bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 129: PAK01: A Synthesized Small Molecule That Enhances Reperfusion, Neuroprotection and Avoids Hemorrhagic Transformation in Rodent Models of Thromboembolic Stroke
Authors: Lin Shinn-Zong , Jiang Xueyun , Zhang Xiaoyi , Wang Yuji , Wang Yaonan , Zhang Yingjie , Gui Lin , Li Shan , Wang Yanming , Yao Kun , Wu Jianhui , Zhao Ming , Peng Shiqi
Published: March 2022

Tissue-type plasminogen activator (t-PA) is currently the only approved drug by the US FDA for treating the acute ischemic stroke within 3 hours of symptom onset, despite the fact that the therapy may cause serious hemorrhagic transformations and neurotoxicity that leads to enhanced brain injury. Here we developed a synthesized small pseudopeptide, PAK01, to address efficacy and safety issues observed in t-PA treatment in acute ischemic stroke by covalently combining a free radical scavenger, a thrombus-targeted platelet aggregation inhibitor and a non-t-PA thrombolytic peptide into a single structure. The thrombolytic activity induced by PAK01 was confirmed in murine
in situ
thromboembolic stroke model where mice were anesthetized before thrombin is injected into middle cerebral artery to produce the clot formation (as described by Orset
et al
.). To induce reperfusion, PAK01 (7.5 mg/kg) or t-PA (10 mg/kg) was administered intravenously 20 minutes after thrombin injection. The results showed that both PAK01 and t-PA promote reperfusion in mice with middle cerebral artery
in situ
thromboembolic occlusion. Furthermore, PAK01 yields better treatment results in reducing infarct volume and neurological deficit with lower risk of hemorrhagic transformation when compared to that of t-PA. In addition, rattus carotid artery thrombosis model where 1.4 mg/kg of PAK01 was intravenously administered 4, 6, and 24 hours after stroke onset showed improvements in neuronal behavior outcome and reductions of brain infarct size. In contrast to 3 mg/kg of t-PA, no bleeding was observed even in 7 mg/kg of PAK01-treated animals. HPLC-FT/MS monitoring indicated that PAK01 can cross blood cerebral barrier. A distinct action mechanism out of plasminogen pathway was also explored. In conclusion, based on a new action mechanism the treatment potential of PAK01, a small molecule, in acute ischemic stroke through enhancing reperfusion and neuroprotection, as well as avoiding hemorrhagic transformation was demonstrated in
in vivo
studies.
Abstract 146: Optimal Workflow and Process Based Performance Measures for Endovascular Therapy in Acute Ischemic Strokes From the Star Registry
Authors: Menon Bijoy K , Goyal Mayank ,   STAR Investigators
Published: March 2022

Introduction:
We report on workflow and process based performance measures and its impact on clinical outcome in STAR, a recent international, multi-center, prospective, single-arm study of Solitaire FR thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hrs of symptom onset.

Methods:
A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada and Australia. The following time intervals were measured: stroke onset to ED arrival; ED to baseline CT; CT to groin puncture; groin puncture to thrombus identification; thrombus identification to start of IA therapy and start of IA therapy to reperfusion. Effects of time of day, general anesthesia (GA) utilization and multi-modal imaging on workflow were evaluated. Patient characteristics and workflow processes associated with prolonged interval times and good clinical outcome (90-day mRS 0-2) were analyzed.

Results:
Distribution of all interval times are illustrated in Figure 1a. Median hospital arrival to final DSA run time was 150 mins (IQR=97 mins). Hospital arrival to final DSA run time was faster in women than men (158 vs. 139 mins). General anesthesia increased CT to groin puncture time by 22 mins and groin puncture to final DSA run by 13 minutes. Time of day or week did not effect interval times. CT based multi-modal imaging reduced time from CT to groin puncture by 24 mins. For each 60-minute increase in time from symptom onset to TICI 2b/3 (or final DSA run), a 33% decrease in odds of good clinical outcome (p<0.01) was noted independent of the effect of increased age (p<0.01), higher baseline NIHSS (p=0.02), and lower ASPECTS score (p=0.02). (Figure 1b)

Conclusion:
Interval times in the STAR study is a reflection of current IA therapy for patients with acute ischemic stroke. Improving workflow processes and reducing time to reperfusion could improve clinical outcomes further.
Abstract 154: Changes in Task fMRI After Stroke Rehabilitation Using Closed-Loop Neurofeedback
Authors: Young Brittany M , Nigogosyan Zack , Nair Veena A , Song Jie , Walton Leo M , Vergun Svyat , Farrar-Edwards Dorothy , Sattin Justin , Chacon Marcus , Jensen Matthew B , Williams Justin C , Prabhakaran Vivek
Published: March 2022

Introduction:
Brain-computer interface (BCI) is an emerging technology for stroke rehabilitation, but little is known about brain changes associated with its use. We examine changes in laterality index (LI) and functional connectivity (FC) during hand movements associated with BCI interventional therapy.

Methods:
We collected anatomical and functional MRI of 8 stroke patients with upper extremity motor impairment before, during, and after up to 6 weeks of therapy using a BCI system with tongue and functional electrical stimulations. We acquired functional images during imagined (MI) and executed (ME) tapping and squeezing of each hand; not all subjects performed all tasks. Two subjects’ scans were flipped so that as a group the lesion was left (L) and the impaired limb right (R). We computed LI using 3 mask sets: whole brain, motor network, and motor cortex. Group-level analyses examined FC changes to motor network seeds using AFNI and Matlab NBS toolbox.

