bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic CT perfusion for acute cerebral ischemia: increasing anatomical coverage with the “toggling table” technique
Authors: Roberts Heidi C , Dillon William P , Tsao Jack W , Fischbein Nancy J , Smith Wade S
Published: July 2021

P17

Computed tomography (CT) has experienced a revival for perfusion assessment in acute stroke. However, so far it is limited by its small anatomical coverage. We studied a toggling table approach to (multislice) dynamic perfusion CT for extended coverage in patients with suspected acute MCA ischemia. In 20 patients with suspected acute MCA ischemia, a dynamic CT perfusion scan was performed on a multidetector scanner. To increase anatomical coverage, 2 distinct “toggling” table positions (each consisting of two 1cm slices) were chosen to represent the MCA territory and scanned in an alternating fashion during the bolus injection of 40mL contrast agent. Dynamic images were evaluated on a ROI and pixel-by-pixel basis, estimating peak density change, time to peak (TTP), integral (rCBV), mean transit time (MTT), and flow (rCBF). Acutely acquired CT perfusion data were compared with follow-up CT or MR (perfusion and diffusion) images. With the toggling table approach, temporal resolution is reduced to approximately 5 secs. Four imaging slices at two distinct locations can be obtained, covering the MCA territory. In 15 patients, perfusion CT revealed focal abnormalities in at least one slice, most commonly on MTT maps. In 14 of these 15 patients, the area of perfusion abnormality was a good predictor of the ultimate infarct. A single table location approach would have underestimated or missed the involved tissue in most cases. In 5 of the 20 patients, perfusion maps failed to delineate any abnormality: in 4 cases, MRI confirmed the absence of ischemia, in 1 case, CT failed to reveal a small ischemic injury visible on diffusion MRI. Addition of the dynamic CT perfusion scan adds less than 5 minutes to a CT stroke protocol and can be coupled with CTA studies to image the cervical and cerebral vasculature in acute stroke. The dynamic CT perfusion technique is a practical and useful tool for the emergency assessment of acute stroke patients. By employing the toggling table approach, perfusion information can be obtained over an extended anatomic area and thus reveal the presence and the extent of presumed tissue ischemia.
Multiparameter MRI ISODATA characterizes ischemic damage
Authors: Soltanian-Zadeh Hamid , Hammoud Rabih , Jacobs Michael A , Lu Mei , Patel Suresh C , Mitsias Panayiotis D , Pasnoor Mamatha , Knight Robert A , Zheng Zhang G , Chopp Michael
Published: July 2021

P23

Purpose:
We present a tissue characterization method to identify viable and non-viable tissue in cerebral ischemia using multi-parameter MRI. The method utilizes T1, T2, proton density, and diffusion weighted images (T1WI, T2WI, PDWI, DWI, respectively). Image Analysis Approach: After pre-processing (intra-cranial segmentation, non-uniformity correction, and noise suppression), we segment tissues using a self organizing data analysis method (ISODATA) and characterize tissues using Euclidean distance measures to score the regions between 1 and N (N determines characterization resolution). Signature or score 1 is assigned to normal white matter and score N is assigned to CSF. Each lesion zone is assigned a score based on its levels of differences (in terms of multi-parametric MRI) from white matter and CSF. Experimental
Methods:
Rats were imaged by a 7T MRI system at one of the three time points (acute, 4–8 hrs; sub-acute, 16–24 hrs; and chronic, 48–168 hrs) after MCA occlusion. Then, they were sacrificed and their brains were sliced and prepared for histological studies. MRIs of 18 slices (8 at acute time in 4 rats, 8 at sub-acute time in 4 rats, and 2 at chronic time in 1 rat) were processed and scored. 2 DWI (b=600, b=800), PDWI, T2WI, and T1WI were used and an MRI score between 1 and 100 (N=100) was found for each tissue region. Segmented tissues were mapped onto the histology images and were scored by an experienced pathologist, from 1 to 10. MRI scores were validated using histology scores. To this end, correlation coefficients between the two scores (MRI and histology) and 95% confidence limits were found.
Results:
The results showed excellent correlations between MRI and histology scores at different time points. Correlation coefficients were 0.90 acutely, 0.82 sub-acutely, and 0.88 overall. The 95% confidence intervals were (0.53,0.98), (0.27,0.97), and (0.68,0.95), respectively.
Conclusion:
The proposed method accurately characterizes tissue damage in cerebral ischemia based on multi-parameter MRI. It is useful for a variety of applications such as evaluating response to treatment, where volume changes for different zones of stroke over time, e.g., tissue recovery, can be evaluated.
Spectroscopy and Histology Demonstrate Lipids in Ischemic Rat Brain after Middle Cerebral Artery Occlusion with Reperfusion
Authors: Graham Glenn D , Wallace James A , Estrada Eduardo Y , Roberts Kristianna K , Rosenberg Gary A , Gasparovic Charles C
Published: July 2021

