bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP120: Brain Plasticity Modulator P75 Neurotrophin Receptor And Its Mechanistically Linked Signaling Molecules Predict Clinical Outcome Across Different Acute Brain Injuries
Authors: Sajanti Antti , Li Yan , Cao Ying , Girard Romuald , Umemori Juzoh , Frantzen Janek , Koskimaki Fredrika , Lyne Séan , Falter Johannes , Rantamaki Tomi , Heino Iiro , Takala Riikka , Posti Jussi , Roine Susanna , Saarenpää Ilkka , Kolehmainen Sulo , Rahi Melissa , Rinne Jaakko , Castren Eero , Koskimaki Janne
Published: February 2022

Introduction:
Brain plasticity and synaptic regeneration are important processes in recovering after acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI). p75 neurotrophic receptor (p75NTR) is a consequential receptor modulating brain plasticity and apoptosis.
Hypotheses:
Measurable changes in serum levels of p75NTR mechanistically linked proteins are associated to recovery of acute brain injuries. Differentially expressed (DE) miRNAs after acute brain injuries target to p75NTR pathway and have association to outcome.

Methods:
Concentrations of p75NTR, NGF, sortilin, IL1β, TNFα and cyclophilin were measured from serum using ELISA. Prospective cohort (n=75) consisted of IS (n=30), aSAH (n=31) and TBI (n=14) patients. Serum samples were collected 24-48h after insults. Late samples (120-192h) were also taken from 12 aSAH patients. Outcome was measured 90 days after injury (mRS favorable 0-4, unfavorable 5-6). We generated characteristic curves and area under the curve (AUC) for weighted linear combination of the biomarkers with a linear discriminant analysis. MiRNAs were extracted from the cohort (early and late samples, n=53).

Results:
In the whole cohort (n=75) combination of cyclophilin, IL1β, sortilin, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.69, p=0.01). In IS group combination of cyclophilin, sortilin, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.84, p=0.02). In aSAH group combination of IL1β, p75NTR and NGF predicted unfavorable mRS (AUC 0.77, p=0.07). In 12 aSAH patient sub-group (late samples included) combination of cyclophilin, IL1β, sortilin, p75NTR and TNFα predicted unfavorable mRS (AUC 1.0, p=0.07). In TBI group combination of cyclophilin, IL1β, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.79, p=0.08). In the aSAH group 2 DE miRNAs were detected, 4 in the IS group and 7 in the TBI group (p<0.05, FDR corrected). MiRNAs targeted
p75NTR
,
NGF
,
IL1
β
, cyclophilin (
PPIA
), and sortilin (
SORT1
).

Conclusions:
p75NTR and mechanistically linked proteins predict outcome across different types of brain injuries suggesting a common mechanism irrespective of the type of brain insult. Identified DE miRNAs targeted studied molecules.
Abstract TMP19: Atn-161 Prevents α5 Integrin-mediated Tight Junction Disruption Caused By Sars-cov-2 And Its Delta Variant In Brain Endothelial Cells
Authors: Narayanappa Amruta , Eskew William , Ouvrier Blake , Biose Ifechukwude J , Hefter Sophie , Gressett Timothy E , Khan Pervez , Bix Gregory J
Published: February 2022

Patients with significant cerebrovascular comorbidities (e.g. brain ischemia, vascular dementia) are more affected and are more likely to have worsened post-acute neurologic sequelae after SARS-CoV-2 infection. This may be due to viral invasion and propagation in brain endothelial cells (BECs) and disruption of the blood-brain barrier (BBB). Viral spike protein used to bind and infect host cells encodes an arginine-glycine-aspartic acid (RGD) motif that it may use to bind integrins cell receptors that play an important role in cerebrovascular integrity. Therefore, integrins may represent an acute and post-acute SARS-CoV-2 therapeutic target. However, the interplay between vascular dysregulation, integrin function, and COVID-19 is unclear. As we have previously demonstrated that activation of the integrin α5 plays a key role in BBB breakdown, stroke injury, OGD/R, SARS-CoV-2 infection, and its inhibition with the clinically validated peptide ATN-161 is therapeutic in these conditions, we hypothesize that SARS-CoV-2 alters BEC α5 integrin (and associated tight junction protein) expression as a means of infecting and altering cerebrovascular integrity, and this can be prevented by ATN-161.

Methods:
Mouse BECs (bEnd3) were inoculated with heat-inactivated SARS-CoV-2 (Isolate USA-WA1/2020) or delta variant of SARS-CoV-2 spike protein for 24 h then later exposed to hypoxia for 6h to model the effects of
in vivo
pulmonary infection. Cells were pretreated with ATN-161 (1, 5, and 10μM) 1h before SARS-CoV-2 challenge and during hypoxia. α5 and claudin-5 proteins were analyzed by immunoblotting.

Results:
Both SARS-CoV-2 inoculations induced integrin α5 and decreased claudin-5 expression (delta > SARS-CoV-2) in a dose-dependent fashion, although higher doses of SARS-CoV-2 (2.5 and 5 μg) had no effect on these proteins. SARS-CoV-2 spike protein challenge at 0.5 μg followed by hypoxia resulted in increased α5 and decreased claudin-5 expression in either hypoxia or SARS-CoV-2+hypoxia combination. ATN-161 (10μM) pretreatment inhibited SARS-CoV-2+hypoxia-induced α5 upregulation and restored claudin-5 loss. In addition to its demonstrated anti-viral effects, ATN-161 may be an important therapy for SARS-CoV-2-mediated cerebrovascular injury.
Abstract TMP21: Impact Of COVID-19 State-level Hospital Capacity On Overall Stroke Mortality In 2020 In The United States
Authors: de Havenon Adam H , Yaghi Shadi , Stulberg Eric , Delic Alen , Anadani Mohammad , Sheth Kevin N , Majersik Jennifer J
Published: February 2022

Background:
Although hospital admissions for stroke declined in 2020 during the COVID-19 pandemic, patients with comorbid COVID-19 and stroke had increased mortality. We explored stroke mortality in 2020 and its association with COVID-19 prevalence and state-level hospital capacities.

