bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP100: Posterior Circulation Ischemic Stroke in Manitoba Children: A Population Based Longitudinal Study of Clinical Presentation and Outcome
Authors: Carey Samantha , Rafay Mubeen
Published: March 2022

Background:
In chidden, the nonspecific presentation of posterior circulation arterial ischemic strokes (PAIS) poses challenges. Additionally, PAIS differ markedly from anterior circulation strokes. Incidence data is lacking and the information about outcome in children with PAIS is limited.

Objectives:
This study was aimed to calculate the incidence of and to review the clinical presentation, outcome and prognostic predictors of PAIS in children.

Methods:
A retrospective review of a population based cohort of children, birth to 18 years, in Manitoba, Canada, with PAIS, from January 1992 to December 2010. Data regarding demographics, clinical features and outcome of children with PAIS was collected.

Results:
Twenty four children with PAIS, 54.2% male, average age 5 years, were identified. Our ratio of PAIS to AIS was 20%, with an estimated incidence rate of 1 person per 10,000 if followed for 15 years. Warning symptoms before stroke onset were present in 33%. Seventy-one percent presented with sensorimotor deficits, 75% with impaired consciousness and 29% with seizures or posturing. Identifiable risk factors were present in two thirds: vasculopathy 25%, infection 21%, trauma 12.5% and congenital heart disease 12.5%. Average Pediatric National Institute of Health Stroke Severity Scale (PedNIHSS) at presentation was 11. Average Pediatric Stroke Outcome Measure (PSOM) at 3 months was 1.35. We found poor outcomes in patients with aboriginal ancestry (45.8%,p=0.003), high PedNIHSS score (p=0.02), bilateral infarction(42%,p=0.003), large artery infarcts (53%,p=0.02), occipital lobe infarcts(42%,p=0.04) and presence of vasculopathy (25%,p=0.05). Presence of abnormalities on vascular imaging trended towards recurrence (p=0.07). Outcome at 3 months correlated with outcome at 12 and 24 months (p<0.001).

Conclusion:
Our study is the first to report a population-based incidence of PAIS in children. The incidence rate and the predictors of outcome provide valuable information that will help direct treatment and prognostication of children with PAIS. Our data calls for close observation and management of children with suspected PAIS, in particular aboriginal patients, patients with bilateral and large infarction and abnormal vascular imaging.
Abstract TMP103: Combined Results of Two Phase 3 Studies of PA32540, an Antiplatelet Therapy of Enteric-Coated Aspirin and Immediate-Release Omeprazole, in Patients with Previous Cerebrovascular Disease
Authors: Alberts Mark J , Goldstein Jay L , Whellan David J , Fort John G , Zhang Ying
Published: March 2022

Introduction:
Antiplatelet therapy with aspirin is a mainstay for secondary prevention of ischemic strokes and other vascular events. Yet, many patients do not take aspirin or discontinue it due to gastrointestinal (GI) side effects. Proton pump inhibitors are often co-prescribed to those who develop aspirin-related dyspepsia or who are at risk for GI complications. We investigated a new aspirin formulation (PA32540), which is a coordinated-delivery tablet of immediate-release (IR) omeprazole (40 mg) and enteric-coated (EC) aspirin (325 mg), in an effort to improve co-prescription compliance, reduce GI side effects, and improve overall antiplatelet therapy efficacy.

Methods:
Two phase 3 double-blind multicenter studies included a subset of subjects with ≥ 1 transient ischemic attack or ischemic stroke who were prescribed aspirin at 325 mg once daily for ≥ 3 months for secondary prevention of cardiovascular (CV) events. All subjects were randomly assigned to once-daily treatment with PA32540 or 325 mg EC aspirin. Use of coumadin was excluded. Endoscopic assessments for gastric or duodenal ulcers were performed at screening and at 1, 3, and 6 months. Major adverse cardiovascular events (MACE) were adjudicated by an independent blinded endpoint committee.

Results:
Baseline characteristics and rates of discontinuation are shown in Table 1. The rate of gastroduodenal ulcers and discontinuations due to upper GI events were significantly lower following administration of PA32540 vs EC aspirin alone over 6 months. No difference in MACE was identified.

Conclusion:
In patients with previous cerebrovascular disease, PA32540 was associated with a significantly lower rate of endoscopic gastroduodenal ulcers, a higher rate of treatment continuation, and no increase in the number of MACE, compared with aspirin alone. These findings support the use of a single tablet prescription of omeprazole and aspirin for improving the overall efficacy of antiplatelet therapy.
Abstract TMP104: Arm Ischemic Preconditioning Prevents Stroke Recurrence in Octogenarians with Intracranial Arterial Stenosis
Authors: Meng Ran , Konakondla Sanjay , Meng Lu , Xi Chunjiang , Liu Yu , Li Guoqing , Li Sijie , Jia Jianping , Ling Feng , Hussain Mohammed , Ding Yuchuan , Ji Xunming
Published: March 2022

Introduction:
Symptomatic atherosclerotic intracranial arterial stenosis (SAIS) has a high incidence of stroke and recurrence, especially in octogenarians. Currently available therapies including stenting are unable to prevent strokes recurrence completely and may result in worse clinical outcomes. Emerging experimental investigations have suggested that remote ischemic preconditioning may be clinically effective in stroke intervention.

Hypothesis:
Brief repetitive bilateral arm ischemic preconditioning (BAIPC) may be safe and prevent stroke occurrence and recurrence in octogenarians with SAIS.

