bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P308: A Four-Year Experience of Symptomatic Intracranial Hemorrhage Rate Following Intravenous Tissue Plasminogen Activator at a Comprehensive Stroke Center
Authors: Wagner Jeffrey C , Orlando Alessandro , Fanale Christopher V , Whaley Michelle , McCarthy Kathryn L , Bar-Or David
Published: July 2021

OBJECTIVE:
To describe the 4-year symptomatic intracranial hemorrhage (sICH) rate at a high-volume comprehensive stroke center.

METHODS:
This was a retrospective observational cohort study. All admitted adult (≥18 years) patients presenting with an ischemic stroke (IS) from 2010 to 2013 were included in this study. Chi-square, Wilcoxon rank-sum, Student’s t-tests and Cochran-Armitage trend tests were used to compare groups and analyze data. sICHs were defined by a 4-point increase in NIHSS within 36h with new ICH seen on CT; sICHs were included only if they were directly related to IV-tPA treatment. Favorable mRS outcome was defined as a score ≤2. In-patient stroke alerts were excluded from door-to-needle (DTN) times.

RESULTS:
2673 patients were admitted with IS. Of these, 627 (23%) were treated with IV-tPA (90% <3h from symptom onset, 69% at an outside facility). There was a significant increase in the percentage of IS patients treated with IV-tPA over the four years (p-trend=0.02). Compared to patients not receiving IV/IA therapy, patients receiving IV-tPA had significantly higher NIHSS scores, higher prevalence of atrial fibrillation, hyperlipidemia, and cardioembolic etiology, and lower proportion of small vessel occlusive IS. The median (IQR) DTN was 41m (32-53). In the 627 IS patients treated with IV-tPA, 11 (1.8%) developed a sICH; in 2013, the sICH rate was 0.6% (1/158). IV-tPA patients who developed a sICH were similar to those who were sICH-free; however, sICH patients had a significantly higher proportion of coronary artery disease (p=0.04) and severe strokes (p=0.19), and higher median symptom to arrival times (237m vs 187m, p=0.19), but similar median DTN (40m vs 41m, p=0.84). The in-hospital mortality rate for the IV-tPA group was 11% (n=71), and 37% had favorable mRS discharge scores.

CONCLUSIONS:
These data show that expeditious care and careful selection of patients for IV-tPA treatment can lead to very low rates of sICHs. The few sICHs subsequent to IV-tPA are likely to be a consequence of long symptom-to-arrival times and stroke severity.
Abstract W P31: Does Portable CT Imaging in a Mobile Stroke Treatment Unit (MSTU) Provide Adequate Quality for Early Critical Decision Making?
Authors: Sheikhi Lila , Itrat Ahmed , Cerejo Russell , Taqui Ather , Buttrick Maureen , Stecker Margaret , Winners Stacey , Ruggieri Paul , Donohue Megan , Rasmussen Peter , Hussain Muhammed , Uchino Ken
Published: July 2021

BACKGROUND:
Our hospital implemented a Mobile Stroke Treatment Unit (MSTU) on July 18, 2014 involving a pre-hospital delivery of stroke thrombolysis. The MSTU team evaluates potential IV tPA candidates using a portable CT head (pCTH) scan in the field. OBJECTIVE: To determine adequacy of MSTU CT quality for early ischemic changes and IV tPA administration. METHODS: A retrospective analysis was performed of patients approached by MSTU who received a pCTH (CereTom, Neurologica, Danvers, MA). Assessment of quality, artifacts, physician confidence and findings (intracranial hemorrhage (ICH), early ischemic changes using Alberta Stroke Program Early CT score (ASPECTS)) was performed. Two neurologists with ASPECTS certification and blinded to patient history reviewed images independently. Inter-rater agreement and Spearman’s correlation of numeric variables between the two reviewers were compared. For comparison inter-rater reliability, control CT scans performed in emergency department (ED) for early stroke evaluation in different sets of 20 patients were assessed by two reviewers. RESULTS: A total of 23 patients underwent pCTH in the MSTU since initiation. Two patients were found to have ICH, later confirmed by a standard hospital CT scan. The remaining 21 patients did not have any evidence of ICH, 10 (48%) of whom had a subsequent hospital CT or MRI confirming absence of ICH. pCTH quality was assessed to be adequate in 18 (85%) subjects by both reviewers to make decisions on thrombolysis treatment. CT artifacts were noted in 15 (71%) scans by reviewer 1 and 16 (76%) scans by reviewer 2 (k 0.4, p=0.2). ASPECTS on pCTH did not have high correlation between two raters (spearman’s rho=0.3, p=0.1). Confidence of ASPECTS was low in both reviewers (52% reviewer 1 vs 66% reviewer 2). In comparison, correlation between ED controls was better between the two reviewers (spearman’s rho= 0.6, p=0.01). Confidence of ASPECT score was high for both reviewers in the control group (95% reviewer 1; 100% reviewer 2). Artifacts were noted in few scans of controls (n=5, 25% reviewer 1; n=3, 15%, reviewer 2). CONCLUSION: The quality of pCTH on the MSTU is adequate for thrombolysis contraindications, but artifacts are common and subtle early ischemic changes are difficult to assess.
Abstract W P318: Ischemic Stroke in the Post-Operative Phase of 2,035 Consecutive Orthotopic Liver Transplantations
Authors: Liebeskind David S , Lening Christopher B , Aksoy Olcay , Liu Dezhi , Hinman Jason D , Scalzo Fabien , Johnson Mark S , Xia Victor W , Busuttil Ronald W , Agopian Vatche G
Published: July 2021

Background:
Cardiovascular morbidity has been cited as a prominent cause of post-operative orthotopic liver transplantation (post-OLT) complications, yet the role of ischemic stroke during this period remains poorly defined. We examined the incidence of post-OLT ischemic stroke, associated risk factors, etiology and neuroimaging features in an extensive single center database.

