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Biomedical subjects

Scott E Kasner

Publications and source records attributed to Scott E Kasner.

At least 19 recordsLinked to original sources
PubMed2006

Safety and tolerability of arundic acid in acute ischemic stroke.

Arundic acid (AA; ONO-2506), a novel modulator of astrocyte activation, may improve neuronal survival after stroke. We conducted a multicenter, dose-escalating, randomized, double-blind Phase I trial of AA in acute ischemic stroke. Subjects were randomized to treatment with AA or placebo in sequential dose tiers of 2-12 mg/kg/h (10-16 patients/group) within 24 h of stroke onset. Study drug was infused for 1 h daily over 7 days, and follow-up terminated at 40 days. Neurological and functional outcomes were evaluated through Day 40 as exploratory endpoints. A total of 92 subjects were enrolled with no dose-related pattern of serious adverse events (AEs). Premature terminations caused by AEs occurred in four (8.2%) patients treated with AA and five (11.6%) treated with placebo. Two subjects treated with AA (4.1%) and four given placebo (9.3%) died. Exploratory efficacy analysis showed a trend toward improvement in the change from baseline National Institutes of Health Stroke Scale (NIHSS) in the 8 mg/kg/h AA group on Days 3 (p=0.023 vs. placebo), 7 (p=0.002), 10 (p=0.003), and 40 (p=0.018). A dose of 8 mg/kg/h AA produced a favorable trend in reduction of NIHSS that should be confirmed in a future clinical trial.

Aged↗
PubMed2006

Effect of arundic acid on serum S-100beta in ischemic stroke.

We prospectively examined the effect of arundic acid (AA; ONO-2506) on S-100beta, an astrocyte-derived protein, in a phase I acute stroke study. Subjects with acute ischemic stroke were randomized to daily infusion of AA or placebo for 7 days. Serum S-100beta levels were assayed pre-infusion on Days 1-7 and post-infusion on Days 1, 3, and 7, and correlated with National Institutes of Health Stroke Scale (NIHSS). Samples were obtained from 86 subjects (46 AA, 40 placebo). Increase in S-100beta protein level from baseline was less in the AA cohort than in the placebo cohort at 7 (p=0.0471; t-test) and 12 (p=0.0095)-hours post-infusion on Day 3. Baseline NIHSS correlated with maximal S-100beta levels between Days 1 and 3 in the AA (r=0.51; p=0.0003) and placebo (r=0.41; p=0.0084) cohorts and in the pooled aggregate (n=86; r=0.46; p<0.0001). The same correlations were observed between Day 10 NIHSS and Day 1-3 maximum serum S-100beta levels. Treatment with AA was associated with lower serum levels of S-100beta after acute ischemic stroke. Our results showing correlation between S-100beta and NIHSS indicate that this protein is a clinically relevant marker of neurological deficit in acute stroke.

Aged↗
PubMed2006

Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack?

BACKGROUND AND PURPOSE: A 6-point scoring system (ABCD) was described recently for stratifying risk after transient ischemic attack (TIA). This score incorporates age (A), blood pressure (B), clinical features (C), and duration (D) of TIA. A score <4 reportedly indicates minimal short-term stroke risk. We evaluated this scoring system in an independent population. METHODS: This was a prospective study of TIA patients (diagnosed by a neurologist using the classic <24-hour definition) hospitalized <48 hours from symptom onset. The primary outcome assessment consisted of dichotomization of patients into 2 groups. The high-risk group included patients with stroke or death within 90 days, > or =50% stenosis in a relevant artery, or a cardioembolic source warranting anticoagulation. All others were classified as low risk. Findings on diffusion-weighted MRI (DWI) were also evaluated when performed and patients classified as DWI+ or DWI-. RESULTS: Over 3 years, 117 patients were enrolled. Median time from symptom onset to enrollment was 25.2 hours (interquartile range 19.8 to 30.2). Overall, 26 patients (22%) were classified as high risk, including 2 strokes, 2 deaths, 15 with > or =50% stenosis, and 10 with cardioembolic source. The frequency of high-risk patients increased with ABCD score (0 to 1 13%; 2 8%; 3 17%; 4 27%; 5 26%; 6 30%; P for trend=0.11). ABCD scores in the 2 patients with stroke were 3 and 6. Of those who underwent MRI, 15 of 61 (25%) were DWI+, but this correlated poorly with ABCD score (0 to 1 17%; 2 10%; 3 36%; 4 24%; 5 13%; 6 60%; P for trend=0.24). CONCLUSIONS: Although the ABCD score has some predictive value, patients with a score <4 still have a substantial probability of having a high-risk cause of cerebral ischemia or radiographic evidence of acute infarction despite transient symptoms.

