bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P65: Early Statin Intervention Can Reduce the Early Neurological Deterioration and Recurrence in Acute Lacunar Stroke
Authors: Fukuma Kazuki
Published: July 2021

Background and Purpose:
Some patients with lacunar infarction show clinical neurological deterioration within few days after the onset. However factors associated with progressive lacunar stroke are unclear. The aim of this study was to identify the factors related to early neurological deterioration and recurrence in acute lacunar stroke.

Methods:
We studied 277 consecutive patients (173 men; mean age, 72 years) with a lacunar infarction admitted within 72 hours after the onset between Jan 2011 and Jul 2013. Progressive infarction (PI) was defined as an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score or recurrence of symptomatic ischemic stroke within 30 days after the onset. Associations between PI and patient characteristics, neuroimaging and acute treatments were evaluated.

Results:
Twenty-four of the 277 patients (8.7%) had PI, 21 patients (7.6%) presented with neurological deterioration and remaining 3 (1.1%) with symptomatic recurrence. In univariate analysis, an initial infarct extent of ≥15 mm was more frequent (P < 0.01), and age (P = 0.04), CRP (P = 0.05) and LDL-C (P = 0.04) were higher in patients with PI than those without. Early statin intervention (newly initiated statin, dose-escalation of pre-treated statin, or switching to strong statin) was significantly more frequent in patient without PI (41.9 vs 20.8%, P=0.04). Early dual antiplatelet or anticoagulant therapy was not associated with PI. In multivariate analysis, age [OR: 1.67 per 10 year; 95% CI: 1.07-2.70, p = 0.02], an initial infarct extent of ≥15 mm [OR: 5.26; 95% CI: 2.01-14.37, p < 0.01], LDL-C [OR: 1.25 per 10mg/dL; 95% CI: 1.09-1.46, p < 0.01], and statin intervention [OR: 0.22; 95% CI: 0.06-0.68, p < 0.01] were related to PI.

Conclusion:
Older Age, higher LDL-C and larger initial infarct extent were related to early neurological deterioration and recurrence in acute lacunar stroke. Further, early statin intervention can reduce the progressive lacunar stroke. Prospective randomized controlled trials are needed to determine whether the early statin intervention can prevent progression in acute lacunar stroke.
Abstract T P72: Baseline Variables Have Little Influence on Early Change in Neurological Status (ΔNIHSS) After Acute Ischemic Stroke: Basis For a Genetic Study
Authors: Heitsch Laura , Cruchaga Carlos , Khoury Naim , Weisenhan Rebecca , Andria Ford L , Guilliams Kristin , Carrera Caty , Fernandez-Cadenas Israel , Montaner Joan , Lee Jin-Moo
Published: July 2021

Introduction:
Neurological deficits can be highly unstable within the first 24 hours after acute ischemic stroke (AIS), with some patients showing dramatic improvement while others rapidly deteriorate. We are interested in genetic influences on early neurological recovery/deterioration. Here, we characterize NIHSS changes within the first 24 hours after stoke onset (ΔNIHSS) in a large cohort to determine baseline clinical variables that influence this outcome measure.

Methods:
AIS patients presenting to two sites (Barnes-Jewish Hospital, St Louis and Vall D’Hebron Hospital Barcelona) between 2008-2013 were prospectively enrolled. Baseline NIHSS was collected within 6 hours and again at 24 hours after symptom onset. ΔNIHSS was calculated as the difference in these stroke scale scores. Demographics, baseline comorbidities and medications, as well as acute treatment variables were recorded for each subject. Stepwise multivariable regression (SAS) was used to determine variables that significantly influence ΔNIHSS.

Results:
There were 954 patients enrolled (St Louis = 433, Barcelona = 521). Table 1 demonstrates the frequencies and means (SD) of the baseline variables. ΔNIHSS follows a normal distribution (figure). All baseline variables listed in table 1 were analyzed for influence on ΔNIHSS. Only baseline NIHSS (R2 = 0.0597, p<0.0001), baseline glucose (R2 = 0.0176, p=<0.0001,) and age (R2 = 0.0106, p=0.0011) independently influenced ΔNIHSS, accounting for only 8.79% of the variance.

Conclusion:
Baseline variables (NIHSS, glucose and age) modestly influence early neurological recovery/deterioration. However, 91% of ΔNIHSS variability remains unexplained, suggesting that other factors such as genetics, could play an important role in early outcomes following AIS. A GWAS of ΔNIHSS is currently underway.
Abstract T P75: Vertex Analysis Demonstrates Significant Changes in Contralesional Thalamus 3 Months After Ischemic Stroke
Authors: Yassi Nawaf , Campbell Bruce C , Bivard Andrew , Malpas Charles , Parsons Mark W , Desmond Patricia M , Davis Stephen M
Published: July 2021

Objective:
Changes in remote brain structures after stroke may correlate with functional outcomes. We sought to investigate contralesional subcortical structural change after stroke.

Methods:
15 patients with carotid territory ischemic stroke underwent 3T MRI within 7 days of onset and at 3 months. Imaging involved a 1mm T1 axial MPRAGE. In 6 patients with left hemispheric stroke, scans were inverted across the midline to allow group comparison. FIRST (Part of FSL) was used to segment subcortical structures including thalamus, pallidum, caudate, putamen, hippocampus, accumbens and brainstem. Analysis was restricted to the non-stroke hemisphere due to the confounding effect of stroke lesions and edema in the lesional hemisphere. Change in volume was assessed as percentage change between the time points. A vertex analysis was performed in order to also identify areas of significant surface atrophy. Briefly, a surface mesh is created for each structure at each time point. Vertex wise statistical analysis then allows for the identifications of areas of significant surface atrophy between baseline and follow-up within the group.

