bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP46: Rotational Ischemic Vertebral Artery Compression (RIVAC) Syndrome Due to Cervical Facet Hypertrophy and Uncinate Process Osteophyte: Review of Seven Consecutive Cases
Authors: Kim Stanley H , Dhablania Nathan , Kim Joshua , Gulati Rishabh , Miley Jefferson , Patel Anant
Published: July 2021

Introduction:
The authors propose a new terminology, Rotational Ischemic Vertebral Artery Compression (RIVAC) syndrome, to describe patients who present with TIA or stroke from compression of the cervical vertebral artery (VA) below C2 by facet hypertrophy or uncinate process osteophyte associated with rotation of the head. The authors review clinical presentation, radiological findings, and management of 7 consecutive cases.

Methods:
Prospective analysis of 7 consecutive cases of RIVAC syndrome was performed between 2004 and 2012. We reviewed peri-operative imaging, method of treatment, and clinical and angiographic outcome.

Results:
A total of 6 patients (mean 66+/- 4 years) presented with stroke (N=2) or TIA including reproducible dizziness, vertigo, or syncope (N=4) associated with rotation of the head. Pre-operative dynamic cerebral angiogram showed near complete occlusion of cervical VA (N=2) or severe stenosis (60 to 80%) (N=5) during rotation of the head. The location of cervical VA compression was as follows: right C3-4 (N=1), left C4-5 (N=3), left C5-6 (N=2) and left C6-7 (N=1). Treatment included endovascular stent placement of VA without open surgery (N=1), endovascular stent placement of VA followed by partial left C5-6 factectomy 2 years later (N=1), posterior surgical decompression of VA along with bilateral facet screw fixation (N=4), and anterior cervical discectomy and fusion (N=1). Follow up dynamic cerebral angiograms and CTA angiogram of neck (6 months to 3 years) showed resolution of VA compression on rotation of head in all patients except for one who had lost in follow up. Clinical evaluation (range of 1 to 48 months) showed no recurrent stroke or TIA in all patients (mRS score of 0, N=6 and mRS of 3, N=1).

Conclusion:
RIVAC syndrome should be recognized as an important cause of posterior circulation TIA or stroke associated with rotation of head. Pre-operative dynamic cerebral angiogram and CT angiogram of neck are essential in localization and characterization of the level and cause of VA compression. Open surgical decompression and fixation appears to be safe and effective treatment of patients with RIVAC syndrome.
Abstract WMP78: Investigating the Utility of Previously Developed Prediction Scores in AIS patients in the Stroke Belt
Authors: Rawal Pawan V , Boehme Amelia K , Shahripour Reza Bavarsad , Palazzo Paola , Albright Karen C , Kapoor Niren , Alvi Muhammad , Lyerly Michael J , Houston James T , Harrigan Mark R , Cava Luis F , Alexandrov Anne W , Alexandrov Andrei V
Published: July 2021

Background:
A number of scoring systems have been developed in different geographic and treatment populations, however, it remains unknown how these scores perform in the Stroke Belt population. We sought to validate and assess the utility of the SEDAN, THRIVE, HIAT and HIAT2 scoring systems among patients receiving systemic (IV tPA) and endovascular (IAT) reperfusion.

Methods:
We retrospectively reviewed all IV tPA and IAT patients presenting to our tertiary care center from 2009-2011. The scores were assessed in IV tPA only patients, IAT only patients and in patients who received both therapies (IV-IA). We tested THRIVE for predicting mRS 3-6, HIAT and HIAT2 for mRS 4-6, and SEDAN for symptomatic intracerebral hemorrhage (sICH). sICH was defined as a Type 2 parenchymal hemorrhage with deterioration in NIHSS score of 4 points or death. ROC curves were used to evaluate each score within the three groups.

Result:
Of the 366 patients who were included in this study, 89 had IAT only, 243 had IV tPA only and 34 had IV-IA. Figure 1a shows their demographic and baseline characteristics. Figure 1b shows the performance of SEDAN, THRIVE, HIAT and HIAT2 scores in our population (ROC range from 0.512-0.818).

Conclusion:
The two scores developed in the Stroke Belt, HIAT and HIAT2, performed well in the patient group for which they were developed (IAT). Additionally, they are also good predictors in other groups (IV and IV-IA). THRIVE performed well for predicting mRS 3-6 in all three groups. SEDAN was only moderately useful in predicting sICH after IV tPA. SEDAN had poor predictive value in IAT and IV-IA. These results highlight the need for validating clinical scores in different patient populations to determine their generalizability to all stroke patients.
Abstract WMP82: The Association Between Cerebral Microbleeds And Arterial Stiffness
Authors: Song Tae-Jin , Kim Jinkwon , Song Dong-Beom , Lee Hye Sun , Nam Chung Mo , Kim Young Dae , Nam Hyo suk , Heo Ji Hoe
Published: July 2021

Background and significance:
Increased arterial stiffness causes vessel damage of the end-organs. Thus, in the brain, small vessels may be susceptible to increased arterial stiffness. Cerebral microbleeds (CMBs) are topographically categorized as non-lobar type, mostly due to hypertensive vasculopathy and lobar type, due to cerebral amyloid angiopathy. When considering CMBs in the nonlobar region are associated with small vessel pathology, arterial stiffness may be related with CMBs in the nonlobar region. We investigated relationship between CMBs by using brachial ankle pulse wave velocity (baPWV) representing arterial stiffness.

