bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9: Cardiac BIN1 Improves Dyad Organization and Calcium Transient in Cardiomyocytes
Authors: Fu Ying , Zhou Kang , Liu Yan , Agvanian Sosse , Xu Bing , Shaw Robin M , Hong TingTing
Published: March 2022

BIN1 (bridging integrator 1) is a membrane scaffolding protein that forms microfolds at t-tubules and organizes dyad microdomains essential for a normal calcium transient. Reduction of cBIN1 has emerged as a new hallmark in heart failure and is associated with impaired calcium transient and increased risk of arrhythmias. We hypothesized that gene transfer of cardiac BIN1 (cBIN1) in vivo can improve calcium transients in disease models. We introduced V5-tagged cBIN1 or GFP through AAV9-mediated expression in adult mice. Confocal imaging of isolated cardiomyocytes was used to assess organization of dyad microdomain. Calcium transients in response to acute administration of isoproterenol (ISO) was measured as functional readout of excitation-contraction (EC) coupling. Here we report that cBIN1 significantly enhanced both basal and ISO-induced increase in calcium transient compared to cells expressing GFP. Immunofluorescent labeling revealed that cBIN1 expression increased both LTCC and RyR at t-tubule. In addition, in a mouse model of ischemic cardiomyopathy, permanent LAD ligation resulted in a marked reduction in ISO-induced increment in calcium transient, indicating blunted beta-adrenergic responsiveness and impaired regulation of EC coupling machinery. In comparison, an ISO-induced increment in calcium transient was largely maintained in cBIN1-expressing cells. These results demonstrate that cBIN1 increases calcium transients by upregulating and organizing dyad proteins at t-tubule microfolds. More importantly, cBIN1 rescues diminished beta-adrenergic responsiveness in ischemic cardiomyopathy and improves EC coupling of viable cardiomyocytes. This work suggests that cBIN1 provides a therapeutic opportunity to improve cardiac function in ischemic cardiomyopathy and heart failure.
Adrenal Medullary Stimulation Induced by Angiotensin I, Angiotensin II, and Analogues
Authors: PEACH MICHAEL J.
Published: March 2022

A structure-activity relationship study was attempted to determine the structural specificity of the no. 8 amino acid residue of [1-asp,5-ileu]-angiotensin II for adrenal medullary stimulation. Isolated cat adrenal glands were perfused retrograde at a flow rate of 1 ml/min with phosphate-buffered Locke's solution at 23 to 25 C. Continuous catecholamine analysis was performed using an automated trihydroxyindole procedure. All drugs were administered either by single injection (0.05 to 0.1 ml) or by perfusion. Angiotensin analogues studied were: [8-(OMe)tyr]-angiotensin II; [8-tyr]-angiotensin II; [8-ala]-angiotensin II; [5-ileu,8-(3-amino-4-phenylbutyric acid)]-angiotensin II (referred to as [8-APB]-angiotensin II); [5-ileu,8-(DL-3-amino-3'-phenylisobutyric acid)]-angiotensin II (referred to as [8-APIB]-angiotensin II); [1-asp(NH
2
),5-val]-angiotensin II; [1-asp,5-ileu]-angiotensin I; tetradecapeptide.

Three peptides (angiotensin II, [8-tyr]-angiotensin II, and [8-ala]-angiotensin II) were studied in vivo for stimulation of adrenal catecholamine secretion. For maximum pressor activity, angiotensin must be an octapeptide with an aromatic amino acid and free COOH group in the no. 8 position. None of these three are structural requirements in adrenal chromaffin tissue. There was cross-tachyphylaxis between angiotensin II and all the analogues studied except two ([8-APB]- and [8-APIB]-angiotensin II).

In vitro studies with 10-leu-C
14
-angiotensin I and angiotensin II antibody indicated that angiotensin I has a marked, direct stimulatory effect on the adrenal medulla. Adrenal medullary catecholamine secretion induced by angiotensin I and II was greatly potentiated by DMAE perfusions. Responses to nicotine were blocked by DMAE and bradykinin-induced catecholamine release was unchanged. The cross-tachyphylaxis and DMAE studies suggest that several of the analogues and angiotensin II are interacting with a common adrenal medullary receptor.
Studies of a Humoral Sodium Transport Inhibitory Activity in Normal Dogs and Dogs with Ligation of the Inferior Vena Cava
Authors: BUCKALEW VARDAMAN M. , LANCASTER CARLTON D.
Published: March 2022

Plasma ultrafiltrates of dogs acutely expanded with saline inhibit toad bladder sodium transport. The present studies were performed to delineate further the chemical and physiological characteristics of this inhibitory activity.

Column chromatography with Sephadex G-10 showed the activity to be present in the fraction ahead of the salt peak. Sodium balance studies in normal dogs were performed to determine the relationship between factor activity and the daily fluctuations of renal sodium excretion. A significant correlation was observed between the presence of humoral inhibitory activity and spontaneous antinatriuresis. In the absence of antinatriuresis, inhibitory activity was absent, regardless of the level of sodium intake. In normal dogs given saline loads acutely, inhibitory activity was present 60 and 120 minutes after the beginning of saline loading. In dogs with constriction of the inferior vena cava, no activity was observed during saline loading for up to 120 minutes.

The data are compatible with the interpretation that the humoral sodium transport inhibitory activity is a natriuretic hormone released in response to expansion of the extracellular fluid volume.
Carotid Stent Thrombosis
Authors: Chaturvedi Seemant , Sohrab Sayyed , Tselis Alexandros
Published: March 2022

Background
—

Carotid stenting is receiving increased attention as an alternative to carotid endarterectomy. Carotid stent thrombosis is a rare complication of this procedure.