Methods:
We analyzed CDC National Vital Statistics System and COVID Data Tracker data from 2017-2020. The primary outcome was age-adjusted stroke (ischemic and hemorrhagic) mortality rate per 100,000. The secondary outcome was % change in state-level stroke mortality rates in 2020 (vs. 2017-19); we report its correlation with state-level 1) prevalence of confirmed COVID-19 infections by 12/31/2021, 2) total COVID mortality by 12/31/20, and the 2020 average state-level % of 3) hospital and 4) ICU beds occupied by COVID-19 patients.

Results:
Figure 1A shows the typical seasonal decline in stroke mortality in quarters 2/3 was attenuated in 2020. The % change in state-level stroke mortality in 2020 (Figure 1B) was not correlated with prevalence of COVID-19 infection (rho=0.05, p=0.74), mortality (rho=0.10, p=0.49), or the % of ICU beds occupied by COVID-19 patients (rho=0.24, p=0.09). There was a correlation with % of hospital beds occupied by COVID-19 patients (rho=0.35, p=0.01) (Figure 2).

Conclusion:
Overall stroke mortality increased in 2020, particularly in Q2/3, the early-to-mid phase of the COVID-19 pandemic. At the state level, the average % of all hospital beds occupied by COVID-19 patients in 2020 was the only COVID-19 metric associated with change in stroke mortality. Future work should determine if this association was due to decreased hospital capacity to deliver standard stroke care.
Abstract TMP25: The Visual Field Rapid Analysis Device (vrad) Is Safe, Effective And Easy To Use
Authors: Solenski Nina , Allende J. A , Aldridge Chad , Dirghangi Arjun , Perch Miah , Weko Andrew , Koyada Prajeeth , Shabo Leah , Gottschalk Carter , Gunter Sonya
Published: February 2022

Background:
Acute telestroke consults rely on a rapid, accurate NIH Stroke Scale. An important sign in cortical-based ischemic strokes is a Visual Field Deficit (VFD) contributing up to 3 points on the NIHSS affecting treatment decisions. Remote confrontational VFD testing
is challenging
and requires a trained assistant. We created a simple, rapid, telecart peripheral device
to remotely administer a standardized VF test
. The “

V

isual fields

R

apid

A

ssessment

D

evice” (
VRAD
) is a wearable eye-glasses device. The device flashes LED lights in the 4 quadrants of each eye via remote control by a teleprovider allowing real-time control and interpretation.

Methods:
The VRAD Phase I study examined FDA-related human design factors of
comfort, speed, and ease of use
with direct use of VRAD. The results guided optimization of the prototype in preparation for the Phase II validation clinical trial. Subjects were randomly-selected, consented adult UVA Stroke Unit inpatients, with confirmed ischemic strokes. Following each VF test, blinded teleproviders, the patient ,and the telepresenter (nurse) completed a brief binary response questionnaire with open-ended comments. Biostatistical analysis: N= 20 subjects; 95% confidence interval with precision of +/- 10%.

Results:
The vast majority of patients, presenters, and providers (95-100%) reported VRAD testing was easy to understand and rapid.
Patients:
The device was comfortable (90%); 10% felt the stimulus light was too bright and 5% too dim. All identified when the light was on and had enough time to respond.
Presenters:
All reported rapid testing; 75% felt the device was easy to don on patients. The device was “sturdy and durable” 90%, “easy to use” 75%, “easy to clean” 70%, and “easy to connect” 60%.
Providers:
Reported the device sufficiently screened standard VFs (90%). All agreed they could remotely administer the test in various settings.

Conclusion:
The VRAD Phase I trial found the device to be safe, effective, easy to use, and comfortable by patients, providers, and presenters. Based on the results, an upgraded prototype was manufactured for our upcoming Phase II Non-Inferiority Validation Trial (Fall 2021). This data is a proof-of-concept of the value of teleneurology peripheral tools in remote settings.
Abstract TMP28: Decision For Tpa Administration, Not Drive Time, Contributes Most To Variance In Thrombolysis Times Onboard Mobile Stroke Unit
Authors: Akkipeddi Sajal Medha K , Ellens Nathaniel R , Schartz Derrek , Rahmani Redi , Kelly Adam G , Benesch Curtis G , Burgett Jason L , Lesperance Joshua , Proper Diana , Mattingly Thomas K , Pilcher Webster H , Bhalla Tarun , Bender Matthew T
Published: February 2022

Introduction:
Hospitals have improved stroke thrombolysis times through rigorous assessment of care delays. While mobile stroke units (MSU) expedite intravenous thrombolysis for acute ischemic stroke, the same rigor has not been applied to this novel setting.

Methods:
We reviewed all cases of intravenous tissue plasminogen activator (tPA) administration onboard our mobile stroke unit in Rochester, NY since its inception in 2019. The dispatch timeline was divided into six intervals: (1) drive time, (2) onboarding time, (3) HCT collection, (4) HCT reading, (5) decision time, and (6) tPA administration. Cases in which tPA was delayed due to medical contraindications or inability to obtain consent were not included in the analysis.

