bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP398: In-Hospital Mortality: Is the Rate Associated with Hemicraniectomy Changing Over Time?
Authors: Khoury Philip R , Sucharew Heidi , Khoury Jane C
Published: March 2022

Introduction:
Although there are recent data which suggest that surgical decompression can reduce mortality in patients with acute ischemic stroke (AIS), hemicraniectomy has remained a hot topic in stroke care, with candidates for this procedure at high risk for excessive morbidity and mortality. We determined in-hospital mortality rates for patients with AIS undergoing hemicraniectomy, and compared these rates to those reported previously.

Methods:
Data from the National Inpatient Sample (NIS), a nationwide administrative database for the year 2009 (>7,800,000 US hospital admissions), and the associated ICD-9-CM diagnosis and procedure codes were used to identify patients. We examined in-hospital mortality associated with hemicraniectomy, with and without thrombolysis in patients admitted emergently, having a discharge diagnosis of acute ischemic stroke and/or precerebral arterial occlusion (multi-level clinical classification software codes 109 and 110).

Results:
From 114982 adult patients (53% Female) with AIS, 118 (0.1%) underwent hemicraniectomy, and 3115 (2.7%) were treated with thrombolysis. Compared with the nonsurgical group, patients treated with hemicraniectomy were younger (mean age 55 vs. 72 years), but had a higher inpatient mortality rate (25% vs. 7%). In patients treated with thrombolysis, mortality was also higher in the hemicraniectomy group compared to the nonsurgical group (27% vs. 10%). Stroke associated complication rates for systemic sepsis (9% vs. 2%) and aspiration pneumonia (9% vs. 4%) were higher in the hemicraniectomy-treated patients. Median cost per stay was $170,600 in the hemicraniectomy treated patients vs. $25,100 nonsurgical. The 2009 mortality rate in hemicraniectomy-treated patients was lower than previously reported in NIS cohorts from 2000-2006 (25% vs. 32%).

Conclusion:
In-hospital mortality remains high for patients treated with hemicraniectomy, but appears to have declined from previous years. Despite the fact that candidates for hemicraniectomy are by definition at very high risk for excessive morbidity and mortality, use of databases such as the NIS can supply valuable information on demographics and trends for inpatient outcomes, and the associated costs.
Abstract WP407: Physician Knowledge Regarding Transcranial Doppler Screening Recommendations Among Children with Sickle Cell Disease
Authors: Reeves Sarah L , Fullerton Heather J , Dombkowski Kevin J , Lisabeth Lynda D
Published: March 2022

Background:
Transcranial Doppler (TCD) screening for stroke prevention among children with sickle cell disease (SCD) is recommended by the National Heart, Lung and Blood Institute (NHLBI); however, screening rates remain low. Little is known about provider knowledge of TCD recommendations. We explored knowledge of current TCD recommendations for children with SCD among pediatric hematologists and neurologists across the US, as well as pediatric primary care physicians (PCPs) of children with SCD in Michigan.

Methods:
Pediatric hematologists and neurologists (n=250 each) were sampled from the American Medical Association Masterfile, a listing of all US physicians. PCPs were pediatricians/family physicians treating children with SCD in Michigan identified through Medicaid claims 2008-2012 (n=206). A mailed survey was administered May 2012 with a 6 week follow-up to non-respondents. The survey included 6 questions regarding knowledge of TCD recommendations based on age and SC subtypes, as well as actions to take based on TCD results. The proportion of correct responses was classified based on NHLBI guidelines and compared across specialty using Fisher’s exact tests.

Results:
Among 638 deliverable surveys, 244 (38%) were returned (83 neurologists, 89 hematologists, 72 PCPs) and 103 indicated the respondent currently treats children with SCD and believes children with SCD should receive TCD screening. Among these respondents, 76% recommend TCD screening and 24% of the knowledge questions were answered correctly (Table 1). Differences in proportion correct overall and for specific questions were noted across specialty, with hematologists having the highest proportion correct.

Conclusions:
Although the majority of physicians recommend TCD screening, knowledge of specific TCD recommendations is low. Opportunities to improve knowledge of TCD recommendations span each physician specialty sampled, but are especially evident among PCPs and neurologists.
Abstract WP415: Prevalence Of Cerebrovascular Events In Patients With Left Ventricular Assist Device - Continuous Flow And Pulsatile Flow Devices Compared
Authors: Yoshioka Daisuke , Toda Koichi , Yoshikawa Yasushi , Sakaguchi Manabu , Okazaki Shuhei , Miyagawa Shigeru , Nishi Hiroyuki , Fukushima Satsuki , Saito Tetsuya , Sawa Yoshiki
Published: March 2022

Background:
A continuous flow left ventricular assist device (c-LVAD) provides a better clinical outcome for patients with severe heart failure than pulsatile flow LVAD (p-LAVD). However, the frequency of cerebrovascular events, crucial complications, is largely unknown, especially in patients with systemic infection. We examined the prevalence of stroke related to systemic infection in patients with these 2 LVAD types.

Methods:
We reviewed 114 consecutive patients (c-LVAD group: n=47, 66.6 patient-years; p-LVAD group: n=67 patients, 63.5 patient-years) who received LVAD support at Osaka University Hospital from 2005-2012. Cerebrovascular complications were defined as a neurological deficit concomitant with a coinciding lesion shown by computed tomography. Anticoagulation was given according to the manufacturer’s recommendation. Stroke frequency was compared between the groups.