Case Descriptions
—

We present 2 case reports from a university medical center. Two patients had angiographically confirmed carotid stent (CS) thrombosis with subsequent fatal strokes. The first was a 63-year-old woman who developed stent thrombosis after the procedure was performed for a postendarterectomy intimal flap. The second patient was a 57-year-old man who underwent CS placement for transient ischemic attacks and developed internal carotid artery occlusion at the level of the stent 3 days later. Neither patient was treated with combination antiplatelet therapy before or after CS placement. Both patients died.

Conclusions
—

CS thrombosis can be a cause of fatal iatrogenic stroke. Combination antiplatelet therapy should be administered to decrease the incidence of this complication.
Late Secondary Injury in Patients Undergoing Vessel Recanalization with Intra-arterial Thrombolysis: Visualization with MRI, Frequency, and Clinical Correlates
Authors: Kidwell Chelsea S , Saver Jeffrey L , Mattiello James , Starkman Sidney , Gobin Y. Pierre , Duckwiler Gary , Vespa Paul M , Jahan Reza , Villablanca J. Pablo , Liebeskind David S , Vinuela Fernando , Alger Jeffry R
Published: March 2022

8

Background:
Late secondary injury following vessel recanalization, recently observed in animal stroke models, may limit the benefit of reperfusion therapy. The frequency and clinical correlates of secondary injury in humans have not been previously characterized.
Methods:
Diffusion-perfusion MRIs were performed prior to treatment, early after recanalization (median 4 hrs), and at day 7 in patients undergoing vessel recanalization with intra-arterial (IA) thrombolytics. Post-treatment MRIs were co-registered to the pretreatment scan to allow a voxel-by-voxel analysis of tissue fate over time.
Results:
Eighteen patients (13 females, 5 males) were studied. Mean age was 71 and median entry NIHSS score 13. Early after recanalization, partial or complete normalization of DWI abnormalities occurred in 8/18 (44%) patients, and of apparent diffusion coefficient (ADC) abnormalities in 13/18 (72%). Among the 8 patients with early DWI reversal, late secondary injury on day 7 (on DWI or T2W sequences) occurred in 5 (63%), and sustained normalization of all reversed tissue in 3 (38%). Across all patients, of tissues showing pretreatment DWI abnormality, 41% of voxels showed no early reversal, 33% early reversal with sustained normalization at day 7, and 18% early reversal but late secondary injury. Pretreatment ADC values were lowest in regions experiencing no reversal (mean ADC 624 um2/sec), intermediate in regions with reversal and secondary decline (641), and highest in regions with sustained reversal (677). Evolution of neurologic deficit (NIHSS) did not differ in patients with secondary injury vs. those with sustained reversal, nor did age, time to recanalization, degree of recanalization, or presence of post-ischemic hyperperfusion.
Conclusions:
Following vessel recanalization with IA thrombolysis, partial or complete reversal of initial DWI abnormality occurs in ∼40% of patients. A late, secondary signature of injury compromising some or all of the initially normalized tissue occurs in over 50% of these patients, but is not associated with clinical worsening.
An Empirical Study of Personality Change After Stroke
Authors: Grattan Lynn M , Ghahramanlou Marjan , Aronoff Jodi , Wozniak Marcella A , Kittner Stephen J , Price Thomas R
Published: March 2022

16

Personality changes after stroke are not well understood. There are three specific areas that need to be examined: 1) the dimensions of personality vulnerable to change post-stroke, 2) the extent to which personality patterns converge to a unitary “Organic Personality Disorder” or reflect exaggerations of premorbid personality features; and, 3) the contribution of pre-morbid personality characteristics to post-stroke depression. Toward this end, close relatives of ischemic stroke patients rated pre- and post-stroke personality patterns with the NEO Personality Inventory-Revised (NEO-PI-R; Costa & McCrae, 1985), a standard personality measure. Non-parametric comparison tests (Bonferroni corrections were used to adjust the alpha level for each set of multiple comparisons) showed significant changes in 3 of 5 personality domains assessed by the NEO. These included higher neuroticism (
p
<.005) (anxiety,
p
<.01; depression,
p
<.001; vulnerability,
p
<.005), lower extraversion (
p
<.001) (reduced activities,
p
<.001; positive emotions,
p
<.005) and less conscientiousness (
p
<.01) (self-discipline, p<.05). Findings were maintained regardless of stroke laterality or frontal vs. non-frontal lesion location. Correlational analyses of pre- and post-stroke scores on the NEO’s personality scales suggested that an exaggeration of premorbid personality features exists among this sample (i.e., 35 of the 36 scales had significant positive correlations). Regression analyses indicated that pre-stroke scores on self-consciousness (R
2
=.26,
p
<.005), gregariousness (R
2
=.19,
p
<.01), straightforwardness (R
2
=.15, p<.05), and deliberation in thinking (R
2
=.25,
p
<.005) were predictive of post-stroke depression as measured by the NEO depression facet. Findings suggest that specific personality changes post-stroke are identifiable, strongly related to premorbid personality and may be predictive of post-stroke depression. This research was funded by NIH/NINDS, grant 1R29NS33608, Favorable Outcome in Stroke Survivors awarded to Lynn M. Grattan, Ph.D.
The time-course of body temperature in acute stroke
Authors: Christensen Hanne , Prof Gudrun Boysen
Published: March 2022

