bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P146: Low Serum Level of Eicosapentanoic Acid (EPA) is Associated with Occurrence of Nonlobar Type Intracerebal Hemorrhage (ICH)
Authors: Akaiwa Yasuhisa , Takano Hiroki , Arakawa Hiroyuki , Ninomiya Itaru , Uemura Masahiro , Toriyabe Masafumi , Shimohata Takayoshi , Nishizawa Masatoyo
Published: July 2021

Background:
: Intake of omega-3 polyunsaturated fatty acids, such as EPA, has been reported to have protective effects on various diseases including ischemic stroke. However, there have been few studies concerning the effect of omega-3 polyunsaturated fatty acids on hemorrhagic stroke. We studied associations of serum levels of EPA with stroke subtypes including primary ICH

Methods:
We have examined serum EPA and arachidonic acid (AA) levels in routine practice since 2009. To calibrate the EPA values, we calculated EPA/AA ratio. A total of 212 consecutive acute stroke patients and 27 control subjects were included. The patients 40 years old or younger were excluded. Ischemic stroke subtypes were determined based on TOAST criteria. Primary ICH was classified into lobar or nonlobar types, according to the region of the brain in which it occurred.

Results:
Of all the 157 ischemic stroke patients (female 47, mean age 72.9 years), 62 were classified with cardioembolic stroke (CES), 25 large-artery atherosclerotic (LAA), 22 small-vessel disease (SVD), and 48 other/undetermined causes (O/U). Of all the 55 ICH patients (female 23, mean age 71.0), 34 patients had nonlobar type, and 21 had lobar one. There were no significant intergroup differences in the mean EPA/AA ratio (p=0.525) among CES (EPA/AA= 0.67±0.42), LAA (0.70±0.30), SVD (0.65±0.45), O/U (0.62±0.38), nonlobar ICH (0.51±0.30), lobar ICH (0.64±0.33), and control (0.60±0.42) groups. However, the EPA/AA ratio of the nonlobar ICH group was considerably low. The EPA/AA ratio of the nonlobar ICH group was significantly (p=0.033) lower than that of the whole other groups (0.65±0.39) and significantly (p=0.003) lower than that of the entire ischemic stroke groups (0.67±0.40). Although the significant differences between the nonlobar ICH and the whole ischemic groups were also observed in systolic and diastolic blood pressure (195±37/107±25 mmHg vs 159±35/82±19 mmHg, p<0.001), multiple linear regression analyses showed the association between the EPA/AA and nonlobar ICH was independent from the blood pressure.

Conclusions:
Although the strongest risk factor for nonlobar ICH is hypertension, low EPA/AA ratio might play a role in the development of nonlobar ICH.
Abstract W P154: Increase in the Rate of Comorbid Diabetes in Stroke Hospitalizations From 1998 to 2011: The National Inpatient Sample
Authors: Khoury Philip R , Khoury Jane C
Published: July 2021

Due to the obesity epidemic in the US Population, there has been a related increase in type 2 diabetes. We sought to examine the trend within patients hospitalized due to stroke in a representative population.

Methods:
Using data from 1998 through 2011 from the National Inpatient Sample (NIS), we aimed to see the trends in diabetes for patients hospitalized with a primary discharge diagnosis of stroke (SAH (ICD code 430), ICH (ICD codes 431 and 432.9) and Ischemic (ICD codes 433x1, 434.11and 434.91). Secondary ICD codes were used to define diabetes. Hospitalizations used in this analysis included patients aged 20 years and over at date of admission.

Results:
For the 14 years examined, there were a total of 1,360,839 records with primary diagnosis of stroke, distributed as; 5.4% SAH, 15% ICH, and 79.6% Ischemic. The sample was 46% male; and 29% had diabetes (93% type 2). The rate of diabetes for each stroke subtype was: 12.2% SAH, 22.2% of ICH, and 31.5% of Ischemic. The proportion of stroke discharges with diabetes showed a significant increase with time, with a year over year increase in 12 of the 13 periods, from 26.5 in 1998 to 30.0 in 2011.

Conclusions:
The proportion of patients hospitalized for stroke who had comorbid diabetes continue to increase year over year, with almost one third of patients hospitalized for Ischemic stroke also having diabetes in 2011. This suggests that control of diabetes, and associated reduction of obesity may lead to reduction of stroke in the US.
Abstract W P213: Leptomeningeal Collateral Growth Is Impaired in Type 2 Diabetic Mice.
Authors: Yukami Toshiro , Yagita Yoshiki , Watanabe Akihiro , Sasaki Tsutomu , Mochizuki Hideki , Kitagawa Kazuo
Published: July 2021

BACKGROUND:
Leptomeningeal anastomoses are the most important collateral pathways, especially after middle cerebral artery (MCA) occlusion, and determine the severity of subsequent ischemic injury of the brain. We previously reported that hypertension impairs leptomeningeal arteriogenesis. Diabetes is also a major vascular risk factor and increases stroke incidence. We hypothesized that arteriogenesis of leptomeningeal anastomoses is also impaired in diabetes.

METHODS:
Male BKS.Cg-m+/+Leprdb/J (db/db) and the non-diabetic and lean heterozygote littermates(db/+) were used. To investigate the influence of hyperglycemia itself, male C57BL/6 mice injected with streptozotocin(STZ,250mg/kg) intraperitoneally 1week before surgery were also used. All types of mice were assigned to the left common carotid artery occlusion(CCAO) group and the sham CCAO group. After 14 days of the surgery, latex perfusion was performed to visualize the leptomeningeal anastomoses and mesure the vessel diameters(n=5, each group), or the left MCA was occluded using electrocoagulation to evaluate the infarct size with TTC staining(n=7, each group).