Results:
BCI intervention led to decreased average LI during tapping. Overall, R taps shifted L to bilateral; all L taps shifted bilateral to R. Trends were consistent across all masks at thresholds p<.05 & p<.001 and were linearly modeled (r2 0.614 to 0.999). During R-ME, FC increased between each thalamus with L M1 and the cingulum. During L-ME, most FC increases were intrahemispheric (R M1 to R thalamus; within L M1). L-ME FC also decreased between each thalamus and contralateral frontal regions and between the cerebellum and frontal lobes. This pattern of inter- and intrahemispheric FC increases during respective R and L movement was also observed with MI, and many FC findings persisted in a subanalysis excluding flipped scans. A network of 6 seeds and 9 edges within the motor network had increased FC during R-ME. All FC changes p<.05.

Conclusions:
BCI interventional therapy of the impaired hand leads to more bilateral brain activity, while more lateralized activation was seen of the unimpaired hand to its corresponding contralateral motor regions. With different patterns of change observed during tasks using the impaired or unimpaired hand, lesioned brain areas may respond differently to BCI than unlesioned counterparts.
Abstract 155: Health-Related Quality of Life in Patients With Unruptured Brain Avm Managed With or Without Interventional Therapy - The Aruba Trial
Authors: Stapf Christian , Moy C. S , Overbey J. , Moquete E. , Parides M. , Vicaut E. , Moskowitz A. J , Mohr J. P ,   for the international ARUBA investigators
Published: March 2022

Background:
Only limited data are available on self-reported Health-related Quality of Life (HRQoL) in patients harboring an unruptured brain arteriovenous malformation (bAVM). Also, the effect of interventional therapy on HRQoL has not been systematically studied.

Methods:
Of the 223 prospective patients enrolled in ARUBA (A Randomized trial of bAVMs), 114 were allocated to medical management plus interventional therapy (IT), while 109 allocated to medical management alone (MM). During prospective follow-up, HRQoL parameters were systematically measured using the EuroQoL EQ-5D health questionnaire.

Results:
After 24 months of follow-up, EQ-5D data were available on 112 patients (53 IT, 59 MM). Compared to IT, those allocated to MM reported on significantly fewer problems with mobility (18.6% vs. 37.7; RR 0.49, 95CI 0.26-0.93), self-care (1.7 vs. 17.0%; RR 0.10, 95%CI 0.01-0.76), and usual activities (27.1% vs. 43.4%; RR 0.62 95%CI 0.37-1.05), but suffered more frequently from anxiety and/or depression (47.5 vs. 24.5; RR 1.93, 95%CI 1.12-3.33). No difference was found for pain or discomfort, nor for overall health state on the EuroQoL visual analog scale.

Conclusion:
For patients with unruptured bAVM who are followed medically over 24 months, clinical self-assessments using the EuroQoL EQ-5D health questionnaire confirms a lower risk of clinical impairment as compared to those undergoing therapeutic interventions. The risk of self-reported anxiety and/or depression, however, seems to be higher in patients living with an untreated bAVM.
Abstract 162: Ipsilateral Ischemic Stroke in Japanese Patients With Asymptomatic Carotid Stenosis on Recent Medical Treatment
Authors: Furui Eisuke , Itabashi Ryo , Yazawa Yukako , Kawata Kenta , Yang Sunghoon , Shigehatake Yuya , Fujiwara Satoru
Published: March 2022

Purpose:
Owing to improvements of recent medical treatment, whether carotid endarterectomy (CEA) is beneficial for patients with asymptomatic carotid stenosis still remains controversial. This study was designed to clarify the risk of ipsilateral ischemic stroke in Japanese patients with asymptomatic carotid stenosis.

Method:
We studied the risk of TIA, ischemic stroke, coronary artery disease and death in 105 patients (mean age 76.2 years; woman 16) with asymptomatic carotid stenosis of 50% or more recruited consecutively from Jan 2009 and given recent medical treatment. Patients with any previous symptoms of ipsilatral TIA or stroke were excluded.

Results:
During a mean follow up of 2.74 years, there were 7 TIAs (one ipsilateral, 6 other territory) and 9 ischemic strokes (3 ipsilateral, 6 other territory). Two patients underwent subsequent CEA or carotid artery stenting, 7 had coronary artery disease, and 4 died during the follow-up period. The average annual event rate of ipsilateral ischemic stroke was 0.64% (95% CI, 0.08 to 4.72).

Conclusion:
The risk of ipsilateral ischemic stroke on recent medial treatment was very low. Benefit from CEA might be small, and selection of patients for CEA should include an assessment of coronary artery disease and life expectancy.
Abstract 204: Xe-Loaded Liposome Reduces Bleeding With Neuroprotection From Early Injury in Subarachnoid Hemorrhagic Stroke
Authors: Peng Tao , Zeng Ning , Miao Yifeng , Moody Melanie , McPherson David , Huang Shao-Ling
Published: March 2022

Background:
Cell death, especially apoptosis occurs in subarachnoid hemorrhage (SAH) due to rapid and massive brain injury from the initial bleeding. Xe-loaded echogenic liposomes (Xe-ELIP) have been reported to have hemostatic effects in SAH. The goals of this study were to quantity the effect of Xe-ELIP on hemorrhage volume and also to evaluate its neuroprotective effects using a SAH brain injury model.

