bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP441: Poor Atrial Fibrillation Management Leads to Unnecessary Thrombectomies in Elderly Patients
Authors: Sur Nicole B , Saini Vasu , Torres Luis F , Krementz Nastajjia , Mannava Sishir , Atchaneeyasakul Kunakorn , Malik Amer M , Yavagal Dileep R , Chaturvedi Seemant
Published: June 2021

Background:
A significant proportion of mechanical thrombectomies for large vessel occlusion (LVO) stroke are avoidable with improved oral anticoagulant (OAC) use in patients with atrial fibrillation (AF). We sought to identify the proportion of avoidable thrombectomies in elderly patients (age ≥70) with stroke due to AF.

Methods:
This study included 348 consecutive MT cases at a high-volume stroke center from Feb 2015 to Sept 2018. A retrospective chart review was conducted to identify patient sociodemographics, presence of AF, use of anticoagulation, stroke severity, CHA
2
DS
2
-VASc scores, and functional outcome

Results:
A total of 191 (55%) patients were ≥70 years (median age 81±7, 61% female), of which 116 (61%) had AF (median age 82±6, 67% female). Elderly patients with AF were more likely to have hypertension and heart failure and be on antiplatelets and OACs. Pre-existing AF was present in 75 (39%) patients, of which 38 (49%) were not on OACs prior to stroke. Of the 39 (51%) patients with known AF on OACs, 10 (68%) had subtherapeutic INR levels and 5 (21%) were not adherent to direct OACs. Overall, 53/191 (28%) patients with known AF were not adequately anticoagulated prior to the index stroke. There was no significant difference in modified Rankin Scale score at discharge or rate of symptomatic intracerebral hemorrhage between the two groups.

Conclusion:
In our study, about 1 in 4 elderly patients with known AF were not adequately anticoagulated prior to stroke and underwent potentially avoidable thrombectomy. Better practice strategies are needed to increase OAC utilization and adherence to reduce the burden of stroke in patients with AF, especially in elderly women.
Abstract TP446: Rosuvastatin Improves Cerebral Hemodynamics in Rats With Chronic Cerebral Hypoperfusion
Authors: Xie Xiaomei , Song Kangping , Huang Li'an
Published: June 2021

Objective:
Chronic cerebral hypoperfusion (CCH) is a common consequence of various cerebral vascular disorders, hemodynamics and blood composition changes, which can lead to neurodegenerative injury and cognitive dysfunction. Therefore, it is important to take measures to prevent or reverse its development.

Methods:
Eighty Sprague-Dawley rats were randomly divided into five groups: Sham group, Vehicle groups (2-week group and 4-week group), Rosuvastatin-treated groups (2-week group and 4-week group). Both vehicle and treated group rats were treated with bilateral common carotid artery occlusion (BCCAO). Then rats in the treated group were intravenously injection with rosuvastatin (0.2 mg/kg/day) daily for 14 days beginning 24 hours after BCCAO. The vehicle groups were given the same amount of saline. The MRI ASL technique was used to scan cerebral blood flow (CBF) at pre-occlusion, BCCAO, 1, 2, 3, and 4 weeks after operation. Morris water maze test detected spatial memory abilities of the treated and vehicle rats after BCCAO. Immunofluorescence staining was used to detect the expression of CD34, GFAP, NeuN and Caspase-3 positive cells in hippocampus.

Results:
CBF decreased significantly after BCCAO in both rosuvastatin-treated and vehicle groups and then increased gradually. The CBF of the treated group was basically recovered to baseline levels at 1 or 2 weeks after BCCAO. But it took the vehicle group 4 weeks to restore to baseline. The vertebral artery (VA) diameter of the treated group was greater than that of the vehicle group (p<0.05), and the recovery of CBF and the dilation of VA were more evident during the administration period. Similarly, the escape latency of the treated group rats was also less than the vehicle group in Morris Water Maze test. In addition, the number of CD34
+
and NeuN
+
cells in the hippocampus of the treated group was more than that in the vehicle group (p<0.01), while the number of GFAP
+
and Caspase-3
+
cells was less than in the vehicle group (p<0.01).

Conclusion:
Rosuvastatin can accelerate the recovery of cerebral blood flow in CCH rats, which may be related to the dilation of VAs and angiogenesis; and its effects on reducing astrocyte activation and neuroprotection may help to ameliorate cognitive dysfunction in CCH rats.
Abstract TP451: Intracerebral Hemorrhage Volume Predicts Neurological Pupil Index
Authors: Aiyagari Venkatesh , Mazhar Khadijah , Olson Daiwai , Stutzman Sonja , Moreno James , Venkatachalam Aardhra
Published: June 2021

Introduction:
Hand-held automated pupillometry reliably evaluates the pupillary light reflex (PLR) at the bedside and there is growing interest in studying its ability to detect midline shift and mass effect. We hypothesized that intracerebral hemorrhage (ICH) volume would correlate with objective measures of PLR, specifically the Neurological Pupil index (NPi).

Methods:
This was a retrospective study of ICH patients with serial pupillometer readings admitted to the Neurocritical Care Unit and enrolled in the END-PANIC registry. CT images were examined to measure hematoma volume using the simplified ABC/2 method, midline shift, hydrocephalus score, and Graeb score to measure interventricular hemorrhage. Demographics were examined with standard measures of central tendency, hypotheses with logistic regression, categorical data with Fisher’s Exact X
2
, and multivariate modeling with constructed MAX-R models.