Results:
The mean ± SD total time between MSU dispatch and tPA was 42 ± 8.4 min (range: 26-60 min; N = 53). The longest interval was (1) drive time (between dispatch and arrival, 12.0 ± 4.7 min). However, the inter-case variation was greatest in (5) decision time (between HCT reading and treatment decision, 6.3 ± 6.2 min). After ranking cases by total time, the interval that had the widest variance between the first and fourth quartiles was decision time (2.45x). The other intervals varied by a factor of 1.50x for (6) tPA administration and less than 1.00x for the other four intervals. Decision time was the interval most closely correlated with total time (Spearman’s ρ = 0.46; p = 0.00051), which was reduced in our second year of operation (38.8 from 44.6 minutes; Mann-Whitney, Z = 2.38, p = 0.02). Decision time was negatively correlated with time since inception of the MSU (Spearman’s ρ = -0.29, p = 0.037), suggesting that improvements in decision time drove improvements in overall thrombolysis time.

Conclusion:
The largest driver of variation in total time from emergency alert to tPA administration is provider decision time in our MSU program. This observation should be investigated in other settings but may ultimately inform MSU training and staffing.
Abstract TMP29: Emergency Department Variability In Use Of Advanced Neuroimaging By Insurance Status
Authors: Mamer Lauren E , Kocher Keith E , Cranford James A , Scott Phillip A
Published: February 2022

Introduction:
Prior data indicate inpatient disparities exist among patients with stroke associated with insurance status for degree of neurologic impairment, hospital length of stay and mortality. Patients presenting to the Emergency Department (ED) with acute neurologic symptoms often require evaluation for acute ischemic stroke and, in 2015, guidelines recommended CTA when LVO is considered. CTP was added in 2018 for select patients. In the ED, the Emergency Medical Treatment and Labor Act (EMTALA) requires anyone presenting to be stabilized and treated, regardless of insurance status and should limit variability in advanced neuroimaging use based on insurance status. We examined ED stroke assessment disparities by evaluating national variability in the use of advanced stroke imaging by primary payer (Private Insurance, Medicare, Medicaid, Self-Pay).

Methods:
Retrospective cohort study using adult encounters admitted to the same hospital in the 2018 National Emergency Department Sample (NEDS), an AHRQ dataset containing a weighted 20% sample of US ED encounters. CTA (head/neck) and CTP imaging use was determined from Common Procedural Terminology (CPT) codes and adjusted by age. Rate per 100,000 ED visits were compared across primary payers using ANOVA with Tukey adjustment.

Results:
Age-adjusted CTP rates varied by payer but did not research statistical significance. Rates of CTA acquisition were significantly different across payer groups (p<0.001). See Table.

Conclusion:
Variability in age-adjusted rates of advanced neuroimaging use in the ED was identified. The variability for CTP, a unique ED imaging modality for stroke, was not significant, however interpretation is limited by confidence interval size. Variability in CTA was significant between groups and will undergo further analysis to evaluate for confounding by other patient or hospital factors.
Abstract TMP34: The Role Of Nondiabetic Hyperglycemia In Patients With Acute Cerebral Infarction
Authors: Jhou Hong-Jie , Chen Po-Huang , Yang Li-Yu , Chang Shuhao
Published: February 2022

Background/Objective:
We aims to investigate the incidence of hyperglycemia (HG) and the association between HG and mortality of nondiabetic patients with acute cerebral infraction (ACI) in intensive care units.

Hypothesis:
We hypothesize that hyperglycemia might increase the mortality rate among nondiabetic patients with ACI.

Methods:
We enrolled the nondiabetic patients with ACI in the Medical Information Mart for Intensive Care IV database from 2008 to 2019. HG was defined as > 140 mg/dL. Propensity score matching (PSM) was performed to balance the group of HG and non-HG patients with confounders including age, sex, Charlson Comorbidity Index (CCI), Acute Physiology Score (APS) III. We conducted a Cox proportional hazards model to determine the nonlinear association between HG and in-hospital mortality among nondiabetic patients with ACI.

Results:
Of the 734 patients, 218 patients (29.7%) had HG. Patients with HG were older (71.4±13.3 v.s. 66.6±15.6; P < 0.001) and had higher CCI (6.9±2.5 v.s. 5.9±2.4; P < 0.001), and APS III (39.2±20.6 v.s. 31.0±14.0; P < 0.001) than those without HG. After 1:1 PSM, there remained 207 pairs. The cohorts were well-balanced based on four covariates between the HG and non-HG groups. HG associated with in-hospital mortality (22.5% v.s. 8.9%; P < 0.001), even after PSM (20.3% v.s. 10.6%; P < 0.001). There was a positive non-linear trend between HG and in-hospital mortality and patients might had twofold hazards ratio when serum glucose more than 160 gm/dL.

Conclusions:
Hyperglycemia is related to poor clinical characteristics, as well as it is an independent short-term risk factor of in-hospital mortality among nondiabetic patients with ACI.
Abstract TMP38: Using Natural Language Processing To Investigate Diagnostic Error In Acute Stroke
Authors: Mayampurath Anoop , Romo Elida , Holl Jane , Prabhakaran Shyam
Published: February 2022

Introduction:
Diagnostic error occurs in approximately 10% of acute stroke (AS) presentations. The diagnostic process includes history, physical examination, and test performance and interpretation. However, critical information for diagnosis is contained in unstructured clinical notes.

Hypothesis:
We hypothesized that natural language processing (NLP) can identify features in unstructured clinical notes associated with potential diagnostic error during ED “catch and release” (CR) encounters prior to AS admissions.

Methods:
Using a retrospective case-control design and ICD-10 codes, we identified index emergency department (ED) admissions with a diagnosis of first-time stroke (cases) and age and sex-matched gastroenteritis (controls) who had an ED CR encounter in prior 30 days. Notes were processed using cTAKES to identify concept unique identifiers (CUI) among clinical narratives from the CR encounters. Regression analysis was utilized to determine CUI terms from the CR encounter that were associated with stroke cases compared to controls. These CUI terms were grouped by clinical experts into 3 aspects of the diagnostic process: history (e.g., risk factors, medications, symptoms), neurologic examination (e.g., mental status exam, cranial nerves, pronator drift), and tests (e.g., labs, CT, MRI).