P73

Background:
Elevated macromolecule signals, as measured by proton magnetic resonance spectroscopy (MRS) after human stroke, are hypothesized to arise from mobile lipids that accumulate within macrophages. However, their chemical identity, cellular location, and clinical significance remain uncertain.
Methods:
Adult Wistar rats underwent a 90 minute middle cerebral artery occlusion with reperfusion. Animals survived for 2 to 5 days prior to sacrifice. Immediately after decapitation, 400 μm slices from an infarcted region of forebrain were prepared and perfused in artificial CSF at 36 degrees C, and studied by gradient-enhanced one-dimensional (1D) MRS and by two-dimensional correlation spectroscopy (COSY). Cryostat coronal sections from other, identically prepared rats were stained for lipid (Nile Red) and immunostained for microglia/macrophages (OX42).
Results:
The 1D spectra from infarcted samples contained broad resonances arising from lipid methylene and other fatty acyl protons that were absent in control samples. These assignments were confirmed by the COSY crosspeaks. Increases in crosspeaks from mobile polypeptides were not detected. The corresponding histologic specimens showed abundant lipid droplets within the infarct that were not seen in contralateral, uninfarcted tissue. These droplets were primarily located within OX42 immunostaining cells.
Conclusions:
Our model studies support the hypothesis that macromolecule signals detected by MRS in subacute stroke arise from mobile lipids concentrated in macrophages. These results help to clarify the spectroscopic findings in humans. Further histologic study is warranted to determine whether cells containing lipid droplets that are not stained by OX42 are also present.
The Effect of the Dendritic Growth Factor BMP-7 on Local Cerebral Glucose Utilization and Blood Flow in Reversible Middle Cerebral Artery Occlusion in Rats
Authors: Liu Yitao , Belayev Ludmila , Zhao Weizhao , Busto Raul , Saul Isabel , Alonso Ofelia , Ginsberg Myron D
Published: July 2021

P79

Bone morphogenetic protein-7 (BMP-7) (=osteogenic protein-1, OP-1) has been shown to enhance dendritic growth and improve functional recovery after experimental stroke. In this study, we examined the effect of BMP-7 on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) following transient middle cerebral artery occlusion. Sprague Dawley rats (n=29) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by poly-L-lysine coated intraluminal suture (1). Rectal and cranial (left temporalis muscle) temperatures were regulated at 37–37.5
o
C. BMP-7 or vehicle (volume, 25μl) was administered intracisternally in blinded fashion at 24h after MCAo. Neurological status was evaluated during occlusion (60 min) and daily for 2 days after MCAo; a grading scale of 0–12 was employed (1). LCMRglu was measured autoradiographically with
14
C-2 deoxyglucose (2-DG) and LCBF with
14
C-iodoantipyrine 48 h after MCAo. Four animals groups were studied: LCMRglu series (BMP-7, n=7; vehicle, n=8); LCBF series (BMP-7, n=6; vehicle, n=8). Average three-dimensional image data sets were constructed for each group and were compared by pixel-based statistical methods (2). Rectal and cranial temperatures, MABP, plasma glucose and blood gases were similar among groups. BMP-7 significantly improved the neurological score compared to vehicle at 48 after MCAo (7.3 ± 0.4 vs. 9.0 ± 0.2, respectively; p<0.0003). Compared to vehicle-rats, BMP-7 significantly increased LCMRglu in ipsilateral basal ganglia, improved LCBF in ipsilateral subthalamus, and decreased LCBF and LCMRglu in contralateral cortical regions. The improved glucose metabolism in ipsilateral basal ganglia of BMP-7 rats is compatible with its salutary influence on neurological recovery. Supported by Creative BioMolecules, Inc., Hopkinton, MA, and by NIH Grant NS 05820. (1)Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD: Stroke 27:1616–1623,1996. (2)Zhao W, Belayev L, Ginsberg MD: J Cereb Blood Flow Metab 17:1281–1290,1997.
Role of P
2
receptors in Cerebral Vasospasm
Authors: Zhang John H , Kimura Hitoshi , Carpenter Robin , Parent Andrew D
Published: July 2021

P87

Introduction:
Extracellular ATP activates P
2
receptors to increase intracellular Ca
2+
, to contract cerebral arteries, and to induce vasospasm in animals. This study examined the mRNA expression of P
2
receptors in a rat double hemorrhage model and explored the therapeutic role of P
2
receptor antagonists in a dog double hemorrhage model.
Methods:
One hundred SD rats were divided into five groups to undergo double hemorrhage by injecting autologous arterial blood into cisterna magna on day 0 and 2. Rats were sacrificed on day 3, 5 or 7. In sham group, rats were injected with saline. In control group, no surgery was conducted. Basilar arteries were harvested for mRNA isolation and RT-PCR or were fixed for transmission electron microscopy (TEM). Eighteen dogs were divided into three groups to have double hemorrhage and sacrificed on day 7. Two groups were treated, intracisternally, with P
2
receptor antagonist suramin (selective for P
2Y
and P
2X
) or PPADS (selective for P
2X1
) (30 μM) from day 3–6. Angiograph was performed before blood injection and before sacrifice. The basilar arteries were collected for TEM.
Results:
Mild to moderate vasospasm (30–40% reduction) was observed on day 3–7 in rats. The mRNA expression of P
2X1
receptor was down-regulated (P<0.05) on day 3 and recovered on day 5 and 7. P
2Y1
and P
2Y2
receptors were up-regulated (P<0.05) on day 5 and remain elevated on day 7. No changes were observed in the shame group. Severe vasospasm was observed on day 7 in dogs. P
2
receptor antagonist Suramin but not PPADS significantly reversed (P<0.01, ANOVA) vasospasm in dogs. Discussion: P
2Y1
and P
2Y2
, but not P
2X1
, may be involved in cerebral vasospasm. Up-regulation of P
2Y
receptor may enable ATP to produce contraction at low concentrations. Suramin reduced vasospasm probably by blocking P
2Y
receptors.
Growth pattern of ischemic lesions with different initial volume in a permanent middle cerebral artery occlusion model
Authors: Meng Xiangjun , Li Fuhai , Silva Matthew D , Sotak Christopher H , Fisher Marc
Published: July 2021