Age Factors↗
PubMed2006

Carotid artery diameter in men and women and the relation to body and neck size.

BACKGROUND AND PURPOSE: To explore relationships among gender, body size, neck size, and the diameters of the common carotid artery (CCA) and internal carotid artery (ICA). METHODS: Using multivariate regression, the best predictors of sonographic diameters of CCA and ICA were determined based on age, height, weight, body mass index, body surface area, neck circumference, neck length, and blood pressure. RESULTS: Measurements were obtained in 500 consecutive patients (age 52+/-15 years; 61% women). Mean diameters of ICA (4.66+/-0.78 mm) and CCA (6.10+/-0.80 mm) in women were significantly smaller than in men: 5.11+/-0.87 mm and 6.52+/-0.98 mm, respectively. Sex significantly influenced the diameters after controlling for body size, neck size, age, and blood pressure. CONCLUSIONS: Carotid arteries are smaller in women even after adjusting for body and neck size, age, and blood pressure.

Adolescent↗
PubMed2006

Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis.

BACKGROUND: Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy. METHODS AND RESULTS: WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke in the territory of the stenotic artery was highest with severe stenosis > or =70% (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P=0.0025) and in patients enrolled early (< or =17 days) after the qualifying event (hazard ratio 1.69; 95% confidence interval 1.06 to 2.72; P=0.028). Women were also at increased risk, although this was of borderline significance (hazard ratio 1.59; 95% confidence interval 1.00 to 2.55; P=0.051). Location of stenosis, type of qualifying event, and prior use of antithrombotic medications were not associated with increased risk. CONCLUSIONS: Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis > or =70%, after recent symptoms, and in women.

Aged↗
PubMed2006

Ischemic strokes after cardiac catheterization: opportune thrombolysis candidates?

Stroke is an important complication after cardiac catheterization procedures, resulting in death and disability for thousands of patients each year. Common risk factors include advanced age, vascular comorbidities, and more complicated and invasive procedures. Several lines of evidence suggest that these strokes are embolic, from either dislodgement of a clot or atheromatous debris off the aortic arch or from thrombus formation on the tip of a guide catheter. These strokes are likely amenable to thrombolysis, although the current literature regarding the use of thrombolysis in this setting is limited to case reports and series. Whether thrombolysis is safe and efficacious remains to be determined, but the existing evidence seems favorable for individual circumstances.

Cardiac Catheterization↗
PubMed2006

Safety and efficacy of thrombolytic therapy in postoperative cerebral infarctions.

Acute ischemic stroke is a common and devastating complication of many surgical procedures. If diagnosed early, however, there are reasonably safe and effective treatment options. Although IV rtPA is the most well studied means of recanalization after ischemic stroke, it should be avoided within 14 days of a surgical procedure in favor of other locally directed techniques that carry a significantly lower risk of bleeding at the surgical site. Only in rare circumstances, when these newer modalities are not available and the surgery is minor, should IV rtPA be considered in postoperative patients. The treatment of choice for carefully selected patients with postoperative strokes is IAT with either rtPA or urokinase. IAT may be attempted up to 6 hours after an acute ischemic stroke and may be assisted by mechanical clot disruption/embolectomy in an attempt to improve recanalization rates. In patients who have had a recent craniotomy or any surgery where surgical site bleeding is expected to be massive or difficult to control or where small amounts of bleeding could be life threatening, IAT should be avoided. In these patients, and in patients who present greater than 6 hours but less than 8 hours after their stroke, mechanical thrombolysis/embolectomy may emerge as the only viable treatment option.

Cerebral Infarction↗
PubMed2006

Clinical interpretation and use of stroke scales.

No single outcome measure can describe or predict all dimensions of recovery and disability after acute stroke. Several scales have proven reliability and validity in stroke trials, including the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS), the Barthel index (BI), the Glasgow outcome scale (GOS), and the stroke impact scale (SIS). Several scales have been combined in stroke trials to derive a global statistic to better define the effect of acute interventions, although this composite statistic is not clinically tenable. In practice, the NIHSS is useful for early prognostication and serial assessment, whereas the BI is useful for planning rehabilitative strategies. The mRS and GOS provide summary measures of outcome and might be most relevant to clinicians and patients considering early intervention. The SIS was designed to measure the patient's perspective on the effect of stroke. Familiarity with these scales could improve clinicians' interpretation of stroke research and their clinical decision-making.

