bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP476: Remarkable Hemorrhagic Imaging Manifestations Might Be Responsible for the Prominent Atrophy and Cognitive Decline in Sneddon Syndrome
Authors: Yao Ming , Zhao Jiuliang , Ni Jun
Published: June 2021

Objective:
Sneddon syndrome is a rare non-inflammatory arteriopathy affecting small and medium-sized arteries, characterized by a generalized livedo reticularis and recurrent ischemic stroke. Hemorrhagic stroke was reported in limited cases, but microbleeds and superficial siderosis were rarely issued, which might be underdiagnosed due to the limitation of technique. We aimed to investigate the hemorrhagic imaging features of Sneddon syndrome and explore the possible mechanism and clinical relevance.

Methods:
Clinical data and cerebral MR imaging including T2* sequence of 6 consecutive patients with Sneddon syndrome were reviewed.

Results:
The most common neurological manifestations were cognitive impairment and stroke attack(66.7%), followed by seizures(33.3%) and movement disorder(16.7%). Cerebral microbleeds were detected in all the patients on T2* sequence,four of whom presented more than 5 microbleeds.The majority of the microbleeds were predominantly cortical restricted and especially located in the cortical watersheds. Multiple superficial siderosis were identified and mainly involved cortical watersheds in 5 cases. Significant cerebral atrophy with prominent secondary white matter hyperintensities in bilateral cortical watersheds were also observed. Abnormal tortuous and multiple focal occlusion of bilateral distal MCA were shown in 1 patient by DSA. No stenosis of proximal segment of cerebral arteries was detected in all the patients.

Conclusions:
This is the first report illustrating abundant cortical microbleeds and superficial siderosis mainly involved the anterior and posterior cortical watersheds in Sneddon syndrome. The surprisingly identical topographic distribution of hemorrhagic lesions and the corresponding obvious atrophy suggest cerebral atrophy might be secondary to the microangiopathy related hemorrhagic lesions and further contribute to the neurological deficit, especially the early cognitive decline in Sneddon syndrome,although further investigation is needed to elucidate the precise underlying pathogenesis. These highlight cortical microbleeds and superficial siderosis located in cortical watershed and the secondary atrophy in youth might be highly indicative of Sneddon syndrome.
Abstract WP478: Microglia Knockdown Reduces Inflammation and Improves Post-Stroke Cognitive Impairment in Diabetic Animals
Authors: Jackson Ladonya , Dumanli Selin , Johnson Maribeth , Fagan Susan , Ergul Adviye
Published: June 2021

Unfortunately, over 40% of stroke victims have pre-existing diabetes which not only increases their risk of stroke up to 2-6 fold, but also worsens both functional recovery and the severity of cognitive impairment. Our lab has recently linked the chronic inflammation that persists in diabetic animals to their poor functional outcomes and exacerbated cognitive impairment, also known as post-stroke cognitive impairment (PSCI). Although we have shown that the development of PSCI in diabetes is associated with the upregulation and activation of pro-inflammatory microglia, we have not established a direct causation between the two. We tested the hypothesis that microglia depletion in the post-stroke recovery period prevents sustained inflammation and attenuates PSCI in diabetes.

Methods:
Diabetes was induced by a high fat diet (HFD) and low dose streptozotocin (STZ) combination. At 13 weeks of age, diabetic animals received bilateral intracerebroventricular (ICV) injections of short hairpin RNA (shRNA) lentiviral particles targeted at the colony stimulating factor 1 receptor (CSF1R), a key factor for microglia survival. After 14 days, animals were subjected to 60 min middle cerebral artery occlusion (MCAO) or sham surgery. Novel object recognition (NOR), and 2-trial Y-maze were utilized to evaluate cognitive function. Brains were analyzed by flow cytometry (B-D slice containing the prefrontal cortex through the hippocampus) and immunohistochemistry (B slice) 3 weeks post-MCAO.

Results:
CSF1R silencing resulted in a drastic 94% knockdown of residential microglia to relieve inflammation and decrease the macrophage infiltration by 74%. This also led to improved myelination of white matter in the brain and improved cognition in diabetic animals.

Conclusion:
Neuroinflammation, through microglial and macrophage polarization, is largely responsible for the development of PSCI in diabetes.
Abstract WP48: Impact of Rapid Complete Recanalization on Clinical Recovery in Cardioembolic Stroke Patients With M2 Occlusion
Authors: Aoki Junya , Kimura Ryutaro , Numao Shinichiro , Sawada Kazutaka , Katano Takehiro , Sakamoto Yuki , Suzuki Kentaro , Kanamaru Takuya , Suda Satoshi , Nishiyama Yasuhiro , Kimura Kazumi
Published: June 2021

Background and purpose:
Recent study reported the impact of complete recanalization beyond significant recanalization. The main of present study is to investigate the impact of complete recanalization in stroke patients with distal (M2) middle cerebral artery (MCA) occlusion.

Methods:
From our prospective endovascular thrombectomy (EVT) registry and multicenter tPA trial (YAMATO study) data bank, data on M2 occlusion and treated with EVT and/or tPA were retrospectively reviewed. In the YAMATO study, all tPA patients were examined using MRA before and at 1 hour after tPA. Thus, we defined the complete recanalization as a modified TICI of 3 at the end of EVT or similar appearances of both MCA on MRA at 1 hour after tPA. Significant recanalization was TICI ≥2b or >50% recanalization of MRA. At 3 months, favorable outcome was defined as mRS ≤ 2.