P94

Background and Purpose:
Diffusion-weighted imaging (DWI) allows measurement of ischemic lesions in a real-time manner and is used increasingly for evaluation of stroke therapy. This study was to determine if lesion growth is different when the initial lesion volumes on DWI are different after permanent middle cerebral artery occlusion (MCAO) in rats.
Methods:
Twelve Sprague-Dawley male rats were subjected to permanent MCAO with the intraluminal suture method. DWI was performed at 30, 60, 90, 150, 210, and 270 minutes after occlusion. The ischemic lesion areas were determined by visually tracing the hyperintense border on DWI, and the lesion volumes were calculated by multiplying the areas by the slice thickness. Based on the initial lesion volume at 30 minutes, the rats were evenly assigned to two groups: group A with smaller initial volume (<130 mm
3
, n=6) and group B with larger initial volume (≥130 mm
3
, n=6).
Results:
The initial lesion volumes at 30 minutes were significantly different between two groups (106±14 mm
3
vs 189±38 mm
3
, p<0.001), and the lesion volumes were also different thereafter (189±35 mm
3
vs 270±76 mm
3
at 270 minutes, p=0.04). The absolute increased volumes at 270 minutes, however, had no difference between two groups (84±32 mm
3
in group A and 82±44 mm
3
in group B, p=0.93). The percent increase of the lesion volume in group A was bigger than that in group B (80±30% vs 42±17% at 270 minutes, p=0.02).
Conclusions:
The growth rate of the ischemic lesion is larger if the initial lesion volume is smaller, but the absolute increase of the lesion volume is similar regardless of the difference of the initial lesion volume. These findings are of importance in evaluating the efficacy of stroke therapy when the initial lesion volumes are different.
NIHSS predicts outcome better than GCS in intracerebral hemorrhage
Authors: Bae Charles , Andrefsky John C , DeGeorgia Michael A
Published: July 2021

P96

Introduction:
The National Institutes of Health Stroke Scale (NIHSS) score has been correlated with outcome in ischemic strokes but not intracerebral hemorrhage (ICH). We sought to validate the use of NIHSS in ICH patients by comparing it to outcomes using the Glasgow Coma Scale (GCS) score and volume of ICH. Use of the NIHSS will allow clinicians to follow the outcome of more specific parameters which may be used in clinical trials.
Methods:
We prospectively followed 61 ICH patients admitted to the Cleveland Clinic within 24 hours of onset. Age, NIHSS, GSC, Barthel index (BI), modified Rankin scale (mRs) were obtained on admission, discharge and at 3 months. An ICH volume was calculated using the AxBxC/2 method from the admission CT scan. Correlation was assessed using the Spearman correlation coefficient (SCC) and 95% CI, with a worst score given to deaths. Patients with a history of ischemic stroke were excluded. The maximum NIHSS for coma was 35.
Results:
The average age of the patients was 66 years old with 35 females and 26 males. On admission, the average NIHSS was 21 for all patients, 28 for those who died at 3 months and 10 for 3-month survivors. The average NIHSS for 3- month survivors was 3. On admission, the average GCS score was 9 for all patients, 7 for those who died and 12 for 3-month survivors. The average GCS of 3-month survivors was 15. The average BI and mRs were 98 and 0 on admission and 86 and 1 at 3 months for survivors. On admission, the average ICH volume was 49 cc for all patients, 66 cc for those who died at 3 months and 24 cc for 3-month survivors. For admission NIHSS of 18 or greater the 3-month mortality was 82% vs 9% for those with NIHSS < 18 (P<0.001). Admission NIHSS correlated strongly with admission GCS (SCC=0.82, CI 0.68, 0.97) and the two scores correlated similarly with volume (SCC=0.45, CI 0.22, 0.68; GCS SCC=0.40,CI 0.16, 0.63). Impressively, admission NIHSS correlated with the 3 month NIHSS (SCC=0.72, CI 0.53, 0.91), 3-month BI (SCC=0.74, CI 0.55, 0.92), 3-month mRs (SCC=0.72, CI 0.53, 0.91) significantly better than did the GCS (SCC=0.57,0.57 and 0.59 for the NIHSS, BI, and mRs, respectively).
Conclusion:
The admission NIHSS predicts 3-month survival in ICH patients better than the GCS.
The effect of platelet function abnormalities on the volume of spontaneous intracerebral hemorrhage(ICH)
Authors: Torbey Michel T , Ziai Wendy C , Bhardwaj Amish , Kickler Thomas , Wityk Robert
Published: July 2021

P106

Objectives:
Impaired platelet function has been associated with increased propensity for ICH. Our objective is to demonstrate that patients with larger ICH volume have abnormal platelet function.
Methods:
This is a prospective cohort study. Platelet function was measured by a standard set of tests within one week of ICH. CT scans were performed within 24 hours of the event and ICH volume determined by the ABC/2 method.
Results:
12 patients were enrolled (5/12 female, 7/12 male). The mean age was 64 years (range 40–85). Four patients were on ASA. Platelet count ranged from 76 to 315 KU/mm
3
. Patients were divided into two subgroups based on ICH size: ≤30cc and >30cc. The two CT subgroups were similar with respect to age, sex, race, history of hypertension and alcohol abuse. We report in Table 1 the distribution of specific platelet abnormalities among the two ICH groups.
Conclusions:
Large spontaneous ICH (>30cc) is associated with evidence of platelet hypoactivity which appear to extend beyong ASA effect.
Low-Dose Endotoxin Reduces Human Cerebrovascular Reactivity and Produces Procoagulant State
Authors: Barreto Maria Perez , Fischberg Glenn M , Paganini-Hill Annlia , Lapakulchai Yodchai , Ameriso Sebastian F , Fisher Mark J
Published: July 2021

