bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract NS11: An Integrated Biplane Angiosuite Within The NICU Reduces Time From CT Imaging To Groin Puncture.
Authors: Glenn Brenda A , Horn Christopher , Sun Chung-Huan , Nogueira Raul G , Belagaje Samir R , Patel Vishal , Thomas Tommy T , Anderson Aaron M , Frankel Michael , Gupta Rishi
Published: July 2021

INTRODUCTION:
Time delays to reperfusion in endovascular therapy for acute ischemic stroke (AIS) are multifactorial. We investigated a prototypical NICU design, consisting of an angiosuite and CT scanner within the same unit, to determine its impact on CT to groin puncture (GP) times. Patients arriving from outside hospitals (OSH) directly to the NICU were compared to patients who went through our local Emergency Department (ED).

METHODS:
We conducted a retrospective analysis of 230 patients from a prospectively maintained database from October 2010- June 2012 who underwent endovascular therapy for AIS. A univariate analysis was performed comparing patient characteristics between the two populations to identify differences in time intervals from CT imaging to GP.

RESULTS:
Of the 195 patients included in the analysis, 125 (64%) patients were from OSH. The patient characteristics in both groups were similar, with the exception of lower rates of hypertension (67% vs 81%; p<0.02), longer times intervals from last known normal to GP (median 310 mins vs. median 221 mins; p <0.01), and lower pre-treatment ASPECTS (48% <8 vs. 25% <8; p <0.01) among OSH patients. Patients transferred from OSH had significantly lower times from in-house CT to GP as compared to patients from the ED (44.2 +/- 33 mins vs. 114 +/- 58 mins; p<0.01). Despite an increased number of non-contiguous multimodal imaging studies performed on ED patients compared to those from OSH (37% vs 5%; p<0.01), exclusion of these patients still resulted in a significant reduction in time from CT to GP (41.9+/- 27 mins vs. 95.8+/-40.3 mins; p<0.01) among OSH transfers.

CONCLUSIONS:
The integration of a biplane angiosuite within the NICU reduces the times from CT imaging to GP, thereby lowering the times to reperfusion, and hopefully, patient outcomes.
Abstract TMP101: Impact of Age at Stroke on Cognitive Outcome in Children: Selective Vulnerability of Younger Children
Authors: Plumb Patricia , Stavinoha Peter L , Holland Alice A , Dowling Michael M
Published: July 2021

Background & Purpose:
Long term cognitive deficits among pediatric stroke survivors have a significant impact on quality of life and long term functional outcome. The degree to which age at stroke relates to cognitive outcome is not clear, with some literature suggesting that younger age at stroke results in worse cognitive outcome. The present study investigated the impact of age at stroke on cognitive outcome measured by IQ in a pediatric sample with mixed stroke etiology.

Methods:
Subjects were 47 children (62% male) with mixed stroke etiology including sickle cell disease (23%), cardiac disease (15%), vascular disease (17%), and traumatic injury (11%) who were seen for neuropsychological evaluation as part of long-term clinical care, at which time an IQ score was obtained. Age at stroke, location, and etiology were gathered from records and considered for analysis.

Results:
Mean IQ for the sample was 83.68, although scores ranged from 45 to 121. There was a significant correlation between IQ and age at stroke (r = .290, p = .048), with younger age at stroke associated with lower IQ. When males and females were studied separately, this correlation was not significant for males (r = .305, p = .106) but was significant for females (r = .612, p = .007). A simultaneous linear regression model including age at stroke, gender, etiology, and stroke location significantly predicted variance in IQ (R = .543, F = 4.382, p = .005). Age at stroke and gender were the only two predictors that significantly contributed to the model.

Conclusions:
We found a significant correlation between stroke age and IQ, with younger stroke age associated with lower IQ. Results suggest a possible gender difference, with females in our sample more vulnerable to lower IQ as a function of younger age at stroke. Combining stroke age, gender, etiology, and stroke location accounted for a significant amount of IQ variance. Further research is necessary to clarify factors associated with outcome in survivors of pediatric stroke and should include factors such as stroke severity and socioeconomic status. Improved understanding of factors associated with cognitive outcome following pediatric stroke may inform clinical management to hopefully improve cognitive outcomes and quality of life in this population.
Abstract TMP105: High Utilization Of CAS Procedures Among The Elderly In The Post Crest Era
Authors: Rayes Mahmoud , Bhattacharya Pratik , Damani Rahul , Chaturvedi Seemant
Published: July 2021

Background:
An important interaction of age with outcome was revealed in Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) where elderly patients ≥70 years had worse outcomes with Carotid stenting (CAS) than with Endarterectomy (CEA). Our hypothesis was that following the CREST study, the proportion of CAS procedures in the elderly would decrease.

Methods:
We performed a retrospective review of carotid revascularization procedures between June 2009 and April 2012 at a large volume urban medical center. Demographics, indications, surgical high-risk criteria and outcomes of in-hospital stroke/death/MI were collected. Data analysis was performed in subjects over 70 years. Time trends were examined in the post-CREST period.

Results:
A total of 701 procedures (CEA 36%, CAS 64%) were performed during the study period, of which 360 (51.4%) were in patients ≥70 years (CEA 33%, CAS 67%). A significant proportion (22.1%) was in those ≥80 years. The choice of procedure did not change following CREST. The majority of CAS procedures in elderly (90.8%) were performed by cardiologists. Asymptomatic patients (47.3%) and patients with non-specific symptoms (18.7%) comprised a large proportion of this subgroup. A third of elderly patients with asymptomatic and nonspecific symptoms did not have any surgical high-risk criterion. The proportion of elderly patients receiving CAS for non-specific symptoms increased progressively over time post CREST (27.9% in the most recent months). A similar rise in non-specific indications was noted in the subgroup of patient ≥80 years receiving CAS. About half of this subgroup did not have any surgical high-risk criterion.

