bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 179: Functional Outcomes of Pre-hospital Stroke Thrombolysis Compared to Conventional Care; the Stroke Emergency Mobile (STEMO) Project
Authors: Kunz Alexander Kunz , Nolte Christian , Fiebach Jochen B , Geisler Frederik , Rozanski Michal , Scheitz Jan F , Villringer Kersten , Waldschmidt Carolin , Weber Joachim , Wendt Matthias , Winter Benjamin , Zieschang Katja , Grittner Ulrike , Kaczmarek Sabina , Endres Matthias , Ebinger Martin , Audebert Heinrich J
Published: July 2021

Background:
Specialized CT-equipped stroke ambulances can shorten time to intravenous thrombolysis (IVT) in acute ischemic stroke. Although efficacy of thrombolytic treatment is known to be time-sensitive, effects of pre-hospital thrombolysis on functional outcomes have not yet been evaluated.

Methods:
We compared outcomes of all consecutive stroke patients who received thrombolysis during the same period cared for either by the Berlin Stroke Emergency Mobile (STEMO) or within conventional care (normal ambulance and in-hospital thrombolysis). Treatment and outcomes were documented in prospective registries. Patients who lived at home without assistance prior to their stroke were included. Primary outcome was modified Rankin Scale (mRS) ≤1 at 3 month. Secondary outcome was 3-month mortality. Outcomes were adjusted in multivariable regression for demographics, co-morbidities and stroke severity.

Results:
From Feb. 5, 2011 to Mar 5, 2015, 427 patients were treated on STEMO and 513 in conventional care. 303 (mean age: 71y, female gender: 48%, median NIHSS: 7) and 357 (mean age: 70y, female gender: 36%, median NIHSS: 7) of them had lived at home without assistance pre-stroke, respectively. Mean onset to treatment time was 34 minutes shorter in STEMO care (96±60 vs. 130±56min). The primary outcome of mRS≤1 was observed in 167 (55%) and 168 (47%) patients (p=0.039); 17 (6%) vs 38 (11%) had died (p=0.02), respectively. Adjusted odds ratios were favorable for STEMO care: OR 1.56 (95%-CI: 1.11-2.20; p=0.01) for mRS≤1 and OR 0.50 (95%-CI: 0.26-0.98; p=0.04) for death.

Conclusions:
The data suggest that earlier start of IVT by specialized prehospital stroke care leads to improved outcome.
Abstract 181: A Systematic Review of Interventions to Increase tPA Administration
Authors: McDermott Mollie , Skolarus Lesli E , Burke James F
Published: July 2021

Introduction:
Rates of tPA administration remain low nationally and globally despite its demonstrated efficacy. We performed a systematic review and meta-analysis of interventions to increase the rate of tPA administration.

Methods:
We searched PubMed and EMBASE to identify all studies (excluding case reports) published between 1995 and January 8, 2015 documenting interventions to increase the utilization of tPA. We screened each study with pre-specified inclusion and exclusion criteria. Design elements and study data were extracted from eligible studies. The principal summary measure was the percentage change in rate of tPA administration. Fixed and random effects meta-analytic models were built to summarize the effect of intervention compared to control as well as intervention subtypes.

Results:
Our search yielded 1457 results of which 25 met eligibility criteria. We identified 13 pre-post studies and 11 randomized or quasi-experimental studies. Included studies utilized EMS (n=14), telemedicine (n=6), and public education (n=5). Intervention settings included urban (n=13), rural (n=4), and combined (n=4). In a fixed effect model, tPA administration was significantly higher in the intervention arm across all studies that limited enrollment to ischemic stroke patients (n=14) with a risk ratio (RR) of 1.71. Interventions involving EMS were associated with an increased rate of tPA administration with a RR of 1.51, (95% CI: 1.43-1.59, p<0.0001); promoting public education RR = 2.62, (95% CI: 1.54-4.43, p<0.01); and utilizing telemedicine RR = 2.97, (95% CI: 2.61-3.39, p<0.0001).

Conclusions:
Interventions to increase tPA use appear to have considerable efficacy. Comparative inferences between intervention types are limited by small sample size and intervention heterogeneity.
Abstract 185: Residual Stroke Morbidity and Post-acute Care Cost: the IMS III Economic Data Cohort
Authors: Simpson Kit N , Simpson Annie N , Hill Michael D , Palesh Yuko Y , Jauch Edward C , Khatri Pooja , Kleindorfer Dawn , Foster Lydia D , Mauldin Patrick D , Broderick Joseph P ,   for the IMS III Investigators
Published: July 2021

Introduction:
The IMS III trial included 1-year follow-up with prospectively collected data on resource use after stroke. While the trial showed no difference in 90-day clinical outcomes by treatment group, this cohort provides invaluable information on cost variations associated with post-stroke morbidity. We report the effect of residual stroke morbidity on cost of stroke care after discharge at 12 months post stroke.

Methods:
Among 470 subjects with moderate to severe stroke for whom economic data were collected (316 randomized to IV t-PA and endovascular therapy, 154 to IV t-PA alone), we estimated cumulative cost post discharge using cost weights derived from a 5% sample of US Medicare patients in 2012 with an admission for acute ischemic stroke with IV t-PA treatment. Cost weights included post-stroke rehabilitation hospital days, emergency care visits, hospital readmissions, medical office visits, rehabilitation therapy visits and nursing home days. Costs were summed at the level of the subject and estimated for the subset defined by NIH Stroke Scale Score (NIHSS) at day 5, and Modified Rankin Score (mRS) and Barthel Index (BI) at 3 months post stroke. Subjects who died during the initial hospital admission or who had no score at day 5 or at 3 months were not included in our analysis. Age-adjusted, log-transformed costs were compared.

