bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP20: The Basilar Artery on Computed Tomography Angiography (batman) Prognostic Score for Basilar Artery Occlusion
Authors: Alemseged Fana , Shah Darshan G , Diomedi Marina , Sallustio Fabrizio , Bivard Andrew , Sharma Gagan , Mitchell Peter J , Dowling Richard J , Yan Bernard , Stanzione Paolo , Parsons Mark W , Levi Christopher R , Davis Stephen M , Campbell Bruce C
Published: June 2021

Background:
Basilar artery occlusion (BAO) is associated with high risk of disability and mortality. This study aimed to assess the prognostic value of a new radiological score: the “Basilar Artery on Computed Tomography Angiography score (BATMANs)”.

Methods:
A retrospective analysis of consecutive stroke patients with a diagnosis of BAO on CT angiography (CTA) was performed. BATMANs is a 10 point CTA-based grading system. We allocated 1 point for each patent segment (proximal, middle and distal) of the basilar artery, 1 point for any patent intracranial vertebral arteries (VA), 1 point for each posterior cerebral artery (PCA) and 2 points for each posterior communicating artery (PcoM) or 1 point for hypoplastic PcoM (<1 mm diameter). Two investigators reviewed the CTA images blinded to clinical outcome. Reliability was assessed with intraclass coefficient correlation (ICC). Good outcome was defined as modified Rankin Scale≤3 at 3 months; successful reperfusion as thrombolysis in cerebral infarction 2b-3. BATMANs was externally validated and compared with the Posterior Circulation Collateral score (PC-CS).

Results:
The derivation cohort (DC) included 83 patients with 41 in the validation cohort (VC). In receiver-operating-characteristic (ROC) analysis, BATMANs had an area-under-curve (AUC) of 0.81 (95%CI 0.7-0.9) in DC and an AUC of 0.74 (95%CI 0.6-0.9) in VC. BATMANs<7 was the optimal threshold for poor outcome in DC (sensitivity=84%, specificity=76%). In logistic regression adjusted for age and clinical severity, BATMANs<7 was associated with poor outcome in DC (OR 5.5, 95% CI 1.4 -21; p=0.01), in VC (OR 6.9, 95% CI 1.4-33; p=0.01) and among endovascular patients (OR 3.8, 95%CI 1.0-14; p=0.05). BATMANs was independently associated with functional outcome after adjustment for revascularization and time to treatment (OR 4.8, 95%CI 1-18; p=0.01); however, it was not associated with recanalization. Inter-rater agreement was excellent (ICC 0.85, 95% CI 0.76-0.89). BATMANs showed higher accuracy in comparison with PC-CS (p=0.03).

Conclusions:
The addition of collateral quality to clot burden in BATMANs appears to improve prognostic accuracy in BAO patients.
Abstract WMP22: Multiparametric CT Perfusion to Determine the Collaterals Status in Patients With Acute Ischemic Stroke: A New Perfusion Index
Authors: Awad Ahmed J , Tadayon Sayedhedayatollah E , Wei Daniel , Haroun Reham R , Oxley Thomas J , Fifi Johanna T , Doshi Amish H , De Leacy Reade A , Bederson Joshua B , Mocco J , Nael Kambiz
Published: June 2021

Introduction:
Good collateral flow is an independent predictor of reperfusion that can be used to extend the treatment window in the new era of endovascular therapies for patients with acute ischemic stroke (AIS). Using a multiparametric approach, we aimed to identify perfusion parameter/s that can represent the extent of collaterals in comparison to CTA.

Methods:
AIS patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion were included. CT perfusion data were processed by Bayesian method to generate arterial tissue delay (ATD) maps at thresholds of 2 & 6 seconds. The volume of mild delayed perfusion (Vol-ATD
>2sec
), moderate delayed (Vol-ATD
2-6sec
) and critical delayed perfusion (Vol-ATD
>6sec
) in addition to corresponding rCBV and rCBF were calculated. Baseline CTA collaterals were scored using an established scoring scale1 and dichotomized to poor or good. The association of perfusion parameters and status of collaterals was assessed by repeated measure of analyses and receiver operating characteristic (ROC).

Results:
In 28 patients included, 16 had good collaterals on CTA. After controlling for age, sex, baseline NIHSS and type of treatment, multivariate logistic regression analysis identified rCBV (p<0.001) and ATD
2-6sec
(p=0.003), but not rCBF, Vol-ATD
>
2sec
or Vol-ATD
>6sec
, as independent predictors of good collaterals. ROC analysis showed AUC of 0.88 (sensitivity/specificity: 75%/100%) for rCBV and AUC of 0.84 (sensitivity/specificity: 93%/67%) for Vol-ATD
2-6sec
. We defined a perfusion collateral index (PCI) calculated from Vol-ATD
2-6sec
x its rCBV, that remained an independent predictor of good collaterals with improved diagnostic accuracy over each measure alone resulting in nominal AUC of 1 (sensitivity/specificity: 100%/100%).

Conclusions:
Multiparametric CT perfusion can be used to assess the status of collaterals in patients with AIS. Perfusion collateral index (PCI) defined as Vol-ATD
2-6sec
x rCBV is a new perfusion index with a nominal diagnostic accuracy of 100% compared to baseline CTA to predict status of collaterals in our small cohort. Our results need to be validated in a larger prospective cohort.
Abstract WMP27: Cerebral Blood Velocity Changes During Dobutamine Administration for Experimental Subarachnoid Hemorrhage in Mice
Authors: Nakamura Kazuhiro , Mutoh Tatsushi , Sasaki Kazumasu , Taki Yasuyuki , Ishikawa Tatsuya
Published: June 2021

Introduction:
Hyperdynamic therapy with dobutamine (DOB) administration on patients with subarachnoid hemorrhage (SAH) is a useful strategy for treating cerebral vasospasm and neurological deterioration. Even some reports have suggested that DOB administration caused the cerebral blood flow (CBF) augmentation by increasing cardiac output, microcirculatory behavior in brain remains unclear.