Results:
Of 44 subjects, 50% were male and the mean age was 65.4 years. ICH location was deep in 56.8% and lobar in 43.2%. There was a significant correlation between ICH volume and NPi of the pupil ipsilateral (r
2
=0.48, p<0.0001) and contralateral (r
2
=0.39, p<0.0001) to the hematoma. Shift of the septum pellucidum also correlated with NPi (ipsilateral[r
2
=0.25, p=0.0006], contralateral[r
2
=0.15, p=0.0106]), as did shift of the pineal gland (ipsilateral[r
2
=0.21, p=0.0017], contralateral[r
2
=0.11, p=0.0328]). No statistically significant correlation was found between hydrocephalus score or Graeb score and NPi. ICH volume was the most predictive of abnormal NPi (Figure 1).

Conclusions:
The NPi correlates with ICH volume and shift of midline structures. Abnormalities in NPi can be predicted by hematoma volume. Future studies should explore the role of NPi in detecting hematoma expansion and worsening midline shift.
Abstract TP48: IV tPA is Associated With Increase in Intracerebral Hemorrhage Rates and Length of Stay in Acute Stroke Patients Treated With Endovascular Treatment Within 4.5 Hours; Should We Bypass IV tPA in Large Vessel Occlusion?
Authors: Hassan Ameer E , Ringheanu Victor M , Preston Laurie , Rabah Rani , Sarraj Amrou , Tekle Wondwossen G , Qureshi Adnan I
Published: June 2021

Background:
Endovascular treatment (EVT) is a widely proven method to treat patients diagnosed with intracranial large vessel occlusions (LVO); however, there has been controversy regarding the safety and efficacy of incorporating intravenous tissue plasminogen activator (IV tPA) as pretreatment for EVT. We compared the outcomes of all LVO patients treated with IV tPA + EVT versus EVT alone within 4.5 hours of stroke onset.

Methods:
Through the utilization of a prospectively collected endovascular database at a comprehensive stroke center between 2012-2019, variables such as demographics, co-morbid conditions, symptomatic/asymptomatic intracerebral hemorrhage (S-ICH/A-ICH), mortality rate, and good/poor outcomes in regard to modified thrombolysis in cerebral infarction score (TICI) and modified Rankin Scale assessment at discharge (mRS dc) were examined. The outcomes between patients receiving IV tPA + EVT upon admission and patients that underwent EVT alone were compared.

Results:
Out of 588 acute ischemic stroke patients treated with EVT, a total of 189 met the criteria for the study (average age 70.44 ± 12.90 years, 42.86% women). Analysis of 109 patients from the EVT + IV tPA (average age 68.17 ± 14.28 years, 41.28% women), and 80 patients from the EVT alone was performed (average age 73.54 ± 9.84 years, 45.00% women); see Table 1 for baseline characteristics and outcomes. Four patients (5.0%) in the EVT alone group experienced S-ICH versus 15 patients (13.8%) in the IV tPA + EVT group (p=.0478); significant increases were also noted in the length of stay for patients treated with IV tPA (8.2 days vs 11.0 days; P=.0055).

Conclusion:
IV tPA in addition to EVT was associated with an increase in the rate of ICH in LVO patients treated within 4.5 hours and in patients’ length of stay. Further research is required to determine whether EVT treatment alone in LVO patients treated within 4.5 hours is a more effective option.
Abstract TP483: Transcatheter Aortic Valve Replacement (TAVR) Does Not Improve Cerebral Hemodynamics or Neurocognition in Patients With Severe Aortic Stenosis
Authors: Lazar Ronald M , Myers Terina , Gropen Toby I , Leesar Massoud A , Davies James E , Gerstenecker Adam , Norling Amani M , Pavol Marykay A , Marshall Randolph S , Kodali Susheel K
Published: June 2021

Objective:
To determine if aortic stenosis (AS) is associated with altered cerebral hemodynamics and impaired neurocognition, and whether TAVR improves hemodynamics and cognition.

Background:
AS results in higher systolic pressure to overcome resistance from the stenotic valve, leading to heart failure and decline in cardiac output. There has been no baseline assessment of CBF with neurocognition in AS, or the effects of valve replacement.

Methods:
In 40 patients with planned TAVR, transcranial Doppler (TCD) assessed bilateral MCA mean flow velocity (MFV); abnormality was
<
30cc/sec. The neurocognitive battery assessed memory, language, attention, visual-spatial skills, and executive function, yielding an average Z-score. Impairment was
<
1.5 SD’s below the normative mean.

Results:
The mean age was 78 years, 59% male, and the mean valve gradient was 46.87%. Mean follow-up was 36 days post-TAVR (range 27 - 55). Before TAVR, the average MFV was 42 cc/sec (SD=10.22), and the mean cognitive score was -0.22 SD’s (range -1.99 to 1.08) below the normative mean. Of the 5 with abnormal MFV’s, none had abnormal cognition (average=0.19 SD’s above the normative mean). After TAVR, the MFV was 43 cc/sec, not different from baseline (p=0.56). The post-TAVR average Z-score was 0.01 SD’s above the normative mean, also not different from baseline (p=0.29). There was no correlation between the change scores in MFV and in neurocognition (r = 0.08, p= 0.69).

Conclusions:
Among patients with severe AS, there was no correlation at baseline between abnormal MFV’s on TCD and abnormal neurocognition. It was therefore unsurprising that there was little impact of valve replacement on these measures of cerebral blood flow and brain function. Prior assumptions about diminished CBF and the relationship to cognitive function may not be supported.
Abstract TP487: Comprehensive Profiling of Secreted Factors in the Cerebrospinal Fluid of Moyamoya Disease Patients
Authors: Abhinav Kumar , Uchino Haruto , Lee Alex G , Pendharkar Arjun V , Bigder Mark , Bet Anthony , Rosenberg-Hasson Yael , Cheng Michelle Y , Steinberg Gary K
Published: June 2021

Background:
Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive occlusion of the internal carotid arteries leading to ischemic and hemorrhagic events. The underlying pathogenesis of MMD remains unclear. In this study we investigated key secreted molecules in the cerebrospinal fluid (CSF) of MMD patients including relation to the extent of neovascularization and eventual functional outcomes.

