bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3024: School is Out : Creating Stroke Detectives through Summer Challenge
Authors: Morrison Kathy , Dillon Judith , Watson Gayle
Published: March 2022

Background:
Childhood obesity and early-onset diabetes are on the rise. The American Heart Association Heart Disease and Stroke Statistics indicate that the unhealthy behaviors that are the risk factors for stroke begin with school-aged children. In 2009, our organization created a stroke awareness program for high schools and youth groups that demonstrated retention of knowledge in a pre-post test format. The content was developed to be relevant for that specific age group.

Purpose:
Building on that success and the need for earlier education, we developed a Stroke Detective Summer Challenge for elementary age children.

Method:
This independent, structured program was made available through the stroke center website. Packets were also placed at three local libraries and provided to 3
rd
graders at a local summer day camp. The program content included the stroke detective pledge (written by the stroke program coordinator), an activity book, an exercise & healthy eating log, and a scavenger hunt. To qualify as a stroke detective, participants were required to: 1) sign the pledge; 2) share their stroke knowledge with 5 people by giving them a F.A.S.T. (face, arm, speech, time) card and getting their signatures; and 3) return the signature page along with their completed exercise & healthy eating log and their T-shirt size.

Results:
A summer’s end celebration for the 22 new “stroke detectives” included stations for making a healthy snack and for some simple physical activity competitions. They each received a detective bag, healthy snack recipes, giveaways, and a Stroke Detective T-shirt. These young detectives, along with their parents and siblings were greeted by our hospital mascot and were given a tour of our helicopter. The students, supported by their parents, enthusiastically described their pride in becoming stroke detectives.

Conclusions:
Our previous successful experience with making educational content relevant for specific age groups was repeated in this unique initiative. We demonstrated that stroke awareness education does NOT have to be complex or scary; in fact, by introducing simple facts at a young age, we may help eliminate the fear and ignorance that has made community awareness of stroke such a challenge in the past. They could become the first generation of adults to know that a stroke does not occur in the heart.
Abstract 3053: Combination Niaspan With Bone Marrow Stromal Cell Treatment Of Stroke In Diabetic Rats
Authors: Chen Jieli , Yan Tao , Ye Xinchun , Cui Yisheng , Zhang Chunling , Zacharek Alex , Cui Xu , Roberts Cynthia , Chopp Michael
Published: March 2022

Background and Purpose:
Our previous studies have found that cell therapy with bone-marrow-stromal cells (BMSCs) improves functional recovery after stroke in non-diabetic, but not in diabetic rats. BMSC treatment of stroke in type one diabetic (T1DM) rats increases brain hemorrhage and arteriosclerosis. Niaspan (a prolonged release formulation of niacin) treatment of stroke increases vascular stabilization and decreases arteriosclerosis in wild type (WT) rats. This study investigated the effect of combination therapy of BMSCs with Niaspan on stroke outcome and arteriosclerosis in T1DM rats.

Methods:
T1DM was induced in adult male Wistar rats by injecting streptozotocin. Non-diabetic and T1DM-rats were subjected to 2hours of middle cerebral artery occlusion (MCAo). The rats were treated with: 1) PBS as control; 2) BMSCs BMSCs (3X10
6
) alone; 3) Niaspan (40mg/kg) alone daily for 14 days; 4) BMSCs (3X10
6
)+Niaspan (40mg/kg, daily for 14 days) combination starting at 24 hours after MCAo and rats monitored for 14 days.

Results:
Functional benefit was not detected in T1DM-MCAo treated with BMSCs rats compared to T1DM-MCAo controls. BMSC treatment in T1DM-MCAo-rats had increased mortality, blood-brain barrier (BBB) leakage and brain hemorrhage. Internal carotid artery neointimal formation and cerebral arteriole narrowing/occlusion were also observed in T1DM-MCAo+BMSCs rats compared to T1DM-MCAo controls (p<0.05). We further studied the underlying mechanisms responsible for BMSC-induced BBB leakage and accelerated vascular damage in T1DM-MCAo-rats. We found that the expression of angiogenin (an angiogenic factor) and ED1 (a marker for macrophages) were significantly increased in the T1DM-MCAo+BMSCs rats in the ischemic brain and in the internal carotid artery compared to non-treated T1DM-MCAo rats. However, combination BMSCs with Niaspan significantly improves functional outcome after stroke, decreases Angiogenin, ED1 and MMP9 expression in the ischemic brain as well as decreases brain hemorrhage and cerebral arteriosclerosis compared to T1DM-MCAo control or T1DM+BMSCs alone groups.

Conclusions:
Combination therapy using BMSCs with Niaspan improves functional outcome and decreases BBB leakage and cerebral artery neointimal formation and arteriosclerosis. This therapeutic benefit may be attributed to the combination mediated decreased expression of angiogenin and anti-inflammatory effects.
Abstract 3071: Automated CT Perfusion Processing For the Evaluation of Transient Ischemic Attack
Authors: Kleinman Jonathan T , Zaharchuk Greg , Mlynash Michael , Castle James S , Straka Matus , Lansberg Maarten G , Singh Inder P , Schwartz Neil E , Bammer Roland , Albers Gregory W , Olivot Jean-Marc
Published: March 2022

Introduction:
The diagnosis of transient ischemic attack (TIA) can be difficult. We evaluated the yield of automated CT perfusion (CTP) in addition to non contrast head CT and CT angiography for the detection of acute ischemic lesions among TIA patients and compare it with multimodal MRI [diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI)] results.

