bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP70: Utilization and Availability of CT Perfusion in Patients With Acute Ischemic Stroke: A Population Based Study
Authors: Lee Songmi , Kim Youngran , Vahidy Farhaan S , Krause Trudy M , Czap Alexandra L , Lopez-Rivera Victor , Fan James Z , Yoo Albert J , Giancardo Luca , Grotta James C , Sheth Sunil A
Published: June 2021

Introduction:
Recent randomized clinical trials have demonstrated benefit for treatment with endovascular stroke therapy (EST) and thrombolysis (IV-tPA) in late presenting acute ischemic stroke (AIS) patients using CT perfusion (CTP). The real-world utilization and availability of this advanced imaging modality is unknown.

Methods:
We identified all inpatient hospitalizations with a primary diagnosis of AIS using ICD-9/10 codes in Texas Medicare claims (2014-2017) and 5% national Medicare sample (2014-2017) and evaluated imaging utilization given at the Emergency Department (ED) prior to admission. Imaging and treatments were identified using CPT and procedure codes. Primary endpoint was ED-based imaging utilization. EST and CTP-capable hospitals were defined as those performing at least one EST or CTP within that calendar year.

Results:
In the Texas cohort, among 50,797 admissions for AIS, 54% were female, median age was 77 [IQR 69-84], and 78% were white. 2% received EST and 9% received IV-tPA. 76% of AIS patients and 80% of those with EST received ED-based neuro-imaging at the treating hospital (Fig. 1). 58% of all AIS patients were evaluated in EST-capable hospitals. 75% of all AIS patients, 54 % of those with EST, and 70% of those with IV-tPA were evaluated at non-CTP-capable hospitals. 9% of IV-tPA and 17% of EST-treated patients underwent CTP; rates of MRI were greater (Fig. 1). These findings were maintained in the nationwide sample. Among 37,507 admissions for AIS, CTA was performed in 17%, MRI in 30%, and CTP in 3%. Among the 3% of AIS patients treated with EST, CTA was performed in 65%, MRI in 66%, and CTP in 14%.

Conclusion:
In this population-based cohort, three out of four AIS admissions and half of EST procedures were at non-CTP performing hospitals. The limited availability and utilization of CTP suggest that an alternative imaging paradigm (e.g. MRI) may be beneficial in delayed time-window EST and thrombolysis.
Abstract TP76: Quantitative Comparison of Multidetector CT and Cone-Beam CT Perfusion Maps in Large Vessel Occlusion Stroke Patients Undergoing Mechanical Thrombectomy
Authors: Ortega-Gutierrez Santiago , Quispe-Orozco Darko , Schafer Sebastian , Aagaard Kienitz Beverly , Strother Charles , Chen Guang-Hong , Garrett John , Holcombe Andrea , Lopez Gloria , Zevallos Cynthia , Samaniego Edgar , Dandapat Sudeepta , Asi Khaled , Derdeyn Colin
Published: June 2021

Cerebral perfusion evaluation using CT or MR perfusion is the gold standard modality to select large vessel occlusion (LVO) stroke patients presenting >6 hours from symptom onset. The availability of cone beam C-arm CT perfusion (CBCTP) in angiography suites could reduce time to endovascular revascularization. We aimed to evaluate the reliability of using CBCTP when compared to multidetector CT perfusion (MDCTP). In this prospective, single-arm, interventional study, 14 LVO anterior circulation thrombectomy patients underwent both a 128 slice MDCTP in the ED and a CBCTP <30 minutes apart prior to groin puncture. CBCTP was acquired using a prototype acquisition mode enabling 10 consecutive C-Arm rotations with nearly continuous data acquisition. A total of 60 cc of contrast layered with 60 cc of saline were injected covering arterial inflow, parenchymal phase and venous outflow. Image data was reconstructed into CBF, CBV, MTT and TTP maps. Three types of measurements were used to compare modalities. In measurement 1, 6 circular regions of interest (ROI) (400mm
2
) were placed in the anterior arterial territory. In measurement 2, circular ROIs were placed in the ASPECTS regions (cortical 300mm
2
, subcortical 200mm
2
). In measurement 3, a ROI was drawn around the entire affected area. All ROIs were placed in the basal ganglia and supraganglionic level of both brain sides. Rates (unaffected/affected area) between MDCTP and CBCTP were compared for all sequences. The intraclass correlation coefficient (ICC) was calculated using a single rater, consistency, two-way random-effects model. Measurement 1 found a moderate degree of agreement between MDCTP and CBCTP in CBF, CBV, MTT and TTP rates with ICCs of 0.58 (CI 0.42 - 0.69), 0.65 (CI 0.53 - 0.74), 0.77 (CI 0.68 - 0.83) and 0.52 (CI 0.35 - 0.65). In measurement 2, moderate agreement was found in CBF, CBV and MTT rates; with ICCs of 0.51 (CI 0.32 - 0.65), 0.57 (CI 0.4 - 0.69) and 0.62 (CI 0.47 - 0.73). The results of measurement 3 found an excellent (ICC=0.95, CI 0.88 - 0.98), good (ICC=0.83, CI 0.62 - 0.9) and moderate (ICC=0.7, CI 0.34 - 0.87), degree of agreement in the CBV, MTT and CBF rates, respectively. These results demonstrate promising accuracy of CBCTP in the evaluating ischemic tissue in patient presenting with LVO acute stroke.
Abstract TP8: Sudden Recanalization: A Game-Changing Factor in Endovascular Treatment of Large Vessel Occlusion Strokes
Authors: Garcia-Tornel Alvaro , Rubiera Marta , Rodriguez-Luna David , Muchada Marian , Requena Manuel , Deck Matias , Boned Sandra , Juega Jesus , Rodriguez-Villatoro Noelia , Pagola Jorge , Piñana Carlos , Olive-Gadea Marta , Tomasello Alejandro , Hernandez David , Molina Carlos A , Ribo Marc
Published: June 2021

Introduction:
First pass recanalization (FPR) is known to be a strong predictor of good outcome in endovascular treatment (EVT) of stroke. The reasons why FPR leads to better outcome than if achieved in multiple-passes (MP) are unknown. We aim to investigate the recanalization pattern and its relation with good outcome.