RESULTS:
In db/+ mice, there were significant increase of leptomeningeal collateral vessel diameters in response to CCAO(CCAO,33.7±1.2μm vs. sham,26.5±1.0μm, P<0.01) and infarct size was significantly attenuated, especially in the cerebral cortex, in the CCAO group compared with the sham group, which was in agreement with our previous study in normal rodents. In contrast, in db/db mice, there were no significant differences in the vessel diameters between the CCAO group and the sham group(27.9±1.0μm vs.26.6±1.0μm) and no reductive effect of infarct size attribute to leptomeningeal arteriogenesis. In STZ induced diabetic mice, there were significant increase of the vessel diameters(29.1±1.1μm vs. 23.6±0.7μm, P<0.01) and significant reduction of infarct size in response to CCAO.

CONCLUSIONS:
Arteriogenesis of leptomeningeal anastomoses is impaired in db/db mice, but is not impaired in STZ induced diabetic mice. These results suggest that the mechanism of impairment of arteriogenesis is not due to only hyperglycemia.
Abstract W P217: The Impaired Leptomeningeal Collateral Flow Recruitment in the Type II Diabetic Mice is Independent of Hyperglycemia
Authors: Akamatsu Yosuke , Lee Chih Cheng , Liu Jialing
Published: July 2021

Introduction:
Previously we found that type II diabetic mice db/db strain exhibited impaired collateral flow recruitment between the middle cerebral artery (MCA) and anterior cerebral artery (ACA) vascular networks during MCA occlusion (MCAO)contributed to the worse stroke outcome when compared to their normoglycemic strain. However, it is unclear whether the underlying etiology in the diabetic stroke mice is attributed to hyperglycemia or other vascular pathology.

Methods:
Adult male db/+ received intraperitoneal injection of dextrose (HG) or normal saline (NG) (n=5-6/group), respectively, 60 minutes prior to distal MCAO. Doppler optical coherence tomography (DOCT) was used to quantify the MCA flow direction and velocity at baseline and 30 min after MCAO. The chosen regions of interest of MCA network were classified according to branching order as segment 1 (seg1), seg2 and seg3, with seg1 most proximal to ACA while most distal to MCA. 5-10 points corresponding to the same location of each segment were selected for quantification.

Results:
Blood glucose level was maintained at approximately 382± 83.8 mg/dl in the HG group during blood flow imaging, compared to 166± 60.1 mg/ml in the NG group. It fell to 141± 36.3 mg/dl and 142± 46.3 mg/dl at 24h after stroke in both groups. Hyperglycemia didn't change baseline flow velocity (NG: 6.8±0.8/9.2±0.7/12.5±0.5mm in seg1/seg2/seg3; HG: 5.7±0.7/8.2±0.5/12.6±0.9 mm/s, NS in all segments). At 30 min after MCAO, collateral flow was induced in both groups and there was no significant difference in flow velocity between groups (NG: -3.8±0.3/-2.7±0.1/-2.7±0.3mm/s; HG: -4.1±0.2/-3.1±0.3/2.2±0.4mm/s, NS in all segments). There was also no significant difference in vessel diameter between the groups both at baseline (NG: 48.9±3.5/55.1±1.6/61.5±2.7μm; HG: 45.6±1.7/48.8±2.7/59.2±2.7μm, NS in all segments) and 30 min after MCAO (NG: 48.4±2.0/50.8±2.6/55.5±2.6μm, HG: 42.6±2.3/49.9±2.0/52.5±2.6 μm in HG, NS in all segments).

Conclusions:
Temporary induction of hyperglycemia doesn't affect collateral flow in normoglycemic mice during acute stroke, suggesting that the observed impairment of collateral flow recruitment in the type II diabetic mice is likely attributed to chronic vascular pathology.
Abstract W P220: Suppression of Interleukin 33 Limits Ischemic Brain Injury and Improves Functional Outcome in Murine Stroke Model
Authors: Zafar Atif , Khan Mohammad M , Zaheer Asgar
Published: July 2021

Background and purpose:
Ischemic stroke is a leading cause of death and disability worldwide, and the treatment options are limited. Interleukin-33 (IL-33) is a newly recognized IL-1 family cytokine which signals via its ST2 receptor, and acts as a key regulator of inflammation. However, the expression of IL-33 in the brain was not well studied and its expression in ischemic stroke remains to be elucidated. In the present study, we measured IL-33 and ST2 levels and examine the correlation of IL-33 expression with brain damage and functional outcome following ischemic stroke.

Methods:
IL-33 expression was examined in ischemic brain hemisphere. Mice were subjected to middle cerebral artery occlusion (MCAO) for 1 hr using a filament model, followed by 23 hrs reperfusion. Briefly, mice were anesthetized with 1-1.5% isoflurane mixed with medical oxygen. Body temperature was maintained at 37°C ± 1.0 using a heating pad. At 23 hours after ischemia/reperfusion, mice were tested for neurological scores and were sacrificed for the estimation of IL-33 and ST2 expression. Expression of IL-33 and its receptor ST2 was monitored by ELISA, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, expression of NF-kB and proinflammatory cytokines were evaluated after ischemia/reperfusion.

Results:
We found significantly increased expression level of IL-33 and ST2 in the MCAO mice as compare to the saline treated control mice. Moreover, treating the MCAO mice with recombinant IL-33 increases the brain injury and worsens neurological deficits in MCAO mice as compare to control mice. Interestingly, increased ischemic brain damage and neurological deficits were largely abrogated in mice treated with IL-33 neutralizing antibody.

Conclusion:
These findings provide the first evidence that IL-33/ST2 signaling plays an important role in the pathogenesis of stroke. Moreover, IL-33 exacerbates inflammatory brain injury after ischemic stroke and treatment with specific IL-33 neutralizing antibody inhibited the ischemic brain injury. Therefore, blocking the IL-33 may represent an efficient therapy in stroke.
Abstract W P224: SOS Score: an Optimized Score to Screen Acute Stroke Patients for Obstructive Sleep Apnea
Authors: Camilo Millene R , Sander Heidi H , Eckeli Alan L , Fernandes Regina M , Santos-Pontelli Taiza E , Pinto Pedro T , Abud Daniel G , Leite Joao P , Pontes-Neto Octavio M
Published: July 2021

Background:
Obstructive sleep apnea (OSA) is frequent in acute stroke patients and is associated with increased mortality and poor functional outcome. Polysomnography (PSG) is the gold standard diagnostic method for OSA, but it is impracticable as a routine for all acute stroke patients. We evaluated how OSA screening tools such as the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS) would perform when administered to relatives of stroke patients in the acute setting, and compared these individual tools against a combined screening score (SOS score).