Results:
In an analytic cohort of 319 stroke cases and 319 gastroenteritis controls, a non-cerebrovascular neurologic diagnosis at the CR encounter was noted in 20.2% of cases versus 6.0% in controls (P<0.01). We identified 120 terms at the CR encounter associated with stroke (OR >2.0 and p<0.05). Grouped by themes, tests accounted for 50 (41.7%), examination for 37 (30.1%), and history for 33 (27.5%) terms. Terms related to neurologic examination had the highest median OR (median OR 6.7, IQR 2.7-11.5) followed by history (median OR 3.8, IQR 3.2-4.9) and tests (median OR 3.5, IQR 2.8-4.6).

Conclusions:
Neurologic presentations to the ED preceded 20% of stroke cases suggesting some of these may represent missed diagnoses for minor stroke and TIA. NLP may be a useful surveillance approach to identify neurologic symptoms, deficits, and tests present at CR encounters and trigger interventions to reduce diagnostic error prior to stroke.
Abstract TMP4: Pulsatile Blood Flow Characteristics Predict Intracranial Aneurysm Growth
Authors: Chien Aichi , Yang Hong-Ho , SAYRE JAMES , Nael Kambiz , Colby Geoffrey , Wang Anthony , Villablanca Juan , Salamon Noriko
Published: February 2022

Introduction:
Oscillations in blood flow over the cardiac cycle are relevant to endothelial function and vascular health. But, as yet the relationship between pulsatile flow characteristics and intracranial aneurysm (IA) growth is unclear. We analyzed time-based hemodynamic indices within unruptured IAs with known growth or stable trajectories. We hypothesize that combining pulsatile parameters can yield a predictive model for IA growth.

Methods:
Unruptured IA cases with at least 3 imaging studies were identified from UCLA Medical Center electronic medical records. Cases with an increase in diameter of at least 10% were assigned to the growing group and all other cases were assigned to the stable group. 16 stable and 20 growing cases from 2018-2020 qualified for the study. For each IA image study, computational fluid dynamic (CFD) flow simulation was performed and pulsatility index (PI) and wall shear stress PI (WSSPI) were recorded at 5 locations: inflow artery, IA neck, body, dome, and outflow artery. Values were compared with MANOVA. A stepwise logistic regression with growth as the outcome variable and WSSPI and PI at all locations as covariates was then performed.

Results:
PI was significantly higher in growing IA at the body (0.81±0.44 vs. 1.76±1.18, p=0.006) and dome (1.22±0.76 vs. 1.91±1.20 p=0.04). WSSPI was significantly higher in growing IA at the inflow artery (0.68±0.05 vs. 0.87±0.36, p=0.049), body (1.07±0.22 vs. 1.55±0.73, p=0.02), and dome (1.15±0.30 vs. 1.64±0.70, p=0.01). Logistic regression yielded a predictive model with 88.2% accuracy and AUC of 0.944: logit(growth) = 2.035 х PI_
body
+ 14.004 х WSSPI_
inflow
+ 4.263 х WSSPI_
body
-17.342.

Conclusions:
Based on a finding of elevated pulsatility in growing IA, we propose a model to predict subsequent IA growth. This should be further tested in larger CFD studies. Upon confirmation, the model may be helpful in guiding clinical decisions.
Abstract TMP40: Standardized Interdisciplinary Team Handoff Communication Improves Thrombectomy Door-to-groin Time In Acute Ischemic Stroke Evaluated By Telestroke
Authors: Yadav Randheer , Zurmehly Joyce , Mion Lorraine , Barr Taura , Tate Judith , Nimjee Shahid M , Forrest Cassandra , Lee Vivien
Published: February 2022

Introduction:
Mechanical thrombectomy (MT) has a time-dependent effect on clinical outcomes in acute ischemic stroke (AIS) patients with large vessel occlusions (LVO). Most AIS patients who need MT evaluation present to a spoke Emergency Room (ER) and require transfer to a comprehensive stroke center (CSC) hub. Delayed or incomplete interdisciplinary team communication are potential barriers to timely MT. The purpose of this quality improvement (QI) project was to evaluate team members’ fidelity and acceptability to a new handoff protocol and effect on treatment times.

Methods:
Our academic CSC has a hub-spoke telestroke model that includes 27 spoke ERs in Ohio. An LVO handoff protocol was designed to ensure a structured process that required the telestroke physician to a) communicate to the receiving in-house stroke team and endovascular team; b) hand-off standardized data from transferring hospital including last known normal, National Institutes of Health Stroke Scale, and neuroimaging findings, and c) communicate a pre-arrival plan. Fidelity was measured by a standardized checklist and Acceptability was measured by Acceptability of Intervention Measure (AIM) questionnaire. Door-to-Groin (DTG) times 4 months pre- and 5 months post- implementation were reviewed.

Results:
Among 83 AIS patients (28 pre- and 55 post-implementation) transferred from a telestroke ER for suspected LVO, the mean age was 70.4 (± 13.7) and 32 (39%) were female. Overall fidelity was 81% with the lowest scores noted on weekends. Acceptability among team members was 96%. Overall DTG mean time was 64.0 minutes (+/- SD 51) for the entire period. The mean DTG improved from pre-protocol to post-protocol period by 29.2 minutes (83.4 vs. 54.2 min, p = 0.0136).