P118

Stroke risk is increased in the presence of some infections. We studied potential mechanisms linking infections and stroke risk. We used endotoxin, a component of gram negative bacteria, as a standardized inflammatory stimulus. We infused low-dose endotoxin (1ng/kg) as a bolus in four healthy men, and analyzed cerebrovascular and hemostatic effects over 24 hours. We measured cerebral vasomotor reactivity, using transcranial Doppler ultrasonography to calculate breath-holding index (BHI); the latter consists of the percent change of middle cerebral artery blood flow velocity over time during breath holding. We also measured thrombin-antithrombin complexes (TAT, an index of thrombin generation), and soluble e-selectin (a marker of endothelial activation). Following infusion of endotoxin, there were substantial physiological changes primarily at three to six hours post-infusion. Temperature peaked at 100 °F (p<.05), with no significant change in mean arterial pressure. BHI showed maximum decline from 1.55 ± 0.88 to 0.33 ± 0.35 %/sec (p<.05). TAT levels increased from 3.0 ± 0.9 to 41.0 ± 21.1 ug/ml (p<.05). Soluble e-selectin levels increased from 66.6 ± 35.2 to 207.4 ± 78.9 ug/ml (p<.05). These findings indicate that a standardized low-dose inflammatory stimulus produces a marked decline in human cerebrovascular reactivity while simultaneously inducing a procoagulant state with endothelial activation . The reduction in cerebrovascular reactivity combined with a procoagulant state may contribute to increased stroke risk in this setting.
Variations in Carotid Bifurcation Anatomy: Differences within and between individuals
Authors: Schulz Ursula Gr , Rothwell Peter M
Published: July 2021

P139

Carotid plaque formation is thought to depend on haemodynamic factors related to vessel anatomy. Side differences in bifurcation anatomy could explain the frequent asymmetry in the extent of carotid plaque
within
individuals. Differences
between
individuals could account for variation in the tendency to develop carotid atheroma. However, there are very few data on the extent of variation in bifurcation anatomy. We studied the inter- and intra-individual variability of bifurcation anatomy in 5395 angiograms from the 3007 patients in the European Carotid Surgery Trial. To minimise changes in bifurcation anatomy secondary to atherosclerosis, we excluded angiograms of vessels with ≥30% NASCET stenosis. We measured the arterial diameters at disease free points and calculated the following ratios: internal to common carotid (ICA/CCA), external to common carotid (ECA/CCA) and external to internal carotid (ECA/ICA). We calculated the 95% ranges to describe the variability of the ratios. To ascertain intra-individual differences we compared the ratios on the symptomatic side with those on the contralateral side in individual patients. Among the 2201 bifurcations with <30% stenosis there was considerable inter-individual variation in the ratios. The 95% ranges were: ICA/CCA (0.44–0.86); ECA/CCA (0.34–0.80) and ECA/ICA (0.55–1.33). Among the 767 patients with <30% stenosis bilaterally we found considerable intra-individual asymmetry in the vessel diameter ratios. Side differences of ≥25% were present in 17% (95% CI 15–20) of angiograms for the ICA/CCA ratio, 27% (24–30) for the ECA/CCA ratio and 32% (28–35) for the ECA/ICA ratio. There are large inter-individual differences in carotid bifurcation anatomy. For example, the normal range of the ECA diameter varies from half that of the ICA to a third more than the ICA. Intra-individual variability is equally considerable. This variability has not been documented previously. It may partly explain why the extent of carotid atheroma is often highly asymmetrical within individuals and why some individuals are more prone to develop carotid disease than others. Prospective studies are required to confirm this.
The New York Islands AVM Study: Detection rates for brain AVM and incident AVM hemorrhage
Authors: Stapf C , Mast H , Sciacca R R , Pile-Spellman J , Mohr J P
Published: July 2021

P159

Background:
Population-based data on the incidence of brain AVM hemorrhage is scarce. We studied detection rates of brain AVM and AVM hemorrhage in a defined population.
Methods:
The New York islands (Manhattan, Staten Island, and Long Island) are a ZIP-code defined area comprising a 8,898,000 population. In a retrospective investigation, major NY islands hospital centers retrieved the number of patients who lived in the study area and were discharged with a diagnosis of brain AVM between 1996 and 1999. Starting March 15, 2000, all major NY islands hospitals prospectively reported data on consecutive NY islands patients with a diagnosis of brain AVM and whether or not the patient had suffered AVM hemorrhage. Referral patients living outside the study area were excluded from the sample.
Results:
The retrospective detection rate of brain AVMs in patients living in the study area (Table 1) was estimated to be 1.2/100,000 person-years (95% CI:1.1–1.4). As of July 14, 2000, 37 prospective AVM patients were encountered leading to a calculated AVM detection rate of 1.25/100,000 pers-yrs (95% CI: 0.9–1.7) with an estimated incidence for first-ever AVM hemorrhage (n=6) of 0.2/100,000 pers-yrs (95% CI:0.1 to 0.5). The prevalence of AVM hemorrhage (n=14) was 0.5/100,000 pers-yrs (95% CI:0.3 to 0.8).
Conclusions:
Our preliminary data suggest similar prospective and retrospective AVM detection rates. More than one third of AVM patients may suffer intracranial hemorrhage.
Increasing the Use of Thrombolytic Therapy by 50% in a Community Hospital, Safely and Successfully.
Authors: Tamulonis Donald J , Sosnowski Cheryl A
Published: July 2021