Results:
During LVAD support, 8 patients (c-LVAD, 1; p-LVAD, 7) died from stroke. As for cerebral infarctions, 10 events in 5 patients occurred in the c-LVAD group and 29 in 23 in p-LVAD (0.15 vs. 0.46 events/patient-year, p=0.02). For intracranial hemorrhage including cerebral parenchymal and subarachnoid hemorrhage, 21 events in 16 patients occurred in the c-LVAD group and 30 in 23 in p-LVAD (0.31 vs. 0.47 events/patient-year, P=0.15). The prevalence of ICH was 0.05%/patient-day in patients without systemic infection. In contrast, those in the c-LVAD group had a bloodstream infection develop into ICH as follows: 0.67%/patient-day within 2 weeks, 0.39%/patient-day from 2-4 weeks, 0.13%/ patient-day more than 4 weeks after bloodstream infection, while those were 0.67%, 0.24%, and 0.04%, respectively, in the p-LVAD group.

Conclusions:
Continuous flow LVAD decreases cerebral infarction frequency, though ICH frequency remains poor. Notably, even in c-LVAD group, bloodstream infection elevates ICH risk in the acute phase and its frequency was almost similar with p-LVAD group. Careful management of anticoagulation is also required for patients with continuous flow LVAD especially in acute phase of blodd stream infection.
Abstract WP418: Insurance Status Influences Blood Pressure Control among Stroke Survivors in the United States
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce
Published: March 2022

BACKGROUND:
Hypertension is the premier modifiable risk factor for stroke. After a stroke, poorly controlled blood pressure (BP) is associated with a higher risk of recurrent vascular events; however, less than half of stroke survivors in the US have BP in the normal range. Uninsured and under-insured adults generally have less access to recommended care and receive poorer quality of care, but it is unclear to what extent insurance status affects BP control after stroke.

METHODS:
We assessed BP control among adults (≥20 years) with a history of stroke who participated in the National Health and Nutrition Examination Surveys from 1999 through 2010. The relationship between insurance type and BP control (ideal: <120/80 mm Hg and good: <140/90 mm Hg) was evaluated using logistic regression before and after adjusting for age, sex, race, body mass index, household income, history of hypertension and major comorbidities, and NHANES cycle.

RESULTS:
Of an estimated 2,253,394 stroke survivors <65 years, 47% had private insurance, 19% were uninsured, 10% had Medicaid, 10% had Medicare, 8% had other government insurance, and 4% had Medicare and Medicaid. Among an estimated 2,927,596 stroke survivors aged ≥65 years, 38% had Medicare, 44% had Medicare and Medicaid, 8% had private insurance, and the remainder had Medicaid, other government insurance, or were uninsured. Overall, 28% of stroke survivors exhibited ideal BP control and 61% of stroke survivors had good BP control. Insurance type was not associated with ideal BP control. However, among stroke survivors <65 years, those with Medicaid were more likely than those who were uninsured to have good BP control (HR 2.41, 95% CI 0.87-6.68; p=0.09). Among stroke survivors ≥65 years, those with a combination of Medicare and private insurance had greater odds of good BP control compared to persons with Medicare insurance alone (HR 1.39, 95% CI 0.97-2.00, p=0.07).

CONCLUSIONS:
Depending on age and insurance type, uninsured or underinsured stroke survivors in the US tend to have lower odds of good BP control. Recent legislation to expand insurance coverage may help bridge these disparities, but intensified efforts aimed at enhancing clinician communication and promoting self-management among these patients may also be warranted.
Abstract WP420: Plasma Interleukin-6 Predicts the Progression of Carotid Intima-Media Thickness in High-Risk Patients Under Intensive Medical Therapy: 10-year Follow-up Study
Authors: Okazaki Shuhei , Furukado Shigetaka , Miwa Kaori , Sakaguchi Manabu , Mochizuki Hideki , Kitagawa Kazuo
Published: March 2022

Purpose:
Although carotid intima-media thickness (IMT) is widely used as a surrogate marker for atherosclerosis, the relationship between long-term IMT progression and plasma inflammatory cytokine levels is only partially clarified. We prospectively investigated the association of 10-year IMT progression and mean circulating levels of inflammatory cytokine during follow-up in atherosclerotic high-risk patients with intensive management of conventional risk factors.

Methods:
We prospectively evaluated 207 atherosclerotic high-risk patients who continued to attend our ambulatory care center and underwent carotid ultrasound in 2001-2003 and in 2010-2012. Participants had to have a previous diagnosis of cardiovascular disease, diabetes, hypertension, dyslipidemia, or current smoking. All participants consecutively received intensive medical treatment and the management of risk factors was evaluated by mean values of annual physical examination and blood tests, including high-sensitive C-reactive protein (hsCRP), interleukin (IL)-6, and IL-18.

Results:
The mean baseline age was 64±8 years, and the mean follow-up period was 9.0±1.0 years. Conventional risk factors were generally well-controlled during follow-up period; mean blood pressure was 134±9/76±7mmHg, mean total cholesterol level was 204±23 mg/dl, and mean HbA1c (JDS) was 5.6%±0.7%. IMT increased 0.28±0.24 mm throughout the observation period. IMT progressions was positively correlated with baseline IMT, age, male sex, mean plasma glucose, HbA1c, hsCRP, IL-6, and IL-18 levels during follow-up, and negatively correlated with mean diastolic blood pressure levels. In multiple regression analyses adjusted for age, sex, conventional risk factors and statin use, mean plasma IL-6 (β=0.39, p=0.047) together with baseline IMT (β=0.45, p=0.044) and mean HbA1c (β=0.21, p=0.0038) were independently associated with IMT progression.