Result:
Data on 122 patients with M2 occlusion (median age 79 [72-85] years; male, 69 [57%], NIHSS score 13 [8-19]) received tPA and/or EVT were analyzed. Onset-to-admission was calculated as 95 (52-189) minutes. Complete recanalization was achieved in 27 (22%) patients, and significant recanalization was in 75 (61%) patients. Neither EVT administration it self, tPA, combined EVT and tPA were related to the complete recanalization (p=0.383, 0,237 and 0.612). At 3 months onset, patients with complete recanalization at the end of EVT/tPA frequently had favorable outcome than those without it (75% vs. 43%, p=0.013), while significant recanalization did not statistically increase the rate of favorable outcome (52% vs. 46%, p=0.673). Age, NIHSS score, DWI-ASPECTS, and plasma levels of d-dimer and brain benign peptide were also related to the favorable outcome (0.031, <0.001, 0.005, 0.011, and 0.010). Finally, multivariate regression analysis found that complete recanalization was an independent parameter related to the favorable outcome (odd ratio, 5.0 95%CI [1.1-23.0], p=0.038) as well as DWI-ASPECTS (odds ratio, 2.1, 95%CI [1.2-3.3], p=0.001).

Conclusion:
Complete recanalization but not significant recanalization was a parameter associated with favorable outcome in M2 occlusion patients. The goal of recanalization therapy may be immediate and complete recanalization even in patients with distal MCA occlusion.
Abstract WP480: Beneficial Effect of Chronic-Remote Ischemic Conditioning (C-RIC) is Dependent Upon Circulating Blood Cell NOS3 in a Vascular Cognitive Impairment and Dementia (VCID) Model
Authors: Khan Mohammad B , Siddiqui Shahneela , Rehman Amna , Blauenfeldt Rolf A , Alam Haroon , Shaikh Muhammad F , Sharma Abhinav , Vaibhav Kumar , Braun Molly , Achyut Bhagelu R , Rashid Mohammad H , Khodadadi Hesamoldin , Baban Babak , Dhandapani Krishnan M , Hess David C
Published: June 2021

Background and Purpose:
Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This effect is lost in NOS3-KO mice. We wanted to determine if the beneficial effect of C-RIC can be restored by bone marrow cell-derived NOS3.

Methods:
We prepared BM chimera from adult WT (B6.SJL-Ptprc
a
; CD45.1) to adult NOS3-KO (B6.129; CD45.2) & vice versa in male mice (5-6 months) following confirmation for BM engrafting with flow cytometry at 2 weeks. Microcoil (0.18 mm) induced BCAS model was used to induce chronic hypoperfusion. Mice were randomly assigned to 3-groups: (1) Sham (2) BCAS and (3) BCAS+RIC. RIC was started 7d post-surgery daily for 3-4 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. We measured whole blood P-NOS3, P-AMPK and VEGFR2/CD31 by flow cytometry.

Results:
C-RIC-therapy for 3-4 weeks improves CBF in engrafted BM of WT into NOS3-KO in the BCAS+RIC groups at both 2 weeks and 4 weeks compared to BCAS (Sham RIC groups).No effect of C-RIC was shown in engrafted BM of NOS3 into WT. There was significant change between the BCAS and BCAS+RIC groups in the functional outcomes and histopathological evidences also reflects major changing in the groups in the BM of WT into NOS3-KO mice. Whole blood P-NOS3, P-AMPK and VEGFR2/CD31 was increased by C-RIC. However, no effect was shown in the NOS3-KO into WT chimera.

Conclusions:
The Beneficial effect of C-RIC is dependent upon bone marrow derived NOS3.Further studies are needed to determine if the red blood cell is the key cell carrying NOS3
Abstract WP482: Early Life Exposure to the Stroke Belt and Later Life Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Howard Virginia J , Howard George , Manly Jennifer J , Glymour M M , Zahodne Laura B , Crowe Michael G , Bennett Aleena , McClure Leslie A , Unverzagt Frederick W , Wadley Virginia G
Published: June 2021

Introduction:
Incidence of cognitive impairment is higher for residents of the Stroke Belt (SB) compared to those living outside it, but the importance of timing of SB residence is unclear.

Methods:
Participants were aged 45+ yrs, and enrolled in 2003-2007 in REGARDS. Cognition was assessed annually, by telephone, using the Six-Item Screener (SIS) in 11,488 black or white stroke-free participants currently living in the SB, and 8,949 currently living outside of the SB. Incident cognitive impairment was defined as SIS score of

<

4 at last assessment among participants with initial SIS >4. Exposures were defined as SB residence all years, some years, or no years of childhood (ages 0-18) and early adulthood (ages 19-30). Demographic adjusted logistic regression models were stratified by SB residence at enrollment, and were used to estimate the demographic-adjusted odds of incident cognitive impairment.

Results:
Among those currently residing in the SB, childhood residence outside the SB for some (OR = 0.82; 95% CI: 0.68 - 0.99) or all (OR = 0.76; 95% CI: 0.65 - 0.90) of the time predicted lower odds of incident cognitive impairment. Similarly, early adulthood residence outside the SB for some (OR = 0.86; 95% CI: 0.74 - 0.98) or all (OR = 0.70; 95% CI: 0.58 - 0.84) of the time predicted lower incident cognitive impairment. Conversely, for those currently living outside the SB, the risk of incident cognitive impairment was higher for those who had spent their entire early adulthood in the SB (OR = 1.51; 95% CI: 1.01 - 2.57), with non-significant increased risk for childhood exposure or some early adulthood exposure to the SB (table).

Conclusions:
These findings suggest that early residence in the SB during childhood or early adulthood increases the risk of cognitive impairment regardless of place of residence in later adulthood. Further research is needed to determine the characteristics of early SB life that are linked to later adult cognitive impairment.
Abstract WP483: Grouped Cortical Micro Bleeds a Unique Radiological Marker in Inflammatory Cerebral Amyloid Angiopathy
Authors: Mittal Sanjay , Tarasaria Karan
Published: June 2021

Background:
Inflammatory Cerebral Amyloid Angiopathy (iCAA) is a rare cause of rapidly progressive cognitive decline. Prior studies have proposed radiological diagnostic criteria and demonstrated evidence of inflammation related to Aβ. Though lacking any therapeutic trials, various authors have suggested a single pulse IV Methyl Prednisolone (MPS) therapy as curative in most patients.

