bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 475: Human Saphenous Vein Progenitor Cells Are Susceptible to Mechanical Stimulation. Novel Insights in Pathologic Programming of Saphenous Vein Bypass Graft Disease
Authors: Garoffolo Gloria , Vono Rosa , Carrara Matteo , Santoro Rosaria , Zoli Stefano , Saccu Claudio , Martelli Fabio , Spinetti Gaia , Madeddu Paolo , Pesce Maurizio
Published: July 2021

Background:
Implantation of saphenous vein (SV) grafts into coronary position determines structural vessel wall remodeling and intimal hyperplasia. The role of the altered wall mechanics and cell-based mechanosensing has been recently implicated in the priming of this pathologic process. We investigated the effects of cyclic uniaxial strain on human saphenous vein progenitor cells (SVPs), a cell type endowed with pericyte stem cell characteristics resident in the adventitia.

Methods:
CD34
+
CD31
-
SVPs were isolated with immuno-magnetic sorting (MACS) from SVs of patients (age 58±12.6, Mean±SD) undergoing saphenectomy. Cells were subject to uniaxial strain (10% elongation; 1Hz) for 24 and 72 hrs using the FlexCell system. Cell orientation, immunofluorescence and western analyses were performed to assess the effects of strain on cell orientation/shape, cell cycle and activity of the YAP/Hippo-dependent mechanotransduction machinery. RNA-sequencing from control
vs.
strained SVPs was performed at both time points using RNA from cells of 5 independent donors.

Results:
Results indicated an increase in the expression of the cell cycle-associated markers Ki67 and pHH3 in mechanically stimulated
vs.
control SVPs at 24 hrs, followed by a significant reduction at 72 hrs of stimulation. Variations in cell shape was observed as verified by a significant change in the nuclei orientation in the strain field as well as in the cell shape index/spread areas at both time points. Immunofluorescence revealed a significant increase in cells showing a nuclear localization of the YAP transcription factor at 72hrs. In line with these findings Western analyses indicated a significant decrease in the ratio between phosphorylated/total YAP and its upstream kinase LATS in mechanically stimulated
vs.
control SVPs, suggesting an inhibition of the HIPPO kinase pathway by mechanosensing. RNASeq gene expression analyses showed a coherent modification of gene expression pathways and the upregulation of a specific HIPPO/YAP/TEAD gene expression signature in SVPs mechanically stimulated for 72hrs.

Conclusions:
These findings demonstrate the direct susceptibility of human SVPs to pathologic strain and identifies this cell population as mechano-perceptors in the vein wall.
Abstract 87: Alterations to Cardiac Mechanics Do Not Preserve Normal Cardiac Function in a Novel Ossabaw Swine Model of Heart Failure with Preserved Ejection Fraction
Authors: Edwards Jenna C , Dionne Madeleine , Olver T. D , Ivey Jan R , Thorne Pamela K , Padilla Jaume , Ford David A , Baines Christopher P , Rector R. S , Emter Craig A
Published: July 2021

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is clinically characterized by an increased incidence in females and many comorbidities including type 2 diabetes (T2D) and obesity. Animal models accurately representing clinical HFpEF are lacking; thus, the purpose of this study was to examine left ventricular (LV) mechanics in a novel Ossabaw swine model of chronic pressure-overload (aortic-banding; AB) and T2D (Western diet; WD) using two dimensional speckle tracking echocardiography (2D-STE). We hypothesized that global LV strain would be decreased primarily in the longitudinal direction in WD-AB animals.

Methods:
Female Ossabaws were randomly divided into 2 groups: CON (n=5) and WD-AB (n=5). LV function and strain were measured at 1 year of age after 6 mo. of AB and 9 mo. of WD via pressure-volume relations and 2D-STE. Significance was set at P < 0.05 using t-test vs. CON.

Results:
In the WD-AB group, ejection fraction (EF%) and end diastolic volume were normal (>50%), and observed in parallel with increased LV weight, lung weight, and LV diastolic wall thickness (i.e. concentric hypertrophy). WD-AB group had increased HOMA-IR and body surface area, two common features in T2D. In WD-AB animals, although global longitudinal systolic strain rate and end systolic displacement were increased, stroke volume index was decreased. Early diastolic rotation rate was decreased, while global longitudinal late diastolic strain rate was increased in the WD-AB group. These changes, considered in parallel with an increased end diastolic pressure-volume relationship in WD-AB animals, are consistent with diastolic dysfunction. In contrast, longitudinal, radial, and circumferential early diastolic strain rates increased in the WD-AB group.

Conclusion:
Contrary to our hypothesis, LV longitudinal strain was increased during both systole and diastole, and observed in parallel with decreased early diastolic untwisting in WD-AB animals. Our results suggest alterations to LV mechanics do not preserve normal systolic and diastolic cardiac function, despite normal resting EF%, in this novel translational model of pressure-overload HF with potential relevance to human HFpEF including associated clinical comorbidities (sex, obesity, and T2D).
Whole-Body Circulatory Autoregulation and Hypertension
Authors: COLEMAN THOMAS G. , GRANGER HARRIS J. , GUYTON ARTHUR C.
Published: July 2021

A possible cause of elevated arterial pressure involves the interrelationship between autoregulation of blood flow and control of arterial blood pressure. An autoregulatory response could theoretically result in an elevated arterial pressure and an elevated peripheral resistance with normal or nearly normal cardiac output. Several experimental studies support this theory.

