bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2378: Right Hemisphere Ischemia is Overrepresented in Patients with Poor Outcomes After tPA is Not Given Because of “Rapidly Improving or Mild Symptoms”
Authors: Hermann Lisa D , Cronin Carolyn A
Published: July 2021

Background and Purpose:
Recombinant tissue-type plasminogen activator (tPA) is currently the only FDA approved treatment for acute ischemic stroke. Rapidly improving or minor symptoms is the most common reason for not treating with tPA, based on the presumption that these patients will have good outcomes without thrombolysis. We reviewed hospital course and discharge outcomes for patients excluded from tPA because of rapidly improving or mild symptoms, with the aim of being better able to identify patients in this group who may benefit from thrombolysis.

Methods:
We used the AHA/ASA “Get with the Guidelines” database to identify consecutive patients between April 2006 and June 2010 from our tertiary care academic medical center who did not receive tPA with “rapidly improving or mild symptoms” indicated as the reason for exclusion. Poor outcome was defined as hospital discharge to location other than home or inability to ambulate independently at discharge. The medical record was reviewed to determine details of hospital course, infarct location, and reasons for poor outcome.

Results:
There were 66 patients excluded from tPA treatment because of rapidly improving or mild symptoms. Eleven patients (16.7%) had poor outcomes. In 6 patients (9%), poor outcome was due to neurologic deficit and in 5 poor outcome was secondary to general medical conditions or deconditioning. Of the 6 patients with continued neurologic deficit, 4 were not treated due to “improvement”. All 6 patients with continued neurologic deficits had right hemisphere strokes, and one also had cerebellar infarcts.

Conclusions:
Patients presenting with rapidly improving or mild symptoms do not universally have good outcomes. This may be particularly true in the case of right hemispheric ischemia where deficits are not fully reflected by NIHSS score. In conclusion, if a patient with a low NIHSS score is otherwise a candidate for tPA, a more detailed exam is warranted to better identify potentially disabling deficits that would be an indication for thrombolysis.
Abstract 2383: The Antiplatelet Effect Of Clopidogrel Is Associated With CYP2C19 *2 And *3 Polymorphism But Not With Pon-1 Q192R Polymorphism In Japanese Patients Undergoing neurointervention
Authors: Matsumoto Shoji , Nakahara Ichiro , Kakumoto Kousuke , Motomura Kyoko , Ainiding Gulibahaer , Watanabe Yoshihiko , Fukushima Yutaka , Urabe Yoshikiyo , Ishibashi Ryota , Gomi Masanori , Tsuji Keiichi , Sanbongi Yoshinori , Hashimoto Tetsuya , Tanaka Yujiro , Torii Takako , Furuta Konosuke , Nakagaki Hideaki , Okura Akira , Hirohata Masaru , Yamada Takeshi , Kira Jun-ichi
Published: July 2021

Background
Patients with cervical carotid or intracranial stenting are routinely premedicated with antithrombotic agents, clopidogrel and aspirin (ASA). A recent study has showed paraoxonase-1 (PON-1) Q192R genotypes impacts on antiplatlet effect of clopidogrel rather than CYP2C19 mutation. We investigate the influence of CYP2C19 *2, *3, and PON-1 Q192R genotypes on antiplatelet effect of clopidogrel in Japanese patients scheduled for neurointervention such as extracranial carotid artery stenting, intracranial artery stenting, or coil embolization of the cerebral aneurysm.

Method
A total of 102 consecutive patients scheduled for neurointervention and treated with ASA and clopidogrel were enrolled. Genotyping of three single-nucleotide polymorphisms (SNPs) defining the two major CYP2C19 alleles *2, *3 and PON-1 Q192R was performed with the use of TaqMan® SNP Genotyping Assays (Applied Biosystems, CA) from stored DNA. Antiplatlet effect of clopidogrel was assessed by VerifyNow P2Y12 assay.

Result
The frequencies of CYP2C19 *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3 were 28 (27.5%), 39 (38.2%), 13 (12.7%), 9 (8.8%), 11 (10.8%), and 2 (2.0%), respectively. On the basis of CYP2C19 genotype, 28 patients (27.5%) were classified as an extensive metabolizer (EM), 52 (51.0%) as an intermediate metabolizer (IM) and 22 (21.6%) as a poor metabolizer (PM). The proportion of patients harboring CYP2C19 loss of function SNPs is 72.5%. The frequencies of PON-1 QQ192, QR192, and RR192 were 8 (7.8%), 52 (51.0%), and 42 (41.2%), respectively. P2Y12 reaction unit (PRU) in the VerifyNow P2Y12 assay was significantly higher in patients with CYP2C19 loss of function SNPs than those without (253.6±100.2 vs. 161.3±85.5, P<0.001). However, the PRU in patients with QR192 or RR192 were not significantly different from those with QQ192 ( 227.0±128.1 vs. 228.8±103.0, P=0.973).

Conclusion:
In Japanese patients undergoing neurointervention, antiplatlet effect of clopidogrel was associated with CYP2C19 genotype *2and *3 but not with PON-1 Q192R genotype.
Abstract 2386: Microembolic Signals in Acute Posterior Circulation Cerebral Ischemia: Sources and Consequences
Authors: Hwang Jaechun , Kim Suk Jae , Bang Oh Young , Kim Gyeong-Moon
Published: July 2021

Background:
The clinical significance of microembolic signals (MESs) in posterior circulation remains unclear. The aim of this study was to investigate the sources and consequences of MESs in acute posterior circulation cerebral ischemia.

Methods:
We evaluated a total of 140 consecutive patients (93 males, mean age 62.9 years) who had acute posterior circulation cerebral ischemia. The MES monitoring was conducted at the basilar artery through the suboccipital window during 30 minutes.