Hypothesis:
Red blood cell (RBC) velocity should be increased under DOB administration. To investigate the cortical microcirculation, two-photon laser scanning microscopy with successive line-scans was used for red blood cell (RBC) velocity estimation.

Methods:
SAH was induced in ten male wild-type C57BL/6 mice (23 - 25g) using endovascular perforation technique. Five days after SAH, a cranial window was prepared for optical access to the cortical vasculature. Then we observed two-photon microscopy with intravenously injected rhodamine-dextran. The RBC velocity was visualized as dark objects against the fluorescent plasma background. The velocity was estimated from dark objects angle in successive line-scans analyzed by Radon function based algorithm. DOB was administrated intravenously at the dose of 6 and 12 μg/kg/min.

Results:
RBC velocity was increased in 8 mice after the DOB administration and 2 mice were reduced. The RBC velocity in increased mice of baseline , 6 , and 12 μg/kg/min was 1.29±0.40, 1.70±0.74 and 1.37±0.53 mm/sec, respectively. In the reduced mice, the RBC velocity was dropped almost half value of baseline at the DOB administration.

Conclusions:
DOB administration was increased RBC velocity in cortical microcirculation. It indicates DOB hyperdynamic therapy on patients with SAH is effective in the viewpoint of cortical microcirculatory control.
Abstract WMP28: Optimizing Cerebral Perfusion in Comatose Patients with Acute Neurological Illness
Authors: Rivera Lara Lucia A , Geocadin Romer , Zorrilla-Vaca Andres , Healy Ryan , Radzik Batya R , Palmisano Caitlin , Mirski Marek , Hogue Charles , Ziai Wendy
Published: June 2021

Introduction:
Several studies have demonstrated the feasibility of individualizing optimal mean arterial blood pressure (MAP) with cerebral autoregulation (CA). However, it is still unclear whether cerebral autoregulation-oriented therapy has the potential to improve outcomes in critically ill patients. This study aimed to determine whether comatose patients with greater duration and magnitude of MAP outside the optimal arterial blood pressure (MAP
OPT
) have worse neurologic outcome than those with MAP closer to their MAP
OPT
calculated bedside by CA monitoring.

Methods:
Cerebral oximetry index (COx) was continuously monitored with near-infrared spectroscopy (NIRS) for up to three days in acutely comatose patients admitted to a neurocritical care unit. MAP
OPT
was calculated using the lowest COx (nadir index) every day of monitoring. Multivariate logistic regression was used to determine if survival at discharge was associated with lesser duration and magnitude of MAP outside the calculated MAP
OPT
.

Results:
A total of 74 patients were prospectively enrolled in the study
.
The median MAP
OPT
was 90 mmHg (IQR: 82.8-102.5 mmHg). The absolute difference between MAP and MAP
OPT
was significantly associated with in-hospital mortality (OR=1.24, 95%CI=1.00-1.52, P=0.046) after adjusting for mRS on admission, brain herniation, midline shift at septum, Glasgow coma scale (GCS) score at the time of monitoring and duration of time under and above the MAP
OPT
. Other variables that reached statistical significance for mortality in the multivariate model were the duration of time under or above the MAP
OPT
(OR=1.11, 95%CI=1.02-1.21, P=0.016), midline shift at septum (OR=1.30, 95%CI=1.03-1.63, P=0.025) and GCS at the time of monitoring (OR=0.44, 95%CI=0.24-0.82, P=0.01).

Conclusions:
We found that mortality at hospital discharge in comatose adults with acute neurological illness was independently associated with greater magnitude and duration of MAP outside the MAP
OPT.
Non-invasive individualized bedside calculation of MAP
OPT
seems to be feasible and might be a promising tool for CA oriented-therapy in comatose patients.
Abstract WMP3: Direct Transfer to Angio-suite to Reduce Door-to-puncture Time in Thrombectomy for Acute Stroke
Authors: Ribo Marc , Tomasello Alejandro , Boned Sandra , Coscojuela Pilar , Juega Jesus , Rodriguez Noelia , Romero Nicolas , Hernandez David , Rodriguez-Luna David , Pagola Jorge , Muchada Marian , Sanjuan Estela , Molina Carlos , Rubiera Marta
Published: June 2021

Background:
We aim to evaluate the feasibility and safety of a direct transfer to the angio-suite protocol for acute stroke patients candidates for endovascular treatment (EVT).

Methods:
Starting June 2016, patients with pre-hospital stroke code activation (RACE≥4) admitted within 4.5h from symptoms-onset were directly transferred on admission to angio-suite (DTA) bypassing the emergency room. After Xpert-CT in the angio-suite for parenchymal evaluation, femoral puncture and EVT were performed as usual. Patients following DTA were compared to all patients with same admission criteria treated with EVT in the previous 2 years (control group, CG).

Results:
Of the 16 patients that followed DTA, 1 (6%) showed an intracranial hemorrhage (ICH) on Xpert-CT and 15 underwent EVT, representing 50% of EVT admitted within 4.5h or 34% of all EVT performed in the study period. 56% of DTA patients had previous neuroimaging at a primary stroke center, 44% were primary admissions with no previous neuroimaging. Baseline characteristics including age (71 Vs 72 years; p=0.71) and admission NIHSS (18.5 Vs 18;p=0.68) were comparable. Median time from admission to groin puncture was significantly shorter in DTA patients (15 minutes IQR:13-19 Vs 65 IQR:45-10;p<0.01). Rate of no treatable occlusion on initial angiogram was 13.3% in DTA Vs 2.4% in CG (p=0.17). Procedural time (36 Vs 55 minutes;p=0.034) was shorter in the DTA group, while recanalization (TICI 2b-3: 86% Vs 81%;p=0.24) and symptomatic ICH rates(6.7% Vs 6.6%;p=0.98) and 24h NIHSS (10 Vs 10.5; p=0.81) were comparable. The total time from admission to recanalization was significantly shorter when DTA was applied (median 52 Vs 123;p<0.01).