22

Objective:
Body temperature on admission has been reported to be of prognostic significance in acute stroke in several studies. Spontaneous hyperthermia has been associated with poor outcome mainly based on body temperature measured 24 - 48 hours after stroke onset. The aim of this study was to describe the time-course of body temperature in the first hours after stroke onset and its relation to stroke severity and outcome. Patients and
Methods:
This work is based on 762 consecutive patients admitted within 6 hours of stroke onset (median: 2 hours) to an acute stroke unit. Body temperature was registered on admission and every 2 hours in the first 24 hours. Stroke severity was assessed by Scandinavian Stroke Scale on admission and functional outcome by modified Rankin Scale after 3 months.
Results:
In the severe stroke patients, both ischaemic and haemorrhagic, we observed a rise in body temperature within 6 - 8 hours after stroke onset. No rise was observed in the less severe strokes. Temperature >= 37.5°C, observed in 4.5 %, on admission within 6 hours of stroke onset was not associated with poor out-come.
Conclusion:
Severe stroke heralds rise in body temperature within 6 - 8 hours, while temperature remains normal in mild strokes unless infection occurs. Elevated temperature on admission had no prognostic significance in this study.
Blood Pressure Status One Year Post-stroke: Findings from the Northern Manhattan Stroke Study
Authors: Boden-Albala Bernadette M , Evers Sarah K , Rundek Tanja , Elkind Mitchell S , Cheng Jian F , Sacco Ralph L
Published: March 2022

34

Objective
To describe blood pressure (BP) status in a multi-ethnic community-based cohort of stroke survivors one year post-stroke. Background Hypertension (HTN) is a critical stroke risk factor with recent studies demonstrating increased risk even in borderline HTN. Further, uncontrolled HTN may contribute to recurrence and mortality among stroke survivors. Despite established treatment for HTN, control of BP in certain populations may be less than optimal.
Methods
As part of the Northern Manhattan Stroke Study, we prospectively followed a cohort of community based stroke survivors annually. At 1 year follow-up we collected outcomes, BP measurements, medical, demographic and behavioral data. BP status at 1 year post stroke was categorized as normal (<140 /90 mmHg), mildly elevated (≥ 140mmHg or ≥ 90 mmHg) or severely elevated (BP≥ 160 mmHg and /or BP ≥ 95 mmHg). Logistic regression was used to investigate predictors of BP status.
Results
There were 655 ischemic stroke cases eligible for follow-up. At one year, 107 were dead and 527 were seen in person. The cohort was 55% women; 17% white, 27% black, 54% Hispanic; mean age 69 ± 12 yrs. At follow-up, 51% (n=271) of cases had elevated BP; 19% (96) were severely elevated. Among the 271 cases with elevated BP, 45% had been discharged on antihypertensives following their stroke. Univariate predictors of elevated BP at 1 year were: < H.S. education (OR 1.7 p<.006), race-ethnicity [Hispanic vs white (OR 2.8, p<.0001) , black vs white (OR 2.0, p<.01)], younger age (OR 1.1, p<.008), and having few friends (OR 1.9, p<.06).
Conclusion
Adequate control of BP 1 year post stroke is sub-optimal. Our results suggest that despite the availability of efficacious treatments for HTN, underlying socio-demographic conditions continue to deter regulation of blood pressure.
Validation of Clinical Prediction Rules for Stroke: Results from the National Registry of Atrial Fibrillation (NRAF) Project
Authors: Gage Brian F , Waterman Amy D , Shannon William , Boechler Michael , Rich Michael W , Radford Martha J
Published: March 2022

38

Background:
Patients who have atrial fibrillation (AF) have an increased risk of stroke, but the absolute rate of stroke depends on age and comorbid conditions. Several classification schemes have been proposed to estimate the risk of stroke in the AF population. We combined 2 existing classification schemes into a new stroke-risk index and then validated all 3 classifications schemes.
Methods:
We formed the new stroke-risk index, CHADS
2
by assigning 1 point for the presence of each of the following conditions-Congestive heart failure, Hypertension, Age greater than 75 years, Diabetes mellitus-and 2 points for a history of Stroke or transient ischemic attack. To test the 3 classification schemes we collaborated with Peer Review Organizations representing 7 states to assemble a National Registry of AF (NRAF) consisting of Medicare beneficiaries who have non-rheumatic AF. The NRAF dataset contained health outcomes based on Medicare part A claims data.
Results:
Of 1733 NRAF cohort members who had not been prescribed warfarin at the time of hospital discharge, 94 were readmitted for an ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c-statistic significantly greater that 0.5, the 2 existing classification schemes predicted stroke better than chance: 0.78 for the scheme developed by the Atrial Fibrillation Investigators and 0.82 for the SPAF 3 scheme. However, the new CHADS
2
index performed better, c-statistic = 0.87. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3–1.7) for each 1-point rise in the CHADS
2
score: 1.9 for CHADS
2
=0; 2.8 for CHADS
2
=1; 4.0 for CHADS
2
=2; 5.9 for CHADS
2
=3; 8.5 for CHADS
2
=4; 12.5 for CHADS
2
=5; and 18.2 for CHADS
2
=6.
Conclusions:
The 2 existing classification schemes and especially a new stroke-risk index, CHADS
2
, can quantify the risk of stroke for patients who have AF. Use of the CHADS
2
index should aid in the selection of antithrombotic therapy for patients who have non-rheumatic AF.
The LAPSS Motor Scale (LAMS): A New Measure for Characterizing Stroke Severity in the Field
Authors: Llanes Jennifer N , Starkman Sidney , Kidwell Chelsea S , Eckstein Marc , Saver Jeffrey L
Published: March 2022

