Biomedical subjects

L N Hopkins

Publications and source records attributed to L N Hopkins.

At least 19 recordsLinked to original sources

PubMed2007

Treatment of unruptured intracranial aneurysms: a nationwide assessment of effectiveness.

BACKGROUND AND PURPOSE: With advances in neuroimaging, unruptured cerebral aneurysms are being diagnosed more frequently. Until 1995, surgical clipping of the aneurysm was the only treatment available. Since then, a less invasive endovascular technique has been found effective in a trial of ruptured aneurysms. No efficacy studies comparing the 2 procedures for unruptured aneurysms exist to guide clinical decisions. The objective of this study was to assess effectiveness and outcomes of endovascular versus neurosurgical treatment for unruptured intracranial aneurysms. METHODS: This was a retrospective cohort study, using data collected over a 1-year time interval (between 1998 and 2000), from 429 hospitals, in 18 states, and representing 58% of the US population. A total of 2535 treated, unruptured cerebral aneurysm cases were evaluated. The measurements used were effectiveness as measured by hospital discharge outcomes: 1) mortality (in-hospital death), 2) adverse outcomes (death or discharge to a rehabilitation or nursing facility), 3) length of stay, and 4) hospital charges. Univariate analyses compared endovascular versus neurosurgical discharge outcomes. Multivariable models were adjusted for age, sex, region, Medicaid insurance status, year, hospital case volume, comorbidity score, and admission source. RESULTS: Endovascular treatment was associated with fewer adverse outcomes (6.6% versus 13.2%), decreased mortality (0.9% versus 2.5%), shorter lengths of stay (4.5 versus 7.4 days), and lower hospital charges (42,044 dollars versus 47,567 dollars) compared with neurosurgical treatment (P < .05). After multivariable adjustment, neurosurgical cases had 70% greater odds of an adverse outcome, 30% increased hospital charges, and 80% longer length of stay compared with endovascular cases (P < .05). CONCLUSIONS: The current analysis indicates that endovascular therapy is associated with significantly less morbidity, less mortality, and decreased hospital resource use at discharge, compared with conventional neurosurgical treatment for all unruptured aneurysms. Endovascular therapy, as a treatment alternative to surgical clipping, should be offered as a viable therapeutic option for all patients considering treatment of an unruptured cerebral aneurysm.

Adult↗

PubMed2006

Saccular aneurysms on straight and curved vessels are subject to different hemodynamics: implications of intravascular stenting.

Our aim was to examine hemodynamic implications of intravascular stenting in the canine venous pouch (sidewall or straight-vessel) and rabbit elastase (curved-vessel) aneurysm models. Flow dynamics in stented (Wallstent) and nonstented versions were studied by using computational fluid dynamics simulations and in vitro flow visualization, with a focus on stent placement effects on aneurysmal flow stagnancy and flow impingement. Results show that sidewall and curved aneurysm models have fundamentally different hemodynamics (shear-driven versus inertia-driven) and thus stent placement outcomes.

Animals↗

PubMed2004

Randomized comparison of intra-arterial and intravenous thrombolysis in a canine model of acute basilar artery thrombosis.

We compared the rates of recanalization cerebral infarct and hemorrhage between intra-arterial (i.a.) reteplase and intravenous (i.v.) alteplase thrombolysis in a canine model of basilar artery thrombosis. Thrombosis was induced by injecting a clot in the basilar artery of 13 anesthetized dogs via superselective catheterization. The animals were randomized in a blinded fashion, 2 h after clot injection and verification of arterial occlusion, to receive i.v. alteplase 0.9 mg/kg over 60 min and i.a. placebo, or i.a. reteplase 0.09 units/kg over 20 min, equivalent to one-half the alteplase dose, and i.v. placebo. Recanalization was studied for 6 h after treatment with serial angiography; the images were later graded in a blinded fashion. Blinded interpretation of postmortem MRI was performed to assess the presence of brain infarcts and/or hemorrhage. At 3 h after initiation of treatment, partial or complete recanalization was observed in one of six dogs in the i.v. alteplase group and in five of seven in the i.a. reteplase group (P = 0.08). At 6 h, no significant difference in partial or complete recanalization was observed between the groups (two of six vs. five of seven; P = 0.20). Postmortem MRI revealed infarcts in four of six animals treated with i.v. alteplase and three of seven treated with i.a. reteplase (P = 0.4). Intracerebral hemorrhage was more common in the i.v. alteplase group (four of six vs. none of seven; P = 0.02). This study thus suggests that i.a. thrombolysis affords a recanalization rate similar to that of i.v. thrombolysis, but with a lower rate of intracerebral hemorrhage.