Methods:
A total of 58 consecutive octogenarians with SIAS (diagnosed by imaging) enrolled in this prospective, single blind and randomized study. All patients enrolled underwent standard medical care. In addition, patients in BAIPC group (n=30) underwent five cycles consisting of bilateral arms 5min ischemia followed by 5min reperfusion twice daily for the total of 180 consecutive days. Blood pressure, heart rate, local skins integrity and plasma myoglobin levels before and during the first 30-days of treatment were documented. Finally, Plasma levels of thrombosis and inflammation markers, clinical outcomes (modified Rankin Scale 0-1) and the incidence of stroke recurrence during the180-days of treatment in the two groups were compared.

Clinical Trial Registration-URL:
www.clinicaltrials.gov
, unique identifier:
NCT01570231
.

Results:
Compared to the controls (n=28), BAIPC had no adverse effects on blood pressure, heart rate, local skins integrity and plasma myoglobin, and BAIPC did not contribute to cerebral hemorrhage. BAIPC decreased plasma levels of hsCRP, IL-6, PAI-1, leukocyte count, platelet aggregation rate as well as increased TPA, improved the 180-days of modified Rankin Scale and decreased the incidences of ischemic stroke recurrence and TIA onset (6.7% and 23.3% in BAIPC group versus 28.6% and 39.3% in control group,
P
< 0.01).

Conclusions:
Our study provides a proof-of-concept that BAIPC is a safe and feasible method to protect the ischemic brain in octogenarians with SIAS. Further investigation in an enlarged trial is ongoing.
Abstract TMP108: Ongoing Use and Withdrawal of Antithrombotic Medication for Medical Procedures in the Greater Cincinnati population
Authors: Broderick Joseph P , Khoury Jane , Alwell Kathleen A , Rademacher Eric , Anderson Aaron , Flaherty Matthew L , Ferioli Simona , Woo Daniel , de los Rios la Rosa Felipe , Adeoye Ope , Khatri Pooja , Mackey Jason , Kissela Brett M , Kleindorfer Dawn
Published: March 2022

Introduction:
Withdrawal of antithrombotic medication for medical procedures is a potentially important cause of ischemic stroke (Broderick, Stroke, 2011). However, population estimates of how commonly persons in the general population withdraw from antithrombotic medication during a given year are not available.

Methods:
Telephone survey respondents were drawn from our biracial population of 1.3 million using random-digit dialing in 2011 to reflect the age, race, and gender distribution of stroke patients, based on an ongoing stroke incidence study in the same region. In addition to demographic and medical history questions, we also asked if they had stopped the medication on request of their physician for scheduled surgery or other procedure during the past 60 days.

Results:
There were a total of 2036 surveyed, 1959 self-identified as either black (544) or white (1415) race. 62% were on antithrombotic medication overall of which 7% were on an anticoagulant and 58% were on an antiplatelet medication and 4% on both (Table 1). Use of antithrombotic medication increased with advancing age (p<0.0001) and was more common in men (64%) than women (60%), p=0.09 and whites (64%) than blacks (55%), p=0.0003. Of those persons 75 years or older, 72% were taking an antithrombotic medication: an antiplatelet agent alone in 60%, anticoagulant alone in 6% and both in 6%. Of those using an antithrombotic medication, 10% indicated that they had stopped the medication in the past 60 days prior to interview. Of those that stopped the meds, 27/134 (20%) were on anticoagulants, and 101/1144 (9%) were on antiplatelet agents.

Conclusions:
Use of antithrombotic medication is widely prevalent in the population as is discontinuance of such medication for medical procedures, particularly warfarin. Withdrawal of anti-thrombotic medications for surgical procedures and diagnostic testing is a potential risk factor for ischemic stroke and is an important area for ongoing study.
Abstract TMP11: Leptomeningeal Collaterals Predict Infarct Growth And 90 Day Clinical Outcome In Acute Ischemic Strokes Given Intra Arterial Therapy.
Authors: Nambiar Vivek K , Sohn sung I , Qazi Emmad , Qazi Abdul , Kosior Jayme , Goyal Mayank , Hill Michael D , Demchuk Andrew M , Menon Bijoy
Published: March 2022

Introduction:
We tried to explore the role of lepto meningeal collaterals, baseline imaging to recanalization time in predicting infarct growth and final clinical outcome in acute ischemic strokes.

Methods:
Data is from a prospective study of consecutive acute stroke patients (2005-2009) from Keimyung University, Daegu,South Korea analysed at University of Calgary. Only patients with M1 MCA+/- intracranial ICA on baseline CT-angio, known stroke onset time with MR DWI at baseline and follow-up were included for analyses. Baseline infarct volume on DWI was calculated using Quantomo, a validated in house software. Infarct growth was calculated as difference in DWI volume between 24 hrs and baseline. Lepto meningeal collaterals at baseline CT-angio assesed using a previously published scale.

Results:
Of the 264 patients analysed 84 patients were eligible for the study. Of 84 patients [mean age 65.2 +/- 13 yrs, 52.4% male, median NIHSS 14 IQR=8.5, median time from onset of stroke symptom to baseline MR 164 mins, IQR 100.5) in the study, 59.5% achieved TIMI 2-3 recanalization and 35.7% good clinical outcome (mRS 0-2). Median baseline DWI volume was 31.6 ml (IQR 75); median infarct growth 29.8 ml (IQR 64.1). We noted significant correlation (spearman’s r=-0.68, p<0.001) between baseline DWI volume and collateral status and between infarct growth and collateral status (r=-0.38, p<0.01). No correlation (r=0.1, p=0.34) was noted between infarct growth and baseline MR to recanalization time. In patients with baseline DWI volume <=18 ml (group 1), 61.3% of patients achieved good clinical outcome when compared to 26.7% in patients with volume 18-80 ml (group 2) and 13% with volume >80 ml (group 3). Median infarct growth was lowest in group 1 (5.9 ml, IQR 52.7) followed by group 2 (30.5 ml, IQR 70.6) and group 3 (63 ml, IQR 108.1).