Conclusion:
In a subgroup of acute stroke patients presenting in the early window, direct transfer and triage in the angio-suite seems feasible, safe and achieves a significant reduction in hospital workflow times.
Abstract WMP32: Cost-Effectiveness of Flow Diverters versus Coiling in the Treatment of Carotid Sidewall Aneurysms
Authors: Piotin Michel , Ciccio Gabriele , Redjem Hocine , Smajda Stanislas , Desilles Jean P , Mazighi Mikael , Robert Thomas , Blanc Raphaël
Published: June 2021

Purpose:
Flow Diverters (FD) have dramatically impacted the manner of endovascular treatment (EVT) of carotid siphon sidewall aneurysms. However, the indications remain unclear when compared to conventional coiling and stent-assisted coiling. We conducted herein a retrospective monocentric study in order to evaluate the safety and cost-effectiveness of EVT, comparing treatment with FD versus coiling.

Materials and Methods:
Based on a prospectively gathered database we selected unruptured sidewall carotid siphon aneurysms treated in our department since the introduction of FD (2008 to 2016) for which the maximum sac diameter was 15 mm. Patient demographics, aneurysm characteristics (sac and neck sizes, dome-to-neck ratio), treatment options (FD, simple coiling or with balloon-remodeling technique [BRT], stent-assisted-coiling [SAC]), procedural and peri-procedural complications, angiographic results at follow-up were collected. Total procedural costs were also recorded. Both groups of patients and aneurysms were compared.

Results:
226 aneurysms in 211 patients (1.1 aneurysm per patient) during 216 procedures (including 158 BRT and 42 SAC procedures) were coiled. 161 aneurysms in 114 patients (1.4 aneurysm per patient) during 126 procedures were treated with FD (no coils). Aneurysms in the FD group had larger neck and lower dome-to-neck ratio. No mortality occurred in both groups. Complication rates were similar in both groups. Angiographic follow-up was longer in the coiling group. There was no difference in term of total aneurysm circulatory exclusion at follow-up between the 2 groups. FD treatment was twice more expansive than coiling (aggregated costs of simple coiling, BRT and SAC).

Conclusions:
In the light of the clinical, angiographic results and costs, there is no rational to consider FD treatment for small and medium sizes carotid siphon aneurysms as the first EVT option. Coiling remains a valid therapeutic alternative in the FD era.
Abstract WMP35: The Characteristics of Infectious Intracranial Aneurysm and Indication of Cerebral Angiogram in Infective Endocarditis (IE)
Authors: Cho Sung-Min , Marquardt Robert , Zhang Lucy , Thatikunta Prateek , Uchino Ken , Wisco Dolora
Published: June 2021

Introduction:
Infectious intracranial aneurysm (IIA) can complicate infective endocarditis (IE). We aim to describe the characteristics of IIA and to assess indications for cerebral angiography.

Methods:
We reviewed IIAs among 116 consecutive active IE by Duke’s criteria with neurological consultation or admission to stroke neurology service in a single tertiary referral center from January 2015 to July 2016. Susceptibility weighted imaging (SWI) hemorrhage was defined as low signal on SWI in sulci or parenchyma that was not apparent on CT.

Results:
Of 116 patients, 74 persons (63.8%, mean age of 54) underwent digital subtraction angiography (DSA). IIAs were identified in 13 (17.6%). All of 13 IIAs were unruptured and only one IIA had unrelated intracranial hemorrhage on CT. None of the IIA was seen with CTA or MRA. Eleven (85%) IIAs had clinical strokes (10 ischemic strokes, 1 intracerebral hemorrhage, median NIH stroke scale 3), and 2 neurologically asymptomatic with abnormal MRI. Six of 9 IIAs had SWI hemorrhage in sulci or parenchyma (5 in sulci, 5 in parenchyma, and 1 in both) and all of the lesions were in the vicinity of IIA. Contrast MRI was performed in 7 IIAs, and 4 IIAs had enhancements, all of which were present near the location of IIAs. Ischemic stroke, intracranial hemorrhage, intravenous drug abuse, and type of valve were not associated with the presence of IIA. Of 13 IIAs, 3 remained on antibiotic alone, 5 had antibiotic with coil embolization, and, 5 had antibiotic with glue embolization. Ten patients with IIAs had valvular surgery, including one person with untreated IIA. Out of all patients with IIA, only one intracerebral hemorrhage occurred as perioperative complication unrelated to treated IIA.

Conclusions:
IIAs were found in approximately one fifth of IE persons who underwent DSA. Imaging characteristics such as SWI hemorrhage in sulci or parenchyma and contrast enhancement appear to correlate with the presence of IIA. DSA should be performed when they are present.
Abstract WMP38: Inhibition of Rip1 Kinase Improves Brain Functional Recovery After Ischemic Stroke via Reducing Astrocytic Scar Formation
Authors: Zhang Huiling , Li Zhong-Sheng , Ni Yong , Zhou Xian-Yong , Qiao Shi-Gang
Published: June 2021