Methods:
All consecutive adult patients undergoing OLT from January 1, 2002 to December 15, 2013 at a single center were analyzed for neurological complications, characterizing post-operative stroke by neurology consultation and CT/MRI. Neurological history, examination, features of atrial fibrillation, concomitant infection, relevant laboratory parameters, and infarct patterns were reviewed in detail.

Results:
Of the 2,035 OLT cases analyzed, including 190 cases where neurology consultation was triggered, post-OLT ischemic stroke was identified in 20 patients (0.98%). Patients with ischemic stroke were significantly more likely to be older (64.4 vs. 53.6 years, p<0.001), have pre-existing coronary artery disease (21.4% vs. 5.6%, p=0.011), higher pre-transplant MELD scores (34 vs 27.7, p=0.018), and greater post-transplant infectious complications both within (45% vs 22.6%, p=0.017) and beyond (65% vs. 24.4%, p<0.001) 30 days post-OLT, and longer post-OLT length of hospitalization (53.2 vs 32.5 days, p=0.033). Comparing patients with and without post-OLT ischemic stroke, there were no significant differences in the incidence of preoperative (4.1% vs 5.0%, p=0.846) or postoperative (6.5% vs 10%, p=0.530) atrial fibrillation. Ischemic stroke was characterized with MRI in 19/20 (95%) and only CT in 1/20 (5%). Scattered, cortical lesions of probable embolic etiology were noted in 12/20 (60%) with only 3/20 (15%) proximal arterial territory lesions.

Conclusions:
Post-OLT ischemic stroke was relatively uncommon in this largest single center series of 2035 consecutive OLTs. Further insight on etiology of these complications may help to further reduce morbidity.
Abstract W P32: CSF Volumetric Analysis Reliably Quantifies Cerebral Edema And Correlates With Clinical Deterioration In Large Hemispheric Infarcts
Authors: Yuan Kristy , Dhar Rajat , Kulik Tobias , Chen Yasheng , Heitsch Laura , Khoury Naim , Guilliams Kristin , Vo Katie , An Hongyu , Ford Andria , Lee Jin-Moo
Published: July 2021

Background:
Large hemispheric infarcts (LHI) may be complicated by cerebral edema. Midline shift (MLS), a standard radiographic measure, only crudely estimates extent of edema. Volumetric analysis of CSF compartments over time may provide a reliable and accurate means of quantifying severity and kinetics of edema after LHI.

Methods:
We retrospectively identified stroke patients with NIHSS≥8 and baseline CT within 6 hours who developed cerebral edema (without hemorrhage) on follow-up (FU) CTs. Two raters outlined the sulci and lateral ventricles ipsilateral (IL) and contralateral (CL) to the infarct on baseline and serial FU CTs (both within 48 hours and at peak edema, 2-5 days post-stroke) and quantified CSF and infarct volumes. Changes in compartment volumes from baseline to peak edema CT were correlated with MLS and edema-related neurologic worsening (need for hemicraniectomy, osmotic therapy, or decline in GCS, associated with MLS≥5mm).

Results:
Ten patients were analyzed (median NIHSS 14, time to early FU CT 30 hours, IQR 15-37 and to peak edema CT 75 hours, IQR 64-95). Inter-rater reliability for volume measures was excellent (intraclass correlation >0.97). CSF volume diminished by 37±20% (49 ml) from baseline to peak edema, over half occurring within 48 hours; net decline in CSF volume correlated with infarct volume (r=-0.63,p=0.05). Greatest reductions in CSF were seen in IL sulci and IL ventricles (Figure, top), but it was % reduction in CL sulci that correlated best with MLS (Fig, bottom), even adjusting for infarct volume (p=0.02). Decline in volumes of IL and CL sulci were greater in the 5 subjects with neurological worsening (89% vs. 56% and 40% vs. 3%, p<0.05), while infarct volume was not.

Conclusions:
CSF volumetrics is a reliable tool for quantifying cerebral edema after LHI and a novel method of studying edema kinetics. Loss of sulcal volume correlates with MLS and is more strongly associated with edema-related deterioration than infarct volume alone.
Abstract W P323: Development of a Nomogram to Predict Hematoma Expansion in Patients with Spontaneous Intracerebral Hemorrhage
Authors: Yao Xiaoying , Selim Magdy , Xu Ye , Siwila-Sackman Erica
Published: July 2021

Background:
Early identification of intracerebral hemorrhage (ICH) patients at risk of significant hematoma expansion (SHE) could facilitate the selection of appropriate patients who are likely to benefit from therapies aiming to minimize ICH growth. Nomograms have been proved to have superior individualized disease-related risk estimations of given outcomes. This study aims to develop a normogram that can be performed during the hyperacute phase to predict the risk of SHE in patients with spontaneous ICH.

Methods:
We reviewed clinical, laboratory, and radiological data from 237 patients diagnosed with spontaneous ICH who had baseline head CT within 12 hours of symptom onset and follow-up CT during the following 72 hours. SHE was defined as an absolute increase in ICH volume > 6ml or an increase greater than 33% from baseline to follow-up CT. To construct the nomogram, we performed logistic regression analyses to determine the predictors of SHE. Each predictor was assigned a point in the graphic interface of a nomogram, and the points were summed up to determine the predicted probability of SHE for a specific ICH patient.

