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Biomedical subjects

L R Wechsler

Publications and source records attributed to L R Wechsler.

At least 19 recordsLinked to original sources

Thrombolytic therapy of acute ischemic stroke during pregnancy.

The authors report eight pregnant women with acute ischemic stroke treated with thrombolysis (rt-PA [recombinant human tissue plasminogen activator] or urokinase). Seven women recovered. Two extracranial and two asymptomatic intracranial hemorrhages complicated treatment; one woman died of arterial dissection complicating angiography. Three patients had therapeutic abortions, two fetuses were miscarried, and two babies were delivered healthy. Although pregnant women may be treated safely with thrombolytics, risks and benefits to mother and fetus must be carefully weighed.

Adult↗

High titers of CA-125 may be associated with recurrent ischemic strokes in patients with cancer.

In addition to etiologies common in the general population, strokes in cancer patients may be caused by hypercoagulable states, hyperviscosity, cardiogenic embolism, and neoplastic vessel infiltration. Intravascular mucins were reported in patients with recurrent thromboembolism. The authors report four patients with metastatic cancer, brain infarcts, and other thromboembolic disease with markedly elevated levels of the tumor marker CA-125 and explore possible associations between this mucinous protein and strokes.

Aged↗

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. METHODS: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. RESULTS: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Adolescent↗

A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients.

BACKGROUND: Citicoline may reduce CNS ischemic injury by stabilizing cell membranes and reducing free radical generation. Previous safety and efficacy trials in patients who have had acute strokes suggested that citicoline may improve neurologic outcome with minimal side effects. OBJECTIVE: To determine the safety and efficacy of citicoline treatment in acute stroke patients. METHOD: An 118-center, randomized, double-blind, efficacy trial in 899 patients compared placebo (n = 446) with citicoline (n = 453) (1000 mg PO twice a day) for 6 weeks, with a 6-week post-treatment follow-up period. Patients with acute (< or =24 hours) ischemic strokes clinically thought to be in the middle cerebral artery territory with NIH Stroke Scale (NIHSS) scores > or =8 were enrolled. RESULTS: Mean time to treatment was 13 hours for both groups and mean age was 67 years for those receiving placebo and 68 years for those receiving citicoline. Mean baseline NIHSS scores were 14.5 for placebo and 13.9 for citicoline (p = 0.06); medians were 14 for placebo and 13 for citicoline (p = 0.04). The incidence and type of side effects were similar between the groups. There were no between-group differences on the planned primary analysis, percent of patients with a > or =7-point NIHSS score change at 90 days (placebo 51%, citicoline 52%). There were no between-group differences on the other planned secondary analyses at 90 days, including mortality. However, post hoc analyses using standard "excellent recovery" measures suggested a possible treatment effect on the modified Rankin 0 or 1 (last observation carried forward: placebo 20%, citicoline 26%; p = 0.025) as well as a global outcome statistic. CONCLUSIONS: Citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke as measured by the planned analyses. Post hoc analyses suggest that a modest treatment effect may have been seen if more traditional analyses had been used.

Acute Disease↗

Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.

OBJECTIVE: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. METHOD: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation. RESULTS: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). CONCLUSIONS: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.

Acute Disease↗

CT-based assessment of acute stroke: CT, CT angiography, and xenon-enhanced CT cerebral blood flow.

BACKGROUND AND PURPOSE: Only a small percentage of acute-stroke patients receive thrombolytic therapy because of time constraints and the risks associated with thrombolytic therapy. We sought to determine whether xenon-enhanced CT (XeCT) cerebral blood flow (CBF) and/or CT angiography (CTA) in conjunction with CT can distinguish subgroups of acute ischemic stroke victims and thereby better predict the subgroups most likely to benefit and not to benefit from thrombolytic therapy. METHODS: An analysis of 51 patients who had a CT, CTA, and stable XeCT CBF examination within 24 hours of stroke symptom onset was conducted. These initial radiographic studies and National Institutes of Health Stroke Scale score on admission were assessed to determine whether they could predict new infarction on follow-up CT or discharge disposition by use of the Fisher exact test to determine statistical significance. RESULTS: Patients with no infarction on initial CT and normal XeCT CBF had significantly fewer new infarctions and were discharged home more often than those with compromised CBF. The same held true for patients with an open internal carotid artery and middle cerebral artery by CTA and normal CT compared with those with an occluded internal carotid artery and/or middle cerebral artery by CTA. Either was superior to CT and the National Institutes of Health Stroke Scale in prediction of outcome. Both enable the selection of a group of patients not identifiable by CT alone that would do well without being exposed to the risks of thrombolytic therapy. This study included too few patients to statistically assess the role of combining CTA and XeCT CBF information. CONCLUSIONS: The combination of CT, CTA, and Xe/CT CBF does define potentially significant subgroups of patients. The utility of this classification is supported by the observation that CTA and XeCT CBF are superior to CT alone in predicting infarction on follow-up CT and clinical outcome. This information may be useful in selecting patients for acute-stroke treatment.

