bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP98: Moderate Physical Exercise Promotes Cognitive Recovery Following Focal Cerebral Ischemia in Rats
Authors: Youbi Mehdi , Cohan Charles H , Stradecki Holly M , Tiozzo Eduard , Dave Kunjan R , Wright Clinton B , Sacco Ralph L , Perez-Pinzon Miguel A
Published: March 2022

The majority of stroke patients suffer long-term disabilities impacting both motor and cognitive function. Physical exercise has been shown to improve functional recovery following focal cerebral ischemia by facilitating brain plasticity. However, the exercise intensity that promotes optimal cognitive recovery needs closer examination. This study seeks to analyze the effects of forced treadmill exercise at various speeds on spatial memory tests after focal ischemia in rats. We hypothesized that, a moderate intensity treadmill regiment will better ameliorate cognitive deficits and improve functional recovery after focal ischemia compared to the high or mild intensity groups. Three-month-old male Sprague Dawley rats were acclimated to the investigator and treadmill for three days. On day four, rats underwent focal cerebral ischemia using the middle cerebral artery occlusion model for 90 minutes or sham surgery and were randomly assigned to an exercise intensity group. Rats had three days of recovery post-surgery followed by forced treadmill exercise for six days. The rats were exposed to a two-minute warm-up period at 5 m/min and then exercised for a period of 30 minutes at 6 m/min for mild, 10 m/min for moderate, and 18 m/min for heavy. Finally, the rats were subjected to contextual fear conditioning where rats were placed in a fear conditioning chamber for 8 minutes with a 2 second 1.5 mA shock delivered at minute 7.5 then returned to chamber 24 hours later. Fear conditioning data showed that, following a stroke rats froze 16.48 +/- 2.75%, compared to the moderate intensity group where rats froze 63.57 +/- 10.72 % (S.E.M, n = 10, p < 0.01, one-way ANOVA, Bonferroni post-hoc). Mild and heavy exercise groups froze 43.3 +/- 10.75% and 38.26 +/- 10.53% respectively. In conclusion, focal cerebral ischemia impairs cognitive function, however moderate intensity physical exercise has the most beneficial impact on cognitive recovery compared to other exercise intensities.
Abstract WMP101: Paramedic Management of Childhood Arterial Ischemic Stroke
Authors: Stojanovski Belinda , Monagle Paul T , Newall Fiona , Churilov Leonid , Mosley Ian , Hocking Grant , Mackay Mark T
Published: March 2022

Introduction and objectives:
Ambulance usage is the most important factor resulting in shorter time to hospital arrival in adult stroke. Prenotification and bypass to stroke centres are associated with increased thrombolysis rates. Sensitivity of paramedic stroke identification in adults varies from 44-66% but there are no published data in children.

Hypotheses and aims:
We hypothesised that emergency medical services call-taker (EMSDCT) and paramedic identification of childhood arterial ischemic stroke (AIS) is suboptimal and contributes to prehospital delays. Our aims were to determine sensitivity of EMSCT and paramedic diagnosis, and to describe patterns and timelines of paramedic care in childhood AIS.

Methods:
Retrospective study of ambulance transported children <18 years with radiologically confirmed AIS, from 2008-2015. Direct admissions to inpatient units were excluded.

Results:
Ambulance records were reviewed for 19 children. Four children were excluded because records were unavailable. 58% were female, median age was 8 years (IQR 3-14) and median PedNIHSS score was 8 (IQR 3-16). EMSCT diagnosis was stroke in 21% of children and Code 1 (lights and sirens) ambulance were dispatched for 72% of children. Paramedic diagnosis was stroke in 26% of children. Prenotification occurred in 42% of children and 64% were transported to adult (6) or pediatric (6) hospitals meeting criteria for primary stroke centres. Median prehospital timelines were: onset to 911 call 13 minutes, call to scene 12 minutes, time at scene 14 minutes, call to ED arrival 54 minutes, and total pre-hospital lag time 71 minutes (IQR 60-85). In contrast post-arrival lag time to radiological confirmation of diagnosis was 568 minutes (IQR 144-799).

Conclusion:
Sensitivity of EMSCT and paramedic childhood AIS diagnosis and pre-notification rates are much lower than those reported in adults. However prehospital factors contribute less to delayed diagnosis than in hospital factors, representing an important difference to adult stroke.
Abstract WMP104: Pediatric Cortical Vein Thrombosis: Frequency and Association With Venous Infarction
Authors: Ritchey Zak , Kenny Amanda , Weitzenkamp David , Fenton Laura Z , Maxwell Emily , Bernard Timothy J , Stence Nicholas
Published: March 2022

Introduction:
Cortical vein thrombosis (CVT) is an uncommon site of involvement in cerebral sinovenous thrombosis (CSVT). Few reports have described pediatric CVT, and none have described its unique features. The aim of our study was to evaluate the clinical and radiographic features of a cohort of children with CSVT, comparing those with CVT to those without CVT.

Hypothesis:
Children with CVT are more likely to experience acute restricted diffusion and chronic venous infarction, as compared to those without CVT.

Methods:
Children diagnosed with CSVT from 2006 to 2014 were enrolled in a prospective cohort study at a single tertiary care center. Inclusion criteria comprised confirmation of CSVT on acute imaging with MRI/MRV or CTV, and availability of follow-up imaging at subacute and chronic time periods. Patients were separated into two groups: those with CVT (CVT group) and those without (non-CVT group). Patient demographics, clinical presentation, and imaging findings were collected and analyzed using a two-tailed Fisher's exact test. Scans were reviewed for clot location and parenchymal abnormalities.

