bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract NS4: Effectiveness in Using a Staff Nurse Coach for Clinical Trial Implementation: A Winning Strategy
Authors: Yarbrough Karen , Tuszynski Stepanie , Bautista Mary Ann , Blaber Bridget
Published: March 2022

Background:
Ischemic stroke is a leading cause of significant life-long disability in the United States. Current treatment options are limited, especially for patients with large stroke and brain edema. The GAMES Pilot Study (Glyburide Advantage in Malignant Edema and Stroke Pilot) was a multicenter Phase IIa trial designed to test the feasibility of enrolling, evaluating and treating with RP-1127 (glyburide for injection). This trial depended on the expertise of the Neuroscience ICU nursing staff to comply with extensive study trial interventions which included: hourly measurements of glucose, daily acquisition of MRIs, and titration of study drug. The goal of this performance improvement project was to evaluate the effectiveness of having a staff nurse function as a unit based clinical trial coach to facilitate clinical trial implementation.

Methods:
Effectiveness of using a staff nurse as a clinical trial coach was determined by assessing the ability to safely enroll 10 study patients with completion of study interventions. The coach was a senior RN and was taught the fundamentals of good clinical practices. The following interventions were developed and implemented by the GAMES coach: 1) facilitated 5 meetings with study staff, ICU management, radiology, and “bed control” to identify barriers for secured admission to Neuroscience ICU and transporting daily to MRI, 2) provided >10 staff nurse inservices, 3) designed study documents, 4) developed resource educational materials about study drug and interventions, and 5) provided expert support to colleagues during enrollment.

Results:
The GAMES Pilot Study enrolled 10 patients. The GAMES coach facilitated inservices to > 85% of the neuroscience ICU staff. 100% of study participants were admitted to the Neuroscience ICU. Staff nurses were 100% compliant in obtaining and documenting glucose measurements. Compliance with obtaining MRIs was 100%.

Conclusion:
Using a staff nurse as a clinical trial coach allowed early identification and removal of barriers for study enrollment. The GAMES Pilot Study coach was instrumental in garnering enthusiasm and support for implementation of a stroke trial. As a result of this study, acute stroke trials will always have a study coach identified.
Abstract TMP111: Phenotypic Alterations of Brain Microvascular Endothelium in a Murine Model of Alzheimer Disease
Authors: Hayashi Shin-ichiro , Sato Naoyuki , Morishita Ryuichi , Kawano Yuhei
Published: March 2022

Background:
Alzheimer disease (AD) is characterized by progressive neuronal disorder that cause dementia, and is recognized as a major cause of death in the elderly population. Recent our in vitro findings suggest the possibilities that autophagy-associated endothelial dysfunction might be involved in the pathogenesis of AD.

Methods:
Electron microscopy (EM) and immunohistological analysis were performed on brain tissues of APP23, a mouse model of AD, and age-matched wild type mice.

Results:
The Morris water maze test showed cognitive disturbance in 8-month old APP23 mice but not in wild type mice. Notably, EM revealed that the densities of hippocampal capillary were significantly lower in APP23 mice as compared to those in wild type mice. The reduction in hippocampal microvessels was more apparent in 24-month old APP23 mice. Immunostaining with antibodies against ß-amyloid (Aß) and alpha-smooth-muscle-actin showed that Aß deposition was not limited to neural cells but to microvessels in hippocampus and cortex. Importantly, EM analysis revealed autophagy induction in hippocampal capillary endothelium in 8-month old APP23 mice. In addition, the number of microvessels with autophagic endothelium was significantly increased in 24-month-old APP23 mice. Furthermore, the advanced stages of autophagy fused with lysosome were detected in both neurovascular endothelium and neural cells.

Conclusions:
The present study indicate that phenotypic alteration of neurovascular endothelium might be the earlier pathological events in brain with AD, suggesting important implications for therapeutic approaches of AD.
Abstract TMP117: Intracranial Dolichoectasia in Patients with Lacunar Strokes: The SPS3 Trial
Authors: Nakajima Makoto , Pierce Lesley , Bazan Carlos , Hart Robert G , McClure Leslie , Benavente Oscar R
Published: March 2022

Background and Purpose:
Intracranial arterial dolichoectasia (IADE) is a common finding in atherothrombotic strokes, but its relationship with lacunar infarcts is less certain. We investigated the prevalence of IADE and its correlation with risk factors as well as with recurrent stroke within the Secondary Prevention of Small Subcortical Strokes (SPS3) study cohort.

Methods:
The greatest diameter of the following arteries was measured on MRA: bilateral internal carotid artery (ICA), middle cerebral artery (MCA), vertebral artery (VA), and the basilar artery (BA). IADE criteria were a diameter of over 7.0 mm for ICA, over 4.0 mm for MCA, over 4.0 mm for VA, and over 4.5 mm for BA. BA elongation was assessed according to Smoker’s criteria.

Results:
Of the 3020 SPS3 participants, 2562 MRAs were assessed. Diameters were: ICA, 4.4 +/- 0.6 mm; MCA, 2.6 +/- 0.4 mm; BA, 3.4 +/- 0.7 mm; and VA, 2.4 +/- 0.7 mm. Of the measured participants 8% met criteria for IADE; 65% had IADE in a single artery, 28% in two arteries, and 7% in more than two arteries. Abnormality in either height of the bifurcation (66.7% vs. 4.6%, p<0.001) or lateral displacement (45.6% vs. 1.4%, p<0.001) of the BA was observed more frequently in patients with IADE than without.

