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S R Levine

Publications and source records attributed to S R Levine.

At least 55 records · Page 3Linked to original sources

Time course of ADCw changes in ischemic stroke: beyond the human eye!

BACKGROUND AND PURPOSE: Using newly developed computerized image analysis, we studied the heterogeneity of apparent diffusion coefficient of water (ADCw) values in human ischemic stroke within 10 hours of onset. METHODS: Echo-planar trace diffusion-weighted images from 9 patients with focal cortical ischemic stroke were obtained within 10 hours of symptom onset. An Iterative Self-Organizing Data Analysis (ISODATA) clustering algorithm was implemented to segment different tissue types with a series of DW images. ADCw maps were calculated from 4 DW images on a pixel-by-pixel basis. The segmented zones within the lesion were characterized as low, pseudonormal, or high, expressed as a ratio of the mean+/-SD of ADCw of contralateral noninvolved tissue. RESULTS: The average ADCW in the ischemic stroke region within 10 hours of onset was significantly depressed compared with homologous contralateral tissue (626.6+/-76.8 versus 842.9+/-60.4x10(-6) mm2/s; P<0.0001). Nevertheless, ISODATA segmentation yielded multiple zones within the stroke region that were characterized as low, pseudonormal, and high. The mean proportion of low:pseudonormal:high was 72%:20%:8%. CONCLUSIONS: Despite low average ADCW, computer-assisted segmentation of DW MRI detected heterogeneous zones within ischemic lesions corresponding to low, pseudonormal, and high ADCw not visible to the human eye. This supports acute elevation of ADCw in human ischemic stroke and, accordingly, different temporal rates of tissue evolution toward infarction.

Acute Disease↗

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group.

Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients. A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002). The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities. Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system.

Acute Disease↗

Role of anticardiolipin antibodies in young persons with migraine and transient focal neurologic events: a prospective study.

Anticardiolipin antibodies (aCL) are a risk factor for cerebral ischemia. In migraine, the association is controversial, with widely varying results in different small series. The controversy in part may be due to the inherent difficulty in distinguishing the transient focal neurologic events (TFNE) of migraine from TIA. To assess the frequency of aCL in migraine, we prospectively evaluated consecutive adults under 60 years of age with migraine without aura and with recent TFNE (<24-hour duration) clinically suggestive of either migraine with aura or TIA. We concomitantly enrolled persons with no CNS disease. Each person was interviewed and had blood drawn for solid-phase ELISA with IgG and IgM aCL isotyping. Neuroradiologic studies were reviewed. Patients with TFNE were followed every 6 months for the duration of the 3-year study. The frequency of aCL positivity (IgG >20, IgG >40, IgM >7.5) for the 645 patients with TFNE (8.8, 3.1, 4.2%), the 518 persons in the TFNE subgroup with migraine with aura (8.9, 3.3, 4.1%), the 497 persons with migraine without aura (7.0, 2.0, 3.6%), and the 366 control subjects (9.3, 3.6, 3.9%) did not differ significantly between groups. In TFNE patients with elevated aCL titer, the association was positive with diabetes mellitus, TFNE duration <15 minutes, and diplopia and was negative with hemiparesis, tinnitus, and family history of stroke. Findings on imaging consistent with cerebral ischemia were more frequent in aCL-positive persons. The short-term risk of stroke was uniformly low. In young persons, aCL is not associated with migraine or with TFNE, although diabetes mellitus, negative family history of stroke, and brief duration of symptoms (including diplopia) may predict immunoreactivity. Imaging studies suggest an ischemic etiology of TFNE in this cohort.

Adolescent↗

Specificity, isotype, and titer distribution of anticardiolipin antibodies in CNS diseases.

