bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP131: Association Of Hemoglobin Over The First Week With Clinical Outcomes And Neuroimaging Characteristics In Patients With Spontaneous Intracerebral Hemorrhage
Authors: Diaz Cruz Camilo , Porosnicu Rodriguez Kori , Gatti John , Zhao David , Avadhani Radhika , Awad Issam A , Hanley Daniel F , Ziai Wendy C
Published: February 2022

Introduction:
Studies have shown independent associations of lower admission hemoglobin (HB) levels with larger spontaneous intracerebral hemorrhage (ICH) volumes and poor outcomes, possibly mediated by hematoma expansion (HE).

Objective:
We retrospectively investigated the association of HB levels over the first week post ICH with functional outcomes (FO) and neuroimaging findings in patients with spontaneous ICH (>30 mL). We explored whether comorbidities modify the effects of HB.

Methods:
We analyzed HB levels from subjects enrolled in the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial (MISTIE III). The exposure was admission HB and the HB nadir in the first week. The primary outcome was good FO at 180 days, defined as modified Rankin Scale of 0-3. Secondary outcomes were good FO at 365 days, 30-day mortality, admission ICH volume, and HE (>6 mL). Linear and logistic regression models were used to test the association of HB with clinical outcomes and neuroimaging findings. All models were adjusted for age, sex, race, treatment (medical Vs. MISTIE), Glasgow Coma Scale, ICH volume, presence of intraventricular hemorrhage, and ICH location (deep Vs. lobar). We investigated effect modification of comorbidities on association of HB with FO.

Results:
A total of 493 of 499 enrolled patients (61% males, mean age 61(SD=12) years, median ICH volume 41.8 (IQR=30.8-51.5) mL) were included. Patients with good FO at 180 days had a higher admission HB (13.2 Vs. 12.6 g/dl, p=0.001) and a higher nadir HB (11.7 Vs. 10.9 g/dl, p<0.001). In adjusted analyses, each additional g/dl in nadir HB (but not admission HB) was associated with higher odds of good FO at 180 (OR 1.29, p=0.005) and 365 (OR 1.18, P=0.048) days. Baseline (B= -1.16, p=0.02) and nadir HB (B= -1.71, p=0.001) were inversely associated with hematoma volumes, but not with HE. There was evidence of heterogeneity in the effects of diabetes on the association of nadir HB with day 180 FO (OR 0.67; p
interaction
= 0.045).

Conclusions:
In patients with ICH > 30 mL, higher nadir HB in the first week was associated with better long-term FO and smaller ICH volumes, but not with HE. Early hemoglobin changes may serve as a prognostic biomarker and a potentially modifiable factor to improve FO.
Abstract TP161: Embolization Of Intracranial Aneurysms Using WAVE Extra Soft Coils, A Part Of The Penumbra SMART COIL System: An Interim Analysis Of The SURF Study
Authors: Schirmer Clemens , Kicielinski Kimberly , Yoo Albert J , Kaminsky Ian , Alshekhlee Amer , Nicholson Andrew , Zaidat Osama , Woo Henry H , Bohnstedt Bradley , Psychogios Marios , Spiotta Alejandro M
Published: February 2022

Introduction:
Initial clinical evidence has shown that coiling with the SMART COIL System (Penumbra, Inc.) is a safe and durable treatment option for intracranial aneurysms. The SURF study is a post-market, prospective, multicenter, single-arm, observational study to assess the utility of the WAVE Extra Soft Coil (WAVE) as fill and finishing coil to support adequate occlusion of intracranial aneurysms.

Methods:
Enrollment began November 5, 2019; this analysis includes data as of July 20, 2021. Patients undergoing embolization of intracranial aneurysms with WAVE as the final finishing coil and Penumbra SMART COIL System accounting for at least 75% of the total number of coils implanted were enrolled consecutively at 34 centers globally. Post-procedure Raymond Roy Occlusion Classification (RROC) was assessed by a core lab. The estimated enrollment will be 800 patients.

Results:
This analysis includes 346 patients, mean age 60.1 (SD 13.03), 73.1% female. Of the target aneurysms, 39.8% (135/339) were ruptured, and 80.5% (269/334) were saccular, and 11.5% (39/338) were previously treated. Post-procedure, 89.2% (206/231, 95% CI 85.2%, 93.2%) of aneurysms were RROC I or II. Device-related SAEs occurred in 1.5% (5/346, 95% CI 0.2%, 2.7%) of patients up to 7 days or discharge. The rate of major ipsilateral stroke was 0.6% (2/346), and the intra-procedural rupture rate was 0.6% (2/346).

Conclusions:
We report interim outcomes from the SURF study. This post-market registry evaluates the safety and performance of the Penumbra SMART COIL System, including WAVE as fill and finishing coil, in the treatment of intracranial aneurysms.
Abstract TP173: Neuroimaging Biomarkers Of Moyamoya Arteriopathy By Age In A Surgical Cohort
Authors: Gatti John R , Gardner Sarah E , Guryildirim Melike , Tekes Aylin , Sun Lisa R
Published: February 2022

Introduction:
Moyamoya arteriopathy (MMA) is a significant risk factor for pediatric stroke. Radiographic signs thought to indicate disease severity guide clinical decision making. We hypothesized that there exists a correlation between age and imaging biomarkers.

Methods:
We retrospectively identified pediatric MMA patients seen at our center that underwent surgical revascularization. Preoperative MRI/MRA imaging was reviewed by two pediatric neuroradiologists who were blinded to clinical characteristics. The following neuroimaging markers were evaluated by consensus: Suzuki staging, cerebrovascular stenosis score (CVSS), the presence of posterior circulation steno-occlusive lesions, ivy sign, and brush sign. Associations of these features with age were analyzed using simple logistic regression and Spearman correlation analyses.