P199

Background and Purpose:
A recent report in JAMA, concerning thrombolytic therapy for AIS in the Cleveland area, suggested the use of tPA for AIS be limited to academic stroke centers, rather than community hospital settings. That study reported that less than 2–6% of AIS patients receive thrombolytic therapy and the incidence ICH following thrombolytic therapy was as high as 15%. This report provides data from a community hospital near Cleveland with success in increasing thrombolytic therapy administration in one year from 2% to 4%. Thrombolytic therapy was successful and safe, with a 0% ICH rate.
Methods:
Data were collected retrospectively for a 2 year period (1998–1999) for AIS patients presenting to a community hospital ED with AIS.
Results:
In 1998, there were 383 patients admitted with stroke; of those, 334 were AIS. 54 (11%) of the patients arrived within 3 hours of symptom onset. Of these, 5 (9%) met inclusion criteria for thrombolytics. The overall tPA acministration rate was 2%. After an educational program consisting of community education, paramedic education and the development of a paramedic protocol for AIS, the 1999 data were 351 patients admitted with stroke; 326 being AIS. Patients presenting within 3 hours increased to 17% and 12 (22%) met inclusion criteria for tPA. Overall, tPA administration in 1999 increased to 4%. During the 2 years of analysis, there were no incidences of ICH following tPA administration. Door to needle times for 1998 and 1999 average 64 minutes and 90 minutes, respectively.
Conclusions:
Our data confirm that thrombolytic therapy in a community hospital setting can safely and effectively be administered with effective protocols and clinical pathways. The success of a program is dependent upon the dedication of the hospital and the stroke program personnel. Education of the community and the EMS personnel are pivotal in bringing tPA candidates into the hospital for evaluation. Education of ED physicians, neurologists, residents, and nurses, with the establishment of strict standards of care can assure safe and successful results. It is, therefore, possible to deliver tPA safely in a community hospital.
Triflusal vs. Aspirin for the Prevention of Infarction: a Randomized Stroke Study (TAPIRSS)
Authors: Culebras Antonio , Rotta-Escalante R , Vila J , Dominguez R , Abiusi G , Famulari A , Rey R , Bauso-Toselli L , Gori H , Ferrari J , Fraiman H
Published: July 2021

P208

Background:
TAPIRSS is a randomized, double-blind, multicenter pilot trial designed to study the efficacy of triflusal for the prevention of secondary ischemic stroke conducted in Buenos Aires, Argentina. Triflusal is an antiplatelet agent structurally related to aspirin. Methods and
Results:
From October 1996 to October 1999 patients were randomized to group #1 (aspirin therapy, 325 mg/daily) or group #2 (triflusal, 600 mg/daily). All patients had experienced either an ischemic stroke (80.9%) or a transient ischemic attack within 6 months prior to randomization. Patients were treated for a median of 586 days. Data for 429 patients were analyzed. Primary endpoints were: cardiovascular death 3.7%(#1)/2.3%(#2)[OR=1.6]; cerebral ischemic infarction 7.4%(#1)/8.0%(#2)[OR=0.92]; non-fatal myocardial infarction 2.3%(#1)/1.9%(#2)[OR=1.24];severe hemorrhage any kind 3.2%(#1)/0.5%(#2)[OR=7.1][p=0.068]. Secondary endpoints were: non-vascular death 2.4%(#1)/0.5%(#2)[OR=5.02]; non-severe hemorrhage 6.0%(#1)/2.3%(#2)[OR=2.66][p=0.058]; systemic thromboembolism 0.9%(#1)/1.4%(#2)[OR=0.65]. Aggregate analysis of primary endpoints showed no significant differences between aspirin and triflusal. Aggregate analysis of secondary enpoints showed a significant difference in favor of triflusal [p=0.038]. Analysis of the combination severe and non-severe hemorrhage showed a significantly reduced incidence of hemorrhagic events with triflusal [8.3%(#1)/2.8%(#2), p=0.013]. Dyspepsia and gastrointestinal discomfort were the most common adverse events in the triflusal group.
Conclusions:
Triflusal shows a protective effect similar to aspirin in the prevention of secondary ischemic stroke with a lesser risk of hemorrhagic complications. Also, triflusal may be safe for the primary prevention of ischemic stroke.
The dispersion and differentiation of the transplanted adult neuronal percursors in the adult striatum
Authors: Zhang Ruilan , Zhang Li , Wang Lei , Zhang LiJie , Zhang Zheng G , Chopp Michael
Published: July 2021

P224

The neuronal precursors persist in the adult subventricular zone (SVZ) and they may also be present in the adult rostral migratory stream (RMS). In the present study, we examined whether the cells derived from the adult SVZ and RMS can survive and retain their ability to migrate and differentiate into neurons when they are transplanted into adult brain. Donor cells were harvested from the SVZ and RMS in the adult Wistar rats and were cultured for ten days before transplantation. To distinguish donor cells from those of the host after transplantation, the donor cells were labeled with bromodeoxyuridine (BrdU). The BrdU labeled donor cells were transplanted into the cortex and striatum of the adult male Wistar rats (n=16). The rats were sacrificed at 7 days (n=8) and 28 days (n=8) after transplantation. Grafted cells were present within the recipient regions in the rats sacrificed 7days after transplantation. However, 28 days after transplantation the BrdU labeled cells derived from both the SVZ and RMS migrated extensively from their implantation site a radial distance of approximately 2 mm in the striatum but not in the cortex. Double immuofluorescent staining revealed that 65% of grafted cells were neurons (both BrdU and MAP2 immunoreactive) and 20% were astrocytes (both BrdU and GFAP immunoreactive). Our data demonstrate that the transplanted adult neuronal precursors from both the SVZ and RMS retain their capability to migrate and differentiate in the adult striatum.
Healthcare Resource Utilization in the Three Months after Acute Stroke: A Report on 1604 Patients from the Glycine Antagonist in Neuroprotection (GAIN) Americas Trial
Authors: Nielsen Kirsten , Phillips Stephen J , Rundek Tanja
Published: July 2021