Methods:
Consecutive patients with a final diagnosis of transient neurological symptoms secondary to ischemia who underwent acute CT, CTP and CTA were enrolled. A subset of the patients underwent multimodal MRI. Presence of symptomatic stenosis was assessed on CTA by the treating team at the time of patient evaluation. The presence and location of acute ischemic lesions was assessed on: CT, CTP, DWI, and PWI. The rater was blinded to the clinical presentation. The presence of a MR or CT perfusion lesion was assessed using TMax. TMax maps for both CT and MR were automatically generated by RApid processing of PerfusIon and Diffusion (RAPID) software.

Results:
Thirty-three patients were enrolled: median age was 66 years old (IQR 58-82); median ABCD2 score was 4 (IQR 3-5); median delay from symptom onset to CTP was 4.6 hours (IQR 2-9.6). MRI was performed in 23 (70%) patients after a median delay of 20.4 hours (IQR 8.3-30.6) after symptom onset and 5.5 hours (IQR 3.4-20.8) after CTP. No patient experienced recurrence between CTP and MRI. Non-contrast head CT did not demonstrate any acute ischemic lesions. CTA found 3 symptomatic vessel lesions. CTP revealed a focal ischemic lesion in 11 patients (33%). The lesion location concurred with the presumed symptom side in all but one patient, and with the 3 symptomatic vessel lesions found on CTA. DWI was performed in 23 patients, and was positive in 7 (30%). Three of these patients had a negative early CTP. CTP was positive in 3 patients with subsequent normal DWI. MR perfusion was performed in 17 patients and found an acute ischemic lesion in 8 (47%) of them. Four of these MR PWI positive patients also had a positive CTP. In 3 patients with a negative MR PWI, CTP detected an acute ischemic lesion. At least 1 of the 3 modalities (CTP, DWI, PWI) was positive among 10/17 (59%) of patients.

Conclusion:
The results of this exploratory study suggest that automatically processed CTP increases the yield of head CT and CTA for the evaluation of TIA patients. In some cases CTP found evidence of transient focal ischemia that was not detected by MRI, in others CTP was negative and DWI or PWI was positive. These findings suggest that CTP and MRI may be complementary techniques to confirm the ischemic nature of transient neurological symptoms.
Abstract 3135: ABCD
2
Score Can Triage Transient Ischemic Attack (TIA) Patients for Hospitalization
Authors: Regan Elizabeth M , Cutting Shawna , Lee Vivien H , Mohammad Yousef M , Prabhakaran Shyam
Published: March 2022

Introduction:
Following TIA, there is an increased risk for ischemic stroke. Admission to the hospital is advocated for observation, rapid performance of diagnostic tests, and potential acute intervention. The American Heart Association (AHA) recommends admission following a TIA for patients with ABCD
2
scores greater than 3. We aimed to determine the relationship between ABCD
2
scores and acute neurologic deterioration (TIA or stroke) during hospitalization.

Methods:
We reviewed consecutive patients admitted to our institution following a TIA between August 1, 2006 and March 31, 2011. TIA was defined as transient focal neurological symptoms that could be attributed to a specific vascular distribution and lasted < 24 hours. We collected data on demographics, clinical symptoms, duration, risk factors, and in-hospital treatments and outcomes.

Results:
Of 251 patients (mean age 64 years; 45% male), the median ABCD
2
score was 4. The majority had motor symptoms (58.6%) and/or speech/language symptoms (51.4%). Diffusion-weighted imaging was abnormal in 25.9%. The median length of stay was 2.0 days. Nine patients (3.6%) had recurrent TIAs or strokes during their stay (6 TIAs and 3 strokes). All 9 had ABCD
2
scores > 3 while no neurologic deterioration occurred in patients with lower scores (5.3% vs. 0%, P = 0.061). Diffusion lesion frequency did not differ between groups. A total of 13 patients (5.2%) required acute revascularization for large vessel stenosis (6 intracranial; 7 extracranial carotid); none were in the group with recurrent events while hospitalized. No patient received intravenous or intra-arterial thrombolysis. ABCD
2
score did not discriminate those requiring acute revascularization from those who did not (P = 0.242)

Conclusions:
Our findings support the AHA recommendation that TIA patients be considered for hospitalization when ABCD
2
scores > 3 based on a 5% risk of in-hospital deterioration. However, interventions to prevent stroke were equally common in those with low or high ABCD
2
scores. Outpatient evaluation should be considered for those with scores ≤ 3, provided that vascular imaging is performed urgently and treatment can be expedited.
Abstract 3142: Exaggerated K
Ca
Channel Current Activity Accounts for Reduced Myogenic Constriction in the Cerebral Vasculature of the Fawn Hooded Hypertensive (FHH) rats
Authors: Gebremedhin Debebe , Harder David R
Published: March 2022