Conclusion:
In atherosclerotic high-risk patients under intensive medical therapy, mean plasma IL-6 level during follow-up period was an independent predictor of IMT progression.
Abstract WP427: Day Eight CT Perfusion Imaging for Evaluation of Delayed Cerebral Ischemia Risk and Decreased Length of Stay Following Aneurysmal Subarachnoid Hemorrhage
Authors: Malaiyandi Deepa , Pandya Dhruvil J , Lynch John R
Published: March 2022

Objective:
Hospital stay alone accounts for 2/3 the cost of aneurysmal subarachnoid hemorrhage (aSAH) management. Our objective was to assess the ability of CT perfusion (CTP) imaging to predict delayed cerebral ischemia (DCI) risk in those who are neurologically intact in order to safely decrease the length of hospital stay for low risk aSAH patients.

Methods:
A retrospective analysis of all aSAH admitted to our neurological intensive care unit (NICU) from 3/2011-3/2012. Per our protocol all patients were admitted to the NICU for 10 days followed by a 4 day ward admission. Additionally, all patients underwent a CTP study on post-bleed day 8 to screen for evidence of radiographic vasospasm. DCI was defined as the presence of neurological deficit not attributable to other etiologies. All CTP images were interpreted by a Neuroradiologist. CTP was considered positive if there was evidence of match or mismatch. Mismatch was defined as decreased cerebral blood flow or increased mean transit time with associated blood volume loss of <20%.

Results:
A total of 58 aSAH were admitted. Day 8 CTPs were performed on 42 (72%) with 71% female, mean age 52.21 (±13.25), mean Fisher 3.38 (2-4) and mean Hunt/Hess 2.39 (1-5). Eighteen (43%) patients had negative CTPs with baseline neurological exams. None of these 18 patients went on to develop DCI during their 14 day admission.

Conclusion:
Our data shows that aSAH patients who are neurologically intact and have a negative post-bleed day 8 CTP are not at risk for DCI. We conclude that an 8 day NICU admission with an additional 2 day in-patient stay is sufficient to safely manage this patient population. Our data is limited by a small sample size and retrospective analysis. Future directions of research include additional prospective studies for reproducibility.
Abstract WP432: Availability of Biplane Angiographic Units Within Hospitals and Outcomes of Patients with Ischemic Stroke or Subarachnoid Hemorrhage-Results of a State Wide Study
Authors: Rahim Basit , Gilani Waqas I , Gilani Sarwat I , Adil Malik M , Qureshi Adnan I
Published: March 2022

Background:
The Brain Attack Coalition identified the availability of neuro-endovascular procedures as an essential component of a comprehensive stroke center. However, there is minimal data regarding availability of angiographic suites within hospitals in a population based study.

Methods:
Statewide estimates of stroke admissions and outcomes, cervicocerebral angiograms, thrombolysis, endovascular ischemic stroke treatments, carotid angioplasty and stent placement or endarterectomy, intracranial angioplasty and stent placements, and endovascular or surgical treatment of intracranial aneurysms per hospital based on availability of monoplane or biplane angiographic suites were obtained. The availability was determined by database of any diagnostic x-ray system installation mandated under Subchapter C - Electronic Product Radiation Control of Food and Drug Administration.

Results:
A total of 15699 (13 hospitals), 16540 (9 hospitals), and 15321(114 hospitals) ischemic stroke patients were admitted to hospitals with monoplane, biplane, and no angiographic suites, respectively. The rate of any thrombolysis (p<0.001) and thrombectomy (p<0.001) was significantly lower in hospitals without any angiographic suites. The rate of none-to-minimal disability was significantly lower among patients in hospitals without angiographic suites (52% versus 65% and 66%, p<0.001). Of the subarachnoid hemorrhage patients, 722, 1006, and 296 were admitted to hospitals with monoplane, biplane, and no angiographic suites, respectively. The rate of both surgical (p<0.001) and endovascular (p<0.001) treatments for intracranial aneurysms was significantly higher among hospitals with biplane angiographic suite. The in- hospital mortality was significantly lower among patients treated at hospitals with biplane angiographic suite (13%) versus those treated at facilities with monoplane (24%) and no angiographic suites (27%, p<0.001).

Conclusions:
Availability of biplane angiographic units within hospitals was associated with better outcomes and lower mortality in patients with ischemic stroke or subarachnoid hemorrhage. However, a large proportion of such patients continue to be admitted to hospitals without such capabilities.
Abstract WP436: Plasma Inflammatory and Endothelial Activation Markers Are Associated with Carotid Intima Media Thickness in HIV-infected Individuals on Stable Antiretroviral Therapy
Authors: Parikh Nisha I , Chow Dominic C , Jalbert Emily , Ndhlovu Lishomwa , Barbour Jason , Liang Chin Yuan , Nakamoto Beau K , Shikuma Cecilia
Published: March 2022

Background:
Stroke risk is increased among HIV-infected persons on stable antiretroviral therapy (ART). Inflammatory cytokines and/or endothelial activation factors caused by HIV or other factors may confer risk beyond traditional cardiovascular (CVD) risk factors. Carotid intima-media thickness (cIMT) is associated with increased stroke risk. We assessed the hypothesis that soluble plasma inflammatory and endothelial activation biomarkers would be associated with cIMT independent of the Framingham Risk Score Category (FRSC), low: <10%, medium: 10-20%, high: >20% 10 year risk of CVD.

Methods:
Cross-sectional analyses were done in HIV+ subjects age > 40 years on > 6 months stable ART, without prevalent CVD. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. CVD risk factors were collected and FRSC calculated. Plasma biomarkers were assayed by multiplex bead immunoanalysis. cIMT was log transformed to account for data non-normality. Univariate analyses were performed followed by sequential multivariate regression analyses for those showing significance with adjustment for age and FRSC.