Conclusions:
Standardized pre-arrival interdisciplinary team communication for AIS LVO patients transferred to CSC in a telestroke hub-stroke model was feasible and associated with improvement in DTG times. Further studied needed for sustainability and ongoing improvement.
Abstract TMP46: Physician Quality Of Communication And Shared Decision Making After Stroke In A Bi-ethnic Community: The Oasis Project
Authors: Zahuranec Darin B , Zhang Guanghao , Shi Xu , Lank Rebecca J , Ortiz Carmen , CASE Erin , Morgenstern Lewis B
Published: February 2022

Objective:
To explore ethnic differences in stroke patient surrogate decision makers’ (e.g. family) impressions of physician quality of communication (QOC) and shared decision making (SDM) in Mexican Americans (MAs) and non-Hispanic Whites (NHWs).

Methods:
Surrogate decision makers who discussed life-sustaining treatments for severe stroke patients (ischemic or intracerebral hemorrhage) from the Brain Attack Surveillance in Corpus Christi (BASIC) project completed validated measures of physician QOC (QOC-overall, QOC-general, and QOC-end-of-life) and SDM (collaboRATE). Regression models with Generalized Estimating Equations were used to investigate ethnic differences in outcome adjusted for pre-specified demographics, severity, mortality, and identified confounders.

Results:
From 4/2016 to 9/2020, 320 surrogates for 257 stroke cases were enrolled. Patient characteristics: median age 75 (IQR 64-87), female 52%, Race-ethnicity (MA 61%, NHW 33%, Other 5%), ICH 25%, median NIHSS 12 (IQR 5-20), deceased 45%. Surrogates had a median age of 57 (IQR 46-66) and were mostly female (77%). Compared to NHW surrogates, MA surrogates were more often women, had lower education, and less use of advance directives, but had more trust in physicians and were more likely to pray daily. Regression results for QOC are shown in the table. MA surrogates reported higher unadjusted scores for QOC-overall and QOC-end-of-life. These associations were stronger after adjustment for demographics, severity, and patient survival, though were no longer significant in the final fully adjusted models. A generally similar pattern was seen for SDM.

Conclusions:
MA surrogates tended to report better physician communication and more SDM than NHWs, though no difference was seen after adjustment for factors such as trust, daily prayer, or advance care planning. Further study of contributions to positive outcomes among diverse populations of stroke surrogates are warranted.
Abstract TMP5: Bone Marrow-derived And Clonally Expanded Alk1
-
Endothelial Cells Contribute To Brain Arteriovenous Malformation In Mice
Authors: Shaligram Sonali , Zhang Rui , Zhu Wan , Ma Li , Luo Man , Li Qiang , Weiss Miriam , Arnold Thomas , Grez NG Santander , Liang Rich , Predo Leandro , Tang Chaoliang , Pan Peipei , Su Hua
Published: February 2022

Background and Purpose:
Homozygous mutation in arteriovenous malformation (AVM) causative genes in a fraction of endothelial cells (ECs) causes brain AVMs (bAVMs). Heterozygous mutation of endoglin, an AVM causative gene, in bone marrow (BM) caused capillary dysplasia in mouse brain. We tested if (1) homozygous mutation of activin receptor-like kinase 1 (
Alk1,
another AVM causative gene) in BM derived ECs (BMDECs) can cause bAVM in brain angiogenic region, (2) Alk1
-
ECs clonally expand in bAVM, and (3) the burden of Alk1
-
ECs correlates with bAVM severity.

Methods:
The BMs of
Pdgfb
iCreER;

Alk1
2

f/2f
;Ai14 mice with EC-specific tamoxifen-inducible Cre and
Alk1
floxed alleles were transplanted into wild-type mice to analyze the role of BMDECs in bAVM development.
Pdgfb
iCreER;

Alk1
2

f/2f
;confetti
+/-
mice with Cre-regulated confetti transgene were used to study EC clonal expansion. Brain AVMs were induced by intra-brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor followed by intra-peritoneal injection of tamoxifen.

Results:
Wild-type mice transplanted with
Pdgfb
iCreER;

Alk1
2

f/2f
;Ai14 BM developed bAVMs after bAVM induction. Recombined BMDECs were detected in bAVMs. The presence of clusters of ECs expressing same confetti color in bAVMs suggests that Alk1
-
ECs had been clonally expanded. Increasing tamoxifen dose increased the number of Alk1
-
ECs and abnormal vessels in bAVMs of
Pdgfb
iCreER;

Alk1
2

f/2f
mice.

Conclusion:
Homozygous mutation of
Alk1
in BMDECs is sufficient to cause bAVM development in brain angiogenic region; clonal expansion of Alk1
-
ECs provides a likely mechanism for how a fraction of mutant ECs causes bAVM; and the burden of Alk1
-
ECs correlates with AVM severity.
Abstract TMP56: Quality Of Ischemic Stroke Care Before And After The Covid-19 Pandemic
Authors: Conforto Adriana B
Published: February 2022

Objective:
To compare metrics of acute care for ischemic stroke (IS) before and after the first cases of COVID-19 were diagnosed and major changes were made to the workflow.

Methods:
Data were prospectively collected as part of the institutional Stroke Database project. Patients with IS > 18 years admitted from January 2019 until March 2020 were considered to be part of the group treated in the “pre-COVID” era and those admitted from April 2020 until December 2020, in the “post-COVID” era. The primary outcome was the door-to-needle time in subjects treated with intravenous thrombolysis. Secondary outcomes were: rate of thrombolysis, rates of complications (pneumonia, urinary tract infection, deep venous thrombosis or pressure injury) and death during hospital admission. Patients’ characteristics, primary and secondary outcomes were compared with unpaired t-tests, Mann-Whitney or chi-square tests, according to the nature and distribution of the data.