The ionic mechanism by which pressure induces myogenic arterial constriction is not completely understood. In the present study we compared the Fawn Hooded Hypertensive (FHH) rat strain bred that does not autoregulate CBF and the FHH.1
BN
rat strain created by transfer of a 2.6 Mb region of a Brown Norway (BN) rat chromosome 1 and introgressed into the FHH genetic background and recovered the myogenic phenotype, with respect to K
Ca
channel activity and pressure-induced myogenic constriction. We investigated the functional role of Ca
2+-
activated K
+
channel in the impaired pressure-induced myogenic response in cannulated and pressurized middle cerebral arterial segments of FHH and compared with that of the FHH.1
BN
rat strain. The cannulated arterial segments of FHH rat strain elicited significantly reduced pressure-induced myogenic constriction, whereas those of the FHH.1
BN
exhibited more than 40-50 % constriction or reduction in diameter during step increases in intravascular pressure from 40 to 140 mmHg. Pretreatment of the he FHH rat cerebral arterial segments with the K
Ca
channel inhibitor iberiotoxin (100 nM) rendered the FHH rat cannulated arterial segments elicit near equal level of myogenic constriction as that of the FHH.1
BN
. The magnitude and density (pA/pF) of a macroscopic whole-cell K
Ca
channel current recorded from FHH and FHH.1
BN
rat cerebral arterial muscle cells during a 10 mV step depolarization from -70 mV to +80 mV was 2- to 3-fold greater in the FHH than that in the FHH.1
BN
rat cerebral arterial muscle cells. Similarly, the NPo of the K
Ca
single-channel currents recorded at +40 mV using symmetrical KCl solution was significantly higher in the FHH (0.0035 ± 0.0002) than in the FHH.1BN (0.0013 ± 0.0003, n =5), albeit the unitary conductances were not different. These findings indicate that exaggerated K
Ca
channel current activity in the FHH rat cerebral arterial muscle cell membrane could account for the impaired pressure-induced myogenic constriction in the FHH rat strain and may have implications for stroke susceptibility in the FHH rat model.
Abstract 3155: Hospitalization Costs for Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis in the United States are Substantially Higher than Medicare Payments
Authors: Brinjikji Waleed , Rabinstein Alejandro A , Cloft Harry J
Published: March 2022

Background and Purpose-
IV rt-PA has become a widely accepted treatment for a select group of patients with acute ischemic stroke. Quantifying the costs of hospitalization is important for understanding the economic impact of these patients on the hospitals that care for them. We evaluated recent data to determine costs associated with hospitalization for acute ischemic stroke patients treated with intravenous thrombolysis, including subgroup analysis to determine the effects of age and discharge status on hospital costs.

Methods-
Using the National Inpatient Sample, we evaluated the costs for hospitalization for patients treated with intravenous thrombolysis for acute ischemic stroke in the United States from 2001-2008. The primary endpoint examined in this study was total hospital costs, and these were correlated with clinical outcome. Costs were compared with 2008 Medicare reimbursement for intravenous thrombolysis without complication, and intravenous thrombolysis with major complication.

Results-
A total of 63472 patients received intravenous thrombolysis for acute ischemic stroke. 24094 patients were <65 years old and 40780 patients were ≥65 years old. Median hospital costs in 2008 dollars were $14102 (IQR $9987-$20819) for patients with good outcome, $18856 (IQR $13145-$30423) for patients with severe disability, and $19129 (IQR $11966-$30781) for patients with mortality. Average 2008 Medicare payments were $10,098 for intravenous thrombolysis without complication and $13,835 for intravenous thrombolysis with major complication.

Conclusions-
Our study of the NIS shows that hospitalization costs in the United States for ischemic stroke patients treated with intravenous thrombolysis are rather high. Medicare payments have not been adequate reimbursement for these hospitalizations. Hopefully, future reconciliation of costs with payments will be feasible, so that hospitals can afford to provide proper care for ischemic stroke patients treated with intravenous thrombolysis.
Abstract 3194: Bevacizumab (Avastin) Crosses the Blood-brain Barrier and Attenuates VEGF-induced Angiogenesis and Vascular Dysplasia in an Adult Mouse Model of Brain Arteriovenous Malformations
Authors: Walker Espen J. , Su Hua , Shen Fanxia , Jun Kristine , Degos Vincent , Amend Gregory , Young William L.
Published: March 2022

Background and Purpose:
The lesional phenotype of human brain arteriovenous malformation (bAVM) includes increased VEGF expression compared to normal brain. We developed an adult mouse model of bAVM by focal VEGF overexpression coupled with regional deletion of the Alk1 gene. Alk1 deletion alone was not sufficient to cause the bAVM phenotype, demonstrating VEGF plays a crucial role in bAVM pathogenesis. Bevacizumab (rhuMab VEGF; Avastin) is used to treat diseases characterized by pathologic angiogenesis. We hypothesized that bevacizumab would attenuate VEGF-induced brain angiogenesis and vascular dysplasia, once established, in the model.

Methods:
Angiogenesis was induced in the brain of wild-type (WT) C57BL/6 mice by stereotactic injection of 2X109 genome copies (gcs) of adeno-associated viral vector expressing human VEGF (AAV-VEGF) into the basal ganglia. Six weeks later, bevacizumab (1, 5, 10, and 15 mg/kg) was administered intraperitoneally (IP) every other day for 10 days. Vessel density and Ki67-positive endothelial cell proliferation was quantified on sections of lectin-perfused brain (n=6/group). Bevacizumab (5 mg/kg) was administered for 10 days to our mouse bAVM model with AdCre (2X107 PFU) and AAV-VEGF (2X109 gcs) injected Alk1 floxed mice (loxP flanking exons 4-6) six weeks after vector injection. Trastuzumab (rhuMab HER2; Herceptin) was used as control treatment (n=7/group). Vessel density, dysplasia index (vessels >15 µm per 200 vessels), and anti-human IgG staining were assessed.

Results:
All doses above 1 mg/kg of bevacizumab inhibited AAV-VEGF-induced brain angiogenesis in WT mice (p<0.05) as compared to trastuzumab (15 mg/kg) treated controls. Positive staining of anti-human IgG was detected in the brain parenchyma at the VEGF-induced angiogenic foci of mice treated with bevacizumab and trastuzumab. Bevacizumab (5 mg/kg) treatment decreased Ki67 positive endothelial cells (p=0.04) as compared to the trastuzumab treated controls. In our mouse model of bAVM, bevacizumab (5 mg/kg) treatment reduced both vessel density (p=0.01) and dysplasia index (p=0.02) as compared to trastuzumab treatment.