Methods:
This study included intraoperative CSF collected from 32 controls (Chiari malformation and cranial nerve hyperactive syndromes) and 73 MMD patients (ischemic: 39; hemorrhagic: 34) that underwent combined direct and indirect superficial temporal artery-middle cerebral artery revascularization procedure. 62 factors were analyzed using multiplex luminex assay, including angiogenic growth factors, cytokines, and chemokines. Cellular retinoic acid binding protein (CRBP1) was also measured using ELISA. Functional outcome was assessed using the modified Rankin scale score (mRS). Matsushima criteria was used for grading the neovascularization.

Results:
Forty molecules were significantly elevated in both MMD subtypes in comparison with controls. The common top highly secreted CSF proteins included platelet-derived growth factor bb, chemokine ligand 5 and plasminogen activator inhibitor 1 (p<0.001). CRBP1 and other growth factors such as brain-derived nerve growth factor and basic fibroblast growth factor were also elevated in both MMD subtypes (p<0.01). Our results also revealed a number of proteins not previously reported in MMD. Ingenuity pathway analysis indicated that the ischemic and hemorrhagic MMD subtypes exhibited similar cellular/molecular functions and pathways including cellular activation, migration and inflammatory response. Interestingly, while neuro-inflammation and dendritic cell pathways were activated in MMD patients, lipid signaling pathways involving nuclear receptors PPAR and LXR/RXR signaling were inhibited.

Conclusions:
CSF analysis revealed that a number of cytokines, chemokines and growth factors are elevated in both MMD subtypes. These molecules potentially contribute to the pathogenesis of MMD and could be potential future therapeutic targets.
Abstract TP488: Postoperative Remodeling of Donor Arteries on MR Angiography Can Predict Development of Surgical Collaterals in Moyamoya Disease
Authors: Uchino Haruto , Yamamoto Shusuke , Kashiwazaki Daina , Akioka Naoki , Kuwayama Naoya , Noguchi Kyo , Kuroda Satoshi
Published: June 2021

Object:
The calibers of donor arteries can change dynamically after bypass surgery in moyamoya disease (MMD). The present study aimed to evaluate the cut-offs of caliber changes in donor arteries associated with good surgical revascularization and to assess the impact of clinical factors potentially related to bypass development.

Methods:
We studied 71 hemispheres of 30 adults and 16 children with MMD, who underwent combined revascularization. We quantitatively measured the calibers of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) with magnetic resonance angiography (MRA) source images and calculated the postoperative caliber change ratios (CCRs), to assess direct and indirect bypass development. They were compared with the findings of digital subtraction angiography, in which revascularization areas were categorized into 3 groups (poor, good, and excellent).

Results:
In both adult and pediatric hemispheres, median STA and DTA CCRs were higher in better revascularization groups (p < 0.05), while MMA CCRs were not significantly different among the groups. Receiver operation characteristic analysis revealed that the cut-off of >1.1 and >1.3 STA CCRs were associated with good direct revascularization in adult and pediatric hemispheres, respectively. The cut-off of >1.6 and >1.2 DTA CCRs were associated with good indirect revascularization in adult and pediatric hemispheres, respectively. Considering these cut-off values, STA and DTA CCRs showed high median values, irrespective of age, severity of cerebrovascular reserve, disease stage, and disease onset type.

Conclusions:
Caliber changes in STA and DTA can be easily measured by MRA, which could be indicators of direct and indirect bypass development. The combined bypass procedure could maximize revascularization in both adults and children with MMD.
Abstract TP56: Endovascular Treatment Decisions in Acute Ischemic Stroke Patients With Low Baseline Aspects: Insights From an International Multidisciplinary Survey
Authors: Ospel Johanna M , Kashani Nima , Menon Bijoy , Almekhlafi Mohammed , Singh Ravinder , Saposnik Gustavo , Hill Michael D , Goyal Mayank
Published: June 2021

Background and Purpose:
Current AHA/ASA guidelines for the early management of patients with acute ischemic stroke restrict level 1A recommendations for endovascular therapy (EVT) to patients with baseline ASPECTS score >5. However, a recent meta-analysis from the HERMES group showed a treatment benefit in patients with ASPECTS ≤5. We aimed to explore how physicians across different specialties and countries approach endovascular treatment decision-making in acute ischemic stroke patients with low baseline ASPECTS.

Methods:
In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 out of a pool of 22 case-scenarios, 3 of which involved patients with baseline ASPECTS < 6 (A: 40-year old with ASPECTS 4, B: 33-year old with ASPECTS 2 C: 72-year old with ASPECTS 3), otherwise fulfilling all EVT-eligibility criteria. Participants were asked how they would treat the patient in the given scenario A) under their current local resources and B) under assumed ideal conditions, i.e. without any external (monetary, policy-related or infrastructural) restraints. Overall and scenario-specific decision rates were calculated. Clustered multivariable logistic regression analysis was used to determine variables associated with EVT decision in patients with low baseline ASPECTS.