Methods:
Xe-ELIP were prepared by a pressurization-freeze method. SAH was induced in Sprague-Dawley rats by endovascular perforation. Rats (n=18) were randomly divided into SAH, SAH with ELIP treatment and SAH with Xe-ELIP treatment groups. Treatments were administrated intravenously at 30 minutes after SAH. Ultrasound was applied over the common carotid artery to trigger Xe release from circulating Xe-ELIP. Hemorrhage volume was quantified by spectrophotometric hemoglobin assay at two hours after SAH. Expression of caspase-3 and positive TUNEL was examined as markers for apoptosis.

Results:
SAH without treatment had the greatest hemorrhage volume (327 ± 25μl); the hemorrhage volume in SAH with ELIP treatment group was 274 ± 37μl (p=0.27
vs.
no treatment); Xe-ELIP treatment decreased hemorrhage volume to 165 ± 9μl (p<0.001
vs.
no treatment; p=0.026
vs.
ELIP treatment). Xe-Elip treatment was also associated with reduced inflammation, suppressed TUNEL positive and caspase-3 staining in the cerebral cortex, and improved neurological testing.

Conclusions:
Early hematoma growth in subarachnoid hemorrhagic stroke correlates with early brain injury. Xe-loaded liposomes minimizes hemorrhage volume and improves neurological outcomes in SAH. The underline mechanism of Xe hemostasis may relate to its cytoprotectant and anti-inflammatory effects.
Abstract 207: Hospital Case Volume is Associated With Mortality in Patients Hospitalized With Subarachnoid Hemorrhage
Authors: Prabhakaran Shyam , Fonarow Gregg C , Smith Eric E , Liang Li , Xian Ying , Peterson Eric D , Schwamm Lee H
Published: March 2022

Background and Purpose:
Prior studies have suggested hospital case volume may be associated with improved outcomes after SAH, but contemporary national data are limited. We hypothesized that high volume compared to low volume centers are associated with lower in-hospital mortality.

Methods:
Using the Get With The Guidelines-Stroke (GWTG-Stroke) registry, we analyzed patients with discharge diagnosis of SAH between April 2003 and March 2012. We assessed the association of annual SAH case volume with in-hospital mortality using multivariable logistic regression adjusting for relevant patient, hospital, and geographic characteristics.

Results:
Among 29,484 patients with SAH from 644 hospitals, the median annual case volume per hospital was 8.4 (25
th
-75
th
percentile 6.5-12.6) patients. Mean in-hospital mortality was 25.7% but was lower with increasing annual SAH volume (figure): 29.7% in quartile 1 (4-6.5 per year), 26.8% in quartile 2 (6.5-8.4 per year), 24.0% in quartile 3 (8.4-12.5 per year), and 22.2% om quartile 4 (>12.6 per year). Adjusting for patient (age, sex, race, medical history, stroke unit care, arriving time on or off hours) and hospital characteristics (bed size, location, teaching status, annual stroke volume, annual thrombolytic volume, and primary stroke center status), higher hospital SAH volume was independently associated with lower in-hospital mortality (adjusted odds ratio 0.80, 95% confidence intervals 0.68-0.95, highest quartile SAH volume hospitals compared with lowest quartile volume hospitals).

Conclusions:
In a large nationwide registry, we observed that patients treated at hospitals with higher volumes of SAH patients have lower in-hospital mortality, independent of patient and other hospital characteristics. Our data suggest that experienced centers may provide more optimized care for these patients.
Abstract 210: A Phase I Clinical Trial of Sildenafil for the Treatment of Cerebral Vasospasm Following Subarachnoid Hemorrhage
Authors: Washington Chad W , Dhar Rjat , Derdeyn Colin , Zipfel Gregory
Published: March 2022

Introduction:
Animal studies have indicated that phosophodiesterase V (PDE-V) inhibition reduces cerebral vasospasm and improves outcomes following subarachnoid hemorrhage (SAH).

Hypothesis:
We hypothesize that sildenafil (an FDA-approved PDE-V inhibitor) is safe when given to patients with aneurysmal SAH and improves cerebral vasospasm.

Methods:
A prospective, non-randomized proof-of-principle trial using a two-phase dose escalation scheme was implemented. Patients with SAH underwent day-7 screening angiography to assess for vasospasm. In phase I, those with moderate to severe vasospasm were given 10mg (low dose) of intravenous sildenafil, followed by repeat angiography 30 mins after infusion. In phase II, patients with any degree of vasospasm were given 30mg (high dose) of sildenafil, followed by repeat angiography.

Safety was assessed by analyzing vital signs, intracranial pressure (ICP) monitoring neurological status, and observing for the development of adverse reactions attributable to sildenafil.

Two blinded reviewers compared pre- and post-sildenafil angiographic images to admission angiography and subjectively graded them as “improvement” or “no improvement” in vasospasm. Unblinded quantitative measurements of vessel diameter change were also made between pre- and post-sildenafil angiograms.

Results:
Eleven of 23 patients enrolled had vasospasm, received sildenafil and underwent repeat angiography (5 received the 10mg dose and 6 the 30mg dose).

There were no adverse effects upon heart rate, ICP, or neurologic status. Sildenafil infusion did result in a transient decline in mean arterial pressure (MAP). With the low dose there was a 16% decline in MAP with an average time to return to baseline of 16 mins. For the high dose the decline was 19% with an average of 33 mins to return to baseline.

Seven of 11 (64%) had angiographic improvement in vasospasm, with 3 of 5 (60%) from the low dose group and 4 of 6 (67%) from the high dose group. The average vessel dilatation in responders was 1.25 mm.