Conclusions:
This is the first study to demonstrate penetration of bevacizumab and trastuzumab into VEGF-stimulated brain after IP injection, indicating that IP-delivered bevacizumab or trastuzumab can penetrate the blood-brain barrier in VEGF-stimulated WT brain regions. Bevacizumab led to a reduction of VEGF-induced brain angiogenesis and endothelial cellular proliferation in WT brain. Bevacizumab also reduced vessel density and cerebrovascular dysplasia in a model of bAVM. Further studies on the use of anti-angiogenic therapy in bAVM are warranted.
Abstract 3207: Pre-procedural International Normalized Ratio and Hemorrhagic Complications associated with Neurointerventional Procedures
Authors: Martin Andrew D , Chaudhry Saqib A , Kainth Hunar , Hussein Haitham M , Rodriguez Gustavo J , Suri M. Fareed K , Qureshi Adnan I
Published: March 2022

Background:
Pre-procedural elevated international normalized ratio (INR) is associated with higher bleeding complication but the role of INR elevation in determining the rate of bleeding complications in minimally invasive neurointerventional procedures is not known.

Methods:
We retrospectively analyzed the rates of hemorrhagic complications associated with consecutive neurointerventional procedures at two comprehensive stroke centers from July 2009 through June 2011. Patients with hemorrhage prior to the procedure were excluded. We ascertained any intra or extracranial hemorrhagic complications within 24 hours of the procedure. The severity of hemorrhagic complications were classified according to the Global Use of Strategies

to Open Occluded Coronary Arteries (GUSTO) classification into severe or life-threatening (either intracranial hemorrhage or bleeding that causes hemodynamic compromise and requires intervention); moderate (bleeding that requires blood transfusion but does not result in hemodynamic compromise); and mild (bleeding that does not meet criteria for either severe or moderate bleeding).

Results:
A total of 551 procedures were reviewed (49% women, mean age [≠SD] 56±17 years). The procedures performed included mechanical thrombectomy/intra-arterial thrombolysis (n=87), endovascular treatment of cerebral vasospasm (n=84), carotid artery angioplasty/stent placement (n=82), aneurysm embolization (n=65), intracranial angioplasty/stent placement (n=47), extracranial vertebral angioplasty/stent (n=29), tumor embolization (n=23), AVM embolization (n=20), and other procedures (n=114). Of these procedures, 21 procedures were performed in patients with pre-procedure INR of 1.5 or greater. After The rates of severe or life-threatening bleeding was higher in patients with pre-procedural INR greater than or equal to 1.5 compared with those with pre-procedural INR less than 1.5 (24% vs. 7.0%, p=0.0165). After adjusting for age and gender, the difference between the groups remained statistically significant (odds ratio 3.80, 95% CI 1.27-11.375). The rates of moderate and minor bleeding complications were similar in patients stratified by pre-procedure INR.

Conclusions:
Our study demonstrates that patients who undergo neurointerventional procedures with pre-procedure INR of 1.5 or greater have a three-fold higher risk of severe or life-threatening bleeding and neurointerventional procedures should be avoided.
Abstract 3216: Early Insulin Intervention Improves Tissue Plasminogen Activator Thrombolytic Therapy In A Focal Embolic Stroke Model Of Diabetic Rats
Authors: Fan Xiang , Lo Eng H , Wang Xiaoying
Published: March 2022

Background:
Stroke patients with diabetes mellitus or post-stroke hyperglycemia are associated with resistance to tPA reperfusion, higher risk of intracerebral hemorrhage and worse neurological outcomes. Our laboratory has established an embolic focal stroke model in type I diabetic rats that closely mimic the clinical situation with worse neurological outcomes observed after tPA thrombolysis. Clinically insulin intervention did not show significant benefit to acute ischemic brain injury, perhaps due to the relatively late infusion time after stroke onset. In this study for the first time we aimed to test effects of early insulin intervention combined with following tPA thrombolytic therapy in neurological outcomes of focal embolic stroke model in type I diabetic rats.

Methods:
Type I diabetic rats were induced by standard Streptozotocin i.p. injection. Six weeks type I diabetes rats were subjected into a focal embolic stroke. Four treatment groups: (1) saline at 1.5 hours after stroke; (2) standard rat dose 10 mg/kg of tPA at 1.5 hours after stroke; (3) insulin (i.h. 4 units and i.v. 2 units) at 1 hours plus saline at 1.5 hours; (4) insulin (i.h. 4 units and i.v. 2 units) at 1 hours plus 10 mg/kg tPA at 1.5 hours. Acute neurological outcomes were measured at 24 hours after stroke onset for brain infarction, hemispheric swelling, and hemorrhagic transformation.

Results:
Blood glucose level of diabetic rats was 484±92 mg/dl at before stroke. Insulin infusion significantly decreased blood glucose levels. At 2.5 hours after stroke, blood glucose levels were 515±94 mg/dl for saline, 509±98 mg/dl for tPA alone, 325±77mg/dl for insulin plus saline, and 295±64 mg/dl for insulin plus tPA, respectively. At 24 hours after stroke, tPA slightly reduced infarction volume than saline group. Insulin significantly reduced 24% of brain infarction in tPA group, but not in saline group (11% reduction) compare to non-insulin controls. Insulin significantly decreased hemispheric swelling in both saline (40% reduction) and tPA groups (43% reduction). tPA treatment significantly increased hemorrhagic volume (6.23μ l/hemisphere), but insulin intervention eliminated the increased hemorrhagic volume (4.45μ l/hemisphere) elevated by tPA thrombolytics.