Method:
Between June 2006 and January 2012, we included 1290 consecutive patients with acute ischemic stroke admitted to hospital within 7 days after symptom onset and who underwent baPWV and brain gradient echo (GRE) and Fluid Attenuated Inversion Recovery (FLAIR) MRI. Patients with potential cardiac sources of embolism or peripheral arterial occlusive disease were not included. BaPWV was measured during ankle-brachial index examination using an automatic device. CMBs were classified as lobar and nonlobar type. Severity of leukoaraiosis was determined using the Fazekas’ scoring system. Binary and multinomial logistic regression analyses were performed to determine variables that were associated with presence and location of CMBs.

Results:
Mean age of the patients was 64±12 years and 61.9% (799/1290) were male. Of 1290 patients, CMBs were found in 28.6%. The patients with CMBs were older than those without CMBs (69±10 years versus 63±12 years, p=0.001). Mean baPWV was higher in patients with CMBs than those without (2240±512cm/s versus 1896±505cm/s, p=0.001). On multivariate binary logistic analysis, baPWV and high grade leukoaraiosis were independent predictors of the presence of CMBs. However, after adjustment of age, sex and variables with p value of less than 0.1on the univariate analysis, baPWV was independently associated with nonlobar CMBs.

Conclusion:
Arterial stiffness was independently associated with nonlobar CMBs but not with lobar CMBs. These findings suggest pathophysiologic association between arterial stiffness and CMBs in the nonlobar region.
Abstract WMP90: Homozygous Short Variation Allele Genotype of the Serotonin-Transporter-Linked Polymporphic Region (5-HTTLPR) is Associated Post-Sstroke Depression- A Meta-analysis
Authors: wakerley benjamin , yeo leonard L , mak Kwok-Kei , Kong Wan Y , mak anslem , ho roger C , sharma vijay
Published: July 2021

Aim:
Polymorphisms of the genes for encoding serotonin transporter, specifically, the length variation in the serotonin-transporter-linked polymorphic region (5-HTTLPR), a single nucleotide polymorphisms, in the 5-HTTLPR (RS25531), and variable number of tandem repeats (VNTR) in the second intron 2 (STin2) have been implicated in the development of post-stroke depression (PSD). We aimed at evaluating this association in the published literature.

Methods:
Random-effects meta-analyses were conducted among studies examining the relations between the polymorphisms of the genes encoding serotonin transporter and the risk of developing PSD. Meta-regression identified patient- and study-related factors that may contribute to heterogeneity.

Results:
Five studies consisting of patients suffering from PSD and stroke patients without PSD were included. Our analyses showed statistically significant evidence of the positive association between the homozygous short (S) variation allele genotype of the 5-HTTLPR (SS) and PSD (random-effects pooled odds ratio (OR) = 2.05, 95% Confidence Interval (CI) = 1.41-2.98, Z =3.79, p< 0.001 ). Our analyses also showed significant evidence of a negative association between the homozygous long (L) variation alleles of the 5-HTTLPR (LL) and PSD (random-effects OR = 0.52, 95% CI = 0.27-0.97, Z =- 2.07, p= 0.039). No statistically significant association of PSD with either heterozygous Short and Long allele genotype for the 5-HTTLPR or other polymorphisms with the RS25531 and the STin2 VNTR were found.

Conclusion:
Our meta-analysis suggests that the 5-HTTLPR SS genotype may be a risk factor for PSD while the 5-HTTLPR LL genotype may be a candidate protective factor against PSD
Abstract WMP93: Uninsured Patients have Longer Hospital Stays and are Less Likely to Receive Rehab than Insured Patients
Authors: Korya Daniel , Drake Kendra , Coull Bruce
Published: July 2021

Background:
In 2010 the estimated direct and indirect cost of stroke was $53.9 billion. The long-term burden to society is thought to be much more costly. Whether or not this sum can be reduced has been a subject of great debate. Recently, healthcare reform has been a priority for policy makers with health insurance as a prevailing issue. We examined the healthcare records of patients in the US who presented with stroke symptoms in a 10-year period from 2001-2011, and compared them to patients in the state of Arizona as well as our University Hospital in the same time period. We then looked for differences in the cost of stroke with regard to variations in insurance status.

Methods:
The records of 978,813 patients with stroke symptoms in the US from January 2001 through December 2011 were compared with 18,875 Arizona (AZ) patients. This data was evaluated and compared with data obtained from the records of 1,123 patients admitted to the University Medical Center (UMC), and separated by insurance status, discharge location and length of stay (LOS) for different stroke subtypes. The information was gathered from the
get with the guidelines
stroke database and only included hospitals that reported their information.

Results:
The mean LOS for stroke patients in the US, AZ and UMC were: 5.25 days, 4.69 and 4.75 days, respectively. When separated by insurance status, the mean LOS for patients at UMC with Medicare was 4.27 days (n=470), for Medicaid it was 6.17 days (n=150) and 5.13 days (n=464) for private insurance. Compared with insured patients, uninsured patients had a LOS of 8.18 days (n=39; p=.001). Uninsured patients were discharged home without rehab 24.4% of the time compared with only 8.8% of insured patients (p=.001), even though 93.5% of uninsured patients were considered for rehab.

Conclusion:
Uninsured patients had a LOS that was 3.3 days longer than insured patients and had an estimated 72% higher cost of hospitalization. Uninsured patients were almost 3 times less likely than insured patients to be discharged with rehab, and consequently were less likely to achieve long-term functional independence. Ultimately, the price of stroke in the uninsured is paid for by taxpayers, since these patients will require social services granted by the government for disability.
Abstract WMP99: Dabigatran: How Does It Fare In The Real World? Mayo Clinic And Regional Experience With A Novel Anticoagulant.
Authors: Adcock Amelia K , Aguilar Maria I , Demaerschalk Bart M
Published: July 2021

Background:
Although not without its limitations, warfarin has provided essential protection against cardioembolic stroke in nonvalvular atrial fibrillation (NVAF) for over 60 years. Dabigatran, the first oral direct thrombin inhibitor to be approved in the United States is reputed to provide the same or better ischemic stroke protection with reduced risk of intracranial hemorrhage. However, it remains to be seen whether its promise will be borne out in everyday practice.