Methods:
We studied clinical, radiological and neuropathological features of 2 of biopsy proven iCAA cases over the past 5 years correlating their neuropathological and radiological features. We also reviewed published literature for radiological findings of proven cases of ICAA Clinical features Case 1: 75/female presented with visual hallucinations, her neurological examination was un-remarkable >Case 2: 84/female presented with language and memory difficulties her neurological examination was remarkable for word finding and object naming difficulties Radiological Features: Gadolinium enhanced brain MRI with fluid attenuated inversion recovery (FLAIR) and susceptibility weighted imaging (SWI) were obtained
Patient 1: SWI artifact
s
in
bilateral cerebral hemispheres
basal ganglia and cerebellum suggestive of cortical micro-bleeds (CMBs
)
there was a cluster of CMBs in the right parietal region
associated with FLAIR changes and gadolinium enhancement
Patient 2
numerous scattered cortical micro-bleeds (CMBs). There
was a
large cluster
of CMBs in
left temporal lobe along with FLAIR
changes
and gadolinium enhancement
Biopsy:
B
oth patient underwent
lesional
biopsy
corresponding to
the
area of clustered CMBs
Neuropathology: demonstrated
histopathological and electron microscopic evidence
of perivascular inflammation and amyloid deposition consistent with
iCAA
Review of literature
:
In
a total of 7 brain MRI
s
in 3 recently published case series 4 had reported CMBs of which 3
patients were
identified
representing
MRI findings
consistent with
Grouped CMBs
associated
with FLAIR changes

Conclusion:
iCAA is a rare and treatable cause of subacute cognitive decline. We suggest grouped cortical micro bleeds (GCMBs) associated with FLAIR changes as a unique radiological feature of this disorder.
Abstract WP485: Racial Differences in the Association Between Central Hemodynamic Parameters and Neuropsychological Assessments
Authors: Buie Joy N , Magwood Gayenell , Sims-Robinson Catrina , Lackland Daniel , Adams Robert
Published: June 2021

Introduction:
Despite a significantly younger at time of stroke, African Americans are at increased risk for post-stroke cognitive impairment compared to whites. Although central arterial stiffness is a well-established correlate of cognitive function in whites, its predictive value in African Americans is not well characterized. We hypothesized that arterial stiffness measures previously associated with declines in cognition may be more robust in African Americans compared to whites.

Methods:
We administered the Mini Mental State Examination (MMSE), Trail Making Test Part-A (TMTA) and Part-B (TMTB), and Symbol Digit Modalities Test (SDMT) to 54 stroke-free adults (28 African Americans and 26 whites). Central hemodynamic parameters including carotid-femoral pulse wave velocity (PWV), central systolic blood pressure (cSBP), central pulse pressure (cPP), and heart rate-corrected augmentation index (AIx@75) were recorded for each study participant. Univariate analysis was used to evaluate age, sex and mean arterial pressure (MAP) mean-adjusted differences in central hemodynamics. We also evaluated associations between central hemodynamics and neuropsychological test by race.

Results:
Mean-adjusted PWV values were significantly higher in African Americans compared to whites with values ranging from 8.8 m/s to 7.8 m/s, respectively. Adjusted mean cSBP and AIx@75 were also significantly increased in African Americans. Among whites, unadjusted PWV values were negatively associated with TMTA and TMTB z-scores. Unadjusted AIx@75 was negatively associated with TMTB z-scores in African Americans but not whites. African Americans with MMSE and SDMT z-scores <0 had higher PWV values compared to whites ((9.4 m/s vs 7.9 m/s) and (9.7 m/s vs 7.7 m/s), respectively) and those with TMTB z-scores <0 had higher cSBP values (123.1 mmHg vs 114.4 mmHg).

Conclusion:
African Americans had higher arterial stiffness compared to whites. Neuropsychological test were associated with arterial stiffness in white study participants but only arterial wave reflections in African Americans. Longitudinal follow-up is warranted to assess specific central hemodynamic parameters associated with cognitive impairments and dementia in African Americans.
Abstract WP487: Retinal Vessel Tortuosity Correlates With White Matter Hyperintensities and Cerebral Microbleeds in Subjects With Cognitive Decline
Authors: Dumitrascu Oana M , Khansari Maziyar M , Shi Yonggang , Fawaz Miller , Cristea Diana , Koronyo Maya , Haacke Mark E , Lyden Patrick D
Published: June 2021

Objective:
Retinal microvasculature analysis is suitable to study cognitive disorders given retinal and brain vessels share similar properties. Using novel automated technologies, we aimed to investigate whether automatically-quantified retinal vascular changes from retinal fundus photographs predict brain imaging abnormalities in patients with cognitive impairment; and what specific retinal vascular parameters are more predictive of dementia.

Methods:
In this cross-sectional study, 34 subjects with cognitive complaints underwent neuropsychometric cognitive testing, retinal fundus photography and brain MRI. Retinal vessel tortuosity index (VTI), inflection index (VII) and length (VL) were automatically computed. The number and volume of cerebral microbleeds (CMB) and white matter hyperintensities (WMHI) were measured using SPIN Software (SpinTech, Bingham Farms, MI). The diagnostic groups were compared for demographic, cognitive, retinal and brain imaging parameters using analysis of variance. The association between brain (intracranial volume (ICV), hippocampal volume (HV), lateral ventricle volume (LVV), WMHI and CMB (volume, number), Fazekas scores) and retinal vascular parameters were assessed by using multiple linear regression models.

Results:
Nine subjects were cognitively normal (CN) and 25 cognitively impaired (CI) (22 with mild cognitive impairment and 3 with dementia). VTI was the only retinal parameter and HV and LVV were the brain parameters that were significantly different between CN and CI subjects (p=0.02). VTI correlated with VL (p=0.02, r=0.33) and branching angle (p=0.004, r=-0.45). The cognitive domains predicted by VTI were abstraction and orientation. VTI correlated with total intracranial volume (p=0.04, r=-0.12). A significant association was demonstrated for VII and WMHI volume (p=0.03, r=0.007), but not Fazekas score. VII and VTI significantly correlated with CMB volume (p=0.04 and 0.03, respectively).