Animals↗

PubMed2002

Particle image velocimetry assessment of stent design influence on intra-aneurysmal flow.

Endovascular stenting appears to be an appealing treatment modality to selected complex intracranial aneurysms. However, stents currently used for endovascular treatment are not specifically designed for the cerebrovasculature. Stent parameters, such as porosity and filament size, have to be carefully optimized for long-term successful treatment. We investigated the influence of the stent filament size on the intraaneurysmal flow dynamics in a sidewall aneurysm model in vitro. Three helical stents with 76% porosity but different filament sizes of 178, 153, and 127 microm were studied using particle image velocimetry. Twenty-four pulsatile flow conditions were investigated. The results show that stenting significantly reduces intra-aneurysmal vorticity and the mean circulation inside the aneurysm is reduced to less than 3% of its value before stenting. For constant porosity, a further reduction of the mean circulation, up to 30% can be obtained by reducing the filament diameter. For a constant Womersley number, this further reduction is accentuated with increase in the peak Reynolds number. Further reduction in the mean circulation inside the aneurysm was not achieved for the 127 microm stent. With further reduction in filament diameter, the helical stent filaments positioned against the aneurysm neck started wavering with the flow transferring added momentum into the aneurysm. For stents of smaller filament diameter, a supporting ultrastructure is required.

Alloys↗

PubMed2002

Angiographic quantification of contrast medium washout from cerebral aneurysms after stent placement.

BACKGROUND AND PURPOSE: Endovascular stent placement is an emerging technique in treating cerebral aneurysms. Thus far, no quantitative method is available to determine the effectiveness of stent deployment in reducing intraaneurysmal flow circulation, and thereby, in excluding the aneurysm from the cerebral vasculature. Our purpose was to develop a mathematical model congruent with flow transport phenomena observed in cerebral aneurysms and based on the washout of angiographic contrast medium from these aneurysms to provide quantitative indices for predicting the likelihood of stable thrombus formation after stent placement. METHODS: Angiographic data from an in vitro experiment involving an elastomer side-wall aneurysm model and data from five patients with cerebral aneurysms were collected and analyzed. A region of interest (ROI) delineating the aneurysm was selected in each case, and the temporal variation in average gray-scale intensity within this ROI was assessed. The mathematical model was fit to the gray-scale intensity curves by using least-squares minimization. Variations in model parameters before and after stent placement were studied. RESULTS: A marked variation in the model parameters was observed in both in vitro cases and when data suitable for mathematical modeling were available from the clinical setting. This variation supported the hypothesis of the model. CONCLUSION: On the basis of our results, we conclude that the model developed herein can be used to quantitatively depict and characterize alterations in aneurysmal blood-flow transport before and after endovascular stent placement. By inference, future versions of the model will be useful in predicting the long-term effectiveness of endovascular stent placement for cerebral aneurysms immediately after the procedure is performed.

Angiography↗

PubMed2001

Ineffective secondary prevention in survivors of cardiovascular events in the US population: report from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Survivors of myocardial infarction (MI) or stroke are at high risk for subsequent cardiovascular events. There is limited assessment of the effectiveness of risk factor modification through current secondary preventive strategies in the US population. We determined the adequacy of risk factor modification in 1252 survivors of MI, stroke, or both in a nationally representative sample of US adults and identified factors related to inadequate control of risk factors. METHODS: The adequacy of control for hypertension, diabetes mellitus, cigarette smoking, alcohol use, and hypercholesterolemia was assessed by personal interview, blood pressure measurements, and serum glycosylated hemoglobin and cholesterol levels in 17 752 US adults who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We also evaluated the role of potentially related factors, including age, sex, race/ethnicity, educational attainment, socioeconomic status, and medical insurance status using multivariate logistic regression analysis. RESULTS: Of 738 known hypertensive persons, hypertension was uncontrolled in 388 (53%). Previously undiagnosed hypertension was detected in 138 others (11%). Of 289 diabetic persons, serum glucose control was inadequate in 141. Of 1252 survivors, 225 (18%) were currently smoking, and heavy alcohol use was observed in 56 persons. Hypercholesterolemia was poorly controlled in 185 (46%) of 405 persons with known hypercholesterolemia. Undetected hypercholesterolemia was observed in 160 persons (13%). In the multivariate analysis, high-risk profiles were more likely to be observed in persons aged 46 to 65 years, women, and African Americans. CONCLUSIONS: High prevalence of inadequate secondary prevention was found in a subset of the US population at highest risk for stroke and MI. Considerable efforts are required to effectively implement risk factor modification strategies after MI or stroke, particularly in middle-aged persons, African Americans, and women.