Results:
Mean age was 71y. Median baseline NIHSS was 9. Vertex analysis demonstrated atrophy over the superior and inferior surface of the contralesional thalamus between baseline and 3 months (figure, p<0.05 multiple comparisons corrected). The median overall change in contralesional thalamic volume was -0.96% (IQR -0.11 - -1.98%), but this difference was not statistically significant (p=0.1). No statistically significant changes in other subcortical structures were found.

Contralesional thalamus (blue) superior (A) and inferior (B) views with areas of significant atrophy (red)

Conclusions:
We have described post stroke surface changes in the contralesional thalamus. This may be a result of deafferentation occurring during the recovery phase. An analysis in a larger number of patients may allow correlation with clinical endpoints.
Abstract T P76: Cerebral Lactate and Monocarboxylate Transporters Are Reduced by Ethanol and Normobaric Oxygen Therapy after Severe Transient and Permanent Ischemic Stroke
Authors: Brogan David , Sy Christopher , Peng Changya , Rastogi Rhadika , Singh Sunpreet , Ding Yuchuan
Published: July 2021

Objectives:
Recent studies conducted by this lab have shown the neuroprotective benefits of ethanol (EtOH) and normobaric oxygenation (NBO), which is partially due to amelioration of aberrant glucose metabolism and a reduction in reactive oxygen species (ROS). In the current study, we sought to identify whether the neuroprotective benefits of EtOH, with or without NBO, attenuates lactic acidosis by reducing expression of monocarboxylate transporters (MCTs), resulting in ROS reduction after transient and permanent ischemic stroke.

Methods:
Sprague-Dawley rats (n=64) were subjected to right middle cerebral artery occlusion (MCAO) for 2 h or 4 h (transient ischemia), or 28h (permanent ischemia) followed by 3h, 24h, or no reperfusion. Rats in each group were randomly assigned to receive either an injection of saline (sham treatment), an intraperitoneal injection of EtOH (1.5g/kg), two doses of EtOH (1.5g/kg at onset of reperfusion followed by 1.0 g/kg 2 h after 1
st
dose), or EtOH + 95% NBO for 6 h (permanent ischemia). Lactate and ROS levels were detected at 3h and 24h following reperfusion. Gene and protein expressions of MCT-1, MCT-2, and MCT-4 were assessed by RT-PCR and Western Blotting, respectively.

Results:
A dose dependent neuroprotection of EtOH administration was found in transient ischemia. Single dose in 2 h MCAO and double dose in 4 h MCAO significantly attenuated lactate levels and ROS generation, MCT-1, MCT-2, and MCT-4 mRNA and protein expression after severe transient ischemia. However, EtOH treatment alone, even with 2 doses, was insufficient for permanent stroke, while combination therapy (EtOH + 95% NBO) resulted in a more potent decrease of all levels and expressions.

Conclusions:
Our study suggests that acute EtOH administration can attenuate lactic acidosis-induced oxidative stress following a transient ischemic stroke. This EtOH-induced attenuation of brain injury was enhanced by NBO in permanent ischemic stroke. Both EtOH and NBO are widely available, inexpensive, easy to administer, and have few side effects. Ultimately, this combination therapy could be an effective approach to future stroke treatments.
Abstract T P80: Inhibition of Ezh2 Leads to Decreased M1 and Enhanced M2 Microglia Phenotypes
Authors: Koellhoffer Edward , Grenier Jeremy , Ritzel Rodney , McCullough Louise
Published: July 2021

Background:
Ischemic stroke results in the activation of microglia, which may polarize toward a pro-inflammatory (M1) phenotype or an anti-inflammatory, neuroprotective (M2) phenotype. Thus, simultaneously suppressing the M1 response and promoting the M2 response could be beneficial in the treatment of stroke. Recently, the epigenetic modulator Jmjd3 has been shown to be essential for M2 polarization. However, Jmjd3 is antagonized by Ezh2 which is associated with M1 polarization. Thus, we hypothesized that inhibition of Ezh2 tilts the balance between Jmjd3 and Ezh2, thereby enhancing polarization toward an M2 phenotype and improved outcome in ischemic stroke.

Methods:
Mixed glial cultures were isolated from P0.5-P2 C57BL/6J mice and cultured for 14 days before microglial isolation. Microglia were rested for 24 hours before treatment every other day with 6uM GSK343 (Cayman Chemical) or DMSO vehicle control. After 7 days, microglia were stimulated with LPS or IL-4 and RNA was isolated at 4hr and 24hr post-stimulation for qRT-PCR analysis.

Results:
LPS-induced IL6 and IL1B expression was significantly abrogated by 71% and 53%, respectively (p<0.05), at 24hr when Ezh2 was inhibited. Additionally, Ezh2 inhibition both increased baseline expression of M2-associated genes ARG1, CD206, and IRF4 by 196%, 257%, and 395%, respectively (p<0.05), and rescued their expression in the presence of LPS at 24hr (p<0.05) in which they were otherwise significantly down-regulated.

Conclusion:
Pharmacological inhibition of Ezh2 limits microglial M1 polarization and enhances M2 polarization.
Abstract T P9: Procedural And Clinical Outcomes Of Intra-arterial Thrombectomy In Acute Ischemic Stroke Patients Over 75 Years Of Age
Authors: Jeong Hye Seon , Kwon Hyon-Jo , Song Hee-Jung , Koh Hyeon-Song , Kim Jei
Published: July 2021

Background & objective:
Age is an important factor related with favorable outcome after intraarterial thombectomy (IAT). However, procedural and clinical limitations of aging in IAT have not been well studied. We evaluated procedural and clinical outcomes of IAT observed in patients over 75 years as compared to the data of younger than 75 years.

Methods:
We retrospectively reviewed procedural and clinical data of 50 patients older 75 years and other 127 patients younger than 75 years old, who received IAT using recently introduced retrievable stent and/or suction device. We compared procedural variables including groin puncture to selection of occluded vessel time, puncture to recanalization time, and recanalization rate. We also compared clinical variables including hemorrhagic complication, mortality, and rate of favorable outcome defined as 0 to 2 of modified Rankin scale at discharge and 3 months.