Conclusion:
Automatically-detected retinal vessel tortuosity indexes predict neuroimaging markers of microvascular disease and total intracranial volume in cognitively impaired individuals. Retinal imaging may be used to screen patients with cognitive disorders.
Abstract WP489: Disrupted Functional and Structural Connectivity Within Default Mode Network Contribute to WMH Related Cognitive Impairment
Authors: Huang Lili , Ye Qing , Chen Xin , Yang Dan , Qin Ruomeng , Luo Caimei , Li Mengchun , Xu Yun
Published: June 2021

Aims:
The prevalence of white matter hyperintensities (WMH) rises dramatically with aging. Both the progression of WMH and default mode network (DMN) have been proven to be closely associated with cognitive function. Thus, we hypothesized that changes in functional connectivity (FC) and structural connectivity (SC) of the DMN contributed to WMH related cognitive impairment.

Methods:
A total of 116 subjects were enrolled from the Cerebral Small Vessel Disease Register in Drum Tower Hospital of Nanjing University, and were distributed across three categories according to Fazekas rating scale: WMH I(n=57), WMH II(n=34), and WMH III (n=25). The clinical and neuropsychological data were collected, and all participants underwent 3D T1 weighted images, T2 weighted images, 3D fluid attenuated inversion recovery (FLAIR) images, diffusion tensor images (DTI), and diffusion weighted imaging (DWI). The alterations of FC and SC within the DMN were further explored in these subjects.

Results:
The study found that age and hypertension were risk factors for WMH progression. Subjects with a larger WMH burden displayed higher DMN FC in the medial frontal gyrus (MFG), while lower DMN FC in the thalamus. After adjustment for age, gender, and education, the increasing FC between the MFG, posterior cingulate cortex (PCC), and ascending mean diffusivity (MD) of the white matter tracts between the hippocampus and PCC were independent indicators of worse performance in memory. Moreover, the decreasing FC between the thalamus, PCC, and ascending MD of the white matter tracts between the thalamus and PCC were independent risk factors for a slower processing speed.

Conclusion:
The changes in FC and SC within the DMN attributed to WMH progression were responsible for the cognitive impairment.
Abstract WP490: The Role of Blood Exosome Mirnas and its Correlation With Cognitive Domains in Cerebral Small Vessel Disease
Authors: Cao Xiang , Cheng Yue , Chen Fangyu , Huang Lili , Yang Dan , Xu Yun
Published: June 2021

Introduction:
Cerebral small vessel disease (CSVD) refers to a group of clinical syndromes involving cerebral arterioles, perforating arterioles, capillaries and venules, which is characterized by abnormal emotion, abnormal gait, urinary dysfunction, stroke, dementia and so on. It’s five to six times as much as stroke, and accounts for 45% of AD. Early forecast and early intervention can slow down the occurrence and development of cognitive impairment. Ethics number: 2016-134-01; Clinical Registration number: ChiCTR-OOC-17010562.

Methods:
195 patients were enrolled in a case-control study and a cohort study. Exosomes were extracted by miRNeasy Serum/Plasma KIT (Qiagen). Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and exosome reference particle size technique were used to identify exosomes, than, miRNA sequencing was performed and the results were analyzed and verified. Patients underwent neuropsychological measurement including the general cognitive examination and multiple cognitive domain assessments.

Results:
There were 5 differentially expressed exosome miRNAs between patients with cognitive impairment and the normal subjects, that was miRNA-330/miRNA-339/miRNA-432/miRNA-625/miRNA-6852 were associated with overall cognitive score (
P
< 0.001). Among the miRNAs, Significant correlations were observed between miRNA-330 and executive function, as well as processing speed (Pearson’s r = 0.30 after log transformation,
P
= 0.002; Pearson’s r = 0.24 after log transformation,
P
= 0.039, respectively). miRNA-432 was significantly correlated to verbal fluency (Pearson’s r = -0.33 after log transformation,
P
< 0.001).

Conclusions:
Peripheral blood exosome miRNAs are markers for overall cognitive impairment and correlates with impairment in the domains executive function, verbal fluency and processing speed. It is of great significance for clinical early prevention and early treatment.
Abstract WP496: Optogenetic Neuronal Stimulation Promotes Myelination After Subcortical Ischemic Vascular Dementia
Authors: Zhai Lili , Xu Yun
Published: June 2021

Introduction:
Subcortical ischemic small vessel disease (SIVD) causing hypoxic-ischemic white matter lesions is one of the major subtypes of Vascular dementia. White matter damage is associated with short-term working memory deficits in which medial prefrontal cortex (mPFC) plays a central role. Recent studies have reported that active neurons may produce white matter changes and enhance connectivity. However, little is known about how white matter damage impairs short-term working memory and whether neuronal activity promotes white matter restore in SIVD. In the present study, we used optogenetics in bilateral common carotid artery stenosis (BCAS) model mice to find the damaged circuit and explore whether neuronal activity could ameliorate white matter damage.

Methods:
Fiber photometry system monitoring in vivo calcium (Ca
2+
) transients was performed to explore the damaged circuit of BCAS model mice. The damaged circuit were labelled using AAV expressing channel-rhodopsin 2 (CHR2). Optogenetics were used to selectively activate neurons expressing CHR2. The thymidine analog 5-ethynyl-2
’
-deoxyuridine (EDU) was administered at the time of optogenetic stimulation to mark dividing cells and immunofluorescence was performed to identify the proliferating cell types. Transmission electron microscope (TEM) was used to evaluate myelin thickness. Y-mazes were performed to evaluated short-term working memory.