Results:
Data from 932 patients with IS in the pre-COVID and 520, in the post-COVID group were prospectively collected. There were no significant differences in age (pre-COVID, 64.2±14.7 years; post-COVID, 63.3±15 years; p=0.296), gender (pre-COVID, 55.5% male; post-COVID, 55% male; p=0.862) or NIHSS scores (pre-COVID, median 5, range 0-38; post-COVID, median 6, range 0-36; p=0.346). Thrombolysis rates were 19.6% pre-COVID and15.7% post-COVID. All eligible subjects received thrombolysis. The increase in door-to-needle time in subjects treated with thrombolysis (pre-COVID, median 36 minutes; post-COVID, median 39 minutes) was statistically significant (p=0.048). Rates of complications in all ISs during admission increased significantly from 8.3% (pre-COVID) to 20.2% (post-COVID) (p<0.001). The increase in death rate from 8.4% (pre-COVID) to 12.1% (post-COVID) did not reach statistical significance (p=0.059).

Conclusions:
The increases in door-to-needle times, complication and death rates, despite the lack of significant differences in age or stroke severity, likely reflect the impact of the COVID-pandemic on public health care. Despite major changes in workflow, door-to-needle times were below 40 minutes in more than 50% of patients treated with thrombolysis.
Abstract TMP6: Computational Hemodynamic Analysis Of Intra-Aneurysmal Effects Due To Flow Diverter Stent Deployment Conformation
Authors: Dinh Huy , Chien Aichi
Published: February 2022

Introduction:
Inflow blockage of aneurysms treated with flow diverter stents is dependent on the deployed braid angle (ϕ)—the angle between the yarns which comprise the stent braids and the longitudinal axis of the braid. We utilized computational fluid dynamic (CFD) analysis to examine the effects of braid angle on intra-aneurysmal hemodynamic parameters associated with long-term treatment success.

Methods:
Two flow diverter stents measuring 3.5 mm in diameter, each containing 88 strands with ϕ = 10° and ϕ = 35° were constructed and deployed into a patient model of an internal carotid artery saccular aneurysm containing pulsatile blood flow. Intra-aneurysmal flow velocity, pulsatility index (PI), turbulence, vorticity, and wall shear stress (WSS) parameters were obtained and compared for the two braid angles.

Results:
Reducing ϕ from 35° to 10° resulted in -2.59%, -1.92%, and -1.41% changes in systolic bulk velocity, and -1.79%, +0.57%, and -1.65% changes in PI at the aneurysm neck, body, and dome respectively. Vorticity changes were insignificant. High turbulence extending through the aneurysm neck peaked approximately 0.04 s later in systole, and was located closer to the parent vessel outlet when ϕ = 10°. Elevated intra-aneurysmal WSS was concentrated at the neck and body on the side of the parent vessel outlet for both ϕ = 10° and ϕ = 35°. Regions of WSS in excess of 10 Pa stretched higher into the aneurysm body when ϕ = 35°.

Conclusion:
Stenting at a lower ϕ resulted in higher blockage of flow and better reduction of WSS for initiating and facilitating long term intra-aneurysmal thrombosis. CFD analysis incorporating precise reconstruction of the stent deployment conformation into patient models can provide detailed visualization of flow parameters for assessing potential treatment efficacy throughout the diagnostic and treatment phases of patient care.
Abstract TMP65: Remote Ischemic Conditioning With Exercise (RICE) Induced Better Neurorehabilitation After Ischemic Stroke
Authors: Wang Qingzhu , Geng Xiaokun , Wills Melissa , Li Fengwu , Ding Yuchuan
Published: February 2022

Objective:
Although early performance is well recognized as an important concept in rehabilitation, the optimal models remain to be determined. Physical exercise has long been considered a promising strategy at the forefront of stroke rehabilitation. However, very early exercise has been demonstrated to exacerbate brain injury. Remote ischemic conditioning (RIC) is safe and feasible within 24 hours after stroke, while it has not been applied to post-stroke rehabilitation. The present study was to establish a novel rehabilitation strategy, the RIC followed by exercise (RICE).

Methods:
A total of 32 adult male Sprague-Dawley rats were used in 4 groups: 1) stroke, 2) stroke with exercise (exercise at day 5 and up to day 28), 3) stroke with RIC (RIC at 6 hours after reperfusion and up to day 28), and 4) stroke with RICE (initiated with RIC at 6 hours after reperfusion followed by exercise at day 5 and up to day 28). Long-term functional outcomes were determined by grid walk tests, rota-rod tests, beam balance tests, forelimb placing tests, and the Morris water maze. Synaptogenesis [synaptophysin (SYN), and post-synaptic density protein-95 (PSD-95)], angiogenesis [vascular endothelial growth factor (VEGF), Angiopoietin-1 (Ang-1), and Angiopoietin-2 (Ang-2)], and regulatory molecules [brain-derived neutrophic factor (BDNF), hypoxia inducible factor 1α (HIF-1α), phospholipase D2 (PLD2) and mechanistic target of rapamycin (mTOR) pathway] were all measured at the mRNA and protein levels with real-time PCR and Western blot.

Results:
Although all rehab procedures induced significant improvement in functional outcomes, including in sensory, motor, and cognitive functions, RICE but not RIC and exercise alone was better able to improve functions after stroke. The functional improvement was significantly associated with gene and protein expressions of molecules for neuroplasticity, synaptogenesis and angiogenesis, with additional increases being induced by RICE. A HIF-1α/PLD2/mTOR signaling pathway was underpinning this processes.