Results:
Patients over 75 years old took longer time intervals from puncture to selection of occlusion sitethan the younger patients (>75, 12.1±10.3, <75 group, 5.9±4.8 min;
p
=0.000). The older patients showed lower number of patients recanalized within 6 hours than younger patients (23, 46% vs. 84 patients, 66%;
p
=0.011). Older patient group had lower rate ofrecanalization (60% vs. 79%;
p
=0.010) and favorable outcome at discharge (20% vs. 43.3%;
p
=0.003) and 3months (24% vs. 55.1%;
p
=0.000). Even though symptomatic hemorrhage was similar between the 2 groups, mortality was higher in older patient group (14% vs. 5%;
p
=0.062). In multiple logistic regression analysis, younger age less than 75 years (OR 3.1, 95% CI 1.18-8.04) and recanalization within 6 hours (OR 3.0, 95% CI 1.23-7.32) were independently related with a favorable 3-month outcome.

Conclusions:
The present study showed that clinical and procedural outcomes of IAT performed for old age over 75 years were worse than those of younger patients. However, even in the older patients, successful recanalization and favorable outcome was also anticipated.
Abstract W MP21: Diagnostic Accuracy of CT-Angiography for Internal Carotid Artery Stenosis - Comparison with a Revisited Multiparametric Ultrasound Approach
Authors: Barlinn Kristian , Floegel Thomas , Kitzler Hagen , Kepplinger Jessica , Siepmann Timo , Zerna Charlotte , Pallesen Lars-Peder , Bodechtel Ulf , Puetz Volker
Published: July 2021

Background:
A novel multiparametric approach from the Neurosonology Research Group (NSRG) of the World Federation of Neurology has been proposed for duplex ultrasound (DUS) grading of internal carotid artery (ICA) stenosis. We aimed to determine the accuracy of CT-angiography (CTA) compared with the widely used NSRG ultrasound criteria for diagnosis of extracranial ICA stenosis.

Methods:
We studied consecutive acute ischemic stroke patients who were admitted to our tertiary stroke center from 01/2012 to 12/2012 and underwent CTA and DUS. On DUS, ICA stenosis and complete occlusion were graded according to the published NSRG multiparametric criteria. Axial CTA source images were independently assessed and NASCET-type measurements were manually performed for each extracranial ICA. In addition, each ICA was reviewed for complete occlusion. We calculated accuracy parameters of CTA for identification of 50-99% and 70-99% ICA stenosis, as well as complete ICA occlusion using DUS as reference.

Results:
A total of 339 patients (age 72±12yrs; 58% men; median NIHSS 4, interquartile range 8) provided 651 DUS and CTA measurement pairs for comparison. On DUS, 50-99% stenosis was found in 28, 70-99% stenosis in 16, and complete occlusion in 29 internal carotid arteries. The sensitivity of CTA against DUS was low for both detection of 50-99% and 70-99% ICA stenosis (64% and 31%, respectively). Further accuracy parameters of CTA were as follows: specificity 97%, PPV 49%, NPV 98% and overall accuracy 96% (18 true positive, 604 true negative, 19 false positive and 10 false negatives), and 99%, 56%, 98% and 98% (5 true positive, 631 true negative, 4 false positive and 11 false negatives), respectively. The highest accuracy of CTA was obtained for discriminating between complete ICA occlusion and non-occlusion: 100%, 96%, 91%, 100% and 99%.

Conclusions:
In comparison with the new and widely used NSRG criteria, CTA NASCET-type measurements seem to underestimate the degree of extracranial ICA stenosis. The validity of the NSRG criteria is currently evaluated in a prospective multicenter validation study utilizing invasive angiography as the gold standard.
Abstract W MP34: Magnetically-Enhanced Diffusion (MED) of Intravenous tPA for Acute Ischemic Stroke: Preclinical Data
Authors: Derdeyn Colin , Bladin Christopher , Levi Christopher , Parsons Mark , Campbell Bruce , Panagos Peter , Creighton Francis
Published: July 2021

Background:
Diffusion of drug to the clot in a no flow environment may be a major factor in the relative ineffectiveness of iv-tPA. The MED system uses an external magnet and magnetic particles (MP) to improve IV-tPA diffusion to clots and to mix tPA at the clot surface. Methods: Diffusion experiments were conducted in a femoral artery ligation model using Evan’s Blue dye as surrogate to tPA. Clot surface interaction experiments were conducted in a jugular vein rabbit model using thrombin-induced occlusions. tPA was locally delivered. Time to recanalization was measured out to 3hrs for 312.5U to 5000U of tPA in ~500uL of blood (0.6U/uL and 9.9U/uL, respectively), with and without MP.

Results:
Femoral dye studies showed a >5X faster diffusion using the MED system in the femoral artery (Figure 1). Jugular lysis studies showed greater variability in the tPA-alone arm, which possessed several failures to recanalize. No recanalization occurred in <30min for tPA doses <2500U. <25% of the 625U doses restored flow in <1hr. Use of the MED system substantially improved tPA lysis reliability (all recanalization <140min for all doses). 67% of the 625U doses restored flow <1hr. Compared to successful tPA recanalization alone, scatter was significantly smaller and time-to-recanalization 2.5X faster (Figure 2).

Conclusion:
This study demonstrates the ability of the MED system to accelerate both tPA transport to a clot and clot lysis. This observation supports efficacy signals seen in the human feasibility trial. These results may provide a new understanding of the variability historically seen in thrombolytic efficacy, which may be related to inefficient thrombolytic contact with the thrombus.
Abstract W MP39: SSRI/SNRI Use Is Not Associated With Increased Risk Of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
Authors: Young Jimmy , Singh Tarun , Fugate Jennifer , Rabinstein Alejandro
Published: July 2021

Objective:
To determine the effect of Selective Serotonin Reuptake Inhibitor (SSRI)/Selective Norepinephrine Reuptake Inhibitor (SNRI) use prior to or during admission for aneurysmal subarachnoid hemorrhage (aSAH) on the risk of symptomatic vasospasm and diffuse cerebral ischemia (DCI).