Clinical Trials as Topic↗
PubMed2006

Stroke associated with Barth syndrome.

Barth syndrome is an inherited disorder characterized by dilated cardiomyopathy, neutropenia, growth retardation, and skeletal myopathy. We describe a case of acute stroke owing to Barth syndrome that required intra-arterial thrombolysis. This case suggests that cardiovascular complications can be observed in patients with Barth syndrome. Stroke prevention measures, including the use of antithrombotic agents, might be warranted.

Adolescent↗
PubMed2006

Treatment of intracranial arterial stenosis.

Intracranial stenosis accounts for 8-10% of ischemic strokes in the USA. Treatment of intracranial stenosis with extracranial-to-intracranial bypass surgery was investigated as a therapy in the 1980s, but was shown to be no better than aspirin alone. The Warfarin vs Aspirin for Symptomatic Intracranial Disease study found a 12% per year risk of recurrent stroke for symptomatic lesions of 50% or higher, with the majority of strokes occurring in the first year. Warfarin was no better than aspirin in the prevention of recurrent stroke and had a higher risk of serious bleeding and death. Subgroup analysis showed that patients with the highest risk of recurrent stroke included those with 70% or more stenosis and/or recent symptoms and women. Angioplasty and stenting of intracranial stenosis have been undergoing rapid evolution in technology and are emerging as a promising therapy. Current treatment recommendations include antiplatelet agents, with consideration for angioplasty alone or angioplasty and stenting in cases refractory to medical therapy.

Angioplasty↗
PubMed2005

Altered hemodynamics and regional cerebral blood flow in patients with hemodynamically significant stenoses.

BACKGROUND AND PURPOSE: Blood oxygen level-dependent (BOLD) contrast largely depends on changes in cerebral blood flow (CBF). Because cerebrovascular disease may result in altered CBF, we assessed the temporal dynamics and magnitude of the BOLD response in patients with major arterial stenoses. METHODS: Seven patients with hemodynamically significant stenoses affecting the anterior circulation (primarily left internal carotid and middle cerebral arteries) were compared with 7 neurologically healthy subjects. Continuous arterial spin-labeled perfusion MRI was used to measure resting CBF globally and within various vascular distributions. The BOLD response was acquired during a visually guided bilateral handball squeeze task while motor performance was recorded by a pressure transducer. RESULTS: Baseline CBF was reduced in bilateral middle cerebral artery and left anterior cerebral artery territories in patients. A prolonged BOLD hemodynamic response was observed in patients in bilateral primary motor cortices but not visual cortex. Patients also exhibited a larger early negative BOLD response, or "initial dip," in left primary motor cortex. There were no differences in motor performance between groups, suggesting behavioral differences were not primarily responsible for the characteristics of the BOLD response. CONCLUSIONS: An initial deoxygenation followed by a delayed hyperemic BOLD response was observed in patients, although resting flow values were not within an ischemic range. A simple visuomotor BOLD activation paradigm can reflect alterations in the hemodynamic response in patients with hemodynamically significant stenoses.

Adult↗
PubMed2005

Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis.

BACKGROUND: Atherosclerotic intracranial arterial stenosis is an important cause of stroke. Warfarin is commonly used in preference to aspirin for this disorder, but these therapies have not been compared in a randomized trial. METHODS: We randomly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin (target international normalized ratio, 2.0 to 3.0) or aspirin (1300 mg per day) in a double-blind, multicenter clinical trial. The primary end point was ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke. RESULTS: After 569 patients had undergone randomization, enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin. During a mean follow-up period of 1.8 years, adverse events in the two groups included death (4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group; hazard ratio for aspirin relative to warfarin, 0.46; 95 percent confidence interval, 0.23 to 0.90; P=0.02), major hemorrhage (3.2 percent vs. 8.3 percent, respectively; hazard ratio, 0.39; 95 percent confidence interval, 0.18 to 0.84; P=0.01), and myocardial infarction or sudden death (2.9 percent vs. 7.3 percent, respectively; hazard ratio, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.02). The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group (P=0.16); the rate of death from nonvascular causes was 1.1 percent and 3.8 percent, respectively (P=0.05). The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group (hazard ratio, 1.04; 95 percent confidence interval, 0.73 to 1.48; P=0.83). CONCLUSIONS: Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial. Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis.

Adult↗
PubMed2004

Transient global amnesia heralding basilar artery thrombosis.