Results and Conclusions:
The structure and function of glutamatergic neurons in the circuit from mPFC to corpus callosum (CC) were damaged in BCAS model mice. And optogenetics stimulation of mPFC projecting glutamatergic neurons resulted in proliferation of oligodendrocyte in CC. Besides, an increase of myelin thickness and improved short-term working memory were found after three weeks of optogenetics stimulation. These results suggest that SIVD affected short-term working memory through damaging neuron projections from mPFC to CC, and optogenetic neuronal activity could regulate myelination and restore white matter damage.
Abstract WP499: Cognitive Function in Patients With Symptomatic Intracranial Stenosis
Authors: Prabhakaran Shyam , Sangha Rajbeer , Ansari Sameer , Sylaja PN , Liebeskind David S , Romano Jose
Published: June 2021

Introduction:
Compared to recurrent stroke risk, data are scarce on cognitive outcomes in patients with symptomatic intracranial atherosclerotic disease (ICAD). We evaluated cognition in patients with symptomatic ICAD at 90 days and factors that predict cognitive function.

Methods:
Using a prospective registry at a single center, we identified consecutive patients admitted between 2012 and 2017 with confirmed ischemic stroke or transient ischemic attack (TIA) and independently adjudicated symptomatic ICAD with stenosis of >50%. A blinded rater assessed infarct pattern: single perforator, territorial, borderzone, or mixed. At 90 days post-stroke, patients or proxies were emailed Neuro-QOL surveys for cognitive and motor function. We also collected data on recurrent stroke in the territory of the stenosis within 3 months. We evaluated baseline and imaging predictors of 90-day cognition T-score using stepwise linear regression adjusting for age, sex, prior stroke, initial NIHSS score, location of stenosis, degree of stenosis, use of dual antiplatelet therapy at discharge, and recurrent stroke.

Results:
Among 212 patients who met study criteria, 125 (59.0%) completed cognition surveys; those who completed surveys were similar to those who did not across demographic, clinical, and imaging characteristics. In the analyzed cohort, the mean age was 68.3 (±12.6) years and median initial NIHSS score was 3 (interquartile range 1-6). Symptomatic ICAD was localized to the anterior circulation in 84 (67.2%) patients and 102 (81.6%) had stenosis >70%. At 90 days, the mean cognition T-score was 50.1 (±10.4) and 25 (20%) had scores <40. In adjusted analysis, increasing age (b=-0.15, p=0.031), higher initial NIHSS score (b=-0.69, p<0.001), and a mixed or territorial infarct pattern (b=-0.39, p=0.028) were associated with lower cognition T-scores.

Conclusions:
In a single-center observational cohort study, cognitive impairment was noted in 20% of patients with symptomatic ICAD at 3 months. Besides age and NIHSS score, baseline infarct pattern was a strong predictor of worse cognitive function. Our data suggest that cognitive impairment is common in patients with symptomatic ICAD and baseline clinical and imaging characteristics may identify those at risk.
Abstract WP50: Cost-Effectiveness of Mechanical Thrombectomy for Acute Ischemic Stroke: An Analysis From RESILIENT Trial
Authors: de Souza Ana Claudia , Martins Sheila , Polanczyk Carisi , Vianna Denizar , Carbonera Leonardo , Lavanholi Neyeloff Jeruza , Lorena Fagundes Chaves Márcia , Pontes-Neto Octávio , Montalverne Francisco Jose , Rebello Letícia , Sampaio Silva Gisele , Abud Daniel , Lima Fabrício , Miranda Maramelia , Carvalho João José , Zetola Viviane , Liebeskind David , Oliveira-Filho Jamary , Saver Jeffrey L , de Freitas Gabriel , Nogueira Raul
Published: June 2021

Background and purpose:
RESILIENT Trial was the first study in a developing country to demonstrate the benefit of mechanical thrombectomy (MT) in acute stroke patients. This economic evaluation aimed to access the cost-utility of MT under the perspective of the Brazilian Public Healthcare System.

Methods:
Analysis was based on a subset sample of the original study (151 of 221 patients) from 4 hospitals. We compared costs and utilities between MT plus standard care (n=78) vs. standard care alone (n=73). Direct medical costs were considered, and utilities were inputted according to each patient’s Utility-Weighted modified Rankin Score (UW-mRS). First-year survival was obtained from trial follow-up and modelled for a life-time horizon adjusted by National Mortality Data. Direct medical costs were converted to I$ using Purchasing Power Parity (PPP). A discount rate of 5% was used. Incremental cost-effectiveness ratio (ICER) is expressed in cost (I$) per Quality-Adjusted Life Year (QALY).

Results:
RESILIENT trial was stopped on its first interim analysis because of early efficacy. The incremental costs and QALYs gained with MT were estimated at I$ 8,369 and 0.75, respectively, compared with standard medical care, yielding an incremental cost-effectiveness ratio (ICER) of I$ 7,256 per QALY.

Conclusion:
The initially higher costs of MT were offset by the clear benefit of the intervention. RESILIENT trial demonstrated that such therapy is likely to be cost-effective despite the economical constraints in the Brazilian healthcare system.
Abstract WP502: Predictors Of First Pass Reperfusion In Anterior Circulation Large Vessel Occlusion Stroke
Authors: Mohammaden Mahmoud , Pisani Leonardo , Perry da Camara Catarina , Bousalma Mehdi , Al bayati Alhamza , Haussen Diogo C , Frankel Michael , Nogueira Raul G
Published: June 2021

Introduction:
The speed and completeness of endovascular reperfusion strongly correlate with functional outcomes. First-Pass Reperfusion (FPR) has been recently established as a critical procedural performance metric for mechanical thrombectomy (MT). We aimed to study the predictors of FPR and its effect on the outcome

Methods:
Review of a prospectively collected database of MT patients with large vessel occlusion strokes (LVOS) from 05/2012-11/2018. Patients were included in the analysis if they had an anterior circulation LVOS that was successfully reperfused (mTICI 2b-3). FPR was defined as the achievement of mTICI 2c-3 after a single pass with any thrombectomy device. Uni- and multivariate analyses were performed to identify the independent predictors of FPR.