Methods:
Review of electronic records at Mayo Clinic, Rochester from Jan. 2001 to Dec. 2013 of consecutive patients with aSAH. The variables collected and analyzed were: age, sex, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3-6) within 1 year.

Results:
583 [females 367 (63%)] patients with a median age of 55 (47-65) years were admitted with aSAH during the study period. WFNS at nadir was IV-V in 243 (41.6%) and modified Fisher score was 3-4 in 438 (75.2%). Eighty one (14.6%) patients were taking SSRI or SNRI prior to admission and these medications were continued in all of them. Symptomatic vasospasm was present in 154 (27.7%), radiological infarction in 172(29.5%), and DCI in 250(42.9%) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p=0.458), symptomatic vasospasm (p=0.097), radiological infarction (p=0.972), or poor functional outcome (p=0.376).

Conclusions:
The use of SSRI/SNRI prior to admission and/or during hospitalization in patients with aSAH was not associated with symptomatic vasospasm or DCI.
Abstract W MP87: PDGF Contributes to BMSC Treatment Induced Neurogenesis and White Matter and Axonal Remodeling in T2DM Stroke Rats
Authors: Zacharek Alex , Yan Tao , Chopp` Michael , Venkat Poornima , Ning Ruizhou , Roberts Cynthia , Chen Jieli
Published: July 2021

Objective:
Our previous studies have found that bone-marrow-stromal cell (BMSC) treatment of stroke in Type two DM (T2DM) rats, initiated at 3 days after stroke, improved functional recovery. Neurogenesis and white matter (WM) remodeling play an important role in neurorestorative effects after stroke. In this study, we tested whether BMSCs regulate neurogenesis and WM remodeling and the underlying mechanisms of BMSC induced neurorestorative effects in T2DM stroke rats.

Methods:
T2DM was induced with streptozotocin injection in addition to a high fat diet. T2DM rats were subjected to 2h of middle cerebral artery occlusion (MCAo), then treated with human BMSCs (5X106) or vehicle control (n=8/group) initiated at 3 days after MCAo and rats were monitored for 28 days. Neuroblast migration, WM changes, and gene and protein expression were measured in the ischemic brain. Subventricular zone (SVZ) explant cell migration and primary cortical neuron (PCN) axonal outgrowth measurements were performed in vitro.

Results:
BMSC treatment in T2DM rats significantly improves functional outcome and increases WM remodeling identified by increased myelin and axonal density. BMSCs also increase the neuroblast migration protein doublecortin (DCX, 25.0±4.3% vs control: 4.5±1.1%), platelet-derived growth factor (PDGF)-AA, and bFGF expression in the ischemic border zone. Angiogenic ELISA array data are consistent with the immunostaining data, showing that BMSC treatment increases PDGF-AA (2.1 fold), PDGF-BB (2.5 fold) and bFGF (1.8 fold) in the ischemic brain. Using an in vitro cell culture model, we found that BMSCs secrete high levels of PDGF. PDGF treatment significantly increases SVZ explant cell migration (1.7 fold) and PCN axonal outgrowth (1.9 fold) compared to non-treatment control. Inhibition of PDGF with neutralized anti-PDGF antibody significantly attenuates BMSC conditioned medium induced SVZ cell migration and PCN axon outgrowth.

Conclusion:
BMSC treatment of stroke in T2DM increases WM remodeling and neurogenesis as well as increases PDGF expression. PDGF not only promotes neuronal migration, but also increases axonal outgrowth. Therefore, increasing PDGF likely contributes to BMSC induced neurogenesis and WM remodeling in T2DM stroke rats.
Abstract W MP97: Post-discharge Pneumonia And Urinary Tract Infection After Hospitalization For Ischemic And Hemorrhagic Strokes
Authors: Moradiya Yogesh , Murthy Santosh , San Luis Christa , Dharaiya Devanshi , Kachhela Jaydeep , Ziai Wendy
Published: July 2021

Background and purpose:
Stroke related disability is a risk factor for infectious complications and the risk persists even after discharge from the hospital. Therefore, we studied the incidence and predictors of pneumonia and urinary tract infection (UTI) up to 1 year after hospitalization for ischemic stroke, spontaneous intracerebral hemorrhage (ICH) and non-traumatic subarachnoid hemorrhage (SAH).

Methods:
We analyzed all adult cases treated in acute care hospitals and emergency departments in California state between 2005 and 2011 using state inpatient and emergency databases of Healthcare Cost and Utilization Project. Patients with principle diagnosis of ischemic stroke (ICD-9 codes 433.x1, 434.x1, 436), ICH (431) and SAH (430) surviving up to discharge were followed up for development of first episode of pneumonia and UTI at 30-days, 90-days and 1-year intervals. Index cases were limited to 2005-2010 to ensure at least 1 year of follow up. Negative binomial regression was used to obtain predictors of post-discharge pneumonia or UTI.

Results:
Among 168,194 ischemic strokes, 26,502 ICH and 10,659 SAH cases, 5.7%, 7.3% and 4.9% developed pneumonia, and 8.6%, 11.5% and 8.8% developed UTI within 90-days after discharge respectively. The incidence rate of pneumonia during first 30 days was 38.8 per 100 person years which decreased to 14.8 per 100 person years between 31-90 days. The rate decreased further during 91-365 days to 7.3 per 100 person years. The rates of pneumonia among ICH and SAH and of UTI among different stroke types showed similar trend with higher risk during immediate post-discharge period. Factors independently associated with post-discharge infections were older age, female sex, non-white race, hypertension, diabetes, congestive heart failure, dementia, liver disease, anemia, atrial fibrillation, mechanical ventilation, gastrostomy and longer length of index admission.