Results:
Microembolic signals were detected in 18 (12.9%) of the 140 patients. Clinical characteristics and laboratory data did not differ between the MES-positive and MES-negative groups. Intracranial vertebrobasilar artery (VBA) stenosis was independently associated with the presence of MES (OR: 9.37, 95% CI: 1.14-79.92, p =0.037), while the patients whose vertebral artery stenosis was limited at the extracranial portion did not show a significant difference. Microembolic signals occurred significantly more frequently in patients with a severe degree of VBA stenosis compared to those with non-significant stenosis (OR: 9.81, 95% CI: 1.21-79.87; p =0.033). In a subgroup analysis of the 79 patients who had lesions on diffusion-weighted images and relevant VBA stenosis, the MES-positive group showed more frequent embolic infarction (p=0.010) and multiple lesion patterns (p=0.007) than they did single perforating infarctions.

Conclusions:
In acute posterior circulation cerebral ischemia, intracranial and severe VBA stenosis is associated with MES and could be its root cause; the presence of MES in VBA stenosis may suggest multiple and embolic type infarctions as the stroke mechanism
Abstract 2412: Intraoperative Dual Monitoring during Carotid Endarterectomy Using Motor Evoked Potential and Near-infrared Spectroscopy
Authors: Uchino Haruto , Nakamura Toshitaka , Kuroda Satoshi , Houkin Kiyohiro , Murata Jun-ichi , Saito Hisatoshi
Published: July 2021

Objective:
Carotid endarterectomy (CEA) is a useful procedure to prevent subsequent ischemic stroke in patients with severe stenosis of internal carotid artery. However, lowering of morbidity is still essential to keep its clinical significance. This study aimed to evaluate the validity of dual monitoring using transcranial motor evoked potential (MEP) and near-infrared spectroscopy (NIRS) during CEA.

Methods:
Transcranial MEP and NIRS monitoring were conducted in 20 consecutive CEA. MEP was recorded in the contralateral extremities. Regional cerebral saturation of oxygen (rSO2) was continuously measured in the ipsilateral forehead. The changes of MEP amplitudes and rSO2 during cross-clamping of carotid artery were compared in each case.

Results:
The amplitudes of MEP significantly decreased when rSO2 reduced to more than 20% during carotid clamping. There was a significant correlation between the changes of MEP amplitude and rSO2 during carotid clamping in a quadratic manner (P<.001, r=0.821). However, NIRS could not detect critical cerebral ischemia in one patient with cerebral infarction in the ipsilateral frontal lobe. On the other hand, MEP could not identify it in one patient with severe motor deficit. No perioperative complication occurred.

Conclusion:
These findings strongly suggest that both MEP and NIRS can detect critical cerebral ischemia during CEA in most of patients. Dual MEP and NIRS monitoring may further increase the sensitivity to identify it, being valuable to prevent perioperative complications due to cerebral ischemia during CEA.
Abstract 2413: Postoperative Cerebral Hyperperfusion after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis and Indirect Synangiosis in Moyamoya Disease: PET and SPECT Study
Authors: Uchino Haruto , Kuroda Satoshi , Nakayama Naoki , Houkin Kiyohiro
Published: July 2021

Background
Postoperative cerebral hyperperfusion is known to occur after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and indirect synangiosis in moyamoya disease. However, the clinical features and pathophysiology still remain to be elucidated.

Objective
To clarify the incidence and pathogenesis of postoperative hyperperfusion after surgical revascularization for moyamoya disease.

Methods
This study included 41 consecutive patients (58 surgeries) who underwent STA-MCA anastomosis and indirect synangiosis for moyamoya disease. Their medical records were evaluated to identify clinical features of postoperative hyperperfusion. Using 15O-gas positron emission tomography (PET), cerebral hemodynamics and metabolism were determined before surgery in all patients. Using 123I-IMP single photon emission computed tomography (SPECT), cerebral blood flow was qualitatively measured on Day 0, 2, and 7 after surgery in all patients. A multivariate logistic regression analysis was conducted to identify the predictors for postoperative hyperperfusion.

Results
Postoperative hyperperfusion was observed in 29 (50.0%) of 58 operated sides. In pediatric patients, it was quite rare. Thus, symptomatic and asymptomatic hyperperfusion occurred in 1 (5%) and 3 (15%) of 20 sides, respectively. In adult cases, however, symptomatic and asymptomatic hyperperfusion were significantly more often (P=0.0037 and P=0.026, respectively) and were noted in 12 (31.5%) and 13 (34.2%) of 38 sides, respectively. A logistic regression analysis revealed that cerebral blood volume (CBV) increase before surgery was a significant predictors for symptomatic hyperperfusion in adults (P=0.036). Furthermore, hyperperfusion immediately after surgery was at significantly higher risk to be symptomatic (7/9=77.7%, P=0.033).

Conclusions
Postoperative hyperperfusion after STA-MCA anastomosis in adult moyamoya disease is not rare. Preoperative CBV increase was closely related to the occurrence of symptomatic hyperperfusion in adult cases. Hyperperfusion immediately after surgery may easily cause neurological deficits or other symptoms. Precise evaluation of cerebral hemodynamics and metabolism before and after surgery would be valuable to predict postoperative hyperperfusion and prevent perioperative complications.
Abstract 2426: A Stroke Campaign of Act FAST for Junior High School Students and Their Parents
Authors: Amano Tatsuo , Yokota Chiaki , Sakamoto Yuki , Shigehatake Yuya , Inoue Yasuteru , Ishigami Akiko , Hagihara Takaaki , Miyashita Fumio , Toyoda Kazunori , Minematsu Kazuo
Published: July 2021

Background and purpose:
Early recognition of stroke signs and symptoms is essential for emergent treatment and improvement of clinical outcomes. We examined efficacy of a stroke education program for junior high school students and their parents.