Objective:
Track initial dabigatran course in patients at Mayo Clinic Arizona and regional stroke centers since its approval in 2010.

Methods:
Retrospective chart review of all dabigatran patients between October 2010 and September 2011. Regional practices were obtained from a nationwide survey of cardiologists and neurologists.

Results:
See table

Conclusion:
During our period of review, dabigatran was well tolerated. A smaller than expected number of patients discontinued the agent or experienced adverse events, as compared to randomized controlled trial predictions. Furthermore, rates of ischemic events (2/159 or 1.26%) were exceedingly low. Our study had several limitations (retrospective review; random bias, sample bias with low numbers and a more elderly population, shorter median follow up). Many of these shortcomings could be addressed with prospective patient tracking. As with any novel therapy, provider surveys afforded an important window into real world practices and perceptions regarding dabigatran. The majority believed it was a reasonable alternative to warfarin, citing fluctuating INR’s as the most persuasive target population followed by patient preference. Cost was an important limiting factor to prescription and considerable uncertainty remains surrounding reversibility and how to approach acute thrombolysis in recurrent ischemic stroke.
Abstract WP105: An Effective Delayed Treatment for Ischemic Stroke Uses Fluoxetine and Simvastatin
Authors: Corbett Adrian , Sieber Scott , Wyatt Nicholas , Lizzi Jenna , Flannery Tiffany , Sibbitt Bethany , Sanghvi Saagar
Published: July 2021

For more than 90% of ischemic stroke patients there exists no standardized drug treatment other than giving aspirin or beginning statin treatment for the prevention of future strokes. The purpose of this study was to develop a delayed pharmacological treatment for ischemic stroke, utilizing a combination of drugs that would enhance adult neurogenesis and brain-derived neurotrophic factor. An endothelin-induced stroke was produced in 10-12 month old rats, which have previously been trained on Montoya Staircase and Forelimb Asymmetry tests. Combination drug treatments were tested against vehicle controls, beginning 20-26 hours after stroke induction and continuing for 31 days. Functional tests were performed at various times post-stroke. Daily treatments of 5 mg/kg fluoxetine in combination with 0.5 mg/kg simvastatin and 20 mg/kg ascorbic acid produced a 19-fold increase in neurogenesis (P=0.001 compared to vehicle control), while fluoxetine alone produced a 10-fold increase in neurogenesis (P=0.007 compared to vehicle control). This combination drug treatment results in almost complete functional recovery as measured by Montoya Staircase (mean recovery to 85% of pre-stroke function, P=0.023) and Forelimb Asymmetry tests (mean recovery to 90% of pre-stroke function, P=0.041 and P= 0.05) in 10-12 month old stroked female Long Evans rats. Additional testing of 5 mg/kg fluoxetine and 20 mg/kg ascorbic acid drug combination as a delayed post-stroke treatment has only given half of the functional recovery seen when all three drugs are included, indicating that the statin is essential for full recovery. Fluoxetine is likely to be the other essential component of this combination treatment as it alone resulted in a significant increase in adult neurogenesis.
Abstract WP115: Netrin-1 Promotes Oligodendrogenesis After Experimental Stroke
Authors: He Xiaosong , Wang Yongting , Li Yaning , Lv Yifang , Tang Yaohui , Lin Xiaojie , Yang Guoyuan
Published: July 2021

Introduction:
oligodendrocyte injury after ischemic stroke influences the integrity of white matter, which ultimately leads to neurological deficits. Netrin-1 (NT-1) plays a crucial role in axon guidance during neural development. Also, it promotes oligodendrocyte progenitor cell proliferation. Our previous study demonstrates that netrin-1 overexpression improves neurobehavioral outcomes after ischemia by promoting focal angiogenesis. In this study, we investigate whether netrin-1 facilitates white matter recovery during focal ischemia and further to explore which specific receptor involves in the white matter reconstruction.

Methods:
sixty adult male ICR mice underwent adeno-associated virus (AAV) mediated AAV-Netrin-1 or AAV-GFPgene transfer. These mice received one hour transient middle artery occlusion (MCAO) and 7, 14, 28 days reperfusion at one week after the gene transfer. Western blot and immunohischemistry were used to determine the location and quantification of exogenous NT-1 expression. Neuronalbehavior test were performed to eveluate the neuralbehavioral outcomes. Oligodendrocyte progenietor cell proliferation, maturation and myelination were examined by immunohischemistry.

Results:
NT-1 was highly expressed in the mouse brain after two weeks of AAV-NT-1 gene transfer, which mainly expressed in neurons and astrocytes. Neurobehavioral outcomes were greatly improved at 7, 14 and 28 days after reperfusion in AAV-NT-1 treated mice compared to the GFP control mice (
p
<0.05), The number of proliferated oligodendrocyte progenietor cells, mature oligodendrocytes and MBP positive neurofilaments in the corpus callosum and the striatum in the ipsilateral hemisphere at 7, 14 and 28 days after reperfusion were increased in the NT-1 treated group compared to GFP control mice (
p
<0.01). NT-1 receptor DCC and Unc5H2 are involved in the proliferation of oligodendrocyte progenitor cells,But only Unc5h2 was involved in the re-myelination process.