Results:
827/6070 responses were available for the low ASPECTS scenarios. Current and ideal treatment EVT decision rates were 57.1% and 57.6% respectively. Current and ideal decision rates were 69.9% and 60.4% for scenario A, 60.0% and 61.5% for scenario B, 41.3% and 40.2% for scenario C respectively. Annual center EVT volume (OR 1.004,p=.004), annual operator EVT volume (OR 1.009, p=.018) and time since symptom onset (OR 4.543,p<.001) were significantly associated with EVT decision-making under current local resources, while annual operator EVT volume (OR 1.007,p<.029) and time since symptom onset (OR 5.687,p<.001) were associated with decision-making under assumed ideal conditions.

Conclusion:
A majority of physicians decided to proceed with EVT despite low baseline ASPECTS. Operators and centers doing more EVT per year were more likely to offer EVT to patients with low ASPECTS.
Abstract TP67: The Contribution of White Matter Pathology to Language Deficits Following Acute Subcortical Left Hemisphere Stroke
Authors: Sharif Massoud , Meier Erin , Hillis Argye
Published: June 2021

Background:
White matter degeneration, or leukoaraiosis (LA), occurs in aging and increases risk of subcortical stroke. Yet, it remains unclear whether frank lesion and LA are independently predictive of language impairments in patients with left hemisphere (LH) acute subcortical stroke.

Methods:
Patients with acute LH subcortical stroke (<10 days post-onset) participated (n=75). We manually traced lesions on DWI scans and calculated lesion volume/location with NiiStat. LH and right hemisphere (RH) LA were rated on T2-weighted images using the Fazekas et al. (1987) periventricular (PVH) and deep white matter hyperintensities (DWMH) subscales. We generated language z-scores reflecting auditory comprehension, naming, and repetition skills. We assessed relationships between demographic and stroke factors and LA using t-tests and correlations. We used hierarchical linear regression to determine independent associations between lesion volume and LA and language deficits.

Results:
For each hemisphere and Fazekas subscale, we found no significant associations between LA severity and lesion volume (r=-.27- -.07, p>.08) or sex (t=.78-1.51, p>.14). Older age was significantly related to more severe LA (r=.40-.49, p<.001). Greater lesion volume was associated with poorer language abilities (t=-2.08, p=.04). When LH and RH PVH ratings were separately added to this model, both multivariate models were significant (F=3.90 p=.03 (LH), F=3.66, p=.03 (RH)), yet neither lesion volume (p=.08 (LH), p=.08 (RH)) nor PVH ratings (p=.06 (LH), p=.10 (RH)) independently predicted language. Models containing lesion volume and DWMH ratings were not significant (p>.11).

Discussion:
Overall, lesion volume but not LA independently predicts language abilities in patients with acute subcortical LH stroke. Future directions include investigating the individual contributions of frank lesion, LA, and hypoperfusion on aphasia in a larger cohort of patients with acute subcortical stroke.
Abstract TP72: Localization of Large Vessel Occlusion (LVO) Stroke in the Posterior Circulation Based on Perfusion Imaging
Authors: Cereda Carlo W , Heit Jeremy , Qureshi Abid , Hinduja Archana , Grigoryan Mikayel , Bianco Giovanni , Pileggi Marco , Bingham Elijah G , Mlynash Michael , Albers Gregory W
Published: June 2021

Introduction:
The vascular territory of an occluded large intracranial vessel can be reliably identified by CT or MR perfusion imaging. Furthermore, prior studies have shown that perfusion imaging can reliably predict the specific vessel that is occluded in anterior circulation large vessel strokes. We evaluated whether perfusion imaging can predict the specific vessel occlusion (vertebral, basilar, or posterior cerebral) in posterior circulation strokes.

Hypothesis:
We hypothesized that the occluded vessel could be inferred from the perfusion imaging results in >80% of patients with an acute stroke due to large vessel occlusion in the posterior circulation using the simultaneous CTA or MRA as the gold standard. Furthermore, the inter-rater agreement between a vascular neurologist and a neuroradiologist would be > 90%. Agreement Coefficients (AC1) were determined.

Methods:
From a multicenter cohort of consecutive patients with posterior circulation stroke, we included patients with documented occlusion of the Basilar Artery (BA) posterior cerebral Artery (PCA) or vertebral artery (VA) who had perfusion imaging (MRI or CT) processed by RAPID software. Perfusion images were evaluated blinded to the angiography or any other brain imaging results. The primary outcome measure was agreement on LVO location based on the CTA/MRA results.

Results:
74 patients were eligible: age 63±2, female 32%, median NIHSS 15 (IQR 5-24). The distribution of large vessel occlusions on CTA/MRA was BA (74%), PCA (14%) and VA (12%). Perfusion imaging was able to correctly predict the occluded vessel in 63 (85%), AC1 = 0.82 (95% CI 0.72-0.92), p<0.001. Interrater agreement (n=41) was high [AC1 = 0.94 (95% CI 0.87-1.0), p < 0.001].

Conclusion:
Perfusion imaging can predict the site of vessel occlusion (vertebral, basilar, or posterior cerebral) in posterior circulation strokes with good accuracy and high inter-rater agreement.
Abstract TP73: Heterogeneity of Occlusive Thrombus Investigated on Pretreatment Imaging in Acute Ischemic Stroke
Authors: Hashimoto Tetsuya , Honda Tristan , Scalzo Fabien , Sharma Latisha K , Hinman Jason D , Rao Neal M , Nour May , Bahr Hosseini Mersedeh , Saver Jeffrey L , Raychev Radoslav , Liebeskind David S
Published: June 2021

Background and Purpose:
Investigation of occlusive thrombus in ischemic stroke is expected to clarify the etiology and mechanism of stroke fueling an optimal treatment strategy. However, in situ propagation due to secondary thrombosis after initial embolic occlusion could obscure the characteristics of initial emboli. Differentiation of the initial embolus and secondary thrombosis using retrieved specimens might be difficult due to fragmentation of whole thrombi. We aimed to investigate the heterogeneity of occlusive thrombi using pretreatment imaging of ischemic stroke.