During the recovery phase of ischemic stroke, one of the major barriers for the spontaneous neuronal axon regeneration is the formation of astrogliosis and glial scar, and targeting astrogliosis becomes a therapeutic strategy for ischemic stroke. However, the mechanism regulating the process of scar components after ischemia still remains poorly understood. The aim of this study was to observe the role of RIP1 kinase (RIP1K), the key regulator of necroptosis (programmed necrosis) in the brain functional recovery after ischemic stroke and in the ischemic stroke-induced astrogliosis and glial scar formation in both
in vitro
and
in vivo
glial scar models. The glial scar formation model
in vitro
or
in vivo
was established by using primary cultured astrocyte subjected to 6 hours of oxygen-glucose deprivation (OGD) following 12 hours or 24 hours reperfusion, or by 90 min of transient middle cerebral artery occlusion (tMCAO) and reperfusion in rats. Western blotting analysis and immunohistochemical assay showed that knockdown of RIP1K by lentivirally-delivered shRNAs against RIP1K (shRNA RIP1K) could decrease several protein levels of glial scar markers such as glial fibillary acidic protein (GFAP), neurocan and phosphacan both in
in vitro
and
in vivo
glial scar models. Furthermore, western blotting analysis showed that knockdown of RIP1K reduced the protein levels of VEGF-D receptor 3 in
in vitro
glial scar models. In addition, knockdown of RIP1K also notably reduced the shrinking volume and ameliorated the behavioral symptoms in the recovery phase of rats after tMCAO. And immunocytochemistry assay demonstrated that RIP1K knockdown promoted the neuronal axonal generation in a neuron and astrocyte co-culture system. Our data indicates that RIP1K might play an important role in the formation of glial scar after ischemic stroke via promoting the function of VEGF-D receptor 3 in astrocytes.
Abstract WMP4: Thrombectomy-only versus Combined Intravenous Alteplase and Thrombectomy: Meta-analysis
Authors: Lin Michelle P , Colby Geoffrey P , Llinas Rafael H
Published: June 2021

Introduction:
Contraindications for intravenous thrombolysis are not infrequent (eg. anticoagulation, recent surgery, unclear last known well). With overwhelming recent evidence supporting the use of endovascular thrombectomy for large-vessel occlusive stroke, we conducted a metaanalysis to compare long-term functional outcome between thrombectomy-alone versus combined IV-tPA and thrombectomy.

Hypothesis:
Patients with acute ischemic stroke ineligible for IV-tPA treated with thrombectomy-alone have equally favorable long-term functional outcomes to patients treated with combined IV-tPA and thrombectomy

Methods:
Searched PubMed from 2014-2016 using pre-specified terms for studies that report odds ratio of improvement in mRS score at 90 days comparing thrombectomy vs IV-tPA stratified by whether patients had received IV-tPA. Multivariate adjusted odds ratios were used for the metaanalysis. Pooled odds ratio estimates across trials were synthesized by using a random-effects model based on Mantel-Haenszel methods. The pooled estimates were compared between thrombectomy-alone and combined IV-tPA and thrombectomy. Forest plots constructed.

Results:
Of the 920 studies, 3 studies reported subgroup analysis with 822 participants, 19.5% (N=160) received thrombectomy-alone, 80.5% (N=662) received combined IV-tPA and thrombectomy. Among patients who received thrombectomy-alone, the pooled odds ratio of good functional outcome at 3 months was 2.48 (1.43-4.30), in the combined IV-tPA and thrombectomy group the pooled odds ratio was 1.85 (1.37-2.49).

Conclusions:
Endovascular therapy was an effective therapy for patients ineligible for IV-tPA presenting with acute ischemic stroke caused by large vessel occlusive disease. While IV-tPA should not be withheld before thrombectomy in IV-tPA eligible patients, prospective studies are needed to select those who may benefit more from thrombectomy-only treatment.
Abstract WMP44: Functional Recovery Following a Combination of Thrombin Inhibitor Argatroban and Tissue Plasminogen Activator (tPA) in Thromboembolic Stroke in Nonhuman Primates
Authors: Suzuki Junko , Itani Yoshitaka , Ogawa Shinya , Yamanaka Kazunori , Hayashi Ikuo , Takamatsu Hiroyuki
Published: June 2021

Introduction:
Early treatment following an acute stroke with the thrombolytic tissue plasminogen activator (tPA) increases functional recovery. Complications of tPA treatment include hemorrhaging and narrow therapeutic time window. Thus, better treatments for acute stroke are needed. While a number of novel treatments for acute ischemic stroke have been derived from preclinical rodent stroke models, to date, none have succeeded in clinical studies. Nonhuman primates are phylogenetically closer to humans than rodents, which could narrow the current translational shortfall between preclinical and clinical findings. The goal of the current study was to test the effect of a combination of argatroban, a thrombin inhibitor, and tPA on functional recovery and brain infarction size following thromboembolic ischemia in nonhuman primates.

Methods:
Autologous blood clots were injected into the internal carotid artery of cynomolgus macaques to induced a thromboembolic stroke. Either tPA (0.9 mg/kg; n = 8) or vehicle (n = 8) was intravenously infused for one hour an hour following the induction of ischemia. In a third group, after completion of tPA infusion, argatroban (0.6 mg/kg; n= 7) was intravenously infused for 22 hours. Doppler ultrasound recorded middle cerebral artery (MCA) blood flow for six hours following induction of stroke. In addition, brain infarct volume (TTC staining) and functional assessment (Neurologic Deficit Score; NDS) were determined 24 hours after ischemia.

Results:
Compared to vehicle treatment, tPA treatment significantly decreased MCA occlusion time, brain infarct volume and NDS. Treatment with the combination of argatroban and tPA decreased occlusion time, brain infarct volume and NDS similar to tPA treatment alone.

Conclusion:
The current study suggests that the addition of argatroban could enhance recanalization rates observed with tPA treatment alone. However, in contrast to previous findings in rats, the combination of argatroban and tPA does not appear to further enhance tissue or functional recovery from a thromboembolic stroke compared to tPA treatment alone.
Abstract WMP46: Exosomes Derived From Bone Marrow Mesenchymal Stem Cells of Type Two Diabetes Rats Promotes Neurorestoration After Stroke in Type Two Diabetic Rats
Authors: Venkat Poornima , Chopp Michael , Zacharek Alex , Chen Jieli
Published: June 2021

Background and Purpose:
Roughly 1 in every 3 stroke patients is diabetic and suffers from an increased risk of stroke recurrence, worse prognosis, and exacerbated vascular and white matter (WM) injury that hinders long term recovery. Hence, there is a critical need to develop therapeutic strategies specifically to improve neurological functional outcome after stroke in the diabetic population. We investigated the neurorestorative effects of treatment of stroke in rats with type 2 diabetes mellitus (T2DM) with bone marrow stem cell (MSC) derived exosomes (T2DM-MSC-Exo) and the mechanisms underlying the therapeutic effect.