Methods:
Ischemic stroke patients were submitted to a full PSG at the first night after symptoms onset. OSA severity was measured by apnea-hypopnea index (AHI). BQ and ESS were administered to relatives of stroke patients before the PSG. We combined elements of the BQ and ESS to create a new screening tool for OSA named Sleep Obstructive apnea score optimized for Stroke (SOS score).

Results:
Thirty-nine consecutives ischemic stroke patients were enrolled in our study. The mean age was 62.3 ±12.2 years. Age was significantly different between those with and without OSA (p=0.02). The mean body mass index and neck circumference were 26.7 ± 4.7 and 38.9 ± 4.0cm, respectively. OSA (AHI ≥ 10) was present in 76.9%. The area under the curve for SOS score (AUC:0.812; p=0.005) was superior to BQ (AUC:0.567; p=0.549) and also to ESS (AUC:0.646; p=0.119 vs. AUC:0.686; p=0.048) for severe OSA (IAH ≥ 30). The threshold of SOS ≤ 10 (present in 20.5% of patients) showed high sensitivity (90%) and negative predictive value (96.2%) for OSA; SOS ≥20 (17.9% of patients) showed high specificity (100%) and positive predictive value (92.5%) for severe OSA. Using SOS as a screening approach would decrease by around 40% the demand for PSG during the acute stroke setting.

Conclusions:
The SOS score when administered to relatives of stroke patients appears to be an appropriate tool to screen acute stroke patients for OSA, while decreasing the need for a formal sleep study during the acute stroke setting. The new derived SOS score is superior to BQ and ESS for identifying patients with OSA and Severe OSA during the acute phase of stroke.
Abstract W P225: The Relationship between Leukocytosis and Time to Neurodeterioration
Authors: Boehme Amelia K , Siegler James E , Albright Karen C , George Alexander J , Monlezun Dominique , Friedant Adam , Gouse Brittany M , Beasley T. Mark , Martin-Schild Sheryl
Published: July 2021

Background:
Previous research has illustrated how leukocytosis after acute ischemic stoke (AIS) is related to poor functional outcome. A main predictor of poor functional outcome is neurodeterioration (ND). We sought to explore the relationship between leukocytosis and time to ND to identify a risk factor for a process that predicts poor functional outcome.

Methods:
Patients admitted to our stroke center (07/08-06/12) were retrospectively assessed. Leukocytosis was defined as WBC >11,000, ND was characterized as ≥ 2 point increase in NIHSS scale and poor functional outcome was classified as modified Rankin Scale (mRS) of 3-6. Patients were grouped into 2 categories: (1) the leukocytosis group- those who developed leukocytosis ≥24 hours after admission and those who presented with leukocytosis and remained at 24 hours and, (2) the non-leukocytosis group- those that did not have leukocytosis and those where the leukocytosis resolved within 24 hours of admission.

Results:
A cohort of AIS patients (N=476) with median age 64 years, 43% female and 69% Black were assessed. Of the patients with ND (27%), median time to ND was 43 hours. In the leukocytosis group (N=84), 42 (50.6%) of them developed ND. In the non-leukocytosis group (N=312), 75 (24.5%) developed ND. Leukocytosis within 24 hours of admission is predictive of earlier time to ND (p<0.0001; Figure 1). Adjusting for age, stroke severity, glucose, tPA and infection, the leukocytosis group had a 2 times greater risk for developing ND (HR 2.49, 95%CI 1.61-3.84, p<0.0001).

Conclusion:
Having leukocytosis persist from admission to 24 hours or developing leukocytosis within 24 hours of admission is a significant predictor of early ND, which often results in poor functional outcome. Identifying such a predictor can enable physicians to identify those at risk for ND and subsequent poor functional outcomes. Future studies are needed to identify if interventions targeting leukocytosis may improve outcome after stroke.
Abstract W P23: Predictors of Time From Groin Puncture to Base Catheter Placement
Authors: Aghaebrahim Amin , Streib Christopher , Rangaraju Srikant , Horev Anat , Demel Stacie , Jadhav Ashutosh , Jovin Tudor
Published: July 2021

Background and Purpose:
Time to reperfusion is recognized as an important predictor of good outcome in endovascular stroke therapy. A significant but unstudied factor in delay to reperfusion is prolonged time from groin puncture to base catheter placement (P2C). The purpose of this study was to assess the factors that influence time from P2C in the cohort of patients in whom procedural steps were collected prospectively.

Methods:
A prospective analysis of patients who had intra-arterial therapy for acute stroke from August of 2012 to August of 2013 was performed. Following characteristics were collected: baseline clinical demographics, aortic arch types, time from P2C, procedural and clinical outcomes.

Results:
Data from a total of 143 patients were collected prospectively {median age 69 years; median baseline NIH Stroke Scale 16; occlusion sites: MCA-M1 71%; MCA-M2 13%, ICA-T 6%, basilar artery 10%, tandem occlusion 26%}. Patients were further divided based on their arch type (type 1: 48%, type 2: 33%, type 3: 13%). Majority of the patients were treated with newer mechanical embolectomy devices (manual aspiration +/- stent-retriever 96%). Recanalization rate (TICI 2b or 3) was 90%. The median procedural times were as follow (minutes): time from P2C: 20, time from baseline catheter to reperfusion: 36, median total procedural times: 85. The rate of favorable functional outcomes at 90 days (mRS 0-2) was 45%. Patients with favorable outcomes had shorter P2C (31 min vs. 19 min p=0.02). In a multivariate analysis the predictors of longer P2C were age (OR 1.04, P=0.05, 95% CI 1.00-1.08), vertebrobasilar location (OR 5.4, P=0.027, 95% CI 1.21-24.1), smoking (OR 3.7, P=0.02, 95% 1.2-11.1), and with trend toward significance for hypertension (OR 3.03, P=0.062, 95% 0.94-0.97).