Aged↗

PubMed2001

Cocaine use and the likelihood of nonfatal myocardial infarction and stroke: data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Numerous case series have implicated cocaine use as a cause of both myocardial infarction (MI) and stroke on the basis of the temporal relationship between drug use and event onset. Increasing cocaine use in the US population, especially in younger individuals, mandates a more extensive investigation of this relationship. METHODS AND RESULTS: We determined the association of cocaine use with self-reported physician diagnosis of MI or stroke in a nationally representative sample of 10 085 US adults aged 18 to 45 years who participated in the Third National Health and Nutrition Examination Survey. A total of 46 nonfatal MIs and 33 nonfatal strokes were reported. After adjusting for differences in age, sex, race/ethnicity, education, hypertension, diabetes mellitus, cholesterol level, body mass index, and cigarette smoking, persons who reported frequent lifetime cocaine use had a significantly higher likelihood of nonfatal MI than nonusers (odds ratio, 6.9; 95% confidence interval, 1.3 to 58) but not stroke. In this age group, the population-attributable risk percent of frequent cocaine for nonfatal MI was estimated as 25%. CONCLUSION: Regular cocaine use was associated with an increased likelihood of MI in younger patients. Approximately 1 of every 4 nonfatal MIs in persons aged 18 to 45 years was attributable to frequent cocaine use in this survey. Behavior modification by public awareness and education may reduce the cardiovascular morbidity associated with cocaine use.

Adolescent↗

PubMed2001

Frequency and predictors for angiographically improved inflow of contrast medium after carotid angioplasty and stenting.

Percutaneous transluminal carotid angioplasty and stenting (PTAS) can result in immediate improvement in cerebral blood flow (CBF) evident through faster transit of contrast medium on angiography. To evaluate frequency and predictors of changes in inflow of contrast medium before and after PTAS, we reviewed 86 patients (mean age 68.6 +/- 9.1 years) treated for symptomatic or asymptomatic carotid stenosis. Clinical data and lesion characteristics were extracted from charts and digital angiograms, respectively. Perfusion change was assessed qualitatively by comparing pre- and poststenting images matched for projection and time from injection. Improved inflow was defined on the basis of spatial or temporal distribution of contrast medium: grade -1: fewer vessels visible after stenting; 0: no change; 1: more distal small arteries visible; 2: time-matched poststenting image showing a capillary blush; 3: time-matched poststenting image showing small veins, 4 time-matched poststenting image showing large veins and sinuses. Faster inflow of contrast medium was observed in 74% of patients (grades 1: 34%,and 4: 4.7%). In linear regression analysis, higher degrees of ipsilateral stenosis were associated with greater changes in inflow of contrast medium (P < 0.05). Right internal carotid lesions were associated with greater change in inflow than left-sided lesions (P < 0.01). In 31 patients (36%) we initially showed contralateral anterior cerebral artery (ACA) filling, and in 39% of these, normal filling was restored after stenting. Lesser contralateral carotid stenosis was associated with crossed ACA filling and with restoration of normal filling pattern after stenting. Faster appearance of a contrast-medium blush is seen in most cases of carotid angioplasty and stenting and depends on the degree of hemodynamic inflow obstruction relieved by stenting.

Adult↗

PubMed2001

Angioplasty for cerebral vasospasm from eclampsia.