Conclusion:
Two years after CREST results, CAS continues to be performed among the elderly, often for non-specific symptoms or in asymptomatic patients. The lack of a decrease in CAS procedures in the elderly raises questions about whether evidence-based carotid revascularization occurs in the real world.
Abstract TMP113: Oxidative stress and Extracellular Signal-regulated Kinase (ERK) Play a Key Role in Impairment of Receptor Desensitization and Prolongation of Vascular Reactivity in the Cerebral Artery after Subarachnoid Hemorrhage
Authors: Hirano Katsuya , Kameda Katsuharu , Hanada Akiko , Hirano Mayumi
Published: July 2021

Cerebral vasospasm is a critical determinant in the prognosis of subarachnoid hemorrhage (SAH). The vasospasm is characterized by not only enhanced but also prolonged contraction. The enhanced response is attributable to an increased receptor expression, while a prolonged response is attributable to impaired receptor desensitization. This study addressed this hypothesis and investigated the mechanism underlying a prolonged contraction, using a rabbit SAH model and A7r5 smooth muscle cells. A thrombin receptor (PAR
1
)-activating peptide (PAR
1
AP) induced a transient contraction in the basilar arteries of the control rabbits. The subsequent second stimulation produced 8% of the first response. PAR
1
AP induced an enhanced and prolonged contraction in SAH, and the second stimulation produced a 75% response. Thrombin induced an enhanced and prolonged contraction in SAH. This contraction irreversibly persisted even after terminating thrombin stimulation. The enhancement and prolongation of the contractile response after SAH was further observed with angiotensin II, vasopressin and PGF
2
α. The heparinization of autologous blood or the intrathecal application of a thrombin inhibitor, argatroban, prevented the enhancement of contraction, while they had no effect on the prolongation of the contraction. The addition of vitamin C or tempol to argatroban restored the transient response, tachyphylactic attenuation of the second response and reversibility of thrombin contraction. The amount of malondialdehyde, an indicator of oxidative stress, in the brain tissues increased after SAH, and this increase was prevented by either argatroban or vitamin C. The Ca
2+
responses to thrombin and PAR
1
AP in A7r5 cells exhibited a phenomenon similar to those seen with the contractile response in an SAH model. ERK inhibitors restored the transient response, tachyphylactic attenuation and reversibility of thrombin response, while the inhibitors of JNK, p38 kinase or Rho kinase had no effect. In conclusion, oxidative stress and ERK activation play a key role in the impaired receptor desensitization and prolonged vascular reactivity after SAH. Targeting oxidative stress and ERK could provide a novel strategy to normalize vascular reactivity after SAH.
Abstract TMP115: Overall Characteristics And Treatment Outcome Of Arteriovenous Malformation Treated With Gamma Knife Radiosurgery: Comparative Study About The Time Dependent Changing Patterns Based On 20 Years Experiences In Single Center.
Authors: Yun Jung-Ho , Kwon Do Hoon , Park Jung cheol , ahn jae sung , Kwun Byung Duk
Published: July 2021

Objective:
The purpose of our study was suggesting of the concepts for postradiosurgery bleeding and total obliteration that could be assisted in the future treatment of AVM by analysis of outcome AVM during last 20 years.

Material and Method:
Total 1050 AVM patients treated with Gamma Knife radiosurgery between May 1990 and December 2010 were included in our study. Gamma Knife radiosurgery of AVMs were divided into two treatment periods (early 1990-2000 period and advanced 2001-2010 period) for systematic review. Retrospective analysis was performed about AVM characteristics and treatment outcome for all AVM patients of each treatment periods. We evaluated the changing pattern of AVMs and the causes of this changing pattern by comparing the two treatment periods statistically.

Result:
The 617 AVM patients in advanced periods (2001~2010) represented more complex nidus as like the following: higher rate of diffuse type (12% vs 7.6%), multiple feeder (39% vs 25%), drain vein (40% vs 36%) and deep vein (43% vs 16%), but less mean radiosurgery volume (2,379mm
3
vs 4,438mm
3
) and lower rate of initial bleeding (49% vs 69%) than 433 AVM patients in early treatment period relatively. In addition, AVM in advanced period showed higher rate of fractionation, repeat treatment and preradiosurgery embolization, but showed less radiosurgery mean marginal dose, lower rate of mortality and complication, rebleeding (6.3% vs 9.5%) and total obliteration than that of early period. Risk factor associated with initial bleeding was only periventricle location (OR:4.2,8.7) that was common included in two treatment periods statistically. On the other hand, risk factors associated with postradiosurgery bleeding were multiple feeders (OR:2.6) and diffuse type (OR:5.2) independently.

Conclusion:
In summary, we present that the effects of radiosurgery in AVM patients have been increased in prevention aspect of rebleeding, mortality and complication due to fractionation and preradiosurgery embolization, but have been a little decreased in aspect of total obliteration rate due to increasing more complex nidus with diffuse type, deep location, multiple feeder and multiple drain vein based on 20 years experiences in our center.
Abstract TMP118:
Alk1
Deficiency Impairs Mural Cell Recruitment During Brain Angiogenesis
Authors: Chen Wanqiu , Guo Yi , Jun Kristine , Wankhede Mamta , Su Hua , Young William L.
Published: July 2021

Background and Purpose:
VEGF stimulation induced dysplasia vessel formation in the
Alk1
-deficient brain. The dysplastic vessels had less mural cell coverage associated with increased extravasation of blood contents. Platelet-derived growth factor B (PDGFB) signaling is important in mural cell recruitment during angiogenesis. Notch signaling is upstream of PDGFB. We hypothesized that
Alk1
deletion impairs pericyte recruitment through downregulation of DLL4/PDGFB signaling. Thalidomide can increase PDGFB expression and was used to test our hypothesis in vivo.