Results:
There was a 6 fold difference in the cost of follow-up care by lowest and highest NIHSS at day 5 (p<.0001). Similarly large differences by outcome category were observed for both the mRS (p<.0001) groups and subjects defined by the BI (p<.0001) at 3 months (see Figure).

Conclusion:
Residual stroke morbidity has a large effect on the long-term cost of stroke care, with an effect size of over 600%. Interventions that improve the residual morbidity after stroke as early as day 5 may be expected to result in substantial post discharge cost savings.
Abstract 197: Time is Brain: Standardized Neuro-interventional Thrombectomy Protocols Lead to Faster Recanalization Times
Authors: Frei Donald , Caputo Lisa M , McCarthy Kathryn , Salottolo Kristin , Bar-Or David
Published: July 2021

Background:
Acute stroke treatment has been proven to be most effective when performed quickly. The objective of our study was to describe the steps taken to improve time metrics for patients receiving intra-arterial therapy (IAT), and compare metrics before and after implementation of these standardized time saving protocols.

Hypothesis:
Through streamlining the evaluation and treatment process of IAT, we predict our times between patient arrival, imaging, groin puncture and recanalization will be reduced.

Methods:
On 6/1/13, we instituted a series of interventions in the Neuro-interventional Surgery department to streamline care, including: requiring the Neuro-interventional team to meet all transferred patients in the CT scanner upon patient arrival, introducing a wheeled stroke cart replete with a stroke tray containing all devices needed to perform the stroke thrombectomy, standardizing the thrombectomy procedure, switching from general anesthesia to conscious sedation for all stroke patients, and no longer shaving the groin or using a foley catheter. We also added an additional biplane INR room, doubling our room capacity. We compared time metrics of patient arrival to CT imaging, imaging to puncture, and puncture to recanalization of acute ischemic stroke patients that received IAT before (1/1/12-5/31/13) and after (6/1/13-5/31/15) the interventions using univariate analysis.

Results:
Three hundred twenty-two patients received IAT during the study period. Nearly three quarters (73.3%) of the population was transferred from a referring facility. There were significantly less female patients in the post-intervention cohort (59.5% v 48.0%, p=0.04); there were no significant differences in age, race, or initial NIHSS. We found statistically significant reductions in time between patient arrival to imaging (19.2±9.6 v 13.6 ±6.7, p<0.000), imaging to puncture (57.9±36.2 v 46.9±40.5, p=0.04), and puncture to recanalization (70.7±47.3 v 53.1 ±40.4, p=.004) after implementation of the interventions.

Conclusions:
Our initiatives allowed us to refine our process of care, resulting in a significant reduction of time between patient arrival and imaging, imaging and femoral artery access, and groin puncture to recanalization.
Abstract 198: Outcomes of Immediate Carotid Stenting With Mechanical Thrombactomy in Large Vessel Anterior Circulation Strokes
Authors: Mehta Tapan V , Mirtchev Dimitre , Hussain Mohammed , Spiegel Gary , Ollenschleger Martin , McCullough Louise
Published: July 2021

Introduction:
Recent clinical trials have established the efficacy of mechanical thrombectomy (MT) for the treatment of acute ischemic stroke (AIS) in patients with large vessel anterior circulation occlusion. There is limited data on outcomes and hemorrhagic transformation (HT) risk in patients that also underwent carotid stenting (approximately 10%) during MT which requires immediate antiplatelet use.

Methods:
We queried the Healthcare Cost and Utilization Project's (HCUP) Nationwide Inpatient Sample (NIS) (from 2006 to 2010) with ICD 9 diagnostic codes for AIS published by HCUP. ICD-9 99.1 was used for intravenous r-tPA and ICD-9 procedure code 39.71 (MT), 00.61 and 00.63 (for Carotid Stenting). This identified AIS patients who received MT w/wo carotid stenting. Primary outcomes were in-hospital mortality, HT (ICD9 430, 431, 432.0-432.9), and significant disability at discharge (to intermediate and long term skilled nursing facility). In addition to demographics, co-morbid vascular risk factors, use of anticoagulation/antiplatelet and in-hospital complications including DVT, PE, sepsis, and hospital acquired infections were controlled as confounders.

Results:
10,475 (weighted N) patients received MT out of which 1175 (11.22%) patients also underwent carotid stenting. After controlling for age, sex, race, Atrial fib, diseases of endocardium, alcohol, tobacco use, diabetes mellitus, hypertension, long-term (current) use of antiplatelet, long-term (current) use of anticoagulation, carotid artery stenosis, hospital acquired infection, sepsis, DVT, PE, year and hyperlipidemia we found that patients receiving carotid stenting had no significant differences in mortality OR 1.02 (95% CI 0.687-1.518; p=0.9178), HT OR 1.183 (95% CI 0.678-2.066; p=0.5535), disability at discharge OR 0.817 (95% CI 0.562-1.189; p=0.2915) compared to controls. Diabetes was an independent predictor of mortality OR 1.375 (95% CI 1.007-1.877) and disability OR 1.446 (95% CI 1.057-1.978).

Conclusion:
Prevention of stent thrombosis with early antiplatelet use does not appear to increase the risk of HT in endovascularly treated AIS patients receiving carotid stenting. There was no significant increased risk of HT, mortality and morbidity in this subgroup.
Abstract 204: Transcranial Doppler Versus Transthoracic Echocardiography for the Detection of Patent Foramen Ovale in Patients With Cryptogenic Cerebral Ischemia: A Systematic Review and Diagnostic Test Accuracy Meta-analysis
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H , Psaltopoulou Theodora , Sergentanis Theodoros , Frogoudaki Alexandra , Vrettou Agathi-Rosa , Ikonomidis Ignatios , Paraskevaidis Ioannis , Parissis John , Bogiatzi Chrysa , Chang Jason , Kyritsis Athanassios P , Alexandrov Anne W , Giannopoulos Sotirios , Alexandrov Andrei V
Published: July 2021

Background & Purpose:
Patent foramen ovale (PFO) can be detected in up to 43% of patients with cryptogenic cerebral ischemia undergoing investigation with transesophageal echocardiography (TEE). The diagnostic value of transthoracic echocardiography (TTE) in the detection of PFO in patients with cryptogenic cerebral ischemia has not been compared with that of transcranial Doppler (TCD) using a comprehensive meta-analytical approach.