Methods:
From February 2010 to May 2011, 349 students in 11 classes of the 1
st
grade of 3 junior high schools (12 - 13 years old) and their parents were enrolled. The subjects were divided into 2 groups; an intervention group (6 classes, 190 students) and a control group (5 classes, 159 students). Students in the intervention group received a 45-minutes lesson on stroke signs and symptoms, the FAST message (Facial droop, Arm weakness, Speech disturbance, Time to call 119), and stroke risk factors. School items consisting of a pen, file, magnet, sticky note with the FAST message, and stroke pamphlets were also distributed to students in the intervention group. Parents of the intervention group were educated indirectly through the stroke pamphlets and items. For all subjects, questionnaires on stroke knowledge were examined at the baseline, immediate post-lesson time and 3-month after the stroke lesson.

Results:
Percentages of correct answers were not significantly different between the 2 students groups at the baseline. Three-months after the stroke lesson, students in the intervention group answered more correctly than the control group in the questions of facial palsy (97% in the intervention group vs. 54% in the control group; P<0.001), speech disturbance (98% vs. 67%; P<0.001), hemiplegia (80% vs. 63%; P<0.001), calling 119 for stroke (88% vs. 57%; P<0.001), alcohol drinking (85% vs. 65%; P<0.001), smoking (70% vs. 51%; P<0.001), hypertension (81% vs. 68%; P=0.004) and the FAST message (96% vs. 10%; P<0.001). Parents of the intervention group also answered more correctly in the question of facial palsy (93% vs. 80%; P=0.001), speech disturbance (95% vs. 86%; P=0.008), hemiplegia (87% vs. 78%; P=0.032), calling 119 for stroke (95% vs. 85%; P=0.004), arrhythmia (31% vs. 19%; P=0.016), and the FAST message (78% vs. 26%; P<0.001) than those of the control group 3 month after the stroke lesson.

Conclusions:
The stroke education program for junior high school students and their parents improved their stroke knowledge, especially of the FAST message.
Abstract 2435: Validation of the 12-Item Stroke-Specific Quality of Life Scale in a Bi-ethnic Stroke Population
Authors: Kerber Kevin A , Brown Devin L , Skolarus Lesli E , Morgenstern Lewis B , Smith Melinda A , Garcia Nelda M , Lisabeth Lynda D
Published: July 2021

Background and Purpose:
The 12-item Stroke-Specific Quality of Life Scale (SSQOL), a shortened version of the original SSQOL, was recently developed in a mixed cerebrovascular disorders population from the Netherlands. Lacking, however, are validation studies of the shortened version specifically in ischemic stroke patients alone and in those from other race-ethnic backgrounds. We aimed to assess the validity of this scale in a bi-ethnic ischemic stroke population.

Methods:
From an on-going population-based study, the Brain Attack Surveillance in Corpus Christi (BASIC) Project, validated ischemic stroke patients who completed the 49-item SSQOL at 90 days post-stroke were identified. Cronbach’s alpha was used to assess internal consistency of the 49- and 12-item scales. An intraclass correlation coefficient (ICC) and linear regression model were used to assess agreement between the two scales and the variance of the 49-item SSQOL explained by the 12-item SSQOL subscale. The Bland-Altman “differences against the mean” plot was used to assess for bias in the 12-item scale across the range of scores.

Results:
Of the 46 ischemic stroke patients, the mean age was 66.3 years (SD, 11.4). Fifty-four percent were female and 52% were Mexican American. The mean score of the 49-tem scale was 3.35 (SD, 0.85) compared with 3.34 (SD, 0.96) from the 12-item scale. Internal consistency was very high for both the 49-item scale (α = 0.96) and the 12-item scale (α = 0.88). More than 96% of the variance in the 49-item scale was explained by the 12-item scale (ICC, 0.98; R
2
, 0.97). The Bland Altman plot revealed that the 12-item scale scores were slightly higher than 49-item scores at high mean scores and slightly lower at low mean scores (
Figure
).

Conclusions:
This study in ischemic stroke patients from diverse race-ethnic backgrounds found that the more efficient 12-item SSQOL is a valid alternative to the full scale for the assessment of health-related quality of life.

Figure.

Bland-Altman plot of the differences between the 49-item Stroke Specific Quality of Life (SSQOL) scale and the 12-item SSQOL. Each circle represents an individual patient. The x-axis is computed as the average of the 49-item and 12-item scores, and the y-axis is the difference between the 49-item and 12-item scores. The dashed horizontal line represents the mean difference and the shaded region represents the mean difference ± 2 standard deviations.
Abstract 2457: Atrial Fibrillation is Associated with Severe Sleep Disordered Breathing TIA and Stroke Patients
Authors: Shibazaki Kensaku , Kimura Kazumi , Uemura Junichi , Sakai Kenichiro , Fuii Shuichi
Published: July 2021

Background and Purpose
Sleep disordered breathing (SBD) was reported to be a risk factor for cerebrovascular disease. We investigated the frequency of SDB in Japanese patients with acute transient ischemic attack (TIA) and stroke and the factors associated with severe SDB in Japan.

Methods
Between May 2010 and April 2011, we prospectively enrolled TIA and stroke patients within 24 hours of onset and performed sleep study up to 7 days after admission. SBD was defined as respiratory disturbance index (RDI: apnea or hypopnea event per hour) ≥5. Patients were divided into 2 groups according to the RDI value as follows: ≥30(severe) and <30(none or non-severe). We demonstrated the frequency of SDB and the factors associated with severe SDB were investigated by multivariate regression analysis.