Methods:
609 consecutive patients underwent EVT in the anterior circulation at a single stroke center. Demographic and imaging characteristics, number of passes and recanalization pattern were recorded. Complete recanalization was defined as mTICI2b-3 at the end of EVT. Good functional outcome was defined as modified Rankin scale (mRs) 0-2 at 90 days. Sudden recanalization(SR) was considered when mTICI score varied from 0-1 to 2B-3 in a single pass. Progressive recanalization (PR) was considered if mTICI 2a was achieved at an interim pass before achieving complete recanalization. Patients were categorized as recanalizers at first-pass (FP) and multiple-passes (MP) or non-recanalizers (NR). 70 (10.3%) patients in MP group were excluded due to missing procedural data.

Results:
509 (83.9%) patients achieved complete recanalization. SR was achieved in 378 (62.1%) patients; 280 (46%) were FP-SR and 98 (16.1%) were MP-SR. MP-PR was achieved in 131 (21.5%) patients. Rates of good functional outcome depending on recanalization pattern were: FP-SR 57.5%, MP-SR 57.1% (FP-SR vs MP-SR, OR 0.9 CI 0.53-1.54, p=0.7), MP-PR 29.8% (MP-SR vs MP-PR, OR 3.06 CI 1.66-5.62, p<0.001) and NR 17% (MP-PR vs NR, OR 1.23 CI 0.49-3.09, p=0.66). In patients with complete recanalization, univariate analysis showed that both FP (OR 1.91, CI 1.34-2.72, p<0.01) and SR (OR 3.18, CI 2.08-4.87, p<0.01) were associated with good functional outcome. Multivariate analysis showed that SR was a predictor of good functional outcome (OR 3.12, CI 1.9-5.1, p<0.01), being FPR non-significant (OR 1.12, CI 0.66-1.9, p=0.666).

Conclusions:
Sudden recanalization is a strong predictor of good functional outcome in patients undergoing EVT, even after previous unsuccessful attempts. Progressive recanalization may reflect clot fragmentation and embolization due to more friable composition, leading to worse outcomes. Benefits of first pass effect are driven by sudden recanalization.
Abstract TP80: Imaging Characteristics of Methamphetamine-Associated Ischemic Strokes
Authors: Hwang Nhayoung , Walia Sandeep , Ng Kwan , Yee Alan
Published: June 2021

Objective:
To examine the clinical and neuroimaging characteristics in patients with acute ischemic stroke and concurrent methamphetamine (meth) use.

Introduction:
Meth is a highly addictive stimulant with harmful effects that lead to cardiovascular disease and stroke. Despite a strong association between meth use and increased cerebrovascular risk, detailed descriptions of clinical and neuroradiologic characteristics in larger cohorts are lacking.

Methods:
Single-center retrospective analysis of consecutive adults admitted for acute ischemic stroke and meth-positive toxicology between 2016 and 2019. Stroke imaging characteristics, including suspected etiologic mechanism as defined by Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, were documented.

Results:
Ninety patients were admitted with radiologically confirmed acute ischemic stroke and meth exposure. The average age was 55 years (range, 36-77 years) and 69% were male. Although 47% were Caucasian, nearly half were from an underrepresented minority ethnic/racial group (24% Black, 8% Hispanic/Latino, 9% Asian/Pacific Islander). A multiplicity of strokes was seen in the majority of cases (57%), and 31% affected the bilateral hemispheres. Although 91% of all cases had subcortical involvement, only 34% were purely subcortical of which one-half had brainstem infarctions. The middle cerebral artery distribution was affected most commonly (71%) while multiple vascular territories were involved in 30% of cases. The most frequently encountered stroke subtypes were small vessel occlusion (27%) and a cardioembolic source (26%) as defined by the TOAST criteria. A substantial proportion of patients (31%) were discharged to a rehabilitation or nursing facility, dispositions with high predictive value for unfavorable post-stroke outcomes. Moreover, 15% of patients died during their hospitalization.

Conclusion:
Meth-associated acute ischemic stroke is a multicultural problem with variable widespread effects throughout the cerebrum. Although small vessel vasculopathy is suspected in most, a significant proportion is due to proximal embolic sources. Long-term care is often required in survivors, and nearly 1 in 6 died during their hospitalization.
Abstract TP81: A Closer Look at MRI-Based Core in Patients With Large Vessel Occlusion Within 6 Hours From Onset
Authors: Luby Marie , Shah Yojan , McCreedy Evan , Kern Kyle , Latour Lawrence L , Leigh Richard , Lynch John K , Hsia Amie W
Published: June 2021

Introduction:
Recent clinical trials including EXTEND-IA and SWIFT PRIME utilized CT and MRI imaging to exclude large core patients from endovascular therapy (EVT) presenting within 6 hours from onset. We hypothesize that patients with clinical-core mismatch, retrospectively defined as admit NIHSS ≥ 6 and core volume ≤20 mL, were more likely to have early neurological improvement versus those who did not.