Conclusion:
In this large and well characterized cohort of lacunar stroke patients, IADE was present in 8%, approximately half of whom demonstrated BA elongation. The relationship between IADE and incidence of recurrent stroke will be presented. Ongoing analyses from SPS3 will likely elucidate if IADE is a risk factor for stroke recurrence in lacunar stroke patients.
Abstract TMP12: MR Diffusion and CT ASPECTS Disparities as a Function of Time From Presentation: Analysis and Implications for Acute Stroke Triage
Authors: Hui Ferdinand , Hussain Shazam , Wisco Dolora , Uchino Ken , Toth Gabor
Published: March 2022

Introduction:
In April of 2010, the Cleveland Clinic switched to an MR based triage for candidates for intra-arterial thrombolysis and thrombectomy, yielding a patient cohort that was imaged with both MRI and CT allowing comparison of imaging characteristics and an analysis of current triage algorithms employed. The investigators sought to ascertain what differences in DWI and MRI ASPECTS scores might be present in this cohort as a function of time from symptom onset, hypothesizing that the degree of mismatch may increase and/or decrease given that the imaging findings of ischemia become apparent on CT and MRI at different rates. Such a difference may have implications for designing imaging triage regimes for stroke centers.

Methods:
The Cleveland Clinic Acute Stroke Database was queried, excluding patients with incomplete data, yielding 291 patients. Time of the latest pre-treatment CT exam, MR exam and CTA exam was recorded as a function of time vs. the time the patient was last known well. ASPECTS score was assessed for each CT, CTA and MR exam. CT and CTA were used to determine a representative CT ASPECTS Score, using whichever was obtained closer to the time of the MRI.

Secondary Analysis:
Using an ASPECTS score of 7 as a discriminator for IA treatment, we assessed whether a given image would or would not have been selected for IA therapy, and assessed whether the DWI information would have resulted in a change in therapy.

Results:
Figure 1 shows a scatter plot of the time between onset and MRI imaging, and the disparity between CT ASPECTS and MRI ASPECTS.

Conclusion:
The mismatch between DWI and CT/CTA appears to be greatest between 180-420 minutes between onset to MRI, suggesting that MRI DWI regimes may be most valuable in patients during this period. Further analysis is needed in order to further refine acute stroke triage paradigms.
Abstract TMP18: Predicting Intracranial Hematoma Formation After IV tPA With MR Permeability Imaging
Authors: Leigh Richard , Jen Shyian S , Sweeney Elizabeth M , Crainiceanu Ciprian M , Hillis Argye E , Krakauer John W , Barker Peter B ,   on behalf of the STIR and VISTA Imaging Investigators
Published: March 2022

Background:
Damage to the blood-brain barrier in stroke patients can be detected using standard MR PWI and is associated with subsequent hemorrhagic transformation. No clear methodology for using the phenomenon to guide clinical management has been put forth.

Purpose:
To design and test a method for predicting subsequent parenchymal hematoma (PH) formation after IV tPA administration using MR PWI

Methods:
An analysis was performed on a database of stroke patients provided by the STIR and VISTA Imaging Investigators. 75 patients were identified who had a successfully acquired DWI, PWI, and GRE images prior to IV tPA and also had follow-up imaging to assess for PH. The pre-tPA MRI scans were analyzed looking for permeability deficits by comparing temporal signal changes in severely hypoperfused tissue with tissue in the contralateral hemisphere. Permeability was calculated as T1-related signal change and expressed as a percent of the CBV. Follow-up GRE images were reviewed for evidence of PH. All analysis was done using Matlab software. ROC curves were generated to evaluate the performance of the mean permeability at predicting PH.

Results:
44 of the 75 patients were women and the mean ± std of the age was 70±17. The mean NIHSS was 12±9. The mean time from onset to tPA was 147±30 minutes. 9 patients developed PH. The mean permeability of the PH group was 6±3.2% compared to the non-PH group which had a mean permeability of 3.7±3%. The ROC curve is seen in Figure 1. The area under the curve is 0.80. The optimal threshold identified for predicting PH was 4.8% which had a sensitivity of 0.67 and a specificity of 0.87.

Conclusions:
A method for quantitatively assessing damage to the BBB was successfully designed and tested. The ability of this technique to predict PH was fairly good considering there is currently no other way to predict who will develop PH after being treated in the IV tPA time window. Further analysis is needed to determine if this technique could be used to guide thrombolytic therapy.
Abstract TMP30: Genetic Variants on 9p21.3 are Associated with Brain Arteriovenous Malformations with Associated Arterial Aneurysms
Authors: Bendjilali Nasrine , Nelson Jeffrey , Weinsheimer Shantel , Sidney Stephen , Zaroff Jonathan G , Segal Mark , Pawlikowska Ludmila , McCulloch Charles E , Young William L , Kim Helen
Published: March 2022

Background:
The 9p21.3 locus is associated with risk of coronary artery disease and intracranial and abdominal aortic aneurysms (rs10757278). We investigated whether previously reported 9p21.3 SNPs are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying flow-related arterial aneurysms.

Methods:
Genotypes for 6 SNPs, including rs10757278, were imputed using 1000 Genomes Phase 1 CEU data (R2>0.9). We tested for association using logistic regression of imputed dosages adjusting for age, sex and top 3 components of ancestry in 338 BAVM cases vs. 504 controls. Of these, 205 cases had aneurysm data available for subgroup analysis: (a) 74 BAVM+(with) aneurysm cases vs. 504 controls, and (b) 131 BAVM-(without) aneurysm cases vs. 504 controls.