Autoregulation of blood flow has been observed in a number of the body's tissues, and the summated effect, whole-body autoregulation, has been demonstrated in areflex dogs. An increase in cardiac output precedes an increase in total peripheral resistance, and a decrease in cardiac output precedes a decrease in total peripheral resistance. The gain of the system was calculated to be slightly greater than three. This same hemodynamic pattern, that is, an increase in cardiac output preceding an increase in resistance, has been observed at the onset of hypertension. We have observed increases in cardiac output at the beginning of salt-induced hypertension in dogs and at the beginning of hypertension secondary to fluid volume expansion in anephric patients, while other investigators have observed this hemodynamic pattern in a number of instances, including labile hypertension, perinephritis hypertension, and Goldblatt hypertension. The increased cardiac output can be caused by several factors, although in many instances the cause appears to be fluid retention.

A hemodynamic response suggesting the involvement of whole-body autoregulation, that is, a decrease in cardiac output precedes a decrease in peripheral resistance, has been observed in the reversal of hypertension. Dehydrating overhydrated (and hypertensive) anephric patients and unclipping the renal artery in Goldblatt hypertension elicits this pattern, as well as administration of diuretics or several other antihypertensive drugs to hypertensives.

Theoretically, the role of the kidney in hypertension is either to initiate the autoregulatory response by causing fluid retention or to allow the autoregulatory response to occur by preventing the loss of fluid in the face of an elevated arterial pressure.
GLIAL GLUTAMATE TRANSPORTER GLT-1 DOES NOT REVERSE ITS FUNCTION IN ISCHEMIC PENUMBRA.
Authors: Zaleska Margaret M , Gonzales Cathleen , Djali Sina , Dawson Lee A
Published: July 2021

4

Functional glutamate uptake systems are critical for maintenance of normal synaptic transmission. Several studies have shown that in severely ischemic brain regions, massive efflux of excitatory amino acids (EAAs) results, in large portion, from the reversal of Na
+
-dependent glutamate transporters. This study was designed to examine the function of the predominant glial transporter, GLT-1, in a brain area representative of ischemic penumbra. Spontaneously hypertensive rats were subjected to a 45 min transient focal ischemia by intraluminal occlusion of the middle cerebral artery (MCAO). In this model, the core ischemic region resides in the medial striatum while the surrounding parietal cortex represents a penumbral area. Temporal profiles of extracellular levels of glutamate [Glu]
e
and aspartate [Asp]
e
were assessed using microdialysis in the parietal cortex. Preischemic [Glu]
e
and [Asp]
e
were constant and no changes were observed in sham operated animals. MCAO induced rapid efflux of EAAs with the peak of 7 and 9 fold increases in [Glu]
e
and [Asp]
e
at 20 min post MCAO, respectively. Levels of both EAAs returned to baseline prior to reperfusion. In contrast, a local infusion (reverse microdialysis) of the GLT-1 selective nontransportable inhibitor, dihydrokainate (DHK, 1 mM) during the ischemic insult,prolonged and increased the efflux of both EAAs throughout MCAO interval resulting in peak 9 and 16 fold increases (p>0.05) in [Glu]
e
and [Asp]
e
, respectively, at 40 min post MCAO. The total ischemic efflux of Glu and Asp (areas under the curve, AUC) was increased by 70% and 98%. Infusion of the voltage dependent Na
+
channel blocker tetrodotoxin (TTX, 10 μM) during the ischemic period attenuated the initial MCAO-induced Glu and Asp efflux from 7 to 2 fold and from 9 to 2 fold, respectively. These data provide the first evidence that within the ischemic brain penumbra, GLT-1 remains functional and displays no evidence of reverse transport. In addition, the attenuation of MCAO-induced EAA efflux by TTX indicates that the source of penumbral release is primarily neuronal.
Improved function and perfusion with pharmacological blood pressure elevation
Authors: Hillis Argye E , Barker Peter , Aldrich Eric , Ulatowski John A , Beauchamp Norman J , Robert Wityk
Published: July 2021

20

A few studies have reported improved function in acute stroke with pharmacological elevation of mean arterial pressure (MAP), but statistical correlations between function and MAP have not been documented. We studied 10 acute-subacute stroke patients before, during, and after MAP elevation (using IV phenylephrine and oral agents), with detailed cognitive tests and serial MR perfusion and diffusion scans to identify relationships between MAP, deficits, and regional perfusion. Cognitive assessment included tests of word and sentence comprehension and naming (for dominant hemisphere stroke), and tests of copying and spatial attention (for nondominant stroke). Separate forms of each test, matched in difficulty, were administered daily. Blinded reviewers measured volume of hypoperfused regions on “time to peak” maps.
Results:
5 patients showed striking correlations between MAP and 1 or more cognitive tests: in 4 aphasic patients MAP was highly correlated with both naming and word comprehension (r=.88–96; p<.0005-.002 across cases); in 1 case of nondominant stroke MAP was associated with copying score (r=.90; p<.04). Another 3 patients showed fairly high correlations between MAP and naming (r=.67; .78; .94, respectively) that did not reach significance (p=.06–0.12) likely due to too few data points. For each of these 8 cases increased MAP was associated with improved language or visuospatial function, and subsequent falls in MAP were associated with deterioration in function. The last 2 patients showed no significant MAP elevation with therapy and showed no substantial change in function. In 8/8 patients who showed increased MAP and improved cognition, serial MR perfusion scans demonstrated reduction of regional hypoperfusion while MAP (and function) increased. In 1 case, when MAP fell and function deteriorated, repeat perfusion scan showed reversal of the prior improved perfusion. Both (2/2) patients with no increase in MAP or function showed no improvement of perfusion with therapy.
Conclusions:
In selected patients with recent stroke, raising MAP can be associated both with improvement in specific domains of cognition and with improved regional cerebral perfusion.
Ineffective Secondary Prevention in Survivors of Cardiovascular Events in the US Population: A Report from the Third National Health and Nutrition Examination Survey.
Authors: Qureshi Adnan , Suri M Fareed K , Guterman Lee R , Hopkins L N
Published: July 2021