Conclusions:
RICE induced a better rehabilitation after ischemic stroke by promoting neuroplasticity. This study established the RICE strategy and provided novel clues to pave future endeavors in stroke rehabilitation.
Abstract TMP7: Racial Differences In Palliative Care Utilization And Impact On Inpatient Mortality Length Stay And Costs Among Patients With Subarachnoid Hemorrhage
Authors: Chaudhry Mohammad Rauf , Fadah Kahtan , Kherani Danish , Chaudhry Saqib A , Singh Baljinder , Kausar Naila , Moreno Jorge , Ghatali Mohammad , Vellipuram Anantha Ramana , Gupta Vikas , Maud Alberto , Piriyawat Paisith , Sheriff Faheem , Rodriguez Gustavo , Cruz-Flores Salvador
Published: February 2022

Background and Purpose:
Palliative is increasingly used in critically ill patients which has lead to shorter length of stays, higher inpatient mortality and lower utilization of aggressive treatment. We performed analysis to evaluate trends in utilization of palliative care among patients with subarachnoid hemorrhage and its effect on in-hospital outcomes over a 10-year period.

Methods:
We obtained data for patients admitted to hospitals in the United States from 2009 to 2018 with a primary diagnosis of subarachnoid hemorrhage (SAH) using a large national database. We determined the overall and sub racial rate of utilization of palliative care in patients with SAH and associated in-hospital outcomes consisting of mean hospital charges, mean length of stay and in-hospital mortality.

Results:
Out of 199928 patients admitted with primary diagnosis of SAH, palliative care was used in 20490 (10.2%). There was a 2.2-fold increase in utilization of PC (6.5%% in 2009 vs 14.4% in 2018; p<0.001). Similarly, there were 1.7, 2.9, 3.2- and 4.6-folds increase in utilization of PC among different races: whites, blacks, hispanics and others respectively, p<0.001. Overall rates of PC utilization among among different races: whites, blacks, hispanics and others were: 11.8%, 6.9%, 7.5% and 10.0%, p<0.001 respectively. The length of hospitalization remained significantly lower in patients undergoing PC compared with those who did not. (6.5±9.9 versus 11.6±12.6, p<0.001). The cost of hospitalization remained significantly lower in patients undergoing PC compared with those who did not. ($120526 ± 193412 versus $ 185116 ± 219434, p<0.001). Patients with PC utilization had significantly higher (72.7% versus 13.6%, p<0.001) in-hospital mortality compared ones with out.

Conclusions:
Between 2009 and 2018, there has been a significant increase in utilization of PC among patients with SAH along with shorter length of stay and lower hospital charges. SAH patients with PC had significantly higher in-hospital mortality.
Abstract TMP74: Direct Oral Anticoagulants Vs. Vitamin K Antagonists In Patients With Cerebral Venous Thrombosis: A Systematic Review And Meta-analysis
Authors: Yaghi Shadi , Saldanha Ian , Misquith Chelsea , Zaidat Bashar , Shah Asghar , Joudi Kareem , Persaud Bianca , Chang Allison , de Havenon Adam H , Barkradze Ekaterina , Mistry Eva , Reagan John , Stretz Christoph , Kala Narendra , El JAMAL SLEIMAN , Cutting Shawna M , Nguyen Thanh , Siegler James E , Al Kasab Sami , Aparicio Hugo J , Tsivgoulis Georgios K , Furie Karen L , Mac Grory Brian
Published: February 2022

Introduction:
Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT.

Methods:
We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology.

Results:
Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I
2
=0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I
2
=0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I
2
=0%; 9 studies).

Conclusions:
Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.
Abstract TMP77: Borderzone Infarction Predicts Recurrence In Patients With Intracranial Atherosclerosis: A Meta-analysis
Authors: Kvernland Alexandra , Mac Grory Brian , DAS SAURAV , Khatri Pooja , Furie Karen L , Mistry Eva , de Havenon Adam H , Romano Jose G , Liebeskind David S , Prabhakaran Shyam , Yaghi Shadi
Published: February 2022

Background:
Patients with symptomatic intracranial stenosis (ICAS) face elevated risks of recurrent cerebrovascular events (RCE) despite optimal medical therapy. Borderzone infarcts (BZI) indirectly correlate with impaired distal perfusion, a known mechanism of recurrence. Studies assessing associations between borderzone infarcts and recurrence rates are observational and have relatively small sample size. We therefore performed a meta-analysis of published studies investigating this association.

Methods:
We performed a Medline and Web of Science search using the key words (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Borderzone OR Infarct Pattern) to identify studies reporting associations between index infarct pattern and RCE, defined as recurrent ischemic stroke or neurological deterioration, or new infarct on follow up neuroimaging in patients with symptomatic ICAS. We included relevant papers and scientific abstracts with more than 20 patients included. For all outcome events we calculated the corresponding risk ratios (RRs) and 95% confidence intervals (95% CI).

Results:
We identified 178 studies using Web of Science and 384 studies using Medline with only 6 studies (591 patients) meeting our inclusion criteria (2 prospective and 4 retrospective). The weighted proportion of patients with BZI was 32.5% (28.7%-36.4%). During a follow-up period of 7-950 days, 33.1% (26.3%-40.5%) of patients with BZI had RCE and 63.6% (30.8%-89.1%) had new infarction on a 6-8 week follow up brain MRI. In meta-analysis, BZI was associated with increased rates of RCE (RR 2.40 95% CI 1.71-3.37) and new infarct(s) on follow up brain MRI (RR 2.55 95% CI 1.31-4.94). The findings were unchanged when the analysis was limited to 90-day RCE risks only (RR 2.22 95% 1.49-3.29).