Discussion:
Shorter P2C is associated with higher rate of favorable outcomes. Independent risk factors associated longer time are age, vertebrobasilar occlusions, active smoking and history of hypertension. Alternative arterial access may be considered in patients who are likely to have longer P2C.
Abstract W P237: IV TPA Can be Safely Given Without CBC Results Back
Authors: Wang David , Parker Sarah , Nair Deepak , Talkad Arun , McNeil Clayton J , Swanson-Devlin Teresa , Beck Judi , Jahnel Jan L
Published: July 2021

Background:
Reducing door to needle time when giving IV TPA is key to resolve ischemic stroke. Currently, precious time is wasted reviewing all inclusion and exclusion criteria for IV TPA, which were used during clinical trials. There is no evidence that harm has been done if these criteria are not followed. Simplifying the criteria may be safe and can shorten door to needle time significantly. Complete blood count (CBC) is one item that may not always be needed if stroke patient has no history of hematological disorder. While CBC and other labs can be obtained first, it may be safe that IV TPA can be given without CBC results are back.

Method:
Data on all patients who received IV TPA before CBC resulted was tabulated and analyzed. Their demographic data, LOS, complications, and discharge destination were examined. Descriptive statistics were used.

Results:
From 01/2012-07/2013, 547patients were directly admitted for ischemic stroke at our CSC and 86 (16%) received IV TPA. Among them, 51 (59%) had IV TPA prior to their CBC resulted. Their average age was 75 and 31 (60%) were female. Normal CBC was found in 50 (98%) patients later but 1(2%) had platelet count of 81,000. This patient had no hemorrhagic event and her stroke symptoms completely resolved by day two of admission. Overall, 22 (43%) went home, 4(7%) had symptomatic ICH despite they had normal CBC, 6(11%) went to rehabilitation, and 6(11%) died.

Conclusions:
In patients presented with acute ischemic stroke who are candidates for IV TPA, it is safe to give IV TPA first before CBC results are available. This will reduce door to needle time by at least 20 minutes. Millions of brain cells can be saved. Therefore, having CBC results back is not essential when IV TPA is considered.
Abstract W P24: Choice of Thrombectomy Device and Degree of Collateral Flow Predict Reperfusion in DEFUSE 2
Authors: Liggins John T , Mlynash Michael , Straka Matus , Kemp Stephanie , Bammer Roland , Marks Michael P , Albers Gregory W , Lansberg Maarten G
Published: July 2021

Background:
Endovascular therapy for acute ischemic stroke is an effective tool for recanalizing occluded vessels. We sought to determine the factors associated with successful reperfusion and whether any differences in reperfusion rates existed between hospital sites.

Methods:
Stroke patients underwent endovascular treatment as part of the DEFUSE 2 study at nine hospital sites between 2008 and 2011. Patients were included for analysis if they had a baseline TICI score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion score of 2b or 3 at the completion of the procedure. Collaterals were assessed using the Collateral Flow Grading System and were dichotomized as poor (0-2) or good (3-4). The relationship between clinical, neuroimaging and treatment variables and TICI reperfusion was assessed using logistic regression.

Results:
Eighty-nine patients had a baseline TICI score of 0 or 1; thirty-six patients achieved successful TICI reperfusion. Patients were treated with the Merci clot retriever (n=25), the Penumbra device (n=19), both Merci and Penumbra (n=17), or other endovascular therapies (n=28). Other interventions included manual aspiration (n=20), stent retrievers (n=7) and angioplasty (n=7). Variables associated with successful reperfusion in univariate analyses were: good collaterals (p<0.01), location of artery occlusion (p<0.05), use of the Merci retriever (p<0.01), and hospital site (p<0.01). In multivariate analysis, good collaterals (p<0.01) and use of the Merci retriever (p<0.05) remained as independent predictors of successful reperfusion.

Conclusion:
In acute stroke patients who undergo endovascular therapy, good collateral flow to the ischemic brain region and use of the Merci retriever are associated with successful reperfusion. The rates of successful reperfusion differed between hospital sites. This may have been driven by variation in the rates of use of the Merci retriever.
Abstract W P257: Predictors of the CT Angiography Spot Sign in Deep and Lobar Intracerebral Hemorrhage
Authors: Radmanesh Farid , Falcone Guido J , Anderson Christopher D , Battey Thomas W , Ayres Alison M , Vashkevich Anastasia , Schwab Kristin , Romero Javier M , Viswanathan Anand , Greenberg Steven M , Goldstein Joshua N , Rosand Jonathan , Brouwers H. B
Published: July 2021

Objectives:
Intracerebral hemorrhage (ICH) patients with CT angiography (CTA) spot sign are at increased risk of hematoma expansion and poor outcome. Since ICH is often the acute manifestation of a chronic cerebral vasculopathy, we investigated whether different clinical or imaging characteristics predict spot sign presence in patients with different underlying vasculopathies. Using ICH location as a surrogate for hypertension-related ICH and cerebral amyloid angiopathy-related ICH, we identified risk factors associated with spot sign.

METHODS:
We retrospectively analyzed a prospective cohort of consecutive spontaneous ICH patients with available CTA. Spot sign presence was ascertained by two independent readers blinded to clinical data. We assessed potential predictors of spot sign be performing uni- and multivariable logistic regression, analyzing deep and lobar ICH separately.