Results:
Analyses were performed on 83 HIV+ subjects (n=72 males, median age 49 years, median CD4 Nadir 140, 72 with HIV RNA < 50, 51 with low FRSC, 12 medium FRSC , 20 high FRSC). In univariate analyses, there were significant associations between the following biomarkers and log cIMT: sVCAM-1, CRP, SAA, IL-6, IL-8, and VEGF. There were no significant associations observed for sE-selectin, sICAM-1, MMP-9, MPO, tPAI-1, SAP, IL-1b, IL-10, TNF-α, MCP1, IFN-γ, and NT-proBNP. When age and FRSC were included in the model for biomarkers showing univariate significance, log CRP
(
β=0.025; p=0.02), log SAA
(
β=0.028; p=0.01), log IL-8
(
β=0.083; p=0.05), and VEGF
(
β=0.0004; p=0.02) remained significantly associated with cIMT.

Conclusions:
In conclusion, the pro-inflammatory markers CRP, SAA, IL-8 and vascular activation marker, VEGF are associated with cIMT independent of age and traditional CVD risk factors in HIV-infected subjects on stable ART and suggest that inflammation and endothelial activation pathways involving these biomarkers may in part contribute to the excess stroke risk in HIV.
Abstract WP44: Acute Damage to Corticospinal Tract Detected by Diffusional Kurtosis Correlates with Motor Outcome at 3 Months After Stroke - A Preliminary Report
Authors: Feng Wuwei , Hui Edward S , Johnson Jenna-Lyn , Helpern Joseph A , Jensen Jens , Tabesh Ali , Bonilha Leonardo , Bowden Mark G , Kautz Steven , Adams Robert J
Published: March 2022

Background:
Diffusional kurtosis imaging (DKI) is a recently developed diffusion MRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis (K) and white-matter-specific metrics (WMM) that may better characterize tissue microstructure after stroke. This study aims to quantitatively test the hypothesis that motor impairment 3 months post- stroke is correlated with the acute damage to the corticospinal tract (CST) measured by kurtosis metrics.

Methods:
DKI was acquired from 15 first-time acute ischemic stroke patients in the acute phase (within 48 hours) with various degrees of motor deficit. Patients were assessed at baseline (between 2 to 5 days from onset of symptom) and at 90 days (+/- 14 days) after stroke using the Fugl-Meyer Motor Scale (FMMS). Kurtosis metrics, including WMM (intra-axonal diffusivity (D
a
), extra-axonal axial (D
e,//
) and radial (D
e,//
) diffusivity ) as well as fractional anisotropy (FA), mean diffusivity (MD), mean Kurtosis (MK) were measured in the lesional CST. Correlation analyses were applied among these metrics and FMMS at 90 days.

Results:
Corticospinal tract intra-axonal environment was altered by acute ischemia. D
a
( r = 0.75, p = 0.001) and D
e,//
( r = 0.52, p=0.048) measured in the acute phase correlated with motor outcome at 3 months. FA, MD, MK and D
e,//
showed no significant correlations.

Conclusions:
The preliminary data supports acute damage to CST detected by WMM with DKI correlated with motor outcome at 3 months. The WMM has potential to be an early imaging biomarker for motor outcome prediction.
Abstract WP440: Relaxin Selectively Affects Brain Parenchymal Arteriolar Structure during Hypertension
Authors: Cipolla Marilyn J , Sweet Julie , Chan Siu-Lung
Published: March 2022

Background:
Cerebral small vessel disease (SVD) is a common hypertension-related vasculopathy of the penetrating arterioles (PA) that causes lacunar stroke, white matter lesions and vascular dementia. We investigated the effect of chronic hypertension on PA structure and if treatment with relaxin, a hormone with cardioprotective effects previously shown to promote selective outward remodeling of PA in normotensive animals, could reverse these effects.

Methods:
Female SHR rats (n=7-8/group) were treated in vivo with relaxin (4μg/hr) or vehicle for 2 weeks and studied at 18 weeks of age. Aged-matched WKY rats were used as controls. Middle cerebral arteries (MCA) and PA from the same animals were isolated and studied under pressurized conditions in zero calcium buffer to obtain structural measurements. Blood pressures were measured using tail cuff after 3 days of training.

Results:
PA inner and outer diameters were smaller in SHR vs. WKY: at 100 mmHg PA inner and outer diameters were 59 ± 3 and 72 ± 3 μm for WKY vs. 50 ± 3 and 63 ± 3 μm for SHR (p<0.01). Relaxin treatment of SHR reversed this rarefaction such that inner and outer diameters were similar to WKY: 58 ± 4 and 69 ± 4 μm (p<0.01 vs. SHR; Figure). The increase in PA size with relaxin treatment was related to a large increase in distensibility (Figure). Percent distensibility of PA for WKY, SHR and SHR+relaxin was: 18 ± 3%, 13 ± 2% and 40 ± 4% (p<0.01). Relaxin treatment had no effect on MCA in SHR that were smaller than WKY: MCA inner and outer diameters were 258 ± 4 and 285 ± 5 μm in WKY, 228 ± 5 and 260 ± 5 μm in SHR and 225 ± 4 and 256 ± 4 μm in SHR+relaxin (p>0.05). Relaxin also did not lower blood pressures that were higher in SHR: MAP for WKY, SHR and SHR+relaxin was: 94 ± 3, 138 ± 2 and 144 ± 5 mmHg (p<0.01 vs. WKY).