42

BACKGROUND:
The Los Angeles Prehospital Stroke Screen (LAPSS) has been shown in a prospective, in the field validation study to identify stroke patients with high sensitivity and specificity. For prehospital clinical trials, it is desirable to develop an instrument that rapidly characterizes stroke severity (clinimetric measure) in addition to stroke recognition tools (diagnostic measure). Shortened versions of the NIHSS have been proposed for this purpose. However, a motor score derived from the LAPSS 3 item motor exam may serve this purpose more efficiently.
METHODS:
The LAPSS Motor Scale (LAMS) was constructed by assigning point values to LAPSS items of facial weakness (0,1), arm strength (0,1,2) and grip (0,1,2) to yield a total 0–5 scale. 87 patients enrolled in UCLA Stroke Network acute stroke clinical trials were analyzed. The presenting LAMS score was derived based on the recorded presenting NIHSS and grip exam. Correlations were calculated between the LAMS and 3 month functional outcomes, including NIHSS, modified Rankin, GOS, and Barthel Index. Predictive performance of the LAMS was compared with that of the initial full NIHSS and the 5 item shortened NIHSS (sNIHSS).
Results:
The average LAMS score was mean 2.6, median 2. LAMS score correlations with the 3 month functional outcome measures were highly statistically significant, and comparable to that of the longer sNIHSS and full NIHSS: 3 mo GOS - LAMS 0.55, sNIHSS 0.51, NIHSS 0.64; 3 mo BI - LAMS 0.49, sNIHSS 0.47, NIHSS 0.57; 3 mo mRS - LAMS 0.45, sNIHSS 0.54, NIHSS 0.54; 3 mo NIHSS - LAMS 0.50, sNIHSS 0.51, NIHSS 0.57. Considering dichotomized 3 mo measures, LAMS scores were markedly lower in patients destined for excellent outcome: 3 mo GOS=1, 3.4 vs 1, p<.0001 ; 3 mo mRS≤1, 3.8 vs 2.6, p=.06; 3 mo BI≥95, 3.6 vs 1.9, p<.0001; 3 mo NIHSS≤1, 2.2 vs 3.7, p<.001.
Conclusions:
A motor score easily and quickly derived from the Los Angeles Prehospital Stroke Screen quantitatively characterizes stroke severity in the field, and predicts functional outcomes with accuracy nearly comparable to that of the full NIHSS. Field use of the LAPSS would allow rapid identification of stroke patients and usefully delineate stroke severity.
Results of a Multicenter Prospective Randomized Trial of Carotid Artery Stenting vs. Carotid Endarterectomy
Authors: Alberts Mark J
Published: March 2022

53

Background:
Carotid artery stenosis (CAS) is a common etiology for ischemic stroke. While carotid endarterectomy (CEA) is a safe and effective treatment for CAS, endovascular therapy using carotid stenting may be a reasonable alternative. This multicenter study was designed to determine if carotid stenting was equivalent to CEA in patients with symptomatic CAS.
Methods:
Patients with symptomatic CAS of 60–99% by cerebral angiogram were prospectively randomized to CEA or carotid stenting. All enrolled patients were reviewed by a multidisciplinary team that included neurologists, surgeons, and interventionalists. Patients in the stent group were treated with the WALLSTENT endoprosthesis and received aspirin 325 mg bid and ticlopidine 250 mg bid for 4 weeks. Neurologic assessments were performed 24 hrs post-procedure, then at 1, 6 and 12 months. The primary end-point was ipsilateral stroke, procedure-related death, or vascular death within 1 year. P-values are from 2-sided Fisher’s Exact Test.
Results:
A total of 219 patients were enrolled; 107 in the stent group (mean age 66.5, 66% male) and 112 in the CEA group (mean age 70, 62% male). The mean baseline degree of stenosis was 76% in the stent group vs 75% in the CEA group. 65% of stent patients had a TIA vs 68% in the CEA group. Median follow-up days for stent and CEA patients were 354 and 341, respectively. The primary end-point rate at approximately one year was 12.1% in the stent group vs. 3.6% for CEA (p = 0.022). The rate of any major stroke was 3.7% for stent vs. 0.9% for CEA (p = 0.204). A post-stent angiogram showed that 97% of patients had less than 30% stenosis. The 30 day peri-procedure complication rate (any stroke or death) was 12.1% for stents and 4.5% for CEA (p = 0.049). The 2 day peri-procedure complication rate was 7.5% for stents and 1.8% for CEA (p=0.055). Other common peri-procedure complications of stenting were severe bradycardia (7%) and groin hematoma (4%).
Conclusions:
This study did not find that carotid stenting was equivalent to CEA in patients with symptomatic CAS. Based on these data and a futility analysis, the study was terminated before the planned maximum of 700 patients were enrolled.
A Descriptive Study of Variables Explaining Functional Recovery Following Motor Stroke
Authors: Hinkle Janice L
Published: March 2022