Results:
We identified 27 patients undergoing 30 individual revascularization procedures between January 2003 and June 2021. There were 29 images of diagnostic quality for analysis. Median age at imaging was 8.5 years. Younger age was associated with posterior arterial lesions (p=0.028). There was no statistically significant association between age and ivy sign (p=0.205), brush sign (p=0.156), Suzuki stage (p=0.671), or CVSS (0.234).

Conclusions:
In this cohort of surgical MMA patients, younger children were more likely to have posterior circulation involvement on MRA. While not statistically significant, all analyzed radiographic signs were more prevalent among younger patients. Further studies correlating neuroimaging biomarkers with clinical outcomes in larger cohorts including non-surgical MMA patients are needed.
Abstract TP197: Early Direct Oral Anticoagulants Therapy After Ischemic Stroke In Patients With And Without Atrial Fibrillation:A Pooled Analysis Of Five Studies
Authors: Alrohimi Anas , Gioia Laura C. , Kate Mahesh P , Ng Kelvin , Dowlatshahi Dar , Field Thalia S , Coutts Shelagh B , Siddiqui Muzzafar , Hill Michael D , Miller Jodi , HART Robert G , Jickling Glen , Shuaib Ashfaq , Buck Brian H , Sharma Mukul A , Butcher Ken
Published: February 2022

Introduction:
Early anticoagulation after acute ischemic stroke is usually avoided due to the risk of hemorrhagic transformation (HT). We aimed to assess the rate of radiological HT associated with direct oral anticoagulant (DOAC) initiation within 48 hours vs. > 48 hours in the post-stroke period.

Methods:
A pooled analysis of five studies of DOAC initiation within 14 days of ischemic stroke onset was conducted. The primary endpoint was incident radiographic HT on follow-up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage (PH1 or asymptomatic PH2), recurrent systemic events, systemic hemorrhagic complications, mortality within the study period, final modified Rankin Scale score. The results were reported as odds ratio (OR) with 95% confidence interval (CI).

Results:
A total of 468 patients were enrolled. Median infarct volume was 1.35 (0-7.5) ml, and National Institutes of Health Stroke Scale was 1 (0-3). Incident radiographic HT was seen on follow-up scan in 29 patients. DOAC initiation within 48 hours from index event onset was not associated with incident HT (adjusted OR 0.67, [0.31 - 1.50]
P
=0.34). No patients developed symptomatic HT. Conversely, 25 patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating DOAC within 48 hours of onset was not associated with a reduction in the risk of recurrent ischemic events (OR 0.47, [0.19 - 1.20]
P
=0.12). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR=6.8, [2.95 - 15.63], p<0.0001).

Conclusions:
Early DOAC initiation after stroke was not associated with increased incident HT risk. Recurrent ischemic events were common and associated with poor outcomes. These data may be useful for estimating outcome rates and sample size calculations in future trials of early versus late DOAC initiation after AF-related stroke.
Abstract TP210: Stroke Subtype-specific Association Of Systemic Blood Pressure And Cerebral Collateral Flow In Acute Ischemic Stroke With Large Vessel Occlusion
Authors: Sim Jae Eun , Chung Jong-won , Seo Woo-keun , Bang Oh Young , Kim Gyeong-Moon
Published: February 2022

Introduction:
Collateral flow in acute ischemic stroke is known as a predictor of acute treatment outcome and long-term prognosis. However, studies on the factors which determine the degree of initial collateral flow are not well known. We investigated the factors related to collateral degree in acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and further analyzed the results according to stroke subtype.

Methods:
This was a retrospective cohort using prospective stroke registry data from October 2014 to May 2021. Patients admitted within 48 hours of symptom onset with middle cerebral artery M1 occlusion on multiphasic CT angiography were included. Collateral score was graded on a six-point scale according to pial arterial filling.

Results:
A total of 74 patients was enrolled (mean age=72.2±11.7 years; men=37.8%). Of whom 57 (77%) were in the cardioembolism (CE) group and 17 (23%) were in the large artery atherosclerosis (LAA) group. In ordinary logistic regression analysis, initial systolic blood pressure (SBP) was associated with the score of collateral flow (odds ratio [OR]=0.982; 95% confidence interval [CI]=0.968-0.997; p=0.017). Considering multivariate models adjusted for age, sex, and atrial fibrillation, initial SBP was an independent predictor of the score of collateral flow (OR=0.977; 95% CI=0.961-0.992; p=0.011). In subgroup analysis, the lower score of collateral flow was independently associated with increased initial SBP in CE group (OR=0.965; 95% CI=0.945-0.983; p<0.001) but not in LAA group (OR=1.009; 95% CI=0.978-1.043; p=0.578). Echocardiographic parameters and anatomical variations of circle of Willis did not show significant association.

Conclusions:
Poor cerebral collaterals in AIS-LVO was associated with increased initial SBP. Subgroup analysis revealed the association was significant in CE group, but not in LAA group. Mechanism underlying differential effects of SBP on stroke subtypes may need further study.
Abstract TP223: Association Between Stroke Severity And Cardiac Troponins In Acute Stroke
Authors: Kuczynski Andrea , Rzyczniak Grace , Cheong Gee Hung Leo , Famiyeh Petra , Vyas Manav V
Published: February 2022

Introduction:
Cardiac troponins are often elevated in patients with acute stroke and have been associated poor outcomes. Whether the elevation in cardiac troponins, a marker of acute myocardial injury, is due to neurogenic mechanisms or the underlying cardiac risk factors is unknown. We evaluated the association between stroke severity and serum cardiac troponin levels in people with acute stroke.

