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Biomedical subjects

Lawrence R Wechsler

Publications and source records attributed to Lawrence R Wechsler.

9 recordsLinked to original sources
PubMed2003

The cortical ischemic core and not the consistently present penumbra is a determinant of clinical outcome in acute middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Patient selection for acute stroke therapy based on physiology rather than on time may lead to expansion of the therapeutic window, improved outcomes, and fewer side effects than currently achieved. This approach requires early determination of both irreversible (core) and reversible (penumbra) ischemia in acute stroke. METHODS: Using established perfusion thresholds, we characterized the relationship among core, penumbra, and brain tissue perfused above penumbral thresholds (non-core/non-penumbra [NC/NP]) in 36 patients with middle cerebral artery (MCA) stem occlusion who underwent quantitative cerebral blood flow (CBF) assessment with xenon-enhanced CT within 6 hours of symptom onset. RESULTS: While great variability in the mean+/-SD percentage of core (37.6+/-18.7) and NC/NP (30.3+/-16.6) was observed, the percentage of penumbra was relatively constant from individual to individual, constituting approximately one third of the cortical MCA territory (32.1+/-7). In univariable and multivariable analyses, percent core and not percent penumbra was significantly associated with outcome. CONCLUSIONS: In acute MCA occlusion, penumbra is consistently present within a relatively narrow range, despite great variability in the size of core. This may explain why the core and not the penumbra is the main determinant of outcome in our group of patients. Recanalization therapy in acute MCA occlusion should ideally be guided by diagnostic methods capable of rapidly and reliably identifying irreversible ischemia.

Adult↗
PubMed2003

Selection of acute ischemic stroke patients for intra-arterial thrombolysis with pro-urokinase by using ASPECTS.

BACKGROUND: Previous studies have suggested that baseline computed tomographic (CT) scans might be a useful tool for selecting particular ischemic stroke patients who would benefit from thrombolysis. The aim of the present study was to assess whether the baseline CT scan, assessed with the Alberta Stroke Program Early CT Score (ASPECTS), could identify ischemic stroke patients who might particularly benefit from intra-arterial thrombolysis of middle cerebral artery occlusion. METHODS: Baseline and 24-hour follow-up CT scans of patients randomized within 6 hours of symptoms to intra-arterial thrombolysis with recombinant pro-urokinase or control in the PROACT-II study were retrospectively scored by using ASPECTS. Patients were stratified into those with ASPECTS >7 or < or =7. Independent functional outcome at 90 days was compared between the 2 strata according to treatment assignment. RESULTS: The analysis included 154 patients with angiographically confirmed middle cerebral artery occlusion. The unadjusted risk ratio of an independent functional outcome, in favor of treatment, in the ASPECTS >7 group was 5.0 (95% confidence interval [CI], 1.3 to 19.2) compared with 1.0 (95% CI, 0.6 to 1.9) in the ASPECTS < or =7 group. After adjustment for baseline characteristics, the risk ratio in the ASPECTS score >7 was 3.2 (95% CI, 1.2 to 9.1). Similar favorable treatment effects were observed when secondary outcomes were used, but these did not reach statistical significance. CONCLUSIONS: Ischemic stroke patients with a baseline ASPECTS >7 were 3 times more likely to have an independent functional outcome with thrombolytic treatment compared with control. Patients with a baseline ASPECTS < or =7 were less likely to benefit from treatment. This observation suggests that ASPECTS can be both a useful clinical tool and an important method of baseline risk stratification in future clinical trials of acute stroke therapy.

Acute Disease↗
PubMed2003

Factors influencing outcome and treatment effect in PROACT II.

BACKGROUND AND PURPOSE: The PROACT II study demonstrated a significant benefit from treatment with intra-arterial pro-urokinase (r-proUK) in patients with middle cerebral artery occlusion treated within 6 hours of stroke onset. The purpose of the current study was to examine baseline factors to determine predictors of good outcome and response to treatment. METHODS: We selected from the baseline clinical, radiologic, and angiographic data variables that considered possibly related to outcome. A univariate analysis was performed to examine the association between these baseline factors and good outcome, defined as a modified Rankin scale score <or=2. A multivariate model then selected the most important variables independently influencing prognosis. A risk score for each patient was constructed on the basis of the patient's individual values for each independent variable. Patients were stratified into risk quartiles based on their risk scores, and an odds ratio for each risk quartile was calculated. The treatment effects of each quartile were compared. RESULTS: In the univariate analysis, screening National Institutes of Health stroke scale (NIHSS) score and age were strongly associated with good outcome. The multivariate model selected age, NIHSS score, and CT hypodensity as the most important prognostic variables. Dividing patients into quartiles based on risk scores achieved a uniform gradient of probability of good outcomes. A trend toward benefit of r-proUK treatment was seen in all risk quartiles, and no differential treatment effect was observed across risk groups. CONCLUSIONS: There was no evidence of differential effect of r-proUK across subgroups of patients stratified by risk.

Adult↗
PubMed2002

Cell transplantation for stroke.

Cell transplantation has emerged as an experimental approach to restore brain function after stroke. Various cell types including porcine fetal cells, stem cells, immortalized cell lines, and marrow stromal cells are under investigation in experimental and clinical stroke trials. This review discusses the unique advantages and limitations of the different graft sources and emphasizes the current, limited knowledge about their biology. The survival, integration, and efficacy of neural transplants in stroke patients will depend on the type, severity, chronicity, adequacy of circulation, and location of the stroke lesion.