Conclusion:
These results suggest that relaxin may be an effective treatment for hypertension-induced rarefaction and increased stiffness of PA that underlies SVD in the brain.
Abstract WP442: Oxidative Stress And Cyclic Strain Mediated Smad6 Regulation In Vascular Endothelial Cells Correlates With Autophagy Induction And Endothelial Dysfunction
Authors: Hayashi Shin-ichiro , Matsushita Hidetsugu , Kawano Yuhei , Tsao Philip S
Published: March 2022

Background:
Vascular endothelial cells (ECs) are subjected to enhanced-oxidative stress and -cyclic strain in hypertension, stroke and atherosclerotic vascular disease. The role for TGF-ß and bone morphogenic proteins (BMPs) has been implied in vascular development and vessel remodeling. Although endothelial specific regulation of their intracellular signaling protein Smad6 was observed under the stimuli of laminar shear stress, little is known about the function of Smad6 in adult vascular endothelium.

Methods:
Human aortic ECs were treated with H202 (10 to 100umol/L) or exposed to 7% uniaxial cyclic strain. For transient knock down, ECs were transfected with siRNA constructs against Smad6 and Smad7. Expression levels of Smad6 and Smad7 were measured by quantitative RT-PCR and western blotting analysis. NO production and BrdU labeling for proliferative cells were measured by ELISA assay. In vitro angiogenesis was evaluated in tube-formed ECs. The process of autophagy was analyzed by electron microscopy. Cells in survival or apoptosis were detected by immunofluorescence cell staining of HMGB1 or cleaved- caspase-3.

Results:
Exposure of ECs to 24 hours of oxidative stress or cyclic strain showed consistent reduction in Smad6 mRNA and protein, while no change in Smad7. Notably, electron microscopic analysis showed that knockdown of endogenous Smad6 expression induced “self-eating” autophagy after 24 hours of treatment, while silencing of Smad7 did not induce autophagy. Immunofluorescence cell staining showed that EC with silencing Smad6 were positive for HMGB1 but negative for cleaved caspase-3. Importantly, ECs with silencing Smad6 represented significant reduction in NO production, prolifereative activities and in vitro angiogenesis as compared to those with silencing Smad7. Furthermore, treatment with TGF-ß1, BMP-2, or BMP-4 did not show synergistic effects on autophagy induction and endothelial function after silencing Smad6.

Conclusions:
These data demonstrate a novel mechanism for functional regulation of Smad6 in vascular ECs, and indicate that dysregulation of Smad6 may have important implications in endothelial autophagy and endothelial dysfunction in the settings of hypertension, stroke and vascular inflammation.
Abstract WP443: KLF2 Protects Against Ischemic Stroke by Regulating Endothelial Blood Brain Barrier Function
Authors: Shi Hong , Sheng Baiyang , Zhang Feng , Zhang Rongli , Wu Chunying , Zhu Junqing , Jameson Stephen C , Lin Zhiyong , Wang Yanming , Chen Jun , Jain Mukesh K , Atkins G Brandon
Published: March 2022

Background
During an ischemic stroke normal brain endothelial function is abrogated resulting in blood brain barrier (BBB) breakdown with subsequent infiltration of activated inflammatory blood cells, ultimately leading to neuronal cell death. Kruppel-like factor 2 (KLF2) is regulated by flow, is highly expressed in vascular endothelial cells, and serves as a key molecular switch regulating endothelial function and promoting vascular health.

Purpose
To determine the role of KLF2 in ischemic stroke.

Methods and Results
—To examine the specific role of KLF2 in the brain and cerebrovascular disease, we performed ischemic strokes and conducted BBB assays in KLF2 deficient (K2-/-), KLF2 overexpressing (K2tg), and control mice. K2
-/-
mice exhibited larger strokes in the transient middle cerebral artery occlusion model (95% greater stroke volume vs. control; n=10-20/group; P=0.001) and significant impairment in BBB function as assessed by in vivo real time quantitative PET analysis and evans blue dye (EBD) assays (86% greater EBD permeability vs. control; n=3/group; P=0.002). In contrast, K2tg mice were protected against ischemic stroke (49% smaller stroke volume vs. control; n=8-9/group, P=0.004) and demonstrated less impairment in BBB function (30% less EBD permeability vs control; n=3/group; P=0.003). In concordance, gain and loss of function studies in primary brain microvascular ECs using transwell assays revealed KLF2 to be BBB protective (32% less permeability in adenoviral KLF2 overexpression vs. control; P=0.005 and 107% greater permeability in siRNA mediated KLF2 knockdown vs. control; P<0.0005). Mechanistically, KLF2 was demonstrated to regulate the critical BBB tight junction factor occludin, both in vitro (7.0±0.3 fold expression in adenoviral KLF2 overexpression vs. control; P<0.0001 and 0.43±0.03 fold expression in siRNA mediated KLF2 knockdown vs. control; P<0.0005) and in vivo (0.56±0.11 fold expression in K2
-/-
vs. control; n=4-7/group; P=0.01 and 2.5±0.5 fold expression in K2tg vs. control; n=3-4/group; P<0.05).

Conclusions
These data are first to identify KLF2 as a key regulator of brain endothelial function and cerebrovascular homeostasis, thereby serving as a novel neuroprotective factor in ischemic stroke.
Abstract WP447: Renal Failure Is Associated With Cognitive Impairment In Ischemic Stroke Patients
Authors: Zurru Maria C , Alonzo Claudia , Brescacin Laura , Villarroel Victor , Orzuza Gabriela , Camera Luis , Waisman Gabriel , Cristiano Edgardo
Published: March 2022

Background and purpose:
Mounting evidence suggests that the presence of chronic kidney disease (CKD) predicts poor clinical outcomes in ischemic stroke patients. However few reports are available about the association of CKD and cognitive impairments (CI) after stroke. The aim of this study was evaluate the presence of CKD in patients with CI after stroke.