Methods:
We conducted a retrospective study of adults (≥ 40 years) with a discharge diagnosis of imaging confirmed stroke admitted to a quaternary stroke centre in Toronto, Canada between January 1, 2018 and December 31, 2018. We collected demographic and clinical information, including stroke severity using the National Institutes of Health Stroke Scale [NIHSS], modelled as a continuous variable. We recorded serum cardiac troponin levels on admission. We modelled serum troponin level both as a continuous and a categorical variable (normal vs. high, ≥ 15 ng/L). We evaluated the association between admission NIHSS and serum troponin level using multivariable negative binomial models and logistic regression models, adjusting for demographics (age and sex) and comorbidities [history of congestive heart failure or stroke, stroke type (ischemic vs. hemorrhagic), ST elevation on ECG, and creatinine levels].

Results:
We included 218 patients with acute stroke (median age 76 years, 48.6% women), of whom 190 (87.2%) had an ischemic stroke. Median NIHSS was 6 (Q1-Q3, 2-14), and median cardiac troponin level was 17 ng/L (Q1-Q3, 9-30), with 108 (53.2%) patients having higher than normal levels. A one-point increase in NIHSS (stroke severity) was associated with a higher serum troponin level in age- and sex- (RR 1.03; 1.00-1.05) and multivariable- (RR 1.03; 1.01-1.05) adjusted models. However, stroke severity was not associated with the odds of having high troponin levels in adjusted models (OR 1.03; 0.98-1.08).

Conclusions:
The modest, yet independent, association between greater stroke severity and higher cardiac troponins in patients with acute stroke could suggest a neurogenic basis for mild cardiac injury in patients with acute stroke. Future work on the association between elevated troponin and poor stroke outcomes should account for stroke severity on admission.
Abstract TP224: Comparing Utility Of Computed Tomography Angiography Of Neck Vs Transesophageal Echocardiography For Detection Of Aortic Plaque.
Authors: Asif Ahmer , Lawal Temitope , Xu Chao , Hacker Ethan A , Sivaram Chittur A , Cornwell Ben O , Zanabria Rosemarie , Tran Jimmy , Paul Aruna , Shoaib Maria , Shoukat Maryum , Sidorov Evgeny V
Published: February 2022

Background:
Aortic arch atherosclerotic plaques of >4mm thickness, evaluated by a transesophageal echocardiogram (TEE) correlate with embolic ischemic stroke. Computed tomography angiography (CTA) of the neck, routinely done during stroke evaluation, is an alternative for the evaluation of aortic arch plaque. We hypothesized that CTA evaluation of the aortic arch plaque is comparable to TEE.

Methods:
We prospectively measured thickness, extent through different parts of the aortic arch (ascending, arch, and descending aorta), location of the maximal plaque thickness, calcification, mobility, and presence of thrombus in the aortic arch plaque on CTA neck and TEE exams in non-consecutive stroke patients from the hospital database. All measurements were done independently by 2 radiologists for the CTA of neck and 2 cardiologists for TEE. Paired t-test was used for mean difference and Wilcoxon signed-rank test for median difference between TEE and CTA.

Results:
Of 63 patients who had both CTA and TEE, 31 (mean age ± SD; 54 ± 14.46 years) were included in this analysis; as in 32 patients, aortic arch was not included on the CTA neck. Although maximal plaque thickness was comparable for both methods (CTA 3.0 ± 1.10 vs TEE 3.18 ± 2.54, p=0.68), CTA more commonly showed the extent of the plaque throughout all areas (ascending, arch, and descending) of the aorta (CTA: 25/31 vs TEE: 15/31, p<0.01), thickest plaque on the stroke embologenic (ascending and arch) location (CTA: 15/31 vs TEE: 6/31, p<0.01), and identified calcified plaque components (CTA: 26/31 vs TEE: 15/31, p<0.01). In addition, CTA exhibited branching patterns of the aorta, while TEE was beneficial to detect mobile plaque debris (8/31) and thrombi (TEE: 1/31 vs CTA: 0/31, p=1.0).

Conclusion:
Both CTA and TEE are useful for aortic arch evaluation in stroke patients, contributing different information. Future investigations in a larger prospective cohort are warranted.
Abstract TP247: Tanshinone IIA Loaded Nanoparticles Enhance Induced Pluripotent Stem Cell-derived Neural Stem Cell Recovery Responses In A Porcine Ischemic Stroke Model
Authors: Kaiser Erin E , Waters Elizabeth , Yang Xueyuan , Fagan Madison , Scheulin Kelly , Sneed Sydney , Jeon Julie , Shin Soo , Kinder Holly , Kumar Anil , platt simon , Duberstein Kylee , Park Hea Jin , Xie Jin , West Franklin D
Published: February 2022

