bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P393: New Pooled Cohort Risk Equations: Application to a Recent Stroke Patient Population
Authors: Park Jong-Ho , Kwon Hyung-Min , Ovbiagele Bruce
Published: July 2021

Background:
In 2013, Pooled Cohort Risk (PCR) equations, which incorporates new sex- and race-specific estimates of the 10-year risk for atherosclerotic cardiovascular disease (ASCVD) including stroke, for ASCVD-free adults was introduced. Given the similarity of primary and secondary stroke risk factors, and benefit of a potential tool to readily identify stroke patients at high intermediate-term vascular risk for appropriate treatment, we evaluated the prediction and discrimination of the PCR and Framingham Cardiovascular Risk (FCR) equations after a recent stroke.

Method:
We conducted an analysis of Vitamin Intervention for Stroke Prevention dataset of 3555 recent ischemic stroke patients aged ≥35 years and followed for 2 years. The PCR and FCR scores were calculated using the coefficients for the equations for calculating an estimate of an individual’s 10-year vascular risk. Subjects were categorized as having low-PCR/-FCR (<20%), high-PCR/-FCR (≥20%), and known-ASCVD. Independent associations of high-PCR/-FCR with recurrent stroke (primary outcome) and stroke/coronary heart disease (CHD)/vascular death (secondary outcomes) were assessed. Model discrimination (c-statistic) was assessed using the areas under the receiver operating characteristic curves.

Results:
Both the PCR and FCR were independently related to both outcomes: compared with low-PCR, high-PCR was associated with stroke (adjusted hazard ratio [AHR], 1.79; 95% CI, 1.25–2.57) and stroke/CHD/vascular death (2.05; 1.55–2.70). Compared with low-FCR, high-FCR was associated with stroke (2.06; 1.34–3.16) and stroke/CHD/vascular death (1.57; 1.12–2.20). The c-statistic of PCR/FCR as a continuous variable for stroke was 0.56 (95% CI, 0.54–0.58) and 0.56 (0.54–0.57), respectively and for stroke/CHD/vascular death was 0.62 (0.60–0.63) and 0.61 (0.59–0.63), respectively.

Conclusions:
Both the PCR and FCR are significant predictors of recurrent vascular events, but neither one of them appear to be an optimal model to discriminate intermediate-term ASCVD prediction among recent stroke patients already receiving secondary stroke prevention.
Abstract T P404: The Influence Of Systemic Inflammatory Response Syndrome, In The Absence Of Infection, On The Relationship Between Intracerebral Hemorrhage Score And Outcomes
Authors: Hays Angela , Boehme Amelia K , Kicielinski Kimberly , Arora Kanika , Kapoor Niren , Lyerly Michael , Miller David , Elkind Mitchell , Harrigan Mark
Published: July 2021

Background and Purpose:
Systemic inflammatory response syndrome (SIRS) has been recognized as a risk factor for poor outcome in critically ill patients. The ICH score has been identified as a predictor of death and poor outcomes in patients with ICH. We examined the relationship between ICH score, SIRS and outcomes.

Methods:
A retrospective review of patients presenting to our center from 2008-2013 with primary ICH was conducted, excluding those who were placed on comfort care. SIRS was defined as having 2 or more of the following: (1) body temperature < 36°C or > 38°C, (2) heart rate > 90, (3) respiratory rate > 20, or (4) white blood cell count < 4000/mm or > 12,000/mm or more than 10% bands for more than 24 hours. Patients with documented infections were excluded. The outcome was discharge modified-Rankin Scale (dmRS) of 4-6. A mediation analysis was conducted to assess the effect SIRS has on the relationship between ICH score and outcomes.

Results:
A total of 249 ICH patients admitted to our stroke center from 2008-2013 met inclusion criteria. A total of 53 (21.3%) developed SIRS during their hospital stay. For each increase in the ICH Score, there was a 45% increase in odds of developing SIRS during hospitalization (OR 1.45, 95% 1.07-1.98, p=0.0169). SIRS was associated with an increased odds of poor functional outcome (OR 6.08, 95%CI 2.86-12.9, p<0.0001). For each increase in the ICH Score, adjusting for SIRS, there was a 2.68 fold increase in the odds of poor functional outcome (OR 2.68, 95%CI 1.82-3.96, p<0.001). Using a mediation analysis we found that 33% of the effect of ICH score on poor functional outcome at discharge explained by SIRS (Sobel 2.11, p=0.03).

Discussion:
In our sample, the odds of poor outcome was significantly associated with ICH score. As expected, the prevalence of SIRS was higher in patients presenting with higher severity of illness. The results of the mediation analysis suggest that SIRS may be one mechanism by which the association of rising ICH score and worsening functional outcome can be explained. This observation raises the question of whether early intervention to prevent or treat incipient SIRS may reduce morbidity and mortality in this high-risk population.
Abstract T P42: Diffusion-weighted Imaging-fluid-attenuated Inversion Recovery Mismatch and Fluid-attenuated Inversion Recovery Vascular Hyperintensities in Onset Time Estimation of Acute Ischemic Stroke
Authors: Homma Kazunari , Koga Masatoshi , Shoichiro Sato , Seki Kenta , Yoshimura Shoei , Miyazaki Yuichi , Nagatuka Kazuyuki , Minematsu Kazuo , Toyoda Kazunori
Published: July 2021

Background and Purpose:
The diffusion-weighted imaging (DWI)-fluid-attenuated inversion recovery (FLAIR) mismatch (DFM) is useful to estimate the onset time of stroke. The presence of FLAIR vascular hyperintensities (FVH) is associated with large diffusion-perfusion mismatch in patients with middle cerebral artery occlusion. We aimed to assess whether the combination of DFM and FVH was useful to predict patients ≤ 4.5 h after stroke onset.