Results
A total of 150 patients (92 males; mean age, 72.8 years) were enrolled in this study; 28 had TIA and 122 had stroke. The mean time from admission to sleep study was 4 days. Mean RDI was 22.2±17.6. SDB was observed in 126(84%) patients. Frequencies of SDB were as follows: 21(75%) patients in TIA, 105(86%) in stroke [8/10(80%) in large artery atherosclerosis, 14/14(100%) in small vessel occlusion, 37/41(90%) in cardioembolism, 46/57(81%) in other cause of stroke/undetermined]. Severe SDB was observed in 44 (29%) patients; 21% in TIA and 31% in stroke. Frequencies of male (75% for the severe SDB group vs. 56% for the non-severe SDB group, p=0.027), atrial fibrillation (39% vs. 23%, p=0.045), body mass index (23.8±3.8 vs. 22.3±3.8, p=0.043), and neck circumference (37.8±4.3 vs. 35.8±4.2, p=0.012) were significantly higher in the severe SDB than in the non-severe SDB. Metabolic syndrome (36% vs. 21%, p=0.057) and waist circumference (88.9±9.8 vs. 85.5±9.3, p=0.080) showed a tendency toward higher in the severe SDB group than in the non-severe SDB group. There were no significant differences in age, prior stroke, vascular risk factors, Glasgow Coma Scale, and NIHSS score on admission. On multivariate regression analysis, atrial fibrillation (odds ratio, 2.5; 95% confidence interval, 1.079-5.836, p=0.0326) was found to be independently associated with severe SDB.

Conclusions
Most Japanese patients with acute TIA and stroke had SDB, and the presence of atrial fibrillation was associated with severe SDB.
Abstract 2473: Ubiquitin Ligase Huwe1 Modulates Prongf/p75ntr In Monkey Cerebral Ischemia-reperfusion Injury
Authors: He Qian G , Yu Lihua , Xu Wenming , Duan Jiachuan , Guo Jian , Chen Ning , He Li
Published: July 2021

Background:
Ischemic neuronal cell apoptosis is a principal neuropathological feature of stroke. The p75 neurotrophin receptor (p75NTR) induces apoptosis associated with JNK-p53-BAX pathway, p53 is the substrate of the HECT domain-containing E3 ubiquitin ligase Huwe1. Recent studies suggest that the precursor form of NGF (proNGF) binds to p75NTR, and withhold the interaction of proNGF/p75NTR is efficacious in reducing neuronal apoptosis. Studies on tumor and phylogeny, show that Huwe1 highly expressed in CNS, playing a role in the regulation of cell apoptosis and a variety of injury types. Our aim is to examine whether Huwe1 modulates proNGF/p75NTR in cerebral ischemia-reperfusion injury.

Methods:
Eight male rhesus monkey were randomly divided into two groups: sham(n=2) and model group(n=6). The model group was administered equal volume of PBS, or silencing huwe1 Lentiviral Vector or empty Vector in right caudatum and putamen using brain stereotaxic technology and subjected to transient right middle cerebral artery occlusion (MCAO) a month later. A battery of neurological evaluation and magnetic resonance imaging (MRI) were employed to evaluate animals. Animals were sacrificed 3 days after MCAO and brains were processed for testing transfection efficiency using GFP fluorescence and evaluating cell apoptosis using TUNEL staining. The related factors in caudatum, putamen, temporal lobe and hippocampus was analyzed with QPCR, western blotting with loading control GADPH, and Immunohistochemistry.

Results:
The model group showed significant functional deficit than sham group with neurological evaluation (p<0.05), whereas the silencing Huwe1 group’s was the most serious. In right caudatum and putament, ischemia-reperfusion injury increased the number of TUNEL+cells(p<0.05 vs sham group) and upregulation of huwe1, proNGF and p75NTR in protein and nucleotides level (p<0.05 vs sham group), but silencing Huwe1 group increased TUNEL+cells most significantly, produced profound modulation with decreased expression of Huwe1 and obvious upregulation of proNGF and p75NTR(p<0.05 vs PBS or empty Vector group) (
Figure 1
). However, there is no significant difference in other positions (data not show).

Conclusions:
Huwe1 modulates proNGF/p75NTR in the cerebral ischemia-reperfusion injury, and p53 may be as a indirect fator involved in this process. Our findings provide a novel mechanism in regulating proNGF/p75NTR signaling, suggesting its potential therapeutic target in ischemic stroke.
Abstract 2477: Moving Toward 100% Stroke Patient Education Compliance
Authors: Fuhrman Susan , Plehn Pam
Published: July 2021

Background:
Evidence has shown that if patients are provided with basic stroke education (i.e. stroke risk factors, warning signs, emergency actions, follow-up considerations, general medication information), they have improved self-care. Provision of stroke education is a performance measure for Joint Commission Certified-Primary Stroke Centers (JC-PSC). In our 2 hospital system, variation in provision of education, effectiveness of materials provided, and documentation of teaching was found.

Purpose:
The purpose of this initiative was to identify barriers to providing optimal stroke education and implement strategies for improvement.

Method:
Current educational delivery methods/materials were clarified with input from multi-disciplinary team members and past/current patients and families. Compliance with provision of this patient education measure was tracked. Barriers to optimal compliance and educational delivery identified included inconsistent patient education provision and documentation methods, handouts of poor visual quality that weren’t helpful for people with visual problems, varying content for discharge instructions, and lack of real time assessment of measure compliance. Improvement strategies implemented included stroke program CNS or RN seeing all known stroke/TIA inpatients, creation of a spiral bound stroke educational booklet and an audio CD version, development of a stroke education teaching screen in the electronic health record, and revision of an individualizable Stoke/TIA Patient Discharge Instruction template that included required content.

Results:
Strategies for improvement took time and involved significant staff education; however improvement in stroke education measure compliance was noted at both of our hospitals during the first year. In the second year of this initiative, continued efforts resulted in 100% compliance with the measure for most months.