Results:
Fifty patients met inclusion criteria, including 12 with CVT. In both groups, children frequently presented with headache and focal neurological deficits. However, the CVT group was more likely to present with seizure (P = 0.0271), altered mental status (P = 0.0271), and a family history of clotting disorder (P = 0.0477). Acute imaging of the CVT group more commonly demonstrated concurrent superior sagittal sinus thrombosis (P = 0.0024) and restricted diffusion (P < 0.0001); and follow-up imaging in the CVT group more commonly showed venous infarction (P = 0.0007).

Conclusions:
The presence of CVT in our pediatric CSVT cohort was significantly associated with seizures at presentation, venous-territory restricted diffusion on acute imaging, and venous infarction at follow up. While further work is needed to confirm our results, involvement of cortical veins in CSVT appears to be associated with an increased risk of infarction in children.
Abstract WMP107: Arterial Tortuosity: an Imaging Biomarker of Perinatal Stroke Pathogenesis?
Authors: Wei Felix , Diedrich Karl , Mineyko Aleksandra , Kirton Adam
Published: March 2022

Background:
Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable but pathophysiological mechanisms are unknown. Arterial tortuosity may reflect inherent vascular biology. We recently demonstrated an association between abnormal tortuosity and specific arteriopathies in childhood stroke.

Hypothesis:
As fetal periventricular infarction (PVI) has been associated with genetic connective tissue disease, we hypothesized that tortuosity would be increased in PVI compared to other perinatal stroke diseases and controls.

Methods:
Subjects were recruited from the Alberta Perinatal Stroke Project (APSP), a population-based research cohort. Inclusion criteria were MRI-classified perinatal stroke syndrome and 3D time-of-flight MR angiography (MRA). A validated imaging software method calculated cerebral arterial tortuosity using source images. Mean tortuosity scores (ANOVA) and variances (Levene’s test) were compared across arterial ischemic, hemorrhagic, and PVI strokes and controls. Effects of age and gender were examined.

Results:
A total of 130 children were studied (61 arterial, 30 PVI, 15 hemorrhagic, 24 controls). Tortuosity scores and variances were consistent with validation studies. Tortuosity was not associated with age at imaging (including infants versus older children) or gender. Variance in tortuosity was much greater in all perinatal stroke groups compared to controls (p<0.0008) with no differences between specific stroke types found. There was no difference in mean tortuosity scores across groups.

Conclusion:
Children with perinatal stroke have an abnormally wide range of arterial tortuosity, suggesting inherent differences in vascular biology. This is consistent with genetic connective tissue disorders associated with PVI while suggesting novel mechanisms for other perinatal stroke diseases.
Abstract WMP12: Thrombectomy Saves Lives AND Saves Money: A Call for Action
Authors: Moussavi Mohammad , Korya Daniel , Panezai Spozhmy , Brar Jaskiran , Mehta Siddhart , Arango Audrey , Qureshi Ihtesham , Kirmani Jawad
Published: March 2022

Background:
Six recent multi-centered prospective randomized control trials (MPRCT)showed mechanical thrombectomy significantly improves outcomes of patients with ischemic stroke due to large vessel occlusion. These results were anticipated to have significant impacts on the healthcare costs associated with ischemic stroke. We performed an analysis to determine the cost and utility of combined intravenous (IV) tissue-type plasminogen activator (tPA) and mechanical thrombectomy compared to IV tPA alone for acute large-vessel ischemic stroke.

Methods:
A meta-analysis of the six most recent MPRCTs was conducted and data was extracted to calculate the number needed to treat (NNT) and number needed to harm (NNH) based on the pooled results. The average costs of hospitalization for various complications associated with ischemic stroke were separately analyzed. There were two groups: "A" were independent (mRS 0-2) after treatment; "B" were disabled (mRS >2). The costs for hospitalization and post-hospitalization were estimated and a comparison was done between the two groups and compared with IV tPA alone versus tPA plus intervention.

Results:
A total of 1,386 patients were included in this analysis from six recent MPRCTs. Of those 698 received IV tPA alone and 688 were treated with thrombectomy and IV tPA. The thrombectomy arm had 46% (n=316) in group A, while the IV tPA alone arm had 27% (n=188) in group A (p=.001). The NNT was 5.1 for patients receiving thrombectomy (p=.001). That translated to 271 more patients becoming independent. The estimated average in-hospital and post-hospital cost for patients in group A was $20,396 and $55,494 for group B. A cost-savings of $14,613,790 would have been achieved, if all patients underwent thrombectomy along with IV tPA.

Conclusions:
The addition of thrombectomy to IV tPA translates to substantial cost benefits. If these figures are extrapolated to all stroke patients, the benefits would substantially lessen the economic burden of the entire healthcare system. Thrombectomy after IV tPA makes sense financially as well as clinically. A strong and urgent consideration for amending Healthcare policy and clinical guidelines should be given.
Abstract WMP120: Radiosurgery Induces Novel Protein Changes on the Endothelium of Arteriovenous Malformations: Potential for Therapeutic Targets
Authors: McRobb Lucinda S , Lee Vivienne S , Thomas Santosh G , Wiedmann Markus , Amal Raj Jude V , Zhao Zhenjun , Grace Michael , Moutrie Vaughan , McKay Matthew , Molloy Mark , Stoodley Marcus A
Published: March 2022

Introduction:
Brain arteriovenous malformations (AVMs) are a significant cause of hemorrhagic stroke. Almost one third are untreatable using current methods. We aim to use stereotactic radiosurgery as a priming tool to elicit novel protein expression on irradiated AVM vessels and targeting with thrombotic antibody-conjugates to induce rapid thrombosis and vessel closure.

Hypothesis:
Radiosurgery induces novel protein changes on the AVM endothelium that are potential therapeutic targets.