26

Background and Purpose:
Survivors of myocardial infarction (MI) or stroke are at high risk for subsequent cardiovascular events. There is limited assessment of the effectiveness of risk factor modification through current secondary preventive strategies in the US population.
Methods:
The adequacy of control for hypertension, diabetes mellitus, cigarette smoking, alcohol use and hypercholesterolemia was assessed by personal interview, blood pressure measurements, and serum glycosylated hemoglobin and cholesterol levels in a nationally representative sample of US adults. We also evaluated the role of potentially related factors including age, gender, race/ethnicity, educational attainment, socioeconomic and medical insurance status using multivariate logistic regression analysis.
Results:
A total of 1252 survivors of MI or stroke were evaluated in the Third National Health and Nutrition Examination Survey. Among the 738 known hypertensive persons, hypertension was uncontrolled (systemic blood pressure >140/90 mm Hg) in 388 (53%) patients. Previously undiagnosed hypertension (systemic blood pressure > 140/90 mm Hg) was detected in 138 (11%)other survivors. Of the 1252 survivors, 225 (18%) persons were currently smoking and heavy alcohol use was observed in 56 persons. Hypercholesterolemia was poorly controlled (serum cholesterol >240mg/dl) in 185 (46%)of the 405 persons with known hypercholesterolemia. Undetected hypercholesterolemia was observed in 160 (13%) persons. In the multivariate analysis, high risk profiles (defined as presence of two or more poorly controlled risk factors) were more likely to be observed in persons aged 45–65 years (OR 2.5, 95% CI 1.3–4.8), women (OR 1.6, 95% CI 1.3–2.1) and African-Americans (OR 1.4, 95% CI 1.01–1.9).
Conclusions:
Our report points out the alarming magnitude of inadequate secondary prevention in the US population. Considerable efforts are required to effectively implement risk factor modification strategies after MI or stroke, particularly in middle aged persons, African-Americans and women.
The Canadian Activase for Stroke Effectiveness Study (CASES): Interim Results
Authors: Hill Michael D , Buchan Alastair M
Published: July 2021

39

Background
Therapy for acute stroke using rtPA was approved in Canada in February 1999. The Canadian Activase for Stroke Effectiveness Study Group was formed to study the use of rtPA in Canada in a 30-month post-marketing study.
Purpose
To both prospectively assess the safety of rtPA in the Canadian context and to examine whether the efficacy of rtPA for acute stroke, demonstrated in the NINDS trial, can be translated into effectiveness in routine clinical practice across Canada.
Methods
The CASES group is a collaboration among the Canadian Stroke Consortium (CSC), the Canadian Stroke Society, the Heart & Stroke Foundation of Canada, Hoffman-LaRoche Canada and physicians across the country. Centres across the country were registered and recruitment is ongoing. The study protocol has been approved by the research ethics board at each centre. Demographics, stroke risk factors, blood pressure, biochemistry, hematology, and CT scans are being collected. NIHSS and mRS scores are being collected prospectively. Outcomes will be monitored at discharge and at 3 months.
Results
In the first 20 months,72 centres are registered and 525 patients have been treated. The median NIHSS score is 14 (range 2–35). 30% of patients have minimal or no neurological deficit (NIHSS 0–1)and 47% are independent (mRS 0–2) at 90 days. The symptomatic hemorrhage rate is 4.0% (95%CI 2.5% to 6.0%). Multivariate analysis has failed to identify predictors of symptomatic ICH. The rate of protocol violations is 10%, the majority of which are time window violations. Based upon a phone survey of hospitals in Canada with CT scanners, the data set is 75% complete.
Conclusions
CASES is an ongoing prospective evaluation of the effectiveness of rtPA in acute stroke. The symptomatic hemorrhage rate is low (4.0%). Alteplase for ischemic stroke is safe and effective in Canada.
Neuroprotection in Acute Ischaemic Stroke
Authors: Ladurner Gunther
Published: July 2021

41

Aim:
This multicentre, double-blind, placebo-controlled trial was conducted to assess the efficacy and safety of an adjuvant administration of Cerebrolysin
®
(CERE) in patients suffering from acute ischaemic stroke.
Methods:
Patients with a first acute ischaemic stroke of the middle cerebral artery were randomised to IV therapy either with placebo (n=68) or with CERE 50ml/day (n=78), for 21 days. Both groups were treated also with acetylsalicylic acid 250mg/day PO and pentoxifylline 300mg/day IV. Treatment was initiated within 24h (mean 12.9±8.1h) after onset of first symptoms. Patients were investigated on treatment days 1, 3, 7, 21 and a follow-up investigation was carried out 3 months after start of treatment. Clinical outcome was recorded on the Canadian Neurological Scale (CNS), Barthel Index (BI) and Clinical Global Impressions (CGI). CERE is a peptide preparation with proven neuroprotective (calpain and caspase inhibitor) and neurotrophic action, produced by a standardised enzymatic breakdown of lipid-free brain proteins.
Results:
Patients in the CERE group showed a significant improvement in motor functions (CNS, section A1) at the end of therapy (t-test p<0.05) when compared to the placebo group. CERE patients treated within 6 hours after onset of stroke showed a significant improvement in the CGI in the acute treatment phase (t-test p<0.05; CERE n=16, placebo n=14). In the subgroup of patients with a right-sided stroke, CERE patients had a significantly better performance in the BI than placebo patients (Mantel-Haenszel test p<0.001). CERE and placebo were well tolerated and safe. Three patients died in the placebo group, and 2 patients in the CERE group.
Conclusion:
CERE seems to be an effective adjuvant treatment for acute ischaemic stroke. Motor functions were significantly better, and subgroup evaluation showed that early CERE treatment was related to improved clinical outcome. Adjuvant CERE demonstrated a fast onset of action and offered the possibility for an accelerated rehabilitation probably due to its neuroprotective effect. Large clinical trials are needed to confirm these results.
Graduating neurology residents’ experience with use of intravenous tPA for acute ischemic stroke
Authors: Cucchiara Brett L , Kasner Scott E
Published: July 2021