Results:
SHE occurred in 74 patients (31.2%). The final model to predict SHE, presented as a nomogram, included: time from onset to baseline CT scan (< 3h vs 3-12h), dementia, current smoking, antiplatelet use, serum creatinine level, Glasgow Comma Scale score, and presence of subarachnoid hemorrhage on baseline CT. The model had satisfactory discrimination ability with a bootstrap corrected c index of 0.77 (95% CI, 0.75-0.82) and good calibration. The in-hospital mortality was higher in patients with SHE (42% vs. 15%; p <0.001).

Conclusion:
We developed and internally validated a novel nomogram model which accurately predicts the possibility of SHE based on seven easily obtainable parameters. This could be useful for treatment decision and stratification. External validation of our nomogram is warranted before its application to other populations.
Abstract W P349: Bridging the Gap: Discharge to Follow-up: A Qualitative Review
Authors: Juntura Anh , Shields Linda , Cudlip Fern
Published: July 2021

Background:
Discharging patients from the hospital is complex and challenging. The discharge process includes discharge planning, medication reconciliation, discharge summation, and patient instruction. The enormity of information and complexity of the process directly impacts patient compliance and re-admission. Given the extent of this process, efforts toward assuring clarity of knowledge have the potential to improve patient compliance. We sought to identify and address gaps in post discharge patient awareness.

Methods:
A follow-up phone interview was conducted 1 week post discharge, with 26 stroke patients. All patients had received verbal and written stroke education prior to discharge. The qualitative assessment tool included 10 questions regarding general wellbeing, follow-up appointment compliance, medication utilization, and stroke knowledge. The patient responses were categorized accordingly. A copy of the patient’s discharge instructions was utilized during the interview for verification and clarification of discharge information.

Results:
Regarding wellbeing, 77% of the patients reported a reasonable sense of well being. The majority (77%) had scheduled follow-up appointments with the remaining 23% requiring clarification. Concerning medication compliance, 92% of the patients were able to obtain and comprehend use of their new medications. Review of stroke type confirmed 54% with understanding, whereas, 44% expressed lack of clarity regarding the subject. The same was true in regards to comprehension of stroke risk factors (56% verbalized understanding and 44% lacked awareness). Lastly, 54% of respondents were unable to identify the signs and symptoms of stroke despite the majority (60%) verbalizing a correct use of the 9-1-1 system

Conclusion:
Our findings imply that a post discharge phone call practice serves to identify information gaps and provide opportunity to clarify stroke awareness, thus, “bridging the gap” of understanding and compliance regarding stroke management and prevention
Abstract W P362: Stroke Coordinators: Surveys from the ASA Southwest Affiliate
Authors: Casper Christy L , Graves Alexandra , Whaley Michelle , Blakie Julie
Published: July 2021

Background:
Stroke coordinators (SC) in Colorado meet monthly to share best practice and collaborate with the ASA and industry representatives. Based on informal observation, we believed that many of the coordinators were new in their roles and desired additional information and education on how to be successful. We teamed with the ASA and hosted two conferences; one for Colorado SCs and a larger conference for ASA Southwest affiliates. Demographic data was collected at both conferences.

Methods:
For the CO conference, surveys were sent to all SCs in the state. For the ASA conference, only those who attended were given the survey. Results were combined and content included: educational preparation, hospital volumes, certification status, reporting structure, orientation plan, role responsibilities, data expectations, and job satisfaction. Partial responses were included.

Results:
94 surveys were returned. 70% were SCs for less than 2 years but 40% worked in their hospital for 1 - 5 years and 38% for >5 years. 32/41 worked at a primary stroke center (PSC) and 6/41 worked at a comprehensive stroke center. The majority (81%) were nurses (36% Diploma, 64% Bachelor’s prepared). 18% were Master’s prepared (NP, CNS, and MS in nursing but not NP or CNS). 43% either had a mentor or a structured orientation plan and exactly the same (43%) made up their orientation. 45% reported to Nursing, 40% to Quality, and few (2%) to Neurology. Respondents liked the ability to be creative and affect change at their hospital but disliked the lack of clarity in their role and the number of job functions they are expected to perform.

Conclusion:
SCs in the Southwest affiliate are primarily nurses with less than 2 years of experience as a SC who had worked at their hospital for at least 1 year but many for over 5 years. Most hospitals are PSCs. They equally had mentorship and training versus developing their role without much direction. SCs enjoy the ability to be creative and affect change but would like additional clarity and expectations to succeed in their roles.
Abstract W P379: Pre-treatment with Selective Serotonin Reuptake Inhibitors is Associated with Improved Short-term Outcome in Acute Ischemic Stroke
Authors: Siepmann Timo , Kepplinger Jessica , Zerna Charlotte , Penzlin Ana Isabel , Reichmann Heinz , Pallesen Lars-Peder , Puetz Volker , Bodechtel Ulf , Barlinn Kristian
Published: July 2021

Background and Purpose:
Treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) following acute ischemic stroke was shown to improve functional and motor recovery independently of depression, possibly mediated by long-term mechanisms such as increased brain plasticity. In animal studies, chronic SSRI treatment is superior over short-term SSRI in evoking neurogenesis but the applicability of this observation to humans remains unelucidated. We hypothesized that pre-treatment with SSRI in acute ischemic stroke patients is associated with improved recovery compared to post-stroke SSRI.

Subjects and Methods:
We performed an exploratory analysis in consecutive acute ischemic stroke patients who were pre-treated or treated de novo either with fluoxetine, citalopram or escitalopram. Effects of SSRI-pre-treatment on short-term clinical (total NIHSS and NIHSS motor items) and functional (mRS) outcome at discharge compared to post-stroke SSRI were assessed using bivariate and multivariate analyses.