RESULTS:
649 patients were eligible, 291 (45%) deep and 358 (55%) lobar ICH. Median time from symptom onset to CTA was 4.5 (IQR 5.2) and 5.7 (IQR 7.4) hours in patients with deep and lobar ICH, respectively. At least one spot sign was present in 76 (26%) deep and 103 (29%) lobar ICH patients. In mutivariable logistic regression, independent predictors of spot sign in deep ICH were warfarin (OR 2.82 [95%CI 1.06-7.57]; p=0.03), time from symptom onset to CTA (OR 0.9 [95%CI 0.81-0.97]; p=0.02), and baseline ICH volume (OR 1.27 [95%CI 1.14-1.43]; p=2.5E-5; per 10 mL increase). Predictors of spot sign in lobar ICH were preexisting dementia (OR 2.7 [95%CI 1.15-6.43]; p=0.02), warfarin (OR 4.01 [95%CI 1.78-9.29]; p=0.009), and baseline ICH volume (OR 1.27 [95%CI 1.17-1.39]; p=5.4E-8; per 10 mL increase). As expected, spot sign presence was a strong predictor of hematoma expansion in both deep (OR 3.52 [95%CI 1.72-7.2]; p=0.0005) and lobar ICH (OR 6.53 [95%CI 3.23-13.44]; p=2.2E-7).

CONCLUSIONS:
The most potent associations with spot sign are shared by deep and lobar ICH, suggesting that ICH caused by different vasculopathic processes share biological features. The relationship between preexisting dementia and spot sign in lobar ICH, but not deep ICH, suggests that ICH occurring in the context of more advanced cerebral amyloid angiopathy may be more likely to have prolonged bleeding.
Abstract W P3: Clinical Outcomes and Safety of Endovascular Therapy for IV tpa Ineligible Patients Who Present Within the IV tpa Time Window
Authors: Aghaebrahim Amin , Rangaraju Srikant , Streib Christopher , Grandhi Ramesh , Reznik Michael , Campbell David , Jadhav Ashutosh , Jovin Tudor
Published: July 2021

Background and Purpose:
Outcomes in patients treated with endovascular therapy who present within the time window for IV tPA, but do not receive IV tPA, are poorly characterized. This information may be necessary in the planning of randomized trials.

Methods:
A retrospective analysis of a prospectively collected endovascular stroke database was performed to identify all patients who arrived within the time window for IV tPA (≤4.5 hours) who had significant neurologic deficits, but were not treated with IV tPA due to contraindications. Procedural, safety and clinical outcomes were assessed by determining rates of recanalization, hemorrhagic transformation and 90-day independent outcome (mRS 0-2).

Results:
Out of 961 patients entered in our endovascular stroke database, we identified 163 {mean age 69±1 years; median baseline NIH Stroke Scale 17 IQR 14-21; occlusion site: MCA-M1 82 (50%); MCA-M2 18 (11 %), ICA-T 33 (20 %), Basilar artery 15 (9 %), ACA-A1 2 (1%), ICA-intracranial 8 (5%)}. The main contraindications to IV tPA were elevated INR or PTT (25%), recent surgeries (34%), previous intracerebral hemorrhage (4%), recent stroke (7%), recent bleeding (5%) and others (25%). Following endovascular treatment, the symptomatic hemorrhage (sICH) rate was 11% and recanalization rates (TICI 2b or 3) was 74.7% (56/75). The rate of good functional outcomes at 90 days (mRS 0-2) was 40% (59/149). The 90-day mortality rate was 34.2% (51/149). There was no significant difference for 90-day good outcome, mortality or sICH with respect to the specific contraindication for IV tPA, but there was trend toward worse outcome and higher mortality rate for patients with elevated INR or PTT compared to other groups (good outcome: 29% vs. 38%, p=0.32, mortality rate: 44% vs. 33%, p=0.24) .

Conclusion:
This dataset provides an estimate of outcomes obtained with intra-arterial therapy in IV tPA ineligible patients over a 12 year period and may serve as preliminary data that can be used for sample size estimation in planned randomized trials. Our outcomes are comparable to patients treated with IV tPA in the IMS III trial and are superior to the natural history of this disease.
Abstract W P307: Utilization of Tissue-Type Plasminogen Activator for Ischemic Stroke in California -Evidence From Ischemic Stroke Outcomes Validation Study
Authors: Wang Limin , Vickrey Barbara , Cheng Eric M , Liu Honghu , Parikh Punam , Wang Yan , Zingmond David , Parker Joseph , Holliday-Hanson Merry
Published: July 2021

Background and Purpose:
A recent ischemic stroke data validation study using California (CA) patient discharge data (PDD) was conducted as part of a public reporting program for the Office of Statewide Health Planning and Development (OSHPD). This validation study demonstrated that use of tissue-type plasminogen activator (tPA) is well-coded in the PDD. Supported by this evidence, we sought to measure tPA usage for ischemic stroke in CA acute care hospitals and to determine whether some hospital or patient characteristics are associated with greater or lower tPA utilization.

Methods:
Using the OSHPD PDD, we selected adult patients with a primary diagnosis of ischemic stroke admitted to CA acute care hospitals between January 2010 and November 2011. Using bivariate analysis, we explored the association between rates of tPA use and patient age, gender, race, and expected payer, as well as hospital teaching status, location, and size.

Results:
Among the 74,586 patients hospitalized with acute ischemic stroke in CA, 4,488 patients (6.02%) received tPA. The observed rate of tPA usage among hospitals ranged from 0% to 22.13%.There were no significant gender differences. Younger patients had a higher rate of tPA usage than older patient groups (7.4% vs. 5.8% and 6.1%, P=0.0029). White patients had a higher rate of tPA utilization than Black and Hispanic patients (6.8% vs. 4.2% and 4.4%, P< 0.0001). Those with Medicare (5.9%) and Medi-Cal (5.1%) had a lower rate of tPA utilization than those with private insurance (7.5%), but higher than self-pay patients (4.4%) (P< 0.0001). There was a significantly higher rate of tPA usage in teaching hospitals than non-teaching hospitals (8.6% vs. 5.7%, P< 0.0001) and tPA utilization was significantly greater at urban versus rural hospitals (6.3% vs. 3.3%,P<0.0001). Higher rates of tPA utilization were associated with increased hospital bed size (P< 0.0001).