54

This prospective correlational study described a cohort of subjects with a motor stroke and assessed the extent to which selected variables measured during the acute phase explained the variation in functional recovery post stroke. Data were collected from a convenience sample of 100 consenting adults recruited during admission to neurology services at two large urban medical centers. Age, lesion volume on MRI, motor strength, cognitive status, and post-stroke functional level data were collected during the acute care hospital admission. Subjects mean age was 65 years (
SD
± 15, range = 20–90), the mean lesion volume in centimeters cubed (cm
3
) was 21.5 (
SD
± 44.7, range = 0 - 225) and the mean National Institute of Health Stroke Scale (NIHSS) was 6.34 (
SD
± 3.55, range = 2–17). Cognitive status was measured using two instruments. The mean Mini-Mental Status Examination (MMSE) score was 24.38 (
SD
± 13, range = 9–30) while the mean Neurobehavioral Cognitive Status Examination (NCSE) was 64.33 (
SD
± 13, range = 12–85). The mean Functional Independence Measure (FIM) score was 94.05 (
SD
± 19.31, range = 38–120). Ninety subjects were available three months post stroke when functional recovery was measured. The Mean FIM score at that time was 117 (
SD
± 13). The results of the multiple regression analysis revealed that age, the NCSE, and the FIM at the time of admission accounted for 42% of the variance in functional recovery three months after stroke. The NIHSS and lesion volume on MRI did not enter the hierarchical regression model. In addition to providing a description of a group of individuals who had a motor stroke, the results of this study will help allied health professionals appropriately focus their time and attention during the fast paced acute phase of stroke care.
Parallel Hypothesis Testing for Science and Industry in a Large Randomized Clinical Trial
Authors: Howard George , Shelton Brent J , Brott Thomas G , Baker Elizabeth A , White Roseann , Kuntz Richard E , Hobson Robert W , Marler John R
Published: March 2022

67

The Carotid Revascularization Endarterectomy/Stenting Trial (CREST) will assess the relative efficacy of carotid endarterectomy (CEA) and Carotid Angioplasty with Stenting (CAS) in the prevention of stroke. As other trials, data from CREST are being used to meet different aims. The NIH and scientific community are interested in establishing if CEA and CAS differ in their long-term efficacy to prevent strokes, while the FDA and industry are interested in establishing if CAS is as safe or safer than CEA at one year of follow-up. The CREST investigators have chosen the novel approach of addressing these needs by having two “primary” analyses. For the scientific community and NIH, a null hypothesis of no difference between two treatments in the average hazard over 4 years of follow-up is contrasted with an alternative hypothesis that one treatment is better (a two-tailed test). This hypothesis will be addressed using proportional hazards analysis. For the FDA, an “equivalency” analysis where the null hypothesis that CAS has an event rate marginally higher than CEA (by δ of 2.6%) at the one-year point in the follow-up is contrasted against the alternative that CAS event rate is as low (within δ of 2.6%) or lower than CEA (a one-tailed test). This hypothesis will be addressed by comparing Kaplan-Meier estimates of survival at one year after the procedure. Having two primary hypotheses that are analyzed using different methods opens the possibility that “discordant” study results may occur. For example, the NIH analysis could conclude that CEA has a lower event rate than CAS, while the FDA analysis could conclude CAS is as good or better than CEA. Such a result would be confusing to the scientific community and lower the confidence placed in CREST study results. The likelihood of discordant findings was evaluated using a simulation approach that considered a wide range of outcomes ranging from CEA being better, to CEA being worse, than CAS. The outcome of the “NIH” and “FDA” analysis were never discordant in 3500 simulations. These findings suggest that the data from CREST can be used to address the different needs of the NIH and FDA with a low likelihood of introducing conflicting results.
Contrast-Enhanced Magnetic Resonance Angiography of the Carotid Arteries: Utility in Routine Clinical Practice
Authors: Johnston Dean C C , Goldstein Larry B
Published: March 2022

68

Background:
Contrast-enhanced magnetic resonance angiography (CEMRA) is a new technique that is being used with increasing frequency for the evaluation of carotid disease in endarterectomy (CEA) candidates. However, evidence supporting the clinical utility of this test is lacking.
Methods:
We reviewed the results of CEMRA in comparison to catheter angiography (ANGIO) in a consecutive series of 50 patients being evaluated for CEA who had both tests. Using a prespecified protocol and indications for CEA based on published recommendations, the rate of misclassification for surgery, sensitivity, specificity, positive and negative predictive values (PPV, NPV) were measured.
Results:
When compared to ANGIO, 24% (95%CI:12,36) of patients would have been misclassified for CEA based on CEMRA alone. The reasons for misclassification were overestimation of the degree of stenosis in 18% and underestimation in 4%. CEMRA failed to detect a complete carotid occlusion on one case. CEMRA correctly classified all patients with high-grade stenosis (defined as >70% in symptomatic patients and >80% in asymptomatic patients). CEMRA had a sensitivity of 92%, specificty of 62%, PPV of 78% and NPV of 89%. Duplex ultrasound (DUS) was performed in 72% of the patients and the results of all three tests were concordant in 67%. The misclassification rate for CEA in comparison to ANGIO for cases in which CEMRA and DUS were concordant decreased to 17% (95%CI: 2,32) with corresponding increases in the sensitivity (100%) and NPV (100%) but a similar a specificity (60%) and PPV (78%).
Conclusion:
This study provides the first formal analysis of the performance of CEMRA in comparison to ANGIO in selecting patients for CEA. Clinicians should be cautious when using CEMRA for decisions regarding CEA as a significant number of patients may be misclassified if this test is used alone. The rate of misclassification is reduced when the results of DUS and CEMRA are concordant.
A novel therapeutic approach for treating antiphospholipid syndrome based on tolerizing anti-β2-GPI B cells
Authors: Linnik Matthew D
Published: March 2022