Methods:
Consecutive patients with acute ischemic stroke who underwent 3.0T or 1.5T MRI including DWI and FLAIR within 12h after onset were registered. Of them, those with middle cerebral artery territory infarction were studied. More than two stroke neurologists judged whether there is DFM. We identified ischemic lesion corresponding to stroke symptom on DWI and then determined whether the FLAIR lesion positivity is negative, subtle (only slightly different from adjacent parenchyma) or evident (a clearly high signal). DFM was defined as the FLAIR negative or subtle corresponding to the DWI lesion. Patients were divided into two groups; the early group, those underwent MRI ≤ 4.5h after onset; and the late group, those underwent > 4.5h.

Results:
Of 129 patients (56 women, 72±12 years old) studied, 103 patients (45 women, 73±12 years old) and 26 patients (11 women, 70±11 years old) were assigned to the early and the late groups, respectively. Initial NIHSS score (median 7 [IQR 2-15] vs. 3.5 [1-6], p=0.032) was higher, and DFM (67% vs. 35%, p=0.003) and FVH (49% vs. 23%, p=0.019) were more frequently observed in the early group than in the late group. On multivariate analyses adjusted for confounders, DFM (odds ratio 3.35, 95% confidence interval 1.29-9.27; p=0.013) was independently associated with the early group. Patients in the early group were detected with a sensitivity of 0.67, specificity of 0.65, a positive predictive value of 0.88, and a negative predictive value of 0.33 using the presence of DFM and with 0.37, 0.92, 0.95, and 0.27, respectively, using the combination of DFM and FVH.

Conclusions:
DFM is useful to detect acute ischemic stroke patients ≤ 4.5h of onset with the acceptable sensitivity and specificity. Furthermore, patients with both DFM and FVH are very likely to be ≤ 4.5h of onset, although the sensitivity is low.
Abstract T P43: Hyperdense Basilar Artery (HDBA) Sign: Its Association With Clinical Signs, Symptoms And Outcome Of Posterior Circulation Ischemic Stroke
Authors: Ugdamina Fritzie R , Macas Mabel M , Aggarwal Vijay K , Gan Herminigildo H
Published: July 2021

Background and purpose:
Posterior circulation ischemic stroke is a clinical syndrome associated with ischemia related to stenosis, in situ thrombosis, or embolic occlusion of the posterior circulation arteries - the vertebral arteries, basilar, posterior cerebral arteries, and their branches. In order to reach the definite diagnosis, different imaging methods can be used, such as CT (computed tomography) and MRI (magnetic resonance imaging), or by conventional angiography. Hyperdense Basilar artery (HDBA) is a radiologic sign seen on unenhanced computed tomography scan suggestive of an early ischemic stroke. In a hospital facility that lacks advancement in neuroimaging, evaluating HDBA sign on unenhanced cranial CT scan can help clinicians in the diagnosis of posterior circulation ischemic stroke.

Methods:
A total of 67 subjects were included in the study. Medical records and neuroimaging of patients with a final diagnosis of posterior circulation ischemic stroke were retrieved. The radiologist who read the Cranial CT Scan was blinded as to the clinical signs, symptoms, and outcome of our subjects. All neuroimaging were reviewed as to location of the posterior circulation infarction, and for presence or absence of HDBA sign.

Results:
There were higher proportions with cerebellar signs and quadriplegia among those with positive HDBA sign, and a higher proportion with ocular signs among those with negative HDBA sign. However, we found no significant statistical difference (P=0.185). Location of infarction (P=0.363), baseline NIHSS (p=0.307), MRS on discharge (P=0.938), and timing of neuroimaging (P=0.227) were also not statistically significant. A positive HDBA sign had low sensitivity (54%), specificity (43%) and positive predictive value (16%). However, it had a high negative predictive value which means that among those found without an HDBA sign, 83% are likely to survive.

Conclusion:
There is no significant association between HDBA sign and clinical findings among patients with a posterior circulation ischemic stroke. Among those found with a positive HDBA sign, there is high likelihood for the presence of infarction and for those with a negative HDBA sign, a higher likelihood for survival.
Abstract T P56: The Safety of Clopidogrel Loading Therapy in Acute Ischemic Stroke Patients with Chronic Hemorrhage on Gradient Echo MRI
Authors: Tiu Jonathan , Monlezun Dominique , Valmoria Melisa , Shaban Amir , Rincon Natalia , George Alex , El Khoury Ramy , Martin-Schild Sheryl
Published: July 2021

Objective:
To determine if an acute loading dose of clopidogrel is safe in acute ischemic stroke (AIS) patients with chronic intracerebral hemorrhage (ICH).

Background:
Clopidogrel loading is a promising therapy for AIS patients not eligible for tissue plasminogen activator (tPA) who are at risk for progressive stroke. Previous ICH is a risk factor for developing a new ICH. However, the acute risk of these events in this population after loading with clopidogrel has not been studied.

Methods:
We examined 1,011 AIS patients presenting to our center from 06/07/07-07/31/13. Only those loaded with at least 300mg of clopidogrel (with or without aspirin) within 6 hours of admission were analyzed. We compared new onset hemorrhagic complications in patients with and without chronic ICH, defined as areas of parenchymal hypodensity on gradient recall echo (GRE) sequencing on MRI. Repeat CT or MRI during admission was evaluated by a vascular neurologist for evidence of new ICH, hemorrhagic infarct using ECASS II criteria, or new ischemic infarct.

