bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 25: Peroxisome Proliferator Activated Receptor - δ Agonist GW501516 Restores Bioavailability Of Tetrahydrobiopterin And Prevents Cerebral Vascular Dysfunction In Tg2576 Mice Overexpressing Amyloid Precursor Protein
Authors: Santhanam Anantha Vijay R , d'Uscio Livius V , He Tongrong , Das Pritam , Younkin Steven G , Katusic Zvonimir S
Published: July 2021

Objectives-
Oxidative stress and endothelial dysfunction precedes cerebral β-amyloid deposits in human Alzheimer’s disease as well as in transgenic mouse models expressing mutations in amyloid precursor protein (APP). In the present study, we hypothesized that uncoupling of endothelial nitric oxide synthase (eNOS) caused by loss of its essential co-factor, tetrahydrobiopterin (BH
4
), in cerebral arteries and microvessels contributes, in part, to oxidative stress and cerebral vascular dysfunction in a APP transgenic mouse (Tg2576) that express the Swedish double mutation of human APP. In addition, we examined whether treatment with Peroxisome Proliferator Activated Receptor-δ (PPARδ) activator -
GW501516
restores bioavailability of BH
4
and reverses oxidative stress in APP Tg2576 mice.

Methods-
APP Tg2576 mice (4-5 months old) were treated with
GW501516
, a selective PPARδ activator (2 mg/kg/day, po, 14 days). Following treatment, cerebral arteries and microvessels were obtained. Biopterin levels, enzymatic activity of GTP cyclohydrolase I (GTPCH I) and superoxide production were measured by HPLC and protein expression was studied by Western blotting.

Results-
Cerebral arteries and microvessels demonstrated increased expression of eNOS, while the bioavailability of its essential co-factor BH
4
was significantly reduced, suggestive of eNOS uncoupling in APP Tg2576 mice. Furthermore, expressions of catalase and manganese superoxide dismutase (MnSOD) were decreased, while superoxide production was increased (P<0.01, n=6) in cerebral microvessels of APP Tg2576 mice. Treatment with GW501516 restored the BH
4
/BH
2
ratio in cerebral arteries and microvessels of APP Tg2576 mice (P<0.05, n-7-8), while the enzymatic activity of GTPCH-I remained unchanged (P>0.05, n=6). PPARδ activation also prevented the attenuation in expressions of MnSOD and catalase, and inhibited the increased superoxide production (P<0.05, n=6) in cerebral arteries and microvessels of APP Tg2576 mice. Interestingly, PPARδ activation significantly inhibited the over-expression of APP in cerebral microvessels obtained from APP Tg2576 mice (P<0.001, n=4).

Conclusion-
Our results suggest that endothelial dysfunction in APP Tg2576 mice may be caused, in part, by reduced bioavailability of BH
4
and uncoupling of eNOS. Treatment of APP Tg2576 mice with PPARδ agonist GW501516 exerted cerebral vascular protection by multiple mechanisms: (a) by inhibiting eNOS uncoupling via increased expressions of MnSOD and catalase, as well as, (b) by attenuating the increased expression of APP in the cerebral microvessels of APP Tg2576 mice.
Abstract 2505: Neuronal-specific Loss of p53 Function in Forebrain Neurons is Protective Against Ischemic Injury
Authors: Luo Yu , Shen Hui , Hoffer Barry
Published: July 2021

The p53 gene is a key regulator of cell apoptosis. It has been suggested that p53 function is involved in cell death in stroke. p53 immunoreactivity has been detected in brain tissue derived from animal models of stroke. Pharmacological inhibition of p53 function leads to decreased ischemic damage in animal stroke models. In addition, a recent study has reported that the human Tp53 Arg72Pro polymorphism correlates with different functional prognosis in stroke patients. However, both the pharmacological inhibitor and genetic linkage studies do not address the question whether p53 function determines the outcome of stroke by directly regulating cell death in neurons. To address this question, we investigated the role of p53 in ischemia-induced neuronal cell death using forebrain neuron-specific ablation of the gene coding for the p53 gene in mice. By expressing Cre recombinase under the control of the Camkinase II promoter, we achieved a selective deletion of functional p53 protein in forebrain neurons. This strategy represents a significant advance because it permits an evaluation of p53 function in these specific cells, compared to non-selective effects of pharmacological inhibitors on multiple cell types in multiple anatomical regions. Effectiveness of specific p53 deletion in forebrain, but no other brain regions and other organs, was confirmed by PCR in Camkinase II -cre/LoxP p53 ko mice. Loss of the p53 gene in forebrain neurons did not lead to abnormal development of the cortex, as demonstrated by normal structure of the forebrain and neuronal cell numbers (NeuN positive cells) in ko mice. This suggests that p53 is not involved in the apoptosis which eliminates excess neurons during development. However, we found that loss of p53 in forebrain neurons in adult mice is protective against ischemic injury after stroke (MCAo). Locomotor behavior measured in automated activity chambers showed that Camkinase II -cre/LoxP p53 ko mice have less locomotor deficits compared to wt mice after MCAo. Therefore, our data suggest that loss of p53 function specifically in forebrain neurons can protect these cells from ischemic injury occurring after stroke and neuronal-specific inhibition of p53 might be a new treatment strategy for improved prognosis.
Abstract 2513: Intraventricular Administration of Cystatin C Attenuates White Matter Injury In Rat Chronic Ischemia
Authors: Mitaki Shingo , Nagai Atsushi , Sheikh Abdullah Md. , Yamaguchi Shuhei
Published: July 2021