Methods:
We performed a systematic literature review according to PRISMA guidelines to identify all prospective observational studies of patients with cryptogenic cerebral ischemia that provided both sensitivity and specificity measures of TTE, TCD or both compared to the gold standard of TEE.

Results:
Our literature search identified 35 eligible studies including 3067 patients. The summary sensitivity and specificity for TCD was 96.1% (95% confidence interval: 93.0%-97.8%) and 92.4% (95%CI: 85.5%-96.1%), whereas the respective measures for TTE were 45.1% (95%CI: 30.8-60.3%) and 99.6% (95%CI: 96.5-99.9%). The summary diagnostic odds ratio (DOR) for TCD (DOR=297.97, 95%CI: 131.18-676.83) and TTE (DOR=193.44, 95%CI: 30.38-1231.67) did not significantly differ (z-value=0.418, p=0.676). TTE was superior in terms of higher positive likelihood ratio values (LR+= 106.61, 95%CI: 15.09-753.30 for TTE vs. LR+=12.62, 95%CI: 6.52-24.43 for TCD; p=0.043), while TCD yielded lower negative positive likelihood values (LR- = 0.04, 95%CI: 0.02-0.08) compared to TTE (LR- =0.55, 95%CI: 0.42-0.72; p<0.001). Finally, the area under the summary receiver operating curve was significantly greater (p<0.001) in TCD (AUC=0.98, 95%CI: 0.97-0.99; Figure A) compared to TTE studies (AUC=0.86, 95%CI: 0.82-0.89; Figure B).

Conclusions:
TCD is more sensitive but less specific compared to TTE for the detection of PFO in patients with cryptogenic cerebral ischemia. The overall diagnostic yield of TCD appears to outweigh that of TTE.
Abstract 207: Signal Averaged Electrocardiogram can Indicate the Arrhythmogenic Potential of Right Insular Stroke
Authors: Park Hee-Kwon , Yoon Cindy W , Kwon Ji-Won , Kim Soo-Jeong , Lee Eung-Seok , Oh Dan-A , Rha Joung-Ho
Published: July 2021

Backgrounds:
The right insular cortical stroke is believed to have arrhythmogenic potential such as secondary atrial fibrillation (AF). The P wave-triggered signal-averaged electrocardiogram (SA-ECG) can reveal the P wave dispersion which is associated with the risk of AF in the future. However, there has been no relevant clinical study and we investigated the P wave dispersion after stroke involving right insula.

Methods:
We recruited acute stroke patients consecutively, who admitted from February 2012 to October 2013 and took routine work-up with SA-ECG. Patients who had AF on admission were excluded. SA-ECG was followed up two years after stroke onset. Significant P-wave dispersion was defined as ‘P-wave duration (PWD) >125ms for the predictor of future AF risk. We analyzed the difference of SA-ECG between the right insular cortex lesion and other stroke.

Results:
A total of 252 subjects were enrolled and 49 among them had right insular involvement. Follow up SA-ECG were available in 69 patients. In acute stroke period, the patients with right insular lesion had longer P wave duration than the other stroke patients (154.0+29.6 vs. 133.5+26.5 ms, p<0.001). In the patients with right insular involvement, prolonged P wave duration in acute period was shortened in follow up SA-ECG after two years (n=17, 164.5+35.2 vs. 131.7+22.3 ms, p=0.003). However, patients with other stroke lesion did not show such interval change. During observation period, AF occurred more frequently in the subjects with right insular lesion than other stroke patients (33% vs 17%, p=0.01).

Conclusion:
Our data suggest that the right insular lesion is associated with increased P wave dispersion transiently in acute stroke period and this might explain the development of secondary AF shortly after right insular cortex stroke.
Abstract 224: Cerebral Hemodynamic Changes in Patients With Long-term Effects of War-time TBI
Authors: Razumovsky Alexander , Kouperberg Ephim , DeGraba Thomas , Neuges Donna
Published: July 2021

Many patients with mild TBI (mTBI) will have post-concussive syndrome and the evaluation of post-concussive symptoms requires an understanding of the multiple factors relevant to the production and maintenance of symptoms following TBI. The purpose of this study was to evaluate the transcranial Doppler (TCD) determined incidence of abnormal cerebral hemodynamics in patients with long-term effects of wartime mTBI.

Material and Methods:
The National Intrepid Center of Excellence (NiCoE) at the Walter Reed National Military Medical Center has advanced a 4-week intensive outpatient program that leverages an interdisciplinary holistic patient and family based approach to evaluate and treat service members (SMs) with unremitting symptoms from combat related mTBI. A retrospective review of TCD studies was performed on 174 SMs (4 females) admitted to the NiCoE with post-concussive headaches (mean 38.5± 6.9 years, range 24 to 52). Demographic data was collected by patient self-reports at time of TCD examinations. The average time after last mTBI was 4.6 ± 3.7 years and there were 151 (87%) and 23 (13%) patients with multiple and single mTBI, respectively. All subjects were consented to Protocol #362504 prior to any data collection and analysis. TCD recordings of mean cerebral blood flow velocities (CBFV in cm/sec) and Pulsatility Indices (PI) were recorded. Comprehensive TCD protocol was applied in all cases.