Results:
Of 365 AIS patients loaded with clopidogrel, 67 had chronic ICH on GRE. Patients with chronic ICH were more likely to be African American (80.0% vs. 65.9%, p=0.028) and male (69.2% vs. 50.9%, p=0.008). These patients were more likely to have existing comorbidities: history of stroke (67.7% vs 37.5%, p<0.001), hypertension (90.8% vs 78.2%, p=0.021), and hyperlipidemia (56.9% vs 42.5%, p=0.036). After logistic regression analysis adjusting for significant covariates, chronic ICH patients did not have significant differences in any new hemorrhagic changes (p=0.709), new infarct (p=0.429), neuroworsening (defined as an increase in NIHSS score by 2 points within 24 hours, p=0.297), poor functional outcome (defined as modifed Rankin Scale > 2 on discharge, p=0.889), or unfavorable discharge disposition (defined as disposition other than home or inpatient rehabilitation, p=0.166).

Conclusion:
The presence of chronic ICH on GRE did not increase the risk of new ICH, hemorrhagic infarct, ischemic event, or neurologic deterioration after administration of an acute loading dose of clopidogrel for AIS.
Abstract T P6: Mobile Endovascular-therapy Team is Alternative System to Patient Transfer for Acute Ischemic Stroke
Authors: Amano Tatsuo , Sato Masayuki , Matsumaru Yuji , Ota Takahiro
Published: July 2021

Background and Purpose:
Stroke centers which can provide endovascular therapy (EVT) for acute ischemic stroke patients are limited. Patients who considered eligible for EVT need to be transferred to hospitals where EVT available. However, delays for interhospital transfers may reduce the opportunity for good outcomes. Besides we accepted patients from outside hospitals, we formed a neurointerventional team which called “Mobile EVT Team (MET)” to offer EVT at outside hospitals. In this study, we compare elapsed time until the beginning of EVT between patients who performed EVT at outside hospitals and who received EVT in our hospital after they were transferred.

Methods:
From July 2012 to June 2014, acute ischemic stroke patients who performed EVT by MET (MET group) and received EVT after they were transferred to our hospital (transfer group) were enrolled. We defined the beginning of EVT as the time of injection from guiding catheter for EVT. In MET group, if guiding catheter was indwelled before MET arrival, the beginning of EVT was defined the time of MET arrival. We compared the time from initial imaging to the beginning of EVT (“picture to treatment” time) among two groups.

Results:
Thirty Patients from one site (distance between hospitals: 16 miles) in MET group and 7 patients from three sites (distance between hospitals: 0.5, 1 and 3 miles) in transfer group were analyzed. There was no difference the frequency of intravenous thrombolysis therapy among two groups. In MET group, time from notification to MET arrival was 72 minutes (interquartile range [IQR], 60-81). In transfer group, time from notification to patient arrival and from patient arrival to groin puncture were 55 minutes (IQR, 50-72) and 36 minutes (25-39). Picture to groin puncture time (MET group vs. transfer group: 68minutes [54-81] vs. 139 minutes [127-217], p=0.0004), picture to treatment time (122 minutes [106-165] vs. 168 minutes [154-241], p=0.0105) and notification to treatment time (90 minutes [78-116] vs. 125 minutes [109-140], p=0.0099) were significantly shorter in MET group than in transfer group.

Conclusions:
MET can provide EVT at outside hospitals without time delay and can be alternative system to patient transfer.
Abstract T P66: Safety and Effectiveness of Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients on Aspirin and Clopidogrel
Authors: Qureshi Mushtaq H , Khan Shayaan M , Jahangir Nauman , Malik Ahmed A , Freese Melissa , Thompson Michelle , Khan Asif A , Suri M. Fareed K , Qureshi Adnan I
Published: July 2021

Background:
The number of acute ischemic stroke patients who are on both aspirin and clopidogrel treatment at time of acute ischemic event is increasing. There is limited data regarding the safety and efficacy of intravenous recombinant tissue plasminogen activator (rt-PA) treatment in such patients.

Methods:
We reviewed the medical records and imaging data of consecutive patients with acute ischemic stroke who received IV rt-PA within 4.5 hours of symptom onset. We stratified the patients based on active regular use of antiplatelet
medications:
monotherapy (aspirin or clopidogrel), combination therapy (aspirin and clopidogrel), and no therapy and compared the rates of symptomatic intracerebral hemorrhage (ICH), neurological improvement (≥4 points in National Institutes of Health Stroke Scale [NIHSS], and favorable outcome (modified Rankin scale [mRS] 0-1) at discharge between the three groups.

Results:
A total of 88 acute ischemic stroke patients (mean age±SD; 69.88 ±15) were treated with IV rt-PA within the study duration. Of the 88 patients 45 (50.6%), 37 (41.6%), and 52 (58.4) were on monotherapy, combination therapy, or no therapy at time of presentation. The proportion of patients who developed symptomatic ICHs were similar (p=0.8) in monotherapy, combination therapy, and no therapy groups (3.3%, 0.0%, and 4.1%, respectively). The rates of neurological improvement were greater in patients on monotherapy (20%) (p=0.03) followed by combination therapy (11.1%), and no therapy groups (2.0%). There was no significant reduction in the rate of favorable outcome at discharge among patients on combination treatment compared with no treatment (odds ratio 0.8 , 95% confidence interval 0.4-1.8 ) after adjusting for age and initial NIHSS score strata (<10, 10-19, and ≥20).

Conclusions:
Compared with patients on no antiplatelet treatment, acute ischemic stroke patients who are actively using aspirin and clopidogrel appear to have similar risks and benefits with IV rt-PA treatment.
Abstract T P70: Outcome of Japanese Minor Stroke Patients Treated Without Intravenous Recombinant Tissue Plasminogen Activator Within 4.5 Hours After the Symptom Onset ~Fukuoka Stroke Registry~
Authors: Fujimoto Shigeru , Osaki Masato , Kumamoto Masaya , Kanazawa Makoto , Tagawa Naoki , Ishitsuka Takao , Kitazono Takanari
Published: July 2021

Background & Purpose:
Patients with minor stroke with the initial NIH stroke scale score of 4 or less were often treated without recombinant tissue plasminogen activator (rt-PA) even when they are admitted within 4.5 hours after the symptom onset. We investigated the outcome of minor stroke within 4.5 hours after the symptom onset without intravenous recombinant tissue plasminogen activator therapy.