Methods:
A model arteriovenous fistula (AVF) formed in rats was irradiated by GammaKnife (20Gy) or sham-irradiated. After 24h, animals were perfused with EZ-link Sulfo-NHS-LC Biotin to label surface-accessible proteins. Biotinylated AVFs were dissected, pooled (n=4/group) and protein extracted. Biotin-labelled proteins were enriched on streptavidin-agarose beads before LC-MS/MS using SWATH acquisition label-free mass spectrometry.

Results:
At 24h post-irradiation, 280 surface-associated proteins were identified in sham and irradiated extracts. Of these, 56 were up-regulated in irradiated AVMs (greater than 1.5-fold change vs sham). Radiation increased fibrinogen α/β (1.5-fold), platelet factor 4 (16-fold) and plasminogen (2-fold), suggesting enhanced adhesion of blood-borne molecules to the vessel wall. Twenty-eight mitochondrial proteins increased, including manganese superoxide dismutase (2-fold), which may reflect radiation-induced changes in subcellular localization or cell lysis causing intracellular molecule release and entrapment. Troponin I (cardiac) and tropomyosin 1α, actin-associated proteins externalized under stress, increased 14- and 4-fold. Secreted and membrane proteins were also identified (e.g. clusterin, 1.5-fold; CD93, 5-fold; Ras-related Rab18, 1.8-fold).

Conclusions:
Using
in vivo
biotin labelling, we have identified a series of novel surface-accessible proteins induced by radiosurgery that are potential therapeutic targets. Externalization of intracellular proteins may provide unique radiation-stimulated candidates for vascular targeting in AVMs.
Abstract WMP27: Differential Gene Expression in Coiled Versus Flow-diverter Treated Aneurysms: a RNA-Seq Analysis in Rabbit Aneurysm Model
Authors: Rouchaud Aymeric , Johnson Collin R , Thielen Evan P , Schroeder Dana J , Ding Yong Hong , Dai Daying , Cebral Juan , Kallmes David F , Kadirvel Ramanathan
Published: March 2022

Introduction:
Numerous endovascular tools exist for the treatment of intracranial aneurysms with an increased use of flow-diverting devices in recent years. However, the biological mechanisms leading to aneurysm healing or potential complications such as delayed aneurysm ruptures after flow-diverter treatment are not yet well established. We used RNA-sequencing technology to identify genes relevant for biological impact of coils and flow-diverters in elastase-induced saccular aneurysms in rabbits and to identify genes and pathways of potential clinical interest.

Methods:
Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery. Aneurysms were treated with coils (n=5) or flow-diverters (Pipeline Embolic Device, Covidien, CA) (n=4). Untreated aneurysms (n=6) were used as controls. Messenger RNA and microRNA were isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed using RNA-seq technology. RNA-seq results were analyzed by using the Ingenuity Pathway Analysis tool.

Results:
Using RNA sequencing for coiled versus non-treated aneurysms, 464 genes were found to be differentially expressed with 58 genes down regulated and 406 genes up regulated. Using the same criteria for the flow-diverter treated aneurysms, 177 genes were found to be differentially expressed with 8 genes down regulated and 169 genes up regulated. Comparing coiled versus flow-diverter treated aneurysms, 13 genes were significantly differentially expressed with 8 down regulated and 5 up regulated genes. Genes identified with the highest interest for aneurysms healing were fibroblast growth factor-23, matrix metalloproteinases (MMP)-1, Scinderin and Basigin (implicated in MMP-2 and MMP-9 regulation). Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions.

Conclusions:
RNA-sequencing analysis of rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and cellular migration that could explain the different biological mechanisms implicated in aneurysms healing either after coiling or flow-diverter treatments and could explain potential device-related complications.
Abstract WMP33: Effects of Organized Stroke Care on In-hospital Mortality and Morbidity of Patients With Ischemic and Hemorrhagic Stroke: J-ASPECT Study
Authors: Kamitani Satoru , Nishimura Kunihiro , Kada Akiko , Sayama Tetsurou , Nishimura Ataru , Kurogi Ryouta , Nakamura Fumiaki , Onozuka Daisuke , Ogasawara Kuniaki , Shiokawa Yoshiaki , Miyachi Shigeru , Yoshimura Shinichi , Toyoda Kazunori , Nakagawara Jyouji , Matsuda Shinya , Okuchi Kazuo , Aruga Toru , Ono Junichi , Nagata Izumi , Miyamoto Yoshihiro , Iwata Michiaki , Hagihara Akihito , Suzuki Akifumi , Kataoka Hiroharu , Ishikawa Koichi B , Iihara Koji
Published: March 2022

Introduction:
Organized stroke care is an integrated approach to managing stroke to improve outcomes. However, the effectiveness of organized stroke care on mortality and morbidity remains uncertain. This study aimed to examine whether Organized stroke care index (OCI), which graded 0-3 based on the presence of rehabilitation, stroke team assessment, and admission to a stroke unit, developed to assess the accessibility to stroke care by Saposnik (Neurology 2010) influenced stroke outcomes in a nation wide hospital cohort.

Hypothesis:
OCI influenced mortality and morbidity of patients with ischemic and hemorrhagic stroke.

Methods:
Of the 1369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding comprehensive stroke care capacities. Among the institutions that responded, data on patients hospitalized between April 1, 2010 and March 31, 2014, because of stroke were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality morbidity was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, Charson Score and the number of OCI fulfilled in each component and in total.