Results:
In our cohort there were 46 (26%) with normal cerebral hemodynamics and 128 (74%) patients with abnormal cerebral hemodynamics. 31(18%) and 28 (16%) demonstrated abnormally high CBFV and PIs in one or more vessels, respectively. Abnormally low CBFV’s and PI’s were in one or more vessels observed in 20 (11.5%) and 75 (43%) of patients, respectively. Majority of studied patients had patchy pattern of abnormal data presented in one or few vessels. There were only 2 (1%) and one (0.5%) patients with abnormally high CBFV’s and PI’s present in all studied vessels.

Conclusion:
These findings demonstrate that cerebral hemodynamics disturbances are frequent findings in the majority of patients with long-term effects of combat mTBI, therefore utilization of TCD examination is recommended for their recognition and subsequent management.
Abstract 29: Common Thrombophilias are not Associated With Specific Perinatal Stroke Diseases
Authors: Curtis Colleen , Leaker Michael , Massicotte Patti , Floer Amalia , Mineyko Aleksandra , Kirton Adam
Published: July 2021

Background:
Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, including arterial and venous ischemic injuries, but pathophysiological mechanisms are poorly understood. Thrombophilia has long been considered a potential contributor but population-based, controlled, disease-specific studies are limited.

Hypothesis:
Thrombophilia is uncommon in children with perinatal stroke.

Methods:
Subjects were recruited from the Alberta Perinatal Stroke Project, a population-based cohort with MRI-classified perinatal strokes: neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), and fetal periventricular venous infarction (PVI). Standardized thrombophilia evaluations were performed prospectively (2008-2015) after 12 months of age on stroke cases and matched controls. Measures included protein C and S, antithrombin III, factors VIII/IX/XI, fibrinogen, lipoprotein a, lupus anticoagulant, and antiphospholipid antibodies. Groups were compared (ANOVA, chi-square), corrected for multiple comparisons.

Results:
A total of 252 children were studied (58 NAIS, 48 APPIS, 69 PVI, 77 controls). Of 14 parameters, no differences were observed in 12 including all common thrombophilias. Prothrombin times were shorter in arterial strokes compared to controls (p<0.001). Factor XI levels were higher in arterial and PVI strokes compared to controls (p=0.004). Rates of genetic thrombophilias including factor V Leiden, prothrombin gene, and MTHFR were low and comparable to population rates.

Conclusion:
Our prospective, population-based, controlled, disease-specific study suggests minimal association between perinatal stroke and thrombophilia. This does not exclude the possibility of disordered coagulation at the time of stroke but suggests testing in childhood is not indicated.
Abstract 36: Mapping and Multilevel Modeling of Climate Change and Air Pollution With Risk of Stroke in the United States and China: Findings From the Drexel-SARI Low Carbon and Healthy City Study
Authors: Liu Longjian , Liu Hui , Yang Xuan , Jia Feng , Wang Mingquan
Published: July 2021

Introduction and Hypothesis:
Stroke is a leading cause of death and the major cause of disability in the world. However, few studies applied multilevel regression techniques to explore the association of stroke risk with climate change and air pollution. In the study, we aimed to test the hypothesis that the disproportionately distributed stroke rates across the counties and cities within a country are significantly associated with air pollution and temperature.

Methods:
We used data from U.S. 1118 counties in 49 states, which had estimated measures of particulate matter (PM)2.5 for the years 2010-2013, and data from China 120 cities in 32 provinces (including 4 municipalities), which had measures of Air Pollution Index (API) for the years 2012-2013. We assessed the association between air quality and prevalence of stroke using spatial mapping, autocorrelation and multilevel regression models.

Results:
Findings from the U.S. show that the highest average PM2.5 level was in July (10.2 μg/m3) and the lowest in October (7.63 μg/m3) for the years 2010-2013. Annual average PM2.5 levels were significantly different across the 1118 counties, and were significantly associated with stroke rates. Multilevel regression analysis indicated that the prevalence of stroke significantly increased by 1.19% for every 10 μg/m3 increase of PM2.5 (p<0.001). Significant variability in PM2.5 by states was observed (p=0.019). More than 70% of the variation in stroke rates existed across the counties (p=0.017) and 18.7% existed across the states (p=0.047). In China, the highest API was observed in the month of December, with a result of 75.76 in 2012 and 97.51 in 2013. The lowest API was observed in July, with a result of 51.21 in 2012, and 54.23 in 2013. Prevalence of stroke was significantly higher in cities with higher API concentrations. The associations between air quality and risk of stroke were significantly mediated by temperatures.

Conclusions:
The study, using nationally representative data, is one of the first studies to address a positive and complex association between air quality and prevalence of stroke, and a potential interaction effect of temperatures on the air - stroke association.
Abstract 47: White Matter Atrophy in Cerebral Amyloid Angiopathy
Authors: Fotiadis Panagiotis , Schultz Aaron , Hedden Trey , Martinez-Ramirez Sergi , Reijmer Yael , Ayres Alison , Schwab Kristin , Viswanathan Anand , Sperling Reisa , Johnson Keith , Greenberg Steven M , Gurol M. Edip
Published: July 2021

Background/Purpose:
Cerebral Amyloid Angiopathy (CAA) leads to leukoaraiosis, lacunar infarcts and cortical tissue loss. We hypothesized that CAA is also associated with white matter atrophy (WMA).

Methods:
We have compared volumetric multimodal MRIs from 72 prospectively enrolled non-demented patients with probable CAA (per Boston criteria), to 3 other well-studied cohorts: 289 Healthy Controls (HC) from the Harvard Aging Brain (HAB) study, 231 HC and 198 patients with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Validated FreeSurfer algorithms were used to calculate White Matter Volume (WMV), white matter hyperintensity volume (WMHv), and cortical thickness. Microbleeds (MBs) were counted on SWI-MRI. Measures were obtained from the contralateral hemisphere if intracerebral hemorrhage present. All volumes were corrected for total intracranial volume (ICV), so reported as percent of ICV.