Methods:
Adult male Wistar rats were induced with T2DM using a combination of high fat diet and low dose Streptozotocin and were subjected to transient middle cerebral artery occlusion (MCAo). Three days after MCAo, rats were randomized (n=10/group) and treated via tail-vein injection with: 1) phosphate-buffered-saline (PBS); or 2) T2DM-MSC-Exo (3х10
11
). A battery of neurological tests was performed and rats were sacrificed at 28 days after stroke for immunohistochemical evaluation.

Results:
In T2DM rats, stroke treatment using T2DM-MSC-Exo initiated at a delayed time point (3 days after stroke) significantly (p<0.05 vs. PBS treated T2DM-MCAo rats) improves functional outcome, reduces blood brain barrier (BBB) leakage and hemorrhage, but does not affect blood glucose or lesion volume. Delayed stroke treatment with T2DM-MSC-Exo in T2DM rats, significantly (p<0.05) increases axon and myelin density, increases oligodendrocytes and oligodendrocyte progenitor cell numbers in the ischemic border zone compared to PBS treated T2DM-MCAo rats. Treatment of T2DM stroke rats with T2DM-MSC-Exo significantly (p<0.05) increases the expression of ATP-binding cassette transporter 1 (ABCA1) and Insulin-like growth factor 1 receptor (IGFR1) compared to PBS treated T2DM-MCAo rats.

Conclusion:
Delayed treatment of T2DM stroke using T2DM-MSC-Exo significantly promotes long term neurological functional recovery and neurorestorative effects. These beneficial effects may be mediated by a decrease in BBB leakage and hemorrhage, increase in axon and myelin density, and up regulation of the ABCA1-IGFR1 pathway.
Abstract WMP49: White Matter Hyperintensities in a High Risk Population Living in Marginal Housing (HOTEL study)
Authors: Zhou Lily W , Panenka William J , Thornton Allen , Smith Geoffrey , Barr Alasdair , Rauscher Alexander , Lang Donna , Su Wayne , Gicas Kristina , Woodward Melissa , Buchanan Tari , Vertinsky Talia , Heran Manraj , Vila-Rodriguez Fidel , MacEwan G. William , Honer William , Field Thalia
Published: June 2021

Background:
White Matter Hyperintensities (WMH) are features of cerebral small vessel disease (cSVD) along with lacunes, cerebral microbleeds and perivascular spaces. Vascular risk factors account for only a small proportion of the variability of the presence of WMH, and the role of additional risk factors including drug use/dependence or infections is not well defined.

Objective:
Examine prevalence and risk factors associated with WMH of presumed vascular origin within the HOTEL cohort, a population living in marginal housing with a high prevalence of prior homelessness, substance dependence, head trauma, mental illness and infectious diseases.

Methods:
Baseline imaging on 3T MRI included T1, T2-FLAIR and SWI sequences. WMH not consistent with vascular origins were excluded. Two raters assessed WMH using the Fazekas scale. Participants were divided into those with or without moderate-severe WMH (periventricular Fazekas score >2 or deep score >1). Potential cSVD risk factors which were significant on univariate analysis were entered into a multivariable stepwise binomial logistic regression to identify independent risk factors for moderate-severe WMH.

Results:
Intraclass coefficient for inter-rater reliability was 0.948 (95% CI, 0.924 to 0.965) for periventricular WMH and 0.848 (95% CI, 0.782 to 0.895) for deep WMH. Baseline prevalence of moderate-severe WMH (mean age 43.6 ± 9.5 years, 78% male) was 24.5%, much higher than in other, older healthy aging cohorts (Table). Age (OR 1.085, 95%CI 1.042-1.130), systolic blood pressure (OR 1.033, 95%CI 1.008-1.058) and regular injection drug use (OR 3.655, 95%CI 1.284-10.403) together explained 23.5% of variance in the presence of moderate-severe WMH within this population, with injection drug use having the largest effect.

Conclusions:
This young cohort appears to have an accelerated burden of cSVD, with injected drug use as a major risk factor. Further research is needed to elucidate potential mechanisms.
Abstract WMP50: Decomposition of Ethnic Differences in Stroke Recurrence--The Role of Education and Biological Stroke Risk Factors
Authors: Morgenstern Lewis , Sanchez Brisa N , Case Erin , Lisabeth Lynda
Published: June 2021

Background:
Race/ethnic disparities in stroke recurrence have persisted in the last decade in the USA. These disparities are often attributed to ethnic differences in risk factor prevalence and socioeconomic status.

Methods:
Incident ischemic stroke (IS) cases were ascertained in the Brain Attack Surveillance in Corpus Christi (BASIC) study, in Texas, USA in 2000-2011. Cases validated by stroke physicians were followed until death or a maximum of 5 years to determine 5-year cumulative stroke recurrence risk. Multivariable regression analyses and effect decomposition analyses (EDA) were used to examine the degree to which ethnic disparities are explained by education and biological risk factors.

Results:
There were 3,184 incident IS cases and 340 recurrent strokes (see Table). The ethnic difference in 5-year recurrence rate was 4.4% (p=0.004) greater in Mexican Americans (MA) than non-Hispanic whites (NHW). The age- and sex-adjusted hazard ratio (HR) of 1.43 (95%CI: 1.13, 1.79) comparing MA to NHW was attenuated after adjustment for education (HR=1.35, 95%CI: 0.91, 2.00), and further adjustment for biological factors (HR=1.28, 95%CI: 0.85, 1.92). EDA revealed that 57% of the recurrence risk disparity was due to differential associations (HR) between observed risk factors and recurrence (see Table). The remaining 43% was due to ethnic differences in risk factor prevalence.