Induced pluripotent stem cell-derived neural stem cells (iNSCs) have shown significant therapeutic promise in rodent stroke models with neuroprotective, regenerative, and cell replacement effects. However, the therapeutic potency of iNSCs has been largely limited by low iNSC survivability in the cytotoxic stroke environment. In this study, we examined the potential of Tanshinone IIA, an anti-inflammatory and antioxidative agent, loaded nanoparticles (Tan IIA-NPs) to improve iNSC survival, engraftment, and recovery responses in a porcine ischemic stroke model. Eighteen Yucatan pigs underwent middle cerebral artery occlusion (MCAO) surgery and were assigned to PBS+PBS, PBS+iNSC, or Tan IIA-NP+iNSC treatment groups. PBS or Tan IIA-NPs were administered intracisternally 1 hour post-stroke and PBS or iNSCs were transcranially transplanted into the penumbra stroke region 5 days post-stroke. Porcine adapted Modified Rankin Scale (mRS) neurologic scores were recorded pre- and post-stroke. Magnetic resonance imaging (MRI) and immunohistochemistry were performed 12 weeks post-iNSC transplantation. mRS evaluations demonstrated that Tan IIA-NP+iNSC treatment led to faster and improved (p<0.05) recovery at 1, 4, and 12 weeks post-transplantation relative to PBS+PBS and PBS+iNSC treatments. MRI results at 12 weeks showed a stepwise decrease in lesion volume and midline shift in PBS+PBS, PBS+iNSC, and Tan IIA-NP+iNSC groups with the Tan IIA-NP+iNSC group showing a significant decrease (p<0.05) relative to the PBS+PBS group. Immunohistochemistry analysis showed that Tan IIA-NPs resulted in increased (p<0.05) iNSC survival and differentiation into NeuN+ neurons and decreased (p<0.05) differentiation into GFAP+ astrocytes. These promising results indicate that the combined Tan IIA-NP+iNSC therapy leads to improved iNSC survival and engraftment, tissue and functional recovery, and may be a viable treatment for human stroke patients.
Abstract TP262: Effect Of Prehospital Blood Pressure Fluctuations On Early Neurological Changes In Acute Ischemic Stroke Patients With Large Vessel Occlusion
Authors: Hariharan Praveen , Tariq Muhammad , Singh Noopur , Yamal Jose-Miguel , Parker Stephanie , Bowry Ritvij , Grotta James C , Czap Alexandra L
Published: February 2022

Introduction:
Blood pressure fluctuations in the acute phase of large vessel occlusion (LVO) ischemic stroke are associated with infarct progression and poor outcomes. We evaluated the association of prehospital blood pressure variations on a Mobile Stroke Unit (MSU) with early neurological change.

Methods:
Prospectively-derived data were analyzed from tPA-eligible LVO patients treated and transported on the MSU, identified by hyperdense artery on CT or arterial occlusion on CTA. Patients were categorized by change in mean arterial pressure (ΔMAP) of > 10 mm Hg vs Δ MAP < 10 mmHg from arrival of MSU on-scene to arrival to the emergency department (ED). A sub-analysis of patients with ΔMAP > 10 mm Hg compared those whose MAP decreased by > 10 mm Hg vs those whose MAP increased by > 10 mm Hg. The primary outcome was 24-hour change in NIHSS. Groups were compared using Chi-square/Fisher’s exact test for categorical variables and Wilcoxon rank sum test for continuous variables.

Results:
A total of 39 tPA-eligible LVO patients were identified, 19 with ΔMAP < 10mm Hg and 20 with ΔMAP > 10mm Hg. Baseline characteristics were comparable between groups including NIHSS (18.0 [11.0, 21.0] vs 20.0 [16.8, 25.8]) (Table 1). A similar percentage from each group received tPA and thrombectomy. Upon presentation to ED, 7/19 (37%) patients with ΔMAP < 10mm Hg had a 30% improvement in NIHSS, compared to 4/20 (20%) patients with ΔMAP >10mm Hg (p=0.417). The 24-hour change in NIHSS was also similar (ΔMAP < 10mm Hg = 7.0 [3.5, 12.0] vs ΔMAP > 10 mm Hg 10.0 [4.0, 16.0], p=0.517). Among patients with ΔMAP of 10mm Hg group, those with MAP decrease by > 10 mm Hg had a 10 point [7.0, 16.0] improvement in NIHSS vs 6.0 [2.5, 15.0] point improvement in those whose MAP increased by > 10 mm Hg (p=0.169).

Conclusion:
Though limited by a small sample size, prehospital blood pressure fluctuations in LVO stroke patients on a MSU were not associated with early clinical changes.
Abstract TP46: Rates Of Symptomatic Intracerebral Hemorrhage After Tpa At Rural Telemedicine Spoke And Hub Sites
Authors: Kambhampati Sarita , Fournier Lauren E , Cohill Kailey , Rasmussen Winkler Jennifer
Published: February 2022

Introduction:
Symptomatic intracerebral hemorrhage (sICH) is the primary bad outcome monitored post-alteplase (tPA) administration for treatment of acute ischemic stroke (AIS). Risk of sICH ranges from 2-7% based on patient population. However, little is reported on sICH with the use of telestroke, particularly in the rural setting. We evaluated rates of sICH after tPA administration for our telestroke process in a rural Texas spoke-hub system.

Methods:
Patient data was prospectively collected from 6/2018 (start of telestroke system) to 5/2021, including age, sex, race/ethnicity, tPA administration, door-to-needle times and sICH. Patients were included if >18 years old and underwent tPA administration at the hub or telemedicine spoke site in a rural Texas healthcare system. Six spokes and one hub were included in this study. Documented sICH was retrospectively abstracted from the database with the primary outcome comparing sICH rate between the hub and spokes. Statistical analysis was conducted by chi-square analysis.

Results:
A total of 160 patients received tPA at the hub and 239 at the spokes. Four patients suffered sICH at the hub and five at spokes (2.5% v 2.1%, p=0.793). Rates of tPA administration were not significantly different. Demographic comparison between spoke and hub were significantly different. Notably, there was a higher proportion of male and non-white patients at the hub compared to spoke sites, adding to the variation in populations. Patients were older at spoke sites.