BACKGROUND AND PURPOSE: There is an association between anticardiolipin antibodies (aCL) and ischemic stroke. There are, however, also occasional reports linking aCL with other CNS diseases (OND), particularly with multiple sclerosis (MS). Hence, we studied the specificity of aCL for ischemic stroke. METHODS: Prospective, consecutively identified patients evaluated for aCL (immunoglobulin G [IgG] and immunoglobulin M [IgM] isotypes) were divided into two groups: ischemic stroke (first ever) and OND (stroke-free subjects affected by OND). RESULTS: The ischemic stroke group (n = 300) and the OND (n = 149) differed in the following risk factors: age (64 +/- 14 versus 58 +/- 15 years; p < 0.001) and proportions of African Americans (67% versus 29%; p < 0.001); current cigarette smoker (26% versus 17%; p = 0.028); hypertensive (69% versus 34%; p < 0.001); diabetic (18% versus 7%; p = 0.001); history of angina (16% versus 8%; p = 0.015) or myocardial infarction (15% versus 3%; p < 0.001). There were higher rates of aCL positivity (26% versus 17%; p = 0.050), IgG-aCL > 10 GPL (23% versus 11%; p = 0.003) or IgG aCL > 20 GPL (12% versus 4%; p = 0.012) among the stroke group than among the OND group. No differences in IgG-aCL positivity were found between the MS group and the rest of the OND group but the MS patients had a higher rate of IgM-aCL positivity than the other OND patients. CONCLUSION: IgG-aCL positivity does not appear to be a marker for CNS disease generally but of ischemic stroke.

Antibodies, Anticardiolipin↗

Thrombolytic therapy for stroke: the new paradigm.

Roughly 80% of patients with acute stroke have thromboocclusive disease and may benefit from clot lysis with recombinant tissue plasminogen activator. To be effective, however, such treatment must be administered within three hours of stroke onset in carefully selected patients. Hospital protocols that mobilize an acute stroke team to minimize delays are needed nationwide.

Acute Disease↗

Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.

OBJECTIVE: To develop an approach for reducing time between emergency department (ED) admission and treatment in patients with acute ischemic stroke to meet the challenge of providing tissue plasminogen activator treatment within 180 minutes. DESIGN: An observational study. SETTING: Forty trial-affiliated hospitals, including 30 community hospitals. PARTICIPANTS: A total of 17,324 consecutive patients admitted to trial-affiliated hospital EDs within 24 hours of possible stroke, from January 1991 through October 1994. INTERVENTION: Appraisal of the process of triage, evaluation, diagnosis, and treatment by means of total quality improvement techniques in each hospital. Staff participating in the process identified sources of variation and modifications by flow charting the process. MAIN OUTCOME MEASURE: Time between ED admission and treatment with study medication. RESULTS: Total quality improvement methods identified hospital-specific process improvements. Many improvements were administrative, requiring no additional resources. More than 50% of screened patients arrived too late to be treated. Only 1268 patients were admitted between 0 and 125 minutes from stroke onset with no other trial exclusion criteria; 48% were treated. Of 243 patients admitted between 126 and 170 minutes from stroke onset with no exclusion criteria, 4% were treated. Mean time from ED admission to treatment was similar in teaching and community hospitals. CONCLUSIONS: Total quality improvement methods identified ED-specific sources of process variability and reduced time between ED admission and treatment. Therefore, these methods should be considered in developing and monitoring emergent stroke treatment protocols.

Acute Disease↗

Cerebral venous thrombosis and anticardiolipin antibodies.

