bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W MP85: MRI Demonstrates Sustained Effect of Early Surgery on Perihematomal Edema
Authors: Mould W. A , Zentar Marc , Muschelli John , Carhuapoma J. R , Hanley Daniel F
Published: March 2022

Introduction:
The clinical implications of perihematomal edema (PHE) on patients with spontaneous intracerebral hemorrhage (ICH) remains an important question. While several studies describe the natural history of this inflammatory response, progression of PHE in conjunction with ICH evacuation is less understood. We compare CT- the most widely accessible image modality in ICH- with MRI- previously described to be the gold standard for assessing PHE- both to validate the use of CT in PHE measurements and to understand the effect of hematoma evacuation upon PHE mitigation at Day 7.

Methods:
We analyzed 43 of 123 patients from MISTIE II (29 surgical, 14 medical). 80 patients were excluded due to missing MRIs at time points T1 (pre-randomization) or T2 (Day 7). MRI edema volume was calculated by manually tracing hyperintense regions on T2-weighted FLAIR sequences and then subtracting the ICH volume measured on the closest CT. CT edema volume was calculated using a semi-automated threshold based approach. A sample set of both MRIs and CTs were assessed by a second blinded reader to assess inter-observer reliability using Pearson correlation.

Results:
There was no significant difference between the two treatment cohorts in age, gender, or initial ICH size. The absolute difference in PHE for surgical patients was similar for both MRI, .92cc, and CT, -3.51cc, with a mean difference of 4.44 cc (p-value=.179). For medical patients , the difference between the two time points was MRI, 29.19 cc and CT, 28.74 cc, mean difference of 0.45 cc (p-value=.92). A similar trend exists between ICH removal and edema volume as in previously published work, the less blood removed the greater the amount of edema. Both modalities were robust measures of PHE with inter-reader reliability scores calculated for MRI, .99 (95% CI, .995-.999) and CT .97 (95% CI, .922-.994).

Conclusion:
This analysis of a multi-site, international patient population confirms the accuracy of using CT for quantification of PHE in comparison to the previously published gold standard of MRI. In addition, patients receiving minimally invasive surgery plus tissue plasminogen activator continue to show a significant difference in edema formation compared to patients receiving standard of care at the Day 7 time point.
Abstract W MP90: APOE Variants are Associated With Increased Risk of Warfarin-Related Intracerebral Hemorrhage
Authors: Falcone Guido J , Radmanesh Farid , Brouwers H. B , Chitsike Lennox P , Devan William J , Battey Thomas W , Viswanathan Anand , Goldstein Joshua N , Greenberg Steven M , Brown Devin L , Worrall Bradford B , Meschia James F , Silliman Scott L , Selim Magdy , Tirschwell David L , Biffi Alessandro , Woo Daniel , Rosand Jonathan , Anderson Christopher D ,   on behalf of the International Stroke Genetics Consortium
Published: March 2022

Background:
Epsilon (e) variants in the Apolipoprotein E (APOE) gene are well-established risk factors for spontaneous intracerebral hemorrhage (s-ICH). We tested the hypothesis that APOE-e variants are also associated with warfarin-related ICH (w-ICH) and examined interactions between APOE and warfarin.

Methods:
Prospective multicenter 2-stage (discovery and replication) study. ICH was classified as lobar and non-lobar based on admission head CT. In the discovery stage, w-ICH cases were matched with warfarin-exposed controls (w-controls). In replication, w-ICH cases were matched with non-warfarin controls (nw-controls). APOE was directly genotyped. Association testing was performed using multivariable logistic regression. Gene-environment interaction between APOE and warfarin was formally tested using a case only approach (combining s-ICH and w-ICH cases).

Results:
The discovery stage included 316 w-ICHs (43% lobar and 57% non-lobar) and 355 w-controls. Results are presented in the Table: APOE-e2 was associated with lobar and non-lobar w-ICH, and APOE-e4 was associated with lobar but not with non-lobar w-ICH. In case-only analysis, 885 s-ICHs were combined with w-ICHs (total n=1201) and no evidence of interaction between APOE and warfarin was found (all p>0.20). The replication included 63 w-ICHs (44% lobar and 56% non-lobar) and 990 nw-controls. The distribution of APOE variants was similar in w-controls (discovery) and nw-controls (replication) for both e2 (p=0.81) and e4 (p=0.88). In replication, APOE-e2 and e4 were associated with lobar but not with non-lobar w-ICH.

Conclusions:
APOE-e variants constitute strong risk factors for lobar w-ICH. An effect may also exist between APOE-e2 and non-lobar hemorrhages, but given the lack of replication larger sample sizes are required to properly assess this association. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary.
Abstract W MP92: The CAVE Score for Predicting Late Seizures after Intracerebral Hemorrhage
Authors: Haapaniemi Elena , Strbian Daniel , Rossi Costanza , Putaala Jukka , Sipi Tuulia , Mustanoja Satu , Sairanen Tiina , Curtze Sami , Satopää Jarno , Roivainen Reina , Kaste Markku , Cordonnier Charlotte , Tatlisumak Turgut , Meretoja Atte
Published: March 2022

Background and Purpose:
Intracerebral hemorrhage (ICH) related seizures have not been thoroughly investigated. We evaluated their frequency, predictors, and influence on patient outcome. We then created and validated a simple score to estimate the risk of developing late seizures (LS).

Methods:
Consecutive ICH patients’ (n=993) province-wide electronic patient records were retrospectively evaluated for onset seizures (OS), acute seizures (AS, occurring within 7 days from stroke), and among 7-day survivors (n=764), also LS occurring >7 days from stroke. A Cox regression model estimating variables associated with risk of LS was used to derive a simple integer-based prognostic score. The score was validated externally in a prospective cohort of ICH patients from Lille, France (n=325).