Methods:
Among consecutive 6246 acute ischemic stroke patients who were admitted to the 7 stroke centers, 963 patients with admission within 4.5 hours after the symptom onset, ischemic lesions on diffusion-weighted image, NIH stroke scale of 4 or less, and prior modified Rankin scale (mRS) of 0 or 1 were included in the present study. Thirty-four (3.5%) of the 963 patients were treated with intravenous rt-PA. In other 926 patients, we observed a neurological deterioration (a NIHSS score worsening of ≥2-point) and stroke recurrence during the first 3 weeks. A good outcome (3 months) at was defined as mRS of 0 or 1.

Results:
Stroke recurrence and neurological deterioration occurred in 3.7% and 9.2% of 926 patients during the first 3 weeks. A good outcome 3 months after admission was observed in 82.3%. Atrial fibrillation and diabetes mellitus were less frequent in patients with than without a good outcome. The initial NIH stroke scale score, LDL-cholesterol, glucose, HbA1c, d-dimer, and CRP values were lower, and the initial HDL-cholesterol and estimated GFR values were higher in patients with than without a good outcome. On multivariate analysis, age (OR 0.94, 95%CI 0.92~0.97), the initial NIH stroke scale score (OR 0.60, 95%CI 0.48~0.74), LDL-cholesterol (OR 0.99, 95%CI 0.98~1.00), and D-dimer (OR 0.92, 95%CI 0.85~0.99) were negatively associated with a good outcome. With regard to the ROC curve analysis, the most accurate cut-off value for predicting a good outcome was 74 years in age, 2 in NIH stroke scale score, 137mg/ml in LDL-cholesterol, and 0.80μg/ml in D-dimer.

Conclusions:
In minor stroke patients treated without rt-PA, age of 75 years or more, NIH stroke scale score of 3 or more, LDL-cholesterol of 138mg/ml or more, or D-dimer of 0.80μg/ml or more could be negative predictor for a good outcome. In such patients, treatment with rt-PA may be considered.
Abstract T P71: Risk Of Ischemic Stroke During Periods Of Warfarin Discontinuation For Surgical Procedures: A Longitudinal Study Of 4060 Patients With Atrial Fibrillation
Authors: Suri M. Fareed K , Jahangir Nauman , Malik Ahmed A , Qureshi Mushtaq H , Khan Shayaan , Qureshi Adnan I
Published: July 2021

BACKGROUND:
The risk of ischemic stroke during periods of warfarin discontinuation for surgical procedures is recognized nut not well characterized. We performed this study to quantitate the risk of ischemic stroke associated with strial fibrillation during periods of warfarin discontinuation.

METHODS:
We evaluated the association of warfarin discontinuation for procedure with the incidence of ischemic stroke using pooled repeated measures and Cox proportional hazards analyses during follow-up after adjusting for age, gender, obesity, diabetes mellitus, hypercholesterolemia, cigarette smoking, and study period in a cohort of A total of 4060 patients were randomized into the AFFIRM study. Patients enrolled in the study had AF plus at least one other risk factor for stroke or death: age >65 yrs, systemic hypertension, diabetes mellitus, congestive heart failure, transient ischemic attack, prior stroke, left atrium 50+ mm, left ventricular fractional shortening <25%, or left ventricular ejection fraction <40%.

RESULTS:
Warfarin discontinuation for procedure occurred in 17 (0.5%) of the 11,116 person observations with a mean follow-up period of 9.9+/-1.0 years. The rate of ischemic stroke was higher among participant with warfarin discontinuation (17 of 3313 person observations versus 209 of 36505 person observations, p=0.047). Warfarin discontinuation was associated with an increased risk for ischemic stroke (relative risk [RR], 2.2; 95% CI, 0.5 to 9.3). among the 11,802 person observations after adjusting for potential confounders.

CONCLUSIONS:
The risk associated with discontinuation of warfarin for procedures must be recognized and considered in the risk benefit analysis of any procedure.
Abstract T P88: Impaired Collateral Status During Unilateral Carotid Occlusion In Type 2 Diabetic Mice
Authors: Nishijima Yasuo , Akamtsu Yosuke , Lee Chih Cheng , Liu Jialing
Published: July 2021

Introduction:
Type 2 diabetes mellitus (T2DM) is major risk factor of ischemic stroke and is associated with poor outcome after stroke. Previously we found that T2DM mice exhibited impaired leptomeningeal collateral flow recruitment after distal middle cerebral artery occlusion (MCAO). The current study aimed to study the collateral status during unilateral carotid occlusion, commonly observed in human patients with atherosclerosis.

Methods:
Adult male db/db and db/+ mice were subjected to permanent unilateral common carotid artery occlusion (CCAO) to simulate the hypoperfusion state in the human carotid artery disease. In vivo imaging of blood flow and flow velocity of the leptomeningeal collateral vessels was performed at various time points after CCAO with doppler optical coherence tomography (DOCT). Diameter of each major artery in the circle of Willis was also quantified by DiI-labeling at various time points after CCAO.

Results:
Imaging of DOCT showed that during occlusion of CCA, db/+ mice showed more robust retrograde filling of several distal branches of the MCA from ACA immediately and 24 hours after CCAO compared to db/db mice. Data with DiI-labeling showed that in both strains, the diameters of Willis ring including ICA, MCA, ACA gradually enlarged after 24 hours following CCAO. However the diameters of these vessels of db/db mice on the ischemic side were significantly smaller at 24 hours and 7 days after CCAO compared to that of db/+ mice.