BACKGROUND: Neurological deterioration in eclampsia is considered to be secondary to cerebral vasospasm. Magnesium sulfate therapy improves symptoms and controls seizures, possibly related to its vasorelaxive effects in spastic arteries. Some cases, however, are refractory to magnesium therapy. To our knowledge, there is no report of angioplasty for vasospasm from eclampsia in the literature. METHODS: A 27-year-old woman presented 10 days postpartum with severe mental status changes and left arm and bilateral leg weakness that were refractory to magnesium therapy. Cerebral angiography demonstrated diffuse, severe vasospasm. We treated her with angioplasty of the bilateral middle and posterior cerebral arteries, basilar artery, and bilateral internal carotid arteries. RESULTS: Angioplasty resulted in excellent angiographic improvement. The patient immediately became responsive and appropriate with improved strength in all extremities. She continued to improve throughout her hospital stay and was discharged 10 days postangioplasty. CONCLUSIONS: Cerebral angioplasty is an effective treatment for vasospasm from eclampsia refractory to magnesium therapy. Angiography should be considered early in the course of neurological deterioration, but delayed therapy may also be effective.

Adult↗

PubMed2001

Superselective intra-arterial carboplatin for treatment of intracranial neoplasms: experience in 100 procedures.

BACKGROUND: The results of animal studies suggest that superselective intra-arterial infusion allows the permeation of a high concentration of chemotherapeutic agents within intracranial neoplasms. In the present report, we review our clinical experience with the 100 intra-arterial infusions of carboplatin in intracranial neoplasms not responsive to other treatment modalities. METHODS: Carboplatin was infused in 100 separate sessions (24 patients) as a mean dose of 286+/-60 mg/m2 (range 34-377 mg/m2). RMP-7, a bradykinin analog, was used as an adjunct in 28 sessions (6 patients). The infusions were performed through superselective microcatheterization of the following arteries: internal carotid (n = 39), middle cerebral (n = 61), posterior cerebral (n = 21) and anterior cerebral (n = 10). The frequency of neurological and non-neurological complications, and survival were recorded. In a subset of 10 patients, tumor volume was measured by serial magnetic resonance images to assess therapeutic response to therapy. RESULTS: The mean age of the patients was 44.5 years (range 26-67 years); 13 were men. The tumors were classified as glioblastoma multiforme (n = 12), metastatic tumor (n = 1), high-grade astrocytoma (n = 6), and anaplastic mixed glioma (n = 5). Follow-up was available for 23 patients (mean 22 months, range 2-69 months). Survival beyond 1 year after initiation of intra-arterial carboplatin therapy was documented in 12 of the 23 patients. A total of 13 neurological complications including seizures (n = 7), transient neurological deficits (n = 5), and ischemic stroke (n = 1) were observed in 100 procedures. A lower frequency of complications occurred in men and in patients who received adjunctive RMP-7. Volumetric analysis of serial magnetic resonance images demonstrated tumor mass reduction in 3 out of 10 patients. An increase in tumor mass ranging from 23% to 230% was observed in the other 7 patients over a period ranging from 2.3 to 37.7 months since initiation of carboplatin therapy. CONCLUSIONS: Superselective intra-arterial administration of carboplatin appears feasible and was associated with predominantly transient neurological complications. The addition of RMP-7 to carboplatin therapy appears to be at least as safe as the administration of carboplatin alone and requires further investigation as a means of chemotherapeutic dose intensification.

Adenocarcinoma↗

PubMed2001

Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders.

OBJECTIVE: Carotid bifurcation angioplasty and stenting (CBAS) has generated controversy and widely divergent opinions about its current therapeutic role. To resolve differences and establish a unified view of CBAS' present role, a consensus conference of 17 experts, world opinion leaders from five countries, was held on November 21, 1999. METHODS: These 17 participants had previously answered 18 key questions on current CBAS issues. At the conference these 18 questions and participants' answers were discussed and in some cases modified to determine points of agreement (consensus), near consensus, (prevailing opinion), or divided opinion (disagreement). RESULTS: Conference discussion added two modified questions, placing a total of 20 key questions before the participants, representing four specialties (interventional radiology, seven; vascular surgery, six; interventional cardiology, three; neurosurgery, one). It is interesting that consensus was reached on the answers to 11 (55%) of 20 of the questions, and near consensus was reached on answers to 6 (30%) of 20 of the questions. Only with the answers to three (15%) of the questions was there persisting controversy. Moreover, both these differences and areas of agreement crossed specialty lines. Consensus Conclusions: CBAS should not currently undergo widespread practice, which should await results of randomized trials. CBAS is currently appropriate treatment for patients at high risk in experienced centers. CBAS is not generally appropriate for patients at low risk. Neurorescue skills should be available if CBAS is performed. When cerebral protection devices are available, they should be used for CBAS. Adequate stents and technology for performing CBAS currently exist. There were divergent opinions regarding the proportions of patients presently acceptable for CBAS treatment (<5% to 100%, mean 44%) and best treated by CBAS (<3% to 100%, mean 34%). These and other consensus conclusions will help physicians in all specialties deal with CBAS in a rational way rather than by being guided by unsubstantiated claims.