Results:
Of 2653 patients screened, 239 were included (aged 69±14 years, mean±SD; 42% men, baseline median NIHSS 7 [IQR, 10]). Compared to post-stroke SSRI (n=188), in the SSRI pre-treatment group (n=51) favorable functional outcome at discharge (mRS≤2) was more frequent (41% vs. 20%; p=0.002), duration of hospitalization was shorter (median: 7 versus 11 days; p<0.0001), and there was a non-significant trend toward improved motor recovery (decrease in NIHSS motor items ≥2 points or 0-1 at discharge; 63% vs. 49%; p=0.08). However there was no such difference in total NIHSS recovery (≥4 points or 0-1 at discharge; p=n.s.). Pre-treatment with SSRI was an independent predictor of favorable functional outcome (mRS≤2) at discharge (OR: 4.00; 95%CI: 1.68-9.57; p=0.002) after adjusting for age, pre-stroke mRS, baseline NIHSS and IV-thrombolysis.

Conclusions:
Our data suggest that pre-treatment with SSRI may be linked to early clinical recovery after acute ischemic stroke and support the hypothesis that pre-stroke SSRI might be superior to post-stroke SSRI.
Abstract W P382: Cognitive Outcome in SAMMPRIS: Medical Therapy vs. Stenting
Authors: Smock Alison P , Turan Tanya N , Cotsonis George A , Lynn Michael J , Derdeyn Colin P , Fiorella David , Janis L S , Lane Bethany F , Montgomery Jean , Chimowitz Marc I ,   for the SAMMPRIS Investigators
Published: July 2021

Background:
It has been hypothesized that revascularization of stenotic cerebral arteries may improve cognitive outcome by increasing cerebral perfusion. We sought to compare cognitive outcome in patients treated with percutaneous angioplasty and stenting (PTAS) and aggressive medical management (AMM) vs. AMM alone in the SAMMPRIS Trial.

Methods:
In SAMMPRIS, 451 patients with recent TIA or stroke attributed to 70%-99% intracranial stenosis were randomized to PTAS plus AMM or AMM alone. Patients with stroke as the qualifying event who had a NIHSS indicating aphasia or neglect were excluded from these analyses. Patients with any ischemic stroke, cerebral infarct with temporary signs (CITS), or ICH during follow-up were excluded from subsequent follow-up visit analyses. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition at baseline, 4 months, 12 months, and closeout (mean 3.05 years in AMM group and 3.12 years in PTAS group). Cognitive impairment was defined as MoCA <26. Mean MoCA scores and the percentage of patients with cognitive impairment were compared between treatment groups at each time point using t-tests and Chi-square tests. Differences in MoCA means from baseline to follow-up time points were compared using mixed model repeated measures ANOVA and Tukey-Kramer tests.

Results:
As shown in the Figure, there were no significant differences between the treatment groups for mean MoCA at any time point. There were significant improvements in mean MoCA from baseline to 4 months, 12 months, and closeout in both groups. The percentage of patients with cognitive impairment in the AMM vs. PTAS groups were not significantly different at baseline (53 vs. 56%), 4 months (38 vs. 44%), 12 months (42 vs. 40%), and closeout (43 vs. 39%).

Conclusions:
Revascularization did not provide any additional cognitive benefit over AMM alone in SAMMPRIS even after excluding patients who had cerebral infarction or ICH during follow-up.
Abstract W P385: Hypertension-Induced Hypoxia Leads to Neurodegeneration in a Novel Model of Accelerated Cerebrovascular Disease
Authors: Raz Limor , Bhaskar Kiran , Rosenberg Gary A
Published: July 2021

Hypertension is a major risk factor contributing to cerebrovascular diseases such as stroke and vascular cognitive impairment (VCI). Elevated blood pressure leads to cerebral small vessel disease, resulting neuronal cell death and cognitive dysfunction. We developed a unique animal model of clinical VCI in the spontaneously hypertensive stroke prone (SHR-SP) rat, characterized by significant white matter disease, neuroinflammation and behavioral deficits induced by a Japanese Permissive Diet (JPD) and unilateral carotid artery occlusion (UCAO). We hypothesized that the SHR-SP rat has neuropathological changes in the cortex and hippocampus due to effects of hypertension on neurodegeneration. To test the hypothesis, we performed permanent right side UCAO (hypoxia) at 12 weeks (12W) of age in male SHR-SP rats (n=5). Following surgery, rats were placed on a JPD and received 1% NaCl in drinking water (hypertension). Control rats were fed a normal diet and underwent right carotid artery isolation (n=4). A preliminary time course of NeuN and Cresyl Violet staining, from hypoxia onset (12W) to sacrifice (16W), showed decreased neuronal survival and elevated neuroinflammatory response (astro- and micro-gliosis by GFAP and Iba1 staining, respectively) in the experimental group as compared to controls. Microbleeds and endothelial cell damage were observed by Hematoxylin and Eosin histology. Immunohistochemistry showed an up-regulation of hypoxia inducible factor-1α (HIF-1α), implicating a hypoxia-mediated mechanism in neurodegeneration. We observed disruption of the blood brain barrier beginning at 13W, with progressive changes by 16W. MRI-T2 imaging showed significantly larger infarct sizes on the left as compared to the right side hippocampus of experimental rats versus controls (1409656.67±262032 and 1174952.89±145886 (mean±SE), respectively; p<0.009). Our results indicate that chronic hypertension may effect neurodegenerative changes, not only in the white matter, but also in the cortex and hippocampus. Supported by NIH/NINDS RO1 NS045847-07A1.
Abstract W P386: Matrix Metalloproteinase Levels May Mediate Ischemic Stroke Incidence and Recovery in Stroke Patients with Metabolic Syndrome
Authors: Petrone Ashley B , Barr Taura L , Devlin Kelly , Fournier Sara B , Devallance Evan D , Lee Kyuwan , Chantler Paul D
Published: July 2021