Results:
Data from 265 institutions and 220,027 emergency-hospitalized patients were analyzed. Patients fulfilled the criteria for admission to a SCU, stroke team assessment and the presence of rehabilitation were 29.9%, 41.2% and 66.5%, respectively. Mortality adjusted for age, sex, Charson score and level of consciousness was significantly correlated with admission to a SCU (OR=0.83, p<0.001), SCU team assessment (OR=0.84,P<0.001), and rehabilitation (OR=0.36, p=0.031). OCI was significantly associated with decreased mortality (OR=0.45, p<0.001) and the highest OCI score was associated with 89.4% decrease of mortality. (OR=0.104, p<0.001) Modified ranking scale 0 to 2 rate were also associated significantly with SCU admission (p<0.001). These association holds for ischemic stroke and subarachnoid hemorrhage.

Conclusion:
A strong association between organized stroke care and lower mortality was apparent. These data suggest that organized stroke care should be provided to stroke patients regardless of stroke subtype.
Abstract WMP34: Use of Intravenous Tissue Plasminogen Activator in Patients Without a Stroke (Stroke Mimics): Findings From the get With the Guidelines Stroke Registry
Authors: Xian Ying , Federspiel Jerome J , Cox Margueritte , Hernandez Adrian F , Kosinski Andrzej S , Bettger Janet P , Schulte Phillip , Lytle Barbara , Fonarow Gregg C , Smith Eric E , Bhatt Deepak L , Schwamm Lee H , Peterson Eric D
Published: March 2022

Background:
The necessity for rapid evaluation and treatment with intravenous tissue plasminogen activator (tPA) in acute ischemic stroke may increase the risk of administrating tPA to patients without a stroke (“stroke mimics”).

Methods:
Using data from the Get With The Guidelines Stroke Registry from 2009 to 2015, we identified 90,746 patients treated with tPA within 4.5 hours of symptom onset. We documented use of tPA in stroke mimics, defined as patients initially thought to have a stroke but without a final diagnosis of one, and compared patient characteristics and outcomes between tPA-treated mimics vs. ischemic strokes.

Results:
Overall, only 0.8% (728) of all tPA cases were given to stroke mimics, ranging from 0.2% in 2009 Q1 to 1.3% in 2015 Q1. The most common documented diagnoses in tPA-treated mimics were migraine (15.6%), functional disorder (9.4%), and seizure (7.2%). Compared with tPA-treated true stroke patients, tPA-treated mimics were younger (median 52 vs. 72 years), had lower prevalence of atrial fibrillation, coronary artery disease, dyslipidemia, hypertension, heart failure, had less severe National Institute of Health Stroke Scale (median 7 vs. 10), but higher prevalence of prior stroke/transient ischemic attack (34.4% vs. 25.5%), all p<0.001. The door-to-needle times were similar in stroke mimics and true stroke groups (median 68 vs. 68 minutes, p=0.82). Rates of symptomatic intracranial hemorrhage (sICH) were quite rare in stroke mimic patients (0.4%, 3/728) as compared with 4.3% (3846/90018) in patients with an ischemic stroke; adjusted OR for sICH (0.19, 95% CI 0.06-0.58). The in-hospital mortality rate was significantly lower in tPA-treated stroke mimics as compared with ischemic stroke patients (0.6% vs. 7.3%, adjusted OR 0.16, 95% CI 0.06-0.43).

Conclusions:
In this large nationwide cohort of patients treated with tPA, only 1 in 125 patients who received tPA for presumed stroke was a false positive and complication rates associated with tPA administration to stroke mimics were quite low. Nonetheless, there still may be opportunities to continue to improve the rapid and accurate diagnosis and treatment of ischemic stroke.
Abstract WMP4: Analysis of Outcomes From the Endovascular Treatment of Posterior Circulation Strokes in the Modern Era of Stent Retriever Thrombectomy
Authors: Mokin Maxim , Sonig Ashish , Sananthan Sananthan , Kan Peter , Duckworth Edward , Venkatasubba Rao Chethan , Arthur Adam , Elijovich Lucas , Goyal Nitin , Linfante Italo , Dabus Guilherme , Turk Aquilla , Turner Raymond , Snyder Kenneth , Levy Elad , Siddqui Adnan
Published: March 2022

Background:
Evidence for endovascular treatment of anterior circulation strokes is well developed. However, patients with posterior circulation strokes have been excluded from recent randomized endovascular stroke trials.

Objective:
To evaluate outcomes of posterior circulation strokes treated with modern endovascular therapy since the FDA approval of stent retrievers, and to identify predictors of clinical outcomes and complications in this specific population of stroke patients.

Methods:
We performed a multicenter retrospective analysis of consecutive patients with posterior circulation strokes who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including the ADAPT approach). We correlated favorable clinical outcomes with demographic, clinical and technical characteristics.

Results:
A total of 84 patients were included in this study (mean age, 63.5 years; mean admission NIHSS score, 19.2). Favorable clinical outcome at 3 months, defined as mRS score 0-2 was achieved in 34 (40%) patients. NIHSS score < 20, the use of conscious sedation rather than general anesthesia and successful recanalization (TICI 2b/3) were significant predictors of favorable clinical outcome at 90 days. The use of baseline advanced imaging (CT perfusion, multi-phase CTA or MRI) for patient selection was not associated with improved outcomes. In patients with the time of symptom onset to femoral puncture < 6 hours, mRS 0-2 at 3 months was achieved in 51.2% of cases. Treatment initiated beyond the 6-hour window resulted in 30.2% rate of mRS 0-2 at 3 months.