Background and Purpose
Cerebral white matter lesions (WMLs) contribute to elderly cognitive deterioration and are usually caused by chronic ischemic insult. Experimental studies have shown that proteases are highly expressed in activated astrocyte and microglia, which are thought to be crucial in the development of WMLs. Cystatin C (CSTC) functions as a major extracellular cysteine protease inhibitor in mammals. Since the concentration of CSTC is 5 times higher in CSF than in plasma, CSTC is thought to be a major inhibitor of cysteine proteases in the central nervous system. We have shown that polymorphisms in the CSTC gene, which results in a decrease of plasma CSTC level, are significantly associated with prevalence of WMLs. However, direct impact of CSTC on the development of WMLs has not been elucidated yet. Here we studied whether direct administration of CSTC into brain has a protective effect on the pathophysiology of WMLs produced by chronic cerebral hypoperfusion in a rat model of permanent bilateral common carotid artery occlusion.

Methods
Adult Wister rats underwent ligation of bilateral common carotid arteries (LBCCA) and were divided into three groups; the CSTC group in which CSTC was injected continuously into the ventricle 14 consecutive days after LBCCA (n=10), the PBS group in which PBS was injected continuously into the ventricle 14 consecutive days after LBCCA (n=10), and the sham group (n=10). All rats were perfused on 14 days after LBCCA. The severity of WMLs and accumulation of microglia and astrocytes in the corpus callosum (CC) and optic nerve (ON) were evaluated. Furthermore, the activity of cathepsin B, one of the major proteases, was measured in the tissue lysates of CC and ON using the assay kit.

Results
Continuous intraventricular infusion of CSTC significantly reduced the severity of WMLs (CC; p<0.001 vs. PBS, ON; p<0.001 vs. PBS) and inhibited the accumulation and activation of microglia (CC; p=0.03 vs. PBS, ON; p<0.001 vs. PBS) and astrocytes (CC; p=0.003 vs. PBS, ON; p=0.04 vs. PBS) both in CC and ON. There were no alterations in cathepsin B activity in these regions.

Conclusions
The present study indicates that CSTC could suppress chronic ischemia-induced WMLs and the inhibition of proteases other than cathepsin B may be implicated in this beneficial effect.
Abstract 2535: Urban Versus Rural Differences In Stroke Risk: The CDC Wonder Estimates Of Mortality, And REasons For Geographic And Racial Differences In Stroke (REGARDS) Estimates Of Incidence And Survival After Stroke
Authors: Howard George , Mullen Michael , Higginbotham John , Kleindorfer Dawn O , McClure Leslie A , Soliman Elsayed Z , Howard Virginia J
Published: July 2021

Introduction:
Rural-urban disparities in stroke are poorly understood and incompletely characterized. US stroke incidence, mortality, and survival after stroke have not, to our knowledge, been previously reported by urban-rural status.

Methods:
Data for US residents over age 45 from the CDC WONDER system were used to describe the age-adjusted stroke mortality rates between 1999 and 2007 for each county in the US, stratified by rurality. Stroke was defined by ICD-10 codes 60-69. Rurality was defined at the county level using the National Center for Health Statistics 6-level classification scheme. Data from the REGARDS Study, a longitudinal cohort study of 30,239 black and white participants aged 45+ from 48 states, were used to estimate the age and sex adjusted hazard ratio for incident stroke, and to assess survival after stroke, using the same urban/rural classification scheme.

Results:
Between 1999 and 2007, stroke mortality (per 100,000) for those aged 45+ was higher in rural counties for both whites and blacks, with a 20% difference in whites (156.6 for rural versus 131.0 for central metropolitan) and a 32% difference in blacks (237.4 versus 179.6). Among 27,740 REGARDS participants who were stroke-free at baseline with follow-up data, 614 adjudicated stroke events occurred over a mean 4.9 years of follow-up. For whites, incident stroke risk did not change with higher urbanization (HR reported in
table
). There was a consistently lower risk of incident stroke with higher urbanization for blacks although this difference did not reach statistical significance (see
table
). Follow-up was available on 609 of the stroke events. Risk of death after stroke appeared consistently (although generally non-significantly) lower with greater urbanization (see
table
) for both blacks and whites.

Discussion:
Greater urbanization appears to be associated with lower stroke mortality for both whites and blacks, although differences may be larger for blacks. This difference in mortality may be due to both decreased incidence and survival following stroke for blacks; however, higher mortality for rural whites appears to be only due to decreased survival. Reasons for differences in incidence and survival following stroke may be related to control of vascular risk factors and access to care although further study is required.
Abstract 2546: Correlation Between Diffusion-weighted Imaging (DWI) Lesion Volume And Alberta Stroke Program Early CT Score (ASPECTS) In Patients Undergoing Acute Stroke Intervention
Authors: Jadhav Ashutosh P , Jumaa Mouhammad , Zaidi Sayed , Salinas Carlos L , Zhu Guangming , Lansberg Maarten , Straka Matus , Bammer Roland , Albers Greg , Wintermark Max , Wechsler Lawrence , Jovin Tudor
Published: July 2021

Background and Purpose:
Selection of patients for endovascular acute stroke therapy is evolving into imaging based paradigms that quantitatively assess infarct core thresholds beyond which reperfusion is considered futile or detrimental. We sought to determine whether a correlation exists between pre-intervention infarct volume as measured by DWI MRI and ASPECT scores on CT in patients with acute stroke treated with endovascular therapy who underwent both a pre-procedure MRI scan and a non-contrast CT scan at our institution.