Methods:
Patients included had confirmed large vessel occlusion in the anterior circulation, presented within 6 hours from last known normal, were screened pre-EVT with multimodal MRI, treated with EVT between January 2015 through July 2019, and consented to Natural History of Stroke Study. Core volumes were calculated using a fully automated algorithm, “coretool”, based on processed DWI and ADC maps thresholded at ≤620 μm
2
/sec. Perfusion deficit volumes were calculated by thresholding Tmax maps at >6 sec delay. Early neurological improvement (ENI) was defined as a decrease in NIHSS≥8 points or NIHSS of 0-1 at 24 hours.

Results:
Fifty-four patients met study criteria with median age 54 years, 59% female, admit NIHSS=19 [13-23], onset=117 min [59-155], onset to groin=212 min [171-265], core volume=9mL [4-31], Tmax volume=82mL [50-107], mismatch volume=51mL [30-86], mismatch ratio=7.5 [2.6-11.9], and 90 day mRS=3 [1-5]. Of the 54 patients, 61% (n=33) had clinical-core mismatch while 39% (n=21) did not. Patients with mismatch had smaller core volumes, median 6 versus 39mL (p<0.001) and larger mismatch ratios, median 8.9 versus 2.6, (p=0.003), but no differences in age, sex, IV tPA treatment, onset time, onset to groin time, admit NIHSS, complete recanalization rate, Tmax volume, mismatch volume, or day 90 mRS. Fifty-five percent (18/33) of patients with clinical-core mismatch had ENI at 24 hours versus 24% (5/21) without (p=0.026).

Conclusions:
Patients with clinical-core mismatch had a significantly higher rate of early neurological improvement at 24 hours post EVT. However, some patients without mismatch but with complete recanalization still did well. Alternative definitions of mismatch, outside of current guidelines, may identify patients that will benefit more from EVT.
Abstract TP9: No Sex Differences in Thrombectomy Outcomes in the Blood Pressure After Endovascular Stroke Therapy Registry: An Exploratory Analysis
Authors: Demel Stacie L , Khatri Pooja , Mistry Eva
Published: June 2021

Intro:
Women have worse functional outcomes compared to men after ischemic stroke in the setting of thrombolytic treatment. Randomized trial cohorts have suggested no difference in outcomes between men and women after EVT. We sought to determine whether these differential outcomes are seen after endovascular stroke treatment in a real-world observational cohort.

Methods:
We compared 90-day functional and procedural outcomes in men and women using our prospective, multi-center, observational study, BEST, that enrolled adult patients with anterior circulation stroke undergoing endovascular treatment from Nov 2017 to Sept 2018 at 12 comprehensive stroke centers across the US. The primary outcome measure was modified Rankin 0-2 (good outcome). A multivariable analysis was performed to adjust for other known predictors of outcome.

Results:
Among 485 subjects (51.3% female) enrolled in BEST, women were older, had higher baseline glucose levels, and smaller baseline penumbral volumes compared to men (Table 1). After controlling for age, baseline glucose, NIH Stroke scale, ASPECT score and prior stroke, we did not detect a difference in good outcome at 90 days between sexes in unadjusted (OR 0.71, 95% CI 0.49–1.04) or adjusted (OR 1.02, 95% CI 0.67-1.57) analyses. Reperfusion rates (TICI 2b/3) and rates of futile reperfusion (TICI 2b/3 with mRS 3-6) were also comparable between sexes.

Conclusions:
We did not detect differences in functional outcomes by sex in our large, multicenter, prospective cohort, suggesting the hypothesis that outcome disparities are attenuated by EVT.
Abstract TP90: Advance: Automated Detection and Volumetric Assessment of Intracerebral Hemorrhage
Authors: Mohammaden Mahmoud , Pisani Leonardo , Perry da Camara Catarina , Rodrigues Gabriel M , Bousalma Mehdi , Barreira Clara , Chung Charlotte , Bhatt Nirav , Belagaje Samir , Anderson Aaron , Al-bayati Alhamza , Haussen Diogo C , Frankel Michael , Nogueira Raul G
Published: June 2021

Introduction:
Intracerebral hemorrhages (ICHs) accounts for approximately 15% of all strokes but carry high rates of morbidity and mortality. The location and volume of hematoma are strongly associated with outcomes. As novel treatments become established, early detection and proper volume measurement are becoming increasingly important. We aim to evaluate an artificial intelligence-based algorithm (Viz-ICH® v1.4) for ICH detection, volume measurement, and its differentiation from intraventricular hemorrhage (IVH).

Methods:
We performed single center retrospective analysis of non-contrast CTs (NCCTs), randomly picked from prospective cohort of acute stroke patients, with and without parenchymal ICHs, admitted to our stroke center from 02/14-03/17. Experienced stroke neurologists graded NCCTs with a semi-automated tool (OsiriX MD v.9.0.1) for presence and volume of ICH, and also presence of intraventricular hemorrhage (IVH). AI- and human-based readings were compared.

Results:
A total of 211 NCCTs were evaluated including 163 ICHs and 48 controls. The ICH location was basal ganglionic in 55.8%, Lobar in 23.3% and posterior fossa in 12% of the cases and 51.5 % of patients had associated IVH with mean volume 41.94 cc. The AI algorithm demonstrated high accuracy for ICH detection and volumetric measurement (Table). The maximal running time of the algorithm was under 15s.

Conclusion:
The presence and volume of ICHs can be accurately detected by AI Viz-ICH Algorithm, with good differentiation from IVH which will help in early triage of these patients.
Abstract WMP14: Association of Systolic Blood Pressure, LDL Cholesterol, and Hgb A1c With White Matter Hyperintensity on MRI in the ACCORDION MIND Study
Authors: de Havenon Adam H , Turan Tanya , Gottesman Rebecca , Yeatts Sharon , Prabhakaran Shyam , Rost Natalia
Published: June 2021

Introduction:
While retrospective studies have shown that poor control of vascular risk factors is associated with progression of white matter hyperintensity (WMH), it has not been studied prospectively.