BACKGROUND AND PURPOSE: The association of cerebral venous thrombosis (CVT) with a variety of pathological states is well established. However, there are only rare isolated reports of CVT associated with anticardiolipin antibodies (aCL). METHODS: To clarify the clinical and neuradiological features as well as outcome of patients with CVT associated with aCL, we reviewed the records of all patients with CVT evaluated at our institution between 1989 and 1996 (retrospective and prospective) and systematically reviewed the pertinent literature. RESULTS: We identified 8 aCL+ and 7 aCL- patients with CVT. No patients with lupus anticoagulant (LA) were identified. The mean age was 23 +/- 11.01 (range, < 1 to 36) years in the aCL+ and 38 +/- 9.30 (range, 25 to 54) years in the aCL- patients (P = .016). Six of 8 aCL+ and 5 of 7 aCL- patients were women. The dural sinuses were involved in all aCL+ and in 6 of 7 aCL- patients, while deep venous system thrombosis occurred in 5 of 8 (63%) aCL+ and 1 of 7 (14%) aCL- patients. In the aCL+ patients CVT was associated with puerperium or oral contraceptive use (n = 6), and sickle cell trait (n = 1), and in the aCL- patients CVT was associated with systemic lupus erythromatosus (n = 1), myelodysplasti syndrome (n = 1), colonic cancer (n = 1), oral contraceptive use or puerperium (n = 3), and dehydration (n = 1). Seven aCL+ patients received either intrasinus urokinase or intravenous heparin sulfate, and 1 received aspirin. Four aCL+ patients developed new onset or worsening of preexisting migraine, 2 developed recurrent peripheral venous thrombosis, and 1 went on to have intracranial hypertension. Twenty additional patients with CVT associated with antiphospholipid antibodies (aPL) were found reported in the literature. The overall mean age was 36 +/- 11.6 (range, 21 to 62) years, and 14 (70%) were women. LA was present in 11 of 18 tested, aCL in 7 (35%), LA and aCL in 1, and the type of aPL was not reported in 3. The mean age for the aCL+ only group was 28 years and for the LA+ (with or without aCL+) was 34 years. Only 1 patient, whose aPL type was not specified, had thrombosis of the deep venous system in addition to involvement of the dural sinuses. CONCLUSIONS: Our series and review suggest that aCL may be an important factor contributing to development of CVT even in the presence of other potential etiologies or risk factors. Onset of aCL+ CVT occurs at a relative young age and with relatively more extensive superficial and deep cerebral venous system involvement than aCL- CVT.

Adult↗

IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study.

BACKGROUND: Anticardiolipin antibodies (aCL) have been associated with an increased risk of stroke and thrombo-occlusive events. Little is known about the influence of aCL on recurrent thrombo-occlusive events. METHODS: Consecutively identified patients (n = 132) with focal cerebral ischemia [stroke = 112, transient ischemic attack (TIA) = 20] harboring aCL of at least 10 GPL units at the time of their index event were prospectively followed to estimate the effect of aCL titer on time to and risk of subsequent thrombo-occlusive events (stroke, TIA, deep venous thrombosis, pulmonary embolism, myocardial infarction) and death. On the basis of prior literature, we divided patients into those with aCL < or = 40 GPL (n = 111; mean age, 63 +/- 14 years; mean follow-up, 1.95 years) and those with aCL > 40 GPL (n = 21; mean age, 54 +/- 20 years; mean follow-up, 1.50 years). RESULTS: There was no difference between groups for prevalence of hypertension, diabetes mellitus, cigarette smoking, atrial fibrillation, prior TIA, or sex. The GPL > 40 group was younger (54 +/- 20 versus 63 +/- 14 years; P = .055), had more prior strokes [9/21 (48%) versus 27/111 (20%); P = .030], more frequent subsequent thrombo-occlusive events and death [15/21 (71%) versus 51/111 (48%); P = .030], and a shorter median time (years) to event (0.15 versus 0.61, log rank P = .005). The risk ratio for recurrent event and death with GPL > 40 obtained from Cox proportional hazards models, adjusted for prior strokes, prior TIAs, hypertension, diabetes mellitus, atrial fibrillation, and cigarette smoking was 1.9 (95% confidence interval, 1.0 to 3.5; P = .051). CONCLUSIONS: Our data suggest that subsequent thrombo-occlusive events and death after focal cerebral ischemia associated with IgG aCL may occur sooner and more frequently with GPL > 40.

Adult↗

Cerebrovascular complications of Fabry's disease.