Methods:
Retrospective review of a prospectively maintained database of acute ischemic strokes treated with endovascular therapy at the University of Pittsburgh Medical Center during 2004-2011. CT-ASPECT scores were prospectively scored by blinded observers. Infarct volume on DWI was determined by automated software analysis (RAPID, n=25 and MIPAV, n=53). The following additional factors were considered: age, NIHSS, time from last seen well (TLSW) to angiography, site of clot occlusion, time between obtaining CT scan and MRI, and parenchymal hematoma (PH) formation.

Results:
Of 77 patients included in the study, there was a significant negative correlation between CT-ASPECT score and DWI volume size (p<0.0001, by ANOVA).
Table 1
outlines the distribution of ASPECTS scores and corresponding mean DWI volumes along with other variables of interest. The mean time between obtaining the CT and MRI scan was 207 minutes.

Conclusions:
A CT-ASPECT score of 7 or greater corresponds to an average DWI volume of 23 ml or less. Recent studies have shown that a pre treatment DWI volume of <25 ml is predictive of favorable outcomes. Therefore, our findings provide further support of the concept that an ASPECT score cut off of 7 or greater corresponds to core volume thresholds that are predictive of good outcomes following revascularization. Future prospective studies are needed to compare the benefit of CT ASPECTS scores alone versus DWI MRI or other advanced imaging modalities as selection tool for acute stroke endovascular therapy.
Abstract 2572: Dual Imaging with MRI and
18
F-FDG PET Can Highly Predict Lipid and Hematoma in Carotid Plaque
Authors: saito hisayasu , Kuroda Satoshi , Hirata Kenji , Magota Keiichi , Shiga Tohru , Yoshida Daisuke , Terae Satoshi , Nakayama Naoki , Houkin Kiyohiro , Tamaki Nagara
Published: July 2021

Background and Purpose -
Recent studies have disclosed that inflamed and vulnerable plaques in the carotid artery are at high risk for subsequent ischemic stroke, suggesting the importance of non-invasive diagnostic modalities with high sensitivity and specificity to detect them in patients with carotid artery stenosis. Although many investigators have reported that MR imaging is a useful tool to predict the components of carotid plaque, its validity is not established. On the other hand,
18
F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be an alternative modality to directly identify the inflamed plaque in carotid artery stenosis. Therefore, this study was aimed to evaluate the validity of MR imaging and
18
F-FDG PET to predict the components of carotid plaques.

Methods -
Totally 19 patients were included in this study. Prior to carotid endarterectomy (CEA),
18
F-FDG PET, black-blood fat-suppressed T1-weighted (FS-T1) imaging, and 3-dimensional time-of-flight (TOF) imaging were performed in all of them. During CEA, macroscopic observation of carotid plaque was performed under surgical microscope. The specimens were stained with primary antibodies against CD68 and MMP9.

Results -
18
F-FDG PET revealed that 11 of 19 patients had the carotid plaque with significantly high
18
F-FDG uptake (SUVmax >2.0). All of them had lipid-rich soft plaque with strong immunoreactivity against CD68 and MMP9. Its sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to identify lipid-rich soft plaque were all 100%. On the other hands, 6 out of 19 patients had the carotid plaque with high signal intensity on both FS-T1 and TOF imaging. Carotid plaque had a large intraplaque hematoma in these 6 patients. Their sensitivity, specificity, PPV, and NPV to identify intraplaque hematoma were 86%, 100%, 100%, and 92%, respectively.

Conclusions -
These findings strongly suggest that MRI and
18
F-FDG PET are complementary to predict the components of carotid plaque. The former would be useful to detect vulnerable plaque with subintimal hemorrhage, and the latter would be sensitive to identify vulnerable plaque with lipid-rich component. Therefore, combination of these two modalities may be quite valuable to non-invasively predict the carotid plaque at higher risk for subsequent ischemic stroke.
Abstract 2584: Inhibition of Mitochondrial Permeability Transition with NIM811 Improves Functional Recovery after Focal Cerebral Ischemia
Authors: Pettigrew Luther C
Published: July 2021

Introduction:
Mitochondrial dysfunction plays a seminal role in acute ischemic neuronal degeneration, the signature injury in stroke. A selective inhibitor of mitochondrial permeability transition (mPT) may prevent collapse of the mitochondrial membrane potential, thereby inhibiting the intrinsic pathway to neuronal death.

Hypothesis:
A novel mPT inhibitor, NIM811, will reduce infarct volume and improve functional recovery after focal cerebral ischemia.

Methods:
NIM811 was obtained as a gift from Novartis Pharma Ltd. (Basel, Switzerland). Focal cerebral ischemia was induced by unilateral carotid and middle cerebral artery occlusion for 2 hrs in male spontaneously hypertensive rats (SHRs). During post-ischemic reperfusion, animals received NIM811 (50 mg/kg at 1- and 24-hrs of post-ischemic reperfusion) or drug-free vehicle. Infarct volume was measured at 24 hrs or 7 days. Functional performance was assessed with 2 measures, fall latency time (FLT) in a Rotarod device and Removal Delay (RD) in a tape removal task, over 28 days.

Results:
When given after 1 hr of post-ischemic reperfusion, 50 mg/kg NIM811 reduced 24-hr infarct volume (63.6 ± 18.7 [SD] v. 89.3 ± 12.5 mm
3
in controls; n = 8 - 10/group;
p
≤ 0.01; unpaired
t
-test). Serial dosing of NIM811 lowered 7-day infarct volume compared to controls (51.9 ± 7.4 v. 61.9 ± 10.3 mm
3
; n = 13 - 16/group;
p
≤ 0.01; unpaired
t
-test). In the Rotarod task, NIM811-treated animals had prolonged FLT over controls at all examination times up to 28 days (n = 7 per group;
p
≤ 0.0001; ANOVA/Scheffe’s test). NIM811-treated SHRs also had shorter RD for discarding tape applied to the paretic forelimb, compared to controls (n = 7 per group;
p
≤ 0.002; ANOVA/Scheffe’s test).