Hypothesis:
We hypothesize that higher systolic blood pressure (SBP) mean, LDL cholesterol, and Hgb A1c will be correlated with WMH progression in diabetics.

Methods:
This is a secondary analysis of the Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes Follow-on Study (ACCORDION). The primary outcome was WMH progression, evaluated by fitting linear regression models to the WMH volume on the month 80 MRI and adjusting for the WMH volume on the baseline MRI. The primary predictors were the mean values of SBP, LDL, and A1c from baseline to month 80. We defined a good vascular risk factor profile as mean SBP <120 mm Hg
and
mean LDL <120 mg/dL.

Results:
We included 292 patients, with a mean (SD) age of 62.6 (5.3) years and 55.8% male. The mean number of SBP, LDL, and A1c measurements per patient was 17, 5, and 12. We identified 86 (29.4%) patients with good vascular risk factor profile. In the linear regression models, mean SBP and LDL were associated with WMH progression and in a second fully adjusted model they both remained associated with WMH progression (Table). Those with a good vascular risk factor profile had less WMH progression (β Coefficient -0.80, 95% CI -1.42, -0.18, p=0.012).

Conclusions:
Our data reinforce prior research showing that higher SBP and LDL is associated with progression of WMH in diabetics, likely secondary to chronic microvascular ischemia, and suggest that control of these factors may have protective effects. This study has unique strengths, including prospective serial measurement of the exposures, validated algorithmic measurement methodology for WMH, and rigorous adjudication of study data. Clinical trials are needed to investigate the effect of vascular risk factor reduction on WMH progression.
Abstract WMP28: A Novel Machine Learning Model for Rupture Prediction of Saccular Intracranial Aneurysm
Authors: Malik Khalid M , Malik Ghaus
Published: June 2021

Background:
Deciding how to deal with unruptured intracranial aneurysms is a complex problem. The research done so far has focused on identifying a contribution of individual risk factor (hypertension, female gender, etc.). However, it is difficult to translate the feature importance of single risk factor to a treatment decision. Recently, PHASES score was presented to predict rupture criticality, however, recent studies show it can't be used in clinical settings.

Methods:
A retrospective data of 915 patient records from an in-house registry of saccular aneurysms from 1997 - 2017 was used. We proposed a novel ensemble learning and apriori association rule mining-based method to define aneurysmal rupture risk in terms of Rupture Criticality Index (RCI), which is a normalized score (from 1 to 10) of the probability of aneurysmal rupture for set of associated features. In order to have interpretable and clinically useful model, we used Apriori algorithm to find what features carry strong association among them in the case of ruptured aneurysms for each combination of location and size. We used voting classifier as an ensemble technique and utilize weighted average probabilities (Soft Voting) to predict the outcome.

Results:
Proposed ensemble method shows precision, recall and f-measure of 75% and accuracy of 76%. The normalized values of RCI were categorized as minor, mild, moderate, severe, and critical by using Jenks natural breaks method. Evaluation results shows 26 ‘critical’, 53 ‘severe’ and 49 ‘moderate’ risk factors combinations. Examples of ‘critical’ combinations (which need immediate treatment) include: patients who are African American, current smoker, having anterior communicating artery (ACoA) Tiny-sized aneurysm (8.3-14.5 mm) with RCI of 8.57; patients who are African American, Male, having ACoA medium-sized aneurysm (8.3-14.5 mm) with RCI of 9.46; African American, Paraclinoid, Tiny-sized (<4.5mm) and current smoker with RCI 8.21, etc.

Conclusion:
The proposed machine learning model is capable of accurately predicting rupture risk over lifetime. Validation on retrospective data shows that results are reliable. Currently we are extending this work to make it as question-answer system using Google-home/Alexa voice assistants.
Abstract WMP31: Dedifferentiation of Smooth Muscle Cells and its Potential Contribution to Pathogenesis of Intracranial Aneurysms
Authors: Oka Mieko , Ohno Nobuhiko , Kawamata Takakazu , Aoki Tomohiro
Published: June 2021

Introduction:
Intracranial aneurysm (IA) affects 1 to 5 % in general public and becomes the primary cause of subarachnoid hemorrhage, the most severe form of stroke. However, currently, no drug therapy is available for IAs to prevent progression and rupture of lesions. Elucidation of mechanisms underlying the disease is thus mandatory. Considering the important role of vascular smooth muscle cells (SMCs) in the maintenance of stiffness of arterial walls and also in the pathogenesis of atherosclerosis via mediating inflammatory responses, we in the present study analyzed morphological or phenotypical changes of SMCs during the disease development in the lesions.

Methods:
We subjected rats to an IA model in which lesions are induced by increase of hemodynamic force loading on intracranial arterial bifurcations and performed histopathological analyses of induced lesions including the electron microscopic examination. We then immunostained specimens from induced lesions to explore factors responsible for dedifferentiation or migration of SMCs. In vitro study was also done to examine effect of some candidate factors on dedifferentiation or migration of cultured SMCs.

Results:
We first found the accumulation of SMCs underneath the endothelial cell layer mainly at the neck portion of the lesion. These cells was positive for the embryonic form of myosin heavy chain, a marker for the dedifferentiated SMCs, and the expression of pro-inflammatory factors like TNF-α. In immunostaining to explore the potential factor regulating the dedifferentiation of SMCs, we found that Platelet-derived growth factor-BB (PDGF-BB) was expressed in endothelial cells at the neck portion of IA walls. Consistently, recombinant PDGF-BB could promote the dedifferentiate of SMCs and chemo-attracted them in in vitro. Finally, in the stenosis model of the carotid artery, PDGF-BB expression was induced in endothelial cells in which high wall shear stress was loaded and the dedifferentiation of SMCs occurred there.