Discussion and Conclusion:
Early insulin intervention may be safe and beneficial to tPA thrombolytics in reducing infarction volume, edema and intracerebral hemorrhage to ischemic stroke with diabetes mellitus or post-stroke hyperglycemia. Further investigations are needed for fully evaluating the early insulin intervention in preclinical settings and define underlying molecular mechanisms, in terms of optimizing its therapeutic effects in both safety and efficacy before clinical tests can be applied.
Abstract 3224: Reasons for Disability after “Mild” Ischemic Strokes: A Retrospective, Exploratory Analysis
Authors: Khatri Pooja , Sucharew Heidi , Alwell Kathleen , Moomaw Charles , Kleindorfer Dawn O , Flaherty Matthew , Woo Daniel , Adeoye Opeolu , Ferioli Simona , Kissela Brett
Published: March 2022

BACKGROUND:
Prior studies have reported that approximately one-third of patients with strokes perceived as mild at onset and not treated with IV rtPA have significant disability at three months. Disability after stroke in this setting could be due to: (1) the initial stroke event, including its early progression, (2) stroke recurrence, or (3) other medical events related to medical comorbidities. We sought to explore these three potential reasons for disability among mild ischemic stroke subjects in a longitudinal study of stroke outcomes in consideration of planning a large-scale randomized trial of acute intervention.

METHODS:
During 2005, a convenience sample of 460 ischemic stroke patients was drawn from a population-based cohort and prospectively recruited. Clinical characteristics were obtained by detailed chart abstractions, and in-person or phone interviews at three months. NIHSS scores at stroke onset were determined retrospectively by chart review using validated methods. This analysis was limited to mild stroke patients (NIHSS 5 or less), with no prior disability (mRS 0-1), not treated with IV rtPA, and with three-month outcome data. We prespecified groups of characteristics potentially associated with each of the three reasons for disability after mild stroke as shown in the
Table
. We also reviewed unstructured patient accounts of reasons for disability at their 90-day interviews.

RESULTS:
Among 460 patients, 291 (63%) were considered mild at onset; 96 with prior disability, 2 with IV rtPA treatment, and 17 missing all three-month outcome data were excluded. Among the remaining 176 patients, 95 (54%) had poor outcomes (mRS 2-6) at three months: 53% mRS2, 33% mRS 3, 9% mRS 4, 2% mRS 5, 3% mRS 6 (dead). Characteristics of those with disability at three months, compared to those without disability, are shown in the table below. Upon reviewing interview notes by study nurses containing self-reported descriptions of 90-day disability, 55 of 95 (58%) disabled patients attributed their disability to focal neurological dysfunction, and an additional 30 (31%) attributed it to unspecified gait difficulties.

CONCLUSIONS:
A substantial portion of disability may be due to the incident stroke event. Stroke recurrence and other medical comorbidities likely play a role in the 90-day disability rates of this patient population as well. This study is limited by its exploratory and retrospective nature. Large-scale prospective data in the setting of a randomized trial of an intervention is justified.
Abstract 3280: Cystatin C, a Novel Indicator of Kidney Function, Reflects Severity of Cerebral Small Vessel Disease
Authors: Oh Mi-Young , Lee Seung-Hoon , Kim Chi Kyung , Ko Sang-Bae , Kim Beom Joon , Ryu Wi-Sun , Kim Do Houng , Park Hong-Kyun , Yoon Byung-Woo
Published: March 2022

Background:
Recent studies reported that lacunar infarction, white mater lesions (WMLs) and microbleeds (MBs) might be associated with kidney disease. Cystatin C is, competitive inhibitors of lysosomal cysteine protease, suggested to be a more accurate and sensitive indicator of kidney function, compared to creatinine, creatinine based estimated glomerular filtration rate (GFR). We investigated whether Cystatin C might reflect the severity of cerebral small disease.

Methods:
Data prospectively collected on subjects with ischemic stroke or transient ischemic attack to a university medical center was analyzed between January 2008 and May 2011. The severity of WMLs was rated using visual rating scale: normal, no lesion or single one, moderate, multiple focal lesion, extensive, multiple confluent lesion scattered throughout white mater. That of MBs was graded according to the number of MB: normal, absence of MB, mild, 1-4, moderate, 5-9, severe, ≥10. GFR were classified to four categories based on the chronic kidney disease criteria. Multivariable ordinal logistic regression analysis, adjusted confounders-age, gender, hypertension, diabetes, hyperlipidemia, smoking, history of stroke, heart disease and total cholesterol, was performed to determine the association between Cystatin C and severity of small vessel disease.

Results:
A total of 699 subjects were enrolled in this study. Subjects with more severe small vessel disease were likely to be older, have hypertension and history of stroke. The proportion of higher grade of WMLs and MBs was increased according to quartiles of Cystatin C. Compared to lowest quartiles(<47.2 nmol/L), higher Cystatin C quartiles (47.2 -54.7, 54.7-65.7, 65.7≥nmol/L) were likely to have more severe WML grades. [Adjusted OR (95%CI), 1.38(0.93, 2.04), 2.67( 1.81, 3.95), 3.32(2.23, 4.93)]. In addition, higher Cystatin C quartiles tended to have more severe MB grades [adjusted OR (95%CI), 0.98(0.61, 1.51), 1.57(1.00, 2.44), 2.19(1.40, 3.40)]. Compared to the lowest categories of estimated GFR (≥60 ml/min/1.73m2), higher categories of estimated GFR(45.0- 60.0, 15.0-45.0, ≤15.0 ml/min/1.73m2) did not show significant association with the grades of small vessel disease.