Methods:
Among consecutive stroke patients with acute embolic occlusion of the anterior circulation eligible for endovascular reperfusion therapy, we retrospectively reviewed 81 patients who underwent both brain non-contrast CT (NCCT) and CT angiography (CTA) on admission from June 2015 to May 2018. Region of interest (ROI) was set on the whole thrombus on NCCT, which was identified referring to the filling defect on CTA, and the size of thrombus was measured. ROI was then divided equally into proximal and distal segments and Hounsfield Unit (HU) densities of those segments were measured respectively. Difference of HU between proximal and distal segments (ΔHU; HU in proximal segment - HU in distal segment) was calculated and analyzed.

Results:
HU density on NCCT in proximal segment was higher than in distal segment (mean difference: 3.75, 95% CI: 2.69-4.80, p<0.01). ΔHU was correlated positively with the length of thrombus (ρ=0.32, p<0.01), and correlated inversely with the time from last-known-well (LKW) to imaging (ρ=-0.29, p=0.01) and blood platelet level (ρ=-0.27, p=0.02). Stroke subtype and vascular risk factors had no significant correlation with ΔHU. On multivariate regression analysis, the length of thrombus (β=0.31, p=0.01) and the time from LKW to imaging (β=-0.30, p=0.01) were associated with ΔHU.

Conclusions:
Density of occlusive thrombi in the proximal segment is higher than in the distal segment. This difference increases as thrombi grow longer and decreases as thrombi get older after embolic occlusion. This time/length-dependent thrombus heterogeneity is suggestive of secondary thrombosis, occurring initially at the proximal side of occlusion.
Abstract TP84: Prognostic Factor of Intracranial Vertebral Artery Dissection: High Resolution Vessel Wall Magnetic Resonance Imaging Study
Authors: Kim Jae-Hwan , Kim Hyung Jun , Kim Ye Sel , Seo Woo-Keun , Bang Oh Young , Kim Gyeong-Moon
Published: June 2021

Background:
Vertebral artery dissection (VAD) is well recognized cause of stroke in young and middle aged individuals. But, prognostic factor of posterior circulation ischemic stroke or transient ischemic attack (TIA) caused by intracranial VAD has been rarely discussed. Our aim was to evaluate the predictors of poor outcomes in posterior circulation ischemic stroke caused by intracranial VAD.

Methods:
We retrospectively reviewed patients with posterior circulation ischemic stroke or TIA caused by intracranial VAD using high-resolution vessel wall MRI who were recruited from Samsung Medical Center Stroke Registry (between January 1, 2011 and April 30, 2019). Poor outcomes were defined as a 3-months modified Rankin scale (mRS) score ≥ 2.

Results:
We registered 96 patients (74 males; mean age, 58.9±14.2 years) with acute posterior circulation ischemic stroke or TIA caused by intracranial VAD. Trauma history associated with VAD was presented in 23 (24%) of patients. Headache and neck pain around neurological symptom onset were presented in 41 (42.7%) and 19 (19.8%) of patients, respectively. Dissecting aneurysm, bilateral vertebral artery involvement, basilar artery involvement and wall hematoma with dissection were presented in 26 (27.1%), 26 (27.1%), 12 (12.5%) and 66 (68.8%) of patients, respectively. Of the 96 VADs, 26 (27.1%) presented with focal stenosis, 21 (21.9%) with multifocal stenosis, and 57 (59.4%) with occlusion. Lateral medulla involvement and multiple territory involvement were presented in 35 (36.5%) and 31 (32.3%) of patients. Recurrence rate of ischemic stroke or TIA within 90 days of symptom onset was 6.25%. Twenty-nine patients (30.2%) had poor outcomes at 3 months. Lateral medulla involvement was an independent predictor for poor outcome (odds ratio=3.293, 95% confidence interval=1.301-8.333, p=0.012).

Conclusion:
Posterior circulation ischemic stroke or TIA caused by intracranial VAD is associated with relatively benign clinical course. But the presence of lateral medulla involvement is independent predictor for poor outcome. Patients presenting lateral medullary infarction caused by intracranial VAD should be monitored closely.
Abstract TP85: The Characteristics of Diffusion Weighted Image Patterns in Different Potential Embolic Source
Authors: Yamamoto Yasumasa , Nagankane Yoshinari , Tomii Yasuhiro
Published: June 2021

Introduction:
Few studies have focused on the characteristics of diffusion weighted image (DWI) pattern in different embolic stroke.

Hypothesis:
Studying the DWI pattern in patients with embolic stroke of determined source may help presume the cause of ESUS.

Methods:
From a prospective registry of 1,764 consecutive patients with acute ischemic strokes , we selected 422 patients with embolic stroke of determined source comprising of 4 groups as follows. 1: continuous atrial fibrillation (cAf) (n=232), 2: paroxysmal Af (pAf) (n=99), 3: paradoxical embolism associated with the foramen ovale (PXE) (n=48) and 4: aortogenic embolism associated with aortic atheroma (≥4mm, ulcer or mobile) (AoE) (n=56). The DWI patterns were classified as follows. First, cortical infarcts were classified according to the affected area of middle cerebral artery (MCA) segments such as M1: the horizontal segment, M2: after the bifurcation segments within the Sylvian fissure and M4: terminal cortical branch. Among patients with M1, pure striatocapsular infarction (SCI) was identified. Moreover, patients with the M2 and the M4 were divided into 2 groups including parietal ascending branches and temporal descending branches. Second, cortical and subcortical small multiple infarcts (<20mm) (sMI) were identified. Finally, infarcts in the anterior cerebral artery (AC) and the posterior circulation (PC) were identified.