Conclusion:
There was no difference in rates of tPA administration and rate of sICH between hub and spokes in a rural Texas telemedicine program. Rate of sICH in this setting was similar to rate reported in the literature. Furthermore, though there was a statistically significant difference between the populations studied, the likelihood of sICH remained similar. These findings further support the safety of telemedicine use for acute stroke care and tPA administration.
Abstract TP65: Evaluation Of Leg Microvascular Function In Chronic Stroke Survivors Using Near Infrared Spectroscopy And The Vascular Occlusion Technique.
Authors: Durand Matthew J , Nguyen Jennifer N , Gutterman David D , Schmit Brian D , Klevenow Emilie A , HYNGSTROM Allison S
Published: February 2022

Background:
Chronic stroke survivors have impaired conduit artery endothelial function, but little is known about peripheral microvascular function post-stroke. Near infrared spectroscopy (NIRS) can non-invasively measure tissue oxygen saturation (StO
2
) of skeletal muscle, and when combined with a dynamic challenge like a vascular occlusion, can indirectly evaluate tissue oxygen utilization during the occlusion period and microvascular function during the post-occlusive hyperemic period. We hypothesized that microvascular function would be impaired in the tibialis anterior (TA) muscle of the affected leg of chronic stroke survivors compared to the non-affected leg as evidenced by a slower oxygen resaturation rate post-cuff release.

Methods:
Fifteen chronic stroke survivors completed this study. The mean age was 57±12 years, 10 were female, and the mean time since stroke was 12±10 years. After resting for fifteen minutes a NIRS sensor was placed over either the affected or non-affected TA. The opposite leg was tested one week later. After recording five minutes of baseline StO
2
, a cuff was placed around the proximal thigh and inflated to 225 mmHg for five minutes. StO
2
was continuously measured during cuff inflation and for five minutes post-cuff release. The rate of change in StO
2
was calculated during the five-minute cuff occlusion and the first 12 seconds post-cuff release.

Results:
There was no difference in baseline StO
2
between the affected and non-affected TA (68±11% vs. 67±6%, respectively; p=0.60). There was also no difference in the change in StO
2
during the occlusion period (affected ΔStO
2
= -31±12 % vs. non-affected -35±19%; p=0.76), or the rate of oxygen desaturation (affected -0.15±0.11 %·s
-1
vs non-affected -0.10±0.04 %·s
-1
; p=0.39). After cuff release, there was a greater oxygen resaturation rate in the non-affected leg compared to the affected leg (3.13±2.08 %·s
-1
vs. 1.60±1.11 %·s
-1
, respectively; p=0.01).

Conclusion:
There was no difference in oxygen utilization between the affected and non-affected TA during the cuff occlusion period. The oxygen resaturation response in the affected TA post-cuff release was slower compared to the non-affected TA, suggesting microvascular function is impaired in the affected muscle.
Abstract TP8: Sodium-glucose Cotransporter 2 Inhibitors Coupled With 40% Carbohydrate Diet Improve Hyperglycemia Safely And Soon In An Acute Stroke Stage
Authors: Mori Takahisa , Yoshioka Kazuhiro , Tanno Yuhei
Published: February 2022

Introduction:
Hyperglycemia must be improved in acute stroke patients. However, effective treatment has not been established.

Hypothesis:
Moderate-carbohydrate (carbo) diet and sodium-glucose cotransporter 2 (SGLT2) inhibitors can lower blood glucose level (BGL) safely and soon in patients with oral ingestion and normal renal function.

Methods:
For the retrospective observational study, we included patients who 1) were admitted within 24 h of stroke onset between Jan 2011 and March 2019, 2) had not undergone insulin therapy, 3) presented hemoglobin A1c ≥ 6.5%, BGL ≥ 11.1 mmol/L, and estimated glomerular filtration rate ≥ 60 mL/min/1.73m2 at admission, 4) took diet and drugs orally during hospitalization, and 5) underwent blood examination on the 6th day. We classified patients into three groups: 60% carbo diet without SGLT2 (C60 group); 40% carbo diet without SGLT2 (C40 group); 40% carbo diet with SGLT2 (C40-SGLT2 group). We calculated daily carbo intake and evaluated sulfonylurea (SU) use during hospitalization, median BGL and median HL at admission and on the 6th day in three groups.

Results:
Of 5724 stroke patients, 84 patients met our inclusion criteria. There were 26 patients in the C60 group, 22 in the C40 group, and 36 in the C40-SGLT2 group. In three groups, median age was 70, 62, and 68 years, respectively, median body mass index was 24.1, 25.1, and 24.3 kg/m2, respectively, median daily carbo intake was 195, 140, and 140 g (p< 0.0001), respectively, 46%, 9%, and 0% of patients used SU (p< 0.0001), respectively, median BGL at admission were 14.2, 14.6, and 14.4 mmol/L, respectively, median HL at admission were 42.4, 44.1, and 43.3%, respectively, median BGL on the 6th day were 7.9, 8.2, and 6.4 mmol/L (p= 0.0003), respectively, and median HL on the 6th day were 40.5, 41.7, and 40.5%, respectively. BGL on the 6th day was decreased in three groups, and it was the most improved in the C40-SGLT2 group. BGL on the 6th day was not different between C60 and C40 groups; however, SU was seldom used in the C40 group. No dehydration occurred.

Conclusion:
SU was seldom necessary for the C40 group and unnecessary for the C40-SGLT2 group. SGLT2 inhibitors coupled with 40% carbo-diet lowered BGL safely and soon in patients with oral ingestion and normal renal function.
Abstract WMP100: Stroke Predictors And Outcomes From The Amplatzer™ Amulet™ Left Atrial Appendage Occluder Randomized Controlled Trial
Authors: Thaler David , Diener Hans-christoph C
Published: February 2022

Introduction:
Left atrial appendage occlusion (LAAO) devices seal off the LAA in order to reduce the risk of stroke in patients with non-valvular atrial fibrillation. The Amulet IDE Trial compared the Amplatzer™ Amulet™ LAA Occluder (Abbott) to the Watchman™ LAA closure device (Boston Scientific). In this analysis we investigate predictors of stroke in the 2 years after trial enrolment.