Results:
rs10757278-G was marginally associated with increased risk of BAVM (OR=1.23, 95% CI=0.99-1.53, P=0.064). Compared to controls, the association was stronger in BAVM+aneurysm (OR=1.52, 95% CI=1.03-2.22, P=0.032) than in BAVM-aneurysm cases (OR=0.98, 95% CI=0.72-1.34, P=0.91). Similar effects were observed for other SNPs in linkage disequilibrium (r2>0.8) with rs10757278 (Table).

Conclusion:
Common 9p21.3 variants showed similar effect sizes as previously reported for aneurysmal disease. The SNP association with BAVM appears to be explained by known association with aneurysms, suggesting that BAVM associated aneurysms share similar vascular pathology mechanisms.
Abstract TMP36: Persistent Stroke-induced Sensory, Motor And Cognitive Deficits Involve Long-term Myelin Loss In Major Fiber Tracts
Authors: Rosenbaum Daniel M , Zhou Jin , Zhuang Jian , Li Jie , Ooi Evelyn , Bloom Jonathan , Poon Carrie , Lax Daniel , Barone Frank C
Published: March 2022

Objectives:
Persistent neurobehavioral deficits and brain changes need validation for future brain restoration research. Here neurological and brain changes were determined post-stroke for this purpose.

Methods:
Two hr middle cerebral artery occlusion (tMCAO) or sham (Sham) surgery was performed in male SD rats. Measurements made over 10 weeks included: (1) sensory, motor, beam balance, hindlimb and forepaw behaviors, and (2) complex active place avoidance learning (APA) and simple passive avoidance retention (PA). Electroretinogram (ERG) was measured at term. Measurements of hemispheric loss (infarction), hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue) staining in several fiber tracts were made.

Results:
Compared to Sham, tMCAO produced significant but acute deficits in forelimb foot fault for only 1 day (max 2144 ± 556 % change, p<0.01) and forelimb cylinder placement for only 2 weeks (max 822 ± 215 % change, p<0.01). Persistent deficits for the 10 week period were exhibited for motor, sensory and beam balance performance and for hindlimb placement (all > 20-fold, p<0.001). Motor behavior and beam balance deficits, although persistent, did decrease 30-40 % over time. tMCAO produced significant, cognitive deficits in APA learning but did not affect PA retention. The impaired APA learning (max 604 ± 83 % change, p<0.001) was prolonged, and in fact exhibited progressive worsening (> 2-fold) over time, thus being most sensitive to brain injury. ERG indicated no difference in visual function. Percent hemispheric loss measured at term was cross-validated by 2 different staining methods (33 ± 4 % for H&E and 34 ± 4 % for TTC). No hippocampus neuronal loss occurred. Fiber tract myelin loss was significant (> 2-fold, P<0.01) in the external capsule and striatum but not in the corpus callosum or anterior commissure.

Conclusions:
Persistent deficits were identified for neurobehavioral end points for use in future restoration research. Fiber myelin loss in the external capsule and striatum contribute to long term deficits, apparently especially important for cognitive control necessary in complex learning. Investigation of myelin protection/regrowth mediated by oligodendrocytes, and perhaps other cells, will be essential to future stroke research.
Abstract TMP39: Identifying Cerebrovascular Reserve Capacity by Arterial Spin Labeling MR in Patients with Moyamoya Disease
Authors: sohn chul-ho , Yun Tae Jin , Paeng Jin Chul , Han Moon Hee , Kang Hyun-Seung , Kim Jeong Eun , Yoon Byung-Woo , Choi Seung Hong , Kim Ji-hoon
Published: March 2022

Background—
The diagnostic accuracy to identify the cerebrocascular reserve capacity (CVRC) by arterial spin labeling (ASL) MR in patients with moyamoya disease is unclear.

Methods—
We conducted a prospective study to examine the accuracy of ASL as compared with single-photon emission CT (SPECT) in patients with moyamoya disease. Preoperative ASL and SPECT images from 61 adult patients with moyamoya disease were analyzed. For 122 hemispheres from the patients, voxels of interest consisting of bilateral ICA and MCA territories were applied to the spatially normalized cerebral blood flow maps from basal and acetazolamide challenge ASL and SPECT. The correlation between cerebrovascular reserve capacity (CVRC) from ASL and SPECT was analyzed by a using Pearson correlation analysis and the area under the receiver-operating-characteristic curve (AUC) was used to evaluate diagnostic accuracy relative to that of SPECT for various cutoff points by CVRC.

Results—
Significant relationships were observed between CVRC from ASL and SPECT for the internal carotid artery (ICA) and middle cerebral artery (MCA) (correlation coefficient
r
= .7093,
P <
.0001 and
r
= .7319,
P <
.0001, respectively) (Table). The diagnostic accuracies of ASL for detecting ICA and MCA areas, in which CVRC are < -5.0%, revealed an AUC of 0.96 (95% confidence interval [CI], 0.91 to 0.99) and 0.96 (95% CI, 0.91 to 0.99, respectively).

Conclusions—
ASL can identify the reduced CVRC with good performance and has the potential as a noninvasive imaging tool for determining CVRC in patients with moyamoya disease. Table. Correlations between CBF and CVRI values from ASL and SPECT
Abstract TMP42: Treatment of Moyamoya Disease in the Adult Population with Pial Synangiosis
Authors: Lin Ning , Aronson Joshua P , Smith Edward R , Scott R. Michael
Published: March 2022

Introduction:
Surgical treatment of moyamoya disease in the adult population commonly employs direct revascularization, the superficial temporal artery to middle cerebral artery (STA-MCA) bypass. Pial synangiosis, a method of indirect revascularization, has been utilized in adult moyamoya patients when STA-MCA bypass is not technically feasible. Although the effectiveness of pial synangiosis has been well described in children, only limited reports have examined its role in adult moyamoya patients. Here we report on our experience with pial synangiosis revascularization for this population.