45

Background:
Intravenous tPA was approved as a treatment for acute ischemic stroke in 1996. One potential barrier to increased use of tPA has been lack of experience and training among neurologists. To date, there has been no formal assessment of neurology residents’ experience with tPA during their training.
Methods:
A 12 item survey was sent in March 2000 to all graduating neurology residents as identified by AMA-GME files. Follow-up surveys were sent in April and May to non-responders. Survey items established residents’ experience and confidence with assessment of the acute stroke patient and use of tPA. Responses were assessed using a 5 point Likert scale. Presence of a dedicated stroke team, ongoing stroke clinical trials, and post-residency career plans were also assessed.
Results:
Of 398 graduating residents for whom addresses were available, 287 (72%) responded. 80% of respondents had personally treated a patient with tPA; 33% had done so without direct faculty supervision. 12% had neither treated nor observed a patient being treated with tPA. 89% had cared for an acute stroke patient in the first hours after administration of tPA. 73% felt comfortable independently treating acute stroke patients with tPA. 65% of residents had formal NIHSS training. Nearly all residents felt confident in their ability to identify hemorrhage (99%) and early infarct signs (94%) on CT. Residents whose institutions had a stroke team were more likely to have provided post-tPA care (93% vs 71%, p<0.001), to have had formal NIHSS training (69% vs 44%, p<0.001), and to feel comfortable independently treating patients with tPA (75% vs 62%, p=0.08). There was no association between career plans (academics vs private practice) and any survey items.
Conclusion:
One fifth of graduating neurology residents had never personally treated an acute stroke patient with tPA; one in ten had never seen tPA administered. One quarter did not feel comfortable independently treating with tPA. Experience with current treatment for acute stroke should be considered an essential part of neurology residency training. Stroke teams may be helpful in accomplishing this goal.
NIH Stroke Scale as a Predictor of Clot Presence, Location, and Persisting Occlusion in Candidates for Thrombolysis
Authors: Burgin W Scott , Wojner Anne W , Grotta James C , Alexandrov Andrei V
Published: July 2021

46

Background:
In acute stroke, few tools are readily available to determine clot presence and location before thrombolysis, nor whether occlusion persists after intravenous TPA. Because the NIH Stroke Scale (NIHSS) is easily obtained in the Emergency Department, we correlated sequential NIHSS scores and arterial occlusion in prospective candidates for IV TPA.
Methods:
Potential thrombolysis patients evaluated with transcranial Doppler (TCD) ultrasound and the NIHSS at the time of presentation were studied. TCD was performed using previously validated criteria for clot detection, localization, and subsequent degree of recanalization after thrombolysis. In patients treated at <180 minutes with conventional dose TPA (0.9 mg/kg), repeat NIHSS scores and diagnostic TCD were performed at the end of infusion.
Results:
119 ischemic stroke patients met inclusion criteria (age 68±15, NIHSS 15±7, median 14, range 2–36), with 83% having occlusion consistent with symptoms. Occlusion was present in all patients with NIHSS ≥22, none with NIHSS <4, and there was a direct relationship between baseline NIHSS and clot presence (p<0.0001). Each additional NIHSS point increased the odds of occlusion by 1.33(95%CI 1.17–1.51). In patients with anterior circulation symptoms (N=80), increasing NIHSS corresponded with increasing M1 MCA and/or ICA occlusion, and decreasing vascular patency or M2 occlusion (p<0.001). In thrombolysed patients with initial vascular occlusion (N=55), end-of-infusion NIHSS was less predictive of persisting occlusion, with 70% of patients with scores ≥6 having persisting occlusion and 20% of patients with scores ≥16 having complete recanalization. The odds of persisting occlusion per end-of-infusion NIHSS point were 1.14 (95%CI 1.06–1.24,p <0.0008).
Conclusions:
Baseline NIHSS accurately predicts clot presence with increasing scores corresponding to increasing clot burden. However, NIHSS becomes less predictive of clot persistence at the end of TPA infusion and may less accurately identify patients for further revascularization efforts.
Selective Estrogen Receptor Modulator LY353381.HCl-Mediated Neuroprotection and BCL-2 Expression After Experimental Stroke
Authors: Rossberg Mark , Alkayed Nabil J , Joh Hung D , Murphy Stephanie J , Trastman Richard J , Hurn Patricia D
Published: July 2021