Intro:
The metabolic syndrome (MetS) is highly prevalent in the US characterized by a combination of risk factors that can lead to cardiovascular disease (CVD). While the association between CVD, inflammation, and stroke risk has been characterized, the immune mechanisms underlying increased risk of stroke in MetS is unclear. While stroke risk is higher among MetS, MetS individuals tend to have better stroke recovery than controls. The immune response may mediate these paradoxical observations in stroke. In particular, matrix metalloproteinases (MMP) enzymes play a role in stroke incidence and recovery. Similar to MetS, MMPs have a dual role in stroke, as they are harmful immediately after stroke, but play a vital role in brain repair and recovery following stroke. We hypothesize that elevated levels of MMPs in MetS may account for the paradoxical increased stroke risk, yet better recovery seen in stroke patients with MetS.

Methods:
MMP protein concentrations were obtained from fasting venous samples and quantified using a Multi-Analyte Profiling Kit (Millipore) on the Luminex®. Each subject was assigned a metabolic risk score (MRS) based on sex, age, SBP, treatment for hypertension, smoking and diabetes status, HDL, and total cholesterol. B-mode ultrasound images of the right common carotid artery were obtained to measure intima-medial thickness (cIMT). Spearman correlations were used to measure the relationship between MRS, cIMT, and MMP levels.

Results:
In n=68 subjects (60% female) with a mean age of 48+14 yrs, MRS of 25+12, and cIMT of 0.57+0.12 mm. MRS was significantly correlated with cIMT (r=0.39, p< .001). Further, cIMT was positively correlated with MMP1 (r=0.025, p=0.04), MMP7 (r=0.5, p=0.01), and MMP9 (r=0.31, p=0.01).

Conclusion:
Plasma concentrations of MMP1, 7, and 9 were significantly correlated with cIMT, indicating that increased severity of MetS is associated with increased inflammation. Elevated MMP protein levels may account for the increased stroke risk, yet better recovery seen in stroke patients with MetS.
Abstract W P417: A Common Variant in a TGFβ Modifier Locus Is Associated with Intracranial Hemorrhage Presentation of Brain Arteriovenous Malformation in Hereditary Hemorrhagic Telangiectasia
Authors: Pawlikowska Ludmila , Nelson Jeffrey , Guo Diana E , McCulloch Charles E , Lawton Michael T , Kim Helen , Faughnan Marie E ,   Brain Vascular Malformation Consortium HHT Investigator Group
Published: July 2021

Introduction:
Hereditary hemorrhagic telangiectasia (HHT) is caused by mutations in TGFβ/BMP9 pathway genes, most commonly ENG or ALK1. HHT patients have arteriovenous malformations (AVM) in brain, lung and liver, leading to severe complications including intracranial hemorrhage (ICH) from brain AVM. ICH presentation of brain AVM in HHT is a marker of high ICH risk. The clinical heterogeneity of HHT suggests a potential role for genetic modifier effects. Common genetic variants in loci that modify phenotype severity in Tgfb knockout mice have been reported to be associated with pulmonary AVM in HHT. We sought to replicate these associations and investigate whether these variants are also associated with brain AVM and ICH presentation of brain AVM in HHT patients.

Methods:
We genotyped 3 variants (PTPN14 rs2936018, USH2A rs700024 and ADAM17 rs10495565) in 665 Caucasian HHT patients enrolled by the Brian Vascular Malformation Consortium (BVMC). Association of genotype with pulmonary AVM, brain AVM and ICH presentation was evaluated by multivariate logistic regression adjusted for age, gender and family clustering, and also stratified by HHT mutation (ALK1 or ENG).

Results:
Of 665 Caucasian HHT patients analyzed, 51% had pulmonary AVM and 20% had brain AVM, of whom 17% presented with ICH. None of the 3 SNPs was significantly associated with pulmonary or brain AVM. Among 130 brain AVM patients, USH2A rs700024 was associated with ICH presentation (OR=3.34, 95% CI=1.22-9.15, p=0.019). The effect size was similar in HHT patients with ALK1 and ENG mutations, but only reached statistical significance among the latter (OR=6.77, p=0.014).

Conclusions:
A common variant in USH2A, rs700024, previously reported to be associated with pulmonary AVM in HHT, was associated with ICH presentation of brain AVM, but not with brain or pulmonary AVM, in the BVMC HHT cohort. Association of the same USH2A variant with different HHT severity phenotypes in different cohorts suggests that it may act as a genetic modifier of HHT phenotype severity in concert with other genetic and environmental factors. Once validated, such genetic modifiers may improve our understanding of the phenotypic heterogeneity of HHT and aid in ICH risk prediction in HHT brain AVM.
Abstract W P80: Predictors of Cognitive Status in Post-Aneurysm Surgery Patients
Authors: Holcombe Andrea , Torner James , Anderson Steven , Bayman Emine , Todd Michael ,   IHAST Investigators
Published: July 2021

Introduction:
Patients who undergo surgical treatment for ruptured intracranial aneurysms may have a different risk profile for a spectrum of cognitive impairment based upon characteristics at presentation of their subarachnoid hemorrhage.