Conclusions:
Rates of tPA utilization in CA acute care hospitals varied significantly by hospital teaching status, location, licensed bed size and patient demographic characteristics.
Abstract W P318: Declining Mortality in Cerebral Venous Thrombosis: A Systematic Review
Authors: Coutinho Jonathan M , Zuurbier Susanna M , Stam Jan
Published: July 2021

Introduction:
Cerebral venous thrombosis (CVT) is nowadays considered a disease with a good outcome in most cases, but in the past these patients were believed to have a grave prognosis. This apparent decline in mortality has not been investigated systematically

Methods:
We performed a systematic review of the literature. Older studies were identified from books and by scanning reference lists. Studies with 40 CVT patients or more that minimally reported mortality at discharge were eligible. Care was taken to exclude duplicate publications based on the same patient cohort. Studies were ranked according to the year halfway the period of patient inclusion. If no time span was reported, we assumed a period of inclusion of 10 years prior to the year of publication.

Results:
Of 4.585 potentially eligible studies, 74 fulfilled the selection criteria and were included in the analysis. The majority of studies were retrospective (80%) and single-center (59%). In total, 23.031 patients were included in the analysis. The number of patients per study varied from 40 to 11.400 (median 79). Seven studies included only children. There was a significant inverse correlation between mortality and year of patient recruitment (Pearson’s correlation coefficient -0.70, p<0.001, figure). In a sensitivity analysis, exclusion of retrospective studies, pediatric studies, single-center studies, or studies from low income countries did not significantly alter the correlation.

Conclusions:
There is a clear trend in declining mortality among patients with CVT over time. Possible explanations include better diagnosis (with identification of less severe cases), improved treatment and a declining incidence of infection related CVT.
Abstract W P333: Medications for Secondary Stroke Prevention at Hospital Discharge in Da Nang, Viet Nam
Authors: Cahill Elizabeth A , Ton Thanh G , Fitzpatrick Annette L , Ly Kiet A , Ngo Quang V , Vo Tung T , Pham Chien H , Longstreth William T , Tirschwell David L
Published: July 2021

Background:
Developing countries, such as Viet Nam, are currently undergoing a health transition from infectious to chronic medical conditions, including vascular diseases. Medications for secondary stroke prevention may be underused. Our objectives were to quantify the frequency of such underuse and to identify patient characteristics associated with it.

Methods:
Data from consecutive patients admitted with stroke to Da Nang Hospital from March 2010 through February 2011 were collected using the WHO Stroke STEPS approach. Patients with ischemic stroke (IS) discharged alive, and not sent home to die, were included. Hypertension (HTN), diabetes mellitus (DM) and hyperlipidemia (HL) were conditions eligible for preventative medications at discharge. "Underuse" was defined as prescribing less than all appropriate medications, given each patient’s conditions. Patients with intraparenchymal hemorrhage were excluded from analyses. Multivariate associations with underuse were assessed for age, gender, number of conditions, stroke symptoms, employment status, level of education, hospital ward, and discharge modified Rankin scale.

Results:
Of 754 patients admitted with stroke, 260 patients met our inclusion criteria with a mean age of 67.2 years and with 42% women. Most had HTN (91.5%), and some, DM (9.6%) and HL (11.2%). Patients mostly had ≥ 2 conditions needing treatment at discharge (93.5 %). Underuse occurred in 69.2%, with only half being discharged on antithrombotic agents. Factors independently associated with underuse included older age (RR=1.06 per decade; 95% CI: 1.0-1.1), admission to the ward caring for most stroke patients (RR=2.3; 95% CI: 1.5-3.5), and completing only primary school education (RR=1.3; 95% CI: 1.1-1.7).

Conclusions:
Stroke patients discharged from Da Nang Hospital in Viet Nam are not consistently prescribed medications for secondary stroke prevention. A specific ward, older age, and lower education were independently associated with underuse of preventative medications. Opportunities exist to increase use of medications for secondary stroke prevention at the time of hospital discharge, but barriers will need to be identified.
Abstract W P339: Anticoagulation Remains Underutilized in the Management of Atrial Fibrillation: Results From the Edmonton Registry of Atrial Fibrillation and StrokE (ERASE) Study
Authors: Basir Ghazala , Shuaib Ashfaq , Tahir Affan , Qureshi Kasim , Zeeshan Hasnain , Khan Khurshid , Buck Brian
Published: July 2021

Background:
Since 2010, three novel oral anticoagulants (NOAC) have been approved and included in the guidelines as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Prior to the introduction of NOACs, studies showed that anticoagulation with warfarin in stroke patients with NVAF is suboptimal with as few as 40% anticoagulated and most subtherapeutic. The goal of this study is to examine anticoagulation usage in a contemporary prospective registry of TIA/stroke patients with NVAF and determine whether the introduction of NOACs has increased anticoagulation usage.

Methods:
This is an ongoing single centre observational study. Consecutive TIA/ischemic stroke admissions (2012-13) to a tertiary hospital in Edmonton, Canada with NVAF were enrolled. Data regarding demographic, clinical, antithrombotic treatment and laboratory parameters were collected in a prospectively maintained database. Those with previously diagnosed NVAF were included in the present analysis (149/181). Clinical characteristics were compared between patients on anticoagulants and those on other/no antithrombotic therapy.

Results:
The 149 included patients had a mean (SD) age of 78.7 (10.0) years. Male were 52.3% and 86.6% (129) had a preadmission CHADS2 score ≥2. At the time of TIA/stroke, 51% (76/149) were on an anticoagulant, 24.2% (36/149) on antiplatelet agents and 28.4% (37/149) were on no antithrombotic therapy. Of the 76 patients on anticoagulants, 81.6% were on warfarin and the remaining (18.4%) were on a NOAC. Only 31% of patients on warfarin had a therapeutic INR at the time of stroke. Patients not anticoagulated had a similar frequency of prior stroke (21% vs. 23%; p=0.80) but tended to have a lower CHADS2 score (p=0.082) than those anticoagulated. In patients with CHADS≥2, 47% were not on an anticoagulant.