Results:
Of the total cohort, 64 (6.5%) had OS and 61 (6.1%) AS. Among the 7-day survivors, during a median follow-up of 2.7 years, 70 (9.2%) patients developed LS. The cumulative risk of LS among survivors was 7.1% at 1 year after ICH, 10.0% at 2 years, 10.2% at 3 years, 11.0% at 4 years, and 11.8% at 5 years. Seizures at any time point were not associated with increased mortality. We created the CAVE score (0 to 4 points) to predict risk of LS, with one point for each of: Cortical involvement, Age<65 years, Volume >10 mL, and Early seizures at onset or within 7 days of ICH. The corresponding risk of LS was 0.6%, 3.6%, 9.8%, 34.8%, and 46.2%, for CAVE scores 0-4, respectively, with AUC-ROC of 0.81 (0.76-0.86). The score stratified risk of LS also in the validation cohort, being 3.1%, 5.0%, 15.8%, 13.5%, and 37.5% respectively, with AUC-ROC of 0.69 (0.59-0.78).

Conclusion:
One in ten patients will develop seizures after ICH. This adverse outcome can be predicted by a simple score based on baseline variables.
Abstract W MP96: The Role of Thrombin in Hydrocephalus after Intraventricular Hemorrhage
Authors: Gao Feng , Liu Fuyi , Chen Zhi , Hua Ya , Keep Richard F , Xi Guohua
Published: March 2022

Background:
Hydrocephalus after intraventricular hemorrhage (IVH) is a common and major complication that causes clinical deterioration and affects recovery. The mechanisms of hydrocephalus are still not clear. Previous studies demonstrated that thrombin is an important factor in brain injury after intracerebral hemorrhage. This study investigated the effect of thrombin on hydrocephalus development in a rat IVH model.

Methods:
There were three parts in this study. First, male Sprague-Dawley rats had an injection of 200μl saline, autologous blood or heparinized blood into the right lateral ventricle and had MRI scanning to determine lateral ventricle size at different times up to 4 weeks. Second, rats had an injection of 50μl saline or 3U thrombin into the right lateral ventricle. Third, rats had an injection of thrombin (3U) with a protease-activated receptor-1 (PAR-1) antagonist, SCH79797 (0.15 nmol), or vehicle into the right lateral ventricle. Lateral ventricle volumes were measured by MRI and the brains were used for immunohistochemistry and Western blot analysis at 24 hours.

Results:
Intraventricular injection of autologous blood induced hydrocephalus from day-1 to -28. Co-injection of heparin with blood resulted in less hydrocephalus at all time points compared with blood injection alone (p<0.05). Intraventricular injection of thrombin, but not saline induced significant hydrocephalus, ventricular wall damage, blood-brain barrier disruption, and PAR-1 upregulation in the periventricular area. Thrombin-induced hydrocephalus was reduced by co-injection of the PAR-1 antagonist SCH79797 (p<0.05).

Conclusions:
Thrombin contributes to hydrocephalus development after intraventricular hemorrhage and thrombin-induced hydrocephalus is through activation of PAR-1.
Abstract W MP99: Seven-Day Mortality After Ischemic Stroke: International Comparison Among Industrialized Nations
Authors: Lee Jin-Moo , Hemmen Thomas , Chen JiaJing , Lumor Richard , Deline Christopher J , Middleton Steve , Bottle Alex , Fenwick Caroline , Randall Marc , Pelly Michael , Thijs Vincent , Rost Natalia , Shaw Louise , Vaux Emma , Alberts Mark J , Janda Nina , Alsop Rachel , Schlagbauer Keith , Spencer Mary , Schechtman Kenneth , Dunnigan Clay , Rinkel Gabriel
Published: March 2022

Introduction:
Stroke is the 2
nd
leading cause of death worldwide, yet best practices for acute stroke care are lacking even among premier hospitals in industrialized countries. We compared 7-day mortality after ischemic stroke between academic medical centers in the Netherlands (NL), United Kingdom (UK), and United States (US).

Methods:
This was an observational study using in-hospital administrative data from select academic medical centers in the NL (n=8), UK (n=10), and US (n=11) from 2005-12. Chi-square was used to compare 7-day in-hospital mortality between countries and across years, and to explore the effect of weekend admission. Multiple logistic regression was conducted to further examine factors associated with mortality, including sex, age, weekend admission, year, and country.

Results:
From 2005-12, 51,409 patients were discharged with ischemic stroke from hospitals in the NL (n=6331), UK (n=25574), and US (n=19204). Mortality was significantly higher in the UK (8.1%) compared to the NL (6.4%) and US (4.8%) (p<0.0001). Moreover, mortality was higher in patients admitted on week-ends compared to weekdays in the UK (9.2% vs. 7.7%, p=0.0001), but not in the NL (6.8% vs. 6.3%, p=0.44) or US (4.8% vs. 4.9%, p=0.73). This “week-end effect” was consistent throughout all hospitals in the UK (p=0.0002) but much more variable in hospitals in the other two countries. In the UK, 7-day mortality improved with time, declining from 10.7% in 2006 to 6.3% in 2012 (p<0.0001). A decline in mortality was also seen in the NL (p=0.03), but remained unchanged in the US (p=0.72). The UK “weekend effect” also disappeared with time. Multiple logistic regression demonstrated that country and weekend admission remained a significant risk factor associated with mortality after controlling for age, gender, and year.