Conclusion:
NT-1 overexpression improves neurobehavioral outcomes and promotes oligodendrocyte progenietor cell proliferation and maturation. Oue results suggest that netrin-1 not only promotes angiogenesis but also enchances remyelination.
Abstract WP116: Early Hypothermia, But Not Delayed Hypothermia Ameliorates Ischemic Stroke Through Anti-inflammatory Process
Authors: Kawabori Masahito , Hokari Masaaki , Tang Xian N , Zheng Zhen , Calosing Cyrus , Yenari Midori A
Published: July 2021

Hypothermia is neuroprotective against many acute neurological insults. We and others have previously shown that protection by hypothermia is associated with the suppression of the inflammatory response that accompanies stroke. However, comparative mechanisms of the anti-inflammatory process through different hypothermic paradigms have surprisingly not been studied. In this study, we treated mice to early (protective) and delayed (not protective) hypothermia in a stroke model and compared the effect of cooling on the inflammatory response. We also explored the influence of a novel protein, triggering receptor expressed on myeloid cells-2 (TREM2), which is thought to be an important receptor involved in the innate immune response. TREM2 has previously been shown to promote phagocytosis of apoptotic neurons. We subjected male C57/BL6 mice to permanent middle cerebral artery occlusion (MCAO). We identified 2 cooling paradigms, one where cooling (rectal temp=30C) began at the onset of MCAO (early) and a second where cooling began 1h later (delayed). In both cases, cooling was maintained for 2h. A 3rd group was maintained at normothermia as a control (36C). Mice were survived 1, 3, 7, 14 & 30d (n=6/group/time point). Mice from the normothermic and delayed cooling groups had similar ischemic lesions sizes and neurological performance, but mice cooled early showed marked protection as evidenced by smaller lesion size and few neurological deficits at all time points (p < 0.05, 40% reduction). Microglia/macrophages and TREM2 were decreased only in the early cooling group (P < 0.05). Immune cells were reduced only where hypothermia was protective and we conclude that inflammation is probably related to the amount of injury present, and not whether cooling occurred.
Abstract WP118: The Flavanol (-)-Epicatechin Improves Functional Recovery In Mice Subjected To Experimental Stroke
Authors: Leonardo Christopher C , Robbins Sean , Ahmad Abdullah A , Dore Sylvain
Published: July 2021

Background:
Epidemiological studies indicate that flavanol consumption reduces the propensity to develop cerebrovascular disease. Available data suggest actions on multiple pro-inflammatory pathways, yet it remains unclear which pathways mediate functional recovery after stroke. Our goal is to begin identifying the mechanisms by which the flavanol (-)-epicatechin (EC) improves anatomical and functional outcomes. Based upon data from initial dose-response experiments, ongoing studies are investigating hypothesized protective pathways involving matrix metalloproteinase-mediated blood brain barrier protection and Nrf2 transcriptional activation.

Methods:
Male, 8-10wk old C57BL/6 mice were pretreated with EC 90m prior to permanent distal middle cerebral artery occlusion. Vehicle or EC was administered by oral gavage to mimic dietary consumption. Mice were evaluated 1, 4 and 7d post-stroke for performance on various sensorimotor tasks prior to histological assessments.

Results:
Initial experiments demonstrated that mice treated with 15mg/kg EC showed reduced latency to remove adhesive tape at 1d compared to vehicle controls (n=12, p<0.01). Similarly, immunoreactivity for the microglia/macrophage marker Iba1 was increased in the ipsilateral hemispheres of mice 7d after treatment with vehicle (p<0.01), whereas pretreatment with 15mg/kg blocked this effect (n=4). Mice treated with 15mg/kg also showed a trend toward reduced infarct volume relative to vehicle controls (n=5-9 per group). In subsequent reduced dosing studies, vehicle-treated mice again showed deficiencies in removing adhesive tape at 1d (n=8, p<0.01). Remarkably, mice treated with 15, 10 or 5mg/kg EC showed no deficits. Similarly, vehicle control mice showed grip strength impairments up to 7d (n=8, p<0.05) that were absent in all groups of EC-treated mice.

Conclusions:
Preventative administration of EC promotes functional recovery in mice subjected to experimental stroke. Investigations are underway to determine the pathways mediated by EC following administration at these therapeutic doses. Together, these data will provide insights into the potential for (-)-epicatechin as a clinical therapeutic.
Abstract WP126: Utility of Transthoracic Echocardiography in Guiding Secondary Stroke Prevention
Authors: Eckerle Bryan J , Southerland Andrew M , Turner Heather , Johnston Karen C , Worrall Bradford B
Published: July 2021

Background and Purpose
Transthoracic Echocardiography (TTE) has long played a role in determining mechanism of, and ultimately secondary prevention for, acute ischemic stroke. We hypothesized that, based on recently published trials regarding secondary stroke prevention in the setting of patent foramen ovale (PFO) and reduced ejection fraction (EF), TTE results may not influence treatment decisions as greatly as they have previously.

Methods
We retrospectively evaluated 583 consecutive TTEs performed at our stroke center from January 2009 through June 2012. Findings of interest that currently or previously would have affected management included chamber thrombus, mitral/aortic valvular disease (including endocarditis), reduced EF (<35%), PFO, intracardiac tumor, and atrial septal or left ventricular aneurysm. Based on the current evidence, only chamber thrombus, valvular disease, and intracardiac tumor were considered still to be management-changing.

Results
A total of 51 cases (8.75%) yielded findings of interest. When excluding reduced EF and PFO in light of recent evidence, in only six cases (1.03%) were results considered to be management changing. The number needed to treat with TTE to diagnose one management-changing finding was 98. The cost of TTE at our center is approximately $500.