Conclusions:
Sildenafil is safe and well tolerated when given for the acute treatment of SAH-related cerebral vasospasm. These findings provide preliminary evidence that angiograpic vasospasm is improved in select patients following sildenafil infusion.
Abstract 36: Parvovirus B19 DNA Prevalence is Increased in Pediatric Stroke Patients Compared to Controls: Pilot Findings From the Vascular Effects of Infection in Pediatric Stroke (VIPS) Study
Authors: Luna Jorge M , Fullerton Heather J , Wintermark Max , deVeber Gabrielle , Hills Nancy , Muhammad Kawthar , Tokarz Rafal , Lipkin W. Ian , Elkind Mitchell S ,   on behalf of the VIPS Investigators
Published: March 2022

Background:
Mechanisms underlying childhood arterial ischemic stroke_and childhood cerebral arteriopathies in particular_remain poorly understood. There is evidence that viral syndromes are associated with stroke onset.

Objective:
We hypothesized that an unbiased pathogen discovery approach utilizing MassTag polymerase chain reaction (PCR), a multiplex assay that permits simultaneous testing, would identify candidate pathogens associated with stroke risk in blood from childhood stroke patients compared to controls.

Methods:
Serum samples from 162 pediatric arterial ischemic stroke cases and 36 stroke-free control children with minor traumatic injuries were collected in the multi-center international VIPS study; parental interview included questions on recent infections. Samples were analyzed by MassTag-PCR for a panel of 28 bacterial and viral pathogens. Presence of arteriopathy was determined by blinded, centralized review of vascular imaging.

Results:
Median (IQR) age of cases was 8.1 (2.8, 16.0) years; 31% were girls; and 34% had a reported infection in the prior 4 weeks. Median (IQR) age of controls was 7.3 (2.5, 14.3) years; and 41% were girls. Viral pathogen DNA was detected in 14 of 163 (9.2%) of cases and 0 of 37 (0%) of controls: parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Copy number of parvovirus B19/microliter of plasma varied from 11 to 1.3 x 104. Among 10 patients with parvovirus B19, 8 had other, non-infectious stroke risk factors, and 5 had a distinct arteriopathy involving a long-segment of the internal carotid artery (Table).

Conclusion:
Parvovirus B19, a virus capable of infecting erythrocytes and endothelial cells, may be a multi-factorial contributor to childhood ischemic stroke, potentially triggering events among children with congenital heart disease or trauma. MassTag-PCR enhances the detection of pathogens potentially associated with stroke in pediatric stroke patients.
Abstract 42: Chronic Endothelial Activation in Childhood Arterial Ischemic Stroke
Authors: Bernard Timothy J , Dowling Michael M , Ichord Rebecca , Friedman Neil R , Kirton Adam , Fullerton Heather J , Weitzenkamp David A , Hollatz Amanda L , Ruegg Katherine A , Manco-Johnson Marilyn J
Published: March 2022

Objective:
Despite evidence suggesting that arterial inflammation plays a role in the pathophysiology of childhood arterial ischemic stroke (AIS), relatively little is known about inflammatory induced coagulation and/or endothelial activation. The object of this study was to compare biomarkers of coagulation activation [D-dimer and thrombin-antithrombin complex (TAT)] and endothelial activation [Plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor antigen (vWF Ag)] in children with AIS as compared to healthy pediatric controls.

Methods:
Sixty patients with childhood AIS (ages 28 days to 19 years) were enrolled in a prospective six-center study. Biomarker samples were collected in the acute (0-3 weeks post-AIS) and chronic (> 3 months post-AIS) timeframes. Healthy pediatric controls were enrolled at the central site. Biomarker differences by group were examined using t-test, chi-square, and, if demographics differed, regression models.

Results:
Age and gender were similar in all case and control groups, except age in acute vWF Ag and D-dimer populations [mean (SD): vWF Ag age = 9.3 yrs. (5.2), control age = 6.9 yrs. (4.3),
P=0.007
; D-Dimer age = 9.4 yrs. (5.2), control age = 7.3 yrs. (4.3),
P=0.032
]. All acute biomarkers were significantly elevated in cases as compared to healthy controls, while only markers of endothelial activation remained significantly elevated in cases during the chronic phase (PAI-1
P=0.0014
; vWF Ag
P=0.0002
; Table).

Conclusion:
Children with AIS have increased levels of endothelial and coagulation activation during the acute phase following stroke, while endothelial biomarkers remain elevated beyond 3 months. These results suggest that endothelial activation persists into the chronic phase of childhood AIS. Future studies with larger cohorts and stroke subtype analysis are needed to evaluate the use of endothelial biomarkers as surrogates of ongoing disease and recurrence risk.
Abstract 50: Oral Contraceptive Use and Incident Stroke in Women With Sickle Cell Disease
Authors: Qureshi Adnan I , Adil Malik M , Zafar Taqi T , Umair Muhammad , Chaudhry Saqib A , Zarar Amna , Suri M Fareed K
Published: March 2022

Background:
Oral contraceptives increase the risk of ischemic stroke among women. However, the effect is not studied in the stroke prone sickle cell disease population.

Objective:
To determine the rate of incident stroke among women with sickle cell disease enrolled a large cohort with longitudinal follow-up.

Methods:
A total of 1263 women aged ≥15 and <45 years, were enrolled in Phase 1 of Cooperative Study of Sickle Cell Disease from 23 centers across the US. Participants underwent a baseline examination for assessment of demographics, prior medical history, lab assessments, and clinical data. Post baseline data included routine follow-up examinations, measures of organ damage, and collection of acute and chronic complications. The effect of oral contraceptive use on incident stroke were assessed after adjusting for age, cigarette smoking, and history of exchange transfusion by Cox Proportional Hazards analysis.