Conclusions:
BZI are associated with over 2-fold increased risk of RCE and recurrent infarct in patients with symptomatic ICAS. Prospective studies are needed to validate these findings.
Abstract TMP91: Healthcare Utilization For Headache And Anxiety After Surgical Revascularization In Children With Moyamoya Vasculopathy
Authors: Andere Ariana J , Dao Jasmin , Gelfand Amy , Fullerton Heather J , Fox Christine K
Published: February 2022

Introduction:
Headache and anxiety are poorly described in children with moyamoya vasculopathy following revascularization.

Hypothesis:
Headache and anxiety in pediatric moyamoya patients are common co-morbidities and result in frequent healthcare utilization.

Methods:
In this single-center retrospective cohort study, children (<18 years of age) with moyamoya syndrome or disease who underwent EC-IC bypass between 2007-2020 were identified from a UCSF registry. Data regarding headache or anxiety were abstracted from medical records of inpatient, outpatient and emergency (ED) encounters using standardized forms. ED encounters were attributed to headache or anxiety when they occurred in the absence of stroke or TIA and documented as the likely cause of symptoms for that visit. Summary statistics were used to describe outcomes.

Results:
We identified 32 children (63% female, 53% white, 22% Hispanic) who underwent initial revascularization surgery at a median age of 8.3 years (range 0.8-17.4). Two or more EC-IC surgeries were completed in 84% of patients. During follow-up after surgery (median 6.7 years, interquartile range 3.2 - 8.2 years), 81% of patients reported headache and 53% reported anxiety (Table). Headaches led to 27 ED encounters among 10 patients (31%). Headache rescue medications were prescribed to 21 patients (66%), and headache prophylaxis was prescribed in 37.5%. Six patients (19%) were referred to a headache specialist. Symptoms attributed to anxiety led to six ED encounters among three patients, and 19% (6/32) reported panic attacks. A referral to mental health services was provided to 44% (14/32) of patients.

Conclusions:
Headaches and anxiety are common symptoms among children with moyamoya after revascularization and may lead to significant healthcare consumption. Symptoms and prevention measures should be explored in future studies to improve quality of life and decrease healthcare utilization.
Abstract TMP93: Limited Value Of Routine Thrombophilia Screening In Childhood Arterial Ischemic Stroke
Authors: Lee-Eng Jacqueline , Persa Laurel , Joshi Sarita , Barry Dwight , Amlie-lefond Catherine
Published: February 2022

Introduction:
Congenital and acquired thrombophilias are associated with childhood arterial ischemic stroke (AIS), especially if multiple thrombophilias or other risk factors are present. The 2019 AHA guidelines recommend thrombophilia evaluation for all children with AIS, although the optimal extent of testing is unknown. The objective of this study was to determine the utility of routine thrombophilia screening in management of children following AIS.

Methods:
Thrombophilia screening sent as part of clinical care was collected from patients with childhood (1 month-18 years) AIS during an 11 year period at a single institution.

Results:
Factor V Leiden was sent on 56%, Prothrombin gene on 47%, homocysteine on 50%, lipoprotein a on 52%, antithrombin on 44%, protein C on 57%, protein S on 54%, and anticardiolipin antibodies on 51% of children. Five percent of patients were FVL heterogenous, and 1% were PT gene heterogenous. Three percent had mildly elevated homocysteine. Twenty percent had elevated lipoprotein a. Two patients had transiently low antithrombin, 4 had transiently low protein C activity, and one had transiently low protein S activity. One patient with sickle cell disease had persistently low protein S activity. One low protein S was not repeated. Ten patients had elevated ACLAs: 6 were transient, two had mildly elevated IgM that was not repeated, and 2 had known APLA syndrome. Two patients (cardioembolic stroke; moyamoya) had two thrombophilias.

Conclusion:
Rates of thrombophilias were consistent with expected incidence for the general population and did not predict stroke recurrence. Patients with elevated lipoprotein a and homocysteine were referred for treatment, otherwise results from the remainder of thrombophilia evaluation did not alter patient care in a population already known to be at risk for thrombosis.
Abstract TMP95: Cerebral Sinovenous Thrombosis In Preterm Infants
Authors: Moharir Mahendranath D , Christensen Rhandi , Krishnan Pradeep , Deveber Gabrielle A , Dlamini Nomazulu , MacGregor Daune , Pulcine Liza
Published: February 2022

Introduction:
Neonatal cerebral sinovenous thrombosis (CSVT) can lead to brain injury and long-term neurodevelopmental impairments. Previous studies of neonatal CSVT have primarily focused on term infants, and studies of preterm infants are lacking. In this study, we examined the clinical and radiological features, treatment and outcome of CSVT in preterm infants.

Methods:
This was a retrospective, consecutive cohort study of preterm infants (gestational age <37 weeks) with radiologically confirmed CSVT. All MRI/MRV and CT/CTV scans were re-reviewed to study thrombus characteristics and the pattern of brain injury. Clinical and radiological data were analysed using descriptive statistics, ANOVA and chi-square tests. Outcome was assessed by the validated Pediatric Stroke Outcome Measure (PSOM).

Results:
A total of 26 preterm infants with CSVT were included. Of these, 65% were late preterm, 27% very preterm and 8% extreme preterm. Most (73%) were symptomatic at presentation with seizures or abnormal exam. Transverse (85%) and superior sagittal (42%) sinus were most common sites of thrombosis. Parenchymal brain injury was predominantly periventricular (35%) and deep white matter (31%) in location. Intraventricular hemorrhage occurred in 46%. Most infants (69%) were treated with anticoagulation. None of the treated infants had hemorrhagic complications. Outcome at follow-up ranged from no impairment (39%), mild impairment (19%) and severe impairment (19%).

Conclusions:
Preterm infants with CSVT are often symptomatic and have white matter brain lesions at presentation. Anticoagulation treatment of preterm CSVT in this small cohort appeared to be safe. Further larger studies and treatment.