Methods:
Human brain microvascular endothelial cells (HBMECs) were infected with a lentiviral vector carrying
ALK1
shRNA. Cells with 80% reduction of
ALK1
gene expression were treated with vascular endothelial growth factor (VEGF; 0, 10, 50, and 100 ng/ml) for 18 hours.
DLL4
and
PDGFB
mRNA were measured using real-time PCR. Pericyte-recruitment was evaluated by co-culturing pericytes with HBMECs. Cerebrovascular dysplasia was induced by co-injection of an adenoviral vector expressing cre-recombinase and an adeno-associated viral vector expressing VEGF into the basal ganglia of
Alk1
-floxed mice. Two weeks later, thalidomide (75 mg/kg, i.p.) or DMSO was administered twice per week for six weeks.

Results:
Knockdown of
ALK1
attenuated the increase of DLL4 and PDGFB in HBMECs following VEGF stimulation.
DLL4
and
PDGFB
expression was highly correlated (R
2
= 0.93).
ALK1
knockdown reduced the ability of HBMEC to recruit pericytes (P = 0.014). In vivo, thalidomide treatment significantly reduced vascular dysplasia (dysplastic vessels: thalidomide vs. DMSO, 3.4±1.2/200 vessels vs. 1.0±0.5, P = 0.003), without affecting vessel density (P = 0.11). Smooth muscle-negative dysplastic vessels decreased in thalidomide-treated mice, compared to DMSO-treated mice (21%±6 vs 47±9, P = 0.0002). Prussian blue-positive area was reduced in the thalidomide group, compared to the DMSO group (P = 0.0011).

Conclusions:
Our findings suggest that
Alk1
regulates pericyte recruitment through DLL4/PDGFB signaling during brain angiogenesis.
Abstract TMP119: Stereotactic Radiosurgery For Dural Arteriovenous Fistula Reflactory To Endovascular Treatment
Authors: Shimizu Tomohisa , Sugiu Kenji , Tokunaga Koji , Hishikawa Tomohito , Hiramatsu Masafumi , Okuma Yu , Date Isao , Sato Kengo , Baba Yoshimi
Published: July 2021

Background:
Although almost all dural arteriovenous fistulas (DAVFs) can be highly curable using endovascular treatment, some of them are reflactory. We evaluated the efficacy of stereotactic radiosurgery for DAVFs reflactory to endovascular treatment.

Methods:
In 178 patients with DAVFs treated by endovascular embolization in our institution, 12 patients were reflactory and treated by CyberKnife (CK) radiosurgery. Patients background, efficacy of CyberKnife radiosurgery and complication were analyzed.

Results:
5 men and 7 women underwent CyberKnife radiosurgery. Ages ranged from 21 to 74 years (mean, 57.5 years). The locations of the fistulas were 10 transverse/sigmoid sinus and 2 cavernous sinus. The Borden classification was I in 3, II in 6, and III in 3 patients. Transarterial embolization (TAE) was performed in 10 patients, TAE and transvenous embolization (TVE) in 2. In all cases, shunt flow could be reduced, but small flow was residual. After embolization, residual fistula was treated by CK with a mean marginal dose of 19.95 Gy. Nine patients could follow up over two years. 8 patients got complete disappearance of the nidus. One patient remained small nidus, but him symptom improved. There was no complication accompanying radiosurgery.

Conclusions:
CyberKnife radiosurgery to residual DAVFs after endovascular treatment showed a remarkable response at high rates in long term. CyberKnife radiosurgery is a safe and effective method of these reflactory and mildly symptomatic patients.
Abstract TMP68: A Pro-inflammatory Monocyte Subset (ccr2+/ly6c
hi
) Is Dominantly Recruited Into Acute Ischemic Brain.
Authors: Kim Eunhee , Beltran Cesar , Cho Sunghee
Published: July 2021

Post-ischemic inflammation has been associated with ischemic brain injury. Infiltrated peripheral immune cells including monocytes/macrophages (MMs) contribute to the stroke-induced inflammation. MM mobilization from the periphery to the brain (MM trafficking) involves spleen, as an immediate storage of monocytes and the circulatory system as a conduit for their transport; however, there has been no systematic analysis of MM trafficking in stroke. There are two monocyte subsets, a pro-inflammatory (CCR2+/Ly6C
hi
) and an anti-inflammatory (CCR2-/Ly6C
lo
). These are sequentially recruited to the injury site in a controlled manner to elicit inflammation and repair/healing respectively. Current study determines the extent of trafficking of the monocyte subsets upon stroke and the role of the subsets on stroke-induced brain injury. Eleven week-old C57BL mice were subjected to transient middle cerebral artery occlusion and then leukocytes were isolated from blood, spleen, and brain prior to, 1d-, and 3d-post ischemia. The cells were incubated with antibodies (lineage marker or CD45 and CD11b to detect MMs, and Ly6C) and then analyzed using flow cytometry/FACS. We observed decreased spleen size following ischemia (>40% reduction in spleen weight at 1d- and 3d-post). Both Ly6C
hi
and Ly6C
lo
MM number in the spleen and blood were significantly decreased in 1d-post ischemic mice, and these levels were sustained until 3d-post ischemia. On the other hand, brain MM numbers were increased at 1d-post and further increased at 3d-post ischemia (Fig. 1). Importantly, the Ly6C
hi
subset was dominantly increased in the ischemic brain compared to Ly6C
lo
subset (Fig. 2). The findings of MM trafficking and predominant increase in Ly6C
hi
MMs in the ischemic brain indicate that the pro-inflammatory monocyte subset might have a critical role in acute ischemic brain injury. Selective targeting of pro-inflammatory subset is suggested to reduce acute stroke-induced brain injury.
Abstract TMP80: A Lipid-soluble Iron Chelator Protects Against Intracerebral Hemorrhage In Mice
Authors: WU HE , Wu Tao , Li Mingchang , Wang Jian
Published: July 2021

Background and purpose:
Intracerebral hemorrhage (ICH) is a devastating form of stroke with no clinically proven treatment. Previous studies have indicated that 2,2’-dipyridyl, a lipid-soluble ferrous iron chelator, can reduce brain injury after cerebral ischemia and reduce cerebral vasospasm after subarachnoid hemorrhage. In this study, we examined the efficacy of 2,2’-dipyridyl after ICH in middle-aged mice (12 months old).