Conclusions:
Risk of infectious complications is highest after ICH among different stroke types. The risk is highest during immediate post-discharge period but remains higher than general hospital population at least up to 1 year.
Abstract W P107: HDAC4 Shuttling in Interneurons and Pyramidal Neurons is Associated with Improved Axonal Density and Myelination after Stroke
Authors: Kassis Haifa , Shehadah Amjad , Chopp Michael , Roberts Cynthia , Zhang Zheng Gang
Published: July 2021

Background:
We have previously demonstrated that stroke induces nuclear shuttling of histone deacetylase 4 (HDAC4) in neurons during stroke recovery. Further examination of the distribution of HDAC4 shuttling in interneurons and pyramidal neurons may provide new insights into mechanisms of HDAC4 mediated neuronal circuitry remodeling after stroke. In the current study, we measured nuclear shuttling of HDAC4 in these two populations of neurons in the peri-infarct cortical layers after stroke. Methods: Adult male Wistar rats (n=6/group) were subjected to permanent middle cerebral artery occlusion (MCAO) and sacrificed at 2 or 14 days after MCAO. Sham operated rats were used as a control. Double immunohistochemistry was performed with antibodies against HDAC4 along with microtubule-associated protein 2 (MAP2, neurons), parvalbumin (PV, interneurons), Ctip2 (pyramidal neurons), phosphorylated neurofilament heavy chain (pNFH, axons) and myelin basic protein (MBP, myelination). Results: HDAC4 nuclear immunoreactivity in MAP2+ neurons of the normal cortex was evenly distributed throughout the upper (L1-4) and lower cortical layers (L5-6). Stroke significantly (p<0.05) increased the percentage of neurons with nuclear HDAC4 in L5-6 at 2 (37%) and 14 days (73%) compared to sham (19%), whereas in L1-4, a significant increase in neurons with nuclear HDAC4 was detected only at 14 days after MCAO (49% vs 17%). Among neurons, stroke significantly increased the number of Ctip2+ and PV+ neurons with nuclear HDAC4 in L5-6 at 2 (Ctip2 57%, PV 66%) and 14 days after stroke (Ctip2 73%, PV 74%) compared to sham (Ctip2 33%, PV 12%). Furthermore, in L5-6, but not in L1-4, nuclear HDAC4 shuttling was positively and significantly correlated with increased axons and myelination as determined by pNFH (r = 0.84, p<0.05) and MBP (r = 0.76, p<0.05) densities, respectively. Conclusion: Stroke induces nuclear shuttling of HDAC4 in pyramidal neurons and interneurons of layers 5-6 of the peri-infarct cortex which is strongly correlated with enhanced axonal density and myelination, suggesting a role for HDAC4 in promoting pyramidal neuron and interneuron axon remodeling during stroke recovery.
Abstract W P11: Factors Affecting Vascular Neurologists' Decisions to Pursue Endovascular Intervention of Acute Ischemic Stroke Patients
Authors: Sarraj Amrou , Martin-Schild Sheryl , Boehme Amelia K , Supsupin Emilio P , Sitton Clark W , Bajgur Suhas S , Choi Jeanie M , Datta Proleta , Wu Tzu-Ching , Bonafante-Mejia Eliana E , Friedman Elliot , Dannenbaum Mark J , Chen Peng R , Sun Chung-Huan J , Barreto Andrew D , Gupta Rishi , Grotta James C , Savitz Sean I
Published: July 2021

Background:
Intra-arterial therapy (IAT) is an approach to promote recanalization in acute ischemic stroke (AIS) patients. While IAT continues to go through further evaluation in multiple phase III trials using new devices and focusing on time improvement, patients with LAO continue to be treated with IAT. Multiple clinical, radiographic and time factors go into vascular neurologists’ decisions whether to pursue IAT or not. We aimed to evaluate factors affecting determination of IAT for stroke amongst patients transferred to tertiary centers.

Methods:
A US multicenter retrospective cohort analysis was conducted on 313 consecutive transferred patients who met vessel criteria from 01/08-4/14. Collateral were measured by the collateral score (CS). ASPECTS decay was defined as a change from good (8-10) to poor (0-7) scores between center CT scans. IAT patients were compared with no IAT patients with regard to factors predictive of IAT.

Results:
Table 1 shows baseline characteristics of the two groups. Age was not a predictor of IAT. NIHSS was associated with IAT, but was not a predictor of IAT. For each escalating point on CS, the odds of IAT increased more than 4 times (OR 4.27, 95% CI 2.86-7.87, p<0.0001). For each declining point on ASPECTS, the odds of IAT decreased by 22% (OR 0.78, 95% CI 0.72-0.85, p<0.0001). ASPECTS decay was associated with an 83% reduction in the odds of IAT (OR 0.17, 95% CI 0.05-0.52, p<0.0001). For every 30 minutes of time between centers, the odds of ASPECTS decay increased by 13% (OR 1.13, 95% CI 1.11-1.17 p=0.0004) and IAT chances reduced by 9% (OR 0.91, 95% CI 0.84-1.00, p=0.05).

Conclusions:
Infarction evolution measured by ASPECTS decay, collaterals status and time from stroke ictus are all major determinants of the vascular neurologist decision whether to proceed with IAT. Our findings further support the time-sensitivity of the process for transferring candidates for IAT.
Abstract W P115: Utilization of Blood Sampling Global Oxygen Extraction Fraction and SPECT to Anticipate Cerebral Hyperperfusion Syndrome Following Elective Carotid Artery Stenting
Authors: Mori Takahisa , Iwata Tomonori , Tanno Yuhei , Kasakura Shigen , Aoyagi Yoshinori , Yoshioka Kazuhiro
Published: July 2021

Background:
It is required to anticipate cerebral hyperperfusion syndrome (CHS) following carotid artery stenting (CAS).