Methods:
The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) is a multi-center, prospective, randomized clinical trial investigation of whether induced hypothermia during surgical treatment for subarachnoid hemorrhage resulted in improved outcomes. Cognitive status was defined by raw Mini-Mental Status Examination (MMSE) cutoff scores. A normal cognition was defined as a MMSE score of 28 or greater. Mildly impaired patients were defined as a score of 24-27, and severely impaired patients were defined as those with a score of less than 24. Age was analyzed by five-year age groups, with the exception of patients 30 or younger and patients 75 and older. Ordinal logistic regression was utilized to determine the final predictors.

Results:
Of the 1,000 patients who were followed for cognitive testing, 61 died and 21 were medically untestable. Five patients refused testing and tests were not administered to 30 patients. A total of 883 patients completed the MMSE at 3 months post-surgery. Based on the raw MMSE scores, the median score for the severely impaired patients was 20 (IQR: 16-22), 26 (IQR: 25-27) for mildly impaired patients, and 29 (IQR: 29-30) for cognitively normal patients. Gender, and race were found to be statistically significant (p<.05) predictors after controlling for age and education. Baseline Rankin Score and the occurrence of a leakage or rupture during surgery were also predictive of cognitive status. The World Federation of Neurosurgical Societies Score, the Fisher’s SAH Score, and aneurysm size and location were not found to be statistically significant.

Conclusion:
Patients with surgical treatment for subarachnoid hemorrhage share several demographic risk factors associated with cognitive changes in the general public, but have additional neurological risk factors associated with SAH and aneurysm procedures.
Abstract W P82: Periprocedural Elevation of Von Willebrand Factor is Associated With Thromboembolic Events in Coil Embolization of Unruptured Intracranial Aneurysms Under Dual Antiplatelet Therapy
Authors: Ideguchi Minoru , Satow Tetsu , Takada Shigeki , Sugata Sei , Ishii Daizo , Maruyama Daisuke , Hamano Eika , Hayashi Masataka , Kanamaru Hideki , Kataoka Hiroharu , Iihara Koji , Takahashi Jun
Published: July 2021

Introduction and Objective:
Although elevation of von Willebrand factor (vWF) is correlated with the outcome in patients with ischemic heart disease, there are no reports regarding the relevance of vWF and thromboembolism (TE) in coil embolization of unruptured intracranial aneurysms (UIAs). The aim of this study is to evaluate the impact of periprocedural elevation of vWF levels and preventive effect of antiplatelet drugs on TE in coiling of UIAs.

Materials and methods:
A total of 63 consecutive patients harboring wide-necked (>4mm) UIAs treated by coiling between February 2011 and July 2014 were prospectively included in this study. All patients received dual antiplatelet therapy (DAPT) starting 4 days prior to the procedure, continuing for at least three months. Patients’ characteristics, procedural profiles (procedure time, mode of technique used) were documented, and periprocedural hematological data including levels of vWF as well as platelet aggregation using light transmittance aggregometry (LTA) and VerifyNow system were measured. Their relevance with TE as defined by abnormalities in postprocedural diffusion weighted images were statistically assessed.

Results:
TE was observed in 30 cases (47.6 %). Elderly age (p=0.048), longer procedure time (p=0.004), low response to aspirin (collagen>21 by LTA, p=0.009), and elevation of vWF (p=0.009) were significantly associated with TE. In cases with longer procedure time (>238 minutes), low response to clopidogrel was also significantly correlated with TE (p=0.04). A weak, but significant correlation was observed between procedure time and elevated level of vWF (correlation coefficient=0.358, p=0.006).

Conclusions:
DAPT prevented the occurrence of TE in coiling of UIAs when their efficacy was confirmed by platelet aggregation studies. Longer procedure time seems to cause the elevation of vWF which reflects the vascular endothelial dysfunction, thus leading to TE.
Abstract W P89: Functional Recovery Depends on Donor Age after Stem Cell Transplantation for Stroke
Authors: Yamaguchi Susumu , Horie Nobutaka , Satoh Katsuya , Nishida Noriyuki , Nagata Izumi
Published: July 2021

Introduction:
Cell transplantation therapy hold great potential to improve impairments after cerebral ischemia. However, it is still unclear whether the donor age affects functional recovery after cerebral ischemia. Here, we investigate the hypothesis that donor age (young vs. old) drastically affects the repair mechanism after cell transplantation for stroke.

Materials and methods:
Male Sprague Dawley rats were subjected to transient middle cerebral artery occlusion. At 24 hours after stroke, rats were randomly assigned to receive PBS (control), human mesenchymal stem cells (MSC) derived from 24 years old man (young MSC) and MSC derived from 64 years old man (old MSC) via internal carotid artery. Behavioral recovery was assessed with modified Neurological severity score (mNSS) until 21 days after stroke. Animals were euthanized at 21 days, and histological analysis was performed regarding inflammatory reaction, neovascularization and endogenous stem cell activation.

Result:
Young MSC showed an significant recovery in mNSS (3.7±0.6) compared with control (6.1±0.5) and old MSC (5.2±0.7) at 21 days after stroke (P<0.01). In histological analysis, infarct volume was not significantly different among the groups. However, IBA-1 positive microglia was significantly inhibited in young MSC (9.3±5.9%) compared with control (22.1±13.1%) and old MSC (15.2%±14.2%) both in the peri-infarct cortex and striatum (P<0.01). Moreover, RECA-1 positive vessels significantly increased in young MSC (5.4±1.1%) compared with control (5.0±1.6%) and old MSC (4.6%±1.5%) in the peri-infarct cortex (P<0.01). Interestingly, Young MSC showed massive GFAP positive reactive astrocyte running radially into the peri-infarct area with Musashi-1 (Msi-1) positive neural progenitor cells.