Methods:
We reviewed the clinical and radiographic records of all adult moyamoya patients (18 years of age or older), who underwent cerebral revascularization surgery using pial synangiosis at a single institution.

Results:
From 1985-2010, 66 procedures (6 unilateral, 30 bilateral) were performed on 36 adult moyamoya patients. The mean age at surgery was 28.3 (range: 19 - 51) and 30 were female. Thirty-one patients (86.1%) presented with either stroke or TIA and 3 (8.3%) with hemorrhage. Pre-operative Suzuki grade was III or higher in 50 hemispheres (75.7%) and 3 patients had prior treatments to the affected hemisphere before pial synangiosis surgery. Clinical follow-up was available for an average of 5.8 years (range 0.6-14.1 years), with 26 (72.2%) patients followed for longer than 2 years. Post-operative angiogram was available for 24 patients and 46 revascularized hemispheres, and 39 (84.8%) demonstrated good collateral formation (Matsushima grade A or B). Peri-operative complications included 3 strokes, 5 TIA’s, and 2 seizures, and there was no stroke or hemorrhage during the follow-up period. One patient required additional revascularization surgery 8 months after pial synangiosis.

Conclusions:
Pial synangiosis is a safe, effective, and durable method of cerebral revascularization in adult moyamoya patients. Our data supports the utilization of pial synangiosis as a treatment option for moyamoya disease in adults, particularly when STA-MCA bypass is not technically feasible.
Abstract TMP46: Self-reported Physical Activity Frequency and Risk of Incident Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: McDonnell Michelle N , Hillier Susan L , Hooker Steven P , Le Anh , Howard Virginia J
Published: March 2022

Background and Purpose:
Adherence to a healthy lifestyle is known to reduce stroke risk, and regular physical activity is an important recommendation for stroke prevention. We compared the associations of self-reported physical activity (PA) with incident stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Methods:
REGARDS recruited 30,239 US blacks (44%) and whites, aged 45 years or older in 2003 to 2007 who are being followed every 6 months for events. After excluding those with prior diagnosed stroke, this analysis involved 27,348 people. Participants reported their frequency of moderate-vigorous intensity PA at baseline according to three categories: none (physical inactivity), 1-3 times/week and ≥ 4 times/week. Stroke and TIA cases were identified and adjudicated during an average of 5.7 years of follow-up. Cox proportional hazards models were constructed to examine whether self-reported PA was associated with the risk of incident stroke.

Results:
Physical inactivity was reported by 33% of participants and was associated with a hazard ratio (HR) of 1.20 ([95% confidence intervals 1.02-1.42], p = 0.035). Adjustment for demographics (age, race, sex) and socioeconomic factors did not affect the HR, but further adjustment for traditional stroke risk factors (diabetes, hypertension, body mass index, alcohol use and smoking) completely attenuated this risk (HR 1.14 [0.95-1.37], p = 0.17). We examined the HR separately for men and women and found no significant association between PA frequency and risk of stroke although there was a trend towards increased risk for men reporting PA 0-3 times a week compared to 4 or more times a week.

Conclusions:
Self-reported low PA frequency is associated with increased risk of incident stroke. Any effect of PA is likely to be mediated through reduction of traditional risk factors such as hypertension, body mass index and diabetes.
Abstract TMP5: Preexisting Interleukin-10 In Susceptible Cerebral Arteries May Decrease Subsequent Brain Injury Caused By Ischemic/reperfusion
Authors: Liang Qiujun , Wang Xinhong , Meng Dan , Le Lili , Quan Jing , Xiang Meng , Chen Alex F , Chen Sifeng
Published: March 2022

Objective:
Recurrent stroke is common with no cure. Systemic interleukin-10 (IL-10) has cytoprotective effects for stroke but with significant side effect. Forced transduction of IL-10 gene in susceptible arteries achieved during interventional treatment management of the first stroke may increase local instead of systemic IL-10 in front and decrease brain damage of recurrent stroke.

Methods:
Recombinant adeno-associated viral vector 1 encoding rat IL-10 (rAAV1-IL-10), rAAV1-YFP, or saline were infused into left cerebral artery, respectively. Three weeks after, all animals were subjected to MCAO for 45min followed by reperfusion for 24h. ELISA and in situ hybridization using three DIG-labeled probes specific for rAAV1 backbone were performed to confirm the expression of IL-10. Neurologic dysfunction and infarct area were evaluated by neurological impaired use scores and TTC staining. Expressions of inflammatory mediators and endoplasmic reticulum stress proteins (ERP), including IL-1β, IL-10, TNF-α, MCP-1, MIP-1α, ICAM-1, TGF-β, VEGF, HO-1, ATF6 and CHOP, infarct boundary zone were measured by reverse transcription real time PCR.

Results:
Left cerebral artery of animals receiving rAAV1-IL-10 or rAAV1-YFP was stained positive for rAAV1 backbone. No positive staining was observed in animals perfused with PBS. The preexisting local IL-10 but not YFP decreased the neurological impaired use scores, infarct area and the number of injured neuronal cells. AAV1-IL-10 transduction decreased pro-inflammatory mediator TNF-α and increased intracellular protective protein HO-1. The increased expression of HO-1 was confirmed by Western blotting and immunohistochemical analysis. Other cytokines and ERP did not changed significantly.