Conclusions:
The findings from the present study imply the role of dedifferentiated SMCs partially recruited by PDGF-BB from endothelial cells in the formation of inflammatory microenvironment at the neck portion of IA walls, leading to the progression of the disease.
Abstract WMP35: Prospective Randomized Study Comparing Clinical, Functional, Aesthetic and Quality of Life Results of Trans-Eyelid and Minipterional Approaches for Treatment of Unruptered Brain Aneurysms
Authors: Mandel Mauricio , Tutihashi Rafael , Figueiredo Eberval G , Rossi Jefferson , Teixeira Manoel J
Published: June 2021

Introduction:
Minimally invasive neurosurgery is already a reality in many centers across the world. However, the real role of these techniques and their effect on the outcome of patients is still obscure.

Objectives:
To evaluate the safety and results of minimally invasive techniques in brain aneurysm clipping and determine the possibility of early hospital discharge.

Methods:
111 adult patients with unruptured anterior circulation aneurysms were randomized and underwent a minimally invasive surgical approach, (36 by trans-eyelid approach (Figure1) and 34 through a reduced minipterional craniotomy) or classical pterional approach (41 patients). Patients in the study group were subjected to a specific protocol for assessment of early hospital discharge.

Results:
In both groups, the demographics and characteristics of aneurysms were similar. The average time of surgery was lower in the study group (214 min. vs. 292 min, p = 0.0008). The need for blood transfusion was lower in the study group (1 patient vs 7 patients, p = 0.018). The number of ischemic events was lower in the study group (patients 4 patients vs. 8, p = 0.07), but events with clinical significance were similar (3 patients vs. 2 patients, p = 0.53). The presence of residual neck on control angiography was lower in the study group (6 patients vs 11, p = 0.021). The paralysis of the frontal branch of the facial nerve was lower in the study group, both temporary (3 vs 14, p = 0.008) and definitive (0 vs. 4, p = 0.032). The atrophy of the temporal muscle was less frequent and less severe in the study group (9 vs 14, p = 0.012). Most patients in the study group (91.4%), were discharged on the next day of the surgery.

Conclusions:
The results showed that the proposed minimally invasive alternatives are safe. Clinical and surgical results are equal or superior to conventional treatment in several topics. Early discharge in these patients is possible and safe. The described approaches (nanopterional or transpalpebral) are better alternatives to the classical pterional craniotomy to treat unruptured aneurysms of the anterior circulation.
Abstract WMP40: Cervical Internal Carotid Artery Tortuosity as a Marker of Non-Atherosclerotic Aging: Results From the Northern Manhattan Study (NOMAS)
Authors: Khasiyev Farid , Rundek Tatjana , Marquez Chensy , Wright Clinton B. , Sacco Ralph , Elkind Mitchell , Gutierrez Jose
Published: June 2021

Background:
Cervical internal carotid artery (ICA) tortuosity has been associated with vascular risk and stroke as well as genetic disorders related to abnormal extracellular matrix remodeling. It is plausible that dystrophic or aberrant arterial remodeling may therefore relate to cervical ICA tortuosity. We hypothesized that cervical ICA tortuosity relates to carotid dilatation, but not to traditional ultrasound (US) markers of atherosclerosis.

Methods:
Subjects of the NOMAS with available time-of-flight MRA were included in our study. Cervical ICA tortuosity was defined as a bend in the distal cervical ICA of > 90° as seen on MRA. We excluded subjects with < 5 cm of the cervical ICA visualized. Distensibility was calculated as the percentage excursion of the right CCA diastolic diameter during systole, which was assessed by high-resolution B-mode US of the right common carotid artery (CCA). We used multivariable logistic regression analyses to estimate odds ratios for the association of cervical ICA tortuosity and Doppler measures of carotid wall aging.

Results:
We visualized cervical ICA tortuosity in 468 NOMAS participants (mean age 64±8 years, 70% women, 70% Hispanic). It was present in 23% of subjects. In unadjusted models, cervical ICA tortuosity was more common in women (OR 2.34, 95% CI 1.34-4.11), Hispanics (OR 1.85, 95%CI 1.06-3.25) and those with higher diastolic blood pressures (OR per mm Hg 1.04, 95%CI 1.01-1.06), and less common among smokers (OR 0.23, 95%CI 0.07-0.78). In models adjusted for demographic and vascular risks, right CCA tortuosity was associated with ipsilateral larger CCA DD (OR 1.42, 95%CI 1.02-1.96) and borderline associated with lower distensibility (OR 0.94, 95%CI 0.87-1.01, P=0.06) but not with ipsilateral ICA IMT (OR 0.26, 95%CI 0.14-4.77), number of plaques (OR 1.08, 95%CI 0.76-1.53), maximum plaque thickness (OR 0.96, 95%CI 0.73-1.27), or plaque area (1.00, 95%CI 0.97-1.05).

Conclusions:
Cervical ICA tortuosity associates with ipsilateral cervical ICA dilatation and lower distensibility, but not with traditional US markers of atherosclerosis. The association with diastolic blood pressure suggests a role of steady, rather than pulsatile, hemodynamics in aberrant cervical ICA remodeling.
Abstract WMP51: Ischemic Stroke Rates in Those With Diabetes in the Black and White Population: An Update
Authors: Khoury Jane C , Madsen Tracy , Alwell Kathleen , Moomaw Charles J , Sucharew Heidi , Woo Daniel , Ferioli Simona , Adeoye Opeolu , Flaherty Matthew L , Khatri Pooja , De Los Rios La Rosa Felipe , Mackey Jason , Martini Sharyl , Mistry Eva , Demel Stacie , Coleman Elisheva , Jasne Adam , Slavin Sabreena , Walsh Kyle , Star Michael , Kleindorfer Dawn , Kissela Brett
Published: June 2021

Background:
We previously reported an increased incidence of stroke in the population with diabetes. This was particularly pronounced in those under 65 years of age. With guidelines now including glycemic monitoring during hospitalization, we examined incidence attributable to diabetes in 2010 and 2015.