Results:
The CAA patients were significantly younger (mean age: 70.1) compared to both HC cohorts (ADNI-HC: 76.0, p<0.001, HAB-HC: 73.8, p < 0.001), and to patients with AD (75.5, p < 0.001). Despite being younger, patients with CAA presented significantly lower global WMV (28% ± 2.6) than both ADNI-HC (29.2% ± 2.2, p < 0.001), HAB-HC (29.0% ± 2.5, p = 0.001), and patients with AD (28.7% ± 2.2, p = 0.02) [Figure]. The association persisted after correcting for age, gender and WMHv. Within the CAA cohort, there was a negative correlation between WMV and lobar MB counts (rho = -0.26, p = 0.03), it remained significant after correcting for age, gender, WMHv (p=0.016). There were no significant associations however between WMV and neither WMHv, nor cortical thickness (both p>0.2).

Conclusions:
Patients with CAA show WMA when compared to older HC and AD. WMA independently correlates with MBs, a marker of CAA severity. Consistent spatial patterns of atrophy especially in posterior regions when compared to both HC and AD [Figure] might represent the “WMA signature of CAA”.
Abstract 5: Analysis of Workflow Aad Determinants of Delays in the Escape Randomized Controlled Trial
Authors: Menon Bijoy K , Sajobi Tolulope T , Zhang Yukun , Rempel Jeremy L , Shuaib Ashfaq , Thornton John , Williams David , Roy Daniel , Poppe Alexandre Y , Jovin Tudor G , Sapkota Biggua , Baxter Blaise , Krings Timo , Silver Frank L , Frei Donald F , Fanale Christopher , Tampieri Donatella I , Teitelbaum Jeanne , Lum Cheemun , Dowlatshahi Dar D , Eesa Muneer , Lowerison Mark W , Kamal Noreen , Demchuk Andrew M , Hill Michael D , Goyal Mayank ,   ESCAPE Investigators
Published: July 2021

Introduction:
The ESCAPE trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of additional endovascular treatment over standard care in patients with disabling acute ischemic stroke. We performed a detailed analysis of workflow and determine modifiable factors resulting in delays.

Methods:
The trial enrolled 316 patients fulfilling eligibility criteria and presenting within 12 hours of stroke symptom onset from 22 sites across 3 continents between February 2013 and October 2014. We considered four specific interval times: onset-to-ED arrival, ED-arrival-to-qualifying CT scan, qualifying CT scan-to-groin puncture, groin puncture-to-reperfusion. Missing times were not imputed. When reperfusion was not achieved, the reperfusion time was considered missing and was not imputed. Interval times from stroke symptom onset to first reperfusion are reported using medians and inter-quartile range. To assess the relationship between patient, hospital and health system characteristics as predictors of longer interval times, a negative binomial regression provided the best fit to the data.

Results:
Stroke symptom onset to arrival in emergency room of endovascular capable hospital time was 42% (34 mins) longer among patients who received intravenous alteplase at the referring hospital (drip and ship) vs. patients directly transferred to the endovascular capable hospital (direct to mother ship) (Figure). Qualifying CT to groin puncture time was 15% (8 mins) shorter among patients presenting during work hours vs. off hours. Time from qualifying CT to groin puncture was 41% (24 min) shorter in drip and ship patients than vs. when intravenous alteplase was administered after qualifying CT (mothership). General anesthesia prolonged this time by 43% (22 min). Balloon guide catheter during endovascular procedure shortened time from groin puncture to reperfusion by 21% (8 mins).

Conclusions:
Inefficiencies in triaging systems, presentation during off hours, intravenous alteplase administration, GA utilization and endovascular techniques offer major opportunities for improvement.
Abstract 60: Multiphase versus Single Phase CT Angiography for Detection of Distal Intracranial Occlusion
Authors: Diederichs Brendan , Menon Bijoy , Jo Patricia , Wallace Carla , Willson Morgan , Joshi Manish , Eesa Muneer , Goyal Mayank
Published: July 2021

Introduction:
Detecting distal intracranial arterial occlusion is of increasing importance as current studies begin to evaluate the potential benefit of tPA in minor acute stroke. Multiphase CTA (mCTA) is a technique used routinely at our centre in the setting of suspected acute ischemic stroke (AIS).

Hypothesis:
We hypothesized that mCTA is diagnostically superior to CTA for detection of distal intracranial arterial occlusion in suspected AIS.

Methods:
Population comprised of patients with suspected AIS who had mCTA, followed by MR brain with DWI within 24 hours. mCTA involves 3 phases of enhanced CT from skull base to vertex following administration of a single iodinated contrast bolus. Prospective interpretation of unenhanced CT followed by single phase CTA was performed by a radiology resident, a stroke fellow, or a neuroradiologist. Unenhanced CT followed by mCTA was interpreted > 1 week after single phase CTA interpretation using the same dataset. MR exams were separately adjudicated to establish each case as positive or negative according to pre-specified criteria that suggests a high likelihood for the presence of an arterial occlusion on CTA (DWI lesion > 2mm diameter, not multiple small infarcts consistent with microembolic shower, not exclusively white matter lesion, not small deep gray matter lesion consistent with lacunar type infarct.

Results and Conclusion:
Of 322 patients, single phase CTA detected 69 occlusions (sensitivity 52.5%, specificity 98.1%) and mCTA detected 113 (sens = 81.8%, spec = 99.5%). mCTA detected a greater number of proximal occlusions (76 vs. 66), and a greater number of distal occlusions (37 vs. 3) than CTA. mCTA demonstrated a greater rate of detection for distal occlusions (relative rate = 9.67, 95% CI 3.76 - 24.84). CTA/MR agreement was moderate (kappa = 0.59) while mCTA/MR agreement was substantial (kappa = 0.81). Mean interpretation time for CTA was 239.8 seconds (95% CI 221.3 - 258.4) and 195.0 seconds (95% CI 176.9 - 213.1) for mCTA.