Conclusion:
Preexisting IL-10 in susceptible cerebral arteries may decrease subsequent brain injury caused by ischemic/reperfusion through correcting pro-/anti-inflammatory balance and increasing intracellular protective proteins. Selective transduction of therapeutic gene in susceptible arteries during interventional stroke managements, such as thrombolysis and placing cerebrovascular stent, of the initial stroke is beneficial for recurrent stroke.
Abstract TMP51: A Validation Study of Recurrence Risk Estimator Score in Acute Ischemic Stroke
Authors: Kim Gyeong-Moon , Noh Hyun Jin , Kim Suk Jae , Lordelo Morgana deJesus , Oliveira Filho Jamary , Helenius Johanna , Ay Hakan
Published: March 2022

Background and Objectives:
The Recurrence Risk Estimator (RRE) is a web-based prognostic score that integrates clinical and imaging information available in the acute setting to quantify early risk of recurrent stroke. The score has been reported to have adequate calibration and good discrimination in the original derivation cohort (AUC=0.81, 95% confidence interval [CI] 0.76-0.87). In the present study, we sought to investigate the validity of RRE score in internal and external datasets.

Methods:
Internal validation was performed in a prospectively collected dataset from 899 consecutive patients admitted to the Massachusetts General Hospital. External validation was performed in a retrospective stroke cohort of 711 patients from 2 teaching hospitals in Brazil and South Korea. The RRE-90 score was calculated by summing up the number of independent predictors weighted by their corresponding beta-coefficients. (Available at: http://www.nmr.mgh.harvard.edu/RRE-90). We assessed the score’s predictive performance by computing the area under the receiver operating characteristic curve (AUC).

Results:
Internal and external validation cohorts differed from each other as well as from the original derivation cohort in age, gender, admission NIH stroke scale score, stroke risk factors, and etiologic stroke subtypes. Stroke recurrence rate during the 90-day follow-up period was 6.5% and 2.7% in the internal and external cohorts respectively. The AUC was 0.76 (95% CI 0.68-0.83) in the internal and 0.75 (95% CI 0.66-0.85) in the external validation cohort.

Conclusions:
RRE score performs well in independent cohorts with different baseline patient characteristics and stroke features. As a reliable, valid, and easy-to-use web-based tool, RRE may find widespread utility in identifying high- and low-risk patients for targeted stroke prevention.
Abstract TMP52: The Role of Non-sustained Short Lasting Runs of Supraventricular Tachycardia and Atrial Fibrillation as a Causative Factor in Ischemic Stroke
Authors: Arsava Ethem Murat , Atalar Enver , Oguz Kader Karli , Topcuoglu Mehmet Akif
Published: March 2022

Background:
The widespread use of ambulatory cardiac monitoring has not only increased the detection rate of chronic or paroxysmal atrial fibrillation (AF), but also made it possible to identify other aberrations such as short lasting (<30 secs) irregular runs of non-sustained supraventricular tachycardia (NS-SVT). Despite their resemblance to AF, these rhythms cannot be classified as paroxysmal AF due to their non-sustained nature. Furthermore, it is currently unclear whether they play a similar role in stroke pathophysiology like their chronic and paroxysmal counterparts. In this study, we determined prevalence of NS-SVT/AF in various subtypes of ischemic stroke and compared imaging features associated with these arrhythmias to imaging findings in chronic AF.

Methods:
This was a retrospective analysis of ischemic stroke patients admitted to a tertiary care center over 2 years. SVTs lasting <30 secs with an irregular RR interval on 24 hour holter were classified as NS-SVT/AF. MRI and angiographic features suggestive of embolism were determined in all patients. Statistical analyses were performed to compare clinical characteristics of patients with and without NS-SVT/AF. Imaging data was analyzed for prevalence of embolic patterns in patients with NS-SVT/AF and chronic AF.

Results:
The study population consisted of 370 patients. Patients with NS-SVT/AF (n=89) were older (p<0.01), more likely to be female (p=0.03) and had more commonly a history of hypertension (p=0.02). The distribution of stroke subtypes and specifically the prevalence of cryptogenic strokes did not significantly differ among both groups (p=0.15 and p=0.53, respectively). Patients with cryptogenic stroke and NS-SVT/AF had less commonly chronic embolic lesions (p=0.03) and angiographic evidence of abrupt-cut off or recanalization (p=0.09) compared to patients with chronic AF.

Conclusions:
The clinical characteristics of patients with NS-SVT/AF differ from patients without these arrhythmias, yet prevalence of NS-SVT/AF is similar among various stroke subtypes. More importantly, imaging characteristics do not entirely resemble patterns observed in patients with chronic AF. Further studies are needed to clarify the role of NS-SVT/AF in ischemic stroke.
Abstract TMP54: Chronic Kidney Disease Does Not Influence Outcome After Acute Stroke
Authors: Lees Jennifer S , Graham Catriona , Turner Neil ,   The Virtual International Stroke Trials Archive Collaboration
Published: March 2022

Background:
Chronic kidney disease (CKD) is a risk factor for development of cardiovascular disease. Limited data describe the association between CKD and outcome following stroke, with contradictory results. One report has suggested that CKD may adversely affect outcome after thrombolysis, but was uncontrolled. We investigated the hypothesis that CKD adversely influences outcome following acute stroke and particularly after treatment with thrombolysis.