Methods:
ICH was modeled by intrastriatal injection of collagenase or autologous whole blood. 2,2’-Dipyridyl or vehicle was administered intraperitoneally 2 h before ICH (pretreatment) or 6 h after ICH (post-treatment) and then once daily for up to 3 days. Mice in the pretreatment group were sacrificed 1 or 3 days after ICH and examined for iron deposition, neuronal death, oxidative stress, microglial/astrocyte activation, neutrophil infiltration, and white matter damage. Mice in the post-treatment group were examined for brain lesion volume and edema on day 3 and for neurologic deficits on days 1, 3, and 28 after ICH.

Results:
Pretreatment with 2,2’-dipyridyl decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, reduced microglial activation without affecting astrocytes or neutrophil infiltration, and attenuated white matter damage (n=5 mice/group, all
p
<0.01). Post-treatment reduced brain lesion volume by 40.5%, lessened edema, and improved neurologic function (n=6-8 mice/group, all
p
<0.05) but did not affect body weight loss or mortality rate.

Conclusions:
The lipid-soluble ferrous iron chelator 2,2’-dipyridyl can reduce brain injury and improve functional recovery after ICH.
Abstract TMP96: Development and Validation of a Certification Test for Scoring the Modified Rankin Scale Using the Rankin Focused Assessment
Authors: Banzon Jacqui , Patel Richa , Sanossian Nerses , Starkman Sidney , Oswald Molly , Conwit Robin , Saver Jeffrey L
Published: July 2021

Background:
The modified Rankin Scale is the most common primary endpoint in acute stroke clinical trials and is a new requirement for Comprehensive Stroke Center clinical practice. The Rankin Focused Assessment (RFA) is a simple, operationalized method to obtain a modified Rankin Scale score and has been shown to have excellent inter-rater reliability. For wide deployment in clinical trials and clinical practice, it is desirable to develop a rater testing and certification process for the RFA method to assign a mRS score.

Methods:
We developed 30 written case vignettes spanning the entire range of the modified Rankin Scale, based on actual patients enrolled in the NIH FAST-MAG Phase 3 trial. Each vignette briefly portrays patient function at 3 months poststroke, based on available sources of information (direct examination, patient report, and family report). The correct mRS score for each patient was determined by two expert physician-investigators (criterion standard). Vignettes were then beta-tested in a group of 15 experienced mRS raters (14 nurses, 1 physician) and 3 were reworded for clarity and retested.

Results:
Among all 30 individual vignettes, rater scores concurred with the criterion standard in 435/443 (98.2%). The final set of 30 vignettes was divided into 5 alternative test sets of 6 vignettes each. A score of 100% (6/6 correct) was required for rater certification in the RFA method to elicit the mRS. On the test sets of 6 vignettes, the rater pass rate was 84.3% (59/70). Raters missed passing by 1 (5 right out of 6) in 14.3% of sets and by 2 (4 right out of 6) in 1.4% of sets.

Conclusion:
A written vignette certification test for the Rankin Focused Assessment method to assign a modified Rankin Scale score has been developed and demonstrated good concurrence of experienced raters with criterion standards. A public service website at which individuals may obtain Rankin Scale certification using the RFA will be demonstrated.
Abstract TP106: N-3 Polyunsaturated Fatty Acid Enhances Neurovascular Remodeling After Acute Cerebral Ischemia
Authors: Zhang Wenting , Hu Xiaoming , Lu Shiduo , Guo Yanling , Cao Guodong , Chen Jun , Gao Yanqin
Published: July 2021

INTRODUCTION:
Ischemic stroke triggers multiple repair responses, including neurogenesis, angiogenesis and oligodendrogenesis. These endogenous processes, however, are insufficient for effective brain repair. Our previous study has shown that omega-3 polyunsaturated fatty acid (N3 PUFA) is a potential neurogenic treatment for stroke recovery. The effect of N3 PUFA on revasularization and white matter recovery, however, remains unexplored.

HYPOTHESIS:
N3 PUFA enhances revasularization and white matter recovery after ischemic stroke, leading to long-term neurological recovery.

METHODS:
Mice were treated with N3 PUFA-enriched diet or regular diet for 3 months and then subjected to MCAO for 60 minutes. Brdu was administered to label newly generated cells. Animals were sacrificed on day 1, 3, 7, 14 or 35 of reperfusion. Functional vessels were identified by transcardial perfusion of FITC-conjugated tomato
lectin
, which labels endothelial cells only in perfused vessels. White matter integrity was evaluated by immunohistochemistry staining of myelin basic protein (MBP), SMI32 and neurofilament (NF) 200.