Conclusion:
Leptomeningeal collateral status determines baseline infarct volume and the extent of infarct growth until recanalization is achieved
Abstract TMP116: AAV-sFLT: A Potential Therapeutic Agent for the Treatment of Brain Angiogenic Diseases
Authors: Mao Lei , Shen Fanxia , Chen Wanqiu , Akinpelu Babatunde , Lawton Michael T. , Young William L. , Su Hua
Published: March 2022

Background and Purpose:
The soluble vascular endothelial growth factor (VEGF) receptor 1 (sFLT) has been tested in both animals and humans for anti-angiogenic therapy, e.g., age-related macular degeneration. We hypothesized that adeno-associated viral vector (AAV)-mediated sFLT expression could be used to treat brain angiogenic diseases, such as brain arteriovenous malformation (bAVM). We tested the anti-angiogenic effect of sFLT and the feasibility of using AAV serotype 9 to deliver AAV-sFLT by intravenous injection (IV) to brain angiogenic lesions.

Methods:
AAV vectors were packaged in AAV serotypes 1 and 2 (stereotactic injection) and 9 (IV-injection). Angiogenic model was induced in adult wildtype (WT) mice through stereotactic injection of AAV1-VEGF (2×10
9
genome copies (gcs)). Brain AVM model was induced in adult mice with floxed Alk1 (a causative gene for hereditary hemorrhagic telangiectasia that causes AVMs in multiple organs) through co-injection of AAV1-VEGF and Ad-Cre. AAV2-sFLT (2×10
9
gcs) was co-injected with AAV1-VEGF to inhibit brain angiogenesis. Gene expression in the brain by IV-delivered AAV9 was tested using intra-jugular vein injection of AAV9-LacZ or AAV9-GFP (1×10
11
gcs). We then compared gene expression mediated by stereotactic injection of AAV1 and by 2 packaged AAV-LacZ vectors.

Results:
Co-injection of AAV2-sFLT with AAV1-VEGF completely abolished VEGF-angiogenic effect (320±30/mm
2
vs 434±86 p=0.01). The vessel density around the injection sites was similar to AAV1-LacZ-injected control mice (p=0.84). AAV2-EV (empty virus) had no effect. Intravenous injection of AAV9-LacZ or AAV9-GFP resulted in a higher level of gene expression in the angiogenic foci or bAVM than in normal brain tissues. Gene expression mediated by AAV1 was about 5 times higher than AAV2.

Conclusion:
AAV mediated sFLT expression inhibited VEGF-induced brain angiogenesis. The sFLT anti-angiogenic effect can be achieved at about 1 to 5 molar ratio of sFLT vs. VEGF. Intravenously injected AAV9 can mediate effective transgene expression in brain angiogenic lesions.
Abstract TMP21: The Increased tPA Utilization in Recent Years has Disproportionately Benefited White Men.
Authors: Bhattacharya Pratik , Chaturvedi Seemant
Published: March 2022

Intravenous tPA utilization has increased in the United States across the last decade. Gender disparities in tPA use are recognized. While blacks are at a disadvantage with regards to tPA use, little is known about stroke care among hispanic patients. We tested the hypothesis that the rise in tPA utilization differentially affected race and gender subgroups. Data from the Nationwide Inpatient Sample (NIS) for the years 2001 through 2009 were analyzed. The data represents a 20% sample of all inpatient hospitalizations in the United States. Patients discharged with a diagnosis of Ischemic stroke were identified using ICD-9 codes. The code 99.10 was used to identify patients who received tPA. Trends in utilization were compared between race and gender subgroups. The NIS had 1,003,533 ischemic stroke discharges over 9 years. Race data was available in 757,238 patients. All races demonstrated significant increase in tPA utilization between 2001 and 2009: 1.15% to 4% among whites; 0.83% to 3.30% among blacks and 0.72% to 2.91% among hispanic (p for trend<0.0001).Upon comparing race and gender subgroups (Fig) tPA utilization was greatest in white men. White women, black men, black women and hispanic women consistently fared worse with regards to tpa utilization when compared with white men. During most years, black and hispanic women demonstrated the lowest rates of tPA utilization. Even in urban teaching hospitals, white men demonstrated the greatest rise in tPA utilization (1.72% to 6.24%), while the use in minority women remained significantly lower. Disparities in race and gender subgroups were mainly in patients older than 45 years. In conclusion, the rise in tPA utilization in the last decade was greatest among white men and lowest among minority women. Social and cultural factors putting minority women at a disadvantage need to be explored and addressed.
Abstract TMP24: Intravenous Thrombolysis For Acute Ischemic Stroke Occurring During Hospitalization For Transient Ischemic Attack: An International, Multicenter Study
Authors: Tsivgoulis Georgios , Sharma Vijay K , Mikulik Robert , Krogias Christos , Haršány Michal , Shahripour Reza Bavarsad , Vadikolias Konstantinos , Heliopoulos Ioannis , Athanasiadis Dimitrios , Teoh Hock Luen , Piperidou Charitomeni , Alexandrov Andrei V
Published: March 2022

Background&Purpose:
There are limited data regarding the safety of intravenous thrombolysis (IVT) in patients who experienced acute ischemic stroke (AIS) during their hospitalization for Transient Ischemic Attack (TIA). We sought to prospectively evaluate the safety and efficacy of systemic thrombolysis in AIS occurring during hospitalization for TIA in an international, multi-center study

Subjects&Methods:
Consecutive patients with AIS that occurred during hospitalization for prior TIA were treated with standard intravenous tissue plasminogen activator (tPA) at five tertiary-care stroke centers. Early arterial recanalization was determined by transcranial Doppler at the end of tPA infusion using the previously validated Thrombolysis in Brain Ischemia flow-grading system. Symptomatic intracranial hemorrhage complicating systemic thrombolysis was evaluated using NINDS rtPA Stroke Study definition. Functional outcome at three months was evaluated using the modified Rankin Scale (mRS).