Methods:
We extracted patient information from the Virtual International Stroke Trials Archive, including age, baseline severity, co-morbidities (diabetes and hypertension) and baseline serum creatinine. We estimated glomerular filtration rate (GFR) using the Modified Diet in Renal Disease equation. We used ordinal logistic regression to calculate odds ratios of poor outcome by modified Rankin Scale at 90 days comparing patients with normal versus abnormal renal function (GFR >90ml/min and <90ml/min respectively) as well as considering GFR as a continuous variable.

Results:
Of 8605 patients with appropriate baseline data for analysis, those with normal renal function were younger [median (IQR): 64.0 (13.6) v. 71.7 (11.3) years respectively] but had comparable baseline severity [median NIHSS: 13.1 (5.6) v. 13.4 (5.8)]. When adjusted for age, baseline severity, stroke type, thrombolysis, diabetes and hypertension, there was no impact of GFR on outcome, neither in normal versus abnormal renal function (OR 1.00, 95% CI 0.92-1.09), nor with GFR expressed as a continuous variable (OR 1.007 per 10 ml/min, 95% CI 0.992-1.022). Outcomes in n=2594 after thrombolysis were unaffected by renal function.

Conclusion:
CKD does not independently influence outcome following acute stroke, nor does it limit response to thrombolysis. Management of acute stroke need not differ in patients with CKD.
Abstract TMP57: Disabling Stroke is Uncommon After An Emergency Department Evaluation and Discharge for Dizziness Symptoms
Authors: Kim Anthony S , Klingman Jeffrey G , Sidney Stephen , Johnston S. Claiborne
Published: March 2022

Background:
Given the general concern about stroke among emergency department (ED) patients with dizziness, we sought to evaluate the short-term outcomes in these patients.

Methods:
We conducted a nested-case control study within a cohort of all adults who presented during 1 year to 19 EDs of a large Northern California integrated health program with a primary complaint of dizziness. Cases were defined as patients with an ischemic or hemorrhagic stroke within 90 days of the index ED visit based on a review of comprehensive medical records. Controls were randomly-selected from among the remaining cohort. A vascular neurologist adjudicated the stroke or stroke-free status of cases and controls. Disabling stroke was defined as stroke requiring inpatient rehabilitation or skilled nursing care. Descriptive statistics were based on the sampling fraction of the entire cohort.

Results:
Among 9,731 patients with a primary complaint of dizziness, 145 (1.5%, 95% CI 1.3%-1.8%) patients were diagnosed with a new stroke. Most were diagnosed with stroke within two days and all new strokes were diagnosed within 10 days of the initial ED visit. Mean age for cases was 69.1 y compared to 63.5 y for controls (t-test, p<0.01). Most cases were already on an antithrombotic (112, 77%) or a statin (100, 74%) prior to the ED visit. Six cases (0.1% overall) had a fatal stroke and 24 cases (0.4% overall) had a disabling stroke, while 115 (1.8% overall) had non-disabling strokes and were well enough to be discharged home directly from the ED or after a brief inpatient stay (median 3 d [IQR 2-4 d]). Nearly all (11/12) of the patients that had initially been discharged home directly from the ED and that were later hospitalized for stroke were subsequently discharged home; one patient who had been diagnosed with a stroke in the initial ED, returned 4 days later to be placed into an inpatient rehabilitation facility.

Conclusion:
Although ED patients with dizziness can develop disabling or fatal strokes, the vast majority of these strokes are recognized in the emergency department or during the subsequent hospitalization. Delayed recognition of stroke appears to be uncommon among dizzy patients evaluated in the emergency department and discharged home and seldom results in a disabling stroke.
Abstract TMP67: Microglia Transplantation Reduces Stroke Injury
Authors: Shimizu Takeru , Mader Sarah , Koerner Ines P
Published: March 2022

Microglia are activated after stroke and may contribute to ischemic brain injury by producing mediators such as inflammatory cytokines and free radicals that are toxic to neurons. Microglia are also likely responsible for the influx of peripheral immune cells after stroke, which further exacerbate injury. In contrast, there is increasing evidence that microglia can also be protective, as ablating microglia before stroke increases infarct size (1) and arterial injection of microglia during global ischemia reduces neuronal death (2). We tested whether increasing the number of resident microglia by transplantation would convey protection from ischemic stroke.

We injected 20,000 primary cultured microglia into the striatum of adult male C57Bl/6 mice. Control groups were injected with a similar number of cultured astrocytes or received no injection. Additional mice were injected with eGFP expressing microglia to allow visualization of transplanted cells. After 14 days recovery, mice underwent 60 minutes of transient middle cerebral artery occlusion. Cerebral blood flow was monitored by laser Doppler. Infarct size was measured by TTC staining 24 hours after reperfusion and expressed as % of contralateral structure.

Transplanted microglia survived and were present in the striatum 14 days after the injection. Infarct size was significantly reduced by microglia transplantation, both in the infarct core (striatum, 69% vs. 80% control) as well as the penumbra (cortex, 42% vs. 52%, P<0.05). Transplantation of astrocytes, in contrast, had no effect on infarct size. Cerebral blood flow was not different between groups.

The number of resident microglia in mouse brain can be increased by transplantation of microglia, which survive for several weeks after injection. Infarct size is reduced after transplantation of microglia. This is likely caused by increased microglial production of neuroprotective and anti-inflammatory mediators after stroke, such as insulin-like growth factor (1) or interleukin-10. Further studies will identify the microglial mediators that are responsible for the observed protection. They may offer new therapeutic options to reduce injury after stroke.