79

Autoantibodies directed against β2-glycoprotein I (β2-GPI) have been implicated in the thrombotic events associated with antiphospholipid syndrome (APS). The presence of these antibodies is an independent risk factor for arterial and venous thrombosis and greatly increases the risk of a recurrent thrombotic event. Our labs have recently demonstrated that anti-β2-GPI antibodies from APS patients specifically target the amino terminal domain (domain 1) of β2-GPI (PNAS 95:15542, 1998). This discovery led to the development of a B cell toleragen-based approach to specifically deplete anti-β2-GPI antibodies and the B cells that produce these antibodies. Four copies of recombinant human β2-GPI (hβ2-GPI) domain 1 were covalently attached to a polyethylene glycol-containing platform to produce a tetravalent bioconjugate of domain 1, LJP 1082. LJP 1082 bound to immobilized affinity purified APS antibodies with a higher affinity than domain 1 alone (Kd’= 42–65 nM for LJP 1082 and 326–376 nM for domain 1 binding to antibodies from 3 APS patients). An immunized rat model was developed to evaluate the ability of LJP 1082 to tolerize β2-GPI B cells
in vivo
. Rats were immunized with hβ2-GPI domain 1 coupled to keyhole limpet hemocyanin (D1-KLH) and treated approximately 3 weeks later with LJP 1082. Five days after exposure to LJP 1082 rats were boosted with D1-KLH and splenic B cells and serum antibody levels were evaluated at 7 days. Vehicle-treated control rats developed hβ2-GPI specific B cells (35 positive cells/10
6
spleen cells) and anti-hβ2-GPI antibodies (7000 U/ml serum). Treatment with a single dose of LJP 1082 (4.5 mg/kg) prior to boosting with D1-KLH caused almost complete tolerance as evidenced by the reduction in hβ2-GPI B cells (< 3 positive cells/10
6
spleen cells) and anti-hβ2-GPI antibodies (< 300 U/ml serum). We conclude that a multivalent conjugate of hβ2-GPI domain 1 is capable of inducing significant B cell tolerance in an immunized rat model. Treatment of APS patients with a B cell toleragen would remove the pro-thrombotic risk factor, anti-β2-GPI antibodies, without the risks associated with current anticoagulation therapy.
Risk, Causes and Prevention of Ischemic Stroke in Elderly Patients with Symptomatic Internal Carotid Artery Stenosis
Authors: Alamowitch Sonia , Eliasziw Michael , Algra Ale , Meldrum Heather , Barnett Henry Jm
Published: March 2022

91

Background.
Atherosclerosis is an important cause of stroke in the elderly. Carotid endarterectomy (CE) benefits patients with 70–99% symptomatic internal carotid artery (ICA) stenosis, less for patients with 50–69% stenosis. The benefit of CE in elderly patients (≥75 years) requires evaluation.
Methods.
Elderly patients with symptomatic ICA stenosis were compared to those 65–74 years and <65 years in regards to baseline characteristics, risk of ipsilateral ischemic stroke at 2 years by degree of stenosis and treatment group and risk of ischemic stroke in the territory of an asymptomatic contralateral carotid artery.
Results.
The risk of ipsilateral ischemic stroke was highest in the medically-treated elderly regardless of the degree of stenosis. Among 659 patients with 70–99% stenosis, the absolute risk reduction (ARR) of ipsilateral ischemic stroke by CE was 28.9% for patients ≥75 years (N=71), 15.1% for 65–74 years (N=285) and 9.7% for <65 years (N=303). Among patients with 50–69% stenosis, the ARR was significant only in those ≥75 years (N=145) with an ARR of 17.3%. The perioperative risk of stroke and death at any degree of stenosis was less in the elderly: 5.1% for patients ≥75 years, 5.4% for 65–74 years and 7.8% for <65 years. The numbers of patients ≥75 years with 70–99% and 50–69% stenosis needed to treat (NNT) by CE to prevent one ipsilateral stroke within 2 years were 3 and 6, respectively. For 60–99% asymptomatic contralateral ICA stenosis, the 2 year risk of stroke was 7.8% in patients ≥75 years and 7.4% in those < 75 years. The risk of ischemic stroke at 5 years in the territory of a 60–99% asymptomatic ICA stenosis was higher in patients ≥75 years (24.8%) than in patients <75 years (14.9%).
Conclusions.
In the prevention of ipsilateral ischemic stroke, elderly patients with 50–99% symptomatic carotid stenosis benefited more from CE than younger patients. To achieve this benefit, patients must be carefully selected, excluding those with other life threatening illnesses.
Hyperhomocysteinemia is a Risk Factor for Progression of Aortic Atheroma in Stroke/TIA Patients
Authors: Sen Souvik , Oppenheimer Stephen M
Published: March 2022