RESULTS:
The vascular reperfusion in the ischemic core and penumbra was preserved in N3 PUFA-supplemented mice since 1 day after MCAO and maintained significantly higher than regular diet group up to 35 days post-injury. Angiogenesis was enhanced by N3 PUFA, as revealed by substantially increased double staining of Brdu with tomato lectin at 7-35 days after MCAO. Importantly, clusters of DCX+ immature neurons localized proximal to revascularized vessels beginning 14 days after ischemia, suggesting interplay between revascularization and neurogenesis. Post-stroke white matter injury was also ameliorated by N3 PUFA, as revealed by enhanced MBP staining for mature myelin and reduced SMI32 staining for abnormally dephosphorylated neurofilament. Meanwhile, axon integrity was markedly preserved in N3 PUFA-treated mice. As a result, N3 PUFA supplementation significantly reduced the infarct volume, which was accompanied by improved neurological functions up to 35 days after reperfusion.
Abstract TP109: Impact of ATP-Induced Mild Hypothermia on Focal Cerebral Ischemia in Rats
Authors: Zhang Meijuan , Li Wenjin , Leak Rehana K , Chen Jun , Zhang Feng
Published: July 2021

Brain ischemia is a devastating disorder without effective therapies. One of the most promising approaches to attenuate ischemic brain injury is mild hypothermia. Recent studies show that adenosine nucleotides can induce hypothermia in mice. The purpose of the present study was to test the hypothesis that ATP, a common form of energy currency, induces mild hypothermia in rats and reduces brain injury following focal cerebral ischemia. ATP solution was dissolved in water and intraperitoneally injected; and focal stroke was induced by a suture model of middle cerebral artery occlusion and ischemic outcomes were evaluated within 24 hr. We found that injections of ATP lowered core body temperature in a dose-dependent manner; the dose appropriate for subsequent experiments was 2 g/kg as it reduced temperature to the range of mild hypothermia for approximately 7 hours. While intravenous injection of ATP was less effective in lowering body temperature. However, when ATP-induced hypothermia was applied to stroke, a neuroprotective effect was not observed. In contrast, the infarct volume grew even larger in ATP-treated rats. Not surprisingly, this was accompanied by an increased rate of seizure events, hemorrhagic transformation, and higher mortality. Continuous monitoring of physiological parameters revealed that ATP severely reduced heartbeat rate and blood pressure. ATP also raised blood glucose to dangerous levels and this was accompanied by severe acidosis and hypocalcemia. Western blotting showed that ATP treatment decreased levels of both phospho-Akt and total-Akt in the ischemic cortex. Our results reveal that, despite inducing hypothermia, ATP is not appropriate for protecting the brain against stroke, as it is associated with exaggerated ischemic outcomes and dangerous systemic side effects.
Abstract TP138: SITS Symptomatic Intracerebral Hemorrhage Risk Score in the Stroke Belt
Authors: Alvi Muhammad , Boehme Amelia K , Lyerly Michael J , Siegler James E , Albright Karen C , Shahripour Reza Bavarsad , Rawal Pawan V , Kapoor Niren , Sisson April , Houston J. Thomas , Alexandrov Anne W , Martin-Schild Sheryl , Alexandrov Andrei V
Published: July 2021

Background:
sICH remains the most feared complication of IV tPA treatment. SITS investigators developed a clinical score to predict sICH in European stroke patients. We aimed to investigate the how this score would perform in IV tPA treated patients at two centers in the US Stroke Belt.

Methods:
We retrospectively reviewed IV tPA treated consecutive patients from two centers in the Stroke Belt (2008-2011). The SITS Symptomatic Intracerebral Hemorrhage Risk Score was calculated using published criteria
.
sICH was defined as a type 2 parenchymal hemorrhage with deterioration in NIHSS score of 4 points or death. Only patients with all 9 variables needed to calculate the SITS sICH scores were included. Logistic regression was used to investigate the predictive ability of the score.

Results:
During the study period, 457 patients were treated with IV tPA (sICH 4.2%). Among the 220 patients with all 9 variables, 19 (8.6%) had sICH. The SITS sICH scores and other variables are shown in the Table. SITS score was not a predictor of sICH in overall patient sample (OR=1.16, 95% CI 0.856-1.57, p=0.3387). The score performed poorly in Blacks (OR 1.18, 95% CI 0.79-1.77, p=0.417) as compared to Whites (OR 1.19, 95% CI 0.77-1.82, p=0.438) for prediction of sICH, Figure. However, SITS score was predictive of mRS 4-6 at discharge (OR=1.34, 95% CI 1.16-1.55, p<0.001).

Conclusions:
SITS sICH score was not predictive of sICH in Stroke Belt patients, particularly among Blacks. The specific components of the 9 variable score needs to be re-evaluated individually for point estimates specific for the Stroke Belt population.
Abstract TP160: The Increasing Treatment Pressure Of External Counterpulsation Continuously Augments Blood Pressure But Not Cerebral Blood Flow Velocity Of Ischemic Stroke Patients
Authors: LIN WEN HUA , Xiong Li , Han Jinghao , Leung Thomas , Soo Yannie , Chen Xiangyan , Wong Ka Sing
Published: July 2021

Background:
External counterpulsation (ECP) is a noninvasive method used to augment cerebral perfusion but the optimal use of ECP in ischemic stroke has not been well documented. We aim to investigate the effects of increasing ECP treatment pressure on cerebral blood flow and blood pressure (BP).

Methods:
We recruited 38 acute ischemic stroke patients with large artery occlusive disease and 20 healthy elderly. Mean cerebral blood flow velocities (CBFV) of bilateral middle cerebral artery were monitored using transcranial dopper. Continuous beat-to-beat BP was measured via finger cuffs. We started ECP treatment pressure from 150mmHg, then gradually increased to 187.5mmHg, 225mmHg and 262.5mmHg. CBFV and BP were recorded before ECP and during each pressure increment respectively for 3 minutes. CBFV data of patients was analyzed based on whether it was ipsilateral or contralateral to the infarct.