Conclusion
TTE has long been part of the routine evaluation of acute ischemic stroke. In our series, the most common potential stroke risk factors identified on TTE were reduced EF and PFO. Currently available data suggest that these findings may no longer drive clinical practice. Cost effectiveness analysis is warranted to investigate the clinical utility of TTE in the evaluation of the acute stroke patient moving forward.
Abstract WP13: Stroke Severity and Revascularization are the Strongest Predictors of Outcome in Large Vessel Occlusion Strokes: Post-Hoc Analysis of the TREVO 2 Trial
Authors: Lutsep Helmi L , Nogueira Raul G , Gupta Rishi , Jovin Tudor G , Albers Gregory W , Walker Gary A , Liebeskind David S , Smith Wade S ,   for the TREVO 2 Investigators
Published: July 2021

Introduction.:
The Trevo Retriever showed higher recanalization rates and better outcomes than the Merci Retriever in patients with ischemic stroke due to large vessel occlusion (LVO) in TREVO 2.

Hypothesis.:
We assessed the hypothesis that except for device-related variables, predictors of good outcome would be similar in TREVO 2 and single arm Merci Retriever studies.

Methods.:
The study evaluated predictors of good outcome, modified Rankin Scale (mRS) 0-2 at 90 days, in TREVO 2 including those with ischemic stroke due to LVO aged 18-85 years with a National Institutes of Health Stroke Scale Score (NIHSS) 8-29 and a first device treatment pass within 8 hours of symptom onset. A secondary analysis investigated mortality predictors. Variables included baseline characteristics of age, sex, NIHSS, IV tPA use, occlusion side, most proximal occlusion site, stroke etiology, body mass index, systolic blood pressure (BP), diastolic BP, glucose; history including hypertension, diabetes, dyslipidemia, smoking, congestive heart failure (CHF), atrial fibrillation, previous coronary or cerebral ischemia; and procedural characteristics of time from symptom onset to arterial puncture, time to TICI ≥2 or end of procedure, device allocation, intubation status, rescue therapy usage and post device revascularization success TICI ≥ 2 per core lab. Variables were assessed with univariate analysis for association with mRS 0-2 and mortality and those with a p-value of <0.15 were eligible for the multivariate model.

Results.:
TREVO 2 data were available for 168 patients. Variables significant on multivariate analysis for an association with good outcome were baseline NIHSS (OR 0.76, 95% CI 0.67, 0.86), post device revascularization success per core lab (OR 117.6, 95% CI 8.40, 1645), diabetes (OR 0.12, 95% CI 0.03, 0.41), intubation (OR 0.11, 95% CI 0.03, 0.41) and left hemisphere involvement (OR 5.11, 95% CI 1.77, 14.71). Predictors of mortality included baseline NIHSS and left hemisphere involvement but also age and CHF.

Conclusions.:
While age did not appear as a predictor of good outcome and diabetes was negatively associated with it for the first time in a Merci analysis, predictors of favorable outcome in TREVO 2 were similar to those previously reported for the Merci Retriever.
Abstract WP151:
18
F-FDG Uptake Identify Vulnerable Carotid Plaque on PET/CT in a Swine Model
Authors: Shi Zhong-Song , Wang Jin-Shan , Zhang Xiang-Song , Jiang Xiao-Bing , Liu Dong-hong , Li Ming-Chang , Shi Xin-Chong , Liu Zhong
Published: July 2021

Purpose:
The imaging modality
18
F-fluorodeoxyglucose (
18
F-FDG) positron emission tomography (PET) has been recently used to identify inflammation in the atherosclerotic plaque. Increased uptake of
18
F-FDG in human atherosclerotic plaque on PET may predict plaque vulnerability, however, there is a lack of histological validation for PET imaging. The aim of this study is to evaluate the association of plaque vulnerability with FDG uptake on serial PET/CT scans in a swine model.

Methods:
Twenty carotid atherosclerotic models was induced in 10 miniswines using partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by carotid angiography. Serial
18
F-FDG PET/CT scans were performed at 0, 4, 8 and 12 weeks. MR scan for imaging-histologic correlation was performed at 12 weeks, and carotid artery sections were obtained for histopathological examination. The atherosclerotic lesions of AHA type IV to VI were defined as advanced plaques. Carotid arteries were evaluated for increased FDG uptake with a maximum standardized uptake value (SUV) and target-to-backgroud ratio (TBR). The association of carotid plaque vulerability with the serial FDG uptake was analyzed.

Results:
Various stages of atherosclerotic plaques were found in carotid segments from 20 carotid arteries. Most advanced plaque had the feature of vulnerability. FDG uptake in 100 carotid plaques were analyzed. Compared with carotid segments without atherosclerosis, significantly higher FDG uptake was observed in carotid segments with atherosclerosis at 4, 8 and 12 weeks (P<0.001). Mean TBR was significantly higher in advanced plaque group than in early atherosclerosis group at 4, 8 and 12 weeks (P<0.01). Maximum SUV was significantly higher in advanced plaque group than in early atherosclerosis group at 12 weeks (P<0.01), whereas this did not reach statistical significance at 4 and 8 weeks. FDG uptake increased continuously in both groups of advance plaque and early atherosclerosis.

Conclusion:
Increased plaque metabolism revealed by PET persists with time and is associated with the complexity of carotid atherosclerotic plaque in a swine model.

FDG PET/CT may be useful for identification of plaque vulnerability and monitoring the progress of atherosclerotic lesions.
Abstract WP152: The Predictive Value of VEGF And SDF-1α For The Functional Outcome In Patients with Acute Lacunar Infarction Superimposed on Silent Brain Infarction
Authors: Lee Jinho , Lee Kyu-Yong , Kim Young-Seo , Kim Hyun Young , Kwon Hyuk Sung , Park Hyun-Hee , Choi Na-Young , Lee Eunhye , Son Jeongu , Yu Hyun-Jeung , Lee Yeong Bae , Koh Seong-Ho
Published: July 2021

Introduction
: Stroke is one of the most common causes of chronic disability and death. Although prediction of stroke outcome is important, outcome predictors still remain unclear. Vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α), macrophage migration inhibitory factor (MIF), and high mobility group box 1 (HMGB1) have been reported to play critical roles in neurovascular remodeling or mediating inflammation at acute and subacute phase after ischemic stroke.