Acute Disease↗

Transcranial Doppler ultrasonography: year 2000 update.

In this update, the main clinical applications of transcranial Doppler ultrasonography are reassessed. A specific format for technology assessment, personal experience, and an extensive review of the literature form the basis of the evaluation. The document is approved by the American Society of Neuroimaging and the Neurosonology Research Group of the World Federation of Neurology.

Brain Diseases↗

Rapidly progressive stroke in a young adult with very low high-density lipoprotein cholesterol.

Ischemic strokes can affect young adults (15-45 years old). Most such strokes are caused by cardioembolic events, small vessel disease, or illicit drug use, and less frequently by large vessel atherosclerosis. Large vessel cerebral atherosclerosis is usually associated with high levels of low-density lipoprotein (LDL) cholesterol, but a low level of high-density lipoprotein (HDL) is also a risk factor for ischemic strokes. The magnitude of increased risk is unclear, particularly with extremely low HDL levels found only in various genetic and inherited disorders. Advanced atherosclerosis developed in the patient in this study, with HDL of 3 mg/dL, leading to rapidly progressive stroke with a fatal outcome. The disease primarily affected the posterior circulation. The course of this case illustrates that very low HDL may be associated with advanced cerebrovascular atherosclerosis and fatal stroke, and as such should be considered in young individuals with stroke.

Adult↗

New developments in endovascular interventions for extracranial carotid stenosis.

We provide an overview of recent developments in carotid interventional technique and equipment, including new stents and emboli protection devices. The newer self-expanding stents lessen the problem of external stent compression associated with balloon expandable stents, but precise deployment and the matching (by length) of stents to lesions remain problematic. We also discuss emerging pharmacologic strategies for cerebral protection in stroke. Multiple randomized clinical trials and multicenter registries are under way to compare percutaneous with surgical strategies for the treatment of carotid stenosis. These include the evaluation of emboli protection devices, and, to a lesser degree, intravenous glycoprotein IIb/IIIa antagonists. Other clinical trials are aimed towards refining the ability to stratify patients by risk, in order to identify the subsets that would benefit most from these complex and expensive procedures.

Angioplasty, Balloon↗

Intra-arterial thrombolysis for carotid circulation ischemia.

Recanalization of acutely occluded arteries in the carotid territory, particularly the middle cerebral artery, by intra-arterial delivery of thrombolytic drugs, has advanced dramatically over the last decade. Randomized prospective studies have begun to show the potential impact of this form of intervention. Still, patient selection, therapeutic window, critical care support, and experience of the management team are clearly the determining features for the success of intra-arterial thrombolysis. The use of thrombolytic agents currently available, and research involving the next generation of these agents, open a field that shows promise for the improvement of outcomes of patients whose typical prognosis is poor.

Brain Ischemia↗

Factors affecting survival rates for acute vertebrobasilar artery occlusions treated with intra-arterial thrombolytic therapy: a meta-analytical approach.

OBJECTIVE: To determine whether recanalization, coma at presentation, or clot location in the basilar artery influences the relative mortality risk after intra-arterial thrombolytic therapy for acute vertebrobasilar artery occlusions. METHODS: Studies were identified using the MEDLINE database for January 1987 to November 1997. Series were included if they involved 10 or more patients with basilar or vertebrobasilar artery occlusions, used urokinase and/or recombinant tissue plasminogen activator, and were written in English. A fixed-effect meta-analysis approach was used to estimate the risk of death with the aforementioned risk factors. Each study was weighted according to sample size. Relative risks were calculated with 95% confidence intervals. RESULTS: As calculated from peer-reviewed published data, the relative mortality risk for patients for whom recanalization was attempted but not achieved was 2.34 (95% confidence interval, 1.48-3.71; n = 126). Coma at presentation was associated with a relative mortality risk of 1.95 (95% confidence interval, 1.26-2.99; n = 145). Clot locations in the distal one-third of the basilar artery were shown to favor survival, compared with clots located in the proximal and/or middle portions of the basilar artery (relative risk, 0.52; 95% confidence interval, 0.31-0.86; n = 126). CONCLUSION: The combined data suggest that coma at presentation has an independent and adverse effect on survival rates. Complete recanalization, distal clot location, and responsiveness at the time of presentation are statistically significant factors for increased patient survival rates.