Conclusions:
Inhibition of mPT with NIM811 significantly reduced infarct volume, when given within a clinically relevant post-ischemic interval. Serial dosing of NIM811 achieved neuroprotective resilience at 7 days. Reductions in infarct volume by NIM811 were complemented by improved functional performance up to 28 days after ischemia. These promising results highlight the potential of NIM811 for neuroprotective treatment of stroke in man.
Abstract 2592: Weakness of ABCD2 Scoring In Transient Ischemic Attack
Authors: Ewins Katie , Zachariah George , Umachandran Velaitham
Published: July 2021

Introduction:
The ABCD2 score is a screening tool used to determine the risk for stroke within the first two days following a TIA. The ABCD2 score is based on 5 parameters: age, blood pressure, clinical features, symptom duration and the presence of diabetes. Each item is scored and added to form a number ranging between 0 and 7. A score of 0-3 predicts a low risk of completed stroke at 2 days (1.0%), 3-4 predicts moderate risk (4.1%) and a score ≥ 5 carries high risk (8.1%). NICE recommends that patients with a score of 4 and above are seen by a stroke physician and investigated within 24 hours of onset. ‘C’, clinical features, is scored out of a maximum of 2 points. Unilateral weakness = 2, speech disturbance = 1, and other presenting symptom = 0. We hypothesised that while the ABCD2 is sensitive for anterior circulation TIA, posterior events will not score in this area, leading to inappropriate risk stratification.

Aim:
The study aim was to establish if the ABCD2 score is equally effective in stratifying stroke risk in all categories of TIA.

Methods:
Data was collected retrospectively from TIA clinic referral documentation for all patients presenting over a 7 month period (N=335). Patients scoring ‘0’ for the ‘C’ arm of the ABCD2 score (N=102) were isolated to establish whether TIA was confirmed as the final diagnosis by a stroke physician, and where patients were treated as TIA, the presenting symptom, and vascular territory involved.

Results:
A ‘C’ score of 0 was present in 103 cases (30%), of which 38 (37%) were diagnosed and managed as TIA . The most common presenting feature in this group was visual disturbance, 20 cases (54%). The majority of these (50%) received a diagnosis of amaurosis fugax, and 25% posterior circulation TIA. The remainder were treated as TIA, but the vascular territory not specified. Facial paraesthesia was described in 5 cases (13%), attributed to carotid artery territory TIA. Ataxia was the presenting feature in 3 patients (8%), attributed to posterior circulation TIA. The remaining 25% had non specific symptoms and the vascular territory not specified on the clinic notes.

Conclusion:
Our study demonstrates that a significant proportion of confirmed TIA cases do not present with classical symptoms of unilateral weakness and speech disturbance. Isolated visual disturbance appears to be a common presenting feature of a TIA, and amaurosis fugax, a known high risk predictor of subsequent completed stroke is not recognised in the ABCD2 score. Transient balance disturbance and ataxic symptoms are highly suggestive of a posterior circulation event and are again not accounted for. When used in isolation, application of the ABCD2 score in these patients may give an inappropriately low stroke risk prediction, and result in delayed referral for investigation and treatment.
Abstract 2600: Refinement of the MR Diffusion-perfusion Mismatch Concept for Thrombolytic Patient Selection: Insights from the Desmoteplase In Acute Stroke Trials
Authors: Warach Steven , Al-Rawi Yasir , Furlan Anthony J , Fiebach Jochen B , Wintermark Max , Lindsten Annika , Smyej Jamal , Bharucha David B , Pedraza Salvador , Rowley Howard A
Published: July 2021

The DIAS-2 study was the only large, randomized intravenous thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore a reevaluation of the penumbra selection strategy is warranted. In post-hoc analyses we assessed the relationships of MRI-measured lesion volumes to clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch to the clinical effect of desmoteplase in DIAS-2 (MRI-selected patients) and in pooled data from MRI-selected 90- and 125-μg/kg dose groups in DIAS, DEDAS, and DIAS-2. In DIAS-2, lesion volumes correlated with NIHSS at both baseline and final time points (P<0·0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, treatment was associated with 47% clinical response rate in desmoteplase (n=143) versus 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size, preferentially decreasing the placebo-response rate. There was a trend of statistically significant differences in effect size in ≤60 mL versus >60 mL baseline mismatch subgroups (P=0.083). The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% CI, 1.16-6.94, P=0.023) for a MMV >60 mL. Increasing the minimum NIHSS for inclusion did not affect treatment effect size. Pooled across all desmoteplase trials, penumbral selection by MRI diffusion-perfusion mismatch favored desmoteplase clinical benefit, especially for larger MMV. Based on these results, a three-fold reduction in future trial sample size requirements would be achieved using a criterion of baseline MMV >60 mL over any visible mismatch. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later-time-window thrombolytic trials.
Abstract 2637: Being Depression Free Helps Return To Work In Younger (<65 Years) Stroke Survivors: Results From The Psychosocial Outcomes In Stroke (POISE) Study
Authors: Hackett Maree , Jan Stephen , Lindley Richard , Li Qiang , Glozier Nick
Published: July 2021

Background:
Each year approximately 12,000 Australians of working age survive a stroke. An ability to participate in paid employment has been identified by younger stroke survivors as having important psychological and economic consequences.