Results:
Systemic tPA (median onset-to-treatment time 70 min, interquartile range 50-150) was given in 25 consecutive patients (mean age 66±10years) who developed symptoms of acute stroke (median NIHSS-score 10 points; interquartile range 8-14) during hospitalization for prior TIA [(median ABCD2-score 5 points, median time-to-symptom recurrence 24 hrs, interquartile range 24-48). No symptomatic intracranial hemorrhage (0%; 95%CI:0-12%) was documented. Early complete recanalization occurred in 64% (95%CI:44%-80%) of the study population; 84% (95%CI:65%-94%) achieved three-month functional independence (mRS-score of 0-2). The rate of three-month functional independence was higher in patients treated with iv-tPA within 90 min from symptom onset compared to those with onset-to-treatment time>90 min (81% vs 33%; p=0.031)

Conclusions:
Intravenous thrombolysis for symptoms of ischemic stroke occurring after hospitalization for TIA appears to be safe. These pilot data support re-setting the clock if new symptoms recur shortly after TIA.
Abstract TMP32: Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to Pleiotropic Effect of Cilostazol
Authors: Omote Yoshio , Deguchi Kentaro , Tian FengFeng , Kawai Hiromi , Kurata Tomoko , Yamashita Toru , Ohta Yasuyuki , Abe Koji
Published: March 2022

Background and Purpose:
This study investigated the efficacy of anti-platelet drugs on stroke, and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R).

Methods:
Stroke-prone spontaneously hypertensive rats (SHR-SP) were treated with vehicle, aspirin, clopidogrel and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow (rCBF), motor and cognitive functions were evaluated. Spontaneous infarct volume, oxidative stress markers and the IGF-1R positive cell ratio in the hippocampus were immunohistochemically examined. IGF-1R expression in the hippocampus was assessed by western blotting.

Results:
Cilostazol and clopidogrel reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (p<0.05) in the memory-related IGF-1R positive ratio and IGF-1R expression in the hippocampus. Cilostazol reduced oxidative stress markers in affected neurons regardless of blood pressure or rCBF.

Conclusion:
The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and cognitive functions. The increase of IGF-1R positive cells in the hippocampus could partly explain the preservation of cognitive function in SHR-SP.
Abstract TMP34: Prostaglandin PGF2a Receptors as a Putative Therapeutic Target in Stroke and Traumatic Brain Injury
Authors: Glushakov Alexander V , Bracy Connor L , Narumiya Shuh , Dore Sylvain
Published: March 2022

Background:
Stroke and traumatic brain injury (TBI) are ones of the leading causes of death and disability in the USA. Secondary brain injury following TBI shares common features with neuropathology of stroke including oxidative stress and neuroinflammation. Although potentially treatable secondary injuries play a key role in the neurological outcomes currently there is no effective treatment and discovery of new therapeutic targets remains critical. Primary injury to the brain promotes upregulation of prostaglandins, notably the proinflammatory PGF2a, and overactivation of its FP GPCR which could exacerbate brain damage. Thus, our study is focused on the investigation of the FP receptor as a target for novel neuroprotective drugs in preclinical animal models of stroke and TBI.

Methods:
We used FP receptor knockout male C57BL/6 mice and post-treatment with the selective FP antagonist AL-8810 (1 and 10mg/kg, IP) in permanent middle cerebral artery occlusion (pMCAO) and controlled cortical impact (CCI) models. Neurological impairments assessed at 24 and 48h after injury using tape removal reflex and neurological deficit score, and brain pathology was assessed at 48h using triphenyltetrazolium chloride or cresyl violet.

Results:
Genetic deletion of the FP receptor or its blockade with AL-8810 at both doses significantly reduced cortical infarct volume and tape removal reflex following pMCAO. In vehicle treated animals, CCI caused cortical lesion with relative volume of 20.5±1.0% and significant hippocampal swelling (146.5±7.4% of contralateral) as compared with sham (P<0.05, n=4). AL-8810 had no significant effect on cortical lesion suggesting irreversible effect of primary CCI injury. However, AL-8810 at both doses reduced CCI-induced hippocampal swelling to the levels not significantly different from the sham. In CCI model, post-treatment with AL-8810 at dose 10mg/kg significantly improved neurological deficit score at 24 and 48h after CCI (P<0.001 and P<0.01, n=9-10); whereas the effect of 1mg/kg dose was not significant.

Conclusion:
This study provided, for the first time, clarification on the respective role of calcium-modulating PGF2a FP receptor as a potential target for disease-modifying CNS drugs for treatment of stroke and TBI.
Abstract TMP35: Optogenetic Stimulation Of Motor Cortex Neurons Promotes Recovery After Stroke
Authors: Cheng Michelle Y , Woodson Wyatt J , Wang Eric H , Wang Stephanie , Sun Guohua , Lee Alex G , Arac Ahmet , Fenno Lief , Deisseroth Karl , Steinberg Gary K
Published: March 2022

Objective:
Functional recovery after stroke has been observed in both animal and human studies and is currently attributed to both brain remodeling and plasticity. Brain stimulation techniques such as electrical stimulation and transcranial magnetic stimulation have been used successfully to enhance recovery. However, what mediates this recovery is not well understood. Elucidating the mechanism(s) is difficult because these stimulation techniques non-specifically activate all cell types near the stimulation site. Here we use optogenetic techniques to specifically stimulate layer V pyramidal neurons in the ipsilesional motor cortex at day 5 post-stroke, and investigate the effects on functional recovery as well as underlying mechanisms.