Conclusions:
Despite therapeutic advances in the treatment of NVAF, anticoagulation usage in TIA/stroke patients with preexisting NVAF remains suboptimal. In this study, only 53% of patients with NVAF and a CHADS≥2 were treated with anticoagulants. This study emphasizes the need for increased efforts to encourage prescribing of oral anticoagulants in high-risk individuals.
Abstract W P348: Evaluating Gaps in the Continuum of Stroke Care
Authors: Tsai Jenny P , Rochon Paula A , Raptis Stavroula , Bronskill Susan E , Bell Chaim M , Saposnik Gustavo
Published: July 2021

Background and Purpose:
Medication adherence is an important factor for secondary stroke prevention in ambulatory care. We aimed to evaluate short-term adherence to antihypertensive and lipid-lowering agents after a new ischemic stroke as a predictor of adherence at one and two years after discharge.

Methods:
A five-year cohort (2003-2008) of patients from eleven institutions participating in the Registry of the Canadian Stroke Network (RCSN) was linked to population-based administrative health records. Patients with a diagnosis of an acute ischemic stroke who were discharged home were included in the study. Medication adherence was assessed through documentation of a filled prescription at seven days, one year and two years from hospital discharge.

Results:
From 2003 to 2008, 6,437 ischemic stroke patients were discharged home from hospital. A total of 1126 patients filled a prescription for antihypertensive and lipid-lowering agents within 7 days of hospital discharge. Patients provided with a prescription at discharge were more likely to be adherent to antihypertensive and lipid-lowering agents at seven days than patients who did not receive a prescription . Adherence at one year (X% vs Y%, p-value=?) was higher in patients who demonstrated adherence at seven days from discharge for antihypertensive (93.8% vs 87.7%, p<0.0001), lipid-lowering agents (88% vs 81.9%, p<0.0001), or both (85.8% vs 79.9%, p<0.0001). Similar findings are noted at two years for antihypertensives (92.2% vs 87.7%, p=0.0003), lipid-lowering agents (82.6% vs 79.0%, p=0.0394), or both (81.1% vs 77.0%, p=0.0099).

Conclusion:
Filling prescriptions within one week of discharge from hospital for acute ischemic stroke predicts adherence for secondary preventive therapies at one and two years. Provision of a prescription at the time of discharge to both prior and new users of anti-hypertensive and lipid-lowering drugs is a simple and effective intervention to improve adherence to secondary preventive medications at seven days, one year and two years after ischemic stroke.
Abstract W P35: Assessment of Collaterals on Day-2 CT Angiography Can Predict Functional Outcome in Thrombolyzed Anterior Circulation Acute Ischemic Stroke
Authors: yeo leonard L , Paliwal Prakash , Teoh Hock Luen , Seet Raymond C , Chan Bernard P , Rathakrishnan Rahul , Ng Kay W , Bharatendu Chandra , Batra Amit , Wakerley Benjamin , Ong Jonathan , Ong Venetia H , Lim Gavin H , Ting Eric Y , Sharma Vijay
Published: July 2021

Background:
Several methods exist that assess the intracranial collaterals on CT-angiography (CTA) of the brain. We compared existing methods for quantification of collaterals on day-2 CTA in thrombolyzed AIS patients to assess their predictive value for functional outcome.

Methods:
Consecutive AIS patients treated with intravenous tissue plasminogen activator (IV-tPA) during 2007-2012 were included. Data were collected for demographics, vascular risk factors, NIHSS scores and stroke subtypes. Intracranial collaterals were evaluated by 2 independent neuroradiologists using 4 existing methods- Miteff’s system (grades middle cerebral artery (MCA) collateral branches with respect to sylvian fissure); Maas system (compares collaterals in affected hemisphere against the contralateral side); Modified Tan’s scale (collaterals in 50% or more of MCA territory classified as good); and 20-point collateral grading scale by Alberta Stroke Program Early CT score (ASPECTS) methodology. Good functional outcome at 3-months was determined by modified Rankin scale (mRS) scores of 0-1.

Results:
Day-2 CTA was performed in 150 patients with anterior circulation AIS treated with IV-tPA. Median age 66yrs (range 33-92), 47% males, median NIHSS 19 points (range 4-34) and median onset-to-treatment time 165 minutes (range 74-274). Overall, 67 (44.6%) patients achieved good functional outcome at 3-months. On univariable analysis- younger age, lower pre-tPA NIHSS scores, atrial fibrillation, good collaterals according to ASPECTS scoring and good collaterals by Maas methodology were significantly associated with good functional outcome. On multivariable analysis, lower NIHSS (OR 1.155 per NIHSS point; 95% CI 1.066-1.251, p=0.001), younger age (OR 1.052 per year; 95% CI 1.012-1.094, p=0.010), good collaterals by Maas methodology (OR 2.805 95% CI 1.122 -7.011, p =0.002) and good collaterals (score of 9 or more) by ASPECTS methodology (OR 3.769 ; 95%CI: 1.327- 10.708, p= 0.013 ) were found as independent predictors of good outcome.

Conclusion:
Of the existing intracranial collaterals scoring systems, only the ASPECTS and Maas methods are reliable predictor of favourable outcome in thrombolyzed anterior circulation AIS patients.
Abstract W P366: Hypothermia Does Not Affect Tissue Plasminogen Activator Activity in Acute Ischemic Stroke Patients as Measured by Thromboelastography
Authors: Archeval-Lao Joancy M , Moser Hope , Riney Stephen A , Kawano-Castillo Jorge , Parker Stephanie A , Cai Chunyan , Rahbar Mohammad H , Ward Eric T , McDonald Mark M , Sangha Navdeep , Grotta James
Published: July 2021

Background:
Currently, t-PA is the only FDA approved treatment for acute ischemic stroke (AIS). Supplementing t-PA with therapeutic hypothermia is being evaluated, but cooler temperatures may affect the enzymatic activity of t-PA. Thromboelastography (TEG) determines coagulation status in whole blood, and has detected hypercoagulability in AIS patients compared to healthy controls. Using TEG, we evaluated the effect of variable degrees of hypothermia on clot formation and lysis in AIS patients receiving t-PA.