Conclusion:
Vascular beds of brain and kidney had similar characteristics. Patients with impaired kidney function would have also cerebral small vessel disease. Cystatin C is more accurate indicator of kidney function to detect subclinical kidney disease. In this present study, Serum Cystatin C reflects severity of cerebral small vessel disease, independent of estimated GFR.
Abstract 3304: Trend of Stroke Incidence in Korean Population: Namwon Stroke Registry, 1998-2007
Authors: Jeong Seul-Ki , Shin Min-Ho , Kweon Sun-Seog , Nam Hae-Sung , Lee Young-Hoon
Published: March 2022

Background and Purpose:
Stroke is the second-leading cause of death and a leading cause of long-term disability in South Korea. However, population studies on stroke incidence and case fatality rates have not been performed. The present study was aimed to determine the incidence of stroke in a defined population of Korea.

Methods:
Data were obtained from the Namwon Stroke Registry, covering approximately 100,000 residents of Namwon city, Jeonbuk province, South Korea. All patients with first-ever stroke that occurred from January 1998 to December 2007 were enrolled. Diagnostic criteria for stroke were guided by World Health Organization and all the possible neuroimaging including computed tomogram and magnetic resonance imaging were reviewed to confirm the subtypes of stroke. The age-standardized incidence rates (ASR) per 100,000 person-years for adults aged 20 yrs and more were calculated.

Results:
About 1229 (men: 563 and women: 666) patients were registered as the first-ever stroke during the 10 years. The mean (± SD) age was 64.1± 12.6 yrs in men and 68.5 ± 11.2 in women. The crude incidence rate (per 100,000) was 221.7 for men and 239.8 for women. The ASR was 171.3 for men and 171.5 for women. Stroke subtype-specific incidence rates were 114.1 for men and 104.2 for women for cerebral infarction, 43.8 for men and 44.1 for women for intracerebral hemorrhage and 13.0 for men and 21.1 for women for subarachnoid hemorrhage. The ASR for ischemic stroke and subarachnoid hemorrhage across the two observation periods (1998-2002 and 2003-2007) has been increased in both sexes (from 110.4 to 117.7 for men and from 96.6 to 112.3 for women in ischemic stroke, and from 11.2 to 14.9 for men and from 18.8 to 23.7 for women in subarachnoid hemorrhage, respectively), while the ASR for intracerebral hemorrhage has been declined in both sexes (from 48.5 to 39.5 for men, from 54.3 to 35.1 for women, respectively).

Conclusions:
The incidences of ischemic stroke and subarachnoid hemorrhage have been increased during the past 10 years, while that of intracerebral hemorrhage has been decreased in both sexes in the Korean population. More efforts are needed for an effective primary prevention of ischemic stroke.
Abstract 3320: There Is No Difference in Outcomes of Wake-Up Stroke vs. Stoke While Awake. An Analysis from The International Stroke Trial: A Large Prospective Randomized Trial
Authors: Moradiya Yogesh , Panichpisal Kessarin , Janjua Nazli
Published: March 2022

Background:
Most acute stroke treatments have restricted therapeutic windows. Approximately a quarter of stroke patients awaken from sleep with symptoms and are precluded from intervention due to extensive times from last known well state. A single center retrospective study showed worse stroke severity and early functional outcomes after wake-up stroke (WUS) compared with stroke while awake (SWA). A population based study has shown demographic and clinical differences between WUS and SWA.

Objective:
The primary aim of our study was to confirm or refute the findings from the previous studies that WUS has worse outcomes. We also compared the demographic and clinical characteristics and inpatient complications between the two groups.

Methods:
Data from the International Stroke Trial were analyzed. Comparisons were made between WUS and SWA using χ
2
, student t-test, and Mann-Whitney-Wilcoxon rank sum analyses. Logistic regression analyses were performed to calculate independent effect of WUS in predicting various clinical outcomes.

Results:
After excluding cases with final diagnosis other than ischemic stroke, 5,152 (29.6%) patients with WUS and 12,246 (70.4%) patients with SWA were included in the analysis. There were no significant differences in age, gender or stroke severity scale between the two groups (
Table 1
). Atrial fibrillation was significantly less common (15.7% vs. 17.8%) and rate of lacunar stroke was higher (27.5% vs. 22.9%) in the WUS group. WUS patients had a lower unadjusted mortality at six months (20.4% vs. 22.2%, p=0.01). We found no differences in adjusted odds of inpatient mortality (OR 0.97; 95%CI:0.81-1.16), complete recovery (OR: 0.93; 95%CI:0.84-1.03), functional independence (OR:1.02; 95%CI:0.93-1.12) and mortality at six months (OR: 0.95; 95%CI:0.84-1.07) between WUS and SWA. The discharge disposition and the rates of recurrent ischemic stroke, intracranial hemorrhage, hemorrhagic transformation of ischemic stroke and major non-cerebral bleeding were also similar (
p
>0.05).