Methods:
Ischemic strokes in the 5-county Greater Cincinnati/Northern Kentucky region were ascertained, then physician verified, at all 15 area hospitals using ICD-9 codes 430 to 436 or ICD10 codes I60 to I68. First ever ischemic strokes in patients aged 20 years and older were included in this analysis. Population age-specific rates of diabetes were estimated using the 2009-2010 and 2015-2016 NHANES databases, then applied to local population numbers, extracted from the US Census Bureau website, to estimate the denominator for calculation of incidence rates. Incidence rates were adjusted by age race and sex, as appropriate, to the 2010 US population. Diabetes was defined as reported in the electronic medical record or glycohemoglobin A1c > 6.4% during hospitalization.

Results:
There were a total of 4141 ischemic strokes; 55% female and 22% black. Stroke rates continue to be substantially higher in those with diagnosed diabetes, than those without diabetes overall and for those less than 65 years in both time periods, as well as those 65 years and older except for the black population in 2010. Racial disparities continue in both the less than 65 and 65 years and older age groups. Stroke rates were higher for Blacks in the less than 65 year age group for those both with and without diabetes; with risk ratios ranging from 1.3 to 2.7. Of note the stroke rate has decreased between 2010 and 2015 for those with diabetes <65 years of age. (Table)

Conclusions:
The population with diabetes continues to be at increased risk of stroke, especially in those less than 65 years of age and those of black race.
Abstract WMP58: The Smoker’s Paradox After Acute Ischemic Stroke, is it Real or a Cloud of Smoke?
Authors: de Havenon Adam H , Mistry Eva , Yaghi Shadi , Khatri Pooja , Prabhakaran Shyam
Published: June 2021

Background:
Although tobacco use, the majority of which is cigarette smoking, increases the risk of incident stroke, there are inconsistent data regarding the effect of tobacco use on neurological outcomes after acute ischemic stroke. Several prior studies have suggested that smoking could be protective after stroke, which has been termed the "smoker’s paradox."

Methods:
We pooled three data sources to explore the effect of tobacco use on neurologic outcome in acute stroke patients. The first was the Blood Pressure after EVT in Stroke (BEST) study, the second was the NINDS tPA trial, and the third was the Interventional Management of Stroke (IMS) III trial. The primary outcome is 90-day mRS 0-2 (good outcome). We fit logistic regression models to good outcome, both unadjusted and adjusted for patient age, NIHSS, and sICH.

Results:
Our pooled cohort had 1,671 acute stroke patients, of which 480 (28.7%) used tobacco. In an unadjusted model, tobacco use was associated with good outcome (OR 1.42, 95% CI 1.15-1.76, p=0.001). However, in the adjusted model, this association was no longer significant (aOR 0.98, 95% CI 0.76-1.25, p=0.868). If we stratify by placebo-treated (n=310), tPA-treated (n=513), and EVT-treated (n=836), we continue to find that tobacco use is not associated with good neurologic outcome in adjusted analyses specific to these subgroups. An additional subgroup analysis of the EVT-treated patients that adjusted for successful procedural recanalization (TICI 2b-3) was not significant. Patients who used tobacco were younger (mean age, 60.5 vs. 69.2 years, p<0.001). Adjusting for age alone rendered the association between tobacco use and good outcome insignificant (aOR 1.05, 95% CI 0.84-1.32, p=0.666).

Conclusions:
This is the first adjusted analysis to examine the association between tobacco use and neurologic outcome in EVT-treated patients. We find that tobacco use is not protective after acute ischemic stroke that is untreated or treated with tPA or EVT. The univariate association of tobacco use with good outcome is accounted for by tobacco users being younger.
Abstract WMP64: From Static Imaging to Hemodynamic Modelling: Validation of Intracranial Blood Flow Simulations Against Population-Based PC-MRI Studies
Authors: Yeo Leonard L , Boopathy Sethu R , Engin Melih , Lange Robin , Cunli Yang , Tang David K , Mohammadzadeh Milad , Monajemi Sadaf , Goh Chin Kong , Tu Tian Ming , Sharma Vijay K
Published: June 2021

Purpose:
Modelling blood flow in cerebral arteries presents an opportunity to go beyond current luminal stenosis. These models could improve stroke prognostication by adding hemodynamic biomarkers such as translesional shear stress and pressure gradient. Such models, however, are rarely validated against real clinical data. We evaluated the accuracy of a computational fluid dynamics (CFD) model which uses allometric scaling laws against population-based Phase Contrast MRI (PC-MRI) measurements of blood flow in the brain.

Methods:
3D models of the anterior circulation of 23 healthy subjects were reconstructed based on their MRA Time of Flight (TOF) images and CFD was used for modelling the blood flow. Lumped parameter Windkessel models were used as boundary conditions and allometric scaling laws were used to divide the flow and tune these boundary conditions, i.e. the resistance at each boundary was automatically adjusted based on the dimensions and branching of upstream vasculature. The results were compared against 4 PC-MRI studies from literature, covering a combined number of 417 healthy subjects.

Results:
The flow rate across 3 major intracranial arteries (ICA, MCA, and ACA) was obtained from the CFD simulations and was in good agreement with population-based PC-MRI studies. The agreement was 82.6% for the ICA, 85.9% for the MCA, and 80.4% for the ACA when comparing the average flow rate. The inter-patient variability of the flow rate (i.e. standard deviation) obtained from CFD simulations matched closely with the variation range measured in the literature. Allometric scaling enabled the model to accurately divide the flow at bifurcations (MCA/ICA flow ratio was 58.6% for the model vs 56.3% in the literature). We observed an average of 8 mmHg in pressure drop along the anterior circulation of healthy subjects (from ICA to MCA-M1 and ACA-A1), which agrees with the physiological range reported in the literature.