62

Estrogen replacement in ovariectomized rats reduces cerebral tissue infarction sustained after experimental stroke. We hypothesized that LY353381.HCl, a selective estrogen receptor modulator (SERM), reduces cerebral tissue infarction after middle cerebral artery occlusion (MCAO), and that the mechanism of protection is not related to preservation of blood flow. After 5–9 days of treatment with LY353381.HCl (LY) or vehicle (VEH), ovariectomized rats were subjected to 2 hours of MCAO under halothane anesthesia, followed by 22 hours of recovery. Ischemia was confirmed by laser-Doppler flowmetry. MAP, blood gases, and rectal and temporalis muscle temperature were controlled. Infarct volumes were measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining and digital image analysis. Ovariectomized (OVX) rats treated with LY (n=16) had smaller infarct volumes in the caudoputamen (CP) than VEH (n=14) treated rats, 49%±6% vs. 64%±4% of ipsilateral CP, respectively,
P
<0.05. Cerebral cortical (CTX) infarct size was not statistically different between treatment groups (7%±3% vs. 13%±4% for LY vs. VEH, respectively). In a second cohort of OVX rats, end ischemic regional cerebral blood flow (CBF) was measured by
14
C-iodoantipyrine autoradiography in LY (n=4) and VEH (n=3) treated rats. Absolute ischemic CBF and tissue volume distribution to low flow zones were similar in both groups. In a final cohort, 22 hours post MCAO, tissue was sampled from representative regions of CTX and CP in OVX (n=5) and LY (n=4) treated groups and analyzed for BCL-2 mRNA expression using ribonuclease protection assay. LY increased BCL-2 mRNA in both ipsilateral CTX and CP. We conclude that LY353381.HCl confers protection from focal cerebral ischemia by mechanisms that are not related to CBF but may involve increased BCL-2 expression.
Paraoxonase Polymorphisms and the Risk of Arterial Ischemic Stroke among Young Adults
Authors: Voetsch Barbara , Damasceno Benito P , Annichino-Bizzacchi Joyce M , Arruda Valder R , Loscalzo Joseph
Published: July 2021

84

Despite extensive investigation, the etiology of arterial ischemic stroke (AIS) in the young remains unknown in one-third of patients. Serum paraoxonase (PON) is an HDL-associated esterase that hydrolyzes products of lipid peroxidation and prevents the oxidation of LDL, thus exerting anti-oxidant and anti-atherogenic effects. PON levels have been shown to be significantly reduced in patients with coronary artery disease. Two common polymorphisms in the PON gene, the 55 Leu (L allele)→ Met (M allele) and the 192 Gln (A allele)→ Arg (B allele) substitutions, influence PON activity in a gene-dose dependent manner. As the association of these polymorphisms with cardiovascular disease and stroke is controversial, we investigated their role in a young population with AIS. We carried out a cross-sectional study including 138 patients (84 women, 54 men; mean age: 32.9 years) with a first AIS before the age of 45 years and 102 age-matched controls. The diagnosis of AIS was based on clinical and neuroimaging findings. Fragments of the coding region of the PON gene encompassing the 192 and 55 polymorphisms were analyzed by PCR amplification and posterior restriction endonuclease digestion. Among patients, 17.4% were found to be homozygous and 46.4% heterozygous for the B allele at position 192, compared to 8.8% and 38.3% respectively among controls. This yielded a significantly higher allele frequency of the 192 B allele among patients than controls: 0.406 vs. 0.279, P=0.0056, OR=1.76 (CI=1.17–2.65). Regarding the PON 55 L allele, there was no significant difference between patients and controls (P=0.59). The presence of hyperlipidemia, diabetes mellitus and smoking, factors known to influence PON levels, were analyzed in the patient and control groups and did not significantly alter the difference in allele frequencies. These findings suggest that the PON 192 B allele is associated with an increased risk of AIS among young adults. However, studies including a larger number of patients and analyzing the effect of PON on atherosclerosis are necessary to better understand the role of these observations in the development of AIS in the young.
SLEEP PATTERNS AND LIKELIHOOD OF STROKE AND CAROTID ATHEROSCLEROSIS
Authors: Qureshi Adnan , Suri M Fareed K , Sharma Mudit , Rana Ghias A , Ali Zulfiqar , Guterman Lee R , Hopkins L N
Published: July 2021

85

BACKGROUND AND PURPOSE:
Sleep patterns may independently affect morbidity and mortality. However, the effect of habitual sleep patterns on the risk for stroke and carotid atherosclerosis is undetermined.
METHODS:
We evaluated the association of nocturnal snoring, sleep duration, and daytime somnolence with stroke and carotid artery stenosis in 1,348 adults who participated in a stroke screening program in Buffalo, New York. A standard questionnaire was used for each person to report sleep habits and cardiovascular risk factors. Each participant underwent carotid Doppler ultrasound testing and an interview by a neurologist or neurosurgeon to determine the presence of carotid stenosis or history of stroke. Logistic regression analyses were used to examine these relationships.
RESULTS:
Of the 1348 persons evaluated, 82 (6%) had a previous stroke and 96 (7.1%) had significant carotid stenosis (stenosis > 60%). The frequency of prior stroke was higher in individuals who routinely slept for more than 8 hours per night (14%) than in those who either slept for 6–8 hours (5.4%) or less than 6 hours (5.4%). Persons who experienced daytime somnolence regularly had a higher frequency of stroke (14%) than those who did not (4%). After adjusting for differences in age, race, gender, cigarette smoking, hyperlipidemia, hypertension, and diabetes mellitus, the risk for stroke was significantly associated with daytime somnolence (Wald s chi-square test 11.8, p=0.018), average hours of sleep (Wald s chi-square test 14.7, p=0.002), and frequency of nocturnal snoring (Wald s chi-square test 13.3, p=0.009). After adjusting for other cardiovascular risk factors, daytime somnolence, average hours of sleep, and frequency of nocturnal snoring were not associated with carotid atherosclerosis.
CONCLUSIONS:
Daytime somnolence, sleeping more than 8 hours per night, and frequent nocturnal snoring increase the likelihood for stroke but not carotid atherosclerosis. This increased likelihood for stroke appears to be independent of atherosclerotic mechanisms and other cardiovascular risk factors.
Reliability and telephone validity of the Stroke-specific Quality of Life (SS-QOL) scale
Authors: Williams Linda S , Redmon Gayle , Saul D’Anna C , Weinberger Morris
Published: July 2021