Results:
A total of 563 patients qualified for the analysis (mean age, 64.4±12.3 years, baseline NIHSS 16.2). FPR was achieved in 202 (35.9%) patients. On univariate analysis, FPR was significantly associated with higher ASPECTS (8.1 vs. 7.8, p=0.008), higher usage of balloon guide catheters (BGC) (88.1% vs. 75.3%, p<0.001), lower use of general anesthesia (9.5% vs. 18.2%, p= 0.006), and shorter procedure duration (mean, 45.5 vs. 79.9 min, p <0.001 and 90.5%). Both BGC (OR, 2.26; 95%CI [1.32-3.87], p=0.003) and ASPECTS (OR, 1.15; 95% CI [1.03-1.28], p= 0.01) were independent predictors of FPE on multivariate regression analysis.

Conclusion:
Higher baseline ASPECTS score and the use of BGC are strong predictors of First-Pass Reperfusion in mechanical thrombectomy.
Abstract WP55: Good Collateral Status Predicts Better Outcomes in Endovascular Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Tseng Fan Shuen , Ng Yu Xin Julia , Tan Yong Qiang Benjamin , Yeo Leong Litt Leonard , Chua Yuan Kit Christopher
Published: June 2021

Introduction:
Endovascular therapy (EVT) for the treatment of acute ischemic stroke in cervical and/or cerebral arterial occlusions is superior to standard medical therapy alone. This however requires careful patient selection and the current criteria utilising time windows and the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is imperfect, limiting its efficacy. We explore the impact of pretreatment collateral status (CS) in predicting EVT outcomes.

Methods:
A systematic literature search was conducted on PubMed and EMBASE for randomized controlled trials and prospective and retrospective cohort studies without language restriction from January 01, 2000 to June 25, 2019. We included studies reporting efficacy and safety outcomes dichotomised by collateral status in patients with acute anterior circulation ischemic stroke that were treated with mechanical thrombectomy and/or intra-arterial thrombolysis. Odds ratios were pooled for good versus poor collaterals for outcomes based on a random-effects model.

Results:
The search strategy yielded fifty-four (54) studies (n=7,599) (mean age 67.6 years; females 47.4%) for quantitative analysis, of which there were 2 pairs of studies with overlapping populations but had reported different outcomes. Thus, there were at least 7,441 unique individuals included in this analysis recruited between May 1992 and September 2018. Analysis showed that good CS was strongly associated with favourable functional outcomes (modified Rankin Scale 0-2) at discharge, as well as at 3 months or follow-up (Table 1). Good CS was also associated with higher revascularization rates, lower rates of mortality and lower rates of symptomatic intracranial hemorrhage.

Conclusions:
Good pretreatment CS strongly predicts good functional outcome and lower complication rates. Pretreatment CS should be considered in the design of future clinical trials and as a selection criteria for EVT.
Abstract WP56: The Hypoperfusion Intensity Ratio is a Poor Discriminator of Infarct Growth in Fully Reperfused Patients
Authors: Ravindran Krishnan , Bouslama Mehdi , Rodrigues Gabriel , Haussen Diogo , Pisani Leonardo , Frankel Michael R , Nogueira Raul G
Published: June 2021

Background and Purpose:
The hypoperfusion intensity ratio (HIR) is a perfusion-weighted imaging parameter defined as the ratio of Tmax>10 seconds : Tmax>6 seconds volume and is believed to be reflective of collateral strength and consequently influence infarct growth. We sought to assess the utility of the HIR in predicting infarct growth in patients undergoing thrombectomy at a comprehensive stroke center (CSC).

Methods:
Consecutive acute ischemic stroke patients transferred to our CSC from 09/2010-11/2018 were identified and included if the following criteria were met: 1)computed tomography perfusion (CTP) imaging enabling assessment of baseline ischemic core volume and HIR 2) follow-up neuroimaging for assessment of final infarct volumes and 3)modified Thrombolysis In Cerebral Infarction scale (mTICI) 2c status or greater post-thrombectomy. Infarct growth rate (IGR) was calculated as the difference between infarct volume on follow-up imaging and the acute DWI lesion volume, divided by time from CTP to reperfusion in hours.

Results:
461 patients (median age, 64 [55-75] years, median baseline NIHSS, 16 [12-21]) were eligible for this analysis. HIR poorly correlated with IGR (Spearman’s rho=0.001, p=0.89). An HIR cut-off of 0.5 was not able to discriminate ‘fast progressors’ (IGR>5 mL/hr) (AUC 0.42, sensitivity 40%, specificity 51%), or IGR at thresholds of either 2.5 or 10 mL/hr (AUC 0.44 and 0.49 respectively, with 95% confidence intervals [0.35-0.52] and [0.41-0.57], respectively). Similarly, an HIR of 0.5 only weakly distinguished ‘fast progression’ in patients reperfused beyond 120 min from imaging and patients with early CTP (last known well to CTP<6 hrs) (AUC 0.59, sensitivity 43%, specificity 68% and AUC 0.50, sensitivity 45%, specificity 55%). On multiple regression analysis, HIR was not predictive of infarct growth (regression equation=18.09+8.48x, F=2.46, p=0.11, R
2
=0.13) but was predictive of ‘fast progression’ (OR 0.22, 95% CI [0.09-0.60], p=0.003, pseudo-R
2
=0.16).