Conclusions:
Ethnic differences in the strength of the associations between risk factors and recurrence, most notably education, diabetes, atrial fibrillation and hypertension explained 57% of the recurrence risk disparity. Further investigation of why some risk factors are more strongly associated with stroke recurrence in one ethnic group compared with others could yield valuable information on ethnic-specific stroke pathogenesis and secondary prevention strategies.
Abstract WMP53: A Sex-specific Genome-wide Association Study of Ischemic Stroke in The Stroke Genetics Network (SiGN)
Authors: Fornage Myriam , Jimenez-Conde Jordi , Kittner Steven J , Markus Hugh S , Mitchell Braxton , Pulit Sara L , Rundek Tatjana , Wassertheil-Smoller Sylvia , Williams Stephen R , Rexrode Kathryn M
Published: June 2021

Stroke is the second leading cause of death and a major cause of severe disability worldwide. Experimental, epidemiological, and clinical studies have consistently documented differences between men and women in stroke incidence, prevalence, outcomes, and risk factors. Although stroke heritability has been reported to differ by sex, the genetic variants that may underlie these sex disparities are unknown. We performed a genome-wide association (GWA) analysis stratified on sex in 12,577 ischemic stroke cases (6811 men, 5766 women) and 25,643 stroke-free controls (12,179 men, 13,464 women ) from the Stroke Genetics Network (SiGN). Testing for heterogeneity of effects between the sexes was conducted using a 1-df Chi-square test. We identified a region on chromosome 19q13.2 harboring common SNPs (minor allele frequency (MAF)=0.11 to 0.25) associated with all ischemic stroke in men (lead SNP P=7.4x10
-8
; odds ratio (OR)=0.81) but not in women (P=0.38; OR=1.03). A common variant (MAF=0.19) on chromosome 10q22.2 showed evidence of heterogeneity by sex (P_het=7.7x10
-8
) with sex-specific associations in opposite direction (OR_men=0.86, P=4.4x10
-6
; OR_women=1.10, P=2.8x10
-3
). Subtype-specific analyses also identified several sex-specific associations. In this sex-stratified GWA analysis, we identified several loci with sex-specific effects on ischemic stroke and its subtypes. The majority of these loci were in intergenic regions of the genome, suggesting that sex-specific effects on stroke may occur via mechanisms acting on gene regulation. Replications and extension of these findings is planned.
Abstract WMP63: Prevalence of Occult Paroxysmal Atrial Fibrillation in Non-Cryptogenic Ischemic Stroke Patients
Authors: Katz Jeffrey M , Gribko Michele , Jadonath Ram , Arora Rohan , Salamon Elliott , Garlitzki Ann , Patel Anand , Wright Paul , Libman Richard B
Published: June 2021

Background:
Paroxysmal atrial fibrillation (PAF) is often asymptomatic and is more prevalent than persistent AF in patients with ischemic stroke (IS). Long-term monitoring with insertable cardiac monitors (ICM) yields an up to 30% PAF detection rate in cryptogenic IS patients. Yet, the prevalence of PAF in patients with a presumed stroke etiology other than AF remains unknown.

Methods:
Prospective cohort study of non-cryptogenic IS patients implanted within 10 days of stroke onset with the Reveal LINQ ICM (n=47 enrolled, 45/47 (95.7%) implanted). Patients were monitored until PAF detection (adjudicated by study cardiologist) or minimum of 12 months. Inclusion required a defined stroke etiology other than AF based on standard stroke evaluation (including ≥24 hour cardiac telemetry), age≥40, and either a virtual CHADS2 score ≥3, or ≥2 PAF related comorbidities (COPD, hyperthyroidism, obesity, prior MI, PR interval >175ms, or renal impairment). Patients with high-risk cardiac sources, recent MI or cardiac bypass surgery, pacemaker or defibrillator, permanent anticoagulation indication or contraindication, and pregnancy were excluded.

Results:
Mean age 64.8 years (range 40-88 years), 15/47 (31.9%) female, mean virtual CHADS2 score 3.5 (range 3 to 5), mean CHA2DS2-VASc score 4.5 (range 3 to 8), and 8/47 (17.0%) had ≥2 PAF comorbidities. Lacunar stroke etiology predominated (n=33), followed by extracranial atherosclerotic stenosis (n=4), cardioembolic (n=3), arch atheroembolic (n=3), intracranial atherosclerosis (n=4), and extracranial dissection (n=2). Five had multiple potential sources. Interim analysis (mean monitoring 264 days, range 0 to 642 days) demonstrates 3/45 (6.7%) implanted patients have PAF (range of longest AF episode: 0.3 to 18.7 hours). Mean time to PAF diagnosis 162.7 days (range 9-356 days). All were started on anticoagulation. There was 1 device related complication (skin erosion) and 1 patient had recurrent stroke.

Conclusions:
Occult PAF in non-cryptogenic IS patients is infrequent and may reflect the background prevalence of PAF in this demographic. Despite this, long-term cardiac monitoring may promote optimization of stroke prevention therapy for a small but unanticipated proportion of these patients.
Abstract WMP65: Association Between Sinus Bradycardia and Ischemic Stroke
Authors: Pishanidar Sammy D , Mir Saad A , Kamel Hooman , Merkler Alexander E , Gialdini Gino , Navi Babak B
Published: June 2021

Background and Purpose:
We assessed whether sinus bradycardia is an early sign of atrial dysfunction that might predispose to atrial thrombogenesis and therefore be associated with stroke risk.

Methods:
We retrospectively used inpatient and outpatient claims data from a 5% sample of Medicare beneficiaries ≥ 66 years old from 2008-2014. Our predictor variable was sinus bradycardia, defined as
ICD-9-CM
code 427.8x. Our primary outcome was ischemic stroke, ascertained using a previously validated diagnosis code algorithm. Patients with ischemic stroke or atrial fibrillation/flutter prior to or at the time of a bradycardia diagnosis were excluded. We used Cox regression analysis adjusted for demographics and vascular risk factors to evaluate the association between sinus bradycardia and the risk of stroke. Patients were censored at the time of a diagnosis of atrial fibrillation/flutter. In a confirmatory analysis, we assessed whether sinus bradycardia was more common in patients with cryptogenic stroke compared to stroke due to large-artery atherosclerosis or small-vessel disease using data from the Cornell AcutE Stroke Academic Registry (CAESAR), which comprises all adults with acute stroke at New York-Presbyterian Hospital/Weill Cornell Medical Center from 2011 to 2014.