Hypothesis
: Wehypothesized that association between silent infarctions and favorable outcome would be affected by expression of angiogenic factors.

Methods
: From January 2009 to March 2011, 68 consecutive patients with first-ever lacunar infarction (50%) intracranial and extracranial stenosis, use of rtPA and strokes of other determined etiologies. We also excluded patients with acute infection, chronic inflammatory disease and cancers. Serum samples were collected from patients immediately after admission and were stored at -80°C. Serum VEGF, SDF-1α, MIF, and HMGB1 were assessed with commercially available quantitative sandwich ELISA kit. Clinical, laboratory, and image findings including NIH stroke scale were obtained at admission and modified Rankin Scale (mRS) was evaluated after 3 months of stroke onset. A favorable outcome was defined as an mRS between 0 to 1.

Result
: Silent brain infarctions were noted in 31 (45%) of the 68 patients. Patients with silent infarctions were associated with hypertension (p=0.055) and advanced leukoaraiosis (p<0.001).

Conclusions
: In patients with lacunar infarction, previous silent infarctions were associated with favorable outcome and early increased expression of VEGF. We suggest that association between silent infarctions and favorable outcome may be affected by expression of angiogenic factors such as VEGF. On the other hand, the finding that SDF-1α reflecting the severity of lacunar infarctions decreased in acute lacunar infarction patients with silent infarctions might suggest that lesser SDF-1α may be related with lesser damage after acute lacunar infarction and then better outcome.
Abstract WP162: Impact of Carotid Artery Remodeling by T1 weighted MR Imaging for the Assessment of Plaque Vulnerability in High-grade Carotid Stenosis
Authors: Fukuda Kenji , Iihara Koji , Yamada Naoaki , Ueda Hatsue
Published: July 2021

Background-
The relationship between coronary artery remodeling and plaque vulnerability has been described on the basis of symptomatology and histology. However, the association with carotid artery remodeling has not been explored in detail. The aim of this study was to validate the relationship between carotid artery remodeling and plaque vulnerability by comparing the degree of outward remodeling calculated using 3D inversion-recovery-based T1-weighted imaging (magnetization-prepared rapid acquisition gradient-echo [MPRAGE]) with the symptomatology and histology of plaques extracted during carotid endarterectomy (CEA).

Methods and Results-
Sixty-one patients with high-grade carotid stenosis who underwent CEA and whose plaque could be examined were included. The average rate of stenosis as per the NASCET criteria was 79.8%. The carotid remodeling index (CRI) was determined by measuring the external cross-sectional vessel area (CSVA) of the maximum stenosis of the internal carotid artery (ICA) and dividing it by the external CSVA of the distal ICA unaffected by atherosclerosis using MPRAGE imaging. The relationship between the CRI and plaque vulnerability was evaluated on the basis of symptomatology and histology. The CRI was significantly higher in symptomatic patients than in asymptomatic patients (1.98 ± 0.26 vs. 1.68 ± 0.24, p < 0.0001). A higher CRI was positively correlated with the necrotic core area (r = 0.568, p < 0.0001) as well as significantly associated with severe intraplaque hemorrhage (p < 0.0001) and the prevalence of cap inflammation with macrophage (p = 0.03) and lymphocyte (p = 0.01) infiltration.

Conclusion-
These results validate the relationship between carotid artery remodeling and plaque vulnerability in high-grade carotid stenosis. MPRAGE imaging is effective to assess plaque vulnerability in terms of the CRI in addition to the signal intensity of carotid plaques.
Abstract WP186: Association Between Blood Pressure, Internal Carotid Artery Flow Parameters And Age-related White Matter Disease
Authors: Aribisala Benjamin S , Valdes Hernandez Maria C , Royle Natalie A , Maniega Susana , Bastin Mark , Deary Ian , Wardlaw Joanna M
Published: July 2021

Background:
White matter lesions (WML) are associated with hypertension. Blood pressure (BP) is transmitted to the brain via the carotid arteries, and autoregulation helps protect the brain. We investigated if BP via carotid waveform parameters were associated with WML.

Methods:
We obtained BP measurements from a cohort of community dwelling subjects at mean ages 70±1 and 73±1 years; brain MRI and carotid artery ultrasound at mean age 73±1 years. We calculated mean values of BP (systolic, diastolic, mean, variability and pulsatility), measured WML by volume, and Fazekas scale. We calculated internal carotid artery (ICA) mean blood flow velocity, pulsatility index (PI), and resistivity index (RI). We tested associations between BP and ICA flow parameters and WML using multiple linear regression, corrected for intracranial volume (ICV), age, gender, BMI, previous MI, diabetes, hypertension, smoking, hypercholesterolaemia, PVD and stroke.

Results:
Amongst 694 subjects, diastolic and mean BP decreased and hence BP pulsatility increased significantly between ages 70 and 73 years. Lower diastolic BP and higher BP pulsatility were associated with higher ICA PI (standardized β, age 70= -0.24, age 73= -0.19, both p<0.001; age 70 β=0.18, p<0.001, age 73 β=0.10, p=0.008 respectively). WML volume was weakly associated with BP at age 70 (diastolic β=0.08, systolic β=0.08, mean β=0.09, all p<0.05) but not with BP variability or pulsatility. Similar but weaker associations were seen at age 73. After adjusting for BP, larger WML volume was associated with higher ICA PI (β=0.10, p=0.012), but not any other measures. All associations were the same for WML Fazekas scores.