Results:
Median NIHSS of stroke patients was 5.5 and mean time after stroke onset was 5.24 days. Mean BP was significantly elevated from baseline in both groups after ECP started. BP increase percentages of two groups similarly kept augmented following raised ECP pressure and reach maximium at 262.5mmHg (patients 16.9% vs. controls 16.52% compared with baseline). Under different ECP pressures, ipsilateral mean CBFV of stroke patients increased 5.15% (150mmHg), 4.35% (187.5mmHg), 4.55% (225mmHg) and 3.52% (262.5mmHg) from baseline. All were significantly higher than baseline but did not differ among different pressures. Contralateral mean CBFV changed likewise (5.16%, 4.02%, 3.7% and 3.34% increase from baseline). Mean CBFV of controls under ECP pressures did not increase from baseline.

Conclusion:
The increasing treatment pressure of external counterpulsation continuously augments blood pressure but not cerebral blood flow velocity of ischemic stroke patients with large artery occlusive disease. Cerebral blood flow velocity of stroke patients significantly increases from baseline under ECP pressure of 150mmHg but it reaches a plateau as ECP pressure further raises. Among 4 ECP pressures above, 150mmHg is the optimal treatment pressure for ischemic stroke due to higher risks of hypertension-related complications in acute stroke with higher ECP pressure.
Abstract TP169: Perioperative Assessment of Cerebral Perfusion Territories using Arterial Spin Labeling Magnetic Resonance Imaging in Patients with Carotid stenosis
Authors: Yamamoto Daisuke , Hosoda Kohkichi , Uchihashi Yoshito , Kohmura Eiji
Published: July 2021

[Background]
Territorial arterial spin labeling (TASL) MRI offers a unique opportunity to visualize non-invasively cerebral perfusion territory (PT) by selective labeling of the feeding arteries without contrast medium. The objective of this study was to evaluate the PT status in patients with carotid stenosis and effect of carotid endarterectomy (CEA) on PT.

[Materials and Methods]
This study included 22 patients with carotid stenosis (20 men and 2 women; mean age 73 years) treated by CEA. All of them underwent TASL preoperatively and on the day after surgery. Ipsilateral internal carotid artery (ICA) blood flow (ICF) was measured by electromagnetic flowmeter just before and after endarterectomy during the surgery. Perfused volume (PV) of each feeding artery was calculated from perfused area and thickness of slices. Cerebral blood flow (CBF) was calculated as ICF/PV.

[Results]
Before CEA, the PV of ipsilateral ICA were significantly smaller than those of contralateral ICA. After CEA, the ipsilateral PV significantly increased and the asymmetry of PV of ICA was corrected (Fig.1 & 2). ICF also increased (82 to 178 ml/min). Accordingly, ipsilateral CBF defined by ICF/PV significantly increased (28 to 50 ml/100cm
3
/min). In a patient with postoperative hyperperfusion (HP), however, ICF remarkably increased from 10 to 200 ml/min while the PV increased only slightly (111 to 127 cm
3
, Fig.2).

[Conclusion]
TASL could evaluate the peri-operative change of cerebral PT non-invasively. CEA corrected the asymmetry of PT measured by TASL in patients with carotid stenosis. In a patient with HP after CEA, however, the increase of PT was small, which may suggest pathophysiological basis for HP.
Abstract TP170: Persistently Elevated Factor VIII In Acute Ischemic Stroke Is Associated With Higher CRP, Lower Baseline NIHSS, And Longer Length Of Hospital Stay
Authors: Dorsey Adrianne M , Boehme Amelia K , Schluter Laurie , Albright Karen C , Chang Tiffany R , Beasley T. Mark , Kruse-Jarres Rebecca , Leissinger Cindy , Martin-Schild Sheryl
Published: July 2021

Objective:
We sought to determine the proportion of patients with elevated factor VIII (FVIII) levels whose FVIII levels remain elevated after the acute phase of stroke, and the patient characteristics that predict sustained elevation of FVIII levels.

Background:
Factor VIII plays a major role in the fluid phase of blood coagulation. Elevated FVIII has been shown to increase risk of venous and arterial thrombosis. The importance of screening for elevated FVIII after a first thrombotic event especially acute ischemic stroke (AIS) has not been adequately investigated.

Design/Methods:
We reviewed FVIII levels taken at baseline and follow-up in patients with AIS treated at our stroke center from July 2008 to June 2012. Elevated FVIII was defined as >150%. Baseline demographics, laboratory data, clinical course, outcomes, and time to follow-up were collected in patients with elevated FVIII at baseline and data was compared in patients who had normalized FVIII with patients whose FVIII remained elevated at least 7 days later.

Results:
Repeat FVIII levels were available for 34/111 patients with elevated FVIII level with AIS. FVIII remained elevated in 68% after a median interval of 110 days. Factors associated with persistent elevation included higher baseline FVIII level (239 vs 185%, p=0.015), elevated CRP (73.3 vs 12.5%, p=0.008), lower baseline NIHSS (4 vs 8, p=0.046), and longer length of hospital stay (8 vs. 3, p=0.0063). Normalization of FVIII was associated with tPA use (54.5% vs 13%, p=0.016). No relationship was found between persistently elevated FVIII and baseline demographics, clinical course and outcomes.