Methods:
all patients included in PROTEGE ACV, a stroke secondary prevention stroke program, were evaluated. Demographic data, vascular risk factors profile and control, CI (abnormal clock drawing test (CDT) or MMSE, adjusted by age and educational level) and CKD (estimated glomerular filtration rate -e-GFR- < 60 ml/min/1.73 m
2
or 24 hours microalbuminuria).

Results:
668 (54% female) ischemic stroke patients were included; mean age 75 ± 10 years.. The main vascular risk factors were hypertension (81%), dyslipemia (70%), metabolic syndrome (48%), obesity (42%) and smoking (41%). Pre-stroke hypertension control was good and 74% were under pharmacological treatment.

Post-stroke CI were associated with hypertension (OR 1.65, 95% CI 1-2.59), impaired eGFR (OR 2.51, 95% CI 1,6-3,8), female sex (OR 2.23 95% CI 1.5-3.2) and cardioembolic stroke (OR 2.32, 95% CI 1.5-3.4) in the univariate analysis. In the logistic regression model adjusted by age, sex and main vascular risk factors, age older than 80 years, female sex, cardioembolic stroke and impaired e-GFR were predictors of CI (figure). No relationship was found between CI and microalbuminuria ≥ 20 mg/24hs.

Conclusions:
cognitive function is negatively affected by impaired e-GFR. Optimal pre-stroke hypertension control could be an explanation for the small number of patients with high microalbuminuria in our cohort.
Abstract WP449: Right Hemisphere Dysfunction is more Accurately Detected by Prosody Impairment than by Hemispatial Neglect
Authors: Dara Chinar , Gomez Yessenia , Davis Cameron , Newhart Melissa , Hillis Argye
Published: March 2022

Introduction
It is well known that right hemisphere ischemic stroke often results in hemispatial neglect. Recent studies have also shown that right hemisphere stroke may cause impairment in processing emotional prosody (tone of voice) as well. We tested the hypothesis that stroke patients are more accurately distinguished from neurologically intact controls by tests of emotional prosody comprehension than by tests of hemispatial neglect.

Methods
We tested a series of 29 patients (mean age - 55 years old and mean education - 14 years)within 48 hours of onset of first right hemisphere ischemic stroke and 23 hospitalized age- and education- matched controls with MRI, a prosody comprehension battery and a battery of hemispatial neglect tests (line cancellation, copying a scene, gap detection, line bisection) . Emotion categorization tasks assessed recognition of 6 emotion categories (happy, sad, angry, surprise, disinterest, neutral) from prosodic cues in 2 conditions with varying verbal demands (neutral sentences and monosyllables). We used Receiver Operating Characteristic curves to identify the scores that most accurately classified stroke patients versus controls, using summary scores for Prosody and Neglect based on all of subtests for each.

Results
The Prosody Score was more effective than the Neglect Score in distinguishing stroke patients from controls, as measured by a Receiver Operating Characteristic (AUC for Prosody Score = 0.86). An overall error rate of > 27% on the prosody comprehension battery had a sensitivity of 89.74% and specificity of 68.18% (correctly classifying 82.0% of participants as patients vs controls). In contrast, the AUC for Neglect Summary Score was 0.55. At most, the Neglect Score could classify 55.8% of patients vs. controls. Of 25 patients who made >27% errors on Prosody Comprehension, 22 (88%) made 0% errors on the Neglect battery.

Conclusion
Prosody impairment may be a better indicator of right cortical dysfunction than hemispatial neglect in acute stroke and may therefore be a better measure of effectiveness of interventions to salvage cortical function, such as reperfusion therapies.
Abstract WP51: Racial Differences in Salvageable Ischemic Penumbra
Authors: Mohamed Wazim , Suchdev Kushak , Bhattacharya Pratik
Published: March 2022

Objective:
African Americans (AA) have a higher incidence of intracranial atherosclerosis than Caucasians. Resulting chronic ischemia may lead to the formation of collateral circulation. Our hypothesis was that AA will have a greater sustainability of their ischemic penumbra from collateral circulation after an acute stroke.

Methods:
Ischemic stroke patients that underwent perfusion computed tomography (PCT) at admission from August 2011 to March 2012 were reviewed. PCT included 4 supratentorial slices, 8 mm thick. Images were processed using Vitrea® to obtain cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT). Areas of increased MTT were traced and marked as ischemic area. Corresponding area of preserved CBV was labeled as penumbra area. The mean CBF, MTT or CBV for the total ischemic area (or penumbra) was estimated by multiplying each ischemic area (or penumbra) by the corresponding CBF (MTT or CBV), adding the value of four slices and dividing by total area. The ischemic and penumbra areas in four slices were added and multiplied by slice thickness (0.8 cm) to give ischemic volume (IV) and penumbra volume (PV) respectively.

Results:
Perfusion abnormalities were found in 43 (65.1 % AA vs. 30.2 % Caucasian) patients. The mean ischemic volume was less in AA as compared to Caucasians (63.64 ±36.7 cm
3
vs. 89.57 ±52.6 cm
3
) as was mean penumbra volume (42.77±28.9 cm
3
vs. 64.36 ± 43.8 cm
3
). Within the penumbra in AA, CBF was increased (28 ±12.2 ml/100 gm/sec vs. 23.11 ±12.5 ml/100 gm/sec) as was CBV (3.46 ±1.4 ml/100gm vs. 2.98 ±1.1 ml/100gm). The penumbra MTT was faster in AA (8.59 ±2.2 sec vs. 9.46 ±2.72 sec). The trends in CBF, CBV and MTT did not reach statistical significance due to the small sample size. A CBF less than 20 ml/100 gm/sec is conventionally defined as vulnerable ischemic tissue. In the area of ischemia, only 36% of AA had CBF less than 20 ml/100 gm/min as opposed to 61.5% in Caucasians (p=0.17).