Purpose:
The purpose of our retrospective study was to investigate whether or not blood sampling oxygen extraction fraction (OEF) and post-CAS CBF increase in SPECT had relation to CHS following CAS.

Methods:
Included in our analysis were patients (1) who underwent elective CAS in our institution between October 2010 and May 2014, and (2) who underwent blood sampling for OEF calculation before and immediately after CAS, and (3) who underwent SPECT before and just after CAS. OEF was calculated from cerebral arteriovenous oxygen difference. Arterial blood was sampled from the common carotid artery and venous blood from the dominant-sided superior jugular bulb. CHS was defined as pulsatile headaches, restlessness, convulsion, and/or new neurological symptoms not due to cerebral ischemia within seven days following CAS. CBF was measured before and just after CAS. CBF increase in the CAS side was defined as follows; (post-CAS CBF ratio - pre-CAS CBF ratio) of more than 10%, where CBF ratio was defined as CAS-sided fronto-parietal CBF divided by ipsilateral cerebellar CBF (%).

Evaluated were baseline features in patients, pre-CAS OEF, post-CAS OEF, CBF ratio, CBF increase and CHS.

Results:
During the study period, 134 patients matched our criteria for analysis. Pre-CAS OEF was 0.41+-0.06, post-CAS OEF was 0.42+-0.08, pre-CAS CBF ratio: 88.7+-15.4%, CBF increase: 1.86+-12.3%. Nine patients presented CHS. Among them, pre-CAS OEF, CBF ratio and CBF increase were significant. ROC curves showed that pre-CAS OEF of 0.46 (p<0.001, OR: 9.3), CBF ratio of 92%(p<0.05, OR: 6.5), CBF increase of 8.8% (p<0.005, OR: 6.6) were cut-off values. Among 10 patients with pre-CAS OEF of more than 0.46 and CBF increase of more than 8.8%, 4 patients presented CHS (p<0.0001, OR;15.9).

Conclusion:
Elevation of pre-CAS OEF and increase of post-CAS CBF were strongly related to CHS.
Abstract W P121: Patterns Of Vessel Involvement In Patients With Intracranial Atherosclerosis Across Ages
Authors: Strohm Tamara , Cerejo Russell , Mathew Jason , Katzan Irene , Uchino Ken
Published: July 2021

Introduction:
Intracranial atherosclerosis has been well studied in the aging population, much less is known about atherosclerotic stenosis in the young. Clinicians seek to control traditional vascular risk factors in this population, but differences in patterns of stenosis may call for varied treatment approaches. This study sought to compare age to the distribution of vessel involvement in patients with moderate-severe intracranial stenosis.

Methods:
This is a retrospective cohort study of patients with intracranial stenosis seen in the stroke clinic of a tertiary center from 2008-2013.

Inclusion criteria were moderate-severe intracranial stenosis clinically felt to be due to atherosclerosis with ≥3 traditional vascular risk factors. Patients with other mechanisms of intracranial stenosis were excluded. Stenosis location and severity were based on cerebral angiography, CTA, or MRA. Patients were divided into young (< 50 yr), middle-age (51-64 yr), or older (≥

65 yr). All 69 patients ≤50 yr were included; a random sample of 69 patients > 50 were selected for this analysis.

Results:
There were similar rates of vascular risk factors except HTN, which was less common in the young group (81.2% young, 100% middle, 96.8% older, p=0.0006). The location of stenoses varied by age category. Older patients had more posterior circulation involvement compared to the younger groups (p = 0.046), with more frequent involvement of vertebral and basilar arteries (p = 0.012) (Table). The occurrence of stenosis in the distal ICA and MCA vessels were similar among age groups. The frequency of ACA stenosis was highest in the young category (p = 0.026).

Conclusion:
There are differences in anatomic locations of presumed intracranial atherosclerosis across age groups with older patients (> 65 yrs) having a higher rate of posterior circulation disease. This suggests potential differences in pathophysiological mechanisms. These findings warrant further investigation.
Abstract W P124: Atherosclerosis Of The Circle Of Willis Is Strongly Associated With Downstream Cerebral Amyloid Angiopathy In Parenchymal Arterioles And Capillaries: Possible Mechanism For Atherosclerosis-related Intracranial Hemorrhage
Authors: Rose Danny R , Jicha Gregory A , Lee Jessica D , Murphy Richard R
Published: July 2021

Introduction:
Atherosclerosis is highly associated with risk for intracranial hemorrhage. Presumed mechanisms include artery to artery embolization, arteriolar disruption by small vessel atherosclerosis, aberrant angiogenesis in poorly perfused vascular beds, and possible involvement of downstream cerebral amyloid angiopathy (CAA). Direct associations between atherosclerosis and downstream CAA have been not been supported in most studies, however these results may be confounded by the distinction between highly prevalent meningeal CAA and less frequent parenchymal CAA.

Hypothesis:
We hypothesized that large vessel intracranial atherosclerosis would be associated with downstream parenchymal, but not meningeal (supplied by extracranial circulation), CAA.

Methods:
Data were derived from the University of Kentucky brain bank (n=741). Atherosclerosis of the circle of Willis was graded on semiquantitative scale (1=0-25% occlusion; 2=25-50% occlusion; 3=50-75% occlusion; 4=75-100% occlusion). Cases were divided into those with absent (with or without meningeal CAA; n=493) and those with parenchymal CAA (n=248). Standard descriptive and comparative statistics were used for the analysis.

Results:
Atherosclerosis in the circle of Willis was highly associated with parenchymal (p<0.001), but not meningeal CAA.

Conclusions:
The strong association seen between severity of atherosclerosis and parenchymal CAA suggests possible shared pathogenesis or perhaps causal development of CAA by high grade atherosclerosis. Further studies exploring this association in animal models would be helpful in clarifying this complex relationship.
Abstract W P138: Hand Asymmetries in the Control of Grasp Force Post-Stroke
Authors: Adamo Diane E , Pardo Vicky , Rajamani Kumar
Published: July 2021

Background and Purpose:
Stroke survivors have difficulty overcoming deficits associated with grasping ability that differ for their right and left hand. However, grasp force deficits unique to each hand are not clearly characterized. The purpose of this study was to determine right and left hand differences in control of grasp force for individuals who were right handed pre-stroke.