Conclusions:
Having the stroke program CNS or RN see the stroke/TIA inpatients improved not only consistency of care delivery but also afforded the opportunity to do ongoing education for staff. Creation of consistent educational materials that could meet individual patient/family needs along with creation of user-friendly documentation methods increased our ability to successfully meet the needs of our patients and show we had excellent stroke education delivery outcomes.
Abstract 2483: No Increased Risk of sICH in tPA Treated Stroke Patients With ECASS Exclusion Criteria
Authors: Cronin Carolyn A , Shah Nikeith , Morovati Tanya , Hermann Lisa D , Sheth Kevin N
Published: July 2021

Introduction:
Only about 2% of ischemic stroke patients are currently treated with IV tPA, with the most common reason for exclusion from treatment being time. The positive results of ECASS III expanded the time window for treatment to 4.5 hours, however it used more stringent exclusion criteria than are in use for <3 hrs in the USA. For patients who present 3-4.5 hours from symptom onset, the scientific advisory from the AHA/ASA recommends use of the more narrow ECASS III criteria. We evaluated the outcomes of patients who had been treated with IV tPA to test the hypothesis that thrombolysis is not safe in patients with one of the additional exclusion criteria (age >80, NIHSS >25, combination of previous stroke and diabetes, aggressive measures required to control blood pressure (IV infusion), or oral anticoagulant treatment).

Methods:
We performed a retrospective analysis of all acute ischemic stroke patients treated with IV tPA at our tertiary care academic medical center between June 2006 and June 2010. 191 patients were identified and stratified based on presence of each of the listed exclusion criteria. The primary outcomes are rate of symptomatic intracerebral hemorrhage (sICH) and in-hospital mortality. Additionally, patients with and without sICH were analyzed for differences in baseline characteristics.

Results:
There were 31 patients older than 80 years, 5 with NIHSS >25, 14 with the combination of prior stroke and diabetes, 19 required continuous IV infusions to control blood pressure below 185/110 mmHg, and 11 were taking oral anticoagulants. No exclusion criterion was associated with increased risk of sICH. There was higher in hospital mortality in patients >80 years (5 of 31 (16%) vs. 6 of 160 (4%), p=0.0186, RR = 3.15, 95% CI: 1.50 to 6.59), and those with NIHSS >25 (2 of 5 (40%) vs. 7 of 159 (4.4%), Relative risk = 11.48, 95% CI: 2.19 to 60.30). sICH was associated with atrial fibrillation (5 of 9 (55%), vs. 35 of 182 (19.2%), p=0.021; RR = 4.72, 95% CI: 1.33 to 16.77), larger final infarct volume (mean 173 ml
3
(SEM 43.3) vs. 42 ml
3
(SEM 6.3),p=0.0002), and elevated glucose (mean 166 mg/dL (SEM 23.1) vs. 127 mg/dL (SEM 4.1), p=0.038).

Conclusions:
In our cohort, none of the exclusion criteria from ECASS III, which were more stringent than those used in 0-3 hour US labeling, were associated with increased risk of sICH. tPA may be safe in these patients, who represent an important patient population of acute stroke patients. In agreement with prior studies, we have found that older patients and those with more severe deficits at presentation have higher mortality after acute ischemic stroke. Prospective studies are urgently needed to determine the safety and efficacy of tPA in this group of patients through all treatment time windows.
Abstract 2494: A Transient Decrease in Spleen Size Following Stoke Corresponds to Splenocyte Release into Systemic Circulation
Authors: Seifert Hilary , Hall Aaron , Recio Jesus , Chapman Cortney , Collier Lisa , Willing Alison , Pennypacker Keith
Published: July 2021

Objective:
Splenectomy is protective in ischemic injuries to renal, hepatic, and gastrointestinal systems, showing that the splenic response promotes cellular degeneration. Removal of the spleen is also protective in ischemic and hemorrhagic stroke. Therefore, we investigated the cellular response of the spleen to brain ischemia.

Hypothesis:
Immune cells are released from the spleen following cerebral ischemia contributing to neural injury.

Methods:
A time course was conducted to investigate splenic size changes in rats over time following permanent middle cerebral artery occlusion (MCAO) and sham-MCAO (n≥3). In a second experiment, splenocytes were labeled
in situ
with carboxyfluorescein diacetate, succinimidyl ester (CFSE). Five evenly spaced splenic injections, 4 mg/ml in DMSO, were given to all groups five days prior to MCAO or sham-MCAO. The experimental groups were: 48 hr post-MCAO (n=4), 48 hr post-sham-MCAO (n=4), 96 hr post-MCAO (n=6), 96 hr post-sham-MCAO (n=4), and a CFSE only group that was euthanized five days following injection of CFSE without undergoing MCAO (n=4). Spleen, brain, thymus, and blood smears were collected for all groups.

Results:
The spleen was found to decrease in size at 48 hrs following MCAO in rats compared to controls (p<0.01). However, by 96 hrs post-MCAO the spleen size returned to levels not different from sham operated rats. CFSE was found to be non-toxic at the 4 mg/ml concentration and five days following injection 15% of the splenocytes were labeled. In the spleen, there was a significant increase (p<0.0001) in CFSE positive cells in the 48 hr sham group versus the 96 hr sham and both 48 and 96 hr MCAO groups. Blood smears showed a significant increase in total CFSE positive cells (p<0.0007) at 48 hrs post-MCAO. CFSE positive cells in the blood were identified by Giemsa staining. A significant increase of lymphocytes (p<0.005), monocytes (p<0.02), and neutrophils (p<0.0005) was found at 48 hrs post-MCAO when compared to the other groups.

Conclusion:
These results demonstrate that CFSE is a viable and safe way to track immune cells
in situ
in an animal model of stroke. The spleen transiently decreases in size post-MCAO in rats and releases splenocytes into systemic circulation at 48 hrs following MCAO. These cells are migrating to the brain or other lymphoid organs, affecting the overall immune response to ischemia. Brains and thymi from the CFSE injected animals will be analyzed for the presence of these cells.
Abstract 2511: Reperfusion Measured by Mean Transit Time Predicts Clinical Improvement in Hyperacute Ischemic Stroke Patients Better Than Time-to-Peak and Tmax
Authors: Ford Andria L , An Hongyu , Vo Katie D , Powers William J , Lin Weili , Lee Jin-Moo
Published: July 2021

Background:
Early reperfusion is associated with improved clinical outcome in acute ischemic stroke; however, there is no consensus regarding which perfusion parameter may best serve as a marker of clinical improvement. We compared three commonly used MRI perfusion parameters, mean transit time (MTT), time-to-peak (TTP), and Tmax, to identify which method of measuring reperfusion best predicted clinical improvement.