P226

Background/objective:
Data on healthcare resource utilization (RU) in acute stroke will assist in evaluation of cost-efficacy and cost-effectiveness of new treatments. We present results of a substudy of resource utilization within GAIN Americas, a multi-center, randomized, placebo-controlled, phase 3 clinical trial of the glycine antagonist
GV150526
in acute stroke, conducted in the US and Canada. Previously reported clinical results showed no difference in clinical outcome by treatment at 3 months.
Methods:
RU data included pre-stroke and Month 3 residence and employment status, hospital length of stay (LOS) by ward type, discharge destination, and outpatient rehabilitation services. There were no treatment differences on RU endpoints, so data were combined across treatment groups.
Results:
The study population comprised 1604 acute stroke patients (85% ischemic; median age: 72; female: 48%; median NIHSS score: 12). Case fatality was 13% in hospital, 21% by Month 3. Median hospital LOS was 9 days (mean=15), including 3 days (mean = 4.5) in intensive care and 4.5 days (mean=6.8) in step-down. Discharge destinations included rehabilitation facility (49%), home (27%) and nursing home (11%). Pre-stroke, 87% lived in own home, but at 3 months only 62% lived at home. Outpatient rehabilitation services included occupational therapy (31%), physical therapy (39%), speech therapy (20%) and psychotherapy (2%). Pre-stroke, 21% were employed full- or part-time; at Month 3, 6% were employed. Of those employed pre-stroke, 60% reported being unable to work for health reasons at Month 3.
Conclusion:
These data describe the social and economic burden of stroke in a well-defined cohort. Such information should be valuable to care providers at many levels of the healthcare system and to health outcomes researchers. Prospective collection of detailed RU data from a large clinical trial is feasible and worthwhile.
Are Outcomes of Ischemic Strokes Improved When a Neurologist is Attending?
Authors: Gillum Leslie A , Johnston S. Claiborne
Published: July 2021

P239

BACKGROUND:
Whether admission of stroke patients to neurologists is associated with improved outcomes is uncertain. Though prior studies suggested ischemic stroke patients under the care of neurologists had lower rates of in-hospital mortality than those treated by internists, these studies were uncontrolled for the possibility that patients with better prognosis were admitted to neurologists.
METHODS:
The University HealthSystem Consortium administrative database contains patient information from 84 large academic health centers and associates. Discharge abstracts for ischemic strokes admitted through emergency rooms 1997–1999 were obtained. Database variables were validated by comparison with a detailed chart review of 927 patients at 36 institutions. Attending physician specialty was evaluated as a predictor of in-hospital mortality using chi-square statistics and multivariable logistic regression. To determine whether hospital rates of stroke admission to neurologists were predictive of in-hospital mortality, generalized estimating equations (GEE) were used. This multivariable method accounts for clustering of observations at institutions, which broadens confidence intervals (CI). All multivariable analyses were adjusted for age, gender, race, admission status, and treatment volume.
RESULTS:
Of 28,571 ischemic strokes admitted through the emergency department, 58% were admitted to neurologists. Univariate analyses demonstrated a lower risk of in-hospital mortality in cases admitted to neurologist (4.7%) compared to non-neurologists (9.4%; p<0.001). Adjustment for case-mix did not alter the association (odds ratio, 0.48; 95% CI, 0.43–0.53; p<0.001). However, risk of death was not lower at hospitals admitting a larger portion of ischemic stroke cases to neurologists (p=0.54) as would be expected if admission to neurologists led to improved outcomes.
CONCLUSIONS:
In academic medical centers, ischemic stroke patients admitted to neurologists are less likely to die in the hospital compared to those admitted to other services. However, this may be due to selection of patients with better prognosis for admission to neurologists.
Cardiovascular complications in patients with massive middle cerebral artery infarction
Authors: Suarez Jose
Published: July 2021

P242

Background:
Patients with cerebral infarction have a high frequency of underlying cardiac diseases. Acute cardiac events may be observed in patients with massive middle cerebral artery (MCA) infarction due to the severity of neurological insult. We performed this study to determine the frequency of acute cardiac events in this patient population and their impact on outcome and management.
Methods:
Patients with massive MCA infarction were identified at five university affiliated medical centers using ICD-9 codes or local stroke registries. The medical and neuroimaging records were reviewed at each center by a neurointensivist or stroke neurologist. Only patients who underwent neurological deterioration, defined as a decline in Glasgow Coma Scale (GCS) score of ≥2, attributable to cerebral edema were included. All cardiac events and treatment required during hospitalization were recorded. Outcome was determined at 1 month using Glasgow outcome scores and modified Rankin scale.
Results:
A total of 54 patients (mean age 62.5±18.0 years; 26 were men) were studied. Underlying cardiac diseases included myocardial infarction (24%), congestive heart failure (20%), and dysrythmias (24%). A total of 16 patients had new cardiac events during hospitalization. These included atrial fibrillation (n=8), atrial flutter (n=1), ventricular fibrillation (n=1), ventricular tachycardia (n=2), myocardial infarction (n=2), and pulmonary edema (n=5); 3 patients had more than one event. Treatment was required for 10 of 16 (62%) events; 3 (19%) were fatal. Overall mortality was higher in patients who developed acute cardiac events during hospitalization (69%) compared to those who did not (40%, p<0.05). The mean Glasgow outcome score was 4.4±1.1 and 3.7±1.1 in patients with or without cardiac events.
Conclusions:
Our study demonstrates the relatively high frequency of acute cardiac events in patients with massive MCA infarction and their impact on outcome. Patients with massive MCA infarctions should be managed in settings suited for effective monitoring and management of cardiovascular emergencies.
Abstract 109: Soluble Epoxide Hydrolase Gene Deletion is Protective Against Delayed Microvascular Vasospasm in a Mouse Model of Subarachnoid Hemorrhage.
Authors: Siler Dominic A , Heinricher Mary M , Wang Ruikang K , Alkayed Nabil J , Cetas Justin S
Published: July 2021

