extremity doppler (LE-VDU) for assessment of DVT with PFO. The primary outcome measure was to report the number of patients with paradoxical embolization as their suspected etiology of stroke due to the presence of DVT, which then will be considered as determined stroke. Others with determined stroke diagnosis were reported using Treatment of Acute Stroke Trial (TOAST) criteria. At discharge, those without etiology of their stroke were grouped under embolic stroke of undetermined source (ESUS). We further analyzed the prevalence of DVT by age group, ≤ 60 years vs > 60 years to describe if the prevalence is higher with younger age and to evaluate if higher Risk of Paradoxical Embolism (ROPE) score will have higher number of DVTs compared to lower ROPE scores. Of the 293, 19 (7%) were strokes due to paradoxical embolism. At discharge, determined stroke were 54% vs ESUS were 46%. The overall prevalence of DVT was 19 (7%); MRV-pelvis 13 (4%), and LE-VDU was 9 (3%). No significant difference was noted using both modalities. However, in multivariable regression analysis, a trend suggested an association between pelvic thrombi and high ROPE score as the etiology of stroke; OR 3.56 (0.98, 12.93); p = 0.054. Detection of DVT was not associated with PFO, high ROPE scores or young age. Our data indicate an over-reliance of testing for DVT, particularly MRV pelvis with contrast, in patients with PFO. Clinical studies are needed to identify other factors predictive of DVT in patients with ischemic stroke and PFO.

Different strokes: differences in the characteristics and outcomes of BCVI and non-BCVI strokes in trauma patients.

BACKGROUND: Although strokes are rare in trauma patients, they are associated with worse functional and cognitive outcomes and decreased mobility. Blunt cerebrovascular injury (BCVI)-related strokes and mortality have decreased, likely due to refined screening and treatment algorithms in trauma literature; however, there is a paucity of research addressing non-BCVI strokes in trauma. The purpose of this study is to evaluate the incidence, etiology, and risk factors of stroke in our trauma population in order to identify preventive strategies. METHODS: This study was a retrospective review of all adult trauma patients admitted to a level 1 trauma hospital who suffered a stroke during trauma admission from 2010 to 2017. Data were collected from the prospectively maintained trauma and stroke databases. Stroke etiology was determined by a vascular neurologist. RESULTS: Of the 43 674 adult trauma patients admitted during the study period, 99 (0.2%) were diagnosed with a stroke during the index admission. Twenty-one (21%) strokes were due to BCVI. Seventy-eight (79%) strokes were due to non-BCVI etiologies. Patients with non-BCVI strokes were older, less severely injured, and had more medical comorbidities compared with patients with a BCVI stroke. While patients with a BCVI stroke were more likely to suffer multiple traumatic injuries from MVC (76% vs 28%, p<0.001), non-BCVI strokes had more isolated extremity injuries from fall mechanism (55% vs 10%, p<0.001). Over the study period, the age and incidence of stroke and BCVI (p<0.001) increased. However, the rate of BCVI strokes decreased while the rate of non-BCVI strokes increased. DISCUSSION: The incidence of stroke has increased despite aggressive screening and treatment of BCVI. This increase is primarily due to non-BCVI strokes which are associated with advanced age and medical comorbidities after low mechanism traumatic injury. Medical optimization of comorbid conditions during trauma hospitalization will become increasingly important for stroke prevention as the population ages.Level of evidence: Level III.

Rapid Infarct Progression in Anterior Circulation Large Vessel Occlusion Ischemic Stroke Patients During Inter-Facility Transfer.