In conclusion, our data suggest mCTA is superior to single phase for detection of distal intracranial occlusion.
Abstract 66: Endothelial α5β1 Integrin is Acutely Upregulated and Destabilizes the Blood-brain Barrier After Stroke
Authors: Edwards Danielle , Roberts Jill , de Hoog Leon , Bix Greg J
Published: July 2021

Repeated opening of the blood-brain barrier (BBB) after ischemic stroke significantly contributes to brain injury. As the β1 integrin receptor family has been linked to changes in BBB permeability via changes to tight junction (TJ) protein expression and function, we hypothesized that the pro-angiogenic fibronectin receptor α5β1 integrin is acutely upregulated in cerebrovasculature after ischemic stroke and contributes to BBB breakdown via affects on the TJ protein claudin-5. First, α5β1 brain immunohistochemistry after transient middle cerebral artery occlusion (MCAo) in mice demonstrated an increase in core infarct and peri-infarct vascular expression of α5β1 as early as 24 hours after stroke that became even more prominent by post stroke day 2. Next, in vitro studies demonstrated an increase in barrier permeability where stroke was simulated using oxygen-glucose deprivation or TNF-α treatment, as measured by trans-endothelial cell electrical resistance and FITC-dextran permeability, that correlated with an increase in α5β1 expression and changes in claudin-5 expression and localization away from the cell-surface (i.e. away from TJ complexes). Importantly, this increased permeability could be completely prevented by addition of the α5β1 inhibitor ATN-161. Finally, MCAo performed in endothelial cell selective α5β1 knockout mice demonstrated significantly increased post-stroke BBB stability, stable claudin-5 expression, and little to no ischemic injury. Collectively, our results demonstrate that endothelial cell α5β1 integrin expression is increased acutely after stroke, may contribute to BBB breakdown and subsequent expansion of brain injury, and therefore could represent a novel stroke therapeutic target worthy of further investigation.
Abstract 73: Improvement of Arm Function Following Intensive Rehabilitation in Chronic Stroke Correlates With Increase in Fractional Anisotropy in Major White Matter Tracts
Authors: Pundik Svetlana , Skelly Peggy , McCabe Jessica P , Tatsuoka Curtis , Daly Janis J
Published: July 2021

Introduction:
White matter changes in response to rehabilitation of chronic motor deficits after stroke has not been well understood. Our hypothesis is that there is a relationship between gains in motor function and changes in structure of white matter tracts.

Methods:
Fugl-Meyer upper limb (FM) score and Diffusion Tensor Imaging (DTI) were collected before and after a 12-week upper limb motor learning therapy. DTI data was processed using the longitudinal Freesurfer Tracula stream where white matter tracts are reconstructed using global probabilistic tractography. The average fractional anisotropy (FA), as well as axial diffusivity (Da) and radial diffusivity (Dr) were computed for 14 major white matter tracts. General linear models were fit where pre-to-post change in FA for a given tract were dependent variables and pre-to-post change in FM was a predictor. The relationship was adjusted for baseline FM score. Spearman correlations were determined between FA, Da and Dr. Wilcoxon test was used for pre-to-post comparisons.

Results:
We evaluated and treated 21 stroke survivors; they were 1.9±1.2 (mean±std.dev) years post stroke, 55.1±12.9 yrs old and 42% female. FM improved from 23±8.75 to 34.1±10.5 (p<0.001). There was a significant association between gain in motor function and the decrease in FA for the following tracts: ipsilesional inferior longitudinal fasciculus (iplsi-ILF), contralesional ILF (contra-ILF) and transcallosal forceps major tract, controlling for baseline FM scores, (for ipsi-ILF: R2=0.4, p=0.006; for contra-ILF: R2=0.38, p=0.004; for forceps major: R2=0.31,p=0.02). According to the correlation analysis, decrease in FA could be explained by increase in Dr, but not by change in Da. Correlation between FA and Dr for ipsi-ILF was r=.75,p<0.001, for contra-ILF - r=.72,p<0.001 and for forceps major - r=.88, p<0.001.

Conclusion:
Improvement in function of chronic motor deficits in the upper extremity is related to structural changes in temporal-occipital and transcallosal occipital tracts that connect visual-spatial processing regions. Furthermore, our results suggest that changes in neuronal activity of the identified tracts may be associated with microstructural changes that increase radial diffusivity.
Abstract 74: An Update on Meta-analysis of Transcranial Direct Current Stimulation in Post-stroke Motor Recovery
Authors: Chhatbar Pratik Y , Kautz Steven A , Feng Wuwei
Published: July 2021

Introduction:
Prior meta-analyses have demonstrated positive summary effect of tDCS on Fugl-Meyer upper extremity scores (FM-UE) improvement as well as dose-response relationship. With new published manuscripts, we are not sure whether this positive effect still holds.

Hypothesis:
tDCS leads to better improvements in post-stroke motor recovery when compared to sham, and in a dose-dependent manner.

Methods:
We identified sham-controlled, randomized studies with ≥5 tDCS sessions from PubMed until July 2015. We derived effect size as standardized mean differences (Hedge’s g) of change scores, defined as FM-UE improvements. We calculated summary effect size by using random effect model, taking any data heterogeneity into account. We plotted current, charge (current х duration), total charge (charge х sessions) and their density counterparts (by dividing each with pad size). To assess the dose-response relationship, inverse-variance-based meta-regression was performed.