Methods:
Thy-1-ChR2-YFP line-18 transgenic male mice were used. Mice underwent stereotaxic surgery to implant a fiber cannula in the ipsilesional M1. All mice were then subjected to an intraluminal middle cerebral artery suture occlusion (30min). Optogenetic stimulation began at day 5 post-stroke and continued until day 14 post-stroke. Sensorimotor behavior tests were used to assess their behavioral recovery at day 0, 2, 7, 10 and 14 post-stroke. Body weights were also measured. Changes in cerebral blood flow were measured at day 14 post-stroke using the Laser Doppler Flowmetry.

Results:
Rotating beam test revealed that stimulated mice recovered significantly faster than non-stimulated control mice at day 10 and 14 after stroke (p<0.05). Stimulated mice also performed significantly better in the adhesive tape test at day 14, with a shorter tape removal time on the contralesional limb (p<0.05). Additionally, a significantly faster regain of body weight was observed in stimulated mice after stroke (p<0.05-0.01). Cerebral blood flow measurements revealed that stimulated mice exhibited significantly larger increase in cerebral blood flow at day 14 post-stroke (p<0.05-0.01).

Conclusion:
These data indicate that optogenetic stimulation of motor cortex neurons can promote behavioral recovery in mice after stroke. Current studies examine the mechanisms underlying this recovery, including genes related to neurovascular coupling and neurotrophic factors after stimulation.
Abstract TMP41: Predictors Of Effective Indirect Bypass In Adult Moyamoya Disease
Authors: Miyamoto Michiyuki , Kuroda Satoshi , Nakayama Naoki , Kazumata Ken , Houkin Kiyohiro
Published: March 2022

Background —
Indirect bypass for moyamoya disease provides quite effective collaterals in most of pediatric cases, but in only a half of adult cases. However, the predictors for effective indirect bypass in adult cases are still unclear. This study was aimed to evaluate the factor that predicts the effectiveness of indirect bypass in adult moyamoya disease.

Subjects and Methods —
This study included totally 26 adult patients (39 sides) who underwent STA-MCA anastomosis and EDMAPS (encephalo-duro-myo-arterio-pericranial synangiosis) since 2000 in Hokkaido University Hospital. There were 6 males and 20 females. Their age ranged from 30 to 71 years. Clinical diagnosis was TIA/cerebral infarct in 30 sides, intracranial hemorrhage in 6, and asymptomatic in 3. Cerebral hemodynamics and metabolism were measured with
123
I-IMP SPECT and
15
O-gas PET before and after surgery. On postoperative cerebral angiography, the development of indirect bypass was judged as good, when it covers more than 2/3 in the MCA territory. Uni- and multivariate analysis was employed to extract the predictors for the well-developed indirect bypass.

Results —
The development of indirect bypass was judged as good in 21 (53.8%) of 39 sides on postoperative cerebral angiography. Univariate analysis revealed that the advanced stage (p=0.018), ischemic onset (p=0.014), low cerebral blood flow (p=0.022) were significant predictors for good indirect bypass. Multivariate analysis demonstrated that the advanced stage on preoperative cerebral angiography can predict the good development of indirect bypass (p=0.025, OR=2.314, 95% CI=1.110~4.824).

Conclusions —
These findings strongly suggest that indirect bypass may provide effective surgical collaterals through indirect bypass in adult patients with advanced stage of moyamoya disease.
Abstract TMP43: Ischemic Stroke Hospitalization Rates by State and Age
Authors: Lichtman Judith H , Leifheit-Limson Erica C , Wang Yun , Goldstein Larry B
Published: March 2022

Background:
Medicare data show regional differences in stroke hospitalizations for older patients, but data on regional patterns for younger patients are limited. We assessed geographic patterns of ischemic stroke hospitalizations rates by state for younger and older U.S. adults.

Methods:
Ischemic stroke hospitalizations (ICD-9 433, 434, 436) were identified using the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project (HCUP) for 2007-2008. Rates were expressed per 100,000 person-years (P-Y) with state-level age- and sex-specific Census data as a denominator. A hierarchical random effects Poisson model estimated state-specific risk-adjusted rates, adjusting for age-sex and applying HCUP sampling weights. Bootstrapping simulation was used to obtain interval estimates of rates for each state and age group (18-64 and 65+). Rates were categorized as being significantly higher, no different, or significantly lower than the national average based on their interval estimates.

Results:
More than half of strokes in older patients occurred in women (54.4%) compared to 43.5% in younger patients. The prevalence of many comorbidities (COPD, HF, HTN, and renal failure) was expectedly higher for older patients, but the prevalence of diabetes was higher in the younger group (36.2% vs. 30.5%, p<0.001). The overall stroke hospitalization rate was 93 per 100,000 P-Y in the younger group and 1134 per 100,000 P-Y for those 65+ yrs. Ten states’ classifications differed between age groups indicating moderate state-level variance, with rates above the national average tending to cluster in the southeast (figure).

Conclusion:
Geographic patterns of hospitalization were moderately different for younger and older patients with ischemic stroke. Understanding factors contributing to regional heterogeneity may help target areas in need of improved stroke prevention interventions.
Abstract TMP44: Incidence and Case Fatality at the County Level as Contributors to Geographic Disparities in Stroke Mortality: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Labarthe Darwin R , Howard George , Peace Fredrick , Safford Monika M , Howard Virginia J , Cushman Mary , Kissela Brett M
Published: March 2022

Introduction:
The CDC provides smoothed county-level estimates of stroke mortality, with higher mortality in the Southeastern Stroke Belt, but showing substantial heterogeneity of both within and outside the Stroke Belt. It is unknown if geographic variations in stroke mortality are attributable to geographic variations in incidence of stroke or case fatality from stroke.