Conclusions:
Severity of admission NIHSS score, recanalization success and the type of anesthesia strongly correlate with clinical outcomes in endovascular therapy of posterior circulation strokes. The highest rate of long-term favorable outcomes was achieved in patients whose thrombectomy was initiated within the first 6 hours of stroke onset. However, even when started beyond the 6 hours window, endovascular treatment of posterior circulation strokes is feasible.
Abstract WMP47: Nrf2 Deficiency Exacerbates Sensorimotor Deficit and Impairs Long-term Functional Recovery After Ischemic Stroke
Authors: Liu Lei , Dweik Yasmin , Weider Matthew , Vollmer Katie , Fernandez Victoria , Doré Sylvain
Published: March 2022

Introduction:
Ischemic stroke is a devastating form of stroke with extremely high disability that affects more than 690,000 adults each year. Over the past decade, the transcriptional factor Nrf2 has emerged as a master regulator of cellular oxidative stress and inflammation that eventually leads to neuronal death through activation of various cytoprotective and detoxification genes, which are the central features of neurodegeneration, including stroke. Whether Nrf2 improves long-term sensorimotor outcome after ischemic stroke is not known.

Hypothesis:
Nrf2 may alleviate sensorimotor deficits and promote long-term recovery after stroke injury.

Methods:
Three- to four-month-old male C57BL/6 mice, including Nrf2 knockouts, were subjected to surgery of permanent distal middle cerebral artery occlusion (pMCAO). The functional outcomes were investigated 3 days prior to and 1, 3, 7, 14, 21, and 28 days after pMCAO with a comprehensive behavioral test battery, including open field, modified cylinder, and corner tests.

Results:
There was no significant difference in behavior tests between Nrf2 knockout and wildtype mice in basal condition. After pMCAO, although Nrf2 knockout and control mice had similar function deficits in the open field test on day 1, Nrf2 deficiency compared to controls dramatically decelerated recovery in open field locomotor activity at the acute stage of cerebral stroke (1-3 days), but not at later time points. In the modified cylinder test, Nrf2-/- mice displayed remarkably severe sensorimotor deficits by the rate of total contralateral forelimb use and forelimb use in first contact events at the acute stage (0-3 days), especially on day 3, and impaired the recovery by forelimb use in first contact events at all lateral time points over 4 weeks. Such findings were supported by results in the corner test.

Conclusion:
These data demonstrate that Nrf2 deficiency exacerbates functional deficits and impairs long-term sensorimotor recovery after pMCAO-induced ischemic stroke damage.
Abstract WMP50: Pregnancy in Advanced Age Increases the Risk of Hemorrhagic Stroke in Post-menopausal Women. Analysis of Women's Health Initiative Study
Authors: Qureshi Adnan I , Saeed Omar , Malik Ahmed A , Jan Degenhardt Jan , Roland Ax-Fliedner Roland , Kohl Thomas
Published: March 2022

Background:
The incidence of pregnancy in advanced age among women is increasing due to availability of assisted reproduction although the complication rates associated with pregnancy are higher. The long-term health consequences in women with pregnancy in advanced age is not known. We determine the effect of pregnancy in advanced age on occurrence of cardiovascular events in a large cohort of post-menopausal women.

Methods:
We analyzed the data for 72,221 women aged 50-79 years who were enrolled in the observational arm of the Women's Health Initiative Study. We determined the effect of pregnancy in advanced age (last pregnancy at age≥40 year) on risk of ischemic stroke, hemorrhagic stroke, myocardial infarction, and cardiovascular death over a mean period (± standard deviation [SD]) of 12±1 years using Cox Proportional Hazards analysis after adjusting for potential confounders.

Results:
A total of 3306 (4.6%) of the 72,221 participants reported pregnancy in advanced age. Compared with pregnancy in normal age, the rate of ischemic stroke (2.4% versus 3.8%, p<0.0001), hemorrhagic stroke (0.5% versus 1.0%, p<0.0001), myocardial infarction (2.5% versus 3.0%, p<0.0001), and cardiovascular death (2.3% versus 3.9%, p<0.0001) was significantly higher among women with pregnancy in advanced age. In multivariate analysis, women with pregnancy in advanced age were 60% more likely to experience a hemorrhagic stroke (Hazards ratio [HR] 1.6, 95% confidence interval [CI] 1.1-2.4) after adjusting for age, race/ethnicity, congestive heart failure, systolic blood pressure, atrial fibrillation, alcohol use and cigarette smoking. There was no significant difference in the risk of ischemic stroke, myocardial infarction, and cardiovascular death among women with pregnancy in advanced age after adjusting for potential confounders.

Conclusions:
Women with pregnancy in advanced age have a higher risk for hemorrhagic stroke in post-menopausal period.
Abstract WMP57: Worsening Migraines in Current Hormone Replacement Therapy Users Predicts Higher Risk of Stroke
Authors: Rahman Haseeb A , Malik Ahmed , Saeed Omar , Thomas Abraham , Qureshi Adnan
Published: March 2022

Background:
There has been a long-standing debate in the role of hormone replacement therapy (HRT) and migraines as risk factors for ischemic stroke. HRT are considered a risk factor for migraines. The risk of ischemic stroke may increase as the severity of migraines increases in patients that are currently using HRT.

Methods:
We analyzed the data for 82,208 women aged 50 - 79 years who were enrolled in the observational arm of the Women’s Health Initiative Study. We determined the risk of ischemic stroke in participants with migraines who had current Hormone replacement therapy (HRT) (unopposed estrogen and/or estrogen plus progesterone), past HRT, and no HRT. We further dichotomized participants with migraines into participants who experienced an increase in migraine severity of one grade or more from baseline on the third-year follow up visit and participants who experienced no change or a decrease in migraine severity from baseline on the third-year follow up visit. The relative risk of developing ischemic stroke was compared between participants who were currently on HRT and participants who were either previously on HRT or never had HRT.