P3

Background/Purpose:
The SS-QOL is a validated 49-item stroke-specific quality of life scale. Scale stability over time, between raters and with different administration modes are necessary for use in large studies. The purpose of this study is to examine SS-QOL test-retest (TR) and inter-rater reliability (IR), and validity of telephone (PH) administration.
Methods:
Ischemic stroke survivors with no significant language or cognitive impairments were recruited as part of an ongoing study of SS-QOL version 2.0. In the TR study (N=47), a trained interviewer re-administered the SS-QOL within 2 hours of the initial interview. In the IR study (N=24), a second trained interviewer re-administered the SS-QOL within 2 hours of the first interview. The PH interview (N=34) was conducted within 48 hours of a face to face interview. Pearson correlations were used to assess the relationship between the overall SS-QOL scores and individual domain scores. Because scores may be highly correlated yet biased, paired t-tests were used to assess response bias. Overall SS-QOL score and domain scores range from 1.0 (worst) to 5.0 (best). Domains are: Mobility, Upper Extremities, Work, Self-care, Energy, Family Roles, Vision, Language, Social Roles, Cognition, Personality, and Mood.
Results:
98–100% of the 3 samples were male, 88–94% were white and mean age was 66–67 years. Mean time since stroke was 4 months in the TR and IR samples and 5 months in the PH sample. SS-QOL scores were highly correlated and unbiased on TR (r=.92), IR (r=.92), and PH (r=.93) testing. All individual domain scores were also highly correlated in IR, TR and PH testing. Cognition and Personality domain scores were slightly higher on re-test and the Language domain score was slightly higher on PH administration. These differences were all < 1/4 of a standard deviation in domain score.
Conclusions:
The SS-QOL has excellent test-retest and inter-rater reliability. Telephone administration of the SS-QOL is accurate and unbiased. Individual domain scores are also highly reliable and observed differences in domain scores are rare and small. Validation of SS-QOL mail administration is ongoing.
Molecular signatures of neurotoxicity in cardiac surgery with cardiopulmonary bypass
Authors: Castillo Jose , Ginesta Vicente , Rodriguez Valentin , Serena Joaquin , Leira Rogelio , Davalos Antonio
Published: July 2021

P12

Background
Neurobehavioral disorders, and stroke are frequently reported after cardiac surgery. Although cerebral neuronal damage may be caused by transient or outlasting hypoxia as a consequence of embolism, the underlying mechanisms remain unsettled.
Objective:
To analyze changes in the biochemical markers of neurotoxicity in 26 patients who underwent CABG (n=14), valve replacement (n=10) or other cardiac surgery (n=2) with cardiopulmonary bypass (CPB).
Methods:
The surgical protocol recorded the total perfusion time, cross-clamp time, minimum nasopharyngeal temperature and mean arterial pressure (MAP). Canadian stroke scale was evaluated prior surgery, at 24h and 48h after CPB. Blood samples were obtained immediately before surgery, just after surgery, at 6h, and at 24h after CPB. Mean perfusion time was 105±36 min, mean cross-clamp time was 67±27 min, and mean lower temperature was 30.6±1.7°C. MAP was lower than 50 mmHg in 4 patients, and remained between 50 and 90 mmHg in 22.
Results:
Glutamate concentrations increased four fold, and L-arginine and GABA levels decreased 30%, just after surgery (all p<0.001). Amino acid concentrations returned to normal values at 24h. Glutamate, L-arginine and GABA levels after surgery correlated with the cross-clamp time (r=0.86, r=-0.69, and r=-0.56, respectively) (all p<0.01), but not with the lower body temperature during intervention. Glutamate levels were higher in patients with MAP<50mmHg (p=0.022). The highest glutamate concentration was observed in a patient who developed a cerebral infarct. No significant changes were found in proinflammatory parameters in blood (IL-6, TNF-α, ICAM-1 and VCAM-1).
Conclusions:
CPB is associated with an important increase of excitatory, and decrease of inhibitory amino acids in the blood. L-arginine consumption might reflect nitric oxide generation. These findings suggest that cerebral excitotoxicity may occur in cardiac surgery. Prophylactic neuroprotection in CPB should be investigated in clinical trials.
The hyperdense sylvian fissure MCA ”dot“ sign: a marker of acute CT ischemia
Authors: Barber Philip A , Demchuk Andrew M , Hudon Mark E , Pexman Warwick , Hill Michael D , Buchan Alastair M
Published: July 2021