Methods:
Twenty-one participants (13 with left hemispheric & 8 with right hemispheric stroke) completed clinical assessments and performed hand-grasp tasks using Instrumented Strain Gauges embedded with force sensors. Pre / post stroke hand preference scores were obtained using the self-reported Edinburgh Handedness Inventory (EHI). A right and left hand Reference Force (RF) was based on 20% of the right and left maximum grasp force. The Matching Force (MF) was performed by the opposite hand. Visual feedback represented by a horizontal line on a computer monitor displayed the 20% RF. MF, performed without visual feedback, indicated whether the participant overshot or undershot the RF and was quantified as the Constant Error.

Results:
EHI scores for right hemispheric stroke patients were 0.86 / 1.00 pre, and 0.92 / 1.00 post stroke, indicating greater right hand use post stroke. EHI scores for left hemispheric stroke patients were 0.91 / 1.00 pre, and 0.59 / 1.00 post stroke, indicating less right hand use and greater left hand use post stroke. The ANOVA showed a significant three-way interaction for matching hand *reference hand* affected side

F(2, 38) =4.42, p < 0.05) for constant error. Right hemispheric stroke patients showed left hand MF undershoots for right hand RF (p < 0.05). Left hemispheric stroke patients showed right hand MF undershoots for left hand RF (p < 0.05).

Conclusions:
Shifts in handedness scores and asymmetries in force matching performance were dependent on lesion location. From a clinical perspective, stroke survivors may not be aware of how hand differences in the control of grasp force influence their ability to perform everyday tasks despite knowing that one hand may be weaker than the other. This suggests using a lesion-side specific treatment technique to improve awareness and function when performing unimanual and bimanual hand-grasp tasks.
Abstract W P152: Twenty Years Later: The Changing Picture of Infective Endocarditis in a Large Urban Center
Authors: Walker Greg , Li Damon , Hahn Nicola , Johnston Dean
Published: July 2021

Purpose:
St. Paul’s Hospital serves a low-SES, high-risk population in Vancouver’s ‘Downtown East Side.’ Our study characterizes the changing epidemiology, neurologic complications, investigation methods and outcomes of this group from 1995 to 2014. To date, our database is among the world’s largest.

Methods:
This retrospective chart review used ICD-9 codes to identify 922 cases of infective endocarditis satisfying Duke Criteria. We collected demographic data including Intravenous drug use (IVDU), HIV and Hepatitis status, and clinical data including neurologic complications, mortality rates and treatment. The cohort was divided into IVDU and non-IVDU and ‘first decade’ (1995-2005) versus ‘second decade’ (2006-2014). Univariate analysis was performed using chi-square and non-parametric t-tests.

Results:
Mortality was not different between the first and second decades [105/669 (15.7%) vs 35/253 (13.8%) p=0.4] but was significantly greater in non-IVDUs than IVDUs in the first decade only [61/297 (20.5%) vs 44/369 (11.9%) p=0.002]. Neurologic complications [141/922 (15.3%)] were more frequent in non-IVDUs versus IVDUs in the first decade only [44/310 (14.2%) vs 33/359 (9.2%) p=0.04]. Neurologic complications were more frequent in the second versus first decade [64/253 (25.3%) vs 77/669 (11.5%) p<0.001]. Mycotic aneurysms (MA) were more frequent in the second decade [11/253 (4.3%) vs 4/665 (0.6%) p<0.001]. In patients investigated for MA, CTA was employed more frequently in the second decade [31/64 (48%) vs 5/77 (6.5%) p<0.001]. Subjects with neurologic complications were more likely to receive cardiac surgery than those without neurologic complications in the first decade (OR=2.4, 95% CI:1.9-2.9) only.

Conclusions:
Our data show a trend toward a reduction in overall mortality from IE, but an increase in neurologic complications, particularly in non-IVDU patients. Embolic stroke remains the most frequent neurologic complication. Mycotic aneurysms remain uncommon. We observed a shift in favor of CTA vs DSA for the detection of MAs, with a corresponding increase in the frequency of MAs. The appropriateness of this practice remains to be determined.
Abstract W P154: Von Willebrand Factor Elevation Threshold for Poor Clinical Outcomes in Patients with Ischemic Stroke
Authors: Samai Alyana A , Boehme Amelia K , George Alexander , Monlezun Dominique J , Dowell Lauren , Leissinger Cindy , Schluter Laurie , El Khoury Ramy , Martin-Schild Sheryl
Published: July 2021

Background:
Elevation in von Willebrand factor (vWF) is an independent risk factor for thromboembolic events and acute ischemic stroke (AIS). Laboratory reference ranges categorize levels >150% activity as abnormal. Our prior research demonstrated worse outcomes with severe (>200%) elevation in vWF. We sought to determine the most clinically relevant threshold value for vWF with respect to patient outcome in AIS.

Methods:
From our stroke registry, patients admitted with AIS between 07/2008-10/2013 were included if vWF levels were measured during admission. Logistic regression was used to assess differences in baseline, in-hospital, and outcome variables in patients with vWF elevation as compared to those with normal levels. Optimal threshold levels were determined by assessing dichotomized vWF levels using a 5-point incremental analysis of levels with respect to outcome, and subsequent determination of the threshold yielding the largest area under the curve (AUC). The outcome was poor modified Rankin Scale (mRS) score on discharge, defined as mRS>2.

Results:
Among 1,453 cases in our registry, inclusion criteria were met for 99 patients. Compared to patients with normal vWF, elevated vWF was associated with age, female gender, and diabetes. vWF elevation threshold of 200% was the best predictor of poor mRS on discharge (OR 2.88, 95% CI 1.32-6.29, p=0.0079) with an AUC of 0.629.