Accumulating evidence supports a role for microvascular dysfunction in the development of delayed cerebral ischemia following subarachnoid hemorrhage (SAH). The mechanism underlying delayed microvascular vasospasm (dMVS) is unknown. Using 3-dimensional, quantitative optical microangiography (OMAG), we assessed early and delayed changes in perfusion and dimensions of cerebrocortical microvessels in a mouse model of SAH. We tested the hypothesis that the development of dMVS after SAH is linked to changes in expression of soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of a group of vasodilator eicosanoids called epoxyeicosatrienoic acids (EETs). Wild-type (WT, n=6) mice and mice lacking the sEH gene (sEHKO, n=4) were subjected to endovascular perforation to induce SAH, and followed for 72 hours to assess dMVS using OMAG. At 24 hours after SAH, no apparent change in cortical perfusion was observed in either WT or sEHKO mice compared to baseline (p>0.05), although both strains experienced constriction of individual cortical microvessels (-7.4 +/- 1.1% and -6.2 +/- 1.2% change from baseline (p<0.05) in WT and sEHKO mice respectively). At 72 hours after SAH, WT mice developed further microvascular vasoconstriction (-9.6 +/- 1% change from baseline (p<0.05 compared to baseline and 24h) ) and sustained a significant decrease (14.5 +/- 4.5% ) in cortical perfusion compared to baseline perfusion (p<0.05), whereas sEHKO mice did not show further changes in microvascular diameters, and were protected from the delayed drop in cortical perfusion. We conclude that genetic deletion of sEH can protect against dMVS in a mouse model of SAH. Our results suggest that EETs pathway may be involved in the pathogenesis of dMVS following SAH.
Abstract 12: Heritability of Ischemic Stroke and its Subtypes
Authors: Bluher Andrew E , Nalls Michael A , Cole John W , Sharma Pankaj , Meschia James F , Cheng Yu-Ching , Kittner Steven J , O'Connell Jeffrey R , Mitchell Braxton D
Published: July 2021

Background and Purpose:
Family-based methods for estimating heritability cannot discriminate between shared genetic and shared environmental exposures. Recently, methods have been developed for estimating heritability in population samples using genome-wide SNPs. We used the approach developed by Visscher and colleagues to estimate the heritability of ischemic stroke in Caucasian subjects. In addition to evaluating the overall heritability of ischemic stroke, we assessed whether stroke heritability varies by age, gender, and stroke subtype.

Methods:
Using publicly available software (GCTA and PLINK), we estimated ischemic stroke heritability stratified by age and gender using genome-wide association (GWA) data from three Caucasian ischemic stroke studies: Ischemic Stroke Genetics Study (ISGS), Bio-Repository of DNA in Stroke (BRAINS), and Genetics of Early-Onset Stroke (GEOS). Weighted means of site-specific heritability point estimates were combined according to a standard fixed effects model.

Results:

Conclusions:
A SNP-based approach may be useful in discerning differences in ischemic stroke heritability between different cohorts and subtypes. Overall, our analysis estimated ischemic stroke heritability to be 31% (SE = 7%), with a suggestion of higher heritability for younger cases. Small vessel stroke showed the highest heritability (58 ± 19%), with cardioembolic showing the lowest heritability (16 ± 14%). It should be emphasized that heritability estimates are population-specific and that the method used only reflects the heritability captured by common SNP variants measured in GWA studies, and not phenotypic variability explained by rare variants.
Abstract 120: A Multicenter Study of the Prevalence and Outcomes of Intracranial Large Artery Atherosclerosis among Stroke and TIA Patients in China
Authors: Wang Yongjun , Liu Liping , Wong Yilong , Soo Yannie , Pu Yuehua , Wong KS Lawrence ,   the Chinese IntraCranial AtheroSclerosis (CICAS) Study Group
Published: July 2021

BACKGROUND
The prevalence, characteristics and outcomes of stroke patients with intracranial large artery atherosclerosis have not been clearly established by large multicenter prospective study.

METHODS
In this prospective multicenter study, we evaluated 2864 consecutive patients (mean age, 62 years) who experienced an acute cerebral ischemia, including ischemic stroke or transient ischemic attack (TIA), within 7 days of symptom onset in 22 hospitals in China. All patients underwent magnetic resonance angiography (MRA), with measurement of diameter of the main intracranial arteries. Intracranial large artery atherosclerosis was defined as at least 50% diameter reduction on MRA.
RESULTS
The prevalence of intracranial stenosis was 46.6% (1,335 patients, including 261 patients with co-existing extracranial carotid stenosis). Patients with intracranial stenosis had more severe stroke at admission and stayed longer in hospitals than those without intracranial stenosis (median NIHSS 3 vs 5, ; median length of stay 14 vs 16 days respectively, both p<.0001). In hospital treatment included antithrombotics (96%), statins (76%), and antihypertensives (51%). After 12 months, recurrent stroke occurred in 3.34% of patients with no stenosis, 3.82% for 50-69% stenosis, 5.16% for 70-99% stenosis and 7.40% for 100% occlusion. Apart from the degree of arterial stenosis, age, family history of stroke, prior history of cerebral ischemia or heart disease and no prior use of antithrombotic drug were independent risk factors for recurrent stroke. The recurrent rate of each group of patients categorized by degree of stenosis and number of risk factor is shown in the
Figure
. The highest rate of recurrence was observed in patients with 100% occlusion with the presence of 3 additional risk factors.