INTRODUCTION: We aimed to identify factors associated with rapid infarct progression during inter-facility transfer for endovascular thrombectomy evaluation and its impact on clinical outcomes. METHODS: Patients with anterior circulation large artery occlusion within 24 h of onset transferred within our 17 hospital tele-stroke network were retrospectively analyzed. Patients were divided into fast progressors and slow progressors. Fast progressors were defined as CT ASPECTS score of ≥6 at the referring hospital (RH) and <6 at the hub hospital. Good clinical outcomes were defined as modified Rankin Scale score (mRS) 0-2 at 90 days. Demographic, clinical and radiologic variables associated with fast progressors and good clinical outcomes were identified using multivariable regression models. RESULTS: Among the 190 patients, 44 (23%) patients underwent rapid infarct progression. Higher stroke severity at presentation [aOR, 1.096, 95% CI,1.023, 1.174; p = 0.009], presence of early ischemic changes (CT ASPECT 6-9) at the RH [aOR, 2.721, 95% CI, 1.22, 6.071; p = 0.014] were positively associated, whereas prior ischemic stroke [aOR, 0.272, 95% CI, 0.078, 0.948; p = 0.04] and higher collateral score (2,3,4) [aOR, 0.138, 95%CI, 0.059, 0.324, p=<0.0001] were negatively associated with rapid infarct progression. Fifty-eight (31%) transferred patients had good outcomes. After adjusting for reperfusion status, age [aOR, 0.96, 95% CI, 0.93, 0.98; p=<0.001], initial stroke severity [aOR, 0.87, 95% CI, 0.81, 0.93; p=<0.001], absolute rate of decrease in CT ASPECTS [aOR, 0.38, 95% CI, 0.19, 0.77; p = 0.007] and internal carotid artery (ICA) occlusion [aOR, 0.34, 95 %CI, 0.12, 0.94; p = 0.038] were negatively associated with good outcome. CONCLUSION: Higher stroke severity, presence of early ischemic changes at the referring facility, absence of prior stroke, and poor collateral scores (CS 0-1) are the factors associated with rapid infarct progression in the telemedicine transfer cohort. Increasing age, higher stroke severity, higher absolute decrease in CT ASPECTS and ICA occlusion determine poor clinical outcomes.

Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial.

BACKGROUND: We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2). METHODS: ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fisher's exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms. RESULTS: Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3-5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured. CONCLUSIONS: We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality.

Telemedicine-guided remote enrollment of patients into an acute stroke trial.

BACKGROUND AND PURPOSE: Enrollment into acute stroke clinical trials is limited to experienced tertiary centers with emergency research infrastructure. Feasibility of remote enrollment via telemedicine into an acute thrombolytic clinical trial has never been demonstrated. METHODS: Using telemedicine, our hub stroke research center partnered with two spoke community hospitals to jointly participate in a randomized, phase III adjunctive thrombolysis clinical trial in the first 3 h after symptom onset to expand recruitment of the trial. Eligible patients were successfully identified, consented, randomized, and received therapy/placebo at the spoke hospitals under real-time direction by hub trialists via telemedicine. RESULTS: Ten patients were identified from May 2013 to July 2014, and six were enrolled via telemedicine. No study procedure delays, safety events, or major protocol violations occurred. CONCLUSIONS: It is feasible to randomize and enroll stroke patients via remote telemedicine into an acute thrombolytic clinical trial. This novel approach could expand access and accelerate completion of clinical trials if widely implemented.

CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: The Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free (CLOTBUST-HF) study is a first-in-human, National Institutes of Health-sponsored, multicenter, open-label, pilot safety trial of tissue-type plasminogen activator (tPA) plus a novel operator-independent ultrasound device in patients with ischemic stroke caused by proximal intracranial occlusion. METHODS: All patients received standard-dose intravenous tPA, and shortly after tPA bolus, the CLOTBUST-HF device delivered 2-hour therapeutic exposure to 2-MHz pulsed-wave ultrasound. Primary outcome was occurrence of symptomatic intracerebral hemorrhage. All patients underwent pretreatment and post-treatment transcranial Doppler ultrasound or CT angiography. National Institutes of Health Stroke Scale scores were collected at 2 hours and modified Rankin scale at 90 days. RESULTS: Summary characteristics of all 20 enrolled patients were 60% men, mean age of 63 (SD=14) years, and median National Institutes of Health Stroke Scale of 15. Sites of pretreatment occlusion were as follows: 14 of 20 (70%) middle cerebral artery, 3 of 20 (15%) terminal internal carotid artery, and 3 of 20 (15%) vertebral artery. The median (interquartile range) time to tPA at the beginning of sonothrombolysis was 22 (13.5-29.0) minutes. All patients tolerated the entire 2 hours of insonation, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device. Rates of 2-hour recanalization were as follows: 8 of 20 (40%; 95% confidence interval, 19%-64%) complete and 2 of 20 (10%; 95% confidence interval, 1%-32%) partial. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate: 8 of 14 (57%; 95% confidence interval, 29%-82%). At 90 days, 5 of 20 (25%, 95% confidence interval, 7%-49) patients had a modified Rankin scale of 0 to 1. CONCLUSIONS: Sonothrombolysis using a novel, operator-independent device, in combination with systemic tPA, seems safe, and recanalization rates warrant evaluation in a phase III efficacy trial. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: CLOTBUST-HF NCT01240356.