Conclusions:
A comparison of 7-day mortality among academic medical centers in industrialized counties reveals stark variability. Although 2006 stroke mortality in UK hospitals was almost double that of US hospitals, dramatic reductions were subsequently seen. Further analysis of national policy or practice changes that have driven these improvements promise to be revealing.
Abstract W P1: Efficacy of IV TPA in Endovascular Trials: A Pooled Analysis
Authors: Alberts Mark J , Connors Buddy J , Novakovic Robin , Olivera Charles
Published: March 2022

Background:
IV TPA is the comparator for many studies of endovascular therapies (EVT) in acute ischemic stroke. We analyzed the efficacy of IV TPA reported in recent large EVTs and compared it to earlier studies. Our hypothesis was that the perceived failure of various therapies in recent EVT trials was due to the unanticipated efficacy of IV TPA alone and not the failure of EVT. This may have adversely affected the design and power assumptions of recent trials.

Methods:
We analyzed baseline and outcome data from recent large trials of IV TPA vs placebo and IV TPA alone vs various EVTs with or without IV TPA. Studies included were ECASS I-III, ATLANTIS, NINDS, SITS-MOST, EPITHET, IMS3, and SYNTHESIS. Onset to treatment times, age, and baseline NIHSS scores were examined. The primary outcome was a modified Rankin of 0-2 at 3 months for the IV TPA only patients. When possible we analyzed patients treated 4.5 to 6 hr after symptom onset to mirror the treatment delays seen in EVT.

Results:
Across all studies there were 8736 IV TPA only treated patients. The median age was consistent across all trials (67-68 years), as was the mean NIHSS score (11-13 for all, except for 16 in IMS3). Good outcomes were achieved in 40% to 46% of IV TPA only treated patients in the EVT trials compared to 49% for those treated in IV TPA vs placebo trials and 55% treated in open-label IV TPA registries. Limiting the analysis to patients treated 4.5 to 6 hr after stroke onset showed 49% of patients had a good outcome with IV TPA alone vs placebo. One EVT trial under-estimated the efficacy of the IV TPA only arm, with an assumed good outcome rate of only 40% (vs 46% in the actual trial).

Conclusions:
Among patients enrolled in EVT trials, IV TPA alone performs quite well, with up to 46% of patients having a good outcome. Any EVTs will have to demonstrate robust efficacy to show a superior clinical benefit when compared to IV TPA alone.
Abstract W P104: Comparison of Carotid Endarterectomy and Stenting for Carotid Artery Stenosis with Coronary Artery Disease
Authors: Maruyama Daisuke , Ideguchi Minoru , Kawamura Yoichiro , Kanamaru Hideki , Kataoka Hiroharu , Satow Tetsu , Morita Kenichi , Mori Hisae , Kobayashi Norikata , Ishii Daizo , Yamauchi Keita , Nakagawara Jyoji , Iihara Koji
Published: March 2022

Objective:
Coronary artery disease (CAD) is a major comorbidity usually developing in patients with carotid artery stenosis and increases the risk of revascularization in these patients. We retrospectively evaluated the impact of CAD on the outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS) at a single center.

Methods:
We reviewed data of 643 lesions (451 CEA and 192 CAS) in 599 patients who underwent carotid revascularization at our institute between 1998 and 2011. We defined a history of myocardial infarction (MI), coronary artery bypass surgery, or percutaneous coronary intervention as previous CAD and >75% stenosis in more than 2 coronary artery areas as multivessel CAD. Periprocedural stroke, MI, or death from any cause and ipsilateral stroke, MI, or death within a year after treatment were recorded.

Results:
Of the 643 lesions, 123 (19.1%) were categorized as “previous CAD” and 73 (11.4%) as “multivessel CAD.” The number of cases of multivessel CAD was significantly higher in the CAS group than the CEA group (14.5% vs. 9.9%, p = 0.009). Of the 102 cases indicated for coronary intervention at a preoperative period, 85 were treated for CAD before carotid revascularization. No periprocedural MI was observed in both the groups, and only 1 case showed MI within a year after CEA (0.2%). The CEA group showed no significant relationship between previous or multivessel CAD and any periprocedural or 1-year postoperative event. In the CAS group, multivessel CAD was identified as an independent risk factor for periprocedural stroke (odds ratio [OR]: 11.23; 95% confidence interval [CI]: 2.96-48.91; p = 0.0004) and ipsilateral stroke and death within a year of treatment (OR: 6.76; 95% CI: 2.09-22.38; p = 0.001).

Conclusion:
Previous or multivessel CAD did not increase the risk of MI or death within 1 year after revascularization of carotid artery stenosis, but multivessel CAD was an independent risk factor for stroke after CAS. Thus, the option of CAS should be carefully considered in cases of carotid artery stenosis with multivessel CAD.
Abstract W P119: Identification of Novel Candidate Biomarkers to Define Moyamoya Disease by CSF Proteome Analysis
Authors: Kashiwazaki Daina
Published: March 2022

Purpose:
Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis or occlusion of the terminal portion of internal carotid arteries. Genetic factors are closely involved in the etiology of moyamoya disease.

However, the post-genomic mechanisms are still unknown. This study was aimed to identify specific biomarkers in the cerebrospinal fluid (CSF) of patients with moyamoya disease.

Methods:
This study included 6 patients with moyamoya disease and three patients with unruptured cerebral aneurysm. Their CSF was obtained from the Sylvian fissure during surgery. A comparative two-dimensional (2D) gel electrophoresis study was performed. Protein spots that showed significant differences between moyamoya patients and controls were selected for further analysis by mass spectrometry.

Results:
On 2D gel electrophoresis, two proteins were upregulated and other two proteins were downregulated in the CSF of moyamoya disease. Further mass spectrometry analysis revealed that haptoglobin and alpha-1-B-glycoprotein were upregulated and apolipoprotein (Apo)-E and Apo-J were downregulated in the CSF of moyamoya disease.