Results:
The distribution of the DWI patterns in the 4 groups (cAf: pAf: PXE: AoE, %) are as follows: M1 (n=100) (76.0: 17.0: 7.0: 0), M2 (n=118) (59.3: 30.5: 7.6: 2.5), M4 (n=50) (50.0: 26.0: 18.0: 6.0), SCI (n=20) (2.1: 4.0: 14.5: 0), sMI (n=49) (18.3: 16.3: 18.3: 46.9), AC (n=13) (46.1: 46.1: 0: 7.6), and PC (n=92) (50.0: 20.6: 15.2: 14.1). Among 162 patients with M2 and M4 infarction, there were 57 involvements of descending branches (35.1%), comprising of 38 patients (41.7%) in cAf, 17 (34.6) in pAf, 1 (6.2) in PXE and 1(7.4) in AoE.

Conclusions:
Infarct sized was large in the Af groups. The involvement of inferior division of the MCA was exclusively found in the Af groups. The SCI was most prevalent in the PX. Multiple small scattered pattern was characteristically found in the AoE. The different DWI patterns relatively well associated with different embolic source.
Abstract TP94: White Matter Tract Integrity After Vascular Insult: Longitudinal Analysis of Hemorrhagic vs Ischemic Lesions
Authors: Rosenbaum-Halevi David , Parsha Kaushik N , George Sarah D , Boren Seth B , Sitton Clark W , Aronowski Jaroslaw , Haque Muhammad , Asgarisabet Parisa , Savitz Sean I
Published: June 2021

Introduction:
White matter tract (WMT) injury occurs in patients with acute cerebrovascular disorders. In this study, we elucidate longitudinal differences in mechanism of injury and repair between ischemic stroke (ISC) and intracerebral hemorrhage (ICH).

Methods:
Twenty patients (10 ISC and ICH) were prospectively imaged at 1, 3, and 12 months of onset on a 3T MRI. 3D anatomical and DTI images were obtained and integrity of the corticospinal tract (CST) assessed at the ipsi and contralesional posterior limb of internal capsule (PLIC). Fractional anisotropy (FA), mean diffusivity (MD) and pixel volume were recorded. A linear regression model was applied for statistical analysis.

Results:
ISC group had 4 men, 6 women whereas ICH group had 7 men, 3 women, both with average age 52. Baseline NIHSS in ISC was 11 (IQR=4.5-20) and ICH 6 (IQR=2-13). All lesions were unilateral, hemispheric, completely subcortical or with a significant subcortical component. The average lesion and hematoma volume at 1 month was 37 and 39 cc in ISC and ICH, respectively. The MD in the PLIC of the ISC increased from 1 to 3m (P <0.05) then plateaued, whereas it decreased in ICH over the entire 12m (Fig 1A). The rFA showed a similar pattern of initial injury and then improvement over time in both ISC and ICH (Fig 1B). The ISC group showed 12% WM atrophy in the PLIC at 12m, wheras 13% expansion (P < 0.05) in ICH over this period, after an initial contraction of 14% at 1m (fig 1C-D). Structural changes of the PLIC correlated with changes in mRS/NIHSS (p<0.05).

Conclusions:
ISC and ICH display unique patterns of WMT changes over one year in which ICH injury reflects a compression of the CST that resolves over time, while in ISC our data show degeneration and microstructural injury. These changes reflect different mechanisms of injury and remodeling on a cellular level. A better understanding of these changes could improve recovery therapies. Larger studies are needed to better characterize long term WMT changes in IS and ICH.
Abstract TP95: Novel Biomarkers of Acute Ischemic Stroke Using MicroRNA Analysis
Authors: King Jason , Sidorov Evgeny , Vanamala Jairam , Bejar Cynthia , Indukuri Vijay , Reddivari Lavanya , Chainakul Juliane , Bappaditya Ray , Sanghera Dharambir , Jorge Ortiz Garcia
Published: June 2021

Background:
Despite recent advances in treatment, early diagnosis and prognosis of acute ischemic stroke (AIS) suffers from significant limitations. Growing number of mostly case-control studies have determined that noncoding, micro-ribonucleic acid (miRNAs) play a role in the pathophysiologic processes related to cerebral ischemia and post-stroke recovery. This pilot project is a longitudinal study, which investigates difference in miRNA regulation in acute vs. chronic stage of ischemic stroke.

Hypothesis:
Expression of some miRNAs is significantly altered in acute stage of ischemic stroke.

Methods:
Blood and urine specimens collected during the acute phase (<72 hours) of ischemic stroke and at follow-up phases (within 3 months) were used to quantify the expression of five selected miRNAs (miRNA 21-5p; miRNA 124-5p, miRNA 126, miRNA 223, and miRNA 298) using 20 sample pairs (N=40) available with urine and blood specimens. Total RNA from frozen blood samples were isolated using the
mir
VANA RNA isolation kit (Ambion, USA). We extracted exosomal RNA from urine samples using exosome kit (Qiagen, USA). We ran miRNA expression assays using TaqMan probes (Applied Biosciences, USA) on 384-well microplates using QuantStudio 6 available in our lab. Each assay was run in duplicates using endogenous (U6) and blank controls.

Results:
The miRNA21-5p was significantly down-regulated (p<0.0001) at the acute phase in both blood and urine; inversely, miRNA124 was significantly upregulated (p<0.0001) at the acute phase vs. the chronic phase. The increased expression of miRNA 124-5p in both urine and serum strongly correlated with a lower stroke scale (NIHSS score (<8)), and its expression was significantly diminished with the increase in stroke severity (NIHSS >10). Expression of exosomal miRNA126 extracted from urine, was significantly upregulated (p<0.0001) during the acute phase, but remained unchanged at the acute and chronic phase (p=0.857) in serum.