Angioplasty↗

PubMed2001

Quantitative analysis of injured, necrotic, and apoptotic cells in a new experimental model of intracerebral hemorrhage.

OBJECTIVE: To develop a new survival model of intracerebral hemorrhage (ICH) in rabbits and study the patterns of cellular injury in different regions 24 hrs after introduction of hematoma. Quantitation and characterization of injured cells in regions adjacent and distant to the hematoma have not been performed. DESIGN: Prospective case-control study. SUBJECTS: Ten New Zealand rabbits. INTERVENTION: We introduced ICH in six anesthetized New Zealand rabbits by autologous blood injection under arterial pressure in the deep white matter in the frontal lobe. MEASUREMENTS AND MAIN RESULTS: Hematoxylin and eosin staining was performed in six animals with ICH after 24 hrs to quantify intact, injured, and necrotic cells in regions proximal and distant to the hematoma, and the results were compared with four control animals. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed to quantify apoptotic cells in specified regions in five animals with ICH, and the results were compared with four control animals. All cell counts were performed by one investigator who used 100x oil emersion microscopy. The presence of localized hematoma was confirmed in all six animals with blood infusion. Compared with controls, animals with ICH had a significantly higher proportion of swollen cells in both the inner (55.9% +/- 3.0% vs. 26.8% +/- 1.7%; p < .05) and the outer (59.8% +/- 4.6% vs. 27.7% +/- 4.5%; p < .05) rim of the perihematoma region. A small proportion of shrunken dark cells were observed in both the inner (4.0% +/- 1.5%) and the outer (3.6% +/- 1.0%) rim of the perihematoma region. The remaining cells were considered morphologically intact. A large proportion of cells trapped within the matrix of the hematoma were either shrunken dark cells (48.8% +/- 16.4%) or swollen (38.8% +/- 15.1%). In the TUNEL-stained sections, a high burden of apoptotic cells was observed in the matrix of the hematoma (17.5 +/- 6.3 cells per high power field) but not in the perihematoma regions (less than two cells per high power field). CONCLUSIONS: A reproducible model of ICH in rabbits is described. At 24 hrs, the perihematoma region contains relatively large proportions of morphologically intact or reversibly injured (swollen) cells, suggesting the possibility of an extended window for therapeutic intervention.

Analysis of Variance↗

PubMed2001

Treating complex nervous system vascular disorders through a "needle stick": origins, evolution, and future of neuroendovascular therapy.

In the past few decades, dramatic improvements have occurred in the field of neuroendovascular surgery. Endovascular therapy today is a well-established treatment modality for a variety of cerebrovascular and nonvascular central nervous system diseases. The foundation of this spectacular evolution was laid by the efforts of pioneering visionaries who often worked alone and under difficult, almost impossible, conditions. Ongoing device development and refinement have revolutionized the field at a dizzying, exhilarating pace. With a better understanding of the molecular basis of diseases and further advancements in gene therapy, neuroendovascular techniques have an enormous potential for application to the entire spectrum of central nervous system diseases as a minimally invasive vehicle for the delivery of biological factors.

Angioscopy↗

PubMed2001

Open-label phase I clinical study to assess the safety of intravenous eptifibatide in patients undergoing internal carotid artery angioplasty and stent placement.

OBJECTIVE: Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor inhibitor with high selectivity and a short half-life, has been demonstrated to reduce the risk of ischemic events associated with coronary interventions. However, its role in neurointerventional procedures needs to be analyzed. We report the results of an open-label Phase I study to evaluate the safety of the use of eptifibatide during carotid angioplasty and stent placement. METHODS: Each study patient received eptifibatide administered intravenously as a 135-microg/kg single-dose bolus, then a 0.5-microg/kg/min infusion for 20 to 24 hours during carotid angioplasty and stent placement. The primary efficacy end point was the 30-day composite occurrence of death, cerebral infarction, transient ischemic attack, and unplanned or urgent surgical intervention, thrombolysis, or subsequent percutaneous revascularization. The primary safety end point was bleeding. Bleeding complications were classified as major (hemoglobin decrease >5 g/dl), minor (hemoglobin decrease 3-5 g/dl), or insignificant. RESULTS: Ten patients (mean age, 73 yr; four men) were treated by use of the study protocol. One patient developed a minor stroke postprocedurally (National Institutes of Health Stroke Scale score of 21 at 24 h that improved to 1 at 7 d). Three patients underwent scheduled coronary artery bypass graft surgery 4 to 12 days after undergoing carotid angioplasty and stent placement. At 1-month follow-up, no new ischemic events were observed. Major or minor bleeding was not observed in any patient. Insignificant bleeding was observed in two patients. CONCLUSION: The use of eptifibatide as an adjunct to carotid angioplasty and stent placement seems to be safe. Further studies are required to analyze the effectiveness and role of eptifibatide in neurointerventional procedures.