Conclusions:
The relatively weak association between BP and WML may be mediated via ICA pulsatility which is largely driven by falling diastolic BP. This questions the nature of the apparent link between BP and WML.
Abstract WP196: Race-Ethnic Disparities in Cardiometabolic Risk among Stroke Survivors with Undiagnosed Diabetes and Pre-Diabetes
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce
Published: July 2021

BACKGROUND
Diabetes/pre-diabetes can be associated with elevated risk of vascular events after stroke, a risk that may be reduced with tight vascular risk factor control. We recently determined that 1 in 3 US stroke survivors are unaware that they have pre-diabetes and 4% have undiagnosed diabetes; however, little is known regarding cardiometabolic factors among these individuals. Understanding race/ethnic variations may guide implementation of targeted interventions.

OBJECTIVE
To assess race/ethnic differences in vascular risk factors among a nationally representative sample of stroke survivors with undiagnosed diabetes/pre-diabetes.

METHODS
Retrospective analysis of adults (≥20 years) with self-reported stroke who participated in NHANES 1999-2010 (n=1070). Among individuals with undiagnosed diabetes and pre-diabetes (HbA1c ≥6.5% and HbA1c 5.7-6.4% without self-reported physician-diagnosis), BP, total cholesterol, LDL, HDL, and triglyceride (TG) levels were compared across race/ethnic groups, adjusting for age, sex, antihypertensive and lipid medication use, HbA1c level, and NHANES cycle. Estimates were weighted in order to obtain nationally representative estimates.

RESULTS
An estimated 1,099,535 stroke survivors had undiagnosed pre-diabetes: 38% of non-Hispanic blacks (NHBs), 32% of non-Hispanic whites (NHWs) and 26% of Hispanics. An estimated 125,832 had undiagnosed diabetes: 7.5% of NHBs, 4.4% of Hispanics, and 3.1% of NHWs. Overall, 10% had HbA1c levels ≥6.5%, 23% smoked, 65% had hypertension, 48% had hypercholesterolemia, 67% were on antihypertensive agents, and 40% were on lipid medications. Mean SBP and DBP were higher in NHBs vs. NHWs (145 vs.135 and 75 vs. 70 mm Hg; p<0.001). Also, NHBs were more likely than NHWs to have BP>130/80 mm Hg (adjusted HR 2.25, 95% CI 1.06-4.74). However, NHBs had higher mean HDL (52 vs. 48 mg/dL; p=0.06) and lower mean TG (116 vs. 148 mg/dL, p=0.03) levels than NHWs.

CONCLUSIONS
Among stroke survivors, cardiometabolic profiles vary by race/ethnicity. NHBs have the highest prevalence of undiagnosed diabetes/pre-diabetes and are over twice as likely as NHWs to have poorly controlled BP; however, they have better lipid profiles, suggesting a need for targeted screening and tailored interventions
Abstract WP199: Higher Stroke Prevalence Rates among Ribeirinhos Compared to Townsmen in the Brazilian Amazon.
Authors: Fernandes Tiotrefis G , Bensenor Isabela M , Lotufo Paulo A
Published: July 2021

There is a lack of epidemiological studies addressing cerebrovascular diseases in remote places as the Amazon river basin. We aimed to calculate the stroke prevalence rates among "ribeirinhos", rural inhabitants who living in riverbanks fishing and extracting fruit and nuts, in the rainforest comparing to townsmen in the same municipality.

Methods:
From May to October 2011, 6216 residents aged over 35 years in the of Coari, a municipality that is coverage by the Family Health Program with of 76 000 inhabitants, 35% of them are "ribeirinhos”. We trained all community health workers to carry out a door-to-door application of the “Stroke Symptom Questionnaire” for people over 35 years-old. This tool was applied first for the family for stroke screening and further for the index stroke case, including questions about six key functional impairment. It was previously translated to Portuguese and validated by a neurologist.

Results:
From a total of of 4897 respondents of urban area and 1028 "ribeirinhos", we calculated crude prevalence of stroke of 6.3% (95% CI; 5.0-7.7) among the "ribeirinhos" and of 3.7% (95% CI; 3.3-4.1) among townsmen. This difference was maintained after sex-age-adjustment. The female:male prevalence ratio was 1.37 (95% CI; 1.02-1.85) in urban area and the rural area of 0.93 (95% CI; 0.57-1.52). Among stroke suffers, the "ribeirinhos" were those with less access to medical care (32.1% vs. 52.5%, p=0.01) and a lower proportion of stroke survivors requiring help with least 1 activity of daily living (16.9% vs. 39.3%, p=0.001) in comparison to townsmen.

Conclusion:
To our knowledge it was the first study that provided a population-based stroke survey in the Amazon rainforest revealing a higher stroke prevalence among "ribeirinhos" compared to townsmen of the same municipality.
Abstract WP214: Cortical Microinfarcts as a Putative MRI Marker for Cerebral Amyloid Angiopathy
Authors: Ii Yuichiro , Maeda Masayuki , Kida Hirotaka , Ito Ai , Shindo Akihiro , Taniguchi Akira , Tomimoto Hidekazu
Published: July 2021

Background:
Cortical microinfarcts (CMIs) are frequently detected in autopsy brains of elderly subjects, and distributed predominantly in the area of predilection for cerebral amyloid angiopathy (CAA). Recently these lesions have been detected on high-filed MRI using double inversion recovery (DIR) and 3D-fluid attenuated inversion recovery (FLAIR). Radiological diagnosis according to Boston criteria for CAA may be reinforced by detecting CMIs.