Conclusion:
Persistently elevated FVIII after AIS may be predicted by higher baseline levels and elevations in CRP. Despite worse baseline stroke severity, patient with normalization of FVIII had similar outcomes as those with persistent elevation, which may be explained by the higher use of tPA in the normalized group. The relevance of elevated FVIII in stroke is not well understood. Our preliminary results suggest elevations persist in the majority and may not merely represent an acute phase reactant.
Abstract TP213: Ischemic And Hemorrhagic Stroke In Patients With Implantation Of Left Ventricular Assist Device
Authors: Sakaguchi Manabu , Kitagawa Kazuo , Mochiduki Hideki , Sawa Yoshiki , Yoshimine Toshiki
Published: July 2021

Background and Purpose:
Stroke is one of the major complications in patients implanted with left ventricular assist device (LVAD). In Japan, the duration waiting for a heart transplant from a LVAD implantation is beyond 800 days. While antithrombotic therapy is often aggressively given, hemorrhagic stroke as well as ischemic one is a major complication that determines the outcome in these patients. However, the type of stroke in patients with LVAD implantation has not been fully investigated. The purpose of this study is to clarify the type and characteristic of acute stroke with LVAD implantation by using CT findings.

Methods:
Between 2005 and 2011, we reviewed 110 consecutive cases underwent LVAD implantation. Among them, 49 cases (126 events in total) suffered from the acute stroke at least once. We analyzed the category, the sites of lesions and the CT findings of each acute stroke events.

Results:
Among 49 acute stroke cases (5-74 yr old, 16 female and 33 male), brain infarction (n=39, 71 events), brain hemorrhage(n=25, 31 events) and subarachnoid hemorrhage (SAH) (n=23, 33 events) were identified. Thus, the incidence of hemorrhagic stroke is equal to that of ischemic stroke in patients with LVAD. In 71 infarct events, CT showed the lesion in the cortex (n=44), in the basal ganglia (n=17) and in the brain stem and cerebellum (n=17). Multiple infarctions were also observed in 29 events. In brain hemorrhage events (n=31), almost all were identified in the subcortical lesion (n=27), and none was seen in the basal ganglia. Hemorrhage in the infratentorial area (n=3) and intraventricular space (n=1) were rare. In SAH (n=33), we identified hemorrhage located only in one sulcus in 25 events. We tentatively called this small characteristic pattern of SAH “petite SAH”. Furthermore, in 12 events of “petite SAH”, fresh cortical infarction was simultaneously observed in CT.

Conclusions:
CT findings of acute stroke after implantation of left ventricular assist device are characteristically multifocal cortical lesions, regardless of brain infarction and hemorrhage. Although the mechanisms underlying petite SAH are unknown, prevention and management of ischemic as well as hemorrhagic stroke is undoubtedly important to improve the outcome of patients with LVAD implantation.
Abstract TP217: Cerebrovascular Events in Glioma Patients Treated with Bevacizumab
Authors: Patel Donika K , John Seby , Hashemi-Sadraei Neda , Ahluwalia Manmeet
Published: July 2021

Introduction:
Bevacizumab, a humanized monoclonal anti-vascular endothelial growth factor antibody, was FDA approved in 2009 for progressive glioblastoma. Phase II clinical trials suggested an increased risk of ischemic stroke (IS) and intracranial hemorrhage (ICH) while on bevacizumab. The incidence, clinical characteristics, and neuroimaging of glioma patients who developed cerebrovascular events while on treatment is lacking. We report our experience using bevacizumab for glioma patients.

Methods:
A retrospective review of glioma patients treated with bevacizumab at our institution from July 2005 to June 2011 was studied. Patients with MRI-confirmed IS and/or ICH while on bevacizumab was investigated and compared to historical data. Patient demographics, vascular risk factors, clinical presentations, tumor characteristics, treatments (surgery, chemotherapy, and radiation), and treatment duration were collected.

Results:
A total of 162 patients (65% male) received bevacizumab and 23 (14%) developed a cerebrovascular event while on treatment, with 3 (2%) IS and 20 (12%) ICH. All IS and ICH patients received prior brain radiation. In the IS group, 2 (66%) patients were symptomatic, with 1 (33%) cardiembolic and 2 (66%) lacunar strokes. None had risk factors besides hypercoagulable state from malignancy. In the ICH group, 3 (15%) patients had a symptomatic bleed and 6 (30%) had associated hypertension. All ICHs were intratumoral and 16 (80%) associated with tumor progression. Median survival after stroke was 9.8 and 3.7 months in the IS and ICH groups, respectively. Length of bevacizumab treatment was not significantly associated with development of IS (
p
= 0.6) and ICH (
p
= 0.3).

Conclusion:
Glioma patients have an inherently elevated risk of IS and ICH because of disease- and treatment-related effects. In our study, 78% of the events were asymptomatic and diagnosed on serial imaging. ICHs were more common, but all were small intratumoral bleeds, mostly in the setting of tumor progression. Development of cerebrovascular events was not associated with the duration of bevacizumab treatment. Our study, however, cannot determine causality and randomized controlled studies are needed to determine the risk of IS and ICH with bevacizumab use.
Abstract TP228: Fluorescent Pegylated Nanoparticles are Localized in Macrophage-rich but Relatively Stable Human Carotid Atheromata
Authors: Lee Su-Kyoung , Kim Hyo-Jin , Choi Young Jun , Kwon Joo Young , Kim Jeong-Yeon , Lee Deok Hee , Kim Jong S. , Kim Dong-Eog
Published: July 2021

Background:
Foam cell macrophages to produce matrix-disorganizing proteolytic enzymes may render atherosclerotic plaques prone to rupture, which causes thromboembolic stroke. Macrophages within atherosclerotic lesions were reported to take up low density lipoprotein (LDL)-sized nanoparticles by fluid-phase pinocytosis, indicating that fluid-phase pinocytosis of LDL is a mechanism for macrophage foam cell formation in vivo.

Objective:
To invesigate if fluorescent pegylated nanoparticles that are taken up by macrophages via pinocytosis could visualize vulnerable areas of human atheromata.