Conclusion
This exploratory analysis showed that AA have a somewhat greater CBF and CBV with faster MTT in the region of penumbra as compared to Caucasians indicating the presence of biological mechanisms to preserve the area at risk. Further analysis to assess collateral cerebral blood flow as a protective mechanism in AA is warranted.
Abstract WP52: A Novel CT-angiogram Based Recanalization Grading System (TICI-CTA) Correlates With Early Neurologic Response After Intravenous tPA Therapy
Authors: Adatia Sweta , Menon Bijoy , II Sohn Sung , Dowlatshahi Dar , Calleja Anna , Poppe Alexandre , Jin Al , Moreau Francois , Boulanger Jean-Martin , Puig Josep , Asdaghi Negar , Nambiar Vivek , Stewart Teri , Aram Heidi , Goyal Mayank , Demchuk Andrew
Published: March 2022

Introduction:
Noninvasive imaging tools to assess the degree of recanalization are limited. CT-angiography (CTA) may be ideal for assessment of recanalization in view of excellent visualization of thrombus and distal vasculature; however no scoring system is available to evaluate extent of recanalization. We sought to derive a score and test it’s correlation to early neurologic response (24 hours NIHSS) within a research study having a post tPA CTA.

Method:
The TICI-CTA score was defined by debulking of thrombus of proximal intracranial arterial occlusive lesion (PIAOL) and forward filling of distal arterial tree.(see graphic) Data is from INTERRSeCT, an ongoing multi-center study evaluating thrombus characteristics and recanalization in acute stroke.

Results:
From 166, 78 patients treated with IV tPA were evaluated. The cohort had 48% males. The median time from symptom onset to baseline CTA was 114 min, and onset to IV tPA bolus was 148 min. Proximal intracranial sites of occlusions were: carotid-T 6.4%, M1-MCA 26.9%, distal MCA 58.9%, PCA 6.4%, and vertebral 1.3%. The symptom onset to follow-up post treatment CTA was 373 min. The recanalization grading TICI-CTA in post iv tPA CTA was: TICI-CTA 0 in 30 (38.4%), TICI-CTA 1A/1B in 3 (3.8%); TICI-CTA 2A/2B/2C in 17 (21.7%); and TICI-CTA 3 in 28 (35.8%). We noted a significant positive correlation between TICI-CTA score and absolute change in NIHSS from baseline to 24 hours (r=0.26, p=0.02). A positive correlation was also noted between TICI-CTA score and proportional change in NIHSS from baseline to 24 hrs (r=0.34, p<0.01).

Conclusion:
The TICI-CTA score based on comparison of pre and post treatment CTA correlates with early neurologic response, thus showing content validity. Further validation is needed. This grading score could be used to evaluate the recanalization efficacy of novel lytics and combination therapies in phase 2 proof of concept or as a predefined CTA sub-study in a pivotal Phase 3 clinical trial.
Abstract WP67: Factors Associated with Reversed Discrepancy between CT and Diffusion-Weighted Imaging in Hyperacute Ischemic Stroke Patients
Authors: Kawano Hiroyuki , Hirano Teruyuki , Nakajima Makoto , Inatomi Yuichiro , Yonehara Toshiro
Published: March 2022

INTRODUCTION:
In patients with hyperacute ischemic stroke, diffusion-weighted imaging (DWI) sometimes fails to detect early CT ischemic lesions showing parenchymal hypoattenuation, which is termed Reversed Discrepancy (RD). The aim of the present study was to elucidate the factors associated to the development of RD.

Method:
One hundred sixty four consecutive patients with hyperacute anterior circulation ischemic stroke were enrolled. All patients underwent both MRI and CT within 3 hours of onset and before treatment. Three stroke neurologists independently and retrospectively evaluated presence of early ischemic changes in each the Alberta Stroke Programme Early CT Score (ASPECTS) region. Presence of RD was defined when the early ischemic change detected on CT was not detected on DWI. Patients’ baseline characteristics, ASPECTS on CT, ASPECTS on DWI, and modified Rankin Scale (mRS) 3 months after onset were compared between patients with RD (RD group) and without RD regions (non-RD group).

Results:
RD was found in 40 (32%) patients (mean age 78.7 years; 50 % men); it was located in the basal ganglia (n=23), the cortex (n=27), and the basal ganglia plus the cortex (n=10). RD group was older (78.7±9.6 vs. 74.1±12.1 years, p=0.03), had a higher NIHSS score on admission (median, 22 vs. 11, p<0.01), a higher rate of atrial fibrillation (75% vs. 42%, p<0.01), a higher rate of ICA/MCA proximal occlusion (55% vs. 28%, p<0.01), had lower grade of ASPECTS either on CT (median 5 vs. 10, p<0.01) or on DWI (7 vs. 9, p<0.01) than non-RD group. Multivariate logistic regression analysis demonstrated that atrial fibrillation was an independent predictor of the presence of RD (odds ratio 2.47; 95% C.I. 1.05-6.12). RD group had less frequently good outcome (mRS 0-1 after 3 months) than non-RD group (15% vs. 34%, p=0.03).

Conclusions:
Atrial fibrillation was related to the presence of RD. Patients with RD had unfavorable outcome.
Abstract WP73: Potentially Fatal Adverse Allergic Events to Intravenous Thrombolytics: An analysis from Adverse Event Reporting System
Authors: Khan Asif A , Zarar Amna , Adil Malik M , Qureshi Adnan I
Published: March 2022

Objective:
Adverse events including intracerebral hemorrhage (ICH) and reperfusion arrythmias are known to occur with thrombolytic therapy.

Due to limited data, our goal is to describe the types of allergic adverse events directly attributable to IV thrombolytics.