Results:
Among 1,417,069 Medicare beneficiaries (mean age 73.4 +/- 7.6 years) who were followed for a mean of 4.36 (+/- 1.8) years, 63,385 patients received a diagnosis of sinus bradycardia. Bradycardia was significantly associated with stroke in unadjusted analysis (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.6-1.8) but not after adjustment for demographics and vascular risk factors (HR, 0.9; 95% CI, 0.8-0.9). Among 608 patients with cryptogenic or non-cardioembolic stroke in CAESAR, 93 (15.3%) had sinus bradycardia. We did not find an association between sinus bradycardia and cryptogenic stroke after adjustment for demographics, stroke severity, insular infarction, and vascular comorbidities (OR 0.9, 95% CI 0.4-1.9).

Conclusion:
We found no association between sinus bradycardia and future stroke risk in stroke-free patients nor an over-representation of sinus bradycardia among cryptogenic strokes versus non-cardioembolic strokes.
Abstract WMP73: Peripheral T Cells From MCAO Mice Contribute to Microglial Polarization
Authors: Ye Dan , Xu Yun
Published: June 2021

Both resident microglia and infiltrated peripheral T cells have been proved to play important roles in the pathology of stroke. It is well accepted that activated microglia exert dual roles, including pro-inflammatory (M1) and anti-inflammatory (M2) functions. However, the mechanism regulating microglial polarization remains elusive. T cells are recruited into the ischemic area within 24 h after stroke, which also exhibit pro-inflammatory (Th1, Th17) and anti-inflammatory (Th2, Treg) functions. The interaction between microglia and T cells after stroke is barely understood, which may be served as modifiers of pathobiology in stroke. Here we described the role of T cells in the microglial polarization in mouse experimental stroke. We isolated T cells from spleens of MCAO mice at 24 h and 72 h, respectively, and then added to cultured microglia for 24 h. Our results indicated that splenic T cells obtained at 24 h after MCAO selectively promoted microglia polarize to a pro-inflammatory (M1) state, while T cells obtained at 72 h, favored microglia polarize to an anti-inflammatory (M2) state. The results of flow cytometry showed that Th1 and Th17 cells increased at 24 h after MCAO while Th2 and Treg cells increased at 72 h after MCAO. This study implicates that distinct subtypes of T cells contribute differentially to microglial polarization after stroke onset. Therefore, treatments aiming at modulating the ratios of T cells to anti-inflammatory cells have the potential to induce microglial polarize to M2 phenotype and improve the outcome of ischemic stroke.
Abstract WMP75: Age- and Sex-Specific Development of Cerebral Microbleeds in a Mouse Model
Authors: Sumbria Rachita , Grigoryan Mher , Vasilevko Vitaly , Ngo Quoc Tuan Pham , Nguyen Kristie , Kim Ronald , Paganini-Hill Annlia , Cribbs David , Fisher Mark
Published: June 2021

Cerebral microbleeds (CMB), a common MRI finding that may predict intracerebral hemorrhage, are based on a pathological substrate of cerebral microhemorrhages (CMH). Recent clinical and laboratory studies have demonstrated the importance of systemic inflammation in the development of CMB. The effects of age and sex on CMB development have not been well-defined. In the current study, we hypothesized that there are age and sex differences in the pathogenesis of inflammation-induced CMB in mice. We studied young (3 months, n=39) and old (17 months, n=25) male and female C57BL/6 mice injected with LPS (1mg/kg, i.p.) or saline at 0, 6, and 24h. 7 days after first LPS injection, cardiac perfusion was performed, mice were sacrificed, and brains were harvested. CMH grossly visible on the brain surface were examined and 40 μm brain sections were prepared and stained with hematoxylin and eosin (H&E) to estimate the acute/fresh parenchymal CMH number, size and total area in young versus old mice. No surface CMH and negligible H&E-positive parenchymal CMH were observed in young and old saline controls. LPS treatment significantly (p<0.001) increased the development of surface CMH in aged male mice (mean±SEM=17±6 surface microhemorrhages/brain) compared to young male mice (2.8±1.5 surface microhemorrhages/brain). Negligible H&E-positive CMH were observed in LPS-treated young mice. Aging increased the number (1.3±0.7 vs 0.09±0.05 CMH/section; p<0.05), size (4510±1431 vs 471±188 μm
2
; p<0.001) and area (0.03±0.02 vs 0.0005±0.0003 % total area; p<0.01) of H&E-positive parenchymal CMH in old LPS-treated male mice compared to young LPS-treated male mice. Consistent with previous studies from our lab, H&E-positive CMH were predominantly located in the cerebellum compared to the cortex and sub-cortex. No significant differences were observed in LPS-induced surface or parenchymal CMH development between young and aged female mice. In summary, effects of aging on LPS-induced microbleed development are demonstrable in males. Aging makes the brain more susceptible to inflammation-induced cerebral microbleeds in male mice.
Abstract WMP78: Prostaglandin D
2
DP1 Receptor Attenuates the Effects of Post-stroke Sleep Disturbance on Stroke Outcomes
Authors: Ahmad Abdullah S , Kamat Pradip K , Hernandez Damian , Dore Sylvain
Published: June 2021

Background:
Post-stroke sleep disturbance is reported to be an indicator of poor stroke outcomes. The strategic location of the PGD
2
DP1 receptor in specific brain regions regulating cerebrospinal fluid and sleep led us to hypothesize that the DP1 receptor may attenuate the deleterious effects associated with post-stroke sleep disturbance.