Methods:
We performed a prospective analysis of 36 patients diagnosed as clinically probable CAA by Boston criteria, including multiple strictly lobar microbleeds as a diagnostic indicator. These patients were recruited at the Department of Neurology, Mie University Hospital from August 2009 to April 2012. 3-tesla MR images including susceptibility-weighted imaging (SWI), DIR and 3D- FLAIR were reviewed.

Results:
CMIs were found in 9 of 36 (25%) patients. Most CMIs were located in close proximity to lobar microbleeds. Cortical superficial siderosis was observed in 6 of 36 (16.6%) patients, among which 5

(83.3%) showed CMIs. There were 5 patients with symptomatic subcortical hemorrhage, and 3 of these (60%) showed both CMIs and superficial siderosis.

Conclusions:
These results indicate that CMIs strengthen radiological diagnosis of CAA if these lesions coexist with multiple strictly lobar microbleeds and cortical superficial siderosis.
Abstract WP216: Cortical Network Dynamics in Acute Ischemic Stroke
Authors: Liu Virginia , Winter William , Xie Kate , Kanjiya Shrey , Tran George , Srinivasan Ramesh , Cramer Steven C
Published: July 2021

INTRODUCTION:
Measures of brain function are a unique source of insight into stroke effects, but the most commonly used methods (fMRI, PET) are difficult to implement in acutely ill patients, and so little is known about changes in brain function in the days after stroke. Advances in dense-array electroencephalography (dEEG) make possible the study of cortical network dynamics at the bedside. The current study addressed the hypothesis that changes in the motor network are measurable in first days post-stroke, and that these network changes are related to behavioral deficits.

METHODS:
Nine patients with acute (<120 hours) ischemic stroke underwent dEEG and behavioral testing that included Box & Blocks score (1 min). The dEEG signals from 256 scalp leads were recorded at 1000Hz, along with bilateral forearm EMG, during cued 0.14 Hz wrist flexions. Nine age-matched healthy controls underwent the same assessments. Cortical network dynamics were assessed in the motor system using EEG coherence between leads, focusing on β range (20-30 Hz) signals. Spectral power in this range was also obtained.

RESULTS:
Patients were 62±13 years old, with median NIHSS score=3 (range 1-12), and could move 26±18 blocks (range 0-50) on the Box & Blocks test, fewer than controls (59±7 blocks, p<0.0001). In patients, as compared to controls, the region overlying ipsilesional hand motor cortex showed increased coherence with [A] contralesional hand motor cortex (0.13±0.06 vs 0.07±0.05, p=0.03) and [B] supplementary motor area (0.27±0.12 vs 0.15±0.07, p=0.02) during flexion of the affected wrist. Spectral power did not differ between groups in these regions. Across all subjects, the magnitude of coherence between hand motor cortex and supplementary motor area was inversely related to Box & Blocks score (r=-0.61, p=0.008).

CONCLUSIONS:
Assessment of cortical dynamics in the motor system is feasible in the acute stroke setting, with hemiparetic patients demonstrating significantly increased β coherence. Increased EEG coherence between two motor cortex regions after stroke might reflect increased functional connectivity due to the reduced cortical inhibition that is seen early after stroke, effects of deafferentation, or increased input from a common area such as the thalamus.
Abstract WP227: Magnetic Resonance Measurement Of Static Global And Regional Cerebral Autoregulation
Authors: Sen Souvik , An Hongyu , Oakes Jonathan , Menezes Prema , Lin Weili , Powers William J
Published: July 2021

Background:
Reliable methods used to test static cerebral autoregulation are time-consuming and/or invasive.

Objectives:
To evaluate if noninvasive magnetic resonance measured oxygen extraction fraction (OEF), cerebral blood flow (CBF), and oxygen metabolic index (OMI=CBF×OEF) can consistently detect expected physiological changes in humans under normal and 10-15% lowered mean arterial pressure (MAP).

Methods:
Static cerebral autoregulation was determined by measuring changes in CBF using a pseudo continuous arterial spin labeling (pCASL) approach and Oxygen Extraction Fraction (OEF) using MRI T2‘-weighted asymmetric spin echo echo-planar imaging (EPI) sequences, in response to 10-15% reductions in MAP in stroke-free controls induced by using IV Nicardipine. Images were acquired in 3T MR scanner (Trio, Siemens Medical Systems Inc). Autoregulation was measured globally and regionally in the anterior (ACA), the middle (MCA) and the posterior cerebral artery (PCA) territories of the brain manually defined using autopsy based model. Autoregulatory Index (AI) was computed (AI = %CBF change/% MAP change) supplemented by CBF associated OEF changes. Baseline regional CBF and OEF, AI, CBF and OEF changes to 10-15% lowering of MAP

Results:
Nineteen normal volunteers (mean age 30, 95% male, 50% white, 40% black, 10% others) were consented to the protocol approved by the institutional review board. MAP lowering was successfully achieved in all subjects (Mean ± standard deviation of MAP lowering of 12.5 ± 5.6 mm Hg). At a global level this resulted in no significant change between pre-MAP lowering CBF (56.0 ± 8.5 ml/100g/min) and post-MAP lowering CBF (55.9± 8.8 ml/100g/min). This translated to a AI of 0 ± 1.2. The CBF results corroborated with no significant change in OEF and OMI. Baseline regional CBF was higher in the MCA territory (66.1 ± 7.6 ml/100g/min) compared with the ACA territory (52.8 ± 8.6ml/100g/min, p<0.001). The AIs were consistent (ANOVA p=0.15) at regional levels across ACA (-1.5 ± 3.1), MCA(-0.3± 2.1) and PCA (-0.1 ± 1.4) territories.

Conclusions:
Global and regional static cerebral autoregulation can be measured using MR measurement of CBF, OEF and OMI, before and after 10-15% reductions in MAP in healthy volunteers.