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Biomedical subjects

J L Saver

Publications and source records attributed to J L Saver.

At least 19 recordsLinked to original sources
PubMed2007

Intra-arterial thrombolysis for acute stroke in patients 80 and older: a comparison of results in patients younger than 80 years.

BACKGROUND AND PURPOSE: Intra-arterial fibrinolytic therapy is a promising treatment for acute ischemic stroke. Few data are available on its use in elderly patients. The purpose of this study was to compare the baseline characteristics, complications, and outcomes between intra-arterially treated ischemic stroke patients aged > or = 80 years and their younger counterparts. METHODS: Patients aged > or = 80 years (n = 33) were compared retrospectively with contemporaneous patients aged < 80 years (n = 81) from a registry of consecutive patients treated with intra-arterial thrombolysis over a 9-year period. RESULTS: The very elderly and younger cohorts were very similar in baseline characteristics, including pretreatment stroke severity (National Institutes of Health Stroke Scale [NIHSS] 17 versus 16), differing only in history of stroke/transient ischemic attack (42% versus 22%, P = .01) and weight (66.8 versus 75.8 kg; P = .02). Significant differences in recanalization (TIMI 2-3) rates could not be detected between the very elderly and younger patients (79% versus 68%, P = .10). Rates of major symptomatic hemorrhage (7% versus 8%) and any intracerebral hemorrhage (39% versus 37%) did not differ. Outcomes at 90 days showed lower rates of excellent functional outcome (mRS < or = 1, 26% versus 40%, P = .02) and survival (57% versus 80%, P = .01) among the very elderly. CONCLUSIONS: Intra-arterial fibrinolysis in the elderly can be accomplished with recanalization rates and hemorrhage rates equal to that in younger patients. Although mortality rates are higher and good functional outcomes are lower than in younger persons, nondisabling outcomes may be achieved in a quarter of patients. These findings suggest that the investigation and use of intra-arterial thrombolytic treatment in very elderly patients should not be avoided but pursued judiciously.

Adult↗
PubMed2006

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis.

BACKGROUND: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. METHODS: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. RESULTS: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. CONCLUSIONS: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

Aged↗
PubMed2006

Early MRI and outcomes of untreated patients with mild or improving ischemic stroke.

OBJECTIVE: To determine the frequency of early neurologic deterioration with infarct expansion (ENDIE) and poor outcomes among ischemic stroke patients not treated with reperfusion therapies because of rapidly improving or mild symptoms (RIMS) and to study the predictive value of hyperacute MRI in these patients. METHODS: We identified consecutive patients with symptoms of acute stroke undergoing multimodal MRI within 6 hours of onset without evidence of hemorrhage on imaging. Medical records were reviewed for evidence of early neurologic deterioration within 48 hours. All deteriorating patients had repeat MRI to ascertain causes of worsening. Poor outcome was defined as a discharge modified Rankin Scale (mRS) score of > or = 3. RESULTS: We identified 74 patients with stroke symptoms < or = 6 hours from onset. Forty had RIMS, and 39 did not receive reperfusion therapies because of RIMS. Among these 39, 4 experienced ENDIE, and 8 were discharged with mRS score of > or = 3. Eight of the 39 patients had large-vessel occlusions on MR angiography. Three of 8 patients with large-vessel occlusion as against only one of 31 patients without occlusion had ENDIE (odds ratio [OR] 18, 95% CI 1.6 to 209, p = 0.02). Four of 8 patients with large-vessel occlusion as against 4 of 31 patients without occlusion had a discharge mRS score of > or = 3 (OR 7, 95% CI 1.2 to 38, p = 0.04). CONCLUSIONS: About 10% of patients eligible for acute reperfusion therapy excluded on the basis of mild or rapidly improving symptoms show early neurologic deterioration with infarct expansion within 48 hours, and about 20% show poor outcome at discharge. Persisting large-vessel occlusion substantially increases the risk of early worsening and poor functional outcome.

Confidence Intervals↗
PubMed2006

Are elevated admission calcium levels associated with better outcomes after ischemic stroke?

Calcium (Ca(2+)) and magnesium (Mg(2+)) influence the molecular pathways of ischemic neuronal death. The authors evaluated the impact of admission serum Ca(2+) and Mg(2+) levels, on incident stroke severity and discharge functional outcome. After adjusting for covariates, higher admission Ca(2+) was significantly associated with lesser stroke severity and better discharge functional outcome. Admission Mg(2+) was not an independent clinical outcome prognosticator.

Adolescent↗
PubMed2006

Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke.