Methods:
The CDC county-level estimated stroke mortality was the primary predictor variable. After adjustment for demographics, the hazard ratio (HR) of death from stroke in REGARDS (having an adjudicated stroke and dying within 90-days) was estimated for 1/1,000 difference in CDC county-level stroke mortality. The risk of incident stroke was similarly characterized by the HR for any adjudicated stroke (fatal or non-fatal), and case fatality estimated by the odds ratio for death within 90-days of an adjudicated stroke.

Results:
CDC-reported county-level stroke mortality (per 1,000/yr) averaged 0.91 (range 0.26 - 2.52) for whites and 1.37 (range 0.50 - 3.32) for African Americans (AA). Over a 5.6 year average follow-up of 27,721 participants stroke-free at baseline (16,528 whites/11,193 AAs), there were 716 (415 in whites/301 in AAs) incident strokes; 125 were fatal (70 in whites/55 in AAs). Risk of death from stroke was marginally (HR = 1.83; p = 0.10) higher in counties with higher CDC-reported stroke mortality, potentially more so for whites than blacks (HR = 2.59 and 1.48 respectively). Both incidence and case fatality contributed to this higher risk, but the contribution of case-fatality may be larger for whites and incidence appears larger for AA.

Conclusions:
REGARDS participants living in counties with higher CDC-reported stroke mortality appear to be at greater risk of death from stroke, with higher incidence and case-fatality potentially contributing to higher mortality. In addition, there may be racial differences in the contribution of incidence and case fatality to stroke mortality.
Abstract TMP53: Elevated Blood Pressure Precedes Arterial Stiffening in Young Adults: The Bogalusa Heart Study
Authors: Chen Wei , Li Shengxu , Srinivasan Sathanur R , Fernandez Camilo , Xu Jihua , Berenson Gerald S
Published: March 2022

Introduction:
Elevated blood pressure (BP) and arterial wall stiffness are key aspects of essential hypertension. However, it is not clear whether elevated BP is a cause or the consequence of arterial wall stiffness or whether they influence each other during the aging process. This study assessed the temporal relationship between BP and arterial wall stiffness in a longitudinal study cohort.

Methods:
The study cohort consisted of 446 adults (342 whites and 104 blacks; age=32-51 years) enrolled in the bogalusa Heart Study. BP and aorta-femoral pulse wave velocity (PWV) were measured at two time points over 6.8 years. A cross-lagged analysis model was performed to examine the temporal relationship between BP and PWV.

Results:
Baseline vs follow-up values of systolic BP (113 vs 115 mmHg), diastolic BP (77 vs 80 mmHg) and PWV (5.1 vs 6.9 m/msec) increased significantly over 6.8 years. Systolic and diastolic BP and PWV values were adjusted for age, sex and race and standardized to Z-scores prior to the cross-lagged analysis. As shown in the figure, the difference between the two cross-lagged path coefficients (0.16 vs 0.04) was marginally significant (p=0.071 for difference). The cross-lagged path coefficient (0.15) from baseline diastolic BP to follow-up PWV was significantly greater than the coefficient (0.02) from baseline PWV to follow-up diastolic BP (p=0.05 for difference). In the model with baseline and follow-up BMI included, the difference between the two cross-lagged path coefficients was significant (systolic BP: 0.17 vs 0.03, p=0.035 for difference; diastolic BP: 0.16 vs 0.01, p=0.024 for difference).

Conclusions:
These findings suggest that elevated BP precedes arterial stiffening, but arterial stiffness does not increase BP in young adults, thereby providing evidence that elevated BP accelerates arterial stiffening process due to increased “wear and tear” on the artery walls and subsequently muscle cell hypertrophy during the period of young adulthood.
Abstract TMP61: The Impact of New Comprehensive Stroke Centers (CSCs) on Ischemic Stroke Treatment Rates
Authors: Shahripour Reza B , Albright Karen C , Boehme Amelia K , Lyerly Michael J , Martin-Schild Sheryl , Gonzales Nicole R , Savitz Sean I , Grotta James C , Alexandrov Anne W , Alexandrov Andrei V
Published: March 2022

Introduction:
We aimed to compare established and new CSCs with respect to treatment rates and safety over time. We also hypothesized that a ceiling effect would be observed prompting consideration of how additional patients could be brought to treatment.

Methods:
Data were assembled from consecutive ischemic stroke patients admitted to one established (Site 1 with a multisite telemedicine system) and two start-up academic CSCs (Sites 2 and 3 without telemedicine) with vascular neurology fellowship-trained leadership and the launch of 24/7/365 services. All centers met Brain Attack Coalition criteria for CSCs. Patient volume, IV tPA and sICH rates were compared over time.

Results:
In 2005-2011, 4017 ischemic strokes were admitted to Site 1. After the start of new leadership (2008-2011), Site 2 had 912 admissions and Site 3 had 1499 admissions. After very rapid initial growth (Figure), all three centers continued to increase stroke admission volumes by factors ranging from 1.8 to 3.6. However, IV tPA treatment rates increased at a steadier pace (1.05-1.6), diminishing at times but still ahead of published national average rates. No significant increase in sICH rates occurred (p=0.49, p=0.75). The established center treated more patients within the 3 hr time window (75% vs 61% vs 59%; p≤0.007).

Conclusions:
The launch of 24/7/365 vascular neurology driven CSCs resulted in rapid and safe increases in IV tPA treatment well above average rates reported nationally. Start-up CSCs will require telemedicine and continuing outreach to more spoke sites to achieve higher and earlier treatment rates. The reported growth in stroke admissions is not paralleled with equally proportionate increase in treatment rates across established and start-up centers suggesting a ceiling effect, and reasons for this effect including proliferation of PSCs with low treatment rates deserve further investigation.
Abstract TMP62: Safety and Efficacy of Endovascular Treatment in the “Hub and Spoke Model”
Authors: Hassan Ameer E , Adil Malik M , Rahim Basit , Chaudhry Saqib A , Cordina Steve M , Khatri Rakesh , Qureshi Adnan I
Published: March 2022

Background:
There are three different pathways for receiving endovascular treatment: primary ED arrival, in-patient, and outside transfer. Each mode has unique attributes that influence the performance and possibly the results of endovascular treatment in acute ischemic stroke patients.