CONCLUSION
Intracranial large artery stenosis is the commonest vascular lesion in patients with cerebrovascular disease in China. Recurrent stroke rates remains high in patients with severe stenosis and other risk factors despite prevalent use of medical treatment such as antiplatelet, antihypertensive and statin therapies.
Abstract 15: Surface Electrical Stimulation Does Not Improve Hand Function in Subacute Stroke
Authors: Chae John , Page Stephen , Delahanty Michael
Published: July 2021

Background and Objective:
Prior studies have suggested that EMG-triggered and cyclic surface electrical stimulation (ES) mediated hand opening exercises facilitate motor recovery of the hemiparetic upper limb. EMG-triggered ES is believed to more effective than cyclic ES due to the addition of cognitive input to trigger the ES. However, these 2 types of ES have not been compared in a placebo controlled randomized clinical trial. This trial tested the hypothesis that EMG-triggered ES is more effective than cyclic ES in facilitating the motor recovery of the hemiparetic upper limb, and that both are more effective than placebo.

Methods:
Stroke survivors who were within 6-mo of their stroke were randomized to treatment with EMG-triggered ES (EMG), cyclic ES (cyclic) or placebo. The EMG group received the ES by initiating volition finger extension. The resulting EMG from the extensor digitorum communis (EDC) then triggered the ES. The cyclic group received the ES to the EDC in a repetitive timed sequence without volitional activation. For the placebo group, a stimulating electrode was placed on the dorsal forearm away from the motor point of the EDC, and the stimulation intensity was set at sensory threshold with no motor activation. Duty cycle was gradually increased from 5 sec on/20 sec off to 5 sec on/5 sec off as tolerated for all participants. All participants were treated 80 min/day, 5 days a week for 8 weeks. Motor impairment (Fugl-Meyer Motor Assessment-FMA) and activities limitation (Arm Motor Abilities Test-AMAT) outcomes were assessed in a blinded manner at baseline, mid-treatment, end of treatment and at 1, 3 and 6-mo after end of treatment. Data were analyzed using repeated measures ANOVA in an intent-to-treat manner.

Results:
A total of 122 participants enrolled in the study (EMG: 41; Cyclic: 39; and placebo: 42). Baseline characteristics were comparable between groups. All three groups experienced significant improvement in FMA (F=54.5, p<0.001) and AMAT (F=21.7, p<0.001) scores. However, there were no differences between treatment groups (FMA: F=0.25, p=0.78; AMAT: F=0.43, p=0.55).

Conclusions:
EMG-triggered and cyclic ES were no more effective than placebo in facilitating the motor recovery of the hemiparetic upper limb. The improvements in FMA and AMAT scores likely represent natural recovery. However, since sensory stimulation without motor activation may not be placebo, the possibility of therapeutic effect of sensory stimulation cannot be ruled out in the present design.
Abstract 151: Enlarged Perivascular Spaces in Lacunar Stroke Patients. The Secondary Prevention of Small Subcortical Stroked (SPS3) trial.
Authors: Ohba Hideki , Pearce Lesly , Potter Gillian , Benavente Oscar
Published: July 2021

Introduction:
Enlarge perivascular spaces (EPVS) are a common finding on MRI with little known about their aetiology or clinical significance. Associations of EPVS with white matter hyperintensities (WMH) and cognitive impairment have been reported. We assessed the prevalence of EPVS in the basal ganglia (BG) and centrum semiovale (CS) and associations with vascular risk factors, MRI abnormalities, and cognitive impairment in a large cohort of MRI documented lacunar stroke patients.

Methods:
All SPS3 participants enrolled in North America (N=1632) were included in the cohort. MRIs were obtained at the time of index stroke. We graded severity of EPVS on T2 in each of the right and left BG and CS as: <10, 11-20, or 20+. We assessed relationships between maximum (max) BG and CS scores and patient demographics, number of subcortical infarcts, WMH, and cognitive impairment using chi-square tests and ANOVA. Logistic regression was used to identify independent associations between max score in the BG or CS (<10 vs. 11+ points) and these factors.

Results:
Of the 1632 MRIs, 1172 had T2-imaging available. EPVS was symmetrical in right and left sides of BG and of CS so max score in each area were used for analyses. In 42% of BG and 69% of CS, the max number of unilateral EPVS was ≥11. Patients with more EPVS in the BG were older (mean 59 vs. 63 vs. 70 years, p < 0.001), had hypertension (75% vs. 84% vs. 86% p < 0.001), and lower eGFR (mean 83 vs. 80 vs. 74 ml/min/1.73m
2
, p = 0.006). More EPVS in the BG were associated with WMH severity as measured by Age Related White Matter Changes total score (median 3 vs. 6 vs. 8, p < 0.001). Patients with more EPVS in the BG more often had multiple infarcts (11% vs. 19% vs. 29%, p<0.001). All findings were similar in the CS. Age (OR 1.9 per each 10 years, 95% CI 1.7-2.1), history of hypertension (OR 1.7, 95% CI 1.2-2.3) and multiple infarcts (OR 2.4, 95% CI 1.7-3.4) were independently associated with a maximum unilateral EPVS score of 2+ in the BG. Mild cognitive impairment was not associated with EPVS in BG (p=0.3) or CS (p=0.5).

Conclusions:
In this well-defined large cohort of lacunar stroke patients, BG EPVS were associated with age, hypertension and multiple infarcts. These findings suggest that BG EPVS share similar risk factors with lacunar stroke and may be a marker for small vessel disease. Unexpectedly, EPVS were not associated with cognitive impairment.