P40

Background:
The hyperdense appearance of the middle cerebral artery is now a familiar early warning of large cerebral infarction, brain oedema and poor prognosis. Less well described, however, is the hyperdensity associated with embolic occlusion of branches of the middle cerebral artery seen in the sylvian fissure (MCA ”dot“ sign). The aim of this study was to define this sign, and to determine the incidence, its diagnostic value, and reliability.
Methods:
Computed tomographic (CT) scans performed on patients with acute ischemic stroke within 3 hours of symptom onset were analysed for signs of thromboembolic stroke and evidence of early CT ischemia. Two neuroradiologists and two stroke neurologists initially blinded to all clinical information, and then with knowledge of the affected hemisphere evaluated scans for the presence of a hyperdense MCA sign (HMCA), a hyperdense sylvian fissure MCA ”dot“ sign, and for early MCA territory ischemic changes.
Results:
Of 100 consecutive patients presenting within 3 hours of symptom onset early CT ischemia was seen in 74 % of the baseline CT scans. The HMCA sign was seen in 5% of CT scans whereas the MCA ”dot“ sign was seen in 16% of which 2 were associated with a HMCA sign. The presence of a HMCA sign was associated with a greater probability of dependence or death than when a MCA ”dot“ sign was observed or no hyperdensity was seen (P<0.05). All 5 patients with a HMCA sign, including 2 with an associated MCA ”dot“ sign were either dead or dependent at 3 months. Patients with a dot sign alone had independent outcomes in 64% of cases (P<0.8). Balanced kappa statistics for both signs were in the moderate to good range when the side of stroke was known.
Conclusions:
The hyperdense sylvian fissure MCA ”dot“ sign is an early marker of thromboembolic occlusion of the distal MCA and of its branches.
Clinical and Sonographic Patterns of Tandem ICA / MCA Occlusion in TPA Treated Patients
Authors: El-Mitwalli Ashraf , Saad Mohamed , Christou Ioannis , Malkoff Marc , Alexandrov Andrei V
Published: July 2021

P54

Background:
The National Institutes of Health Stroke Scale (NIHSS) has limited ability to identify clot location in the anterior circulation. We describe clinical and sonographic patterns that are associated with tandem ICA and MCA occlusions. Subjects and
Methods:
Consecutive patients receiving intravenous tissue plasminogen activator (TPA) were studied. Pre-treatment NIHSS scores and bedside transcranial Doppler (TCD) were obtained in all patients.
Results:
A total of 95 patients treated with iv TPA at 132±60 minutes from stroke onset were studied: 48 had isolated MCA occlusion (mean NIHSS 16.8±5.8, median 17 points, range 5–28); and 16 had tandem ICA/MCA occlusion (mean NIHSS 18.8±5.8, median 22 points, range 8–29, ns). Patients with tandem occlusions had NIHSS scores similar to isolated MCA occlusion. In both groups, respectively, 19% and 11% had NIHSS scores less than 12 points. Lower NIHSS scores were attributable to partial arm and/or leg paresis, higher number of collateral channels and low resistance flow at the M1 origin suggesting perfusion of perforating arteries on TCD. Although TCD can not differentiate between high grade ICA stenosis or occlusion, collateral flow patterns and stenotic signals at the terminal ICA identified tandem lesions from isolated MCA occlusion (p<0.01) with no false positive results at subsequent angiography (n=12).
Conclusions:
Tandem ICA/MCA occlusion was found in 17% of all iv TPA treated patients. NIHSS scores were similar in patients with isolated MCA and tandem occlusions. TCD can be used to accurately identify patients with tandem lesions. Collateral flow and patent perforators are associated with lower NIHSS scores.
Cerebral vasomotor reactivity in brain dead patients
Authors: Suarez Jose , Zaidat Osama O
Published: July 2021

P61

Background:
Cerebral vasomotor reactivity (CVMR) is a measure of the changes in arteriolar resistance in response to changes in arterial C0
2
concentration. CMVR is easily performed at the bedside using transcranial Doppler ultrasound (TCD). CVMR has not been studied in brain death.
Methods:
Patients with a clinical diagnosis of brain death, confirmed by a neurointensivist, were studied. CVMR was determined at the time of the apnea test. An experienced sonographer used a Pioneer TC 2020 (Nicolette) with a 2 MHz probe to insonate a middle cerebral artery of these patients. Continuous middle cerebral artery blood flow velocity (MCAV), systolic blood pressure (SBP), heart rate (HR), body temperature, oxygen saturation, and end-tidal C0
2
was performed during the procedure.A confirmatory arterial blood gas was obtained at baseline, five and ten minutes into the apnea test, and three minutes after hyperventilation. CMVR was calculated as follows: (MCAV at hypercapnia/MCAV at baseline)x100 - (MCAV at hypocapnia/MCAV at baseline)x100.(Normal in adults: 86±16%) CMVR was then divided by the absolute change in C0
2
to yield the percentage change (%Δ) in MCAV per mmHg C0
2
(Normal in adults: 2–4%).
Results:
Ten patients were studied (8 men) with a mean age 47±16 years.Their underlying disease varied: 3 ischemic strokes, 3 ICH, 2 SAH and 2 anoxic encephalopathy. Values of parameters monitored during the apnea test for this population: SBP:140±25 mmHg, HR:90.6±31/min, temperature: 35.8±2, PC0
2
at baseline: 40.6±9, at end of test: 74.6±13, at hyperventilation: 33.3±5. CMVR was 43.5±20% and %Δ was 1.3±0.4. All these patients had MCAV patterns compatible with brain death.
Conclusion:
CMVR is severely reduced or exhausted in brain dead patients. This test should be considered when TCD is used as a confirmatory tool in clinically brain dead patients.
Modification of Synaptic Plasma Membrane Ca
2+
-ATPase in Ischemic Injury in an Animal Model of Global Ischemia
Authors: Zaidi Asma , Cross Angela M , Bean Jennifer L , Michaelis Mary L
Published: July 2021