Recent data suggest that women obtain greater benefit than men from IV fibrinolysis for acute ischemic stroke. It is unknown whether this gender-thrombolysis advantage extends to those treated with intra-arterial (IA) thrombolysis. The authors evaluated the independent effect of gender among ischemic stroke patients treated with IA fibrinolysis and found no differences in short-term clinical and angiographic outcomes between men and women who received IA thrombolysis for acute ischemic stroke.

Aged↗
PubMed2006

Statin treatment and adherence to national cholesterol guidelines after ischemic stroke.

BACKGROUND: National cholesterol guidelines have defined high vascular risk individuals as those who could potentially benefit most from statin therapy. The authors aimed to determine the rate of statin use, its predictors, and the achievement of national guideline target lipid goals among ischemic stroke survivors. METHODS: The authors abstracted data from the Vitamin Intervention for Stroke Prevention (VISP) study database from the United States and Canada to incorporate into algorithms for initiating statin therapy according to the National Cholesterol Education Program (NCEP) guidelines for high-risk individuals. The authors applied these algorithms to all study subjects. Univariate as well as multivariate associations for target lipid levels and statin implementation were then evaluated utilizing pertinent demographic, clinical, and laboratory data. RESULTS: Of 2,894 subjects in the analysis dataset, 38% were women; 71% were recruited in the United States and 29% in Canada. Of 769 high-risk subjects, 262 (34%) had a low-density lipoprotein (LDL) level > or =130 mg/dL and 124 of these (47%) were not on statin. Among those high-risk persons on statin treatment, only 42% had an LDL < or =100 mg/dL. Subjects in the overall cohort were more likely to be on a statin if they were treated in the United States or had a history of hypertension or coronary artery disease. CONCLUSIONS: Approximately one out of three guideline-eligible high vascular risk ischemic stroke patients in this study had low-density lipoprotein cholesterol concentrations above qualifying levels for pharmacologic therapy, but half of these patients were not taking a statin, and of those receiving statin treatment, less than half were within recommended lipid goals.

Adult↗
PubMed2006

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↗
PubMed2006

Magnesium sulfate neither potentiates nor inhibits tissue plasminogen activator-induced thrombolysis.

BACKGROUND: Increasing circulating magnesium concentrations to 2-fold over normal baseline may afford a neuroprotective effect in patients with acute cerebral ischemia. OBJECTIVES: As patients receiving magnesium sulfate (MgSO(4)) in human clinical trials may also be candidates for subsequent thrombolytic therapy with tissue plasminogen activator (t-PA), preclinical assessment of possible inhibition or potentiation of fibrinolytic activity by MgSO(4) has important clinical relevance. METHODS: We utilized an in vitro system, in which D-dimer release served as a reflection of t-PA-induced clot lysis, to measure the effect of magnesium at the target concentration being tested in human stroke clinical trials, and at 2- and 3-fold higher levels. Clots from normal volunteers were exposed to t-PA at concentrations that correspond to therapeutic or endogenous plasma t-PA levels. RESULTS: MgSO(4) had no effect on t-PA-induced clot lysis at up to 3-fold target magnesium concentration (6x normal serum concentration). CONCLUSIONS: MgSO(4) concentrations well above the targeted level in therapeutic stroke trials does not affect t-PA-induced fibrinolytic activity, and therefore is a suitable agent for trials of combined neuroprotective and thrombolytic therapy in patients with acute ischemic stroke.

Dose-Response Relationship, Drug↗
PubMed2005

Premorbid antiplatelet use and ischemic stroke outcomes.

OBJECTIVE: To evaluate the independent effect of premorbid antiplatelet use on incident ischemic stroke severity and outcome at discharge. METHODS: The authors studied consecutive patients presenting within 24 hours of ischemic stroke over a 1-year period. National Institutes of Health Stroke Scale (NIHSS) score at presentation was used as index of stroke severity and a modified Rankin scale of 0 to 1 at discharge as index of good functional outcome. Patients were categorized according to their premorbid antiplatelet use as antiplatelet-inclusive (AI) and no antiplatelet (NA). Demographic data, risk factors, pertinent laboratory tests, other medications, and stroke mechanisms were controlled for across the two groups using multivariate logistic regression. RESULTS: A total of 260 individuals met study criteria: 92 patients were on antiplatelet agents prior to admission, 168 were on no antiplatelets. Pretreatment with antiplatelet was associated with lower presenting median NIHSS (4.5 vs 7, p = 0.005). Antiplatelet use was associated with less severe stroke at presentation in those having no history of stroke or TIA (4.8 vs 8.0, p = 0.03) but not in those with a prior history of stroke or TIA (4.9 vs 4.9, p = 0.987). The likelihood of a good outcome was increased in those on antiplatelets after adjusting for other variables (OR 2.105, p = 0.0073). CONCLUSIONS: Prestroke use of antiplatelet may be associated with reduced severity of incident ischemic strokes in those with no prior history of stroke or TIA, and with an increased likelihood of a good discharge outcome regardless of prior cerebrovascular event history.