Methods:
Acute ischemic stroke patients underwent two MR scans: within 4.5 hours (tp1) and at 6 hours (tp2) after stroke onset. Co-registered MTT, TTP, and Tmax maps were generated to measure regions of perfusion deficit at tp1 and tp2. Perfusion deficit was defined as prolongation of MTT, TTP, or Tmax beyond four pre-specified thresholds for each parameter (4 thresholds were chosen to ensure results were not spuriously based on one threshold). Commonly-used thresholds (relative to contralateral median) were selected for each parameter: for MTT: >3, 4, 5, or 6 seconds (s), for TTP: >2, 4, 6, or 8s, and for Tmax: >2, 4, 6, and 8s. The volume of reperfusion (Vreperf) was defined as the volume of tissue with perfusion deficit at tp1 and no perfusion deficit at tp2. Clinical improvement was defined as: Admission NIH Stroke Scale (NIHSS) - 1 month NIHSS (ΔNIHSS). A multivariable linear regression model identified if Vreperf as measured by MTT, TTP, or Tmax was an independent predictor of clinical improvement after adjusting for patient age, admission NIHSS, tPA treatment, and volume of tp1 perfusion deficit.

Results:
Thirty-nine acute ischemic stroke patients were prospectively scanned at 2.8±.8hr (tp1) and 6.4±.4hr (tp2) after stroke onset (mean age=64, 44% female, 36% Black, mean NIHSS=14, 74% received IV tPA). Across the four thresholds, mean volume of perfusion deficit ranged from 58-96ml for MTT, 56-116ml for TTP, and 51-113ml for Tmax. Mean Vreperf ranged from 15-22ml for MTT, 15-23ml for TTP, and 14-21ml for Tmax. In the multivariable linear regression analysis, after adjusting for age, admission NIHSS, tPA treatment, and volume of tp1 perfusion deficit, Vreperf predicted ΔNIHSS for MTT=4s (p=0.007), MTT=5s (p=0.005), and MTT=6s (p=0.010), whereas Vreperf did not predict ΔNIHSS for any TTP or Tmax threshold (
Table
).

Conclusion:
Reperfusion, defined by MTT, was an independent predictor of clinical improvement, while reperfusion defined by TTP and Tmax were not. Therefore, MTT may be the best time-based perfusion parameter to define clinically-relevant reperfusion after stroke.
Abstract 2552: Lipoprotein-associated phospholipase A2 predicts atherosclerotic stroke risk: The Northern Manhattan Study
Authors: Katan Mira , Moon Yeseon P , Gervasi-Franklin Palma , Paik Myunghee C , Wolfert Robert L , Sacco Ralph L , Elkind Mitchell S
Published: July 2021

Background:
Lipoprotein-associated phospholipase A2 (Lp-PLA2) has pro-inflammatory properties and may contribute to atherosclerosis, plaque rupture, and stroke. Lp-PLA2 levels may improve risk stratification, though whether this ability extends to all populations and stroke subtypes remains uncertain. We hypothesized that Lp-PLA2 levels would predict first ischemic stroke in a multiethnic, urban, population.

Methods:
Serum samples from stroke-free community participants in the Northern Manhattan Study were assayed using a microplate based ELISA to measure the mass concentration of Lp-PLA2 (PLAC Test, diaDexus, Inc). Participants were followed annually for stroke, and stroke subtype was determined according to the TOAST criteria. Cox proportional hazard models were fitted to estimate hazard ratios and 95% confidence intervals (HR, 95% CI) for the association of Lp-PLA2 mass levels with ischemic stroke, unadjusted and after adjusting for demographic, behavioral and medical risk factors.

Results:
Serum samples were available in 1946 participants with median follow up of 11 years; 151 subjects (7.8%) experienced a first ischemic stroke, of which 26 were large artery atherosclerotic strokes. Mean age was 69 (SD 10), 35.6% were men, 20% non-Hispanic Whites, 22% Blacks, and 55% Hispanics. The mean Lp-PLA2 level was 308.7 (SD 88.5) ng/mL. In non-Hispanic Whites, there was a trend toward increased risk of ischemic stroke with Lp-PLA2 levels (adjusted HR per SD 1.44, 95% CI 0.98-2.11), but not in Blacks (p for interaction with white=0.045); or in Hispanics (p for interaction with white=0.13). Lp-PLA2 levels were predictive of large artery atherosclerotic strokes (LAA) in the entire cohort (adjusted HR per SD 1.55, 95% CI 1.17-2.04). When analyzed by quartile, there were dose-response relationship with LAA (compared to the lowest quartile, 2nd quartile HR= 1.43, 95% CI 0.23-8.64; 3rd quartile HR=4.47, 95% CI 0.93-21.54; 4th quartile HR=5.07, 95% CI 1.07-24.06). When the analysis was stratified by race, Lp-PLA2 was associated with increased risk of LAA among whites, but not blacks or Hispanics (chi-squared 2 degrees of freedom, p for interaction=0.01).

Conclusion:
Lp-PLA2 was associated with risk of atherosclerotic stroke among non-Hispanic White participants, but not in other race-ethnic groups in the cohort. Further study is needed to confirm these race-ethnic differences and the reasons for them.
Abstract 2571: Quantitative Analysis of Cobalt Alloy Clip Artifacts in 64 channel Three Dimensional CT Angiography and Introducing Strategies for Minimizing Metallic Artifacts
Authors: Sim Sook Young , Choi Chi Hoon , Han Dae Hee
Published: July 2021

Objective
Clip artifacts on postoperative CT scans after aneurysmal clipping, can create confusion, especially in cases of cobalt alloy clips. Mathematic analysis of the parameters influencing the degree of clip artifact in 64-channel 3 dimensional CT angiography (3D CTA) was conducted to develop methods for minimizing metallic artifacts.