Objective:
To compare the rates of various outcomes among patients who receive endovascular treatment through primary ED arrival, in-patient, and outside transfer modes.

Methods:
We performed a review of acute ischemic stroke patients presenting to our facility who received endovascular treatment from 2004 until 2012. Patient route (ER, inpatient, transfer), rates of poor outcome at discharge (modified Rankin score [mRS] of >3), intracerebral hemorrhages (ICH), as well as patients’ clinical characteristics were obtained and analyzed.

Results:
Among the total 336 patients that underwent IA thrombolysis, 68 patients (mean age 69.1± 16.6; 54% men) were transferred, while 38 patients (mean age 61.1± 14.5; 58% men) were in-patient strokes. Demographics, clinical characteristics, and outcomes are detailed below (Table 1 & 2). The mean admission NIHSS was significantly higher in the transferred patients (16.2± 9.5 versus 15.5± 6.2, p<0.001), though there was no difference in discharge NIHSS. After adjusting for all potential confounders there was no significant difference in good outcomes (odds ratio [OR] 2.0 95% Confidence interval [CI] 0.9-4.3, p=0.06), ICH (OR 0.6 95% CI 0.3-1.3, p=0.2), or mortality (OR 0.6 95% CI 0.3-1.4, p=0.2) between ER patients and transferred patients.

Conclusions:
Despite the increased baseline stroke severity, there appears to be no significant risk of increased poor outcomes, ICH, or mortality in acute ischemic stroke patients transferred to endovascular centers. This further justifies the safety and efficacy of the hub and spoke model.
Abstract TMP64: Development of a Thrombolysis Protocol for Acute Ischemic Stroke Patients Treated with Dabigatran.
Authors: KATE MAHESH P , SZKOTAK ARTUR , WITT ADAM , SHUAIB ASHFAQ , BUTCHER KENNETH
Published: March 2022

Introduction:
Acute ischemic stroke thrombolysis in patients taking dabigatran is controversial, due to a presumed increased risk of symptomatic hemorrhagic transformation. The lack of a standardized test of anticoagulant activity or defined coagulation markers to select patients safely, makes thrombolysis in dabigatran treated patients challenging. Using data from our hematopathology laboratory, we aimed to develop a protocol for selection of thrombolysis candidates amongst acute ischemic stroke patients taking dabigatran.

Method:
A thrombin time (TT)-dabigatran concentration curve was calculated using dabigatran plasma calibrators (Aniara, West Chester, OH). The effect of dabigatran on activated partial thromboplastin time (aPTT) was also calculated. A table of dabigatran concentration, TT and aPTT was produced and distributed to all stroke team members. A protocol was developed, in which a dabigatran concentration of <47 ng/ml (corresponding to a TT <19.7 s and aPTT <37 s) was selected as the upper limit for safe thrombolysis. In tertiary stroke centres, a TT and aPTT were both ordered, while in peripheral telestroke centres, the aPTT alone was used to determine dabigatran activity.

Results:
In the 4 months since development of the protocol, eight potential thrombolysis candidates taking dabigatran were assessed with CT at a median (IQR) time of 192 (143) minutes. The median NIHSS was 16 (12). Based on TT/aPTT, only 2 patients were ineligible for thrombolysis (dabigatran concentrations >118 ng/ml). Another three patients were not treated due to minor/resolving symptoms and a fourth due to intracerebral hemorrhage. Two patients were treated with intravenous tPA (0.9 mg/kg). A repeat CT head at 24 hours revealed no hemorrhagic transformation in one patient and asymptomatic petechial hemorrhagic transformation (European Cooperative Acute Stroke Study Grade Hemorrhagic Infarction Type 1) in the other.

Conclusion:
It is possible to safely administer intravenous tPA in dabigatran treated patients, provided a reliable method of measuring anticoagulant activity is available. Although, TT and aPTT dabigatran concentrations do vary between laboratories, individual protocols can and should be developed at acute stroke treatment centres.
Abstract TMP65: Endovascular and Surgical Treatment of Subarachnoid Hemorrhage Patients in Trauma Setting: Analysis from National Trauma Data Base (NTDB)
Authors: Majidi Shahram , Adil Malik M , Rahim Basit , Watanabe Masaki , Qureshi Adnan I
Published: March 2022

Background:
Traumatic subarachnoid hemorrhage (tSAH) occurs in up to 60% of patients with traumatic brain injury (TBI) and is associated with higher death and disability in TBI patients. Vascular injury in the form of aneurysms, dissections, and transections may require treatment to prevent further bleeding episodes. We aimed to compare endovascular treatment with surgical treatment in tSAH patients.

Methods:
tSAH and related endovascular and surgical procedures were identified by ICD-9-CM codes from the National Trauma Data Bank (NTDB), using data files from 2009 to 2010. NTDB represents one of the largest trauma databases and contains data from over 900 trauma centers across the United States. Surgical and endovascular treatment groups were compared by variables of patient demographics, initial injury severity score (ISS) and Glasgow Coma Scale (GCS) assessment in the emergency department (ED), hospital course, and treatment outcomes.