Aged↗
PubMed2005

Hemispheric asymmetry of gaze deviation and relationship to neglect in acute stroke.

Using data from the Trial of Org 10172 in Acute Stroke Treatment (TOAST), the authors studied the anatomy of gaze deviation (GD) after stroke and its co-occurrence with neglect. GD was more frequent and persistent after right hemisphere damage. GD was most common with lesions involving the frontal lobes, although rates with lesions restricted to other hemispheric regions were not significantly different. There was no difference in its rate of co-occurrence with neglect between right- and nonright-handed patients.

Acute Disease↗
PubMed2005

Angiotensin 2 type 2 receptor activity and ischemic stroke severity.

BACKGROUND: Drugs that increase angiotensin 2 formation, including thiazides, calcium channel blockers, and angiotensin 2 type 1 (AT1) receptor blockers, may be more effective in stroke prevention than angiotensin 2 suppressive drugs such as angiotensin-converting enzyme inhibitors and beta-blockers. OBJECTIVE: To assess whether angiotensin 2 formation increasing drugs reduce incident stroke severity compared with angiotensin 2 formation suppressive drugs. METHODS: Consecutive patients presenting within 24 hours of first-ever ischemic stroke over an 18-month period were studied. Subjects were only included if they were on only angiotensin 2 formation increasers, only angiotensin 2 formation suppressors, or no antihypertensive agents. NIH Stroke Scale (NIHSS) score at presentation was used as the index of stroke severity. Demographic data, risk factors, admission blood pressures, other medications, and stroke mechanisms were controlled for across the three groups using least absolute deviation linear regression. RESULTS: One hundred seventy-five individuals met study criteria. Mean age was 67.4 years; 45% were women. Forty-nine patients were on angiotensin 2 formation suppressors and 16 on angiotensin 2 formation increasers. Age at admission, atrial fibrillation, previous antithrombotic use, cardioembolic and large-vessel atherosclerotic mechanisms, and mean systolic and diastolic blood pressure were significant univariate predictors of presenting median NIHSS score. On multivariate analysis, the adjusted median NIHSS score was lower in the angiotensin 2 increasers (median = 2.2; p = 0.005) and trended lower for angiotensin 2 suppressors (median = 4.4; p = 0.054) compared with the no-antihypertensive group (median = 6.0). There was no difference in stroke severity between angiotensin 2 increasers compared with angiotensin 2 suppressors (p = 0.123). CONCLUSIONS: Angiotensin 2 formation increasing agents did not reduce ischemic stroke severity more than angiotensin 2 formation suppressing agents. However, the prestroke use of antihypertensives was associated with reduced severity of incident ischemic strokes.

Adrenergic beta-Antagonists↗
PubMed2004

PROTECT: a coordinated stroke treatment program to prevent recurrent thromboembolic events.

OBJECTIVE: To assess the impact of the Preventing Recurrence of Thromboembolic Events through Coordinated Treatment (PROTECT) Program on achievement of its eight secondary prevention goals at the time of discharge. METHODS: Achievement rates for the eight program goals at time of discharge were compared in all patients discharged from a university hospital-based stroke service with a diagnosis of ischemic stroke or TIA during a 1-year period after implementation of the PROTECT Program vs rates obtained from a comparable group of patients admitted to the same service during the preceding year. RESULTS: Demographic and medical features were comparable in the baseline and intervention cohorts for all patients with cerebral ischemia presumed due to large-vessel atherosclerosis or small-vessel disease (baseline year n = 117, intervention n = 130). Implementation rates in patients without specific contraindications increased for all four medication goals: 97 to 100% for antithrombotic agents, 68 to 97% for statins, 42 to 90% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 14 to 70% for diuretics. Although data were not collected on baseline lifestyle instruction rates, instruction in the program's four lifestyle interventions was achieved by discharge in 100% of the intervention cohort. CONCLUSION: Implementation of this single-center, systems-based, in-hospital program to initiate secondary stroke prevention therapies was associated with a substantial increase in treatment utilization at the time of hospital discharge.

Adult↗
PubMed2004

Frequency, risk factors, anatomy, and course of unilateral neglect in an acute stroke cohort.