Conclusion:
Our results demonstrate an impairment of leptomeningeal collateral recruitment and a deficiency in collateral vessel growth in the circle of Willis after CCAO in db/db mice. These findings might underlie the increased risk of ischemic injury in T2DM patients with carotid disease or stroke.
Abstract T P94: Differential Response to Treatment of Stroke in Rats With T1dm With Bone Marrow Stromal Cells Derived From Normal or T1DM Rats
Authors: Cui Chengcheng , Chopp Michael , Ye Xinchun , Zacharek Alex , Ning Ruizhuo , Yan Tao , Roberts Cynthia , Chen Jieli
Published: July 2021

Objective:
Treatment of stroke with bone-marrow-stromal cells (BMSCs) derived from normal rats (Nor-BMSCs) at 24h after stroke onset improves functional recovery in non-DM rats, but not in type-one DM (T1DM) rats. In the present study, we tested the differential therapeutic effects and mechanisms of action of the treatment of T1DM stroke with BMSCs derived from DM rats (DM-BMSCs) or Nor-BMSCs.

Methods:
T1DM rats were subjected to 2h of middle cerebral artery occlusion (MCAo) and were treated with DM-BMSCs, Nor-BMSCs or vehicle control (n=8/group) initiated at 24h after MCAo. A battery of functional tests, and vascular and white matter (WM) changes and in vitro cell culture experiments were performed.

Results:
Compared with Nor-BMSCs, treatment of stroke in T1DM rats with DM-BMSCs significantly improved functional outcome. DM-BMSCs increased vascular remodeling identified by cerebral vascular density and cerebral artery density, increased Bielschowsky silver (axon marker) and Luxol fast blue (myelin marker) expression in the ischemic border zone (IBZ) compared to T1DM-MCAo rats (p<0.05). However, DM-BMSC treatment also increased artherosclerosis-like changes identified by an increased internal carotid wall thickness, artery intimae thickness, and decreased cerebral artery diameter (p<0.05) compared to T1DM-MCAo control. DM-BMSCs treatment significantly increased PDGF, but decreased RhoA and ROCK expression in the IBZ. In vitro, DM-BMSCs have higher miR133b (1.9 fold) expression compared to Nor-BMSCs. DM-BMSC conditioned medium increased brain endothelial cell, smooth muscle cell and oligodendrocyte progenitor cell survival, as well as increased subventricular zone explant cell migration and primary cortical neuron axon outgrowth compared to Nor-BMSC conditioned or control medium.

Conclusion:
Treatment of stroke in T1-DM rats with DM-BMSCs have dual effects on stroke, i.e. significantly increases neurovascular remodeling, improves neurological recovery, and induces artherosclerosis-like vascular changes. The miR133b/RhoA/ROCK pathway may play a role in the DM-BMSC induced neurorestorative effects.
Abstract T P99: Development of Liposomes Loaded With Computed Tomogratphy Contrast Agent for Thrombus Imaging
Authors: Koudelka Stepan , Cimflova Petra , Turanek Jaroslav , Mikulik Robert
Published: July 2021

Introduction:
Liposomes are the most established nanocarriers that can be loaded with contrast agents as well as tailored for targeting to the desired tissue. Targeted CT liposomes represent a novel approach for rapid thrombus imaging. They allow specific and selective accumulation in thrombus providing significant contrast enhancement (expressed as HU) over the surrounding tissue.

Hypothesis:
We hypothesize that preparation technology will produce homogenous liposomes with sufficient level of loaded CT contrast agent.

Methods:
Liposomes were composed of distearoyl phosphatidylcholine, cholesterol, and distearoyl phosphatidylethanolamine - polyethylene glycol 2000 (molar ratio, 55/45/5). CT liposomes were prepared by lipid film hydration with iohexol (Omnipaque 350, GE Healthcare) followed by freeze-thaw extrusion (100 nm). Subsequently, they were purified by dialysis (Slide-A-Lyzer, cut-off 10 kDa) to remove un-loaded ioxehol. After purification, liposome-associated iohexol was determined by UV/VIS spectrophotometry and CT. Size distribution of final CT liposomes was assessed by dynamic light scattering.

Results:
Preparation technology produced homogenous liposome population having appropriate size distribution (90-110 nm and PD index, 0.05-0.10). Iohexol that remains associated in final CT liposomes represented only 5% of its initial level entering the preparation process. Almost 95% of iohexol was released and its final content was found to be 5 mg iodine/ml.

Conclusions:
Liposomal CT formulation was prepared with satisfactory size distribution and homogenity. Although the significant portion of iohexol was released, these CT liposomes were still detectable in vitro by CT. This basic liposomal platform will be optimized to achieve higher iohexol loading and will be further developed for thrombus imaging such as targeted CT liposomes.
Abstract W MP101: Palliative Care Consultations for Stroke Patients in Washington State
Authors: Creutzfeldt Claire , Huffer Andrew , Kalani Rizwan , Tirschwell David L
Published: July 2021

Background:
Patients with stroke have a high risk of death, physical and cognitive impairments and therefore have a high degree of palliative care (PC) needs. The goal of this study is to explore the prevalence of and associations with PC consultation in stroke patients.

Methods:
Using the administrative hospital discharge database of Washington State, we reviewed all patients discharged with stroke (based on ICD-9 codes) from 2009-2011. Strokes were subclassified as ischemic, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). We collected information on demographics, outcome and presence of a “Palliative Care encounter” as defined by the ICD-9 code V66.7.