Discussion and Conclusion:
Upregulation of haptoglobin and alpha-1-B-glycoprotein may result from inflammatory reactions and/or angiogenesis. Downregulation of Apo-E and Apo-J may promote the cascade of endothelial apoptosis in carotid terminations. Furthermore, Apo-E is produced in the astrocytes and microglia and contributes to lipid transport to the neurons. Therefore, the downregulation of Apo-E may also be involved in the neuronal damage in moyamoya disease. The findings strongly suggest that these novel four proteins could be the candidate biomarkers to define moyamoya disease, and may shed the light on the pathogenesis of moyamoya disease, although further studies would be warranted.
Abstract W P120: Effect of Prior Aspirin Use on Initial Stroke Severity and Hemorrhagic Transformation
Authors: Park Jong-Moo , Han Moon-Ku , Cho Yong-Jin , Lee Kyung Bok , Lee Soo Joo , Park Tai Hwan , Lee Jun , Cha Jae-Kwan , Ko Youngchai , Kim Young A , Lee Ji Sung , Lee Juneyoung , Bae Hee-Joon
Published: March 2022

Background and Purpose:
The effect of prior aspirin use on the severity and safety of index ischemic stroke have not been well investigated. We studied the effect of prior aspirin use on initial stroke severity and also on the hemorrhagic transformation in initial MRI.

Methods:
Using a prospective multicenter stroke registry, patients who were hospitalized due to ischemic stroke and had relevant lesions on MRI were selected. Patients who were on anticoagulants or whose stroke subtype was categorized as stroke of other determined etiology or undetermined etiology were excluded. Baseline stroke severity was measured using the NIHSS scores at presentation, and was compared between no prior aspirin (non-PA) users and prior aspirin (PA) users with stratification by stroke subtypes. Prevalence of the hemorrhagic transformation in initial GRE-MRI was also compared between those two groups.

Results:
Among the 11,183 patients, a total of 2,664 (23.2%) patients reported use of an aspirin within a week of stroke onset. In crude analysis, the overall baseline NIHSS score was lower in non-PA group than PA group (5.69 vs. 6.08, P=0.005). The interaction between prior aspirin use and stroke subtype was significant (P = 0.031) in a multivariable analysis. When the study subjects were stratified by stroke subtype, the baseline NIHSS in PA groups was significantly lower in large artery atherothrombosis group (5.77 vs. 5.21, P=0.001), but not in those with cardioembolism as well as small-vessel occlusion before and after adjustments. Hemorrhagic transformation in initial GRE-MRI was more frequently observed in PA groups (4.3% vs. 7.6%, P<0.001) irrespective of stroke subtypes.

Conclusions:
Our study suggests that the reduction of initial stroke severity in the prior aspirin users may differ by stroke mechanism, which was only significant in patients with large artery atherothrombotic stroke.
Abstract W P122: Cerebral Small Vessel Diseases May be Associated With Aortic Arch Calcification in Patients With Acute Stroke
Authors: Ueno Yuji , Okuzumi Ayami , Watanabe Masao , Tanaka Yasutaka , Yamashiro Kazuo , Tanaka Ryota , Hattori Nobutaka , Ueno Takao
Published: March 2022

Background:
Aortic arch calcification (AoAC) on chest X-ray represents systemic atherosclerosis and is associated with ischemic cardiovascular diseases. However, the relationship between ischemic stroke and AoAC has yet to be fully elucidated. This study focused on the relationship between AoAC and stroke subtype, and the factors linked with AoAC in patients with acute ischemic stroke were investigated.

Methods:
This study prospectively enrolled patients with acute ischemic stroke who were undergoing chest X-ray, blood examinations, and brain MRI. Classification of ischemic stroke subtype was based on the Trial of Org 10172 in Acute Stroke Treatment classification with minor modification. The extent of AoAC on chest X-ray was divided into four grades: no visible calcification (grade 0); small spots or a single thin area of calcification (grade 1); one or more areas of thick calcification (grade 2); and circumferential calcification (grade 3). Clinical characteristics, biochemical findings, and extent of AoAC in each stroke subtype were assessed.

Results:
175 patients (age, 70 ± 13 years; 115 males) were enrolled in the study. 33 patients (19%) had small artery occlusion (SAO), 42 (24%) had large artery atherosclerosis, 49 (28%) had cardioembolism, 24 (14%) had stroke with other determined etiologies, and 27 (17%) had stroke with undetermined etiologies. Among stroke subtypes, the extent of AoAC was the highest in patients with SAO (p=0.036). Multinomial logistic regression analysis showed that the extent of AoAC was negatively correlated to other stroke subtypes compared to SAO (all p<0.05). Age (OR: 1.14; 95% CI: 1.08 to 1.19; p<0.001), hypertension, (OR: 3.44; 95% CI: 1.23 to 9.66; p=0.019), diabetes mellitus (OR: 2.19; 95% CI: 0.99 to 4.85; p=0.054), white matter lesions (OR: 1.54; 95% CI: 1.00 to 2.36; p=0.048), and SAO (OR: 1.38; 95% CI: 1.02 to 1.89; p=0.040) were significantly associated with high-grade AoAC.

Conclusions:
SAO was closely associated with AoAC. Age, hypertension, and possibly diabetes mellitus can increase the risk of cerebral small artery diseases including SAO and white matter lesions, and aortic arch calcification in patients with acute ischemic stroke.
Abstract W P129: Association Between Acute Stroke Location and Sleep-Disordered Breathing
Authors: Stahl Stephanie M , Taylor Stanley , Ofner Susan , Qin Li , Yaggi Klar , Ivan C. Simona , Bravata Dawn M
Published: March 2022

BACKGROUND:
A high prevalence of sleep-disordered breathing (SDB) has been demonstrated among stroke patients. The literature about the relationship between SDB and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of obstructive sleep apnea (OSA) (apnea hypopnea index [AHI] ≥ 5 events/hour) and sleep apnea severity (defined by AHI).