OBJECTIVE: To delineate the frequency, course, risk factors, and neuroanatomy of hemispatial neglect in a large stroke cohort. METHODS: One thousand two hundred eighty-one patients with acute stroke were enrolled in a multicenter trial of an anticoagulant. Presence and severity of neglect were assessed with the NIH Stroke Scale (NIHSS) neglect item, assessing tactile extinction and visuospatial neglect at entry, daily for 1 week, and at 3 months. Head CT scans were obtained on day 7, and infarct location and size were characterized. RESULTS: Neglect was common at presentation, occurring in 43% of right brain-lesioned (RBL) patients and 20% of left brain-lesioned (LBL) patients (p < 0.001). At 3 months, neglect was present in 17% of RBL patients and in 5% of LBL patients (p < 0.001). In RBL patients, neglect was most frequently associated with lesions involving the (in descending order) temporal, parietal, frontal, occipital lobes, basal ganglia, and thalamus. Neglect was more common and persistent with cortical than with subcortical lesions. Increasing age was associated with increased risk of neglect in RBL patients, whereas gender and handedness did not significantly affect neglect frequency. CONCLUSIONS: This series confirms that hemispatial neglect may occur with damage to several supratentorial structures but is most common and persistent with lesions of the right temporoparietal cortex. Increasing age is associated with neglect, particularly after right brain lesions. Gender and handedness do not exert a marked effect on the likelihood of the occurrence of neglect.

Acute Disease↗
PubMed2003

Establishment of primary stroke centers: a survey of physician attitudes and hospital resources.

OBJECTIVES: To survey US physicians involved in acute stroke care to determine the proportion of hospitals that currently meet the recommended Brain Attack Coalition (BAC) criteria for Primary Stroke Centers (PSC) and obtain opinions regarding the value of stroke centers. METHODS: A survey regarding the BAC guidelines for the establishment of stroke centers was mailed to 3,245 US neurologists, neurosurgeons, and emergency physicians. RESULTS: A total of 1,032 responses were received. Seventy-nine percent (range by specialty 58 to 98%) of respondents believed there was a need for stroke centers. If formal stroke center designation were established, 81% (range 72 to 90%) would like their hospital to become a PSC. Although 77% of respondents believed that their hospital currently met recommended criteria for a PSC, only 7% actually meet all recommended elements. However, 44% of hospitals already provide most acute stroke services. The BAC criteria most frequently lacking were continuing medical education for professional stroke center staff, stroke training for emergency department staff, formal establishment of a stroke unit, and designation of a stroke center director. CONCLUSIONS: The majority of emergency medicine and neuroscience physician respondents involved in acute stroke care support the designation of primary stroke centers. Although respondents globally overestimated the extent to which their facilities currently meet BAC recommended criteria for PSC, detailed responses suggested that over 40% of hospitals possess substantial existing acute stroke care resources and are poised to function as PSC with modest additional administrative and financial commitment.

Adult↗
PubMed2001

Diffusion-perfusion MRI characterization of post-recanalization hyperperfusion in humans.

BACKGROUND: Animal and human studies have demonstrated that postischemic hyperperfusion may occur both early and late timepoints following acute cerebral ischemia. OBJECTIVE: To use diffusion-perfusion MRI to characterize hyperperfusion in humans following intra-arterial thrombolysis. METHODS: MRI were performed before treatment, several hours following vessel recanalization, and at day 7 in patients successfully recanalized with intra-arterial thrombolytics. RESULTS: Hyperperfusion was visualized in 5 of 12 patients within several hours after recanalization (mean volume, 18 mL; range, 7 to 40 mL), and in 6 of 11 patients at day 7 (mean volume, 28 mL; range, 4 to 45 mL). Within the core region of hyperperfusion, mean cerebral blood flow was 2.1 times greater than in the contralateral homologous region at the early time point, and 3.1 times greater at day 7. Seventy-nine percent of voxels with hyperperfusion at day 7 demonstrated infarction at day 7, whereas only 36% of voxels (within the initial hypoperfusion region) not showing hyperperfusion at day 7 demonstrated infarction at day 7. Mean pretreatment apparent diffusion coefficient (ADC) and perfusion values were more impaired in voxels that subsequently developed hyperperfusion compared with other at-risk voxels (all p values < 0.0001). There were no significant differences in the degree of clinical improvement in patients with regions of hyperperfusion versus those without, although sample size limited power to detect group differences. CONCLUSIONS: Postischemic hyperperfusion, visualized with perfusion MRI in humans following recanalization by intra-arterial thrombolytic therapy, occurred in about 40% of patients within hours and in about 50% of patients at day 7. Hyperperfusion developed mainly in regions that went on to infarction. Compared with other abnormal regions, tissues that developed postischemic hyperperfusion had greater bioenergetic compromise in pretreatment apparent diffusion coefficient values and greater impairment in pretreatment blood flow measures.

Adult↗