Results:
A total of 281 (22.2%) of 1263 women with sickle cell disease reported use of oral contraceptives. There was no difference in the mean age (±SD) of the women who reported use compared with those without of oral contraceptives (27 ±6 versus 27±8, p=0.9). History of exchange transfusions (24.2 % versus 15.0 %, p=0.003) and cigarette smoking (24.7 % versus 18.5 %, p=0.03) were more common among women who report use of oral contraceptives. The age adjusted annual incidence of incident stroke among women who used oral contraceptives was four folds higher than those who did not report use (1.4% versus 0.3%, p= 0.04). After adjusting for exchange transfusion and cigarette smoking, oral contraceptive use was not associated with rate of ischemic stroke (HR, 0.3 95% CI 0.06-1.3, p= 0.2) or stroke free survival (HR, 0.98 95% CI 0.6-1.6, p= 0.9).

Conclusions:
The four fold higher risk of incident stroke associated with use of oral contraceptives in women with sickle cell disease can be mitigated by avoiding cigarette smoking.
Abstract 59: Patients With Ischemic Stroke Have More Than Three-Fold Higher Rates of In-Hospital Mortality If Their Troponin is Elevated
Authors: Peddada Krishi V , Lim Michael J , Kennedy Kevin F , Feen Eli , Stolker Joshua M
Published: March 2022

INTRODUCTION
Stroke and heart disease have similar risk factors. Some patients admitted with acute stroke have elevated serum troponin levels concerning for simultaneous myocardial infarction (MI). However, the relationship between troponin elevation and stroke outcomes has not been described.

METHODS
We identified patients with ischemic stroke treated at a stroke network referral hospital whose data were available in the prospectively-collected “Get With The Guidelines” registry. Additional clinical data were obtained from the hospital laboratory, pharmacy, and billing departments. Characteristics of patients with and without abnormal troponin levels were compared, and logistic regression was used to evaluate the association between troponin elevation and mortality after accounting for clinical factors with nominal statistical significance (p<0.1 level) in the bivariate comparisons.

RESULTS
Of 1145 patients treated for ischemic stroke from 2008-2012, troponin was elevated in 199 patients (17.3%). Troponin-positive patients had more cardiovascular risk factors, cardiology consultations, and referral for coronary angiography and intervention (Table). Medical therapy was similar between groups, although patients with troponin elevation were more likely to be treated with intravenous heparin drip early during the hospitalization. Most notably, these individuals had markedly worse in-hospital mortality than those without troponin elevation (27% vs. 8%, p<0.001). This relationship persisted after adjustment for 14 clinical characteristics (odds ratio 4.28 [2.40-7.63]).

Conclusions:
Patients with ischemic stroke and simultaneous troponin elevation have greater burdens of medical comorbidities, higher use of cardiology services, and more than three-fold higher in-hospital mortality than patients without troponin elevation. Further study of these patients is needed to identify potential etiologies behind this high mortality rate.
Abstract 69: The Effect of Patching in Carotid Endarterectomy (CEA) on Reducing The Risk of Restenosis and Stroke in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)
Authors: Malas Mahmoud , Moore Wesley S , Lal Brajesh K , Hughes Susan E , Voeks Jenifer H , Brott Thomas G
Published: March 2022

Objective:
To compare the perioperative risk of any stroke, death and MI and the long-term risk of re-stenosis and stroke following CEA with patching (a prosthetic or vein patch sutured to the arterial opening to widen the closure) versus CEA with primary closure in CREST.

Methods:
We included patients who were randomized and underwent CEA in CREST. We compared peri-procedural and 4-year event rates and 2-year restenosis rates, in addition to rates of reoperation between the two groups. Re-stenosis was defined as elevated peak systolic velocity ≥3.0 m/s on carotid duplex US. Treatment differences were assessed using proportional hazard models adjusting for age, sex, and symptomatic status.

Results:
There were 1,148 patients who underwent CEA (755 {66%} patch; 328 {29%} primary closure). We excluded 43 patients who underwent eversion CEA and 24 patients missing CEA data (5%). There was no significant difference between the two groups with respect to age, sex, race and comorbidities (Table 1). There were significant reductions in the risk of any periprocedural stroke and death (HR 0.35, 95% CI 0.15-0.82, P<0.02), in re-operation (OR 0.33, 95% CI 0.14-0.80, P<0.01), in the 4-year risk of stroke (HR 0.52, 95% CI 0.28-0.97, P<0.04) and in the 2-year risk of re-stenosis (HR 0.26, 95% CI 0.14-0.45, P<0.0001) in the patch compared to the primary closure group (Table 2).

Conclusion:
Patch closure should be considered for all CEAs because of the association of patch closure with reductions in risk of periprocedural stroke and death, re-operation, and long-term clinical and anatomic durability.
Abstract 87: Evolution of the 24-Hour In-House Stroke Team
Authors: Pearson Cari S ,   Providence St. Peter Hosp Stroke Team
Published: March 2022

Background and Issues:
In 1998, Providence St. Peter Hospital (PSPH) created its first stroke team. An on-call Stroke RN/neurologist duo responded to pages from the emergency center and inpatient attending physicians and nurses 24 hours a day, 365 days a year. By late 2010, the responsibilities of the stroke team members had significantly increased, but only two Stroke RNs and one neurologist participated on the team. It became clear that the 100% on-call model had become resource limited and processes were now inconsistent. The development of a sustainable new stroke model was critical.

Purpose:
The purpose of the project was to create a sustainable in-house stroke patient care process that would meet the community’s need for excellent stroke care while maintaining Joint Commission Primary Stroke Center certification.