The cause of transient global amnesia (TGA) remains controversial. Focal cerebral ischemia, seizure, venous congestion, and migraine have all been proposed as underlying mechanisms. We describe a patient presenting with typical TGA who two days later developed a posterior circulation stroke due to basilar artery occlusion. He was treated successfully with intra-arterial thrombolytic therapy. Shortly thereafter, he had recurrent basilar artery thrombosis and jugular vein thrombosis, and was found to have a mucinous adenocarcinoma believed to be causing a hypercoagulable state. We believe this case supports the hypothesis that TGA can on occasion be caused by cerebral ischemia.

Amnesia, Transient Global↗
PubMed2004

Prediction of hospital disposition after thrombolysis for acute ischemic stroke using the National Institutes of Health Stroke Scale.

BACKGROUND: Early determination of discharge destination after acute stroke may promote earlier rehabilitation and reduce costs by shortening the duration of hospitalization. OBJECTIVE: To determine whether the National Institutes of Health Stroke Scale (NIHSS) score predicts disposition in stroke patients treated with thrombolysis. DESIGN: Cohort study. SETTING: Academic and community hospitals from 3 countries. PATIENTS: Five hundred forty-six patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rt-PA). INTERVENTIONS: Medical records were reviewed for demographic information, vascular risk factors, location of stroke, initial NIHSS score, acute hospital disposition, and complications of symptomatic or asymptomatic intracerebral hemorrhage (ICH). MAIN OUTCOME MEASURE: Discharge destination to home, acute rehabilitation, or nursing facility. RESULTS: In multinomial regression analysis, increasing NIHSS score was a robust and independent predictor of discharge to rehabilitation or nursing facilities, roughly doubling for each 5-point increment. Patients who developed symptomatic ICH were never discharged to home, but asymptomatic ICH had no significant independent effect on disposition. CONCLUSIONS: Stroke severity as determined by the admission NIHSS score is the major independent predictor of disposition after hospitalization and treatment with rt-PA for acute stroke in a broad-based population. However, symptomatic ICH after rt-PA is a catastrophic event that may preclude discharge to home.

Acute Disease↗
PubMed2004

Early impairment in consciousness predicts mortality after hemispheric ischemic stroke.

OBJECTIVE: Early predictors of poor outcome after acute ischemic stroke may be useful in selecting patients for potentially beneficial but high-risk interventions. DESIGN: Cohort study of patients given placebo in a randomized clinical trial. SETTING: Multicenter trial at 139 U.S. and 14 Canadian hospitals. PATIENTS: A cohort of 564 placebo-treated patients with major anterior circulation ischemic stroke enrolled in the Clomethiazole in Acute Stroke Study-Ischemic Stroke (CLASS-I) trial. Patients did not have significant impairment in consciousness at baseline and were enrolled within 12 hrs of symptom onset. INTERVENTIONS: Prospective data collection of a number of clinical variables including use of a 6-point level of consciousness scale (1 = awake, 6 = no reaction to pain) to measure patients' level of consciousness at enrollment and 12 additional times during the first 24 hrs after enrollment. The ability of level of consciousness score and additional clinical data to predict 30-day mortality was assessed. MEASUREMENTS AND MAIN RESULTS: At 1 month, 114 of 564 patients (20%) had died. In univariate analysis, factors significantly associated with mortality included older age, white race, higher National Institutes of Health Stroke Scale score, higher serum glucose, atrial fibrillation, and any impairment in level of consciousness (p <.05). After controlling for these factors, increasing level of consciousness score at 3 hrs after enrollment and at all but one subsequent time point was significantly associated with increased mortality (odds ratio, 1.8 per point; 95% confidence interval, 1.2-2.6; p =.003 at 3-hr time point). Maximum level of consciousness score during the initial 24 hrs of monitoring also predicted mortality (odds ratio, 1.9 per point; 95% confidence interval, 1.4-2.5; p <.001). CONCLUSION: The development of a decreased level of consciousness within the initial hours after stroke onset, as evaluated by a simple six-point scale, is a powerful independent predictor of mortality after major anterior circulation ischemic stroke.

Age Distribution↗
PubMed2004

Pseudo-subarachnoid hemorrhage: report of three cases and review of the literature.

Subarachnoid hemorrhage (SAH) appears on CT as hyperdensity in the subarachnoid space. In rare circumstances a similar appearance may occur in the absence of subarachnoid blood, a finding that has been termed "pseudo-subarachnoid hemorrhage." We describe three patients who presented with abrupt alterations in mental status in whom CT falsely suggested SAH, and we review the literature regarding this imaging finding. In contrast to prior reports, all three of our patients had a favorable outcome.

Adult↗