Results:
Overall, there were 33102 stroke patients with a mean age of 71.1 (SD 16), 52% were female and 49% white. The majority of patients had ischemic strokes (28581, 86%) followed by ICH (9.6%) and SAH (4%). A PC encounter was found in 1682 patients (5%) and was more common in patients with older age, hemorrhagic stroke types, those discharged from larger hospitals and in more recent years (all p<0.05). A trend for higher rate of PC encounters was found for women (OR 0.89, 95% CI 0.77-1.02). For those patients where race data was available, blacks and Hawaiian/Pacific Islanders had less use of PC than whites (all p <0.05). One tenth of patients died in hospital (n=3327), only one third of which (n=1024) received a PC encounter. PC encounter was significantly associated with hospital death, and led to a shorter length of stay in those who died (4.5 days, 95% CI 4.2-4.8 vs. 6.6 days, 95% CI 6.2 vs. 7.0, p < 0.05).

Conclusions:
PC encounters are becoming more common for stroke patients, especially in larger hospitals and are strongly associated with hospital death (i.e. more commonly used in more severe strokes). The unequal distribution across age, gender, stroke type and race suggests a need for more standardized methods to identify patients’ need for PC consultation such as validated PC consultation triggers.
Abstract W MP105: Regionalization of Care and Increased Burden on Specialized Stroke Centers
Authors: Chauhan Nabeel , Ali Syed F , Hinduja Archana , Johnson Debra M , Bianchi Nicolas
Published: July 2021

Introduction:
Many patients are transferred to specialized stroke centers for advanced ischemic stroke (AIS) care, especially after tPA. We sought to determine differences in the baseline characteristics and outcomes between AIS cases presenting directly to our academic stroke center as compared to those transferred from outside facilities (OSH).

Methods:
Using our institutional GWTG stroke registry, we analyzed 1,726 AIS cases (01/09 - 02/14). Univariate and multivariable models explored differences in patients presenting directly at our center as compared to transferred from OSH.

Results:
46% percent of all AIS were transferred patients. Compared to those presenting directly at our center, transferred patients were older, more often Caucasian, with more vascular risk factors. They had worse median NIHSS, more often had limb weakness or aphasia and received IV tPA. In-hospital mortality was nearly double in transferred patients. Transfer-in patients had a longer hospital length of stay and were more often discharged to inpatient rehab. Independent predictors of in-hospital mortality were increasing age, A. fib, coronary artery disease and initial NIHSS. Transfer status was not independently associated with in-hospital mortality.

Conclusions:
Transferred patients differed significantly from those presenting directly, they have more stroke risk factors and present with severe strokes. Accepting such patients increase the burden at specialized stroke centers. Despite having more severe strokes on arrival, transfer patients had similar in-hospital mortality after adjusting for stroke severity (NIHSS) lending support to the concept of regionalized stroke care.
Abstract W MP110: INR reversal of Oral Anticoagulant-Associated Intracerebral Hemorrhage
Authors: Testai Fernando , Mukarram Faisal , Culpepper Andrew , Hillmann Maureen , Sekar Padmini , Flaherty Matthew L , Ringer Andrew , Osborne Jennifer , Moomaw Charles J , Langefeld Carl , Woo Daniel
Published: July 2021

Background:
The use of oral anticoagulants (OAC) is associated with poor outcome in intracerebral hemorrhage (ICH). In this study we investigated the effect of delayed INR reversal and the factors influencing it in patients with OAC-associated ICH (OAC-ICH).

Methods:
Data were obtained from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study which is a prospective, multi-ethnic multicenter study of ICH. Exclusion criteria included missing initial hematoma volume, INR or ED arrival time and being on heparin. Baseline characteristics, INR at baseline and 12h, hematoma location and volume, treatment received, hematoma expansion at 24h, and mortality at 3 months were recorded. INR reversal was defined as INR<1.4 at 12h post admission. Variables associated with INR reversal and case fatality at 3 months in non-OAC users and OAC users with and without INR <1.4 were compared.

Results:
A total of 1,746 of 2,276 subjects were included in the analysis. A higher proportion of OAC users (n=185) were white and had hypertension, diabetes, hypercholesterolemia, and lobar ICH than non-users (P<0.05). Baseline INRs for the OAC group were 3.1 (28.7%). Subjects on OAC received fresh frozen plasma (FFP, 44%) monotherapy, either recombinant factor VII or prothrombin complex (FVII/PCC, 7%), or a combination of FFP/FVII/PCC (11%). Increasing age (OR=0.96, 95% CI 0.94-0.98), elevated baseline INR (OR=0.34, 95% CI 0.26-0.43), and use of FFP only (OR=0.07, 95% CI 0.04-0.13) was associated with lack of INR reversal at 12h. Median INR at 12h (IQR) were 1.4 (1.3-1.6), 1.1 (0.9-1.1), and 1.0 (1.0-1.3) for the FFP, PCC/FVII, and FFP/FVII/PCC groups, respectively (p1.4 did not influence the rate of hematoma expansion at 24h. Case fatality at 3 months was 22% for non-OAC-ICH, 34% for OAC-ICH with INR<1.4, and 44% for OAC-ICH with INR>1.4 (p=.0005).

Conclusion:
In the ERICH study, patients treated with FFP monotherapy were less likely to have a normalized INR at 12h and this was associated with increased case fatality at 3 months. The use of FVII/PCC may shorten time to INR correction and improve outcome in OAC-ICH.
Abstract W MP22: Impact of Difference in Definitions of M1 and M2 segment of Middle Cerebral Artery on Acute Stroke Endovascular Therapy
Authors: Gulati Deepak , Ducruet Andrew , Aghaebrahim Amin , Jankowitz Brian , Jadhav Ashutosh , Jovin Tudor
Published: July 2021

BACKGROUND:
The involvement of the different segment of middle cerebral artery has different implications in terms of acute stroke endovascular therapy as learnt from recent trials. It has been suggested in prior trials that M1 segment occlusion might benefit more from acute endovascular therapy as compared to M2 segment. Ongoing trials have different definitions for segments of middle cerebral artery.