Materials and Methods
CT images from 60 cases with single straight Sugita cobalt alloy clips (Mizuho Ikakogyo Co., Tokyo) were analyzed. The degree of the angle between the imaging acquisition gantry angle and clip blade on the CT axial scan (x, y) and on the lateral scout view (z) was measured as independent variables. The length of the clip blade was also measured. Analysis of whether the spring of the clip was included in the 5mm thick scan slide was performed. The dependent variables were the maximal diameter of the white artifact, degree of the symmetrical angle of the streak artifact and the maximal diameter of clip artifact in 3D volume rendering. Univariate and multivariate analysis was conducted to elucidate relationship between each parameters and each type of clip artifacts.

Results
The degree of the angle between z axis and clip blade was negatively correlated with the amount of white artifact (p<0.0001, R=-0.589) and positively with the streak artifact (angle of the streak artifact: p<0.0001, R=0.636; number of the streak artifact: p<0.0001, R=0.505). When the spring of the clip was included parallel in scan section, the amount of white artifact was increased (p<0.0001). On multiple linear regression analysis, angle of clip blade to z axis was the major parameter influencing all kinds of artifacts (white artifact: p<0.005, angle of the streak artifact: p<0.0001, number of the streak artifact: p<0.0001).

Conclusions
Metallic artifact was increased when the degree of angle between the clip blade and z axis became near to zero. Clip artifacts after aneurysmal clipping could be minimized with simple maneuvers such as minimal changes of the scan gantry angle on the lateral scout view if the clip blade was parallel to the gantry angle or the clip spring portion was included in the scan cross section.
Abstract 2595: Vascular Occlusion as an Imaging Biomarker for Selecting Acute Ischemic Stroke Patients for Treatment with Desmoteplase
Authors: Fiebach Jochen B , Al-Rawi Yasir , Wintermark Max , Furlan Anthony J , Rowley Howard A , Lindsten Annika , Smyej Jamal , Eng Paul , Warach Steven , Pedraza Salvador
Published: July 2021

Desmoteplase is a novel, highly fibrin-specific and non-neurotoxic thrombolytic agent. Evidence of safety and efficacy was obtained in two phase II trials (DIAS and DEDAS). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings. Post-hoc analyses were performed with the aim of predicting treatment responders based on CT and MR angiography. The predictive value of infarct volume and TIMI grade at baseline with respect to drug response measured by clinical outcome at Day 90 was investigated using DIAS-2 data. Patients were grouped according to vessel status (TIMI grade) for logistic regression of clinical response, applying the data from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2. In DIAS-2, a substantial number of mismatch-selected patients (126/179, 70%) presented with a normal flow/low-grade stenosis (TIMI 2-3) at screening, the majority having a favorable outcome at Day 90. In contrast, favorable outcome rates in patients with vessel occlusion/high-grade stenosis (TIMI 0-1) were 18% with placebo versus 36% and 27% with desmoteplase 90 and 125 μg/kg, respectively. The clinical effect size based on the pooled data from DIAS, DEDAS, and DIAS-2 was borderline statistically significantly different (P=0.05) in the TIMI 0-1 and TIMI 2-3 subgroups. It was favorable for desmoteplase-treated patients presenting with TIMI 0-1 at baseline (odds ratio, 4.144; 95% CI, 1.40-12.23; P=0.010), while there was no desmoteplase treatment benefit in patients presenting with TIMI 2-3 (odds ratio, 1.109). In this sample of patients diagnosed with a mismatch, proximal vessel occlusion or severe stenosis was associated with clinically beneficial treatment effects of desmoteplase. Selecting patients using CT or MR angiography in clinical trials of thrombolytic therapy is justifiable.
Abstract 2597: Centralized and Study-specific Phenotyping in a Large-scale Stroke Genetics Study: An Analysis from the NINDS Stroke Genetics Network (SiGN)
Authors: Worrall Bradford B , Rabinstein Alejandro , Gamble Dale M , Barrett Kevin M , Malik Shaneela , Ossi Ra'id , Southerland Andrew M , Arsava Ethem , Biffi Alessandro , Helenius Joanna , Lorenzano Svetlana , Huq Mohammed , Katsnelson Michael , Meschia James F , Kittner Steven , Furie Karen , Rosand Jonathan , Cortellini Lynelle , Woo Daniel , Markus Hugh , Rundek Tatjana , Sacco Ralph L , McArdle Patrick , Ay Hakan , Brown Robert D
Published: July 2021

Background:
The Stroke Genetics Network (SiGN) funded by the NINDS aims to identify genetic risk factors in ischemic stroke using whole-genome association studies (GWAS). High quality phenotyping is crucial to successful application of GWAS. As a heterogenous disorder, stroke poses specific challenges. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification is a broadly used, but its validity is challenged especially when performed by multiple investigators with differing interpretations of the system. The Causative Classification System for Ischemic Stroke (CCS) system is a new, web-based, and computerized algorithm that integrates clinical, diagnostic, and etiologic stroke characteristics in an evidence-based manner (
ccs.mgh.harvard.edu
) to generate subtypes.

Methods:
In planning the SiGN proposal, a sample of 20 coded charts were collected from a subset of participating studies to assess feasibility of central adjudication and comparability to study-specific TOAST. Two central adjudicators reviewed all records and generated TOAST and CCS subtypes. These were compared to study-specific TOAST subtype and the CCS phenotype generated for SiGN by local trained adjudicators. CCS data is now available for 7134 included cases using both a 5 and a 7 category system as defined in the
table
.

Results:
All 4 phenotypes were available for 115 ischemic stroke cases from 6 studies in SiGN. Basic demographics were 54% women, 63% white, and median age between 65-74.