Conclusion:
This study shows the potential of accurately modelling blood flow based only on static images and demonstrates the validity of using allometric scaling in intracranial CFD simulations. The current modelling approach can potentially assist in stroke prognostication by obtaining hemodynamic risk factors from standard MRA TOF or CTA.
Abstract WMP74: Cofilin-Actin Rod Formation in Experimental Stroke is Attenuated by Therapeutic Hypothermia and Overexpression of the Inducible 70-kDa Heat Shock Protein (Hsp70)
Authors: Kurisu Kota , You Je Sung , Won Seok Joon , Zheng Zhen , Swanson Raymond A. , Yenari Midori A.
Published: June 2021

Background and Purpose:
Cofilin-actin rods are covalently linked aggregates of cofilin -1 and actin. Under ischemic conditions, these rods have been observed in neuronal processes, but their significance is unknown. Here, we explored a potential role of these rods in two different models of neuroprotection from experimental stroke—therapeutic hypothermia and the 70-kDa heat shock protein (Hsp70).

Methods:
Male C57/BL6 mice were subjected to distal middle cerebral artery occlusion (dMCAO), and treated with hypothermia. Cooling (31°C, 2hrs) was begun at the onset of dMCAO. A neuroprotective effect of hypothermia was validated by functional assessments and infarct volume measurement. Cofilin-actin rod formation was assessed by histological analysis at 4 and 24hrs after dMCAO. Its expression was analyzed in three different regions, infarct core (the center of the infarct), penumbra (area salvaged by intervention and a fixed distance from the midline), and ischemic borderzone (border of ischemic lesion). In addition, Hsp70-overexpressing transgenic (Tg) mice and Hsp70-deficient (Ko) mice were also subjected to dMCAO, and cofilin-actin rod expression was assessed in same manner.

Results:
As shown previously by our lab, both hypothermia and Hsp70 Tg mice had smaller lesion sizes and improved neurological outcomes compared to normothermic and wildtype (Wt) mice. Hsp70 Ko mice had larger lesion sizes and worsened neurological outcomes. Following dMCAO, cofilin-actin rods were increased, but were reduced by hypothermia in the ischemic core (24hrs, p<0.05), penumbra (4 and 24hrs, p<0.05), and ischemic borderzone (4 and 24hrs, p<0.05). Among Hsp70 Tg mice, cofilin-actin rod formation was decreased in the ischemic borderzone (4 and 24hrs, p<0.05), while Hsp70 Ko mice showed increased rod formation in the penumbra (4 and 24hrs, p<0.05).

Conclusions:
Cofilin-actin rod formation was suppressed under conditions of improved neurological outcome, and increased under circumstances where outcome was worsened. This suggests that cofilin-actin rods may act to participate in or exacerbate ischemic pathology, and warrants further study as a potential therapeutic target.
Abstract WMP76: Interleukin-33 Protects Against Transient Ischemic Stroke by Enhancing Regulatory T-Cell Expansion and Accumulation
Authors: Liu Xinjing , Hu Ruiyao , Pei Lulu , Xu Yuming , Song Bo
Published: June 2021

Background:
The interleukin (IL)-33 could promote proliferation of regulatory T lymphocytes (Tregs) which are negatively related with brain damage after ischemic stroke. How IL-33 works on Tregs after stroke is unclear. The purpose of this study was to investigate the role of IL-33 for Tregs-mediated neuroprotection and further expounded the mechanisms of protection in mice.

Methods:
In vitro study, primary mice neuronal cells were subjected to 3h oxygen-glucose deprivation (OGD). The vehicle or drug conditioned Tregs were applied to neurons at the time of induction of hypoxia respectively. Neuronal apoptosis, Tregs related cytokines were measured by MTT assay, Western blotting and enzyme-linked immune-sorbent assay (ELISA). In vivo study, Tregs were depleted by intraperitoneal administration of anti-CD25Ab. Intraperitoneal injection of IL-33 immediately post 60 min transient middle cerebral artery occlusion (tMCAO) modeling. The neurological function test at days 1, 3, 5, 7 and 14 after tMCAO. Infarct volume, Brain edema, cell death, percentage of Tregs and related cytokines were respectively measured by 2,3,5-triphenyltetrazolium chloride or MAP2 staining, dry-wet method, TUNEL staining, flow cytometry and immunofluorescence, Western blotting and ELISA.

Results:
The supernatant of IL-33-treated Tregs reduced neuronal apoptosis in the OGD model meanwhile elevated the production of Tregs related cytokines IL-10, IL-35 and TGF-
β
in vitro. Intraperitoneal administration of IL-33 significantly reduced infarct volume and stroke-induced cell death and improved sensorimotor functions. Notably, the protective effect of IL-33 was abolished in mice depleted of Tregs. IL-33 increased CD4+CD25+Foxp3+ Tregs in spleens, blood, and brain in vivo. Yet, ST2 blocking muted these IL-33 activities. Mechanistically, the protection of IL-33 was associated with reduced apoptosis protein and production of Tregs related cytokine.