P83

Regulation of [Ca
2+
]
i
is altered in neurons during ischemic injury in stroke, but the precise mechanism(s) underlying the Ca
2+
dysregulation are not known. The plasma membrane Ca
2+
-ATPase (PMCA) is one of the two main Ca
2+
extrusion systems that play a critical role in maintaining neuronal Ca
2+
homeostasis. We have substantial evidence showing that this enzyme is very sensitive to oxidative stress. When exposed to very low concentrations of physiologically relevant oxidants, the PMCA has been shown to form high molecular weight aggregates and this is accompanied by the decline in its enzymatic activity. Because stroke-induced hypoxia is associated with the overproduction of reactive oxygen species (ROS) and a loss of Ca
2+
homeostasis, we carried out studies to determine if the PMCA is modified in an
in vivo
animal model of stroke. Global ischemia was induced in Sprague Dawley rats by occlusion of the common carotid arteries for defined time periods. The V
max
of PMCA activity in brain homogenates as well as in purified synaptic plasma membranes was significantly reduced following occlusion of the vessels, and the reduction was proportional to the time of ischemia. The loss in PMCA activity could not be reversed by addition of exogenous ATP, suggesting an alteration in the protein itself. Immunoblots of the synaptic membranes run under non-reducing conditions showed crosslinking of PMCA molecules to form high molecular weight adducts, and this too increased with increasing periods of ischemia. The PMCA aggregates were partially reversed under reducing conditions, indicating the involvement of sulphydryl group oxidation. These observations support the hypothesis that increased formation of ROS under ischemic conditions can oxidatively modify specific proteins critical for the regulation of free [Ca
2+
]
i
levels. Such oxidative damage is likely to contribute to the loss of neuronal Ca
2+
regulation and neuronal viability in stroke. (Supported by AHA 9960343Z, AG 12993, and the Higuchi Biosciences Center, University of Kansas)
Discriminant Validity of the Stroke Impact Scale
Authors: Dr Sue-Min Lai , Dr Stephanie Studenski , Dr Pamela W Duncan , Dr Subashan Perera
Published: July 2021

P123

Purpose:
The purpose of this study was to determine the discriminant validity of the Stroke Impact Scale (SIS) by comparing function and quality of life in stroke patients to assessments from stroke-free community dwelling elderly.
Methods:
The SIS was administered at 90 to 120 days post-stroke to subjects who participated in the Kansas City Stroke Registry (KCSR). The same impact scale was also administered cross-sectionally to community dwelling elderly who were recruited from primary care clinics for participation in an ongoing prospective study of health and function (Merck). All subjects were queried for responses to 64 items of the SIS including eight domains: strength, memory and thinking, emotion, communication, ADL/IADL, mobility, upper extremity, and social participation. Regression analyses were used to examine differences between stroke patients and stroke-free elderly in each of the eight SIS domains while controlling for demographics and comorbidities.
Results:
One hundred and sixty KCSR subjects and two hundred and forty-three subjects from the Merck study were included in the present analysis. The mean ages were 73±10.1 and 74±5.1, respectively. Gender and race were similar in both groups. The 90-days post-stroke mean Barthel ADL was 80±23 in the stroke patients. Mean scores of all 8 SIS domains were significantly lower in stroke patients than those in the stroke-free community dwelling elderly even after controlling for differences in age and comorbidities (all p values < 0.0001). Mean scores of the 7 SIS domains (except strength), even in stroke patients who had Barthel ADL > 90 at 90-days post-stroke, remained lower than those in the stroke-free community dwelling elderly (p values < 0.01).
Conclusion:
The SIS was able to discriminate well between stroke patients with disability and stroke-free elderly subjects. Patients who had recovered basic ADLs continued to have residual disability and impaired quality of life when compared to non-stroke patients.
Incidence of Silent Stroke in the United States
Authors: Leary Megan C , Saver Jeffrey L
Published: July 2021

P134

Background:
Recent estimates of stroke incidence in the US range from 715,000–750,000 annually. These estimates, however, do not reflect silent infarcts and hemorrhages. Since population-based studies have found that prevalence of silent stroke is 10–20 times that of symptomatic, estimates of stroke incidence based solely on symptomatic events may substantially underestimate the annual burden of stroke. Silent strokes contribute to vascular dementia, gait impairment, and other major adverse patient outcomes.
Methods:
Incidence of silent infarcts for different age strata were derived from two US population-based studies of the prevalence of silent infarct-like lesions on MRI, Atherosclerosis Risk In Communities and Cardiovascular Health Study. Prevalence observations in these studies and age-specific death rates from the US Census Bureau were inputted to calculate silent infarct incidence (method of Leske et al). Similarly, incidence rates of silent hemorrhage at differing ages were extrapolated from population-based prevalence observations employing MR GRE imaging in the Austrian Stroke Prevention Study. Age-specific incidence rates were projected onto age cohorts in the 1998 US population to calculate annual burden of silent stroke.
Results:
Derived incidence rates per 100,000 of silent infarct ranged from 6400 in the age 50–59 strata to 16400 at ages 75–79. Extrapolated incidence rates of silent hemorrhage ranged from 230 in the age 30–39 strata to 7360 at ages > 80. Incidence rates of both subclinical infarcts and hemorrhage increased exponentially with age. Overall estimated annual US occurrence of silent infarct was 9,039,000, and of silent hemorrhage 2,130,000.
Conclusion:
In 1998, nearly 12 million strokes occurred in the United States, of which ∼750,000 were symptomatic and over 11 million were subclinical. Among the silent strokes, ∼81% were infarcts and ∼19% hemorrhages. These findings demonstrate that the annual burden of stroke is substantially higher than suggested by estimates based solely on clinically manifest events, and suggest that greater research and clinical resources should be allocated to stroke prevention and treatment.