METHODS:
Data were obtained from 236 patients participating in an ongoing randomized controlled trial (NCT01446913) that is evaluating the effectiveness of a strategy of diagnosing and treating SDB among patients with acute ischemic strokes and transient ischemic attacks. As part of this trial, all intervention patients receive polysomnography. Demographics, pre-stroke disability, comorbidities, National Institutes of Health Stroke Scale, clinical and laboratory parameters, and Epworth Sleepiness Scale are also recorded. Stroke location was classified by brain imaging (MRI or CT) reports as follows: lobe (frontal, parietal, temporal, insular, occipital), subcortical (thalamus, basal ganglia, internal capsule, corona radiata, corpus callosum), brainstem (midbrain, pons, medulla), cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for SDB presence and negative binomial regression for AHI.

RESULTS:
Among 94 patients with complete polysomnography and stroke location data, 72 (77%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence of SDB or its severity. Similarly, in multivariable modeling accounting for baseline characteristics that were associated with SDB (e.g., neck circumference), stroke location was not associated with SDB presence.

CONCLUSIONS:
These results confirm that SDB is present in the majority of stroke patients and suggest that stroke location cannot be used to identify a group with higher risk of SDB. Given this high overall prevalence, strong consideration should be given to providing polysomnography for all ischemic stroke patients.
Abstract W P136: SOS CARE: The Stroke East Saxony Pilot Project for Integrated Care Pathway and Case Management After Stroke
Authors: Kepplinger Jessica , Helbig Uwe , Barlinn Kristian , Pallesen Lars-Peder , Zerna Charlotte , Siepmann Timo , Reichmann Heinz , Puetz Volker , Bodechtel Ulf
Published: March 2022

Background:
We developed a standardized pathway for post-stroke care facilitated through a case manager (CM) to ensure minimization of risk factors, life-style changes and continuation of secondary prevention medication.

Methods:
Consecutive acute stroke patients were prospectively assigned to a certified CM. The 1-year post-stroke care pathway comprised initial educational discussion, personal patients’ home visits and quarterly telephone contacts. Further personal contacts were conducted when judged necessary. Target values for vascular risk factors were pre-defined according to current stroke guidelines, compared with regular check-ups and intervened when necessary. A closing meeting including assessment of stroke recurrence was performed.

Results:
Between 12/2011 and 07/2013 we enrolled 74 of 111 screened patients: 57% male, mean age 71+/-14 yrs, median NIHSS 2 (range 0-16), 76% ischemic, 4% hemorrhagic stroke and 20% TIA. Of 74 patients, 10 refused follow-up care. Overall, 356 home visits (4.8/patient) and 1233 phone contacts (16.7/patient) were conducted. One hundred-eighty seven specific interventions were necessary mostly due to missing medication, non-compliance and social needs. Achieved vascular risk factor goals are presented in the Table. No recurrent stroke occurred. Among screened patients who refused CM, stroke recurrence rate was 22% after 12 months.

Conclusion:
The preliminary data of our pilot project suggest that case management is capable of achieving predefined goals for secondary prevention. To investigate its impact on stroke recurrence risk and prevention of long-term care dependency, we initiate a randomized controlled trial.
Abstract W P138: Pregnancy Associated Cerebral Ischemia in Women with Sickle Cell Disease
Authors: Qureshi Adnan I , Adil Malik M , Zafar Taqi T , Suri M Fareed K
Published: March 2022

Background:
Cerebral ischemia is commonly seen in patients with sickle cell disease but little information is available regarding such occurrence during pregnancy.

Objective:
To determine the rates of pregnancy associated cerebral ischemia in women with sickle cell disease and affect on outcome of pregnancy.

Methods:
We analyzed data collected as part of the Cooperative Study of Sickle Cell Disease, which was a multicenter, prospective study on the natural history of sickle cell disease. A total of 1043 adolescent and 1183 adults were enrolled in phase 1 of the study period 1978-1988. Data regarding pregnancy and outcome was ascertained throughout the follow-up period. We tested the effect of pregnancy associated cerebral ischemia as an interaction in the multivariate analysis assessing the effect of predictors on abortion or miscarriage.

Results:
Of the 1024 women enrolled, 297 (29%) women experienced one or more pregnancy. Thirteen of the 297 women experienced an episode of cerebral ischemia during pregnancy. Patients with pregnancy associated cerebral ischemia had a higher rate of previous history of stroke (9 of 13 versus 107 of 284, p=0.01). There was a trend towards higher rate of pre-eclampsia among patients with cerebral ischemia (3 of 13 versus 28 of 284, p=0.1). A total of 102 of 297 first pregnancies resulted in abortion or miscarriage. After adjusting for age, history of previous stroke, and alcohol use, the interaction between pregnancy associated cerebral ischemia and abortion or miscarriage was not significant (p=0.2).

Conclusions:
There appears to be high rates of cerebral ischemia and abortion or miscarriage among pregnant women with sickle cell disease but occurrence of cerebral ischemia does not influence subsequent abortion or miscarriage.
Abstract W P141: Cerebral Microbleeds and White Matter Hyperintensities as Predictors for Early Stroke Recurrences in Transient Ischemic Attack: Korean TIA eXpression Study
Authors: Lee Yong-Seok , Kim Gyeong-Moon , Bang Oh Young , Bae Hee-Joon , Kwon Hyung-Min , Lim Jae-Sung , Hong Keun-Sik , Park Jong-Moo , Lee Seung-Hoon , Rha Joung-Ho , Koo Jaseong , Yu Kyung-Ho , Seo Woo-Keun , Lee Kyung Bok
Published: March 2022

Background:
Patients within 24 hours from symptom onset of transient ischemic attack (TIA) are particularly at high risk of early recurrent stroke. Neuroimaging variables are increasingly recognized to help better identify patients at high risk. The Korean TIA eXpression study aimed to determine the risk of early recurrent stroke and its clinical and imaging predictors.