Conclusion:
Donor age drastically affect the host environment, endogenous progenitor cell activation and functional recovery after cell transplantation for stroke.
Abstract 108: Women and Minorities Have Lower Patient-reported Functional Status 3 Months Post-stroke
Authors: Bushnell Cheryl , Prvu-Bettger Janet , D'Agostino Ralph , Ambrosius Walter , Bishop Laura , El Husseini Nada , Gesell Sabina
Published: July 2021

Background:
Functional outcomes after stroke are important to patients but not found in administrative data. Using a hospital quality improvement program to assess outcomes 3 months after discharge, we examined the relationship between outcome measured with the Stroke Impact Scale-16 (SIS-16) and sex, comorbidities, depression, and risk factors.

Methods:
We enrolled patients with ischemic/hemorrhagic stroke or TIA in an ongoing hospital-supported quality improvement program focused on transitional care and outcomes (TRAnsition Coaching for Stroke or TRACS). SIS-16 assesses self-reported mobility, arm strength, and basic/instrumental ADLs. Transformed scores range from 0 (worst) to 100 (best). Questionnaires were mailed 3 months post-discharge or collected by phone if no mailed response. Bivariate associations between baseline covariates and SIS-16 were analyzed, followed by stepwise linear regression modeling to assess independent predictors of SIS-16, adjusted for NIHSS.

Results:
We captured 90-day outcomes on 129 patients from 9/2011 to 4/2015; mean age was 66.0 y -(+12.3), 45.7% women, 73% white, and mean NIHSS 4.0 + 5.2. Twenty-eight percent had diabetes, 82% hypertension, 15.6% CAD, 35% prior stroke/TIA, 7% pre-stroke depression. Therapy types included 37% with none, 14.7% inpatient, 24% home health, and 23.2% outpatient. Overall SIS-16 was 81.1 (+21.01). Women, non-white race, and NIHSS were associated with lower SIS-16 (table). In a stepwise linear regression model adjusted for NIHSS (p<0.0001), female sex (p=0.007), and non-white race (p=0.002) were associated with poorer functional status, with a trend in those with prior stroke/TIA (p=0.095). This model explained 31% of the variance in SIS-16.

Conclusion:
Controlling for stroke severity, women, minorities, and those with prior stroke had lower functional status 3 months after stroke. Future quality improvement projects could target improving outcomes in these groups specifically.
Abstract 13: Wall Shear Stress Associated to Intracranial Aneurysm Wall Inflammation
Authors: Cebral Juan , Chung BongJae , Mut Fernando , Robertson Anne , Tulamo Riikka , Frosen Juhana
Published: July 2021

Introduction:
Inflammation has been proposed as a possible mechanism involved in the degradation and weakening of the walls of intracranial aneurysms.

Hypothesis:
Abnormal wall shear stress (WSS) levels induce wall inflammation which then affects the wall structure and mechanics

Methods:
A total of 20 aneurysms which underwent surgical clipping were studied. Patient-specific computational fluid dynamics models were constructed from pre-surgical CTA images. Numerical simulations were carried out using pulsatile flows. After clipping the aneurysm, a tissue sample was resected from the dome and analyzed histologically with CD45 to search for evidence of wall inflammation. For analysis, the aneurysm series was divided in two different manners. First, aneurysms were classified into an “inflammation” group if the number of CD45+ cells was larger than the median of CD45+ cells in the entire sample of 20 aneurysms; otherwise they were classified as “no-inflammation”. Hemodynamic variables were then statistically compared between these two groups. Secondly, aneurysms were subdivided into three groups according to their mean WSS: 1) “low WSS” if WSS<0.5*median(WSS), 2) “high WSS” if WSS>2*median(WSS), and 3) “mid WSS” otherwise. The numbers of CD45+ cells in each group were then statistically compared.

Results:
Aneurysms in the “inflammation” group had significantly larger mean WSS (p=0.018), shear rate (p=0.015), vorticity (p=0.018), and viscous dissipation (p=0.015) than aneurysms in the “no-inflammation” group. Conversely, aneurysms in the “high WSS” group had significantly larger numbers of CD45+ cells (p=0.0046) than the “mid WSS” and “low WSS” groups. Interestingly, aneurysms with stable flow patterns also tended to have larger numbers of inflammatory cells (p=0.040) than aneurysms with unstable flows.

Conclusion:
These preliminary results suggest that there is a connection between intra-aneurysmal flow characteristics and wall inflammation in cerebral aneurysms. In particular, inflamed walls seem to be associated with higher levels of wall shear stress.
Abstract 132: Chronic Optogenetic Stimulation of Thalamocortical Projections Promotes Axonal Rewiring and Accelerates Recovery of Function After Somatosensory Cortex Stroke
Authors: Brown Craig E , Tennant Kelly
Published: July 2021