Lalancette-Hebert et al. J Neuroscience 2007

Imai et al. JCBFM 2007
Abstract TMP7: Acute Stroke Involving More Than 1/3 Mca Territory On Plain Ct Brain Is Not A Contraindication For Iv Thrombolysis.
Authors: yeo leonard L , dalakoti mayank , Ahmad Aftab , wakerley benjamin , paliwal prakash , ng kay , Ong Jonathan , kusuma yohanna , rathakrishnan rahul , hock luen teoh , chan bernard , seet raymond , sharma vijay
Published: March 2022

Background and Purpose:
Intravenously administered tissue plasminogen activator (IV- tPA) remains the only approved therapeutic agent to achieve arterial recanalization in acute ischemic stroke (AIS). Involvement of more than one-third of middle cerebral artery (MCA) territory on initial brain CT is a relative contraindication for IV-tPA and often associated with poor functional outcome at 3 months. We present the results of IV-thrombolysis among these patients at our tertiary center.

Methods:
Data for consecutive stroke patients treated with IV-tPA within 4.5 hours of symptom onset were retrospectively analyzed. Data was collected for demographic characteristics, vascular risk factors, National Institute of Health Stroke Scale (NIHSS) scores, and blood pressure levels before IV-tPA bolus. The presence of early stroke signs involving more than one-third of the MCA on the initial CT scan was measured by Alberta Stroke Program Early CT score (ASPECTS <8). Outcomes were assessed by modified Rankin Scale (mRS) score at 3 months.

Results:
A total of 97 AIS patients with more than one-third MCA involvement received IV-tPA during the study period. Median age was 70 yrs (range 38-89), 54% male, median NIHSS score 20 points (range 3-30) and median onset-to-treatment time 152 minutes (range ). Forty-two (43.5%) patients achieved good functional outcomes at 3 months (mRS score 0-1). The factors associated with good outcome at 3 months on univariate analysis were younger age and lower NIHSS score at presentation. After multivariate analysis, lower NIHSS scores at presentation was noted as the only independent predictor of good outcome at 3 months (OR 0.918 95%CI 0.880 - 0.958 p=0.001. 1/3 MCA involvement on the initial CT scan (ASPECTS <8) was not significantly associated with a poorer functional outcome at 3 months (OR 1.495 95% CI 0.881-2.540; p=0.136).

Conclusions:
Patients with acute stroke involving more than one-third of the MCA on initial brain CT scan, especially if associated with lower NIHSS score, should not be excluded from systemic thrombolysis.
Abstract TMP70: Reduced Hippocampal Synapses Underlie Loss of Long-Term Potentiation after Experimental Subarachnoid Hemorrhage
Authors: Han Sang Myung , Wan Hoyee , Tariq Asma , Ai Jinglu , Macdonald Robert L
Published: March 2022

Background:
Patients who survive aneurysmal subarachnoid hemorrhage (SAH) often have deficits in learning, memory and executive function, although structural brain damage may not be detectable. We previously reported that rodents with SAH develop cognitive deficits and loss of long-term potentiation (LTP), a probable electrophysiological correlate of learning and memory. We hypothesize that loss of LTP may be caused by diminished synapses and/or dysfunction of synaptic molecules responsible for LTP, and that this occurs without neuronal death.

Methods:
SAH was created by injection of 300 μl of fresh, unheparinized arterial blood into the prechiasmatic cistern of Sprague-Dawley rats (300-350g). Controls were injected with the same amount of saline. Cell death was detected with Fluoro-jade B and TUNEL staining. The number of synapses in dendritic layer of CA1 was quantified by double immunohistochemical staining of MAP2 and synaptophysin, or directly by transmission electron microscopy. Glutamate receptor subunits (GluR1/2) and CaM kinase II were quantified by immunohistochemical staining. Superoxide and nitric oxide (NO) concentrations in freshly homogenized hippocampal tissues were detected by spectrophotometry with DAF-2DA and MCLA dyes.

Results:
In the dendritic area of CA1, the number of synapses was significantly decreased after SAH compared to controls (54±4/image for SAH, 74±3 for controls, p<0.001). Similarly, the expression of GluR1, GluR2 and CaM kinase II was decreased in SAH rats. Decreased superoxide (0.038±0.006 for SAH, 0.059±0.01 for control p<0.001) but increased NO was detected in rats with SAH as compared to controls (1251±118 for SAH, 518±118 for controls, p<0.001). Fluoro-jade B and TUNEL staining disclosed no to minimal CA1 cell death.

Conclusions:
Loss of LTP after SAH in rats may be due to a synaptic plasticity rather than cell death. Decreased immunoreactivity to GluR1, GluR2 and CaM kinase II suggests reduction in key proteins that mediator LTP may also contribute. Decreased superoxide and increased NO suggest oxidative stress is involved in the loss of LTP.
Abstract TMP73: Factors Associated with Length of Hospitalization in Patients Admitted with Transient Ischemic attack
Authors: Qureshi Adnan I , Adil Malik M , Zacharatos Haralabos , Suri M Fareed K
Published: March 2022

Background:
Approximately 70% of all patients presenting with transient ischemic attack (TIA) are admitted to the hospital in United States. The duration and cost of hospitalization and associated factors are poorly understood. We performed this analysis to identify the proportion and determinants of prolonged hospitalization and to determine the impact on hospital charges using nationally representative data.

Methods:
We determined the national estimates of length of stay, mortality, and charges incurred in patients admitted with TIA (Diagnosis related code 524) using Nationwide Inpatient Survey (NIS) data from 2002 to 2010. NIS is the largest all-payer inpatient care database in the United States and contains data from 986 hospitals approximating a 20-percent stratified sample of U.S. community hospitals. All the variables pertaining to hospitalization were compared in three groups based on length of hospital stay (<1 day, 2-6 days, and ≥7 days).