Methods:
We conducted a hospital-based, multi-center prospective cohort study. TIA was defined by transient focal neurological deficits which result from ischemia and last less than 24 hours. Inclusion criteria were: 1) patients who admitted within 24 hours after symptom onset, 2) those who underwent magnetic resonance imaging and angiography, and 3) age of 45 years or older. We collected baseline data of demographics, vascular risk factors, clinical manifestation, potential mechanism of TIA, neuroimaging findings of acute ischemic lesions, white matter changes, microbleeds, vascular status, and laboratory test results. The primary endpoint was recurrent stroke within 90 days.

Results:
A total of 500 patients (mean age 64.4, male 58%, mean ABCD2 score 4.3 ± 1.4) were enrolled and completed 90-day follow-up. The primary endpoint of recurrent stroke developed in 25 (5.0%) patients within 90 days. From univariable analyses, we identified the following potential predictors (p < 0.20) of recurrent stroke within 90 days: ABCD2 scores, crescendo TIA, lacunar TIA, symptomatic extracranial occlusion, old lacune, white matter hyperintensities, and cerebral microbleeds. In a multivariable logistic regression analysis, crescendo TIA (adjusted odds ratio (OR) 4.4, 95% confidential interval (CI) 1.3-14.7), lacunar TIA (OR 2.5, 95% CI 1.1-6.1), white matter hyperintensities (OR 2.4, 95% CI 1.1-5.4), and cerebral microbleeds (OR 4.9, 95% CI 1.9-12.8) were independently associated with recurrent stroke within 90 days.

Conclusion:
In conclusion, the current study suggests that microangiopathy may be a predictor for early recurrent strokes after TIA. Our novel findings need to be validated in future studies.
Abstract W P142: Can Peripheral Arterial Disease Markers Predict the Outcome of Non-cardioembolic Stroke Patients?
Authors: Yoshimoto Takeshi , Hosomi Naohisa , Neshige Shuichiro , Hara Naoyuki , Kubo Satoshi , Takeshima Shinichi , Himeno Takahiro , Sato Kota , Yunoki Taijun , Takamatsu Kazuhiro , Ota Taisei , Kuriyama Masaru , Matsumoto Masayasu
Published: March 2022

Introduction:
In acute stroke patients, ankle-brachial index (ABI)>0.9 is a clear predictor of increased stroke recurrence risk. However, it has not been defined whether clinical markers of peripheral arterial disease could predict the outcome of non-cardioembolic stroke.

Hypothesis:
We assessed the hypothesis that clinical markers (e.g. ABI and pulse wave velocity [PWV]) of peripheral arterial disease could predict the outcome of non-cardioembolic stroke.

Methods:
In our Brain Attack Center, 5432 acute ischemic stroke patients were admitted in January 2007 to December 2012. Among them, 686 lacunar or atherothrombotic stroke (TOAST criteria) patients (248 female and 438 male, median age 70.0 (range 35 to 96)) who admitted within 7 days after their onset and evaluated ABI and PWV during hospitalization were retrospectively examined in this study. Baseline characteristics and NIHSS scores at admission were noted, and modified Rankin scale (mRS) scores 3 months after stroke were evaluated. The patients were categorized into normal (≥0.9) and decreased (<0.9) ABI groups, and into good-outcome (mRS score, 0,1) and poor-outcome (mRS score, 2_6) groups.

Results:
ABI was decreased in 28 (5.7%) of 496 good-outcome patients and 22 (11.6%) of 190 poor-outcome patients (p=0.008). PWV was increased in the patients with poor-outcome (2116.6±477.5 cm/s) compared with the patients with good-outcome (1934.9±415.6 cm/s, p<0.001). The patients were categorized into low- or high-PWV with a cutoff (2163 cm/s) determined from a receiver operating characteristics curve against the patients’ outcome. The poor-outcome of patients were predicted with high-age (≥75years), NIHSS score at admission, low-ABI, and high-PWV, independently (overall Χ
2
=86.7, R
2
=0.107, n=686, p<0.001; low-ABI: odds ratio 2.13 [95% confidence interval 1.12 to 4.01], p=0.022; high-PWV: odds ratio 2.36 [95% confidence interval 1.61 to 3.45]).

Conclusion:
Our results showed that the poor-outcome of patients were predicted with ABI and PWV even after controlling age and NIHSS score. It is important to evaluate clinical markers (ABI and PWV) of peripheral arterial disease in the non-cardioembolic stroke patients.
Abstract W P145: Shift in Sex Ratio Over Time in Cerebral Venous Thrombosis
Authors: Coutinho Jonathan M , Zuurbier Susanna M , Stam Jan
Published: March 2022

Background:
In contemporary studies on cerebral venous thrombosis (CVT) there is a predominance of female patients. The change in sex ratio over time, however, has not been systematically studied

Methods:
We performed a systematic review of the literature up to April 2013. Studies with ≥ 40 CVT patients that reported outcome were eligible. Pediatric studies, studies which selectively included women and those in which no sex ratio was reported were excluded. We ranked studies according to the year halfway the period of patient inclusion. If no time span was reported, we assumed a period of inclusion of 10 years prior to the year of publication.

Results:
Fifty-three studies, with a total of 20.881 patients were included. The mean age was 36 years (SD 4.7) and 71% of patients were women. In studies that reported gender specific risk factors, 25% had a pregnancy related CVT and 37% used oral contraceptives at the time of diagnosis. There was a significant correlation between the period of the study and the percentage of women (Pearson correlation coefficient 0.37, p=0.006, figure). Similarly, there was a significant increase of oral contraceptive use among female patients, from a mean of 14% in studies before 1970 to a mean of 39% in those after 2001 (correlation coefficient 0.34, p=0.05). In contrast, the percentage of pregnancy related CVT cases did not increase over time (correlation coefficient 0.01, p=0.96).