Methods:
Subjects were at a high risk of stroke or systemic embolism defined as CHADS2 score ≥ 2 or a CHA2DS2-VASc score of ≥ 3 and randomized to LAAO with one of the 2 devices. Screening for outcomes occurred at discharge, 45 days, 3, 6, 9, 12, 18, and 24 months. Annual follow-up for years 3-5 is ongoing. The Questionnaire for Verifying Stroke Free Status was administered at each study visit. All suspected strokes or TIAs were referred for neurological assessment. For confirmed strokes, TEEs and neurological assessment scores were obtained. All events were adjudicated by an independent clinical events committee who also determined relatedness to the procedure and/or device. Predictors of stroke were determined through a univariable and multivariable analysis. For a post-hoc analysis, strokes were classified as disabling (mRS score ≥2, with an increase of at least 1 point compared to pre-stroke baseline) or non-disabling.

Results:
At 108 sites, 1,878 subjects were randomized to an Amulet occluder (N=934) or a Watchman device (N=944) of whom 1,644 completed the 2-year follow-up visit. Baseline characteristics were well-matched between the two groups. Strokes occurred in a total of 67 patients (3.6%) and TIAs in 31 patients (1.7%). Outcome predictors include prior history of stroke/TIA and increased CHA2DS2-VASc score. Disabling strokes and device specific outcomes will be discussed at the time of presentation.

Conclusions:
The predictors of stroke at 2-years and device-specific outcomes will permit comparison of the long-term effectiveness of the Amulet™ occluder compared to the Watchman™ device.
Abstract WMP102: Prevalence Of Genetic Mutations In 15 Mendelian Stroke Genes In Young Stroke Patients
Authors: PARK Hong-kyun , Lee Keon-joo , Park Jong-moo , Kang Kyusik , Lee Soo Joo J , Kim Jae , Cha Jae-kwan , Kim Beom J , Park Tai Hwan , Lee Kyung Bok , Lee Jun , Hong Keun-sik , Cho Yong-jin , Lee Byung-chul , Oh Mi Sun , Kim Joon-tae , Choi Kang-Ho , Kim Dong-Eog , Ryu Wi-Sun , Choi Jay Chol , Kwon Jee-hyun , Kim Wook-Joo , Sohn Sung-il , Hong Jeong-ho , LEE JUNEYOUNG , Bae Joon Seol , Bae Hee-joon
Published: February 2022

Introduction:
Although the heritability of stroke might be higher in young-age stroke population, it is even uncertain how many of them has monogenic causes of stroke. We aimed to estimate the prevalence and clinical characteristics of 15 monogenic disorders associated with stroke in a large, unselected young-age stroke population

Methods:
From a prospective, nationwide, multicenter, acute stroke registry of consecutive patients admitted to 15 academic or regional stroke centers in Korea, we enrolled all patients aged 55 years or younger except those who refuse to participate in this study. We performed genetic analysis using a customized targeted next-generation sequencing panel (
GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP
) to find clinically relevant genetic variants, and reviewed clinical information of the patients.

Results:
Genetic analysis was performed in 1,033 patients (male 70.7%, mean age 45.8±7.9). Twenty-eight clinically relevant genetic variants were identified in 131 (12.7%) patients, and were found most frequently in RNF213 (59, 5.7%) followed by ABCC6 (53, 5.1%) and NOTCH3 (15, 1.5%). Genetic variants were more commonly observed in younger group than older group (17.1% vs. 9.3%, p=0.021), but were not different according to vascular risk factor burden. Patients with premature (<60y) family history of stroke had genetic variants more frequently than those with family history at ≥60y (23.7% vs. 11.4%, p=0.047). Typical neuroimaging abnormalities were observed in only 25% of patients with RNF213 variants and 27% of those with NOTCH3 variants. Variants of uncertain significance were found in 15.4%.

Conclusion:
Clinically relevant genetic variants were not uncommon than expected. We might have opportunities to improve our daily practice by genetic counseling patients and their families to reduce the future stroke.
Abstract WMP12: Disparities In Acute Stroke Care According To Pre-stroke Functional Status
Authors: Mistry Eva , Sucharew Heidi , De Los Rios La Rosa Felipe , Mackey Jason , Ferioli Simona , Demel Stacie L , Coleman Elisheva R , Jasne Adam , Slavin Sabreena , Walsh Kyle B , Star Michael , Haverbusch Mary , Alwell Kathleen , Woo Daniel , Kleindorfer Dawn O , Kissela Brett M
Published: February 2022

Introduction:
Disparities in acute ischemic stroke (IS) care due to patients’ pre-stroke disabilities remain understudied. Using the Greater Cincinnati Northern Kentucky (GCNK) Stroke Study, we aimed to understand the differences in acute stroke presentation and care according to patients’ pre-stroke functional status.

Methods:
We ascertained all hospitalized IS patients ≥18 years old presenting to emergency departments in the GCNK region in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46; all cases were physician-reviewed. Trained nurses ascertained pre-stroke functional status from the medical record. Acute IS presentation, time metrics, and treatment were compared between patients with pre-stroke mRS 0-1 vs ≥2 using Wilcoxon rank-sum or chi-square tests. Logistic regression was used to evaluate the association between pre-stroke mRS and intravenous thrombolysis (IVT) and endovascular treatment adjusting for age, presenting NIHSS, time to presentation, and baseline anticoagulation use.

Results:
Of 2191 patients with IS, 1134 had a pre-stroke mRS ≥2. Patients in the latter group were older, more likely be female, had higher rates of medical comorbidities, had higher presenting NIHSS (3[1-8] vs 2[1-5], p<0.01, Table). They were less likely to receive IVT (aOR 0.43[0.28-0.68], p<0.01, for patients presenting within 0-4 hours) and EVT (aOR 0.32[0.13-0.78], p=0.01, for patients presenting within 0-23.5 hours). They had a higher rate of presentation via EMS, but the time from stroke onset to ED presentation was longer.