Bone Marrow Transplantation↗
PubMed2002

Innovative strategies in the management of acute stroke.

Advances in acute stroke therapy are rapidly changing our approach to management of patients with ischemic stroke. Intravenous tissue-plasminogen activator (tPA) was the first treatment demonstrated in a randomized controlled trial to improve outcome if given within the first 3 hours of stroke onset. Subsequent trials failed to extend the time window for intravenous therapy beyond 3 hours. Intra-arterial thrombolysis provides an alternative approach, with several advantages over intravenous therapy. The major drawback is the additional time needed for the interventional procedure, and the equipment and personnel requirements. New strategies aimed at reducing the total time from stroke onset to recanalization of occluded arteries include a combined intravenous/ intra-arterial delivery of thrombolysis and mechanical devices. For the millions of stroke survivors, investigations are now underway into the possibility of improvement of function through neuronal transplantation.

Fibrinolytic Agents↗
PubMed2002

Absence of a diastolic velocity notch does not indicate hyperemia in traumatic brain injured patients without elevated cerebral blood flow velocity.

Elevated blood flow velocity (BFV), measured by transcranial Doppler (TCD), has been associated with hyperemia and cerebral vasospasm. This study examined whether the lack of a diastolic notch within the TCD waveform was associated with relative hyperemia within 5 days after injury in 35 traumatic brain injured (TBI) patients. Hyperemia (avD(O2) of < 4 ml/dL) was present in 16 patients and absent in 19 patients. Two clinicians independently coded TCD waveforms based on the presence of a diastolic notch (88% agreement). There was no significant difference in the presence of a diastolic notch by group; a diastolic notch was present in 57% (11/19) of patients without hyperemia and 81% (13/16) of patients with hyperemia. Sensitivity and specificity of detecting hyperemia using the diastolic notch was 18.7% and 57.9% respectively. The results showed that relative hyperemia was present without an elevation in blood flow velocities, and that the lack of a diastolic notch did not detect the presence of hyperemia in the TBI patient.

APACHE↗
PubMed2002

Computed tomographic findings in patients undergoing intra-arterial thrombolysis for acute ischemic stroke due to middle cerebral artery occlusion: results from the PROACT II trial.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the role of noncontrast CT in the selection of patients to receive thrombolytic therapy for acute ischemic stroke and to predict radiological and clinical outcomes. METHODS: One hundred eighty patients with stroke due to middle cerebral artery (MCA) occlusion were randomized 2:1 within 6 hours of onset to receive intra-arterial recombinant prourokinase plus intravenous heparin or intravenous heparin only. Four hundred fifty-four CT examinations were digitized to calculate early infarct changes, infarct volumes, and hemorrhagic changes among the 162 patients treated as randomized (108 recombinant prourokinase-treated patients and 54 control patients). CT changes were correlated with baseline stroke severity, angiographic clot location, collateral vessels, and outcome at 90 days. RESULTS: Baseline CT scans, 120 (75%) of 159, showed early infarct-related abnormalities. The baseline CT abnormality volume was not correlated with the baseline National Institutes of Health Stroke Scale (NIHSS) score (r=-0.11) but was correlated weakly with the outcome (r=0.17, P<0.05). Compared with patients with M2 occlusions, patients with M1 MCA occlusions had significantly higher baseline NIHSS scores (P<0.05), more basal ganglia involvement on CT, and larger hypodensity volumes on follow-up CTs. Compared with patients with partial or no collateral supply, patients with full collateral supply had lower baseline NIHSS scores, significantly smaller baseline CT infarct volumes, and less cortical involvement (P<0.05). CONCLUSIONS: Noncontrast CT is not correlated with baseline stroke severity and does not predict outcome in patients with stroke due to MCA occlusion. However, baseline CT changes, clinical presentation, and the evolution of CT changes are influenced by clot location and the presence of a collateral supply.

Acute Disease↗
PubMed2002

Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women.

BACKGROUND AND PURPOSE: The purpose of the present study was to compare the prevalences of genetic polymorphisms in persons with cryptogenic stroke with those among stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke). METHODS: We compared the prevalences of genetic polymorphisms thought to be related to thrombi formation in young stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke; controls; n=79) with those in young stroke patients without such sources (cryptogenic stroke; cases; n=67). Common variations in the genes encoding factor V, prothrombin, angiotensin I-converting enzyme, 5,10-methylenetetrahydrofolate reductase, endothelial cell nitric oxide synthase, tissue plasminogen activator, plasminogen activator inhibitor-1, and fibrinogen were evaluated. We also compared the allele prevalence of these genes among all stroke patients with those among a large pool of historical controls assayed for these genes. RESULTS: None of these genetic polymorphisms was statistically significantly related to cryptogenic stroke. With respect to a comparison of all ischemic stroke with historical controls, only the prevalence of tissue plasminogen activator D allele among stroke subjects was statistically significantly higher than that of the historical controls (P=0.0014). CONCLUSIONS: These findings generally do not support the hypothesis that genes associated with a prothrombotic state are risk factors among a subgroup of young people with stroke of undetermined cause. Except for the D tissue plasminogen activator allele, the findings also indicated that these genetic factors are unrelated, or only weakly related, to all ischemic stroke.

Adult↗