Methods:
Fresh carotid specimens from 36 patients undergoing carotid endarterectomy (after 3T carotid MRI) were tissue-cultured in DMEM (4 mL) with the fluorescent molecular imaging probe in 37°C CO
2
incubator. Before and 4 hours after the incubation, molecular optical imaging was performed using a Cy5.5 near-infrared fluorescent (NIRF) imaging machine with a charge-coupled device camera. The atherosclerotic plaques were classified according to the American Heart Association Report using 35 microsections (5μm thickness) from various pre-determined regions of selected carotid tissues (n=11). Immunohistochemical staining for macrophages (CD68) was performed using the avidin-biotin-peroxidase method.

Results:
High risk lesions (AHA Type IV ~ VIII) tended to show more frequent plaque regions with strong CD68 immunoreactivity (22 / 27) than did low risk lesion (2 / 8, p = 0.003). Unexpectedly however, low risk lesions (Type I: intial lesion with foam cells; Type II: fatty steak with multiple foam cell layers) tended to show more frequent in plaque regions with both strong CD68 immunoreactivity and high Cy5.5 NIRF signal (11 / 14) than the others (10 / 21, p = 0.07), suggesting that the nanoparticles could be taken up by relatively fresh foam cells in early atherosclerotic lesions rather than end-stage apoptonecrotic macrophages in advanced atheromata.

Conclusion:
Preliminary analysis of this on-going prospective study shows that fluorescent pegylated nanoparticles may localize macrophage-rich but relatively stable regions of human atheromata.
Abstract TP23: Feasibility Of The Combination Of The Restore
™
Thrombectomy Device And The Reflex
™
Access And Aspiration Catheter For The Treatment Of Acute Ischemic Stroke
Authors: Schramm Peter , Schramm Ramona , Knauth Michael
Published: July 2021

Introduction:
Larger distal access catheter systems for treatment of acute intracranial vessel occlusion enable both clot aspiration and introduction of flow restoration devices. We present the first clinical data of a large lumen hyperflexible intracranial distal aspiration catheter (ReFlex™ 5F, 058” ID x 125cm, Covidien, Irvine, CA) combined with the ReStore™ Thrombectomy microcatheter (Reverse Medical, Irvine, CA) for endovascular treatment of acute ischemic stroke.

Patients and Methods:
The ReStore™ consists of a flexible, tapered microcatheter with a braided mesh retrieval element attached to its distal segment. The retrieval element is deployed through the advancement of a guidewire or the ReAct™ stylet through the lumen to radially expand the retrieval element. Infusion of rt-PA within the thrombus is possible through small side holes of the ReStore™. Nine patients (62 y - 88 y, 5f/4m) with acute occlusion of the MCA were treated with the combination of ReStore™ and the ReFlex™ aspiration catheter within 6 hours after symptom onset. Median NIHSS score upon arrival was 16 (range 8 - 18). TICI flow in the target vessel segment was assessed prior and after recanalization procedure.

Results:
Thrombectomy with the combination of ReStore™ and ReFlex™ was performed as initial mechanical treatment in 8 cases. In one case, prior treatment with other stentriever systems failed, whereas the combination of ReStore™ and ReFlex™ lead to TICI 3. TICI 2b or 3 was achieved in 7 patients (77.8%); in 2 patients, TICI 2a was achieved. Immediate flow restoration while activating ReStore™ was accomplished in all 9 cases. Mean time from first angiopgraphy to first perfusion was 39.1 min (range 9-88 min). In 4 cases, additional rt-PA (10 mg) was administered directly into the thrombus through the ReStore™. In 2 cases, subsequent implantation of a permanent intracranial stent was performed. The mean number of ReStore™ activations to achieve final TICI score was 2.2 ± 1.1. One patient experienced periprocedural subarachnoid hemorrhage as a severe adverse event.

Conclusion:
The combination of ReStore™ and the ReFlex™ aspiration catheter is a promising new treatment option for both flow restoration and aspiration in patients suffering from acute intracranial arterial occlusion.
Abstract TP259: Ischemic Postconditioning Protects Against Focal Ischemia in Mouse
Authors: Joo Sungpil , Xie Weiying , Zhao Heng
Published: July 2021

Ischemic Postconditioning Protects Against Focal Ischemia in Mouse

Background:
Ischemic postconditioning(IPost) has been shown to attenuate cerebral ischemia/reperfusion injury in a few rat models. Here we further established a IPost model in mice, which offers oppotunities to study protective mechanism of IPost in mice with various genetic backgrounds.

Material and Methods:
Focal ischemia was induced by middle cerebral artery (MCA) suture occlusion for 45min. IPost was conducted by a series of repetitive, brief occlusion/reperfusion via withdrawl and insertion of the suture in the internal carotid artery. Infarction sizes were measured 3 days or 2 weeks after stroke. Functional neurological scores were also assessed.

Results:
we found that rapid IPost with three cycles of occlusion/reperfusion (15sec/30sec), or with two cycles of occlusion/reperfusion ( 60sec/60sec), which were performed 2 min after reperfusion, significantly reduced infarct sizes as measured 3 days post-stroke. Delayed IPost performed 3 hours after reperfusion aslo significantly reduced infarct sizes( n=9, P<0.01). Rapid IPost with 3 cycles of occlusion/reperfusion(15/30s) initiated 2 min after reperfusion resulted in the smallest infarct size. The spared infarct area were seen in border zones between the cortical territories of the anterior cerebral artery(ACA) and those of the MCA, as well as in the ventromedial and dorsolateral striatum. Delayed brain injury measured by silver staining 2 weeks after stroke and mortality were also reduced by rapid IPost.

Conclusions:
IPost reduces cerebral infarction and improve functional neurological status in mice, which offers a model to investigate the underlying protective mechanism of postconditioning using mice with various genetic backgrounds in the future.