Results:
A total of 119 tSAH patients were identified who required treatment for intracranial vascular injury. Of these, 53% received endovascular treatment and 47% were treated surgically. No differences in demographic characteristics between these two groups were observed. The mean Injury Severity Score (ISS) [23(19-26) versus 15(12-18); P=0.03] and frequency of skull base fracture (30% versus 2%; P<.0001) were significantly higher in the endovascular treated group than in surgical group. Admission GCS scores were also significantly lower in the endovascular treated group (P=0.007). ICU days in the endovascular treatment group were significantly lower than in the surgical group [14(10-17) versus 16(13-17); P=0.04]. ICU days remained significantly lower in the endovascular group after adjusting for admission GCS, ISSAIS, skull base fracture, and other characteristics [0.4 (0.2-0.8); P=0.009]. Although the mean length of hospital stay was 3 days less in the endovascular group, this difference was not statistically significant.

Conclusion:
Despite more severe injury and lower admission GCS scores, patients who received endovascular treatment had lower ICU day requirement and similar discharge outcomes. Such observations support the preferential use of endovascular treatment in trauma settings.
Abstract TMP72: L-carnitine Enhances Axonal Plasticity Via Akt/mammalian Target Of Rapamycin Pathway In A Rat Chronic Cerebral Hypoperfusion
Authors: Ueno Yuji , Shimura Hideki , Hattori Nobutaka , Urabe Takao
Published: March 2022

Background and Purpose:
Chronic cerebral hypoperfusion (CCH) induces white matter lesions with oligodendrocytic damage and causes cognitive impairment. Oxidative stress has been elucidated as a pivotal role of its pathophysiology. Damage of axon can be also involved in CCH, however, mechanisms that associated with axonal damage under CCH have not been fully studied. In the present study, we analyzed axonal plasticity and damage of oligodendrocytes in a rat CCH model using L-carnitine, antioxidant agent.

Methods:
Adult rats subjected to ligation of bilateral common carotid artery (LBCCA), were randomly divided into two groups: vehicle-treated rats; and L-carnitine-treated rats (600mg/kg/day), and were sacrificed at 7, 14, 21 and 28 days after LBCCA (n=7/group). Sham operated rats (n=7) were used as a control group. The Morris water maze was performed to evaluate spatial learning and memory tasks, and immunohistochemical and Western blot analysis were studied.

Results:
Rats subjected to LBCCA substantially increased escape latency on the Morris water maze in a time-dependent fashion. L-carnitine-treated rats significantly reduced escape latency compared to vehicle-treated rats at 28 days after LBCCA (P<0.05). Protein levels of phosphorylated neurofilament heavy protein (pNFH), a marker of axons, were reduced after LBCCA, however, L-carnitine significantly increased pNFH levels compared to levels in vehicle-treated rats at 28 days after LBCCA (P<0.01). Concurrently, increases of phosphorylated Akt (P<0.05) and mammalian target of rapamycin (mTOR) (P<0.05) were detected in L-carnitine-treated rats compared to vehicle-treated rats at 28 days after LBCCA. 4-hydroxy-2-nonenal (HNE)+ and 8-hydroxy-deoxyguanosine (8-OHdG)+, markers of oxidative stress, oligodendrocytes substantially increased until 28 days after LBCCA (P<0.001). L-carnitine-treated rats significantly reduced HNE+ and 8-OHdG+ oligodendrocytes at each time point after LBCCA (P<0.001).

Conclusion:
Our results indicated that L-carnitine increased axonal plasticity via Akt/mTOR pathway and ameliorated oxidative stress in oligodendorocytes damaged by LBCCA, and thereby resulting an improvement of cognitive impairment in a rat CCH model.
Abstract TMP76: Earlier And Later Recovery After Acute Ischemic Stroke By Immediate Recanalization
Authors: Kim Beom Joon , Yoon Susie , Kang Jihoon , Jang Min Uk , Hong Jeong Ho , Han Moon-Ku , Park Seong-Ho , Bae Hee-Joon
Published: March 2022

Backgrounds:
Recanalization in acute ischemic stroke patients is alleged to improve functional outcomes, but its influence on early or late recovery has not been elaborated yet. The aim of this study is to evaluate the association between recanalization within 24 hours after onset and recovery pattern in earlier or later period after stroke.

Methods:
From a total of 5602 acute ischemic stroke patients who had admitted to our stroke center over 8-year period, we selected 462 cases documented to have steno-occlusive major arteries and received revascularization treatment. We excluded 122 subjects due to in-hospital mortality, loss of functional outcome information and lack of post-thrombolytic angiography evaluations within 24 hours. Recanalization was blindly and independently evaluated by two authors (BJK and SY) with excellent agreement (κ=0.85). Post-thrombolytic angiography of TICI grade ≥2a and MR or CT angiography of ≤70% stenosis were considered to be recanalized. mRS score at 3 month was collected through structured telephone interview. Early neurological improvement (ENI) was defined to have decreased NIHSS score ≥4-point over hospitalization period, and late recovery was rated using difference of mRS score between at the time of discharge and at 3-month after stroke onset.

Results:
Of a total of 340 analyzed cases, 88 (26%) cases were treated with IV thrombolysis, 129 (38%) with IA revascularization, and 123 (36%) with combined IV and IA revascularization. Immediate recanalization within 24 hours occurred in 261 (77%) subjects. ENI was detected in 185 (54%) subjects. Late improvement (mRS score difference ≥1) was documented in 132 (39%) cases, fixed deficit (difference =0) in 145 (43%), late aggravation (difference ≤-1) in 63 (19%), and mortality in 26 (7.6%). After adjusting for relevant covariates, immediate recanalization remained significant with increased odds of having ENI (adjusted OR, 2.51; 95% CI, 1.39 - 4.53) and with decreased odds of having late aggravation (adjusted OR, 0.38; 95% CI, 0.19 - 0.75); but not with late improvement (adjusted OR, 1.50; 95% CI, 0.81 - 2.80).

Conclusion:
We documented that beneficial effects from immediate recanalization were associated with earlier improvement and with deterrence of later deterioration.