Conclusions:
Though predictive of fast progression, the HIR is a poor discriminator of infarct growth in successfully reperfused thrombectomy patients who undergo perfusion imaging at a CSC, and thus should not be factored into treatment decision-making.
Abstract WP57: Acute Carotid Stenting Following Intracranial Thrombectomy Has Comparable Safety and Efficacy in Early versus Late Time Window Stroke
Authors: Mitchelle Amer , Lau Fiona S , Cheung Andrew , Wenderoth Jason , McQuinn Alexander , Cappelen-Smith Cecilia , Cordato Dennis , Hodgkinson Suzanne , Blair Christopher , McDougall Alan , Zagami Alessandro S , Manning Nathan W
Published: June 2021

Introduction:
Endovascular thrombectomy (EVT) is beneficial in late time window stroke. However, patients with tandem extracranial carotid and intracranial occlusions are under-represented in previous trials. We analysed our acute anterior circulation strokes with tandem occlusions treated with EVT and extracranial internal carotid artery stenting.

Methods:
A prospectively maintained database of EVT patients treated in two Australian comprehensive stroke centres between January 2016 and May 2019 was screened for acute anterior circulation ischaemic stroke patients treated with EVT and extracranial internal carotid artery stenting. The cohort was divided into patients treated in early (
<
6 hours from symptom onset) and late (>6 hours from symptom onset) time windows.

Results:
Endovascular thrombectomy with acute carotid stenting was performed in 96 patients (mean age 71years, 78.3% male, mean time to reperfusion 13.5 +/- 10.1 hours, median NIHSS 15). Treatment >6hours after symptom onset occurred in 61 (63.5%) patients. No significant difference was seen between the two groups with respect to age, sex, presenting NIHSS, or mTICI score. At 90-day follow-up, good functional outcome (mRS 0-2) was similar for patients treated in the late versus early time windows, 19 (54.3%) vs 34 (55.7%), p=0.89 respectively. No difference was seen for symptomatic intracranial haemorrhage, 5 (7.2%) vs 3 (8.1%) p=0.87, or mortality at 90-day follow-up, 15 (24.6%) vs 6 (17.1%) p=0.40.

Conclusion:
Carotid stenting in late time window has comparable safety and efficacy to early time window stroke.
Abstract WP6: Safety of Acute Carotid Stenting Treatment in Acute Symptomatic Patients
Authors: Quispe-Orozco Darko , Limaye Kaustubh , Zevallos Cynthia , Holcombe Andrea , Dandapat Sudeepta , Ansari Sameer , Asi Khaled , Samaniego Edgar , Hasan David , Derdeyn Colin , Ortega-Gutierrez Santiago
Published: June 2021

Carotid stenting (CAS) has been shown to be equivalent to carotid endarterectomy in symptomatic patients; however its optimal timing remains unclear. In this study, we aim to evaluate the safety of CAS when performed within the first 48 hours of symptom onset. We performed a retrospective analysis of a prospectively collected database of consecutive CAS patients admitted to our comprehensive stroke center with TIA/stroke and ipsilateral symptomatic carotid stenosis >50% from 2014 to 2019. Medical records were retrospectively reviewed for demographic, clinical and procedural data and outcomes. Acute and delayed treatment were defined as ≤48 and >48 hours from last known well (LKW) respectively. The primary endpoint was procedure-related major complications (stroke with NIHSS increase of ≥4, myocardial infarction, parenchymal hemorrhage type 2 or death) ≤30 days after CAS. Secondary endpoints were procedure-related minor neurological (stroke with NIHSS increase of <4 and reperfusion injury) and non-neurological (groin puncture hematoma, acute anemia and arrhythmia) complications. Functional outcome was assessed by discharge and 90 days mRS, dichotomized as good (0-2) and bad (3-6). A total of 72 patients were included in the analysis, 36 in each group. There was no difference in age, NIHSS at presentation, gender, incidence of TIA as presentation or percentage of TPA received. The acute group differed significantly from the delayed group in number of thrombectomies (36.1% vs. 5.6%, p=0.001) and median time from LKW to CAS (15.9 hours vs. 88.0 hours, p<0.001). There were significantly more carotid occlusions in the acute group when compared to the delayed group (37.8% vs. 2.2, p<0.0001). Overall, the acute group did not show significant difference from the delayed group in major (2.8% vs. 5.6%, p=1.0), minor neurological (13.9% vs. 2.8%, p=0.09) and minor non-neurological complication rates (13.9% vs. 8.3%, p=0.7). Rates of good outcomes were not significantly different between the two groups at discharge (52.8% vs. 50%) or 90 days (75% vs. 63%). CAS can be performed safely in acute symptomatic carotid stenosis patients within the first 48 hours from symptom onset.
Abstract WP62: Delayed Appearance of DWI Lesions in Clinically Suspected DWI-Negative Stroke: DWI-CONVERSION Score
Authors: Kim Kitae , Kim Beom Joon , Huh Jaewon , Yang Seong Kyu , Han Moon-ku , Jung Cheolkyu , Choi Byung Se , Kim Jae Hyoung , Bae Hee-joon
Published: June 2021

Introduction:
Our aim was to determine the prevalence and factors associated with delayed appearance of DWI lesion among initially DWI-negative clinically suspected stroke patients in the follow-up DWIs during in-hospital care.

Method:
Among 5271 patients admitted to stroke unit as clinically suspected stroke/TIA within 7 days from symptom onset in our hospital via ER for 2010~2017, we selected subjects based on the following criteria 1) initial negative DWI (n=827), 2) follow-up DWI within 14 days (n=751). Then, we excluded 57 cases (hemorrhagic cases (n=4), cerebral angiography studies between MRIs (n=53)). Finally-included 694 cases were divided into two cohorts for temporal external validation (2010~2015 (n=488) as derivation; 2016~2017 (n=206) as validation).

Results:
Of 5271 cases, 827 cases (15.7%) showed initial negative DWI. In 694 finally-included cases, 22.5% (n=156) showed delayed appearance of DWI lesion. In derivation cohort, factors showing significant relationship with positive conversion comprised: medical histories such as atrial fibrillation (aOR 6.17, 3.23-12.01); symptoms including objective hemiparesis (aOR 4.39, 1.90-10.32) (Table 1). These factors were used to construct DWI-CONVERSION score (Table 2a). Its c-statistic was 0.813 in derivation cohort and 0.808 in validation cohort, which is significantly higher than that of ABCD2 score in validation cohort (c-statistic=0.678; P<0.01 for comparison; Table 2b).