Fabry's disease (FD) is a rare, sex-linked disorder resulting from alpha-galactosidase deficiency. Cerebrovascular complications have been reported in the literature but have not been systematically analyzed. We report 2 patients and review 51 previously reported cases (descriptive meta-analysis) to clarify the clinical, radiologic, and pathologic features. The average age at onset of cerebrovascular symptoms was 33.8 years for hemizygous individuals (n = 43) and 40.3 years of heterozygotes (n = 10). The most frequent symptoms and signs were as follows (in descending order of frequency): hemiparesis, vertigo/dizziness, diplopia, dysarthria, nystagmus, nausea/vomiting, head pain, hemiataxia, and ataxia of gait, in the hemizygote group; and memory loss, dizziness, ataxia, hemiparesis, loss of consciousness and hemisensory symptoms, in the heterozygote group. The vertebrobasilar circulation was symptomatic in 67% of the hemizygotes and 60% of the heterozygotes. Intracerebral hemorrhage was found in 4 patients (3 hemizygotes and 1 heterozygote). Elongated, ectatic, tortuous vertebral and basilar arteries were the most common angiographic and pathologic features. For the hemizygotes, the recurrence rate for cerebrovascular disease was 76% and the death rate was 55%; 86% of the heterozygotes had recurrent cerebrovascular event(s) and 40% died. The cerebrovascular manifestations of FD, in both hemizygotes and heterozygotes, are predominantly due to dilative arteriopathy of the vertebrobasilar circulation, frequently recur, and portend a poor prognosis.

Adolescent↗

Effects of ramipril and enalapril on cerebral blood flow in elderly patients with asymptomatic carotid artery occlusive disease.

We wished to determine in asymptomatic hypertensive patients with > or = 70% stenosis of an internal carotid artery the change in regional cerebral blood flow (rCBF) produced by ramipril and enalapril and to evaluate the influence of age on drug-induced changes in rCBF. In a prospective, randomized, single-blind, placebo-controlled investigation, using the 133Xenon inhalation technique, we assessed baseline rCBF in 15 patients (9 men and 6 women aged 60-79 years) after a 24-h antihypertensive drug-free period. All patients then received a single 5-mg oral dose of ramipril, enalapril, or placebo. rCBF was reassessed 2 h postdose. There was no significant change in the median rCBF in any of the three treatment groups. Neither did we observe any lateralization of BF to any specific cerebral region in any of the three groups. There were no observed or patient-reported adverse events (AE). Single 5-mg oral doses of either ramipril or enalapril did not decrease CBF significantly in asymptomatic hypertensive patients with > or = 70% stenosis of an internal carotid artery and are probably safe starting doses in such patients. In addition, this effect was not modified by age.

Age Factors↗

Neurological aspects of antiphospholipid antibody syndrome.

Antiphospholipid antibodies (aPL) have been associated with a variety of neurological disorders, mostly linked to focal neuroparenchymal ischemia or infarction. Cerebral ischemia associated with the antiphospholipid syndrome (APS) occurs at a younger age than typical atherothrombotic cerebrovascular disease, is often recurrent, and high positive GPL values are usually linked to the presence of a lupus anticoagulant. When other features of the syndrome are not present and cerebral ischemia occurs only associated with anticardiolipin immunoreactivity, there appears to be no discerning features of these patients unless GPL > 40 for which recurrent thrombo-occlusive events appear to occur more frequently. Other neurological manifestations associated with aPL include cerebral venous sinus thrombosis, ocular ischemia, dementia, including ischemic encephalopathy, and chorea. The role of aPL in migrainous events is controversial and may not play a role in recent, large case-controlled studies. Most seizures in patients harboring aPL are associated with focal brain infarction.

Antiphospholipid Syndrome↗

Treatment of neurologic complications of antiphospholipid antibody syndrome.