The majority of stroke survivors must cope with chronic disability of the limbs. Improved limb use is generally accompanied by neuroplasticity in surviving brain areas surrounding the stroke. Modulating this innate plasticity should promote further gains in recovery. One relatively unknown issue in stroke research concerns the role of the thalamus, the brain’s relay center for sensory information en route to the cortex. Unpublished data from our lab has shown that while peri-infarct thalamocortical axons are relatively resilient to the effects of ischemia, they are highly unstable and lose a significant number of synaptic boutons in the first few weeks after stroke. We now expand on this by hypothesizing that optogenetic stimulation of peri-infarct thalamocortical projections will promote axonal rewiring and improve recovery from somatosensory cortex stroke. Axons projecting from the VPL nucleus of the thalamus to primary forelimb somatosensory cortex were co-transfected with a fluorescently tagged adeno-associated virus that expressed channelrhodopsin-2 and mCherry. A chronic cranial window was then implanted to allow for longitudinal in vivo two-photon imaging of superficial thalamic axon terminals before and at various times after photothrombotic stroke. Optogenetic stimulation was driven by a blue LED (475 nm, 6-10mW/mm2) magnetically attached to the cranial window. Optical stimulation (5 ms pulses at 5 Hz every 5 seconds) or control procedures were initiated 3 days after stroke in freely moving mice for 1 hour/day, 5 days/week for 6 weeks after stroke. Behavioural performance on the Tape Removal Test and Ladder Walking Test were assessed once weekly throughout the entire recovery period. Preliminary data show that optogenetic stimulation of thalamocortical projections is associated with an attenuated period of thalamocortical bouton elimination, increased bouton formation and greater stability/persistence of newly formed boutons. Importantly, stimulated mice showed less severe forepaw deficits and faster recovery of sensorimotor function. These studies offer encouraging new insights into the application of optogenetic approaches for improving stroke recovery.
Abstract 148: Age Disparities in Acute Stroke Treatment: An Analysis of Six Years of US Hospital Discharges
Authors: Lyerly Michael , Albright Karen C , Gropen Toby I , Booth Katrina , Harrigan Mark R
Published: July 2021

Introduction:
For each decade beyond age 55, the risk of ischemic stroke more than doubles; however, studies suggest that the elderly may receive acute treatments less frequently. Recently, several trials have shown benefit for endovascular thrombectomy (IA). Many of these trials included elderly patients. It remains unclear if previously described age disparities will continue to be seen as strategies for acute stroke therapy evolve. The purpose of this analysis was to establish the proportion of older adults that received acute revascularization treatment prior to the publication of these new endovascular trials.

Methods:
We used the National Inpatient Sample to obtain data on primary ischemic stroke diagnosis discharges from US hospitals between 2006 to 2011. Among these discharges, utilization of IV tPA or endovascular thrombectomy was identified using procedure codes. Discharges were further classified by age ≥75 and year.

Results:
Over the 6 year period, nearly half (47%) of the 2,592,269 ischemic stroke discharges were age 75 or older. Despite this, they represented only 27% of tPA administrations and 34% of endovascular procedures (Figure 1). For all ischemic stroke discharges during this period, tPA was administered in a lower proportion of patients ≥75 years compared to those <75 (3.7% [95% CI 3.5-4.0] vs. 4.5% [95% CI 4.3-4.8%]). Both tPA utilization and endovascular procedures increased each year for all age groups (p<0.001, Figure 1).

Conclusions:
Despite the fact that approximately half of stroke discharges were age 75 or older, they account for only about 30% of those receiving acute stroke therapies. As the US population ages, these findings raise concern that fewer older patients will receive the only acute therapies shown to improve functional outcome in ischemic stroke. Providers should be cognizant of potential age biases when selecting candidates for acute therapy and should continue to enroll the elderly in therapeutic trials.
Abstract 159: Posterior Communicating Artery Flow Diversion in Middle Cerebral Artery Stroke: Angiographic Evidence from IMS III
Authors: Liebeskind David S , Demchuk Andrew M , Jovin Tudor G , Menon Bijoy K , Nogueira Raul G , Zaidat Osama O , Scalzo Fabien , Hill Michael D , Carrozzella Janice , von Kummer Ruediger , Khatri Pooja , Goyal Mayank , Yan Bernard , Foster Lydia D , Yeatts Sharon D , Palesch Yuko Y , Broderick Joseph P , Tomsick Thomas A , Yoo Albert J ,   for the IMS III Investigators
Published: July 2021

Background:
Only 20% of adults have a “fetal” posterior communicating artery (PCOMM) with carotid flow to the posterior cerebral artery. Dynamic pressure changes at the circle of Willis due to proximal artery occlusion may restore such collateral blood flow patterns. We investigated the findings and implications of PCOMM blood flow in middle cerebral artery (MCA) stroke at angiography in IMS III.

Methods:
The angiography core lab prospectively evaluated PCOMM blood flow and collateral circulation in proximal MCA or M1 occlusion. Proximal or distal M1 occlusion was noted with PCOMM flow scored (0-2) on ipsilateral carotid injections before and after endovascular therapy, correlating PCOMM status with ASITN/SIR leptomeningeal collateral grade, TICI reperfusion and subsequent clinical outcomes.

Results:
122 patients with M1 occlusion at angiography (60 proximal, 62 distal) had peri-procedural evaluation of PCOMM status and associated collateral grade. Ipsilateral carotid injections revealed PCOMM flow diversion in 87/122 (71%) prior to revascularization, including 41/60 (68%) in proximal M1 and 46/62 (74%) in distal M1 (p=0.61) occlusions. After treatment, PCOMM patency was noted in 86/122 (71%), with 40/60 (67%) in proximal M1 and 46/62 (74%) in distal M1 (p=0.48) occlusions. Decrease in PCOMM score after therapy was noted in 11/122 (9%); 9/11 (82%) had mTICI 2B-3 reperfusion compared to 48/111 (43%) mTICI 2B-3 reperfusion in those with PCOMM unchanged (p=0.03). PCOMM flow (n=85) was associated with worse ASITN/SIR collaterals (median 2, IQR 2-3) than those without (n=29; median 3, IQR 2-3), p=0.09. PCOMM patency before treatment had 90-day mRS median of 4 (2-6) versus 3 (1-4), p=0.37.

Conclusions:
PCOMM flow diversion is common in MCA stroke, revealing an inverse correlation with leptomeningeal collaterals and dynamic changes following reperfusion.