Conclusions:
Clinical severity and rates of inpatient complications are similar between WUS and SWA. Even though mortality at six months is lower with WUS, the effect is non-significant when controlled for confounding factors. Outcomes at six months are similar between the two groups.
Abstract 3327: The Combination Therapy of Chemical Chaperone and n-NOS inhibitor Affords Enhanced Neuroprotection in a Rodent model of Ischemic Stroke associated with Comorbid Type 2 diabetes
Authors: Srinivasan Krishnamoorthy , Sharma Shyam S
Published: March 2022

Ischemic stroke involves complex and multiple pathomechanisms along with underlying comorbidities. Combination therapies have long been recommended by STAIR committee for the successful stroke treatment. The augmentation of nitrosative and endoplasmic reticulum (ER) stress has been postulated in pathogenesis of cerebral ischemia/reperfusion (I/R) injury associated with diabetes. We investigated whether combination of tauroursodeoxycholic acid (TUDCA), a chemical chaperone and 3-bromo- 7-nitroindazole (3-BNI), nNOS inhibitor would protect against diabetes-exacerbated focal cerebral I/R injury. Transient focal cerebral ischemia was induced in high fat diet-fed and low-dose streptozotocin-treated type 2 diabetic rats. Histological (brain infarct, oedema volume) and functional outcomes (neurological score) were evaluated after 2 hours/22 hours of I/R in diabetic rats. Further, immunohistochemical and TUNEL analyses were performed for detecting the changes in in-situ expression of ER stress/apoptosis markers [GRP78 and CHOP/GADD153] and DNA fragmentation in penumbral brain region, respectively. The diabetic rats after cerebral I/R showed significant increase in brain infarct, oedema volume and functional neurological deficits compared with sham-operated rats. Acute administration of TUDCA (100 mg/kg) or 3-BNI (10 mg/kg) per se exhibited no significant neuroprotective effects as compared to vehicle-treated diabetic I/R rats. Interestingly, the combination of TUDCA (100 mg/kg) and 3-BNI (10 mg/kg) showed synergistic and enhanced neuroprotection as evidenced by significantly greater reduction in brain infarction, oedema volume and functional neurological deficits as compared to respective monotherapy. Further, there was marked lowering of apoptotic DNA fragmentation accompanied in parallel with enhanced reduction of GRP78 and CHOP/GADD153 immunoreactivity. The effects were observed independent of changes in blood glucose level. The results of our study demonstrates the enhanced neuroprotection with combination of TUDCA and 3-BNI in ischemic stroke model associated with comorbid type 2 diabetes which may be attributed to greater attenuation of ER stress/apoptosis.
Abstract 3338: Marked Increase in Proportion of Patients over 80 years Treated with iv Thrombolysis and Registered in SITS (Safe Implementation of Treatments in Stroke) Coincides with Publications
Authors: Wahlgren Nils G , Ford Gary A , Lees Kennedy R , Ahmed Niaz , Toni Danilo ,   SITS Investigators
Published: March 2022

Objectives
. A prompt increase in patients treated in the extended time window 3-4.5 h after stroke onset was noted in the SITS registry after publication of the results of ECASS III (NEJM 2008) and the SITS-ISTR 3-4.5 h cohort (Lancet 2008). Within a few months the proportion increased from around 7% to a plateau of 20%. In November 2010, three studies were published describing SITS and VISTA (Virtual International Stroke Trials Archive) data on safety and efficacy of i.v. thrombolysis in the elderly population (Mishra et al, Stroke 2010, Ford et al, Stroke 2010; Mishra et al, BMJ 2010). We tested for a similarly rapid response to the publications of results in the elderly .

Methods:
Between 1
st
January 2007 and 30
th
June 2011, 36,753 patients treated with i.v. thrombolysis were registered in SITS, of whom 4,458 were over 80 years (12.1%). We examined the quarterly rates and 95% confidence intervals of patients over age 80 treated with i.v. thrombolysis. Since all 3 studies were published around November 2010, we compared the rates in the intervals Q1 2007-Q3 2010 and Q4 2010- Q2 2011.

Results:
The proportion of elderly (over 80 years) was 11.1 % (95% CI 10.8-11.5) across Q1 2007 to Q3 2010, From Q4 2010 to Q2 2011 it increased to 17.5 %, (95% CI 16.5-18.5, (p<0.0001). The proportions during 2010 Q1-Q3 were 10.6%, 11.9%, 11.3% (pre-publication) and during 2010 Q4 to 2011Q216.9%, 16.4% and 19.3% (post-publication).

Conclusions:
A statistically significant increase in the proportion of elderly treated with i.v. thrombolysis was observed from the fourth quarter of 2010. The relative increase approached 60% and coincided with three publications of safety and efficacy of i.v. thrombolysis in the elderly based on VISTA and SITS data. Our observations suggest a rapid implementation of new data by the medical community and underline the value of analyses of observational data from SITS and VISTA for the very elderly who were excluded or under-represented in the key clinical trials.
Abstract 3370: Symptomatic Intracranial Haemorrhage And Heparin: Interrelation Between Dose, Timing And Stroke Severity In The International Stroke Trial (ist)
Authors: Bath Philip M , Hogg Cheryl , Berge Eivind , Wardlaw Joanna , Sandercock Peter
Published: March 2022

Background:
Heparin increases the risk of haemorrhagic transformation following acute cerebral infarction but the relationships to dose and timing of treatment is unclear.

Method:
The relationship between symptomatic intracerebral haemorrhage (SICH), heparin dose and timing, and patient factors were explored with data from the International Stroke Trial. This study was a factorial randomised controlled trial of subcutaneous heparin (given twice daily as 5,000 or 12,500 iu), aspirin (300 mg daily), both, or neither started within 48 hours and given for up to 14 days after acute ischaemic stroke. Of 19,435 randomised patients, 17,398 with CT-confirmed ischaemic stroke were included in the present analysis. Multiple variable analyses were adjusted for age, sex, severity (number of neurological impairments, 0-8), heparin dose, aspirin treatment and time to randomisation (as a surrogate for time to treatment).