Results:
A total of 949,558 patients were admitted with the diagnosis of TIA during the study period. The length of hospitalization was <1 day, 2-6 days, and ≥7 days in 232732 (24.4%), 662909 (70) %), and 53917 (5.6%) patients respectively. The mean hospitalization charges (95% confidence interval) were $ 8,348 (8123-8572), $14,471(14030-14911), and $34,035 (32280-35790) for patients hospitalized for <1 day, 2-6 days, and ≥7 days, respectively. The rates of atrial fibrillation (8.3%, 13.1%, and 22.6%, p<.0001), congestive heart failure (1.1%, 1.9%, and 3.7%, p<.0001), chronic lung disease (11.4%, 14.7%, and 20.0%, p<.0001), coagulopathy (0.8%, 1.3%, and 2.7%, p<.0001) and renal failure (3.1%, 5.1%, and 11.7%, p<.0001) were associated with length of hospitalization. The use of thrombolytics (0.03%, 0.09%, and 0.1%, p<.0001) for ischemic stroke was very low among the three strata defined by length of hospitalization.

Conclusions:
Approximately 75% of patients admitted with TIA stay in the hospital for 2 or more days with the most important determinants being pre-existing medical co-morbidities. Longer duration of hospital stay is associated with 2-5 fold greater hospitalization cost.
Abstract TMP75: Atrial Fibrillation In Ischemic Stroke: Predicting Response To Thrombolysis And Clinical Outcomes
Authors: Saposnik Gustavo , Gladstone David , Raptis Stavroula , Zhou Limei , Hart Robert G ,   on behalf of the Registry of the Canadian Stroke network (RCSN),   for the Stroke Outcomes research canada (SORCan) Working group
Published: March 2022

Background:
Atrial fibrillation (AF) increases the risk of stroke and is associated with poorer stroke outcomes. Few tools are available to evaluate clinical outcomes and response to thrombolysis in stroke patients with AF.

Methods:
We applied the iScore (
www.sorcan.ca/iscore
), a validated risk score, to consecutive patients with an acute ischemic stroke participating in the RCSN. The main outcome was the proportion of patients with a favorable outcome (defined as a modified Rankin scale 0-2) at discharge after thrombolysis. Secondary outcomes included death at 30-days and at 1-year stratified by terciles of the iScore.

Results:
Among 12,686 patients with an acute ischemic stroke, 2,185 (17.2%) had AF. Among patients in the highest iScore tercile, those with AF had higher mortality at 30 days (34.7% vs.28.2%; p<.001) and at 1-year (53.6% vs.45.0%; p3) at discharge (RR 1.26, 95%CI 1.18-1.33; Figure 1) and an increased risk of intracranial hemorrhage (any type) (16.5% vs. 13.1%; RR 1.42, 95%CI 1.05-1.91) after thrombolysis. In the Poisson regression analysis, the benefit of tPA declined more rapidly at lower iScore values among AF patients than for others (p-value for interaction <0.001; Figure 2).

Conclusion:
The iScore predicted a differential response after tPA between patients with and without AF. Stroke patients with AF have higher mortality, greater risk of ICH, and reduced response to thrombolysis compared with non-AF patients for a given high iScore.

Figure 1

Figure 2
Abstract TMP78: Do Hospital Complications Justify Excluding Elderly Patients from Stroke Clinical Trials?
Authors: Guerrero Waldo R , Vahidy Farhaan , Pandurengan Renganayaki , Peng Hui , Wu Tzu-Ching , Savitz Sean I
Published: March 2022

Background and Objectives:
There is a paucity of data from recent trials analyzing outcomes and hospital complications in octogenarians after acute ischemic stroke (AIS). Stroke trials often set an arbitrary upper age limit (usually age 80) as an inclusion criterion. We hypothesized that based on hospital complication rates and outcome, age ≥80 does not justify exclusion from clinical trials testing new AIS therapies.

Methods:
From our prospectively compiled stroke registry, we identified AIS patients older than 50 from January 1, 2007 to March 30, 2012. Patients were excluded if they 1) had a baseline mRS >2, 2) received intra-arterial therapy, or 3) were enrolled in a trial. Demographic and clinical data were analyzed in patients ≥80 and 50-79 to determine if age ≥80 raises the odds for hospital complications and worse outcomes.

Results:
We identified 526 patients ≥80 and 1572 aged 50-79. Compared with their younger counterparts, patients ≥80 had a higher incidence of vascular risk factors, higher NIHSS scores, higher IV tPA rates, and a 1.3 times higher odds (95% confidence interval 1.01 - 1.7) of developing in-hospital complications, after controlling for all co-variates (including NIHSS, t-PA, vascular risk factors). However, higher complication rates appeared to be driven by UTIs. A stratified analysis of age cutoffs at 5 year intervals for all complications other than UTI did not show that ages 85 and above have significantly higher odds of complications as compared to those aged 50-74. Older patients had higher odds (OR 2.11 95% CI 1.34 - 3.31) of a poor outcome at 90 days (mRS >2) compared with younger patients, after adjusting for co-variates.

Conclusion:
Age ≥80 is a predictor of in-hospital complications but only the rates of UTI were significantly higher. These findings support re-considering age >80 as an exclusion from participating in clinical trials testing new AIS therapies. The higher odds for poor outcome also raise the need to design therapies for patients ≥80.