Methods:
First, to test the effect of sleep deprivation on locomotor activity, wildtype mice were individually housed and their activity was monitored 20h/d for 3d. Day zero was used to obtain baseline, while for the next two days, mice were subjected to sleep disturbance for 10h during the sleep phase followed by 10h of no sleep. Second, to test whether a selective DP1 receptor agonist decreases locomotor activity, mice were given an intraperitoneal injection of the agonist and locomotor activity was monitored. Third, to test the effect of post-stroke sleep disturbance on stroke outcomes, wildtype and DP1
-/-
mice were subjected to 45min of MCAO and 7d of reperfusion. After MCAO, mice were subjected to post-stroke sleep disturbance for 12h/d for 3d during the mouse sleep phase.

Results:
Sleep disturbance resulted in higher activity (awake like) during the sleep phase and lower activity during the awake phase. The distance travelled during the awake phase after sleep deprivation was significantly lower (P<0.001). These data suggest that sleep deprivation attenuated locomotor activity. The total ambulatory distance covered by DP1 agonist-treated group 4h post-treatment was 2161.2±846.4cm compared with the vehicle group activity of 7093.5±1953cm (P<0.01), suggesting that the selective pharmacological agent induced sleep. Analysis of the Cresyl violet-stained sections revealed a significantly larger (P<0.05) infarction volume and neurologic deficit in post-stroke, sleep-disturbed DP1
-/-
mice compared to similarly treated WT mice.

Conclusion:
These data show that the PGD
2
DP1 receptor plays a vital role in attenuating the deleterious effects of sleep disturbance on stroke outcomes. Additional studies are underway to further investigate mechanisms and optimal therapeutic conditions. [This work was supported by UF-CTSI (to A.S.A.) and R01NS046400, R01AT007429 (to S.D.)]
Abstract WMP8: Thin-sliced Reformatted CT Imaging: Validation of a Safer and Faster Technique to Assess Clot Size and Vessel Diameter in Large Vessel Occlusions
Authors: Kulhari Ashish , Mehta Siddhart , Bhaskara Venkat , Arango Audrey Z , Suhan Laura , Panezai Spozhmy , Kirmani Jawad F.
Published: June 2021

Background:
Thin-sliced reformatted non-contrast CT head are not widely used to detect the thrombus. The purpose of this study was to investigate whether thin-sliced reformatted non-contrast CT scans could be reliably used to detect and measure size of the thrombus size in patients with acute ischemic stroke due to LVO and therefore serve as a potential substitute of CT Angiogram (CTA). Success of this paradigm could reduce stroke decision algorithm to nonenhanced CT scan before a code neurointervention is activated; hence saving time and contrast.

Methods:
Comprehensive prospective analysis of patients who underwent acute endovascular intervention for LVOs at a community based, university affiliated comprehensive stroke center during one year period (Jan 2015-Dec 2015) was done. The raw data of non-enhanced CT scans and CTAs were collected. All raw data were reconstructed with thin slices of 0.625 mm using standard GE software. Two observers independently evaluated the 5-mm maximum intensity projections of the thin slices and CTA in coronal and axial projections for best assessment of vessel diameter and thrombus length. Inter-observer agreement was measured using Cohen κ.

Results:
There were 749 patients who presented with acute ischemic stroke during the specified time period. Of those 67 were large vessel circulation strokes; of which, 22 had both CT and CTA done. Mean clot length measured was 14.75 (SD +/-4.95) on thin slices CT and 15.02 (SD +/-5.47) on CTA. Vessel diameter measured was 2.77 (SD +/-0.47) on thin sliced reformatted CT and 2.41 (SD +/-0.49) on CTA. There were no instances where clot size or vessel diameter could not be measured on thin slice reformatted CT. Inter-observer agreement was higher for both CTA (κ, 0.83) versus thin-slice nonenhanced CT reconstructions (κ, 0.80).

Conclusions:
Thin-sliced reconstructions of standard cranial nonenhanced CT raw data can be reliably used to detect and measure the thrombus size in LVOs. It also reliably measures the vessel diameter, making intervention planning possible. Larger multicenter trials are needed to validate our data.
Abstract WMP88: Temporal Trends in the Rates of Endovascular Treatment for Patients Presenting with Acute Ischemic Stroke
Authors: Ali Syed F , Leslie-Mazwi Thabele M , Onteddu Sanjeeva R , Akdol Mehmet S , Amole Adewumi D , Schwamm Lee H
Published: June 2021

Introduction:
Endovascular therapy is the current standard of care for eligible patients with acute ischemic stroke (AIS) due to large artery anterior circulation occlusion. All patients with moderate to severe symptoms and a treatable occlusion should be considered for EVT. We sought to evaluate temporal trends in the rates of EVT use at the two large academic stroke centers in the US.

Methods:
Using GWTG stroke registry data from MGH and UAMS, we analyzed 7,505 consecutive stroke admissions from 01/09 - 06/16. We evaluated the temporal trends in patient characteristics, clinical care and timeliness of care among the population of all patients and those treated within 6 or 12 hr from last known well (LKW).

Results:
Of the total 7,505 AIS patients, 3,722 (49%) presented within 12 hr of LKW and 2,716 (36%) within 6 hr. There were a total of 404 EVT performed at the two centers (334 ≤ 12 hr and 304 ≤ 6 hr). We observed a significant increase in the rates of EVTs performed over the past eight years with a near doubling of EVT and the sharpest rise in 2013-14 after the MR CLEAN results were presented (Figure 1). While patient characteristics remained largely unchanged, care got faster with significant decreases in time from door to CT, to tPA and to EVT. In addition, rates of drip and ship tPA cases increased from 26% to 39%.

Conclusion:
At two major academic stroke centers, rates of EVT increased sharply after high quality evidence supporting its use were presented. An ongoing national emphasis on improving door to tPA times appears to be working, and to be associated with improvements in EVT delivery as well. Further work is needed to improve prehospital triage and inhospital delays to increase access to rapid EVT.