METHODS:
Retrospective review of latest 71 cases of either M1/M2 confirmed on Digital Subtraction Angiography (DSA) in prospectively maintained database of acute stroke interventions at our institute is performed. Of these, 49 cases have CTA performed prior to DSA (69%). Stroke Neurologist has blindly reviewed CTA angiogram. Conventional angiogram findings are considered accurate for the exact site of occlusion. Two definitions from REVASCAT trial and SWIFT PRIME trial are then scored based on CTA and assessed in respect to findings in DSA

RESULTS:
As per RESVASCAT defintion, 34 out of 49 cases on CTA/MRA (69%) have M1 occlusion on CTA. Of these 34 cases, 32 are then found to have M1 occlusion on DSA as well. The number of M2 occlusions were 9 out of 49 (18%) on CTA and all of them were found to have M2 occlusion of DSA as well. The accuracy of RESVASCAT definition of M1 and M2 were 32/34 (94%) are 9/9 (100%) respectively.

As per SWIFT PRIME definition, 27 out of 49 cases (58%) on CTA/MRA have M1 occlusions on CTA. Of these 27 cases, all cases were found to have M1 occlusions on DSA as well. The number of M2 occlusions were 15 out of 49 (31%) on CTA and 9 were found to have M2 occlusions on DSA. The accuracy of SWIFT PRIME definition of M1 and M2 were 27/27 (100%) and 9/15(60%).

6 cases (12%) with M1 occlusions on CTA as per REVASCAT definition were defined as M2 occlusions as per SWIFT PRIME.

CONCLUSIONS:
The examination of angiographic data found discrepancies between these two definitions. The accuracy of REVASCAT definition was better for M2 whereas the accuracy of SWIFT PRIME definition was better for M1. The different definition of middle cerebral artery segments could potentially lead to discrepancies in the eligibility criteria for acute endovascular interventions. The criteria used in determining the M1 and M2 segments should be consistent across the field.
Abstract W MP25: Intravenous Thrombolysis in India: The Indo-US Stroke Project
Authors: Pandian Jeyaraj D , Khurana Dheeraj , Kaul Subash , Sylaja PN , Padma Vasantha , Arora Deepti , Kaur Paramdeep , Thankachan Tissy , Singhal Aneesh
Published: July 2021

Background:
There is limited information concerning stroke thrombolysis in developing countries like India. We investigated the frequency, barriers and outcomes after thrombolysis in 5 high-volume hospitals across India.

Methods:
The Indo-US Stroke Registry and Infrastructure Development Project, jointly funded by NINDS and the Indian Department of Biotechnology, currently include 5 geographically diverse centers in North and South India and one in Boston, USA. Trained MD co-investigators and research coordinators prospectively collect data on consecutive adult patients with imaging-confirmed ischemic stroke <2 weeks after symptom onset. Data is entered into a central web-based electronic database.

Results:
From Nov-2012 to July-2014, 1944 patients were enrolled. Two hundred and eighty six were eligible for tPA. A total of 215 patients (11% of the total cohort and 75% of tPA-eligible patients) received thrombolysis including 139 of 188 patients who arrived <3h after onset and 76 of 98 who arrived between 3-4.5 h. Mean age was 59±15 years (range 48-69 years) and 68% were male. Stroke risk factors included hypertension (75%), diabetes (48%), hyperlipidemia (18%), coronary artery disease (27%), rheumatic heart disease (12%), atrial fibrillation (9%) and myocardial infarction (10%).The median NIHSS score was 10 (Interquartile range: 6-14). Hospital arrival was via EMS (3%), private transportation (50%) and transfer from another hospital (49%). Symptomatic intracranial hemorrhage was documented in 15 patients. Barriers of thrombolysis among patients otherwise eligible for thrombolysis included inability to afford tPA (n=15), patients/family refusal (n=32), delay in stroke diagnosis (n=6), and/or other in-hospital delays (n=9).

Conclusions:
Thrombolysis is frequently administered in large academic hospitals in India, with acceptable safety. The relative lack of ambulance services, delay in arrival and diagnosis, and high cost of tPA are opportunities for infrastructure development.
Abstract W MP26: Blood Brain Barrier Permeability and Neurovascular Unit Markers of Hemorrhagic Transformation After Rt-pa Administration
Authors: Castellanos Mar , van Eendenburg Cecile , Sobrino Tomás , Puig Josep , Blasco Gerard , García-Yébenes Isaac , Lizasoain Ignacio , Silva Yolanda , Terceño Mikel , Castillo José , Serena Joaquín
Published: July 2021

Objectives:
The administration of rt-PA increases the risk of hemorrhagic transformation (HT) due to an increase in the permeability of the neurovascular unit which allows the extravasation of erythrocytes. In this study we compared the predictive capacity of different neurovascular unit components and their correlation with blood brain barrier (BBB) permeability abnormalities evaluated by advanced neuroimaging.

Patients and methods:
Eighty-three patients with hemispheric stroke treated with rt-PA who had angio-CT perfusion before fibrinolysis were evaluated. Lesion volumes were calculated on perfusion and permeability maps. HT was assessed in the cranial CT at 24±12h after rt-PA and classified following ECASS II criteria. HT was considered symptomatic (sHT) when it was associated with an increase ≥ 4 points in the NIHSS. The levels of cellular-fibronectin (cFn), total MMP-9, laminin, heparan-sulphate, collagen type IV and protein S100β pre-rtPA and at 2, 24 and 72h post-rtPA were analyzed.