Methods:
Adverse Event Reporting System (AERS) is a database that contains information on adverse event and medication error reports submitted to FDA. A systematic review of AERS database was performed for allergic adverse events occurring in conjunction with IV thrombolytics, including alteplase, tenecteplase, urokinase and reteplase. Allergic reaction was defined as any non-hemorrhagic sensitivity reaction which occurred as a direct result of administration of IV thrombolytic. We reviewed 924 adverse events which occurred between 2004-2010 associated with thrombolytics and further requested 33 detailed ISR reports of allergic reactions.

Results:
Out of the 33 reports, there were 12 cases (age range 57 to

93 years) of adverse allergic reaction directly attributable to IV thrombolytics. Allergic reactions included angioedema, facial swelling, urticaria, skin rash, cutaneous hypesthesia, hypotension, seizure, anaphylactic shock and death. Of the patients who were reported to suffer from allergic adverse events 11 received IV alteplase, and 1 received IV reteplase. Four of these patients were taking ACE inhibitors at the time of allergic reaction. In the remaining 21 events, the IV thrombolytics remained as a possible secondary cause of allergic reaction, but concomitantly administered medications made this difficult to ascertain. Most reactions associated with IV alteplase resolved with withdrawal of medication and treatment with diphenhydramine and steroids +/- epinephrine. There was 1 death directly attributable to allergic reaction in a patient who received IV reteplase for MI.

Conclusion:
Although IV alteplase is identical to endogenous tissue plasminogen activator, it appears to be the most common cause of allergic reaction amongst currently used thrombolytics, with or without concomitant administration of ACE inhibitors. A greater awareness among physicians may result in prompt recognition and treatment.
Abstract WP78: Identifying Aneurysm Growth Based on Imaging: A Size Increase of 0.8-0.9 mm is the Optimal Threshold to Classify Growth
Authors: Patel Suraj V , Chien Aichi
Published: March 2022

Introduction:
Documenting aneurysm growth is the key to monitoring the risk of aneurysm rupture. While aneurysm size changes can be found through imaging, the threshold which defines significant growth is important for clinical aneurysm management and consistency between studies. The purpose of this study is to investigate which threshold constitutes significant growth and best separates aneurysms into growth/no growth categories.

Hypothesis:
An optimal growth threshold that delineates aneurysm growth can be identified by a detailed study of longitudinal aneurysm data and risk factors.

Method:
A retrospective study was performed, examining 290 aneurysms longitudinally followed with CTA. Our study included 29 males and 177 females with a mean age of 61±13.22 years. We used the Chi-Square Test and Two-Way ANOVA to evaluate risk factors which included the initial aneurysm size, patient’s age and sex, multiplicity/number of aneurysms, lobulation, calcification, and aneurysm location. For each risk factor, growth thresholds ranging from 0.5-1.0 mm with a 0.1 mm interval were tested to classify aneurysm size change as “Growth” or “No Growth.” Independent T-Tests were also performed using these thresholds to compare the follow-up period between “Growth” and “No Growth” aneurysms.

Results:
The Chi-Square Test showed that the patient’s age and initial aneurysm size were statistically significant (p<0.05) for most growth thresholds. The Two-Way ANOVA revealed a significant interaction (p<0.05) between the patient’s age and initial aneurysm size. The Independent T-Tests showed a significantly longer (p<0.05) follow-up period for aneurysms with growth. Additionally, we ranked the growth thresholds for each test (based on which thresholds produced the lowest p-value) and summed up the ranks for each threshold. The thresholds of 0.8 mm and 0.9 mm produced the lowest p-values, making them the optimal thresholds.

Conclusion:

Patients under 50 years old and patients with aneurysms larger than 9.5 mm have an increased risk of aneurysm growth of 0.8 mm or more, and these aneurysms may need frequent follow-up and careful monitoring. Additionally, aneurysms that grow at least 0.8mm are growing significantly and may require intense clinical management.
Abstract WP83: Racial and Gender Disparities in the Treatment of Cerebral Aneurysms in the United States: The Gap is Narrowing
Authors: Claus Elizabeth B
Published: March 2022

Abbreviations:
SAH, subarachnoid hemorrhage. BWH, Brigham and Women’s Hospital, Boston. ISAT, International Subarachnoid Aneurysm Trial.

Background:
Cerebral aneurysms may be treated with surgical clipping or endovascular coiling. We investigate treatment choice and outcome of cerebral aneurysms by race and gender in the United States over the past decade.

Methods:
Data are the Nationwide Inpatient Sample data from 1998 to 2007. Patients undergoing treatment for cerebral aneurysm were identified by ICD-9 codes with hospital mortality and adverse discharge disposition (other than home) examined as as outcome parameters using logistic regression.

Results:
Of all aneurysms treated in the U.S. from 1998-2007, 20134 were ruptured and 14765 were unruptured. Over this decade, the use of endovascular coiling increased in all racial and gender subgroups for both ruptured and unruptured patients. Whites were more likely than non-whites to undergo coiling for a ruptured aneurysm (Odds Ratio [OR]: 1.30; 95% Confidence Interval [95%CI]: 1.13-1.48), and males with unruptured aneurysms were more likely than females to undergo coiling (OR: 1.26; 95%CI: 1.13-1.40). Hospital mortality and adverse discharge disposition were more likely in black females with unruptured aneurysms than other subgroups. Treatment selection and outcome across racial and gender subgroups did not vary by geographic areas or hospital teaching status. By 2007 differences in treatment selection by gender and racial subgroups were decreased or statistically non-significant.

Conclusions:
Racial and gender disparities exist in cerebral aneurysm treatment and outcome in the United States, although the differences in treatment selection were decreased over time.