Thrombosis associated with antiphospholipid antibodies (aPL) occurs in both venous and the arterial circulation. The most common arterial thrombo-occlusive event is cerebral infarction. We briefly review treatment strategies aimed at patients with cerebrovascular disease and aPL. Besides general treatment issues, we discuss primary prevention and secondary prevention. Most regimens include antithrombotics or immune modulation. Prospective studies (currently underway) are required to better estimate the rate of recurrent thrombo-occlusive events on standardized therapy before one therapy can be recommended over another with reasonable evidence.

Antiphospholipid Syndrome↗

Cocaine-associated intracranial hemorrhage: absence of vasculitis in 14 cases.

Complications associated with the use of cocaine are varied, and include cerebral hemorrhage and ischemia, with vasculitis and vasospasm as possible etiologies. We reviewed selected brain samples from 14 autopsy cases of cocaine-related cerebrovascular disease. Intracerebral or subarachnoid hemorrhage was present in 12 cases. Intracranial arterioles were either normal or showed nonspecific changes. From these observations, we suggest that intracranial hemorrhages occur in the absence of readily detectable vascular abnormalities.

Adult↗

Cerebrovascular disease with antiphospholipid antibodies: immune mechanisms, significance, and therapeutic options.

There has been a recent, dramatic surge in interest in antiphospholipid antibodies and associated clinical disorders, especially focal ischemic cerebrovascular disease. Antiphospholipid antibodies are a heterogeneous group of antibodies with varying specificities. Coagulation assays will detect lupus anticoagulants while enzyme-linked immunosorbent assays detect anticardiolipin antibodies. There are numerous potential links between antiphospholipid antibodies and coagulation disorders, including interaction of antiphospholipid antibodies and a cofactor, beta 2-glycoprotein I, which itself is involved in coagulation mechanisms. While the specific mechanism of antiphospholipid antibody-related coagulopathy is unknown, it is clear that antiphospholipid antibodies are associated with an immune-mediated prothrombotic state. Patients with the highest titers of IgG antiphospholipid antibodies have a relatively high risk of recurrent thrombotic events, especially stroke, deep venous thrombosis, and spontaneous abortion. Because of limited controlled, prospective data, current therapy remains empiric and directed at coagulation mechanisms, immune mechanisms, or both.

Adrenal Cortex Hormones↗

Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome.

We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7-year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false-positive Venereal Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo-occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow-up during a mean prospective follow-up of 3 years. Over one-half of the cohort had at least one recurrent thrombo-occlusive event during follow-up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo-occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.

Adult↗

Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from patients with ischemic stroke and transient ischemic attacks.

Leukocytes may have an important role in the pathogenesis of brain injury after ischemia. Expression of adhesion molecules on leukocytes and/or endothelia is needed for leukocytes to adhere to endothelia and infiltrate into the injured brain. The purpose of the present pilot study is to delineate whether the expression of leukocyte adhesion molecules, CD11a and CD18, are upregulated in patients with ischemic stroke and transient ischemic attack. Ten patients with ischemic stroke, 6 with transient ischemic attack (TIA), and 11 age and risk factor matched controls were studied. Using immunofluorescence phenotyping and flow cytometry, leukocyte membrane expression of CD11a and CD18 were measured within 72 h after onset of ischemia. Follow-up measurements were performed at 5-7 days after ictus in 6 patients with stroke, and at 3-5 days after ictus in 3 patients with TIA. CD11a immunofluorescence (IF) was significantly increased within 72 h after onset of symptoms in patients with stroke as well as TIA compared with the control group (p < 0.017). IF of CD18 also increased in both patient groups, but significance was reached only in the TIA group (p < 0.05). No difference of CD11a and CD18 IF was detected between stroke and TIA groups. Follow-up measurement of CD11a and CD18 showed a trend of decrease, but CD11a IF remained significantly elevated compared with the control group (p < 0.017). Expression of leukocyte adhesion molecules CD11a, and CD18 are upregulated in patients with ischemic stroke and TIA. Although these data are preliminary, our data suggest that these molecules are associated with cerebrovascular disorders including ischemic stroke and TIA.

Aged↗