Results:
Out of the 82,208 women, 37680 (45.8%) were currently using HRT and 44528 (54.2%) were either past users or had never used HRT therapy. Compared with never or past users of HRT, rate of increase in severity of migraines was significantly higher among those who were currently on HRT therapy (17.3% versus 18.7% versus 20.6%, respectively, p<0.0001). Odds ratio (OR) of ischemic stroke for patients who never used HRT or used HRT only in the past compared to those who were current users and experienced no change or a decrease in migraine severity was 0.91 [confidence interval (CI) 0.88 - 0.94] versus 1.1 [CI 1.1 - 1.2], (p<.0001). OR of ischemic stroke for patients who never used HRT or used HRT only in the past compared to those who were current users and experienced an increase in severity of migraines was 0.81 [CI 0.74 - 0.88] versus 1.3 [CI 1.1 - 1.5] (p<.0001).

Conclusions:
Patients that are current users of HRT that have an increase in severity of one grade or more of migraines are shown to have an increased risk of ischemic strokes. Future studies are required to further investigate these correlations.
Abstract WMP60: Interactive Children's Stroke Program Yields High Profiecency Scores on 6 Month Assessment
Authors: Wheeler Janie L , Swope Cindy
Published: March 2022

Background:
Although community stroke recognition has improved slowly over the last 2 decades, currently 1 in 3 Americans cannot recall any stroke signs or symptoms. This has impact beyond an individual level as 66% of stroke cases are identified by someone other than the person experiencing symptoms.

Purpose:
To implement a 1 hour interactive program emphasizing the FAST acronym for stroke signs and symptoms for school aged children in the Central Ohio area and at 6 months have 80% of students able to recognize signs and symptoms of stroke and call 911.

Method:
We developed 5 interactive rotating stations each lasting 5-10 minutes (total program of 1 hour). Each station used adaptive equipment to mimic a stroke deficit. To reinforce FAST, other signs and symptoms of stroke and the importance of calling 911, and to start conversations in homes and educate those beyond the classroom, a coloring booklet with a stroke story, facts and activities was given to each child at the end of the program. Grade appropriate baseline knowledge assessments were given 1 week prior to program participation. The same assessments were given 1 week post program to measure knowledge gained based on group's overall average score and at 6 months measuring knowledge retention defined as 80% of individuals scoring at least 80% or above in recognizing signs and symptoms of stroke.

Results:
There were 839 children educated across 15 schools (12% 3rd grade, 46% 4th grade, 42% 5th grade). Every class for every grade demonstrated improvements in knowledge from the pre-to post-assessment. The aim for 6-month knowledge retention across participants was met (Figure 1).

Conclusion:
Addressing gaps in community stroke recognition through a 1 hour interactive children's stroke program yielded >80% knowledge proficiency after 6 months. Further research is warranted to determine the association between educating with adaptive equipment compared with standard printed materials and/or lecture.
Abstract WMP67: Stroke Screening Tools Have High Specificity for Detecting Large Vessel Occlusion in a Southeastern US Prospective Cohort Study
Authors: Qureshi Sakib , Janjua Ahmad Umair , Raza Syed Ali , Brasher Cynthia , Anderson Aaron , Belagaje Samir , Ranagaraju Srikant , Frankel Michael R , Nogueira Raul , Haussen Diogo C , Greene James , MacDonald Paul , Javalkar Vijayakumar , Dharia Robin , Obideen Mahmoud , Dehkharghani Seena , Camp Debbie , Lugtu James , Ehleben Carole , Nahab Fadi
Published: March 2022

Introduction:
Previously reported stroke screening tools used to identify large vessel occlusion (LVO) have been developed based on retrospective analyses or cohorts enrolled in a clinical trial.

Hypothesis:
Stroke screening tools may have lower specificity for detection of LVO when tested in a prospective cohort study of patients identified by emergency medical services (EMS) to have stroke signs and symptoms.

Methods:
Consecutive patients presenting to a stroke center with stroke symptoms or a positive FAST screen by EMS within 6 hours from stroke onset or wakeup were included in this prospective analysis. All patients were initially evaluated by a neurology attending or resident and underwent non-contrast CT (NCCT). Patients identified to have a stroke mimic on initial assessment or hemorrhagic stroke on NCCT did not undergo intracranial large artery imaging (iLAI); all remaining patients underwent iLAI. Sensitivity and specificity for LVO with the following screens were assessed: NIHSS ≥ 15, LAMS ≥ 4, RACE ≥ 5 and CPSSS ≥2.

Results:
Of 92 patients (mean age 69±17 years, mean NIHSS 8) evaluated over the 3 month study period, 41 (45%) were identified to have a stroke mimic and 9 (10%) had a hemorrhagic stroke on NCCT; 19 (21%) patients had LVO. The remaining 42 patients underwent iLAI within <24 hrs (median time from last seen normal time to imaging 215 minutes). Sensitivity and specificity for NIHSS, LAMS, RACE and CPSSS scales to detect LVO are shown in the Table; there was relatively high specificity among all scales which improved after excluding patients with stroke mimics and hemorrhagic stroke on NCCT.

Conclusion:
Previously published stroke screening tools have high specificity for detection of LVO when tested in a prospective cohort study of patients identified by EMS to have stroke signs and symptoms.
Abstract WMP71: Multimodal Imaging Yields Low Number of Stroke Mimics Treated With Thrombolytic Therapy Without Sacrificing Door-to-Needle Times
Authors: Arch Allison E , Starkman Sidney , Yoo Bryan , Alfonso Rodel , Shkirkova Kristina , Huang Josephine , Nour May , Tarpley Jason , McManus Michael , Kleinman Jonathan T , Vespa Paul M , Buitrago-Blanco Manuel , Ng Kwan L , Kim Doojin , Hinman Jason D , Rao Neal , Ali Latisha K , Liebeskind David S , Saver Jeffrey L
Published: March 2022

Introduction:
Speed is critical in fibrinolytic therapy for acute ischemic stroke (AIS), but rapid decision-making may increase tPA use in stroke mimics. Complications from lytics in mimic patients, though uncommon, can be severe. Mimic treatment rates when using non-contrast CT as the only initial imaging modality have increased to as high as 34% with intensified efforts to reduce door to needle (DTN) times. Efficient imaging with MRI or multimodal CT may potentially avoid high mimic treatment rates without prolonging treatment.