Methods:
The POISE study (Psychosocial Outcome In StrokE
1
) is the largest cohort of young (<65 years of age) stroke survivors. Consecutive participants <65 years of age were recruited within 28 days of stroke from hospitals and stroke units in the greater Sydney metropolitan region, NSW Australia. Stroke was defined according to WHO standard criteria. A range of validated demographic, clinical, mental health, cognitive and disability measures including return to paid employment were obtained over the 12 months following stroke. Multivariate logistic regression was used to determine factors associated with returning to paid employment within 12 months of stroke.

Results:
Among 441 participants, 218 were in paid full-time and 53 in paid part-time work immediately before their stroke, of whom 202 returned to paid part- or full-time work within 12 months of their stroke. Being free of depression at 28-days was the only independent predictor of return to work (OR 2.6, 95% CI 1.1 to 6.5) following adjustment for age, sex, and history of depression before stroke (C statistic 0.73).

Conclusion:
Three quarters of previously employed participants returned to paid employment within 12 months of stroke, with those not depressed most likely to return. Depression is potentially modifiable and early management of depressive symptoms may increase the proportion of those able to return to paid employment.
1
Hackett M, Glozier N, Jan S, Lindley R. Psychosocial Outcomes In StrokE: the POISE observational stroke study protocol. BMC Neurology 2009, 9:24
Abstract 2640: Montreal Cognitive Assessment as a Short and Valuable Cognitive Evaluation in Acute Stroke
Authors: POGGESI ANNA , PASI MARCO , SALVADORI EMILIA , INZITARI DOMENICO , PANTONI Leonardo
Published: July 2021

Background:
Stroke patients are at high risk of developing dementia, but no agreement exists on what instrument should be used in the acute stroke phase to detect patients at higher risk of cognitive decline. Our aims were to investigate: 1) the feasibility and applicability of the Montreal Cognitive Assessment (MoCA) test in the acute phase of stroke; 2) the predictive value of MoCA on the diagnosis of cognitive impairment.

Methods:
Consecutive stroke patients (ischemic or hemorrhagic) admitted to our Stroke Unit were evaluated with MoCA between 5-9 days after stroke. Pre-morbid functional and cognitive status were assessed by a structured interview to caregivers. Neuroimaging information was collected regarding index and pre-existing lesions (number and site of lesions, leukoaraiosis, atrophy). Clinical and neuropsychological follow-up was scheduled after 6 months.

Results:
From December 2009 to December 2010, out of 208 patients with stroke, 138 (66%) were enrolled [mean age 69.1+/-15.0; males 62%; mean NIHSS score 5.7+/-7.7]. Non-enrolment was mostly due to unfitting of the time window inclusion criteria. MoCA was applicable to 114/138 (83%) of enrolled patients and the mean score was 17.9+/-7.2. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR(95% CI)=1.4(1.2-1.7) for each point] and left sided lesions [OR(95% CI)=13.3(1.8-97.9)]. After 6 months, 73 patients (53%) have been re-assessed: 40 had cognitive impairment (6 dementia, 34 MCI), while the remaining 33 did not show any cognitive impairment. Using logistic regression model, considering clinical variables such as age, gender, years of schooling, NIHSS, and pre-morbid cognitive status, MoCA was the only predictor of cognitive decline [OR(95% CI)=1.4(1.2-1.6) for each test point]. When adding neuroimaging features to the model, the independent effect of MoCA was only slightly attenuated [OR(95% CI)=1.4(1.1-1.7)]. The other independent predictor of cognitive decline turned out to be leukoaraiosis severity [OR(95%CI)=0.4(0.2-0.9) for each point of the van Swieten scale].

Conclusions:
Our preliminary results indicate that the MoCA is feasible and applicable in the acute phase of stroke. Moreover, MoCA seems to have a predictive effect on the diagnosis of cognitive decline at 6-month follow-up, making it a good candidate for cognitive screening in stroke setting.
Abstract 2663: The Impact of Preoperative Magnetic Resonance Plaque Imaging on Treatment Results of Carotid Artery Stenosis
Authors: Yoshimura Shinichi , Yamada Kiyofumi , Egashira Yusuke , Enomoto Yukiko , Kawasaki Masanori , Iwama Toru
Published: July 2021

Background and Purpose:
Selection of carotid artery stenting (CAS) or carotid endarterectomy (CEA) remains controversial. The aim of this study was to elucidate whether treatment selection based on preoperative magnetic resonance (MR) plaque imaging can improve treatment results of carotid artery stenosis.

Methods:
A total of 205 consecutive patients with high-grade carotid artery stenosis scheduled for elective revascularization with CAS or CEA were analyzed. From 1 2004 to June 2007 (period I: 3.5 years), 95 patients were treated regardless of preoperative plaque imaging. From July 2007 to March 2011 (period II: 3.5 years), 110 patients received time-of-flight MR angiography (TOF-MRA), and CEA was basically selected when a high intensity signal (HIS) was observed on TOF-MRA (
Fig.1
a), because this finding indicates intraplaque hemorrahge (
Fig.1
b,c). Periprocedural clinical events and clinical outcome at 30 days later were analyzed.

Results:
In period I, 5 patients (5.3%) were treated using CEA and the other 90 patients (94.7%) were treated with CAS (Table). In period II, 35 patients (31.8%) were treated with CEA and the other 75 patients (68.2%) were treated using CAS. Major adverse events including any stroke, myocardial infarction and death, were significantly more frequent in period I than in period II (9.5% vs 1.8%; p=0.034). Ischemic stroke was significantly reduced from period I to period II (7.4% vs 0.9%; p=0.043). In particular, a striking difference in incidence of stroke existed between the periods in HIS-positive plaques (21.7%, 2.0%, respectively; p=0.018, Fig.2).