Conclusions:
The sex ratio among CVT patients has significantly shifted over time, with a gradual increasing percentage of women. Our results suggest that this change is related to the increased proportion of women using oral contraceptives.
Abstract W P150: Incident Cancer in Stroke Survivors: Analysis of the Vitamin Intervention for Stroke Prevention (VISP) Trial
Authors: Qureshi Adnan I , Adil Malik M , Rodriguez Gustavo J , Chaudhry Saqib A , Suri M Fareed K
Published: March 2022

Background:
Subclinical cancer can manifest as a thrombo-embolic event and may be detected at a later interval in stroke survivors.

Objective:
To determine the rate of incident cancer in a large cohort of stroke survivors.

Methods:
An analysis of the VISP trial was performed which was a randomized, double-blind trial conducted in 3680 adults with nondisabling cerebral infarction. The primary intervention was best medical/surgical management plus a daily vitamin B
6
, vitamin B
12
, and folic acid supplementation. The incidence of new cancer was identified using Kaplan Meir analysis over a mean (±SD) period of 24 (±1.4) months. Unadjusted survival probabilities were estimated by the Kaplan-Meier method for patients with and without incident cancer.

Results:
A total of 3247 patients (mean age (±SD) of 66 (±11); 2013 were men) were cancer free at the time of enrollment. The incidence of new cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 month, 1 year, and 2 years, respectively. Patients with incident cancer had lower body mass index (27.8±5.0 vs. 28.4±5.8, p=0.02), high density cholesterol (42.4±12.5 vs. 45.4±15.2, p=0.007) and triglyceride levels (160.1±88.4 vs. 175.6±162.3, p<0.0001) at baseline evaluation. The unadjusted 2 year survival was significantly lower in patients with incident cancer than those without incident cancer (85% versus 95.3%, p=<.0001). The rate of combined endpoint of recurrent stroke, myocardial infarction, and death was higher among those with incident cancer (24.6% versus 16%, p=0.01).

Conclusions:
Incident cancer is not uncommon and is associated with lower survival among stroke survivors.
Abstract W P162: Utilization of Vascular Imaging in Stroke: A Population Based Study
Authors: Vagal Achala , Sucharew Heidi , Alwell Kathleen , Khoury Jane , Khatri Pooja , Woo Daniel , Flaherty Matthew , Kissela Brett , Adeoye Opeolu , Ferioli Simona , De Los Rios La Rosa Felipe , Martini Sharyl , Mackey Jason , Kleindorfer Dawn
Published: March 2022

Introduction:
Rates of diagnostic workup in stroke have increased over time. However less is known about utilization of vascular imaging for stroke from a population perspective. We sought to evaluate the utilization and predictors of vascular imaging modalities in years 2005 and 2010 in a population-based study.

Methods:
Stroke and TIA patients were identified in a metropolitan population of 1.3 million served by 15 different inpatient hospitals in the Greater Cincinnati area in the calendar years of 2005 and 2010. Patient charts and imaging records were abstracted by research nurses and reviewed by study physicians. The proportion of vascular imaging use including CT angiogram (CTA), MR angiogram (MRA), digital subtraction angiogram (DSA) and carotid ultrasound was computed. Multivariate logistic regression modeling for the following variables was performed: age, race, gender, and insurance, NIHSS, ED presentation and hospital type.

Results:
In 2005, there were 3558 stroke/TIA events with imaging data available in 3307 patients and, in 2010; there were 3597 stroke/TIA events with imaging data in 3374 patients. Overall, vascular imaging has increased from 72% in 2005 to 77% in 2010 (p-value <0.001). Specifically, use of CTA increased from 2% in 2005 to 11% in 2010 (p-value <0.001), MRA decreased from 38% to 37%, ultrasound increased from 48% to 53% (p <0.001) and DSA decreased from 6% to 3% (p-value <0.001) (table). In the combined study periods, 22% of 7115 events had multiple vascular imaging studies. Younger age, ischemic stroke subtype, ED and academic hospital were associated with increased vascular imaging use.

Conclusion:
Vascular imaging, particularly noninvasive studies showed increase over time, with CTA studies demonstrating the maximum increase in this population-based study.
Abstract W P170: Hemodynamic Effects in Carotid Occlusion Using Arterial Spin Labeling and Transcranial Doppler
Authors: Marshall Randolph S , Lazar Ronald M , Pavol MaryKay A , Dharssi Shazia , Slane Kevin , Asllani Iris
Published: March 2022

Background:
High grade carotid stenosis produces hemodynamic effects on the brain, but the relationship between cerebral autoregulation, absolute CBF and neurovascular coupling has not been well-delineated.

Methods:
Twelve subjects (age 74±9, 3F) with unilateral ICA stenosis (80-100% occluded) but no infarct (asymptomatic or TIA only) underwent dynamic cerebral autoregulation (DCA) testing with transcranial Doppler by comparing phase shift (PS) of spontaneous oscillations in blood pressure (measured with finger photoplethysmography (Finapres)) versus MCA flow velocities at frequencies .06-.12 Hz using transfer function analysis, lower degree of PS indicating worse autoregulation.Neurovascular coupling was assessed by amplitude of absolute increase in CBF in bilateral Brodman area (BA) 4 during a bilateral repetitive hand closure task using continuous arterial spin labeling (CASL) MRI. Four activation (ON) periods were averaged and subtracted from 4 rest (OFF) periods. Resting CBF for each hemisphere’s motor cortex was determined by averaging the OFF periods.