Methods:
In a prospectively maintained registry, we examined all patients treated with IV tPA from January 2010 to June 2015. Institutional policy was to perform MRI first in AIS patients and start tPA on the MR table after DWI showed ischemia and GRE excluded hemorrhage; if MRI could not be performed, multimodal CT with CTA and CTP was performed.

Results:
Among 319 IV tPA treated patients, age was 71 (±15), 50% were female, and NIHSS was 13.3 (±8.0). Imaging modality before tPA was MR in 193 (61%) and CT in 126 (39%). In the entire population, the DTN time was 54 (IRQ 42-73) mins and the proportion of mimic patients was 3.1%. DTN times decreased steadily throughout the 5.5 year study period, and did not differ among patients imaged with MR vs CT (Figure). The reduction in DTN times was not associated with an increase in mimic-treated rates (Figure). Among the mimic patients, final diagnoses were migraine - 4, seizure - 3, meningitis - 1, PE - 1, and cardiac dysrhythmia - 1. Imaging modalities in mimic patients were MRI in 5 and CT in 5. Preliminary imaging reads suggested abnormality in 2/10, but final reads were normal in all. In 3/10 mimic patients, tPA infusions were stopped before full dose when ongoing imaging further clarified diagnosis.

Conclusion:
A rapid stroke assessment protocol using MRI or multimodal CT permits swift start of thrombolytic therapy and low rates of stroke mimic treatment.

Figure.
Door-to-needle time and percent stroke mimics by year.
Abstract WMP77: Neurovascular Complications During Long-term Left Ventricular Assist Device (LVAD) Support: Single Center Experience
Authors: Izzy Saef , Renault Simone , Rubin Daniel , Vaitkevicius Henrikas , Smallwood Jennifer , Givertz Michael M , Feske Steven K
Published: March 2022

Introduction:
Left ventricular assist devices (LVAD) have emerged as the standard of care for treating patients with advanced heart failure refractory to maximal medical therapy. Postoperative cerebrovascular complications are an important cause of morbidity and decreased quality of life. However, the literature contains little data on the incidence, predictors, and outcome of stroke.

Hypothesis:
We aimed to determine the incidence of cerebrovascular complications, their type, and association with stroke risk factors and anticoagulation therapy.

Methods:
Data were collected prospectively on all patients with LVADs implanted at BWH. Categorical variables were tested by Chi-square.

Results:
From 2007 to 2015, 151 patients (123 male; median age 57) underwent implantation of HeartMate II LVAD: 79 bridge to transplant, 62 destination therapy, and 10 bridge to candidacy.

Strokes occurred in 31 patients (21%). Risk of stroke did not correlate with sex (25 male, 6 female) or age (median at stroke onset 57). Seventeen acute ischemic strokes (AIS) occurred in 16 patients and 17 intracerebral hemorrhages (ICH) occurred in 15 patients. Four of the AIS were complicated by secondary hemorrhage. Events occurred at a mean of 362 days from implantation (range 5 days-6 years 8 months).

All patients except one were on warfarin at time of stroke (goal INR 2-3.5). Mean INR at AIS onset was 2.3 compared to 3.0 for ICH. Of the 15 ICH patients, 3 had supratherapeutic INR > 3.5. Eleven of the 16 AIS patients were also receiving ASA, 1 ASA + dipyridamole, 1 ASA + dipyridamole + bivalirudin. One received ASA only. All ICH patients and all those with AIS with secondary hemorrhage were on ASA.

Patients with COPD were more likely to have a stroke (p = 0.0006); 30 of the 151 patients had COPD and 13 of them (43%) had strokes. Risk of stroke did not correlate with DM, HTN, hyperlipidemia, CKD, PAD, AF, or prior stroke.

Nineteen of 31 patients with stroke versus 22 of 120 without stroke died (mortality 61 v 18 %; p << 0.001).

Conclusions:
Stroke is an important cause of major morbidity and mortality in patients on LVAD support. Patients with COPD are at an increased risk of stroke. Further studies addressing post-LVAD stroke risk, prevention, and treatment are warranted.
Abstract WMP78: Follow-up High-Sensitivity C-reactive Protein is Associated With Early Recurrent Ischemic lesions in Acute Ischemic Stroke
Authors: Tateishi Yohei , Kanamoto Tadashi , Nakaoka Kenjiro , Hamabe Jumpei , Morofuji Yoichi , Horie Nobutaka , Izumo Tsuyoshi , Matsuo Takayuki , Tsujino Akira
Published: March 2022

Background:
Early recurrent ischemic lesions (ERILs) on diffusion-weighted imaging (DWI) after acute ischemic stroke have been considered as a potential marker of early recurrent symptomatic stroke. The aim of this study to explore the impact of High-sensitivity C-reactive protein (hsCRP) levels at different time points on ERILs.

Method:
We prospectively enrolled 484 patients with acute ischemic stroke who underwent DWI and whose plasma and serum biomarkers (hsCRP, D-dimer, and brain natriuretic protein [BNP]) within 24 hours of onset and subsequently at 7 days after onset. Baseline characteristics, stroke features, initial National Institutes of Health Stroke Scale (NIHSS) score, and DWI lesion volume were recorded. ERILs were defined as new ischemic lesions on 7-day DWI, which were outside the vascular territory of index stroke with arterial occlusion and the same or outside the vascular territory of index stroke with arterial stenosis.