Conclusions:
Acute IS patients with pre-stroke disability presented later, with more severe strokes, and were less likely to receive reperfusion treatments. Further research into factors driving acute stroke medical decision-making for patients with a pre-stroke disability is needed to ensure optimal acute neurovascular care for all IS patients across the nation and worldwide.
Abstract WMP18: Protection Against Dementia In Mouse VCID By Repetitive Hypoxic Conditioning: Cortical Proteomics Defines Disease And Disease Resilient Phenotypes
Authors: Broyles Emrey E , Harman Jarrod C , Guidry Jessie J , Gidday Jeffrey M
Published: February 2022

Introduction:
Vascular cognitive impairment and dementia (VCID) exerts huge morbidity costs, and efficacious therapies are lacking. In a well-established mouse model of VCID, we recently documented
in vivo
an epigenetically-induced resilience to reference memory deficits by 2 mo of repetitive hypoxic conditioning (RHC) treatment prior to bilateral carotid artery stenosis-induced chronic cerebral hypoperfusion (CCH). The present study was undertaken to define the phenotypic basis of this cognition-protective effect.

Methods:
Samples of prefrontal cortex from untreated and RHC-treated mice were obtained after 4 mo of CCH, along with samples from age-matched sham-CCH controls, and analyzed by mass spectrometry using TMTpro labels for quantification. Differentially expressed proteins were bioinformatically analyzed using IPA (Qiagen), with rigid thresholds/filters for fold-change, z-scores, and statistical significance applied.

Results:
5071 proteins were identified - 3975 of which were quantified - in the 3 experimental groups. Relative to the cortical proteome of controls, the cortex of memory-impaired CCH mice exhibited a downregulation of proteins involved in Nrf2 signaling and synaptogenesis signaling pathways, and an increase of proteins and related proinflammatory mediators participating in leukocyte extravasation signaling. In addition, gamma secretase levels were increased. Treatment with RHC prior to CCH abrogated the aforementioned Nrf2, synaptogenesis, and leukocyte signaling changes, increased proteins driving oxidative phosphorylation, Rho-mediated CXCR4 signaling, DNA repair, and diverse cell survival networks, and reduced protein enrichments in both apoptosis and necrosis signaling, and reactive oxygen species generating, pathways. Levels of both amyloid precursor protein and amyloid-beta levels, as well as tau, were also lower in RHC-treated, dementia-resilient mice.

Conclusions:
These novel findings reveal potential mechanistic insights into relatively early changes in phenotype that characterize VCID and, in turn, how this phenotype is modified by an efficacious epigenetic therapeutic. Causal studies designed to confirm these multifactorial mechanisms of cognitive protection are warranted.
Abstract WMP3: Hyperglycemic Control In Acute Ischemic Stroke Patients Undergoing Endovascular Treatment: Post-hoc Analysis Of Stroke Hyperglycemia Insulin Network Effort Trial
Authors: Bains Navpreet K , Huang Wei , ISHFAQ Muhammad , French Brandi R , Siddiq Farhan , Gomez Camilo R , Qureshi Adnan I
Published: February 2022

Background and Purpose:
Hyperglycemia has been associated with higher rates of death or disability in acute ischemic stroke patients undergoing endovascular treatment. However, it remains unclear whether intensive serum glucose reduction can reduce the rates of death or disability in patients undergoing endovascular treatment.

Methods:
We analyzed the effect of intensive (serum glucose <110 mg/dl) glucose treatment (compared with standard treatment, serum glucose <180 mg/dl) in patients who received endovascular treatment in the Stroke Hyperglycemia Insulin Network Effort (SHINE). We further analyzed the effect of area under the curve of serum glucose, proportion of the time blood glucose was < 140mg/dL, and glucose variability defined as glucose range during 72-hours. The primary outcomes of interest were neurological deterioration within 72 hours and outcome at 90 days.

Results:
A total of 146 patients (mean age 68.1±13.9, 50.7% were men) underwent endovascular treatment for acute ischemic stroke; 72 and 74 patients were randomized to intensive and standard treatments, respectively. The rates of death (20.3%, and 22.2%), favorable 90-day primary outcome (17.6% and 19.4%), and serious adverse events (41.9% and 56.98%) were similar between the two groups. The area under the curve of serum glucose was not associated with death within 90 days (OR 1, 95% CI 1-1) or favorable outcome at 90 days (OR 1, 95% CI 1-1). Glucose variability was not associated with death or favorable outcome at 90 days. Intensive treatment was not associated with cerebral hemorrhagic events.

Conclusion:
We did not identify any beneficial effect of intensive glucose reduction on rates of death or favorable outcomes at 90 days among acute ischemic stroke patients undergoing endovascular treatment. We also did not observe any relationship between various glycemic parameters and death or favorable outcomes at 90 days.
Abstract WMP42: Trajectory Of Global Disability During First 90 Days Poststroke: Foundational Data For Early Rehabilitation Intervention Trials
Authors: Taleb Shayandokht , Duncan Pam , Cramer Steven C , Bahr-hosseini Mersedeh , Starkman Sidney , Avila Gilda , Hochberg Arielle , Hamilton Scott , Conwit Robin A , Saver Jeffrey L
Published: February 2022

Background:
Novel recovery interventions may be particularly beneficial started 3-10d poststroke, when patients become eligible for intensive inpatient rehabilitation and biologic neuroplasticity is at its peak. To design recovery clinical trials in this population, it is important to characterize the evolution of global disability through 3mo of conventional care.