Conclusion:
Our study showed the dysregulation of important miRNAs in acute stage of stroke. The upregulation of miRNA 124-5p in strokes with lower NIHSS may serve as early prognostic biomarker. Once replicated in larger scale studies, it will provide novel insights on understanding stroke pathophysiology.
Abstract TP97: Neuronal Loss of Cd200 Signaling is Sufficient to Impact on Ischemic Stroke
Authors: Mamun Abdullah A , Sharmeen Romana , Xu Yan , Liu Fudong
Published: June 2021

Introduction:
CD200 is primarily expressed on neurons and endothelial cells. It binds to its receptor CD200R on immune cells to form an endogenous inhibitory signaling that reduces the activation of leukocytes. Once a stroke occurs, ischemic neurons have compromised CD200 signaling that could impact on post-stroke inflammation and outcomes. Research efforts aimed at altering neuronal CD200 signaling have high translational value. In the present study, we hypothesized that neuronal CD200 signaling plays a critical role in the immune response to stroke.

Methods:
Neuronal CD200 conditional knockout (CKO) mice (8-12 weeks) generated by a cross between CD200 floxed and enolase (Eno2) Cre mouse were subjected to a 60-minute middle cerebral artery occlusion (MCAO). Stroke outcomes (infarct size and behavioral deficits) were evaluated at 3, 14, and 30 days after MCAO. Fluoro-Jade B (FJB) and TUNEL staining were used to detect degenerating and apoptotic neurons. BrdU and neurofilament-L immunostaining were performed to assess neurogenesis and axonal growth respectively at 14 and 30 days after injury. Resident and peripheral immune cell infiltration in the brain was examined by flow cytometry (FC). MultiPlex was used to measure plasma and brain cytokine levels.

Results:
After MCAO, CD200 CKO mice had larger infarcts (3d), more brain tissue atrophy (14d and 30d) and worse behavioral outcomes compared to CD200 floxed control mice. FJB and TUNEL staining revealed significantly more neuronal death and apoptosis in CD200 CKO vs. floxed mice. Neurogenesis and axonal regeneration were also significantly compromised by CD200 CKO. FC results showed that microglia exhibited an enhanced pro-inflammatory phenotype in CKO mice, and there was significantly more peripheral immune cell infiltration in the ischemic brain. CD200 CKO also induced higher plasma pro-inflammatory cytokine levels (TNFα, IL1β, and IL-6).

Conclusion:
Neuronal loss of CD200 is detrimental in stroke. Neuronal CD200 signaling potentially provides a promising therapeutic target for treatment of neuroinflammatory diseases including stroke. Our future work will focus on over-expression of CD200 in neurons by lentivirus technique, in the hope of inducing beneficial effects in stroke.
Abstract TP99: Human Lung Endothelial Cell Anti-Inflammatory and Regenerative Responses in Acute Ischemic Stroke
Authors: Satani Nikunj , Giridhar Kaavya , Wewior Natalia , Norris Dominique D , Olson Scott D , Aronowski Jaroslaw , Savitz Sean I
Published: June 2021

Background:
Inflammatory responses after stroke consists of central and peripheral immune responses. The role of the spleen after stroke is well-known, however the role of the lungs has not been studied in detail. We explored the relation between stroke severity and immunomodulatory changes in lung endothelial cells.

Methods:
Human pulmonary endothelial cells (hPECs, Cell Biologics) were cultured at passage 3. Serum from stroke patients with NIH Stroke Scale (NIHSS) severity ranging from 0 to 20 was collected at 24 hours after stroke. hPECs were exposed to media with 1) 10% FBS alone (N=6), 2) 10% serum from stroke patients (N=72), or 3) 10% serum from stroke mimic patients (N=6). After 3 hour of exposure, fresh media was added and secretomes from hPECs were measured after 24 hours. We isolated RNA from hPECs after 3 hour of serum exposure and measured gene expression (N=6 for each group). Secretome and gene changes in hPECs were analyzed based on stroke severity, tPA treatment, and co-morbidities.

Results:
Serum from stroke patients reduced the secretion of IL-8, MCP-1 and Fractalkine (p<0.01), and increased the secretion of VEGF and BDNF (p<0.01) from hPECs. These effects were more pronounced depending on stroke severity (Fig). There was no effect of tPA or T2DM on hPECs secretomes. There was significantly reduced gene expression of IL-6, IL-8, MCP-1 and IL-1β and significantly higher expression of ICAM1, IGF-1 and TGF-β1 as compared to stroke mimics.

Conclusion:
Exposure of hPECs to serum from stroke patients alters their immunomodulatory properties. Higher severity of stroke leads to more protective response from hPECs by reducing the secretion of pro-inflammatory factors, while increasing the secretion of anti-inflammatory factors.
Abstract WMP10: The Role of Intravenous Thrombolysis Before Mechanical Thrombectomy: A Subgroup Analysis of the RESILIENT Trial
Authors: Sampaio Silva Gisele , Miranda Maramelia , Barros Felipe , Frudit Michel , Pontes-Neto Octavio , Montalverne Francisco Jose , Rebello Leticia , Carbonera Leonardo , Abud Daniel , Lima Fabricio , de Souza Ana Claudia , Liebeskind David , Mosmann Gabriel , Bezerra Daniel , Saver Jeffrey , Buchidid Cardoso Fabrício , Nogueira Raul , Martins Sheila
Published: June 2021

Background:
Mechanical thrombectomy (MT) in addition to intravenous thrombolysis (IVT) is now the recommended treatment for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). The positive trials also demonstrated that MT alone among patients ineligible for IVT is an effective therapy for AIS. Whether MT alone is as effective, worse, or better than pretreatment with IVT before MT among IVT-eligible AIS patients with LVO is debatable. We aimed to assess the effect of IVT on the clinical outcome of MT in the RESILIENT trial.