Conclusions:
This study elucidated that IL-33 afforded neuroprotection against ischemic brain injury by enhancing ST2-dependent regulatory T-cell expansion and activation, which suggested a promising immune modulatory target for the treatment of stroke.
Abstract WMP86: Persistent Gender and Racial Disparities Among Neurology Residents and Vascular Neurology Fellows Over the Past 10 Years
Authors: Zelnick Pamela J , Fournier Lauren E , Zhu Liang , Savitz Sean I , Sharrief Anjail Z
Published: June 2021

Introduction:
Women and minorities are underrepresented in academic medicine. There is little in the literature about gender and racial disparities among neurology or vascular neurology trainees. At the International Stroke Conference, women overall and women physicians have been underrepresented as invited speakers and abstract first authors, and there is recent momentum for improvement.

Methods:
Data were collected from the Accreditation Council for Graduate Medical Education public website. Dataset included neurology resident and vascular neurology fellow gender data from 2007 to 2017 and race data from 2011 to 2017. Data were analyzed by chi-square test and one-sample proportion test.

Results:
From 2007-2017, women represented 45% of all neurology trainees and only 33% of all vascular neurology fellows, both significantly lower than 50% (p<0.0001). There was no trend in the proportion of gender by year for vascular fellows (p=0.11) or neurology trainees (p=0.39). However, each year, except for 2012-2013 and 2015-2016 for vascular fellows, varied significantly by gender where men represented the largest proportion. Race varied by year for vascular fellows (p=0.03) and neurology trainees (p=0.017). Blacks and Hispanics represented the lowest proportions and Whites represented the highest proportion of both vascular and neurology trainees. When comparing Whites vs Non-Whites for both fellows (43% vs 57%; p=0.76) and residents (50% vs 50%; p=0.14), there was no trend in the proportions by year.

Conclusions:
Women, Black and Hispanic physicians remain underrepresented as vascular neurology trainees. The low representation of women and underrepresented minorities has not changed in the last decade. Addressing gender and racial disparities among trainees should be a high national priority for future medical and scientific contributions from these groups.
Abstract WMP89: Outcomes No Different in Real World Including Direct vs Drip-and-Ship Patients: Power of Reperfusion From Mechanical Thrombectomy
Authors: Shah Darshan G , Loganathan Aravi , Truong Dan , Chan Fiona , Campbell Bruce , Whitley Justin , Leggett David , Redmond Kendal , Ong Meilisa , Brown Helen
Published: June 2021

Background:
Mechanical thrombectomy (MT) became standard care in 2015 after positive trials in patients presenting with acute ischemic stroke and large vessel occlusion (LVO) 0-6h and in 2018 for selected patients up to 24h from symptom onset.

Objective:
To evaluate whether patients receiving MT at our center would have comparable outcomes in patients presenting to our comprehensive stroke center (direct) vs transfer patients (drip-and-ship)

Methods:
This is a retrospective observational study utilising prospectively collected stroke database for patients receiving MT for LVO in anterior and posterior circulation in South Brisbane network of 7 hospitals (6 drip-and-ship centers and 1 MT-capable center), Australia which serves 1.6 million. Day 90 modified Rankin scale (mRS) was used to assess functional outcomes via outpatient follow up at direct or referral center. The association of drip and ship versus mothership treatment with day 90 mRS was tested in ordinal logistic regression adjusted for age, baseline NIHSS and IV thrombolysis.

Results:
Of 191 patients who underwent Mechanical Thrombectomy from 2015 to June 2018 at our center, 22 patients were excluded from analysis as either their baseline mRS was >1 (13) or follow up data was missing (9). The mean age was 64.4 years. Median (inter-quartile range, IQR) NIHSS was 16 (9-21) on admission and 7 (2-18) on day 1. Thrombolysis in Cerebral Infarction (TICI) ≥2b was achieved in 88.9%. At 90 days, 50.9% achieved excellent functional outcome (mRS 0-1), 61.4% achieved good functional outcome (mRS 0-2) and 69% achieved favorable outcome (mRS 0-3). Median mRS was 1 (IQR 0-5) in 96 patients presenting directly to the endovascular center and 1 (IQR 1-4) in 73 drip-and-ship patients (common odds ratio 1.07 (95%CI 0.62-1.83), p=0.82)

Conclusion:
Our 7-center network experience confirms real world reproducibility of trial results, interestingly with no difference in functional outcomes for direct vs drip-and-ship patients.
Abstract WMP9: Procedural Parameters Predicting Reduced MRI Infarct Growth in Mechanical Thrombectomy
Authors: Andrapalliyal Nirmal , Mulpur Bhageeradh , Handshoe Lacy Samuel , Uchino Ken , Hussain M. Shazam
Published: June 2021

Background:
Successful recanalization after a single pass and shorter procedural duration during mechanical thrombectomy (MT) in emergent large vessel occlusion (ELVO) have been associated with both rapid neurologic improvement and long-term clinical outcome, although conflicting data exists regarding their direct effect on infarct growth. We aimed to determine whether less device passes or shorter procedural times are associated with decreased infarct growth.

Methods:
We reviewed consecutive patients presenting to a comprehensive stroke center from January 2016 to December 2018 with (ELVO). Standard protocol included pre-procedural MRI imaging and only those with post-procedural MRI were included in this study. Number of passes attempted and procedural times were recorded. Infarct volume on MRI was measured using region of interest analysis blinded to procedural outcomes. MRI infarct growth was analyzed using linear regression as a function of procedural times and number of passes.

Results:
Of 173 patients undergoing MT after MRI, 118 patients had MRI imaging post-procedure. Successful recanalization (TICI >2b) was achieved in 106/118 patients. For each additional minute of procedural duration, MRI infarct growth increased by 0.23 mL (p=.04). Average MRI infarct growth was different amongst the passes (p=0.001): 14.65 mL in cases with only one pass (n=67), 25.67 mL with two passes (n=26), 28.68 mL with three passes (n=17), and 98.42 mL with four or greater passes (n=8).

Conclusion:
Longer procedural duration and increased number of passes are associated with increased MRI infarct growth.