Table 1

provides the agreement between the various subtypes.

Table 2

describes the types of disagreement.

Conclusions:
Central adjudication with only two adjudicators and curated medical records yielded more consistent subtyping independent of phenotyping system. The agreement for TOAST was higher than published rates by independent groups (∼0.50). In contrast, the agreement for CCS was lower than previously published (0.85-0.95). Site adjudicators' familiarity with TOAST and inexperience with CCS may contribute. Although CCS is an automated algorithm and has a number of user friendly features, our findings suggest that formal training and certification process before starting to use CCS may be worthwhile to achieve optimal benefit from the system.
Abstract 2627: Outcomes After Endovascular Treatment For Anterior Circulation Stroke Presenting Beyond 8 Hours Of Time Last Seen Well Do Not Differ In Wake-up Strokes Vs. Witnessed Onset Beyond 8 Hours
Authors: Aghaebrahim Amin , Leiva-Salinas Carlos , Zaidi Syed , Jumaa Mouhammad , Urra Xabi , Amorim Edilberto , Zhu Guangming , Reddy Vivek , Hammer Maxim , Jankowitz Brian , Wintermark Max , Jovin Tudor
Published: July 2021

Objective:
Patients with wake-up stroke are thought to have different outcomes compared to patients with known late time of onset. We thought to verify this hypothesis by determining clinical outcomes, mortality and rate of parenchymal hematoma (PH) in patients with anterior circulation large vessel occlusion stroke (ACLVOS) treated with endovascular therapy at our center.

Methods:
Retrospective review of a prospectively acquired database from consecutive patients meeting the following criteria: (1) ACLVOS, (2) endovascular treatment initiated beyond 8hrs from time last seen well (TLSW). Treatment selection was based on the presence of a small infarct core/large penumbra assessed through visual inspection on MRI or CTP by the treating physician. In patients undergoing MRI (n=55) pre-procedure infarct volumes on DWI were measured through automated volumetric analysis.

Results:
We identified 130 patients (mean age 64; mean baseline NIHSS 14, male gender 55%). Patients were divided into three groups. Group 1: patients with wake-up stroke (39%, n=51). Group 2: patients with witnessed onset beyond 8hrs from TLSW (55%, n=72). Group 3: patients without witnessed onset but TLSW>8hrs (5%, n=7). Occlusion locations were as follows: M1-55%, M2-12%, ICA terminus-32% and ICA origin (tandem occlusion)-28%. Successful recanalization (TIMI 2/3) was achieved in 109 patients (84%). The rate of 90 day favorable outcome (modified Rankin score (mRS) ≤ 2) was 55% (n=68/124). PH occurred in 15/130 (12%) patients and the 3 month mortality rate was 18% (n= 22/124). Favorable outcome rates amongst Group 1 (50%, n=24/48), Group 2 (59.5%, n=41/69) and Group 3 (42.9%, n=3/7) were not significantly different (p=0.49, by ANOVA). Mean pre-procedure DWI lesion volume was 18.7 cc in Group 1 vs. 18.3 cc in group 2 (p=0.9). No difference was noted between Group 1, Group 2 and Group3 regarding PH (13.7%, 8.3%, 13.3% respectively, p nonsignificant) or mortality at 3 months (18.7%, 17.4%, 14.3% respectively, p nonsignificant). Multivariate logistic regression model identified only successful recanalization (OR 2.9, p 0.001, CI 1.59-5.44) and age (OR 0.96, p 0.03, CI 0.93-0.99) as predictors of favorable outcome.

Conclusion:
In patients with ACLVOS presenting beyond 8 hours from TLSW who are selected based on similar imaging characteristics, clinical outcomes following endovascular treatment do not seem to differ according to mode of presentation relative to TLSW.
Abstract 2650: Reliability and Validity of Retrospective Extraction of the ABCD
2
Score From Medical Records
Authors: Ishida Koto , Raser Jonathan M , Wilson Christina A , Kasner Scott E , Mullen Michael T , Messe Steven R , Cucchiara Brett L
Published: July 2021

Background and Purpose:
The ABCD
2
score is increasingly used for risk stratification of TIA patients. Many of the studies assessing the utility of the ABCD
2
score have retrospectively extracted the score from medical records, but the reliability of estimation based on chart review has not been reported. We sought to determine whether the ABCD
2
score can be estimated retrospectively from medical records.

Methods:
We compared ABCD
2
scores that were prospectively determined by a board certified vascular neurologist to scores determined retrospectively from medical record review. All ED records and initial neurology consult resident notes were abstracted with explicit ABCD
2
scoring redacted. ABCD
2
scores were then estimated by two independent blinded trained raters using these records. Estimated component, total scores, and ABCD
2
risk category (0-3, 4-5, 6-7), were compared both between raters and with the prospectively obtained scores. Reliability was assessed using unweighted kappa statistics.

Results:
Records were analyzed for 55 consecutive TIA patients. For the two raters of retrospective ABCD
2
scores, interrater reliability was good with 75% exact agreement in total score between raters (κ=0.68) and 84% agreement for ABCD
2
category (κ=0.74). Interrater agreement on individual items was greatest for age and diabetes, and poorest for clinical features and duration. Retrospectively estimated total ABCD
2
scores were identical to prospective scores in 52% of patients. Agreement between raters and the prospectively obtained score was >90% for age, blood pressure, and diabetes, but was only ∼70% for clinical features and duration. Retrospectively estimated ABCD
2
category was identical to the prospective category in 64% of patients (
Table
). Dichotomizing at an ABCD
2
score ≥4, retrospective assessment had a sensitivity of 83% (CI 70-95%) and specificity of 67% (CI 40-95%) compared to the prospective score.

Conclusions:
The ABCD
2
score can be abstracted from medical records with good interrater reliability but limited validity, which may lead to misclassification of risk category in over one-third of patients.