Results:
Fourteen patients (16.8%) had HT, which was symptomatic in 3 (3.6%). On comparing patients with and without HT independently of the type, only MMP-9 and protein S100β levels at 24h were found to be higher in the HT group. However, baseline cFn levels were higher in patients with PH2 (12.5±5.6 vs. 6.6±3.8μg/mL, p=0.013) and sHT (13.8±6.7 vs. 6.7± 3.9μg/mL, p=0.003) and laminin levels were also lower in patients with PH2 (1.5±0.8 vs. 3.5±2.5ng/mL, p=0.016). In the multivariate analysis, only cFn levels remained as an independent predictor of sHT (OR 1.40;CI 95%, 1.02-1.93; p=0.037). The analysis of the permeability maps yielded cut-off values for the prediction of HT with high specificity and negative predictive values regardless of the threshold used for visualization of the abnormal permeability area.

Conclusions:
Among different neurovascular unit markers, this study seems to confirm the utility of cFn levels as potential predictors of sHT after rt-PA. Permeability maps would seem to predict the likelihood of not bleeding with high probability.
Abstract W MP28: Safety of Parentral Antiplatelet Regimen Within 24 Hours of Intravenous tPA Administration: Challenging the Conventional Paradigm
Authors: Ahmad Javaad , Hussain Mohammed , Mehta Siddhart , Brar Jaskiran , Chahal Harina , Nizam Shayaan , Panezai Spozhmy , Moussavi Mohammad , Kirmani Jawad F
Published: July 2021

Background and Objective:
It is considered unconventional to initiate antiplatelet regimen within 24 hours of IV tPa administration in acute ischemic strokes. There has been an increasing amount of literature assessing combination therapy of IV r- tPA and IV Eptifibatide in acute ischemic stroke. Our objectives were to evaluate the safety (hemorrhagic complications) and efficacy (discharge mRS) of administering IV Eptifibatide within the first 24 hours of receiving full dose IV r-tPA respectively.

Materials and Methods:
All patients that presented to our university affiliated stroke center from 2010-13 with an acute ischemic stroke were included and retrospectively classified into two groups. Group A underwent full dose IV r- tPa (.9 mg/kg) (+/- Endovascular intervention). Group B underwent full dose IV r-tPa (.9mg/kg) and IV Eptifibatide (+/- Endovascular intervention). Epitafibide was administered as a bolus of 135 mcg/kg IV followed by .5 mcg/kg/min for 20 hours. The primary endpoint of bleeding is classified as major (symptomatic intracranial hemorrhage or hemoglobin decrease by >5 mg/dl), minor (asymptomatic intracranial hemorrhage or hemoglobin decrease by 3-5 mg/dl) and insignificant as proposed by TIMI score. The efficacy endpoint was discharge mRS of 0-1 as favorable, with 2 and above being unfavorable.

Results:
We reviewed 2,016 patients with ischemic stroke, of which 170 received IV tPA. Among the group, 118 received IV r-tPa alone and 52 received combined modalities of IV r-tPa and IV Eptifibatide. In group A, there were 7 patients who had a major complication of symptomatic intracranial hemorrhage, while 1 patient had a minor complication of asymptomatic intracranial hemorrhage. In group B, there were 3 patients who had major complication of symptomatic intracranial hemorrhage and 5 with minor complications of asymptomatic intracranial hemorrhage. In group A , 9% (n=4) had a favorable outcome (OR=2.389, 95% CI 0.6645 to 8.589, p= 0.2217). Of the 52 patients in group B, 18% (n=8) had a favorable outcome.

Conclusion:
IV Eptifibatide, within the first 24 hours of ischemic stroke in combination with full dose IV r-tPA was found to be safe and efficacious. Further, larger prospective trials are needed to corroborate our findings.
Abstract W MP47: Roles of Macrophage PPARγ on Intracranial Aneurysmal Rupture
Authors: Korai Masaaki , Shimada Kenji , Furukawa Hajime , Wada Kosuke , Wei Yuan , Tada Yoshiteru , Kuwabara Atsushi , Shikata Fumiaki , Kitazato Keiko T. , Nagahiro Shinji , Hashimoto Tomoki
Published: July 2021

Background and Purpose:
Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in regulating not only lipid and glucose metabolism but also atherosclerosis and inflammation which are associated with intracranial aneurysmal rupture. It has been suggested that PPARγ is present in various kinds of cell types including macrophages which we reported to contribute to intracranial aneurysm formation. In addition, macrophage PPARγ regulates inflammatory cytokines negatively. Therefore we hypothesized that macrophage PPARγ is protective against intracranial aneurysmal rupture. We tested this hypothesis by using our own established mouse model of intracranial aneurysm.

Methods:
Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle or PPARγ agonist (pioglitazone:PGZ) or clodronate liposome. PPARγ antagonist (GW9662) was added to PGZ treatment. We induced aneurysms to macrophage-specific PPARγ knockout mice and treated them with vehicle or PGZ with the same protocol mentioned above. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage.

Results:
Both PGZ and depletion of macrophage by clodronate liposome reduced the incidence of ruptured aneurysms and rupture rate. PGZ treatment decreased the inflammatory cytokines that were increased in cerebral arteries of mice with aneurysm induction compared to mice without aneurysm induction. To examine whether the macrophage PPARγ is associated with intracranial aneurysmal rupture, we administered PGZ to macrophage-specific PPARγ knock out mice. PGZ did not have protective effect against aneurysmal rupture in macrophage-specific PPARγ knock out mice although it exerted protective effects in wild type mice.

Conclusion:
PPARγ activation is protective against intracranial aneurysmal rupture by suppressing inflammatory cytokines and macrophage PPARγ is associated with this protective effects.