Conclusions:
Despite a laboratory cut-off of 150% as a normal value, elevation of vWF >200% is the most clinically useful threshold for the prediction of poor clinical outcome in the setting of AIS based on data from our center.
Abstract W P165: Acetaminophen Use and Risk of Stroke and Myocardial Infarction in a Hypertensive Population
Authors: Fulton Rachael L , Walters Matthew , Dominiczak Anna , Mcinnes Gordon , Meredith Peter A , Morrison David , Padmanabhan Sandosh , Touyz Rhian , Dawson Jesse
Published: July 2021

Introduction:
Recent data suggest self-reported acetaminophen use is associated with increased risk of cardiovascular events and that acetaminophen causes a modest rise in arterial blood pressure. There are no randomized studies, studies using verified prescription data or studies in high risk patients that investigate this relationship.

Hypothesis:
We aimed to assess the relationship between acetaminophen prescription data and risk of stroke and myocardial infarction in patients with hypertension.

Methods:
We performed a retrospective data analysis using data contained within the UK Clinical Research Practice Datalink. This includes verified prescription data. Multivariable Cox proportional hazard models were used to estimate hazard ratios for stroke or MI associated with acetaminophen use over a 10-year period. Acetaminophen exposure was a time dependent variable. A propensity matched design was also used to reduce potential for confounding.

Results:
We included 24496 hypertensive individuals aged 65-years or older. Of these, 10878 were acetaminophen exposed and 13618 were not. There was no relationship between risk of stroke, MI or any vascular event and acetaminophen exposure on adjusted analysis (OR 1.09, 95% CI 0.86 to 1.38; OR 0.98, 95% CI 0.76 to 1.27; OR 1.17, 95% CI 0.99 to 1.37 respectively). Results in the propensity matched sample (n=4000 per group) were similar and high frequency users (defined as receiving a prescription for >75% of months) were also not at increased risk.

Conclusions:
In summary, use of acetaminophen was not associated with an increased risk of stroke or myocardial infarction in a large cohort of hypertensive patients.
Abstract W P17: Spontaneous Dilatation of Stents at Three Months After Carotid Artery Stenting Without Post-Carotid Artery Stenting Balloon Dilatation
Authors: Tanno Yuhei , Mori Takahisa , Iwata Tomonori , Aoyagi Yoshinori , Kasakura Shigen , Yoshioka Kazuhiro
Published: July 2021

Objective:
The aim of our retrospective study was to investigate how wide stents were spontaneously dilated at three months after carotid artery stenting (CAS) without post-CAS balloon dilatation (BT).

Methods:
We included in our analysis patients 1) who underwent elective CAS without post-CAS BT from January 2012 to March 2014, 2) who underwent follow-up conventional angiography at 3 months after CAS, Patients’ baseline characteristics, stent types (open cell: OP or closed cell: CL), stent diameter (SD) at the site with minimum width on the lateral projection immediately and at 3 month after CAS were evaluated.

Results:
Sixty-two lesions in fifty-nine patients were analyzed. Their average age was 74.9 years old, median SD immediately after CAS was 3.27mm(3.08_3.64:interquartile range), median SD at 3 months was 3.99mm(3.58-4.27), and thus SD was spontaneously dilated (p<0.0001). In OP types (18 cases), median SD changed from 3.59 to 4.05 mm and in CL types (44 cases) from 3.22 to 3.85 mm. Median SD after deployment was wider in OP type anytime (p<0.05), whereas dilatation rate seemed to be bigger in CL type.

Conclusion:
Stents were spontaneously dilated about 10 to 20% without post-CAS balloon dilatation. SD at 3 months was wider in OP type, whereas dilatation rate at 3 months was bigger in CL type.
Abstract W P188: Cardiac Disorders in Patients with Stroke in Multiple Vascular Territories (MVT)
Authors: Giannakidis Dimitrios , Shah Jignesh , Benson Richard , Lynch John
Published: July 2021

Stroke in multiple vascular territories can be defined as an imaging pattern of non-contiguous acute ischemic lesions in >1 vascular territory. Stroke in MVT has been reported with a number of medical disorders and may represent a pattern of injury at high risk of recurrent stroke. The goal of this study was to determine the frequency and etiology of cardiac abnormalities among patients who present with stroke in MVT.

Methods:
The study population was derived from the NINDS LESION Study, a consecutive cohort of ischemic stroke patients (N=1193) admitted to two primary stroke centers (Washington Hospital Center, Washington, DC; Suburban Hospital, Bethesda, MD) between 01/1999 and 10/2009. All patients received an acute MRI (1 DWI +/ADC + MRI abnormality in multiple vascular territories (bilateral anterior, anterior-posterior, or all 3 regions). Cardiac studies (EKG, echocardiogram, and cardiac telemetry) on stroke admission were reviewed for each patient. The etiology and prevalence of cardiac abnormalities were determined for patients with stroke in MVT.

Results:
Overall, 84 patients were included in the study, the median age was 69.5 yrs, 57% were African American, and 54% were female. Preadmission cardiac risk factors (AF, LVH, and CAD) were reported in 50% of patients. EKG abnormalities were identified in 76% of patients on admission. These included, HR abnormalities (tachy or bradycardia) in 51%, conduction disorders (AV or BB blocks) in 25%, and arrhythmias (supra or ventricular) in 25% of patients. Echocardiography abnormalities included; 61% with left ventricular abnormalities (hypertrophy, hypokinesis), 54% with left atrial enlargement, 37% with low EF (<50%), 27% with aortic arch abnormalities, 19% with mitral valve disorders (annular calcification, prolapse), and 7.3% with atrial septal defects.

Conclusion:
EKG and echocardiography abnormalities are common in patients who present with stroke in MVT. An extensive cardiac evaluation is warranted to determine etiology and implement stroke prevention strategies.