Conclusion:
We identified prevalence and clinical factors significantly associated with delayed appearance of DWI lesions in clinically suspicious stroke patients. DWI-CONVERSION score is a simple tool to predict it.
Abstract WP64: Perfusion Imaging Can Identify Basilar Occlusion Patients With a Favorable Response to Thrombectomy
Authors: Cereda Carlo W , Heit Jeremy , Bianco Giovanni , Pileggi Marco , Qureshi Abid , Hinduja Archana , Grigoryan Mikayel , Bingham Elijah G , Mlynash Michael , Albers Gregory W
Published: June 2021

Introduction:
Perfusion imaging can identify patients who respond favorably to endovascular therapy (EVT) in the anterior circulation; no data are available for the posterior circulation. We evaluated perfusion patterns, assessed with RAPID software, in a consecutive cohort of patients with basilar artery occlusion treated with EVT and assessed the association between reperfusion and favorable clinical outcome based on the perfusion profile.

Hypothesis:
We hypothesized that patients with limited regions of severe hypoperfusion (Tmax > 10s) would have a favorable response (mRS 0-2) to reperfusion (mTICI 2b-3) while patients with multiple critical brain regions severely hypoperfused would have poor outcome (mRS 4-6) despite reperfusion.

Methods:
From a multicenter cohort of perfusion imaging in posterior circulation stroke, we included patients with basilar artery occlusion and EVT. We pre-specified a Critical Area Perfusion Score (CAPS, 0 - 8 points) to identify severe hypoperfusion (Tmax >10s) in the following regions: inferior and/or superior cerebellar hemisphere (1-4 points), pons (2 points), midbrain/thalamus (2 points). We compared the outcome between reperfusers and non reperfusers based on the CAP score with univariate and multivariate analysis.

Results:
38 patients met the inclusion criteria. Mean age was 63±17, 34% female, NIHSS 17±11. In patients who reperfused (n=30, 79%) 63% had favorable outcome, while no patient without reperfusion survived, p=0.003 OR=29 (95%CI 1.5-547). Ninety percent (19/21) of reperfused patients with CAPS ≤2 had a favorable outcome, while none of the 9 with reperfusion and a score >2 survived, p<0.001, OR=148 (95%CI 6.5-3,333). In univariate analysis, favorable outcome was associated with NIHSS OR=0.87 (95% CI 0.80-0.96), p=0.003, and mismatch volume OR=0.98 (95% CI 0.97-0.997) p=0.013. In the multivariate analysis, only CAPS was an independent predictor of favorable outcome.

Conclusions:
Patients with limited regions of severe hypoperfusion (Tmax > 10s) had a robust response to basilar artery EVT, however, all patients with multiple critical brain regions severely hypoperfused died despite successful reperfusion. Perfusion imaging profiles may help identify optimal patients for basilar EVT.
Abstract WP66: Impaired Collaterals Are Associated With Intracranial Thrombus Extension: Evidence From MRI, Catheter Angiography, and Retrieved Thrombus Composition
Authors: Rao Neal M , Atchaneeyasakul Kunakorn , Hongquan Jiang , Solano Laura , Yong William H , Lucey Greg , Abdaljaleel Maram , Vinters Harry V , Szeder Viktor , Jahan Reza , Tateshima Satoshi , Duckwiler Gary R , Nour May , Colby Geoffrey , Kim Doojin , Raychev Radoslav , Bahr Hosseini Mercedeh , Hinman Jason D , Sharma Latisha K , Starkman Sidney , Saver Jeffrey L , Liebeskind David S
Published: June 2021

Background:
Clot propagation after initial occlusion may increase target thrombus burden and its pathophysiologic basis has not been extensively studied in acute human ischemic stroke. We investigated whether clot characteristics on MRI, catheter angiography, and thrombus histopathology indicated that impaired collaterals may be associated with extension of acute intracranial occlusions via stasis clotting in slow flow arterial segments.

Methods:
Analysis of consecutive AIS-LVO endovascular thrombectomy patients at 2 academic medical centers with: 1) pretreatment MRI, and 2) retrieved thrombi. GRE MR susceptibility vessel sign presence and extent of ASITN collateral scores were rated by blinded assessors. Extracted clots were fixed in formalin, stained by hematoxylin and eosin, and RBC, WBC and fibrin percent composition quantified by a neuropathologist blinded to clinical details. We evaluated the correlation of collateral grade with clot size by susceptibility vessel sign (SVS) and clot composition by RBC%. Non-parametric values were computed via Spearman correlation.

Results:
Among the 48 patients, mean age was 71.4 (SD 17.7), 56.3% female, and mean presenting NIHSS was 15.5 (SD 7.41). A susceptibility vessel sign was present in 65%, with mean SVS length 15.6 mm (SD 8.3). Collateral scores were mean 2.3 (SD 1.2). The number of passes per procedure was mean 1.98 (SD 1.30) The presence of a susceptibility vessel sign correlated with higher RBC% in retrieved thrombi (r
s
=0.36 p=0.011). Worse collateral grades correlated with longer SVS length (r
s
=-0.50 p=0.004) and greater SVS width (r
s
=-0.54 p=0.002). Worse collateral grade also trended toward correlation with higher RBC% in retrieved clots (r
s
=-0.19 p=0.18).

Conclusion:
Impaired angiographic collaterals are associated with longer RBC-rich thrombi on susceptibility imaging and trend toward association with higher RBC% in retrieved thrombi. These findings support that, in LVO acute ischemic stroke, clot propagation after initial occlusion occurs by stasis clotting accelerated by impaired collaterals.