Results:
We identified 9 studies with 234 subjects comparing active stimulation (anodal, cathodal or bihemispheric) with sham stimulation against FM-UE change scores. Stroke patients receiving tDCS improved significantly better than sham (summary Hedge’s g = 0.65, 95% CI = [0.18, 1.13], p = 0.03), with superior results in patients with chronic stroke (average time since stroke >2 years, summary Hedge’s g = 1.11, 95% CI = [0.43, 1.83], p = 0.001) than those with acute stroke (average time since stroke <2 months, summary Hedge’s g = 0.18, 95% CI = [-0.30, 0.66], p = 0.47). Dose-response relationship showed that FM-UE change scores correlated positively with charge density (R2 = 0.20, p = 0.036) and negatively with pad size (smaller the pad, better the effect; R2 = 0.58, p = 0.002).

Conclusion:
This updated meta-analysis supports that tDCS leads to better improvement in UE motor outcome than with sham, especially in patients with chronic stroke.
Abstract NS6: To Rest or Mobilize... When to Start Early Mobilization in Acute Stroke: a Systematic Review
Authors: Whaley Michelle , Dusenbury Wendy , Alexandrov Andrei V , Tsivgoulis Georgios , Alexandrov Anne W
Published: July 2021

Background:
Recent nursing initiatives encourage early mobilization of neurocritical care patients, but whether this intervention can be safely generalized to acute stroke is debatable. We performed a systematic review of findings from recent studies to provide direction for patient management and future research.

Methods:
An exhaustive literature search was performed in Medline, SCOPUS and the Cochrane Central Register of Controlled Trials to identify published clinical trial research using a very early mobility intervention (within 24 hours) in acute ischemic stroke patients. The primary efficacy outcome supporting the search was neurologic disability reduction or improved functional outcomes, and the primary safety outcome was neurologic deterioration. Studies were critically reviewed for inclusion by 3 separate investigators, findings were synthesized, and an overall recommendation for very early mobilization use in acute stroke was assigned according to GRADE criteria.

Results:
We initially identified 12 papers focused on early mobilization in acute stroke; of these, 6 observational studies were excluded, 1 study was excluded due to an ambiguous population, and 3 studies were excluded due to first initial mobilization out of bed occurring greater than 24 hours after admission. Two prospective randomized outcome blinded evaluation (PROBE) studies were retained, consisting of a total 2160 patients; ischemic stroke subtype was not disclosed in either study, limiting an understanding of the impact of very early mobilization on small versus large artery occlusion. Slower mobilization occurring beyond the first 24 hours was associated with higher rates of favorable outcome (mRS 0-2) at 90 days, whereas very early mobilization within the first 24 hours was associated with a number needed to harm of 25.

Conclusions:
In acute stroke, evidence supports a rested approach to care within the first 24 hours of hospitalization (GRADE: Strong recommendation, high quality of evidence). Similar to acute myocardial infarction, vascular insufficiency experienced in stroke likely warrants a more guarded approach to mobility. Additional studies exploring timing beyond 24 hours and dose of mobility interventions are warranted in discreet populations.
Abstract TMP103: New Blood Velocity Indices Can Improve the Accuracy of Transcranial Doppler to Detect Vasospasm After Subarachnoid Hemorrhage
Authors: Ryu Jaiyoung , Hu Xiao , Shadden Shawn C
Published: July 2021

Background and Objectives:
Early diagnosis of vasospasm after subarachnoid hemorrhage (SAH) can prompt aggressive treatment and improve neurological outcomes. Transcranial Doppler (TCD) is the only diagnosis modality that is noninvasive and available bedside. The purpose of this study was to numerically evaluate the relevance of various blood velocity indices in detection of unbalanced cerebral blood flow due to vasospasm, and to improve the accuracy of diagnosis using TCD.

Methods:
We employed a well-validated numerical model of arterial blood flow coupled with a sophisticated intracranial model to generate a cerebral blood flow database. Anterior (MCA and/or ACA) and posterior (PCA and/or basilar arteries) vasospasms were considered under normal and impaired cerebral autoregulation conditions. For each case, mean blood velocities and their ratios between ipsilateral and contralateral, downstream and upstream, and anterior and posterior arteries were monitored during the progress of vasospasm.

Results:
Blood velocities at vasospastic arterial segments demonstrated non-monotonic behavior, i.e. the velocities increased initially with mild and moderate vasospasm, however further vasospasm leads to decreasing values. This may lead to false-negative decisions clinically. Blood flow rates, however, decreased monotonically at the affected arteries. Blood velocities upstream of the vasospastic artery decreased in proportion to the blood flow rates (e.g. for MCA vasospasm, 30% and 20% reduction at ICA and CCA). For all vasospasm locations considered, normalization of velocities by upstream and contralateral velocities provided more robust detection. Moreover, the improvements were most compelling in cases with impaired cerebral autoregulation.

Conclusions:
The velocity indices and diagnosis strategy proposed in this study can improve the accuracy of TCD diagnosis for cerebral vasospasm. These indices are particularly effective in cases of severe vasospasm where traditional indices (e.g. absolute velocities, Lindegaard index) become problematic.
Abstract TMP119: High Homocysteine Level is not Associated With White Matter Changes, Dementia nor Mortality After Ischemic Stroke
Authors: Melkas Susanna , Curtze Sami , Sibolt Gerli , Oksala Niku K , Putaala Jukka , Soinne Lauri , Pohjasvaara Tarja , Kaste Markku , Karhunen Pekka , Erkinjuntti Timo
Published: July 2021

Background:
Association between high homocysteine level and cerebral small-vessel disease has been implicated in cross-sectional studies, but results from longitudinal studies have been less clear. The aim of this study was to investigate whether homocysteine level at 3-months poststroke relates to the occurrence of white matter changes (WMC), the surrogate of cerebral small-vessel disease. We also investigated whether it relates to the prognosis after ischemic stroke regarding the risk of dementia at 3-months and mortality in long-term follow-up.