Methods:
Among all ischemic stroke (IS) and intracranial hemorrhage (ICH) patients enrolled in an NIH multicenter acute treatment trial (FAST-MAG), we analyzed disability course among patients discharged to acute inpatient rehabilitation facilities (IRFs) 2-9 days poststroke.

Results:
Among 1426 IS and ICH patients, 255 (17.9%) were discharged to IRFs, including 12.8% within 2-9d and 5.1% beyond 9d. Among IS patients, rate of 2-9d discharge to IRFs was 13.0% (135/1041), age 71.1 (±12.4), 42% female, NIHSS on first hospital arrival 10.3 (±6.8), and global disability on day 4 mRS=3 in 15.9% and mRS=4 in 43.8%. Among ICH patients, rate of 2-9d discharge to IRFs was 12.2% (47/385), age 62.4 (±11.7), 32.9% female, NIHSS on first hospital arrival 11.5 (±5.7), and global disability on day 4 mRS=3 in 12.2% and mRS=4 in 45.1%. Among Day 4 mRS 3-4 patients, mRS improvement by 90d among ICH and IS patients was 83.0% vs 72.6%, p = 0.17. Mean mRS change for ICH and IS was -1.5 (±1.1) vs -1.3 (±1.4) (Figure). Final 90D mRS among ICH and IS patients was mean 2.2 (±1.1) vs 2.4 (±1.5).

Conclusion:
In this broad acute stroke patient cohort, 1 in 8 patients were transferred to inpatient rehabilitation within 2-9d days poststroke. Intracranial hemorrhage patients had nominally greater improvement on the mRS by 90d than ischemic stroke patients. This course delineation provides a roadmap for future rehabilitation intervention studies.
Abstract WMP43: Optimizing Therapy Intensity For Inpatient Stroke Rehabilitation: A Linear Programming Model For Cost
Authors: Akpan Folakemi , Taghavi Majid , Kamal Noreen
Published: February 2022

Background:
Although the best practice guidelines in Canada recommended that stroke patients in inpatient rehabilitation receive a minimum of 3 hours of therapy 5 days per week, very few patients receive this amount of therapy as the national average is 90 minutes of therapy 5 days a week. Administrators have stated that is not feasible to provide the best practice amounts of therapy due to budget constraints. Therefore, the purpose of this study was to develop a linear programming model which assessed the feasibility of meeting Canadian guidelines for therapy amount in inpatient stroke rehabilitation.

Methods:
A linear programming model was developed based upon previously published works on the impacts of increasing therapy amount to the Canadian best practices. The objective function was to minimize cost. Decision variables included the hours of physiotherapy, occupational therapy, and speech-language pathology a moderate patient receives. Constraints included minimum and maximum hours of therapy, the relationship between therapy amount of length of stay, and the therapy time ratios

Results:
The optimal solution found that cost, when minimized with moderate patients, were provided with 1.2, 1.2, and 0.6 hours of physiotherapy, occupational therapy, and speech-language pathology respectively. This results in a 24.3-day length of stay. The total modeled cost was $18,253.55 per moderate patient. Based upon this model, the current Canadian average length of stay and therapy amount costs an additional $1,470.13 per moderate patient compared to the model solution.

Conclusion:
This work demonstrates that providing the best practice amount of therapy to patients may result in cost savings due to the reduction in length of stay, contradicting the commonly held notion that providing more therapy is not feasible from a financial point of view.
Abstract WMP67: Evaluation Of The Implementation Of An Ai Tool For Large Vessel Occlusion: Impact On Radiologists’ Workflow And Patient Outcomes
Authors: Nagamine Masaki , Zolyan Anna , Elstrott Sebastian , Mclouth Joel , Vu Viet , Yu Wengui , Soun Jennifer
Published: February 2022

Timely and accurate diagnosis of a large vessel occlusion (LVO) is critical for prompt initiation of thrombectomy treatment to reduce morbidity and mortality in acute ischemic stroke patients. Recently, artificial intelligence (AI) tools to aid stroke triage have shown promise for their accuracy and speed. However, little is known about the impact of the clinical integration of AI on efficiency metrics and patient outcomes. This study aims to evaluate the impact of an AI-based LVO detection tool on three main areas: (1) performance metrics, (2) radiologist workflow, and (3) ischemic stroke metrics and outcomes. This single center retrospective analysis includes patients with suspected acute stroke who underwent CT angiograms (CTA) in a three month period before and after the implementation of an AI-based LVO detection tool. CTA of 224 patients pre-implementation and 144 patients post-implementation of the tool were evaluated. The tool correctly identified 93/107 cases, with an accuracy of 87%, sensitivity of 91%, and specificity of 86%. The PPV was 0.64 and the NPV was 0.97. The mean radiology report turnaround time (TAT) using the tool was significantly reduced at 19.9 minutes (SD 32.4) compared to 33.7 minutes (SD 34.7) without the tool (p=0.001). There was a significant improvement in the resident trainee TAT with the LVO tool, with a mean TAT of 17.9 minutes (SD 32.6) compared to 38.4 minutes (SD 33.6) without (p=0.0002). Baseline stroke risk factors were similar between the pre and post-implementation groups. There were no significant differences in stroke metric medians for door-to-image, door-to-needle, door-to-puncture, and door-to-revascularization times and there were no statistically significant differences in NIHSS on arrival, post treatment NIHSS, discharge mRS, or mortality. The findings in clinical outcomes and stroke metrics may be attributable to small sample size. This study validates an AI-based tool in the detection of LVO and demonstrates a significant associated reduction in report TAT, allowing for faster communication of critical findings to ordering clinicians. Further research is needed to evaluate the impact of these tools on stroke benchmarks and clinical outcomes and to establish their role in stroke triage for clinicians.