Aged↗

PubMed2001

Angioplasty of intracranial occlusion resistant to thrombolysis in acute ischemic stroke.

OBJECTIVE: Thrombolysis has been demonstrated to improve revascularization and outcome in patients with acute ischemic stroke. Many centers now apply thrombolytic therapy locally via intra-arterial infusion. One therapeutic benefit is the ability to cross soft clots with a guidewire and to perform mechanical thrombolysis. In some instances, reopened arteries reocclude as a result of either thrombosis or vasospasm. We report the use of balloon angioplasty during thrombolysis for acute stroke. METHODS: From June 1995 through June 1999, 49 patients underwent intra-arterial therapy for acute stroke. In this group, nine patients (seven men and two women) were treated with balloon angioplasty after inadequate recanalization with thrombolytic infusion. The mean age of these patients was 67.9 years. Nine matched control patients who underwent thrombolysis alone without angioplasty were chosen for comparison. RESULTS: In the group of nine patients who had angioplasty, the mean National Institutes of Health Stroke Scale score at presentation was 21.8 +/- 5.4. Four patients had residual distal occlusion after angioplasty, and one patient had a hemorrhagic conversion. Of the five patients in which recanalization was successful, none had reocclusion of the balloon-dilated vessel. The mean score at 30 days for the five survivors was 12.6 +/- 14.9, for an improvement of 7.0 +/- 14.2. Among the nine control patients, the mean score at presentation was 20.3 +/- 5.2; the mean score at 30 days for the five survivors was 19.4 +/- 7.7, for an improvement of 4.2 +/- 7.8. CONCLUSION: In our experience, balloon angioplasty is a safe, effective adjuvant therapy in patients who are resistant to intra-arterial thrombolysis. The use of balloon angioplasty may prevent reocclusion in a stenotic artery and permit distal infusion of thrombolytic agents.

Aged↗

PubMed2001

Intra-arterial third-generation recombinant tissue plasminogen activator (reteplase) for acute ischemic stroke.

OBJECTIVE: We prospectively evaluated the safety and recanalization efficacy of intra-arterially administered reteplase, a third-generation recombinant tissue plasminogen activator, for treating ischemic stroke in patients considered poor candidates for intravenously administered alteplase therapy. METHODS: Patients were considered poor candidates for intravenously administered therapy because of severity of neurological deficits, interval from onset of symptoms to presentation of 3 hours or more, or recent major surgery. We administered a maximum total dose of 8 U of reteplase intra-arterially in 1-U increments via superselective catheterization. Adjunctive angioplasty of the occluded artery was performed in seven patients. Angiographic evidence of perfusion and thrombus was graded by use of modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Neurological examinations were performed before and 24 hours and 7 to 10 days after treatment. RESULTS: Sixteen consecutive patients were treated (mean age, 64.1 +/- 16.4 yr; seven were men). Initial National Institutes of Health Stroke Scale scores ranged from 10 to 26. Time from onset of symptoms to treatment ranged from 2 to 9 hours. Occlusion sites were the cervical internal carotid artery (n = 4), intracranial internal carotid artery (n = 4), middle cerebral artery (n = 6), and vertebrobasilar artery (n = 2). Complete or near-complete perfusion (TIMI Grade 3 or 4) was achieved in the arteries in 14 patients (88%), with partial recanalization (TIMI Grade 2) or minimal response (TIMI Grade 1) in the arteries in one patient each. Neurological improvement (defined as decrease of four or more points in National Institutes of Health Stroke Scale score) was observed in 7 (44%) of the 16 patients at 24 hours. Symptomatic intracerebral hemorrhage occurred in one patient; three other patients experienced intracerebral hemorrhages that did not result in neurological worsening. The overall mortality during hospitalization was 56%, related to massive ischemic stroke (n = 7), withdrawal of care at the family's request after the development of aspiration pneumonia and renal failure (n = 1), and a combination of intracerebral hemorrhage and massive ischemic stroke (n = 1). CONCLUSION: In this study, intra-arterially administered reteplase in doses up to 8 U with or without angioplasty resulted in a high rate of recanalization. This strategy should be considered in treating patients considered poor candidates for intravenous thrombolysis.