Results:
ERILs were observed in 146 patients (30.2%). In univariate analysis, atrial fibrillation (p=0.040), higher initial NIHSS score (p<0.001), larger DWI infarct volume (p<0.001), stroke subtype (p<0.001), elevated initial and follow-up BNP (p=0.014 and p=0.003) and D-dimer (p=0.009 and p=0.011), and elevated follow-up hsCRP (p<0.001) were positively associated and combination of anticoagulation and antiplatelet therapy after admission (p=0.002) was negatively associated with ERILs. In multivariate analysis, combination of anticoagulation and antiplatelet therapy after admission (Odds ratio [OR], 0.462; 95% confident interval [CI], 0.272 to 0.785; p=0.004) and follow-up log hsCRP (OR, 1.389; 95% CI, 1.054 to 1.830; p=0.020) were independent predictors of ERILs.

Conclusions:
Underlying inflammation after acute ischemic stroke may be associated with ERILs.
Abstract WMP79: Sex-related Differences in Anti-thrombotic Therapy, Risks of Both Recurrence and Cerebral Bleedings as Well as Functional Outcome, in Patients With Atrial Fibrillation and Acute Stroke
Authors: Antonenko Kateryna , Caso Valeria ,   on behalf of the RAF study
Published: March 2022

Background and purposes:
Recent evidence suggests that women have a higher frequency of atrial fibrillation (AF) compared to men, and those women with AF have a higher associated risk for thromboembolic events compared to men with AF. The aim of this study was to evaluate the sex-differences in patients with acute stroke and AF, regarding anti-thrombotic therapy, risks of both recurrence and cerebral bleedings as well as functional outcome.

Methods:
Data from the RAF study, a prospective, multicentre, international study that included patients with acute stroke and AF were analysed. Patients were followed-up for 90 days. Disability was measured with modified Rankin Score (3 to 6 = disabled or dead).

Results:
Of the 1,029 patients enrolled, there were 561 women (54.5%) (p<0.001), and they were younger (p<0.001) compared to the enrolled men. In patients with known AF, women were less likely to receive oral anticoagulants before index stroke (p=0.026) as well, more women were less likely to receive anticoagulants after stroke (28.8% versus 21.6%, p=0.009). There was no sex difference regarding the time when the anticoagulant therapy was initiated between the two groups (6.4±11.7 days in men versus 6.5±12.4 days in women, p=0.902). Men presented with more severe strokes at onset than women (mean NIHSS 9.2±6.9 versus 8.1±7.5, p<0.001). Within 90 days, women had 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings compared to 30 (6.4%) and 18 (3.8%) respectively in men (p=0.28 and p=0.74). At 90 days 57.7% of the women were disabled or dead compared to 41.1% of the men (p<0.001). On multivariate analysis, this significance was not present.

Conclusions:
This study reveals that women with AF were less likely to receive oral anticoagulants prior to stroke and following stroke as secondary prevention compared to men with AF. On admission, women had a less severe stroke compared to men. At 90 days, there were no differences in both recurrent ischemic event and bleeding between the sexes as well as function outcome.
Abstract WMP81: Collaterals and the Severity of Hypoperfusion in Acute Ischemic Stroke are Independent of Dehydration or Volume Status
Authors: Liebeskind David S , Woolf Graham W , Sanossian Nerses , Liu Dezhi , Lopez Brandon , Sheth Sunil A , Liang Conrad W , Ali Latisha K , Kim Doojin , Hinman Jason D , Rao Neal M , Starkman Sidney , Jahan Reza , Gonzalez Nestor R , Tateshima Satoshi , Duckwiler Gary R , Saver Jeffrey L , Yoo Bryan , Scalzo Fabien ,   for the UCLA Stroke Investigators
Published: March 2022

Background:
Systemic hemodynamic factors may affect blood flow to the brain, yet the influence of volume status and the use of fluid administration to improve perfusion in acute ischemic stroke remains unproven. We correlated the presence of dehydration and volume status defined by initial lab values with perfusion MRI and collaterals at angiography in middle cerebral artery (MCA) stroke patients.

Methods:
Retrospective analysis of a consecutive series of isolated M1 MCA occlusions was conducted at an expert core lab to quantify acute Tmax volumes, Tmax hypoperfusion severity ratios and ASITN collateral grade on digital subtraction angiography (DSA). Blood urea nitrogen (BUN) and creatinine (Cr) measured during triage were correlated with hypoperfusion and ASITN/SIR grade. Statistical methods included correlations and ANOVA.

Results:
95 patients (median age 74 (24-101) years; 71 women; median NIHSS 16; median time to MRI, 4h06min) with acute stroke due to M1 occlusion (52 proximal, 43 distal) had contemporaneous BUN/Cr, perfusion MRI and DSA during a 6-year period. Dehydration was noted in 38% (BUN/Cr>20) and 71% (BUN/Cr>15) of patients. Tmax>6sec volumes were median 197 cc (IQR 102-347), with Tmax hypoperfusion severity ratios of 10/6 (median 0.80 (IQR 0.72-0.87)). DSA collateral grade was median 2 (IQR 2-3). Volume status or BUN/Cr was distinct from Tmax hypoperfusion severity at all thresholds, including Tmax>6s (r=0.143, p=0.166), Tmax 10/6 (r=0.114, p=0.271). Direct correlation between BUN/Cr and DSA collateral grade was also unapparent (r=0.034, p=0.744).

Conclusions:
Dehydration and the degree of volume depletion may be common, but are not associated with the severity of collateral perfusion in acute M1 MCA occlusion. Collateral grade defined by DSA and the associated severity of hypoperfusion in the brain is unrelated to intravascular volume status.