Methods:
In early 2011, an interdisciplinary team convened to develop the new process. Members included RNs and physicians from neuroscience, emergency center, and primary care, radiologists, CT technicians, pharmacists, and phlebotomists. Stroke clinical guidelines, best practices and outcome data were reviewed. Operational, financial and clinical opportunities for improvement were identified.

Results:
As a result, two separate initiatives were implemented, (a) in-house acute stroke response and (b) emergency center acute stroke response, both which are active 24 hours per day, 365 days per year. Seven neurologists now rotate call as the stroke neurologist. One of sixteen neuroscience RNs is onsite 24 hours a day as the Stroke RN. Acquisition of a telestroke robot enables the stroke neurologist to assess the patient immediately and make treatment decisions that are initiated before the neurologist arrives at the hospital. Procedures are outlined for all involved departments, ensuring timely diagnostics completion, appropriate medication administration or intervention, and consistently high standards of care.

Conclusions:
In conclusion, the revised stroke patient care management processes have proven to be sustainable and effective in ensuring timely intervention and positive outcomes for stroke patients. The program is reviewed and updated monthly.
Abstract 96: Stroke in the Young: Preliminary Results for Temporal Trends in the Age of Stroke Incidence in a Large, Bi-Racial Population
Authors: Kissela Brett M , Alwell Kathleen , Khoury Jane , Moomaw Charles , Woo Daniel , Adeoye Opeolu , Flaherty Matthew , Khatri Pooja , Ferioli Simona , Martini Sharyl , de los Rios La Rosa Felipe , Mackey Jason , Kleindorfer Dawn
Published: March 2022

Introduction:
Previously, we reported that stroke incidence in the young (age < 55) significantly increased in both blacks and whites over three study periods between 1993 and 2005. Here we further describe this temporal trend, adding data from 2010.

Methods:
The Greater Cincinnati/Northern Kentucky region includes 2 southern Ohio counties and 3 contiguous Northern Kentucky counties (estimated population, 1.3 M). Our study determined first-ever hospital-ascertained strokes that occurred in the population between 7/1/93 and 6/30/94 and in calendar years 1999, 2005, and 2010 by screening ICD9 codes of all inpatient and emergency department visits. Cases were abstracted by study nurses and verified by study physicians. Results for 2010 are preliminary. The denominator for the calculation of incidence rates (in those aged ≥ 20years) was extracted from the U.S. Census Bureau website (www.census.gov). Age- and race-specific incidence rates and 95% confidence intervals (CI) were calculated assuming a Poisson distribution. We tested for differences in age trends using Student’s t-test, chi-square, and Poisson regression as appropriate.

Results:
The mean±SD age of onset was 71.3±13.6 in 1993-94, 70.9±14.4 in 1999, 68.4±15.5 in 2005 and 68.5±15.6 in 2010 (p<.0001 for trend). The proportion of all strokes under age 45 were 4.6%, 5.4%, 7.3%, and 6.1% in 1993-94, 1999, 2005, and 2010, respectively; Poisson regression showed a shift toward younger strokes across the four periods studied (p<.0001). Age-specific stroke incidence rates by study period are presented in the Table.

Discussion:
The disturbing trend of increasing stroke in the young (age < 55) seems to have leveled off slightly in 2010 but is still of great public health significance as younger strokes carry the potential for greater lifetime burden of disability. Further study is needed to determine the reasons for these trends.
Abstract NS3: The Hospital Anxiety and Depression Scale Has Limitations in Inpatient Post Stroke Depression Screening
Authors: Casal Stephanie L , Finley-Caulfield Anna , Tai Waimei Amy
Published: March 2022

Background and Purpose:
While the prevalence of post stroke depression (PSD) is high (ranging from 33% to 50%), it is often underdiagnosed and undertreated, impairing recovery for stroke survivors. Comprehensive Stroke Center designation now mandates depression screening. We aimed to evaluate the Hospital Anxiety and Depression Scale (HADS) as a depression screening tool in the inpatient setting for stroke patients.

Methods:
A single academic medical center initiated use of the HADS to screen for depression during acute hospitalization in patients with a primary stroke diagnosis. All stroke patients who met the following inclusion criteria between Sept. 2012 and June 2013 were screened: (1) Length of stay (LOS) ≥ to 5 days (2) medically stable (3) cognitively intact (4) no aphasia and (5) English speaking. NCHS data indicate the average inpatient LOS is 5.3 days, as such, we modified the HADS to ask patients to reflect upon their experience over the last five days. Therefore, patients were evaluated on ≥ hospital day 5.

Results:
423 patients were hospitalized with stroke as their primary diagnosis, 44 (10.4%) were eligible to be screened for depression. Short LOS and cognitive/language impairments comprised 75% of the excluded patients. Twenty-six of 44 eligible patients (59%) completed the HADS. Only two patients who were screened had a positive screening result, both of whom were known at admission to have a comorbid diagnosis of depression. No detections of post stroke depression were made.

Conclusions:
While identification and treatment of post-stroke depression is critical to support maximal recovery in stroke survivors, the HADS has significant limitations as a screening tool. Many stroke patients had LOS <5 days, which may be too short of a time frame to use the HADS. Alternative instruments for inpatient screening of depression or utilization of other in-hospital prediction models may show promise. Recent research describes a clinical prediction model with accompanying risk-assessment table to identify patients at risk for post stroke depression. Validated screening tools and predictive models for patients with cognitive impairment and communication difficulties should also be explored.
Abstract T MP106: Impact of Enrollment Volume on Risk Factor Control and Outcomes in the SAMMPRIS Trial
Authors: Chiu David , Klucznik Richard P , Turan Tanya N , Lynn Michael J , Nizam Azhar , Derdeyn Colin P , Fiorella David , Lane Bethany F , Montgomery Jean , Katz Lawrence B , McCane C. D , Janis L. S , Chimowitz Marc I ,   SAMMPRIS Investigators
Published: March 2022

Background and Purpose:
There are limited data on the impact of site enrollment volume on risk factor control and outcome of patients in secondary prevention trials. We sought to compare outcomes and risk factor control between high and low enrolling sites in the stenting and medical groups in SAMMPRIS.