Methods:
RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone. A total of 221 patient were enrolled. The trial showed a strong benefit to thrombectomy (90-day mRS ordinal shift, OR 95%CI). All eligible patients received intravenous tPA within the 4.5-hour-window. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with the use of intravenous tPA as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value < 0.05 was considered statistically significant.

Results:
Among 221 randomized patients (median NIHSS, 18 IQR [14-21]), 155 (70%) were treated with IV tPA. The frequency of good recanalization (TICI 2b> ) and of hemorrhagic transformation was not affected by IVT. There was no significant difference in the treatment effect size across patients who received intravenous tPA versus those who did not in terms of overall functional disability (ordinal mRS shift: aOR: 2.63, 95%CI [1.48-4.69] vs. 1.54, 95%CI [0.63-3.74]; p=0.42) or functional independence (mRS 0-2: aOR: 3.06, 95%CI [1.37-6.48] vs. 1.71 95%CI [0.55-5.33], p=0.40) at 90 days.

Conclusions:
The large effect size of MT on LVO outcomes was not significantly affected by IVT. Further studies directly evaluating the role of IVT before MT are of utmost importance.
Abstract WMP102: Pilot Study of a Non-invasive Radiofrequency Method to Monitor Intracranial Hemorrhage: A First-in-Human Study
Authors: Flaherty Matthew L , Korfhagen Joseph , Shaw George J , Adeoye Opeolu , Knight William
Published: June 2021

Introduction:
Intracerebral hemorrhage (ICH) is a devastating form of stroke. Hemorrhage expansion after ICH occurs in ~40% of patients and leads to worse outcomes. Currently, ICH patients are monitored for hemorrhage expansion by neurologic exam and head CT. CT studies are a source of radiation exposure and can require transporting the patient out of the ICU. There is a clinical need for a non-invasive bedside monitor of ICH.

Methods:
A radiofrequency based monitor (RFM) was developed as a non-invasive method to monitor ICH at the bedside. The RFM consists of a 9-antenna array mounted around the head, cables, and driving electronics. A 913 MHz signal is transmitted from a given antenna, crosses the brain, and is received by the remaining 8 antennae. A complete measurement consists of one cycle with all antenna serving as the transmitting antenna. As the signal traverses the brain, it is partially scattered and absorbed by the ICH, thus changing the signal at the receiving antennae. The altered signal can be compared to signals at earlier times to detect changes induced by ICH expansion. Based upon pre-clinical work it was hypothesized that ICH expansion of ≥3 ml would be detected by the RFM. The RFM device was approved for human study under an IDE from the FDA. The device was tested on 10 ICH subjects admitted within 24 hours of stroke onset. All subjects received a baseline head CT and a repeat head CT at 12 (+/- 6) hours. ICH volumes were determined by a blinded neuroradiologist. Subjects were scanned with the device every 10 minutes.

Results:
Data from one subject was lost due to user error. Among the remaining nine, two experienced hemorrhage expansion of ≥ 3ml (3 and 8.2 ml respectively). The RFM readings were 100% concordant with CT scans in identifying presence and absence of hemorrhage expansion. The figure shows monitor readings from a subject with expansion.

Conclusion:
The RFM may be useful in detection of real-time hemorrhage expansion in ICH patients. A pivotal clinical study is planned.
Abstract WMP104: Fully Automated Segmentation Algorithm for Volumetric Analysis of Perihematomal Edema After Spontaneous Intracerebral Hemorrhage
Authors: Ironside Natasha , Chen Ching-Jen , Mutasa Simukayi , Sim Justin , Ding Dale , Roh David , Mukherjee Sugoto , Johnson Karen , Southerland Andrew , Mayer Stephan , Lignelli Angela , Connolly Edward
Published: June 2021

Background:
Perihematomal edema (PHE) is a promising marker of secondary injury in patients with spontaneous intracerebral hemorrhage (ICH). It can be challenging to accurately and rapidly quantify. The aims of this study are to derive and internally validate a fully automated segmentation algorithm for volumetric PHE analysis.

Methods:
Inpatient CT scans of 400 consecutive adults with spontaneous supratentorial ICH enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) were separated into training (n=360) and test (n=40) datasets. A fully automated algorithm was derived from manual segmentations in the training dataset using convolutional neural networks and its performance was compared to manual and semi-automated segmentation methods in the test dataset.

Results:
The mean volumetric Dice similarity coefficients for the fully automated algorithm were 0.838±0.294 and 0.843±0.293 with manual and semi-automated segmentations as reference standards, respectively. PHE volumes derived from fully automated vs. manual (R
2
=0.959;p<0.001), fully automated vs. semi-automated (R
2
=0.960;p<0.001) and semi-automated vs. manual (R
2
=0.961; p<0.001) methods had strong between group correlations. The fully automated algorithm (mean 18.0±1.8 seconds/scan) quantified PHE volumes at a significantly faster rate than manual (mean 316.4±168.8 seconds/scan; p<0.001) and semi-automated (mean 480.5±295.3 seconds/scan; p<0.001) methods.

Conclusions:
The fully automated algorithm accurately quantified PHE from CT scans of supratentorial ICH patients with high fidelity and greater efficiency compared with manual and semi-automated segmentation methods.