Adolescent↗

Ischemic core and penumbra in human stroke.

BACKGROUND AND PURPOSE: The ischemic core and penumbra have not been thoroughly characterized after acute cerebral thromboembolic occlusion in humans. Differentiation between areas of potentially viable and irreversibly injured ischemic tissue may facilitate assessment and treatment of stroke patients. METHODS: Cerebral blood flow (CBF) was measured in 20 patients with acute middle cerebral artery (MCA) occlusion between 60 and 360 minutes after stroke onset, with the stable xenon computerized tomography (CT) technique. Threshold displays were generated at a single level, and the percentages of hemisphere with CBF </=6, </=10, 11 to 20, 21 to 30, and >30 cm3. 100 g-1. min-1 were measured. The corresponding images on 12 available follow-up CT scans were similarly assessed to determine the area of final infarct. Comparisons were analyzed with a paired Student's t test and Pearson's correlation coefficient. RESULTS: Discrete and confluent areas of CBF </=20 cm3. 100 g-1. min-1 were identified in all patients, ipsilateral to the symptomatic MCA territory. The average area of CBF </=20 cm3. 100 g-1. min-1 within the ipsilateral hemisphere was 66+/-17% compared with 36+/-12% contralaterally (P<0.001). A difference in the extent of low CBF was due primarily to areas with CBF </=10 cm3. 100 g-1. min-1 (48+/-18% versus 16+/-7%, P<0.001). The area of most severe ipsilateral ischemia (</=6 cm3. 100 g-1. min-1) best corresponded to the final area of infarction (37+/-18% versus 40+/-24%; correlation coefficient, 0.866; P<0.01). The acute ischemic core destined to infarction was not surrounded by a widened rim of moderate ischemia because the area with CBF 11 to 20 cm3. 100 g-1. min-1 was similar bilaterally (19+/-4% versus 20+/-7%, P=0.792, thus not significant). CONCLUSIONS: Our study in acute human stroke involving MCA occlusion indicates that a severely ischemic core (CBF </=6 cm3. 100 g-1. min-1), observed between 1 to 6 hours after stroke onset, corresponds to the cerebral tissue destined to infarction. The ischemic penumbra with flow values between 7 and 20 cm3. 100 g-1. min-1 surrounding the ischemic core is very narrow. Therefore, strategies to improve the outcome of many patients with acute MCA occlusion must either include interventions to reverse the ischemic process within a few minutes of onset or increase the cerebral tolerance of ischemia and thereby prolong the potential therapeutic window.

Acute Disease↗

Advanced CT imaging (functional CT).

Computed tomography can provide anatomic and functional information about the brain. The conventional CT of the brain can be coupled with a cerebral blood flow examination using the stable xenon CT technique and with a CT angiography. Distinct subgroups of patients based on variations in cerebral blood flow and vascular pathology have been demonstrated. The addition of the functional information has become extremely important in triaging and determining the appropriate intervention in the patient with an acute neurological deficit.

Brain↗

Relation between cerebral blood flow and neurologic deficit resolution in acute ischemic stroke.

BACKGROUND AND OBJECTIVE: Early intervention remains the key to acute ischemic stroke therapy. Many patients whose deficits would later resolve without intervention are exposed to the risks of stroke treatment without benefit. The purpose of this study was to determine whether patients with transient deficits could be distinguished from patients with evolving strokes on the basis of acute cerebral blood flow (CBF) measurements before any clinical distinction could be made. METHODS: Fifty-three patients who presented with acute hemispheric stroke symptoms and who underwent xenon-enhanced CT (XeCT) CBF studies within 8 hours of onset of symptoms (and before any clinical improvement) were studied. RESULTS: Eight patients (15%) had a complete resolution of their symptoms within 24 hours (not related to treatment). All eight patients with deficits that resolved had normal CBF in the symptomatic vascular territories (mean time to XeCT = 3 hours, 51 min). Mean CBF in the regions of interest of the symptomatic vascular territories of patients who had deficits that resolved was 35.4 +/- 8.1 mL x 100 g(-1) x min(-1) compared with 17.3 +/- 9.3 mL x 100 g(-1) x min(-1) of patients with evolving strokes (p = 0.00058). CONCLUSIONS: Patients with ischemic neurologic deficits that will later resolve can be acutely distinguished from patients with evolving cortical infarctions using XeCT CBF measurements. CBF measurements may assist in the triage of patients for acute stroke therapy by selecting patients with a favorable prognosis and may not benefit from therapy but would still be exposed to the potential risks and expense of treatment.