92

Background
and
Purpose
Aortic atheroma, an independent risk factor for stroke, is known to undergo temporal progression. The clinical correlates of such progression are not known. The objective of this study was to identify if the stroke risk factors and/or stroke sub-types correlated with progression of aortic atheroma in stroke/TIA patients.
Methods
We prospectively investigated 78 patients (38 Males, 58 Blacks, 12 Whites)with recent (≤7 days) stroke/TIA (57 stroke and 21 TIA patients). Sequential multiplanar transesophageal echocardiograms(TEEs) were performed ≤7 days and 9 months from the stroke/TIA. Aortic atheroma was graded according to the maximal thickness as <1 mm, 1–3.9 mm and ≥4 mm at each time point by cardiologists blinded to the patient information. The stroke risk factors, usage of anticoagulant/antiplatelet drugs and hypolipidemic drugs, clinical (OCSP), neuroradiological (large vs small vessel distribution stroke), and etiological (TOAST) subtypes of stroke were recorded and compared in patients with and without progression of aortic atheroma. Fisher’s exact test was used to compare categorical data and t-test was used to compare continuous data.
Results
Of the 78 patients investigated 29 (37%) progressed and 49 (63%, 32 unchanged + 17 regressed) did not. Most patients progressed at the aortic arch. Regression occurred mostly at the descending aorta. Most patients without aortic atheroma remained unchanged on the sequential TEE. Hyperhomocysteinemia (>14.0 mcm/l), TACI and large artery atherosclerosis significantly (p<0.05) correlated with progression of aortic atheroma. The stroke risk factors and medications did not appear to influence the progression of aortic atheroma in stroke TIA patients.
Conclusions
Patients with TACI and large artery atherosclerosis as presumed cause of stroke are at higher risk of progression of aortic atheroma. Patients with aortic atheroma need to be assessed for homocysteine levels to assess the risk of progression. Further studies need to be conducted to investigate if the vitamin therapy used to treat hyperhomocysteinemia may also prevent progression of aortic atheroma in stroke/TIA patients.
Validity of a structured interview for the Modified Rankin Scale: Comparison with other stroke assessment scales
Authors: Schulz Ursula , Baird Tracey , Grant Marie , Bone Ian , Muir Keith W , Hareendran Asha , Wilson Lindsay
Published: March 2022

98

Background & aims:
We have recently developed a structured interview for the Modified Rankin Scale (MRS-SI) to improve the inter-rater reliability of this measure of outcome. The purpose of the current study was to investigate the relationship between the MRS-SI and other measures commonly used to assess functional state after stroke.
Methods:
119 patients (60 males) were recruited to the study 3 to 24 months after stroke. The median age of patients was 67, and the median interval since stroke was 13 months. Patients were assessed on the Modified Rankin Scale using the structured interview. In addition patients were assessed on the same occasion using the Scandinavian Stroke Scale, the National Institutes of Health Stroke Scales, the Barthel Index, the extended Glasgow Outcome Scale (GOSE) and the Short Form 36 (SF-36).
Results:
Spearman correlations were computed between ratings on the MRS-SI and other assessments. The MRS-SI was most strongly related to the GOSE. There were also strong correlations with the Barthel Index, the Scandinavian Stroke Scale, and the National Institutes of Health Stroke Scales. However, there was evidence of substantial ceiling effects on all three of these assessments. The MRS-SI correlated significantly with individual subscales of the SF-36, and was particularly strongly related to Physical Function and Social Functioning. However, not all stroke patients were able to complete the SF-36.
Conclusions:
Systematic relationships observed between the MRS-SI and other established measurement are evidence of the validity of the structured interview. The stroke scales and the Barthel Index discriminate the more disabled groups (Rankin 3 to 5), but are insensitive to functional differences among less severely disabled patients (Rankin 0 to 2). Self-report measures such as the SF-36 indicate differences in health outcome in the less severely disabled groups, but not all stroke patients are able to complete this assessment. A particular strength of the Modified Rankin Scale is the ability to chart the complete spectrum of disability and handicap after stroke.
Self-assessment of stroke recovery correlates with neurologic evaluation
Authors: Cramer Steven C , Bodwell Julie A , Billheimer Dean
Published: March 2022

99

Recent studies have emphasized the utility of patient self-assessments in measuring stroke recovery. We explored the validity of two such methods by comparing patient self-assessments with standard neurologic evaluations. Patients with an ischemic stroke were asked to rate stroke-affected arm use for 10 motor tasks, from Motor Activity Log (MAL). Next, each was asked to rate difficulty in using the stroke-affected hand for the 5 hand function tasks from the Stroke Impact Scale (SIS). Neurological exam was performed, then scoring on NIH Stroke Scale, arm motor Fugl-Meyer scale, and, for each arm, Purdue Pegboard test. Self-assessments were compared with neurologic evaluations using Spearman rank correlation test. Thirty three patients were studied, with mean age 63 years and mean time post-stroke 80 days. Of these, 13 reported no hand use and 5 reported full return of hand use to pre-stroke levels; correlations were performed with and without these 18 patients. Correlations with these patients were consistently stronger than without. However, self-assessment is of greatest interest in patients with intermediate scores, so correlations are reported only for this group (n=15). MAL correlated significantly (p<.01) with strength in several muscles including hand interossei (r=.83), but not deltoid or leg muscles. MAL correlated with NIH score (r=-.76) and Fugl-Meyer score (r=.85), as well as # pegs placed by the paretic hand in 30 seconds (r=.86); but not with index finger proprioception, level of any deep tendon reflex, or # pegs placed by the non-stroke hand. Among patients with intermediate SIS values (n=14), SIS correlated with paretic finger proprioception and strength, arm tone, and # pegs placed (r=.63-.81, p<.05) but not reflexes. MAL and SIS inter-correlated well (r=.91). MAL and SIS show concurrent validity with standard neurologic tests, and correlated more closely with motor evaluations as compared to sensory, strength as compared to deep tendon reflexes, arm evaluations as compared to leg, and hand evaluations as compared to shoulder. These observations are consistent with MAL and SIS content. MAL and SIS are rapid, valid methods for assessing motor status after stroke.
Dietary Behaviors of Ambulatory Care Stroke Patients
Authors: Hawkins Irana W , Becker Kyra J
Published: March 2022