Results:
All subjects showed: 1) hemispheric asymmetry in baseline CBF with the occluded side being on average 25mL/100g*min (+/- 14 mL/100g*min) lower than the unoccluded hemisphere. 2) hemispheric asymmetry in motor activation: unoccluded hemisphere average activation (mean_CBF_ON - mean_CBF_OFF) in BA4 was 23.7mL/100g*min, representing a 21% increase in local CBF due to activation; occluded hemisphere mean activation was 14 mL/100g*min, representing 18% percent increase in local CBF. 3) Hemispheric asymmetry in DCA, PS=33.1 deg ± 31 on the occluded side vs. 43.5 deg±23 on the non-occluded side. Both the hemispheral difference in baseline CBF (impaired flow) and the difference in DCA measurement (impaired autoregulation) were good predictors of the lower activation (neurovascular coupling) on the occluded hemisphere: R
2
= 0.85 and 0.80, respectively.

Conclusion:
Both impaired resting CBF and impaired cerebral autoregulation appear to contribute to decreased neurovascular coupling in carotid artery occlusive disease, representing a potential mechanism for occult neuronal dysfunction such as mild cognitive impairment in this patient population.
Abstract W P173: The Use of Mass Spectroscopy-Based Proteomics to Identify Novel Biomarkers of Cerebral Ischemia
Authors: George Paul M , Adams Christopher M , Mlynash Michael , Kjaergaard Christian H , Kuo Calvin J , Kemp Stephanie , Garcia Madelleine , Albers Gregory W , Olivot Jean Marc
Published: March 2022

Background:
Cerebral ischemia and its mimics are often difficult to differentiate. While MRI is the gold standard for stroke diagnosis, a marker for TIA remains elusive. Proteomics offers a unique method to identify biomarkers of ischemic disease. Through the use of mass spectrometry-based proteomics, we analyzed the serum of patients with transient neurologic symptoms in our emergency department to determine candidate proteins to serve as indicators of cerebral ischemia.

Methods:
Patients with transient neurologic symptoms were prospectively enrolled and their serum was obtained. Mass spectrometry was performed on the samples, and the results were searched against the Human Uniport database to identify the most likely proteins. The student’s t-test was utilized to compare protein levels between the different clinical conditions, and significance was determined by using the Benjamini-Hochberg false discovery rate (FDR) controlling procedure for multiple comparison adjustments.

Results:
Twenty patients with TIAs, fifteen patients with minor strokes, and twelve control patients (i.e. migraine, seizure) were enrolled. Ceruloplasmin (p = 0.00027) and complement component C8 gamma chain (p = 0.00105) were increased in TIA and minor stroke compared with the control group, while platelet basic protein (p = 0.00010) was decreased. TIA patients tended to have higher Ig kappa chain 6 region AG and platelet basic protein levels and lower apolipoprotein F levels than stroke patients (p <0.05), but these differences were not significant after FDR adjustments.

Conclusions:
Mass spectroscopy-based proteomics is a potential new tool to help identify biomarkers for cerebral ischemia. Ultimately, a panel of proteins may serve as a marker for cerebral ischemia or TIA. We have identified three candidate proteins as possible indicators for cerebral ischemia. Larger studies are needed to confirm our results.
Abstract W P175: Diagnostic Yield of Echocardiography in Patients Presenting with Transient Ischemic Attack
Authors: Wilson Christina A , Tai Waimei , Desai Jamsheed A , Olivot Jean-Marc , Coutts Shelagh B , Albers Gregory W , Cucchiara Brett L
Published: March 2022

Background:
Transthoracic (TTE) or transesophageal (TEE) echocardiography is often performed to identify a cardioembolic (CE) source as part of the TIA evaluation. However, TTE/TEE can be difficult to obtain on an urgent basis, and the diagnostic yield in TIA remains undetermined.

Methods:
Patients with presumed TIA (defined as acute onset of focal symptoms lasting <24 hours likely due to a vascular cause) within 48 hours after presentation were prospectively enrolled at 3 stroke centers. Data regarding clinical features, medical history, results of diagnostic testing including TTE/TEE, treatment at discharge, and 90-day outcome were recorded. TIA etiology was determined by the enrolling investigator from all available information. CE sources were defined using a modified version of the Causative Classification of Stroke system.

Results:
A total of 633 TIA patients were included. Mean age was 66 ± 15 years, 52% were male, and the median ABCD
2
score was 4 (IQR 3-5). The 90 day stroke rate was 2% (12/633). TIA mechanism was determined to be CE in 16% of subjects. Echocardiography was performed in 495 subjects (TTE alone in 444, TTE+TEE in 44, and TEE alone in 7). TTE revealed a CE source in 45/488 (9%) patients. TEE revealed a CE source in 17/51 (33%) patients, of whom 9 had either negative TTE or TTE was not performed. Therefore, the overall yield of TTE/TEE for a CE source was 54/495 (11%). The most common CE source detected on TTE/TEE was dilated cardiomyopathy; CE sources not detected on TTE/TEE consisted mostly of atrial fibrillation. Anticoagulation was initiated because of a CE source found on TTE/TEE in 19/495 (4%) patients. Of those who underwent an MRI, 169/495 (34%) were DWI+. Yield of both TTE and TEE tended to be higher in DWI+ compared to DWI- subjects (TTE: 17/146 [12%] vs 17/235 [7%], p=0.14; TEE: 12/27 [44%] vs. 1/15 [7%], p=0.01).

Conclusions:
TTE and TEE identify a CE source and prompt a change in antithrombotic regimen with sufficient frequency to consider their inclusion in the diagnostic evaluation of patients with TIA. The yield of these tests, particularly TEE, is higher in patients with diffusion restriction on MRI.