Acute Disease↗

PubMed2001

Absence of early proinflammatory cytokine expression in experimental intracerebral hemorrhage.

OBJECTIVE: We sought to analyze the regional concentrations of proinflammatory cytokines in the acute period of intracerebral hemorrhage (ICH) and to test the hypothesis that ICH is associated with the expression of proinflammatory cytokines in the acute period. Although the expression of cytokines and their role in neuronal injury and inflammation is well characterized in cerebral ischemia and head injury, no information exists regarding expression of cytokines in ICH. METHODS: We introduced ICH in eight anesthetized mongrel dogs by autologous blood injection (6 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. Samples of arterial blood and cerebrospinal fluid were collected, and tissue extracts were prepared from different regions of the brain for immunoassay of tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 concentrations in animals with and without ICH. RESULTS: The tumor necrosis factor a levels (+/- standard error) in the cerebrospinal fluid 1 hour after ICH did not differ significantly between the ICH group and the control group (7.1 +/- 1.3 pg/ml versus 10.8 +/- 2.3 pg/ml, P = 0.22). Levels in the perihematoma region in the ICH group (96.6 +/- 3.1 pg/ml) were not significantly different from those in the control group (93.4 +/- 6.7 pg/ml, P = 0.7). IL-6 levels (+/- standard error) in the perihematoma region in the ICH group (116.3 +/- 13.3 pg/ml) did not differ significantly from those in corresponding regions in the control group (122.3 +/- 12.8 pg/ml, P = 0.7). IL-1beta levels were below 5 pg/ml in serum, cerebrospinal fluid, and extracts of different brain regions. CONCLUSION: The early pathophysiology of ICH does not involve significant expression of tumor necrosis factor a either in the perihematoma region or other regions of the brain. The observation suggests that the pathophysiology of ICH in the acute period is different from both cerebral ischemia and traumatic brain injury.

Animals↗

PubMed2001

Risk factors for subarachnoid hemorrhage.

OBJECTIVE: Cigarette smoking has been demonstrated to increase the risk of subarachnoid hemorrhage (SAH). Whether cessation of smoking decreases this risk remains unclear. We performed a case-control study to examine the effect of smoking and other known risk factors for cerebrovascular disease on the risk of SAH. METHODS: We reviewed the medical records of all patients with a diagnosis of SAH (n = 323) admitted to Johns Hopkins Hospital between January 1990 and June 1997. Controls matched for age, sex, and ethnicity (n = 969) were selected from a nationally representative sample of the Third National Health and Nutrition Examination Survey. We determined the independent association between smoking (current and previous) and various cerebrovascular risk factors and SAH by use of multivariate logistic regression analysis. A separate analysis was performed to determine associated risk factors for aneurysmal SAH. RESULTS: Of 323 patients admitted with SAH (mean age, 52.7+/-14 yr; 93 were men), 173 (54%) were hypertensive, 149 (46%) were currently smoking, and 125 (39%) were previous smokers. In the multivariate analysis, both previous smoking (odds ratio [OR], 4.5; 95% confidence interval [CI], 3.1-6.5) and current smoking (OR, 5.2; 95% CI, 3.6-7.5) were significantly associated with SAH. Hypertension was also significantly associated with SAH (OR, 2.4; 95% CI, 1.8-3.1). The risk factors for 290 patients with aneurysmal SAH were similar and included hypertension (OR, 2.4; 95% CI, 1.8-3.2), previous smoking (OR, 4.1; 95% CI, 2.7-6.0), and current smoking (OR, 5.4; 95% CI, 3.7-7.8). CONCLUSION: Hypertension and cigarette smoking increase the risk for development of SAH, as found in previous studies. However, the increased risk persists even after cessation of cigarette smoking, which suggests the importance of early abstinence from smoking.

Case-Control Studies↗