Conclusions:
Preoperative MR plaque imaging appears useful for improving treatment results of carotid artery stenosis when it was used for treatment selection.
Abstract 2682: Tracking Inter-hospital Transfer Process to Reduce Time from Initial Presentation to Neurovascular Intervention in Acute Stroke
Authors: Seagraves Karen B , Zimmermann Susan , Connelly Kerrin M
Published: July 2021

Evaluating Inter-hospital Transfer Process to Reduce Time from Initial Presentation to Neurovascular Intervention in Acute Stroke

Background
As neurovascular intervention becomes a viable option for large vessel ischemic stroke, establishing a process for rapid transfer from Primary Stroke Center (PSC) to Comprehensive Stroke Center (CSC) is imperative to providing timely intervention.

Purpose
To establish a process for defining key data elements and quality measures for improving inter-hospital transfer time for acute stroke patients in need of neurovascular intervention.

Methods
Nursing coordinators in a rapidly growing multi-hospital acute stroke referral network in North and Central Georgia provide feedback on the patient transfer process and key indicators that can accelerate treatment times. Data from inter-hospital transfers are reviewed. Concurrent and retrospective chart reviews from the PSC and the CSC are utilized for data abstraction. Team members include vascular neurologists, Emergency Department (ED) physicians, referring neurologists, ED and Intensive Care Unit nursing staff, Stroke Coordinators, and Emergency Medical Services.

Results
Time sensitive data elements include arrival at PSC (PSC-Arr), departure from PSC (PSC-Dep), arrival at CSC (CSC-Arr), and groin puncture for angiogram. Key process measures include calculated times for the following: a) PSC-Arr to MD discussion regarding transfer, b) PSC-Arr to PSC-Dep, c) PSC-Arr to CSC-Arr), d) CSC-Arr to intervention, e) PSC-Arr to intervention. Process improvement focuses on improving PSC ability to rapidly do the following: identify patients, initiate physician communication between PSC and CSC, initiate and complete transfer process, notify EMS transport, and providing a process for rapid registration at the CSC. Other key improvements that enhance the transfer process include real time image sharing between PSC and CSC, EMS education, and clinical feedback from CSC to PSC.

Conclusion
Evaluation of data elements in the transfer process identifies opportunities to reduce transfer time between Primary Stroke Centers and Comprehensive Stroke Centers. In a multihospital referral network, process improvement in acute stroke should focus on the timely and efficient transfer of patients from a PSC to a CSC. By analyzing the key components of the transfer process, we identified opportunities to decrease time to neurovascular intervention in acute ischemic stroke. With the exponential growth of the vascular neurology field and interventional options, tracking these elements can identify areas to expedite treatment.
Abstract 2716: Patients with Leukoaraiosis Have Poor Recruitment of Collaterals After Middle Cerebral Artery Occlusion
Authors: Arsava Ethem Murat , Topcuoglu Osman Melih , Akpinar Erhan , Oguz Kader K , Topcuoglu Mehmet Akif
Published: July 2021

Background:
Previous studies have shown reduced penumbral salvage in ischemic stroke patients with higher leukoaraisosis (LA) volume. Although unproven, decreased cerebral vessel density and diminished capacity of cerebral vessels to dilate in response to reduced blood flow in severe LA, are considered among the factors that might explain the association between LA burden and infarct growth in ischemic stroke. Both of these factors, in theory, might negatively affect the extent of collateral blood flow, an important predictor of tissue and clinical outcome in patients with acute ischemic stroke. In this study, we therefore analyzed whether extent of LA adversely affected the degree of collateral circulation in a cohort of patients presenting with middle cerebral artery occlusion.

Methods:
We retrospectively analyzed a consecutive series of patients admitted with a diagnosis of middle cerebral artery occlusion. Computed tomography angiography source images (CTA-SI) were used to assess the degree of collateral circulation, based on a previously validated scoring system which grades collateral vessels in the sylvian fissure and leptomeningeal convexity separately on a scale from 1 to 5, with 1 being the worst and 5 the best. The extent of LA was determined on FLAIR images by using the Fazekas scale. Multivariate analysis was used to explore the relationship between extent of LA and degree of collateral circulation, adjusted for other covariates like age, gender, vascular risk factors and time from symptom onset to CTA imaging.

Results:
A total of 51 patients (31 female, 20 male) were included into the study. LA severity was significantly and negatively correlated with the degree of collateral supply (r=-0.31, p=0.03). LA severity (OR 5.9, 95%CI 1.5-24.0) and history of prior stroke (OR 7.8, 95%CI 1.0-59.3) were the only significant variables associated with insufficient collaterals (defined as a combined sylvian and lepotmeningeal collateral score of 5 or less) in the multivariate logistic regression analysis.

Conclusion:
Patients with higher LA burden have a poor recruitment of collateral vessels after middle cerebral artery occlusion. This association might contribute to reduced penumbral salvage and increased susceptibility to infarct growth observed in patients with severe LA.
Abstract 2722: Anti-hypertensive Treatment Prolongs tPA Door-to-treatment Time: Secondary Analysis Of The Increasing Stroke Treatment Through Interventional Behavior Change Tactics (INSTINCT) Trial.
Authors: Skolarus Lesli E , Scott Phillip A , Burke James F , Adelman Eric E , Frederiksen Shirley M , Kade Allison M , Kalbfleisch Jack D , Meurer William J
Published: July 2021

Background/Purpose:
Increased time to tPA treatment is associated with worse outcomes. Thus, identifying modifiable treatment delays may improve stroke outcomes. We hypothesized that pre-thrombolytic anti-hypertensive treatment (AHT) may prolong door to treatment time (DTT).