Acute Disease↗

Relationship between cerebral blood flow and the development of swelling and life-threatening herniation in acute ischemic stroke.

OBJECT: The purpose of this study was to determine whether cerebral blood flow (CBF) measurements in acute stroke could be correlated with the subsequent development of cerebral edema and life-threatening brain herniation. METHODS: Twenty patients with aggressively managed acute middle cerebral artery (MCA) territory strokes who underwent xenon-enhanced computerized tomography (Xe-CT) CBF scanning within 6 hours of onset of symptoms were retrospectively reviewed. The relationship among CBF and follow-up CT evidence of edema and clinical evidence of brain herniation during the 36 to 96 hours following stroke onset was analyzed. Initial CT scans displayed abnormal findings in 11 patients (55%), whereas the Xe-CT CBF scans showed abnormal findings in all patients (100%). The mean CBF in the symptomatic MCA territory was 10.4 ml/100 g/minute in patients who developed severe edema compared with 19 ml/100 g/minute in patients who developed mild edema (p < 0.05). The mean CBF in the symptomatic MCA territory was 8.6 ml/100 g/minute in patients who developed clinical brain herniation compared with 18 ml/100 g/minute in those who did not (p < 0.01). The mean CBF in the symptomatic MCA territory that was 15 ml/100 g/minute or lower was significantly associated with the development of severe edema and herniation (p < 0.05). CONCLUSIONS: Within 6 hours of acute MCA territory stroke, Xe-CT CBF measurements can be used to predict the subsequent development of severe edema and progression to clinical life-threatening brain herniation. Early knowledge of the anatomical and clinical sequelae of stroke in the acute phase may aid in the triage of such patients and alert physicians to the potential need for more aggressive medical or neurosurgical intervention.

Acute Disease↗

Quantitative cerebral blood flow determinations in acute ischemic stroke. Relationship to computed tomography and angiography.

BACKGROUND AND PURPOSE: The advent of new modalities to treat acute ischemic stroke presents the need for accurate, early diagnosis. In acute ischemic stroke, CT scans are frequently normal or reveal only subtle hypodense changes. This study explored the utility and increased sensitivity of xenonenhanced CT (XeCT) in the diagnosis of acute cerebral ischemia and investigated the relationship between cerebral blood flow (CBF) measurements and early CT and angiographic findings in acute stroke. METHODS: The CT scans, XeCT scans, and angiograms of 20 patients who presented within 6 hours of acute anterior circulation ischemic strokes were analyzed. RESULTS: CT scans were abnormal in 11 (55%) of 20 patients. XeCT scans were abnormal in all 20 (100%) patients, showing regions of interest with CBF < 20 (mL/100 g per minute) in the symptomatic middle cerebral artery (MCA) territories. The mean CBF in the symptomatic MCA territories was significantly lower than than of the asymptomatic MCA territories (P < .0005). In patients with basal ganglia hypodensities, the mean symptomatic MCA territory CBF was significantly lower than that of patients who did not exhibit these early CT findings (P < .05). The mean symptomatic MCA territory CBF in patients with angiographic M1 occlusions was significantly lower than that of patients whose infarcts were caused by MCA branch occlusions (P < .01). CONCLUSIONS: These results show that XeCT is more sensitive than CT in detecting acute strokes and that CBF measurements correlate with early CT and angiographic findings. XeCT may allow for the hyperacute identification of subsets of patients with acute ischemic events who are less likely to benefit and more likely to derive complications from aggressive stroke therapy.

Acute Disease↗

Ultrasonography for diagnosis and management of carotid artery atherosclerosis. A position paper of the American Society of Neuroimaging.

The importance of identifying patients with carotid artery stenosis has attained greater significance in light of recent treatment trials of the efficacy of medical and surgical treatment of both symptomatic and asymptomatic carotid stenosis. Doppler and B-mode ultrasonography can accurately diagnose and quantify stenosis at the cervical carotid artery bifurcation. The development of duplex color-flow instruments has enhanced the sensitivity and specificity of this examination. Ultrasonography should be employed as an initial examination to identify patients with carotid artery stenosis and determine whether further evaluation or treatment is necessary.

Blood Flow Velocity↗