Materials and Methods:
451 patients with recent TIA or stroke attributed to 70%-99% intracranial stenosis were randomized to aggressive medical management alone or stenting plus aggressive medical management. We compared the Kaplan-Meier (K-M) curves for the primary endpoint (any stroke or death within 30 days of enrollment or ischemic stroke in the territory beyond 30 days) using the log-rank test and the percentages of patients with mean LDL < 70 mg/dl and mean systolic blood pressure (SBP) < 140 mmHg (< 130 mmHg if diabetic) during the study using the chi-square test between patients at high (≥ 12 patients) and low enrolling (< 12 patients) sites in the stenting and medical groups.

Results:
In the stenting group, the K-M curves for the primary endpoint were not significantly different between high vs. low enrolling sites (p=0.93) with rates of 13.5% vs. 14.7% at 30 days and 19.0% vs. 20.6% at 2 years. In the medical group, the K-M curves for the primary endpoint were significantly different between high enrolling sites vs. low enrolling sites (p=0.0005) with rates of 1.8% vs. 9.8% at 30 days and 7.3% vs. 20.9% at 2 years. Control of LDL and SBP during the study at high vs. low enrolling sites in the medical and stenting groups are shown in the table
.

Conclusions:
High enrolling sites had significantly lower 30-day and 2 years rates of the primary endpoint in the medical group but not in the stenting group compared with low enrolling sites in SAMMPRIS. One contributing factor to the lower event rate in the medical group at high enrolling sites may be the significantly higher percent of patients who achieved a mean LDL < 70 mg/dl during follow-up at high enrolling sites.
Abstract T MP29: Impaired Vasodilatory Reserve on Acetazolamide-Challenged 99tc-hmpao-Spect is a Strong Predictor of Stroke Recurrence in Patients With Severe Steno-Occlusive Disease of Intracranial Carotid or Middle Cerebral Artery
Authors: Paliwal Prakash , Yeo Leonard , Sinha Arvind K , Batra Amit , Rathakrishnan Rahul , Ning Chou , Tsai Tseng , Teoh Hock Luen , Chan Bernard P , Chong Vincent F , Sharma Vijay
Published: March 2022

Background:
Intracranial stenosis carries an increased risk for cerebrovascular ischemia. In severe stenosis, cerebral autoregulation may be impaired due to inadequate cerebral vasodilatory reserve (CVR) & intracranial steal phenomenon (reversed-Robin Hood syndrome-RRHS). Identification of patients with inadequate CVR and RRHS may help in identifying high-risk patients.

Methods:
In this prospective study, we included patients with symptomatic and severe stenosis of intracranial carotid (ICA) & middle cerebral artery (MCA). CVR was evaluated with transcranial Doppler (TCD) and breath-holding index (BHI) <0.69 determined inadequate CVR. RRHS was detected as transient velocity reduction in affected artery when flow increased in the reference artery. Patients with RRHS were further evaluated with acetazolamide-challenged 99Tc-HMPAO-SPECT.

Results:
126 patients (80 male, mean age 56yrs; range 23-78yrs) fulfilled our TCD criteria for inadequate CVR. HMPAO-SPECT showed impaired CVR in 84 (67%) patients. RRHS noted on TCD in 38 (45%) patients (median steal magnitude 14%; inter-quartile range, IQR 10) was confirmed by acetazolamide-challenged HMPAO-SPECT (median perfusion deficit 8%; IQR 13%) in 35 (92%) cases (sensitivity 82%, specificity 96% with positive predictive value 96%). A strong relationship between RRHS on TCD and SPECT was noted on ROC curve analysis (area under curve 0.93; 95% confidence interval 0.87-0.98;p<0.00001). Linear relationship was observed between impaired vasodilatory reserve and stroke recurrence during follow up (mean 35months; range 8 to 49months)- 56% in patients with RRHS versus 20% in patients with moderately impaired CVR versus 4% in patients with mildly impaired CVR (chi-square 18.42; df=2; p<0.001 for trend). RRHS on HMPAO-SPECT was an independent predictor of recurrent cerebral ischemic events (RR 1.9, 95%CI 1.2-4.2; p=0.03).

Conclusions:
Among patients with severe intracranial stenosis, intracranial steal phenomenon is associated with high risk of cerebral ischemic events. Acetazolamide-challenged HMPAO-SPECT is reliable in the quantification of vasodilatory reserve for selecting a target group of patients for possible revascularization.
Abstract T MP56: Challenges in Telethrombolysis: Is Underestimation of Early Ischemic Changes by Stroke Neurologists Associated With Symptomatic Intracranial Hemorrhage?
Authors: Zerna Charlotte , Gerber Johannes , Pütz Volker , Bodechtel Ulf , Kepplinger Jessica , Barlinn Kristian , Pallesen Lars-Peder , Siepmann Timo , von Kummer Rüdiger
Published: March 2022

Background:
The Stroke Eastern Saxony Network (SOS-NET) provides telemedical consultations for patients with acute ischemic stroke. Stroke neurologists recommend intravenous (IV) thrombolysis based on cerebral CT scan evaluation with the Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether: 1) underestimation of early ischemic changes (EIC) was associated with symptomatic intracranial hemorrhage (sICH); 2) whether high ASPECTS predicted favorable outcome after telethrombolysis.