Methods:
Secondary data analysis of consecutive tPA-treated patients at 24 randomly selected Michigan community hospitals in the INSTINCT trial. DTT among stroke patients who received pre-thrombolytic AHT were compared to those that did not receive pre-thrombolytic AHT. We then calculated a propensity score for the probability of receiving pre-thrombolytic AHT using a logistic regression model with covariates including demographics, stroke risk factors, antiplatelet or beta blocker as home medication, stroke severity (NIHSS), onset to door time, admission glucose, pretreatment systolic and diastolic blood pressure, EMS usage and location at time of stroke. A paired t-test was then performed to compare the DTT between the propensity matched groups. A separate generalized estimating equations (GEE) approach was also used to estimate the differences between patients receiving pre-thrombolytic AHT and those that did not while accounting for within hospital clustering.

Results:
A total of 557 patients were included in INSTINCT, however onset, arrival or treatment times were not able to be determined in 23, leaving 534 patients for this analysis. The unmatched cohort consisted of 95 stroke patients who received pre-thrombolytic AHT and 439 stroke patients who did not receive AHT from 2007-2010 (
table
). In the unmatched cohort, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 9 minutes; 95% confidence interval (CI) 2-16 minutes) than patients who did not receive pre-thrombolytic AHT. After propensity matching (table), patients who received pre-thrombolytic AHT had a longer DTT (mean increase 10.4 minutes, 95% CI 1.9 - 18.8) than patients who did not receive pre-thrombolytic AHT. This effect persisted and its magnitude was not altered by accounting for clustering within hospitals.

Conclusion:
Pre-thrombolytic AHT is associated with modest delays in DTT. This represents a feasible target for physician educational interventions and quality improvement initiatives. Further research evaluating optimum hypertension management pre-thrombolytic treatment is warranted.
Abstract 2731: CFD Reveals Hemodynamic Differences Between Unruptured And Ruptured Intracranial Aneurysms During Observation
Authors: Takao Hiroyuki , Murayama Yuichi , Ishibashi Toshihiro , Yuki Ichiro , Otsuka Shinobu , Suzuki Takashi , Masuda Shunsuke , Mohamed Ashraf , Sen Itsu , Yamamoto Makoto , Abe Toshiaki
Published: July 2021

Background and Purpose:
Although various studies have been performed, the mechanism leading to the rupture of cerebral aneurysms has not yet been elucidated. Accurate assessment of cerebral aneurysm rupture risk is important because current treatments carry a small but significant risk that can exceed the small natural risk of rupture. Various hemodynamic parameters have been proposed for estimating the risk of rupture of cerebral aneurysms, with limited success. We evaluated several hemodynamic parameters to predict rupture in a dataset of initially unruptured aneurysms in which some aneurysms ruptured during follow-up observation.

Methods:
Geometry of the aneurysm and blood vessels was extracted from CTA images and analyzed using a mathematical formula for fluid flow under pulsatile blood flow conditions. Fifty side-wall internal carotid posterior communicating artery (ICA-pcom) aneurysms and fifty middle cerebral artery (MCA) bifurcation aneurysms of medium size were investigated for Energy loss (EL), Pressure Loss Coefficient (PLC), wall-shear-stress (WSS) and oscillatory shear index (OSI). During a follow-up observation period, 6 ICA-pcom and 7 MCA aneurysms ruptured (44 and 43 remained unruptured, respectively, with the same location and a similar size as the ruptured cases).

Results:
A significant difference in the minimum WSS between aneurysms that ruptured and those that remained unruptured was noted only in ICA aneurysms (P<0.001). EL showed higher tendency in ruptured aneurysms but statistically not significant. For PLC, a significant difference was noted in both ICA (P<0.001) and MCA (P<0.001) aneurysms. All other parameters did not show significant differences between the two groups.

Conclusion:
A significant difference was noted in WSSMIN only in ICA aneurysms. For PLC, a significant difference was noted in both ICA and MCA aneurysms, suggesting that PLC may be one, out of possibly other useful parameters to predict cerebral aneurysm rupture.
Abstract 2753: Initial and 24h After Admisson DWI Can Predict Recurrence of Ischemic Event of TIA Patients
Authors: Iguchi Yasuyuki , Kimura Kazumi , Aoki Jyunya , Kobayashi Kazuto , Sakai Kenichiro , Shibazaki Kensaku , Uemura Jyunichi , Yamashita Shinji , Matsumoto Noriko , Watanabe Masao , Inoue Takeshi , Shimoyama Tkashi , Fujii Syuichi , Shiromoto Takashi
Published: July 2021

Background and Purpose
Our aim is to investigate the diagnostic utility of diffusion weighted magnetic resonance imaging (DWI) for transient ischemic attack (TIA), not only admission but also 24 h after first study.

Methods
We prospectively enrolled TIA patients who were admitted within 24 h of onset. We examined trans-thoracic echocardiography, 24 h Holter electrocardiography, and carotid duplex ultrasonography in order to give the best medication. All of patients received DWI immediately after admission. At first, when we observed hyper-intense lesion considered as ischemia, additional DWI examination was not conducted. When there was no hyper-intense lesion on initial DWI study, we conducted follow-up DWI 24 h after initial examination. We defined a recurrence of ischemic event as an occurrence of symptomatic ischemic stroke or TIA at 3 months after onset. Regarding initial DWI study, we compared proportional frequency of recurrence between patients with ischemic lesion (i-positive group) and without any lesion (i-negative group), and also compared recurrence rate between patients with ischemic lesion on initial and/or follow-up studies (if-positive group) and without any lesion on both studies (if-negative group).