104

Background:
Diet plays an important role in the management of the chronic diseases that increase the risk of stroke. Health care providers may not adequately stress the need for dietary modification.
Methods:
A Nutrition History (NH) form was developed in a referral based ambulatory care stroke clinic to evaluate patients’ dietary habits. The form included a Fat Intake Scale (FIS), created and validated by the Northwest Lipid Clinic. An FIS score > 24 indicates the need for dietary modification. A person with a Body Mass Index (BMI) > 25 is considered overweight. Statistics are descriptive and non-parametric.
Results:
Of the 103 patients that completed the NH, 89% were Caucasian, 75% had a stroke or TIA, 48% were hyperlipidemic, 37% were hypertensive and 13% were diabetic. The body mass index (BMI) was 26 ± 6.6 (60% > 25). Among patients with stroke or TIA (n=77), 58% were hyperlipidemic, 45% were hypertensive and the BMI was 27 ± 7.2 (61% > 25). In hyperlipidemic patients with stroke or TIA (n=45), the BMI was 28 ± 7.7 (68% > 25) and the FIS score was 28 ± 6.1 (76% > 24); 66% of these patients had never been counseled by a Registered Dietitian (RD). Only 43% of hyperlipidemic patients with TIA or stroke were being treated with lipid-lowering agents; use did not differ as a function of age or gender. Among patients with hypertension, 68% used sodium when cooking and only 32% of reported eating five or more servings of fruits and vegetables a day; 71% of hypertensive patients had never been counseled by an RD. Persons with diabetes were more likely to have been counseled by an RD than persons without diabetes (p=0.032), but persons with hyperlipidemia, hypertension, overweight persons, and persons with TIA or stroke were not more likely to have been counseled by an RD than persons without those conditions.
Conclusions:
These data show that persons with hypertension and hyperlipidemia, especially those who have had TIA or stroke, are not fully engaged in the recommended dietary practices to help control their diseases. Furthermore, lipid-lowering agents appear to be underutilized. Greater attention to preventive measures, such as appropriate referral for nutrition counseling, needs to be incorporated into routine practice.
Gender differences in carotid bifurcation anatomy and the distribution of atherosclerotic plaque
Authors: Schulz Ursula Gr , Rothwell Peter M
Published: March 2022

105

Flow models suggest that plaque formation partly depends on vessel anatomy. The carotid bifurcation is a common site for atheroma, but there are few data on variability in bifurcation anatomy, in particular the possibility that anatomy might be related to gender. Carotid plaque is more common in men and asymptomatic carotid bruits are more frequent in women. This may be due to sex differences in absolute vessel size, but may also indicate other anatomical differences. We studied 5395 bifurcation angiograms from 3007 patients in the European Carotid Surgery Trial. To minimise changes in vessel anatomy secondary to atherosclerosis we excluded angiograms of vessels with ≥ 30% stenosis (NASCET method). We measured arterial diameters at disease free points and calculated the following ratios: internal to common (ICA/CCA), external to common (ECA/CCA) and external to internal (ECA/ICA) carotid arteries. We related these to sex and other baseline characteristics. We then compared the distribution of plaque in men versus women in the whole trial population. There were 2971 angiograms with <30% stenosis. The mean ICA/CCA ratio was larger (p<0.0001) in women (0.67, 95% CI 0.66–0.68) than men (0.62, 0.61–0.63), whereas the mean ECA/ICA ratio was larger (p<0.0001) in men (0.91, 0.90–0.92) than in women (0.84, 0.82–0.85). These differences were independent of other baseline variables. There were also sex differences in the distribution of plaque. Men were more likely to have the point of maximum stenosis distal to the bulb of the ICA (OR 2.29, 95%CI 1.33–4.01, p=0.001), whereas women were more likely than men to have plaque in the ECA (OR 1.54, 95%CI 1.30–1.85, p<0.0001), particularly stenosis ≥50% (OR 2.0, 95%CI 1.56–2.57, p<0.0001). Gender differences in carotid bifurcation anatomy are not limited to absolute vessel size. In addition, women have proportionately larger ICAs and men have proportionately larger ECAs. These findings may partly explain the sex differences in the distribution of plaque in the carotid bifurcation, sex differences in the prevalence of asymptomatic carotid bruits, and they also have implications for the measurement of carotid stenosis.
The risk of intracranial saccular aneurysm enlargement determined by serial MR Angiography
Authors: Phan Thanh G , Huston John , Brown Robert D , Wiebers David O , Piepgras David G
Published: March 2022

106

Background and Purpose:
To determine the frequency of unruptured intracranial aneurysm enlargement using serial MR angiography, and to determine if there are factors predicting change in aneurysm size.
Methods:
We retrospectively reviewed MR angiography studies performed between January 1991 and December 1999. Fifty-seven patients had 62 unruptured, untreated saccular aneurysms. The ratio of females to males was 2.6: 1. An average of 3 measurements of the maximal dimension as measured on source images was defined as the aneurysm size. Both the mean and median aneurysm diameter was 5 mm (range 2–15 mm). An aneurysm was defined to have enlarged if it increased in size by more than 1 mm when the size of the aneurysm was less than 5 mm and more than 2 mm when the aneurysm was equal to or larger than 5 mm. The mean and median time between studies was 50 months and 47 months respectively, with a range of 17–90 months.
Results:
No aneurysm ruptured during the period of follow-up. Four (7%) of the aneurysms increased in size with the median time to aneurysm growth of 40 months (range 23–66 months). None of the aneurysms less than 9 mm diameter increased in size. Four of the 9 aneurysms (44%) 9 mm or larger increased in size. Factors which predicted aneurysm growth includes size (p = 0.002), and multiple lobes or daughter sacs (p = 0.02). Aneurysm location did not predict an increased risk of enlargement.
Conclusions:
Patients with medium or large size aneurysms and multiple lobes or daughter sacs may be at increased risk for aneurysm growth and should be considered for follow up imaging if left untreated.