Methods:
Between June 2012 -July 2013, venous blood from 18 AIS patients receiving t-PA within 4.5 hours of symptom onset was collected prior to and 10 minutes after t-PA bolus. Blood samples were analyzed by TEG at 30°C, 33°C, and 37°C. The variables of interest were R (initiation of clot formation), K (speed of clot strengthening), Angle α (rate of clot formation), and LY30 (percentage of clot lysis over 30 minutes) (see figure). All statistical analyses were performed using SAS 9.3.

Results:
Baseline R averaged 6.0, 5.6, and 4.6 minutes at 30°C, 33°C, and 37°C (p=0.02),K averaged 2.5, 2.3, and 1.4 (p=0.01),and Angle averaged 59.1, 62.4, and 69.3(p=0.01), indicating slower clotting at lower temperatures. Post t-PA LY30 averaged 93.9, 93.9, 89.8 (p= 0.61, N=18) indicating no effect on t-PA lytic activity at lower temperatures.

Conclusions:
Our data suggest that hypothermia progressively slows clot formation in AIS patients but has no effect on the lytic effect of t-PA as measured by TEG.
Abstract W P369: Inhibitory Effect of FTY720 on Neuroinflammation in Cerebral Ischemia-reperfusion
Authors: Xu Haoliang , Shah Pratik , Pelligrino Dale , Testai Fernando D
Published: July 2021

Background:
Neuroinflammation is a key contributor to brain injury in cerebral ischemia-reperfusion (CIR). FTY720 has been shown to be neuroprotective in animal stroke models. In most studies, FTY720 treatment was initiated either before or shortly after the cerebral insult. The goal of this study is to investigate the effect of FTY720 on CIR-associated neuroinflammation and outcome using a therapeutic window similar to the one utilized in clinical practice.

Methods:
We used the rat middle cerebral artery (MCA) occlusion model for CIR. The right MCA was occluded for 1h followed by reperfusion. Animals were treated with vehicle or 0.5 mg/kg FTY720 intraperitoneally at 3h post-reperfusion. Neurobehavioral test battery (scale from 0 to 21 points with lower scores representing increased neurological deficits), grid-walking test, infarct volume, and brain water content were determined 24h post CIR. A cranial window was established at 24h post occlusion and leukocyte trafficking behavior was monitored by direct microscopic observation of surface venules. Pial venular leukocyte adhesion was expressed as the % of vascular area occupied by adherent rhodamine-6G-labeled leukocytes. Statistical analysis was performed by
t
test.

Results:
Compared to the vehicle group (n=10), FTY720 animals (n=10) had improved neurological score (8.6±1.9 vs. 13.7±1.9; p<0.001) and better motor performance throughout all subsections of the grid test (p<0.001). FTY720 treatment also decreased infarct volume (vehicle: 342±182; FTY720: 122±138 mm
3
; p=0.04) and ipsilateral brain edema, measured as water content (vehicle: 84.5±1.05%; FTY720: 79.4±0.87%, p=0.003). Leukocyte trafficking study showed a significant increase in vascular leukocyte adhesion 24 h post reperfusion in the vehicle group which was markedly decreased by FTY720 treatment (sham: 3.0±0.6%; vehicle: 11.4±2.6%; FTY720: 5.2±1.4%; p<0.001).

Conclusion:
FTY720 given at 3h post reperfusion reduces infarct volume, brain edema, neurological disability, and vascular leukocyte adhesion. These results support the beneficial effect of FTY720 when used in a clinically relevant timeframe and provides direct evidence of the anti-inflammatory effect of FTY720 on CIR.
Abstract W P57: Thrombolytic Therapy in Patients With Mild Stroke: An Observational Study
Authors: Romano Jose G , Smith Eric E , Liang Li , Gardener Hannah , Camp Sara , Shuey Laura , Campo-Bustillo Iszet , Khatri Pooja , Bhatt Deepak L , Fonarow Gregg C , Sacco Ralph L , Schwamm Lee H
Published: July 2021

Objective:
Mild stroke has traditionally been excluded from thrombolytic treatment trials and only few series have reported outcomes after IV rtPA in this group. The objectives of this study are to determine the proportion of mild stroke patients treated with IV rtPA and evaluate complications and short-term outcomes in this population.

Methods:
We analyzed patients in the Get With The Guidelines-Stroke registry that arrived within 4.5 hours from symptom onset with a mild ischemic stroke defined as a baseline NIHSS ≤5 who received IV rtPA between May 2010 and October 2012. The following outcomes and complications were analyzed: in-hospital mortality, home discharge, independent ambulation, length of stay (LOS), in-hospital death, and symptomatic intracranial hemorrhage (sICH) <36 h. Multivariable analysis was performed for predictors of outcomes and complications.

Results:
Of 147,917 patients who arrived <4.5 hours, 39,821 were treated with IV rtPA, of whom 8,243 (20.7%) had an NIHSS ≤5. We analyzed 5,910 treated patients with NIHSS ≤5 and complete data. The mean baseline NIHSS was 3.5 (median 4); 98.2% arrived within 3 hours and 78.6% were treated within 3 hours. Outcomes and predictors of worse outcome are described in the table. There was no difference in short-term outcomes amongst those treated at 0-3 vs. 3-4.5 hours.

Conclusions:
A sizeable minority of ischemic stroke patients treated with IV rtPA have a NIHSS ≤5. sICH occurred at a low rate of 1.8% and about 30% of these patients were unable to return home and could not ambulate independently. Longer-term outcomes are needed to define predictors of poor outcome in this population and which patients may benefit most from treatment.