Methods:
We retrospectively analyzed prospectively collected data of SOS-NET patients who received IV telethrombolysis from 10/08 to 07/12. Two experienced neuroradiologists re-evaluated cerebral CT scans blinded to clinical findings providing reference standard. We defined underestimation of EIC by stroke neurologists as ASPECTS deviations > +1 point and favorable outcome as modified Rankin scale (mRs) scores of 0 to 2 at discharge. We analyzed whether underestimation of EIC was associated with sICH by ECASS-2 criteria and whether ASPECTS dichotomized at 8-10 versus 0-7 was associated with favorable outcome.

Results:
Of 647 patients who received IV telethrombolysis during the study term, clinical and imaging data were available for 344 patients (median age 76 [IQR 70 - 81] years, NIHSS score 11.5 [IQR 6 - 18], 54.8% female, onset-to-treatment-time 143 minutes [IQR 110 - 190]). At discharge, 91 patients (27.2%) had a favorable outcome. Overall 14 patients (4.2%) suffered thrombolysis-related sICH. Compared to reference, stroke neurologists underestimated EIC extent in 30 patients (9%). ASPECTS deviations were not associated with thrombolysis-related sICH (3.3% vs. 4.3%; p=1.0). Patients with higher ASPECTS (n=299) were more likely to have a favorable outcome than patients with low ASPECTS (n=35) (35.3% vs. 10.3%; p=0.006).

Conclusion:
Underestimation of EIC by stroke neurologists was rare and not associated with thrombolysis-related sICH in our telestroke network. ASPECTS of 8 - 10 on pretreatment CT is associated with favorable clinical outcome following telethrombolysis.
Abstract T MP60: Limited Role for Neurosurgical Hematoma Evacuation for Post-Alteplase Ischemic Stroke Patients: Impact on the Role of Neurosurgical Coverage for Primary Stroke Patients
Authors: Venizelos Alexander , Roper Debbie , Hansen Paul A , Pandhi Abhi , Coulson Jeff , Gianatasio Ryan , Robins Scott , janardhan Vallabh
Published: March 2022

Introduction:
Hemorrhage is a well documented consequence after the administration of intravenous alteplase (IV-tPA) in the therapy of ischemic stroke. Serious intracranial bleeding may occur in 6.4 percent of patients within thirty-six hours. Primary stroke centers certified by The Joint Commission (TJC) require neurosurgical coverage or transfer protocols to ensure neurosurgical services are available within two hours.

Hypothesis:
We assessed the hypothesis that patients receiving IV-tPA for ischemic stroke would not require any type of neurosurgical intervention within two hours.

Methods:
Ischemic stroke patients who received IV-tPA from January 2010 to June 2013 across 11 hospitals with a regional stroke network were analyzed retrospectively. Of those patients we assessed the prevalence of brain hemorrhage, and further the need for neurosurgical intervention (craniotomy, craniectomy, burr-hole placement, extraventricular drain (EVD) placement) during that inpatient admission.

Results:
Of the 17,319 inpatient admissions in our regional stroke network, 6,500 patients were admitted for ischemic stroke. Only 2% of all patients treated with IV-tPA had symptomatic brain hemorrhages (10/520). One patient underwent craniotomy for hematoma evacuation after an observation period of six hours (0.2%; 1/520).

Conclusions:
Symptomatic brain hemorrhage after IV-tPA requiring emergent neurosurgical intervention is rare. The results of this study underscore the relevance of transfer protocols to ensure neurosurgical services are available within two hours but question the need for neurosurgical coverage at designated primary stroke centers.
Abstract T MP62: Persistent Racial Disparities in Outcomes for Middle-aged People With Intracerebral Hemorrhage in the US Stroke ‘Buckle’
Authors: Boan Andrea D , Feng Wuwei , Adams Robert J , Ovbiagele Bruce , Lackland Daniel T
Published: March 2022

Background:
Intracerebral hemorrhage (ICH) has no cure and is associated with substantial morbidity and mortality. While the burden of ICH on Black patients (vs. Non-Hispanic White counterparts) has long been recognized, recent comparative trends in the racial characteristics of ICH among people < 65 years of age within the stroke-prone, Southeastern region (‘buckle of the stroke belt’) of the United States, have not been fully examined.

Methods:
Utilizing the South Carolina hospital discharge database, patients (age 25-64 years) discharged with a primary diagnosis of ICH (ICD9 431) from 2001 to 2012 were identified. Black to White disparity rate ratios for stroke hospitalizations and in-hospital mortality were calculated based on rates per 100,000 population by discharge year. Clinical characteristics were compared by multivariate logistic regression adjusting for age and gender.

Results:
There were 4,285 (Blacks = 2,557 and Whites = 1,728) ICH hospitalizations from 2001 to 2012 in patients < 65 years of age. Black patients had significantly worse clinical characteristics as compared to Whites (table); and experienced almost 4 times the rate of ICH hospital admissions and 3 times the rate of in-hospital mortality compared to White patients (figure). These racial disparity differences did not significantly vary over the time period.

Conclusions:
Over the last 12 years, rates of hospital-based ICH outcomes remained persistently and considerably poorer among middle-aged Black vs. White patients within the US Stroke Buckle. Intensified efforts aimed at mitigating the personal and societal burden of this lingering racial disparity are warranted.