Results
We registered 100 TIA patients (men; 63, median age; 74 years, ABCD2 score <3; 32). On initial DWI study, 34 patients had ischemic lesion (i-positive group) and 66 had no lesion (i-negative group). Among 66 patients of i-negative group, 12 (19%) had hyper-intense lesion in follow-up study. Finally, there were 46 patients in if-positive group and 54 in if- negative. Recurrence ischemic event occurred in 19 (19%) of 100 patients. There was no significant difference of recurrence rate between i-positive and i-negative groups (27% vs. 16%, p=0.172). However, recurrence rate was significantly higher in if-positive group than these of if-negative group (29% vs. 12%, p=0.024)

Conclusions
New ischemic lesions on follow up DWI appeared in approximately 20% of TIA patients who did not have ischemic lesion on initial DWI. Only initial DWI but initial and follow-up DWI was important role of predicting the recurrence of ischemic events in TIA patients.
Abstract 2771: Incidence of High Risk Atherosclerotic Lesions in Intracranial and Extracranial Carotid Arteries in Patients with Acute Ischemic Stroke: A 3.0T Magnetic Resonance Imaging Study
Authors: Zhao Xihai , Zhao Huilin , Li Feiyu , Sun Jie , Cao Ye , Xu Jianrong , Yuan Chun
Published: July 2021

Introduction
Rupture of vulnerable atherosclerotic plaques in the intracranial and extracranial carotid arteries could trigger ischemic stroke. However, the incidence of high risk atherosclerotic lesions in these vascular beds is not well known. This study sought to investigate the incidence of high risk atherosclerotic lesions in intracranial and extracranial carotid arteries in stroke patients using magnetic resonance (MR) imaging.

Methods
Seventy-five patients (mean age 62.7 years, 56 males) with acute ischemic stroke underwent MR imaging for index carotid arteries, assigned as the same side as the brain lesions, with a Philips 3.0T MR scanner. Intracranial carotid MR angiography was performed using 3D TOF sequence with FOV of 23 × 23 cm
2
, matrix of 256 × 256, and a slice thickness of 1mm. The multi-contrast vessel wall images (3D TOF, T1W, T2W, and MP-RAGE) were acquired for extracranial carotid arteries with FOV of 14 × 14 cm
2
, matrix of 256 × 256, and slice thickness of 2 mm. The intracranial artery includes middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA). The extracranial carotid artery was divided into internal carotid artery (ICA), bulb, and common carotid artery (CCA). Luminal stenosis for each intracranial and extracranial carotid segment was measured and graded (normal or mild = 0-29%, moderate =30-69%, severe=70-99%). Normalized wall index (NWI = wall area/total vessel area × 100%), and presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) and/or fibrous cap rupture in each extracranial carotid segment were determined.

Results
MCAs developed more severe stenotic lesions (24.6%), followed by extracranial carotids (16.5%), PCAs (5.4%), and ACAs (4.1%) in stroke patients (
Figure 1
A). For extracranial carotid arteries, ICAs showed the largest plaque burden as measured by NWI (44.3%±13.1%), followed by bulbs (39.4%±13%), and CCAs (37%±6.8%). Compared to CCAs, ICAs and bulb regions had more LRNCs (38.4% and 49.3% for ICA and bulb respectively) and IPH and/or rupture (11% and 9.6% for ICA and bulb respectively) (
Figure 1
B). Conclusions In patients with acute ischemic stroke, high risk atherosclerotic plaques can be found in both intracranial and extracranial carotid arteries, particularly in the MCA, ICA and bulb regions. Compared to extracranial carotid arteries, intracranial arteries develop more high risk lesions. The findings of this study suggest the necessity for early screening to detect high risk atherosclerotic lesions in these carotid vascular beds prior to cerebravascular events.
Abstract 2820: Benchmarking Demonstrates Quality of Telestroke Network TEMPiS
Authors: Hubert Gordian , Müller-Barna Peter , Boy Sandra , Haberl Roman
Published: July 2021

Objective:
The integrative telestroke network TEMPiS aims to provide high standard stroke care in non-urban areas by implementing a teleconsultation service and setting up telestroke units in the network hospitals (TSU). Since treatment in a neurological stroke unit (SU) rather than a TSU is the gold standard of stroke care in Germany, the objective of this study was to compare process and outcome parameters in TSU and accredited SU in Bavaria.

Methods:
The data are collected from the Bavarian Stroke Registry (BAQ). Quality indicators have been developed by the committee of the German Stroke Registry and reflect the quality of acute in-hospital treatment. The 2010 data of the 15 TSU are compared to those of the 19 Bavarian SU.

Findings:
All registered patients in 2010 (6634 in the TSU and 13.728 in the SU) were included in the study. Patients in TSU were slightly older than patients in the SU (76 vs. 74y.) and had the same stroke severity (NIH-Stroke Scale: 4). The results of the quality indicators are shown in
table 1
.

Five quality indicators (information, dysphagia screening, speech- and language therapy, early cerebral imaging, early platelet inhibitors) were significantly better in TSU, two (carotid artery diagnostic, rehabilitation) in the SU. All other quality indicators (9) showed no significant difference.

Conclusion:
A comparison of the hospitals of the integrative telestroke network TEMPiS and the accredited stroke units in Bavaria indicates equally high quality of the processes and outcome parameters. The integrative telestroke network is a concept that implements high standard stroke care in non-urban areas.