Methods:
A total of 321 consecutive acute ischemic stroke patients aged 55 to 85 were included in the study and followed up to 12 years. Plasma homocysteine level and occurrence of WMC in MRI were measured 3 months poststroke and dementia according to DSM-III was evaluated at the same time.

Findings:
The median homocysteine level was 13.50 μmol/l (interquartile range [IQR] 10.60-18.50 μmol/l). Total of 81 patients (25.2%) had homocysteine level above 18.50 μmol/l. In logistic regression analysis, homocysteine level above 18.50 μmol/l was not associated with severe WMC nor with dementia at 3 months poststroke. In Kaplan-Meier analysis, homocysteine level above 18.50 μmol/l was not associated with survival in 12-year follow-up. For further analysis, the group was divided in quartiles according to homocysteine level. The quartiles did not differ in occurrence of severe WMC at baseline, in the risk of dementia at 3 months, nor in the risk of mortality in 12-year follow-up.

Interpretation:
In our poststroke cohort homocysteine level is not associated with WMC. Further, it does not relate to impaired prognosis manifested as dementia at 3 months or mortality in 12-year follow-up.
Abstract TMP12: Does Prehospital Magnesium Sulfate Differentially Improve Outcome in Hyperacute Stroke Patients With Higher Pretreatment Blood Pressure?
Authors: Johnson-Black Phoebe H , Starkman Sidney , Sanossian Nerses , Liebeskind David , Stratton Samuel , Eckstein Marc , Pratt Frank , Conwit Robin , Hamilton Scott , Hemphill Claude , Saver Jeffrey
Published: July 2021

Introduction:
Magnesium sulfate (Mg) has blood pressure (BP) lowering, cerebral blood flow enhancing, and neuroprotective effects in preclinical and clinical studies. In the IMAGES phase 3 trial, Mg up to 12h after onset showed no benefit in acute stroke, but was associated with improved outcome in patients with higher blood pressure at entry.

Hypothesis:
We tested the hypothesis that ultra-early Mg improves functional outcome in acute stroke patients with higher baseline BP.

Methods:
FAST-MAG is a multicenter, double-blind, randomized, placebo-controlled trial of paramedic-initiated Mg, administered to patients with suspected stroke within 2h of symptom onset. The primary analysis showed neutral effect of Mg. This secondary analysis examines rates of functional independence (mRS 0-2) at 3m for Mg and placebo for different field BP groups.

Results:
Among 1622 patients with acute cerebrovascular disease, age was 69.6 (±13.4), 42% female, entry deficit severity in the field was LAMS 3.8 (±1.2), and first post-enrollment NIHSS in the ED was 11.5 (±9.9). Systolic blood pressure prior to enrollment was higher among patients with intracerebral hemorrhage (ICH) than acute cerebral ischemia (ACI), 175 (±25) vs 155 (±27), p < .001. The Figure shows the Forest plot for Mg vs placebo and functional independence among blood pressure groups. Heterogeneity of treatment effect was noted in the all-cerebrovascular patients population (p < .01), with fewer independent outcomes with Mg than placebo among patients with higher entry BPs.

Analysis of Functional Independence (mRS 0-2) at 90 Days in Prespecified Subgroups

Conclusion:
This analysis did not confirm the prior finding of magnesium sulfate benefit among acute stroke patients with elevated blood pressure (and actually provided a signal in the opposing direction). Mg was not demonstrated to improve outcome when started in the first 2h of onset among patients with acute cerebrovascular disease and higher blood pressures.
Abstract TMP13: The Prevalence of Microbleeds in Moyamoya Disease and Moyamoya Syndrome in the United States
Authors: Chen Mo , Salehian Sepand , Mukawa-Sawada Maki , Pinho Marco , Welch Babu , Shang Ty
Published: July 2021

Introduction:
Silent cerebral microbleeds (CMB) are common in Moyamoya Disease (MMD) and Moyamoya syndrome (MMS) in Asia. The incidence was reported to be 30-40%. The presence of CMB was found to be a predictor for subsequent cerebral hemorrhage in MMD. The significance of CMB in MMD/MMS in non-Asian population has not been reported. We try to investigate the prevalence of CMB in MMD/MMS in United States and its predictive value for subsequent cerebral hemorrhage.

Methods:
Moyamoya Database was established in our institution after reviewing patients with ICD9 code of Moyamoya Disease or Moyamoya Syndrome or cerebrovascular occlusive disease from 2007 to 2015. Patients in the database were reviewed retrospectively and included in the study if there were MR images (including GRE, SWI or T2* sequences) at diagnosis or during follow up and available for review. Patients with poor image quality were excluded. Patients were noted to have microbleeds if it was found on initial or follow up MRI. Multivariate logistic regression analysis was used to identify clinical and imaging predictors of CMB.

Results:
Sixty-three females and fourteen males were included with average age of 39 ± 13 at the time of diagnosis. The majorities were MMD (79.2%) and presented with ischemic events (79.2%). Hemorrhagic stroke was found in 9 (11.7%) patients before diagnosis. Ethnicity included Caucasian (61%), Asian (10.4%), Black (11.7%), and Hispanic (16.9%). Of total 77 patients, 7 (9.1%) had CMB but none of them presented with hemorrhagic stroke. During follow up of average 36 ± 29 months in these 7 patients, no cerebral hemorrhage was reported while ischemic events occurred in 2 (28.6%) patients. Of 70 patients without CMB, 51 had follow up of average 47 ± 46 months. One (2%) had cerebral hemorrhage while 12 (23.5%) had ischemic events. No independent predictors for CMB were identified among age, gender, ethnicity, etiology, presenting stroke, and comorbidities.

Conclusions:
Silent CMB was less prevalent in MMD/MMS in United States than in Asia. No specific risk factors were identified to be associated with the presence of silent CMB. It was not associated with increased risk of subsequent cerebral hemorrhage in non-Asian population. Further studies are needed to confirm these findings.