Results:
SICH occurred in 122 (0.7%) of patients within 14 days of randomization and peaked on day 1 post-randomisation. SICH was associated, in univariate analyses, with younger age (odds ratio, OR 0.98, 95% confidence intervals, CI 0.97-0.99), male sex (OR 1.52, 95% CI 1.05, 2.20), severe stroke (OR 1.49 per impairment, 95% CI 1.29, 1.71) and medium dose heparin (OR 4.93, 95% CI 3.20, 7.61), and inversely with time to randomisation (OR 0.97, 95% CI 0.95-0.98). In multiple variable analysis, SICH remained associated with the same factors, in particular severe stroke (OR 1.49, 95% CI 1.29, 1.72) and medium dose heparin (OR 4.97, 95% CI 3.22, 7.67), and inversely with time to randomisation (OR 0.97, 95% CI 0.96-0.99).

Conclusion:
The risk of SICH increased with severity of stroke, heparin dose and a short time from stroke to treatment. The potential risk of SICH with early anticoagulation should be considered if heparin therapy is required in patients with acute ischaemic stroke.
Abstract 3376: Utilization of Physician Services within the First Month after Hospitalization for Ischemic Stroke
Authors: Lichtman Judith H , Jones Sara B , Wang Yun , Leifheit-Limson Erica C , Goldstein Larry B
Published: March 2022

Background:
Stroke poses significant burdens on patients, their families, and informal caregivers in the days following hospitalization. Limited data are available assessing patient use of immediate poststroke outpatient services. Service utilization patterns have implications for understanding continuity of care and may affect 30-day mortality and readmission rates, measures being used in other conditions as indicators of the quality and efficiency of hospital-leve care.

Objective:
To determine physician specialty, frequency, and most common reasons for physician office visits for Medicare beneficiaries within 30 days of hospital discharge after an ischemic stroke.

Methods:
Data were derived by linking a 5% sample of Part B Medicare data (physician carrier file) with Part A inpatient data. The study cohort included fee-for-service beneficiaries 65+ years of age with a primary discharge diagnosis of ischemic stroke (ICD-9 433, 434, 436) in 2006 with linked in-patient and physician visit data. The 10 most frequent reasons for physician office visits were identified using principal ICD-9 diagnosis codes. Physician specialty was identified using the CMS provider specialty code.

Results:
Among 10,230 identified ischemic stroke patients, 9,523 were discharged alive and included in the study. Of these patients, 16% were rehospitalized for any cause, 42% had at least one hospital outpatient visit, and 88% had at least one physician office visit within 30 days. Primary reasons for physician office visits included stroke, atrial fibrillation, hypertension, diabetes, and heart failure (
Table
). Internists were seen most frequently, followed by radiologists, cardiologists, and family practice physicians. There were 1,449 visits to neurologists and 1,355 visits to physical medicine and rehabilitation physicians.

Conclusion:
Almost 90% of Medicare beneficiaries discharged with ischemic stroke were seen in a physician’s office within the first month. Reasons for visits included stroke as well as other cardiovascular conditions and common stroke risk factors. Additional research is needed to determine the accuracy of physician codes for follow-up visits as well as to assess how the utilization of outpatient services within the early recovery period influences 30-day mortality and readmission rates.
Abstract 3389: Why Warfarin was not used for Stroke Prevention in Atrial Fibrillation: A Detailed Review of Electronic Medical Charts
Authors: Roseman Marc B , Baker Layla , Jing Yonghua , Makenbaeva Dinara , Meissner Brian , Simon Teresa A , Wiederkehr Daniel
Published: March 2022

Purpose:
In an automated analysis of Regenstrief Medical Record System (RMRS) data, approximately half of patients with atrial fibrillation or flutter (AF) and a CHADS2 score of ≥2 had not been treated with warfarin for stroke prevention. The automated query of diagnoses and other coded patient data identified predefined barriers to warfarin use (e.g. history of bleeding, alcohol abuse, or history of falls) in only about half of these patients. Therefore, a detailed review of electronic medical charts (including text reports) was conducted to explore why patients with AF at high risk of stroke are not treated with warfarin.

Methods:
This retrospective study was a review of records from 1998 to 2007. Patients older than 18 with a diagnosis of non-valvular AF, CHADS2 score ≥2, at least one RMRS encounter within one year after the first record of AF diagnosis, and no barrier to warfarin in the automated RMRS analysis were included. A structured chart abstraction form was used to extract data. To confirm AF diagnosis, a record of AF in a clinical problem list, admission/discharge/progress report, or EKG report was required. In patients with confirmed AF, reasons why warfarin had not been prescribed were searched for, through one-by-one review of the patients, in the clinicians’ user interface. This interface displays laboratory results, diagnoses, medications, and text reports such as hospital admission and discharge summaries. Explicit (treating physician’s rationale) and implicit (potential barriers that were documented but not explicitly attached to the warfarin decision) reasons why warfarin was not used were reported using descriptive statistics.

Results:
Among 408 patients (mean age 73.6; 62% women), the distribution of CHADS2 scores at baseline was 2: 49%; 3: 34%; 4:12%; and 5+:6%. AF diagnosis was confirmed in 319 patients, 41% (132) of whom did not have any records in the RMRS explaining why they were not on warfarin. Among the 59% (187) with reasons (explicit 47%, or implicit 53%) why warfarin had not been started, the most common category (52% of 187) was indicative of the risk of bleeding: either the risk of fall (40%) or a history of recent bleeding (13%). The second most common category (16% of 187) reflected that the patient was back in sinus rhythm: the AF was “intermittent,” “situational,” or paroxysmal, or had been converted or ablated. Other reasons included the patient’s desire not to take warfarin, use of enoxaparin, loss to follow up, or death.

Conclusion:
Many patients with AF and at high risk of stroke are not treated with warfarin, and reasons for not using warfarin could not always be identified in patient records. Among patients with reasons recorded in charts, the most common reasons for not prescribing warfarin were indicative of avoiding the increased risk of bleeding.