MRI characteristics of cerebral air embolism from a venous source.
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Biomedical subjects
Publications and source records attributed to G W Albers.
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BACKGROUND: Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA). METHODS: The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging. RESULTS: Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB. CONCLUSIONS: The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.
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OBJECTIVE: To determine whether spinal manipulative therapy (SMT) is an independent risk factor for cervical artery dissection. METHODS: Using a nested case-control design, the authors reviewed all patients under age 60 with cervical arterial dissection (n = 151) and ischemic stroke or TIA from between 1995 and 2000 at two academic stroke centers. Controls (n = 306) were selected to match cases by sex and within age strata. Cases and controls were solicited by mail, and respondents were interviewed using a structured questionnaire. The medical records of interviewed patients were reviewed by two blinded neurologists to confirm that the patient had stroke or TIA and to determine whether there was evidence of arterial dissection. RESULTS: After interview and blinded chart review, 51 patients with dissection (mean age 41 +/- 10 years; 59% female) and 100 control patients (44 +/- 9 years; 58% female) were studied. In univariate analysis, patients with dissection were more likely to have had SMT within 30 days (14% vs 3%, p = 0.032), to have had neck or head pain preceding stroke or TIA (76% vs 40%, p < 0.001), and to be current consumers of alcohol (76% vs 57%, p = 0.021). In multivariate analysis, vertebral artery dissections were independently associated with SMT within 30 days (OR 6.62, 95% CI 1.4 to 30) and pain before stroke/TIA (OR 3.76, 95% CI 1.3 to 11). CONCLUSIONS: This case-controlled study of the influence of SMT and cervical arterial dissection shows that SMT is independently associated with vertebral arterial dissection, even after controlling for neck pain. Patients undergoing SMT should be consented for risk of stroke or vascular injury from the procedure. A significant increase in neck pain following spinal manipulative therapy warrants immediate medical evaluation.
CONTEXT: Tissue plasminogen activator is the only thrombolytic agent approved in the United States for treatment of acute ischemic stroke, and has limitations. Aptiganel hydrochloride is a novel and selective ligand for the ion-channel site of the N-methyl-D-aspartate receptor-channel complex and a promising neuroprotective agent in animal models of focal brain ischemia. OBJECTIVE: To determine whether aptiganel improves the clinical outcome for acute ischemic stroke patients. DESIGN: Nested phase 2/phase 3 randomized controlled trial conducted between July 1996 and September 1997. SETTING: One hundred fifty-six medical centers in the United States, Canada, Australia, South Africa, England, and Scotland. PARTICIPANTS: A total of 628 patients with hemispheric ischemic stroke (50.3% male; mean age, 71.5 years). INTERVENTIONS: Patients were randomly assigned within 6 hours of stroke to receive 1 of 3 treatment regimens: high-dose aptiganel (5-mg bolus followed by 0.75 mg/h for 12 hours; n = 214); low-dose aptiganel (3-mg bolus followed by 0.5 mg/h for 12 hours; n = 200); or placebo (n = 214). MAIN OUTCOME MEASURES: The primary efficacy end point was the Modified Rankin Scale score at 90 days after stroke onset. Secondary end points included mortality and change in National Institutes of Health (NIH) Stroke Scale score at 7 days after stroke. RESULTS: The trial was suspended by the sponsor and the independent data and safety monitoring board because of both a lack of efficacy and a potential imbalance in mortality. There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, -0.8 points vs for high-dose aptiganel, 0.9 points; P =.04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P =.06). Mortality in the low-dose aptiganel group was 22.5% (P =.39 vs placebo). CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.
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BACKGROUND: Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke. METHODS: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years. RESULTS: The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery). CONCLUSIONS: Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.
OBJECTIVE: To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion. METHODS: Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion. RESULTS: Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size. CONCLUSION: Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.
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BACKGROUND: Knowledge of the natural evolution of ischemic brain lesions may be a crucial aspect in the assessment of future stroke therapies. OBJECTIVE: To establish daily changes of ischemic cerebral lesion volume using diffusion-weighted magnetic resonance imaging. DESIGN: Prospective cohort study. SETTING: Referral center. PATIENTS AND METHODS: Serial magnetic resonance imaging scans were performed in consecutive untreated stroke patients. The baseline scan was obtained within 48 hours after symptom onset; subsequent scans, 12 to 48 hours, 3 to 4 days, 5 to 7 days, and 30 days after baseline. Lesion volumes were measured on each scan by 2 independent observers. MAIN OUTCOME MEASURE: Daily change in lesion volume. RESULTS: A total of 112 magnetic resonance imaging scans were obtained in 24 patients. An early increase in lesion volume was seen in all patients. Maximum lesion volume was reached at a mean of 74 hours. Lesion volumes increased by a mean (+/- SEM) of 21% +/- 12% during day 2 and 10% +/- 12% during day 3. No significant change occurred during day 4. During days 5, 6, and 7, statistically significant mean (+/- SEM) decreases of 6% +/- 8%, 3% +/- 4%, and 4% +/- 5%, respectively, were observed. CONCLUSIONS: Ischemic lesions follow a relatively consistent pattern of growth during the first 3 days and subsequent decrease in size. These data in conjunction with data regarding the evolution of lesion volume during the first 24 hours after symptom onset may be useful in the design of pilot studies of therapies for acute stroke.
Atherosclerosis involving the cervical vessels, intracranial vessels, or the aorta is the most common cause of ischemic stroke. Occlusive lesions of small penetrating brain arteries cause small "lacunar" strokes, which account for about 20% of ischemic strokes. Emboli from a variety of cardiac sources, particularly atrial fibrillation, account for about 25%. Efforts to prevent and treat ischemic stroke are complicated by the variety of etiologies underlying it and the selection of antithrombotic or thrombolytic therapy appropriate to the particular etiology.
Intravenous tissue plasminogen activator (tPA) is an effective therapy for treatment of acute ischemic stroke when administered within 3 hours of symptom onset. Three large randomized clinical trials that have attempted to extend the time window for tPA treatment beyond 3 hours have failed to demonstrate convincing evidence of efficacy. A recently published prospective, monitored, multicenter study of 389 patients, who were treated with tPA for ischemic stroke at 57 medical centers (24 academic, 33 community) across the United States, demonstrated favorable outcomes and low rates of symptomatic intracerebral hemorrhage. Recent advances in neuroimaging, including diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI), have the potential to differentiate salvageable ischemic brain tissue from irreversibly injured tissue. Preliminary data suggest that acute stroke patients who present with a PWI lesion that is considerably larger than the initial DWI lesion may be good candidates for intravenous thrombolysis, even beyond 3 hours after symptom onset. Additional research is required to clarify the optimal use of these diagnostic techniques and their cost-effectiveness.
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BACKGROUND AND PURPOSE: Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age. METHODS: Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke. The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)). RESULTS: The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter. The lesion ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old. All signal intensities remained high throughout follow-up. SI(DWI) showed no significant change during the first week but decreased thereafter. SI(T2) initially increased, decreased slightly during week 2, and again increased after 14 days. SI(FLAIR) showed the same initial increase as the SI(T2) but remained relatively stable thereafter. CONCLUSION: Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age. Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values.
Hyperperfusion syndrome is a well-documented complication of carotid endarterectomy, as well as internal carotid artery angioplasty and stent placement. We report a similar complication after distal intracranial (middle cerebral artery [MCA] M2 segment) angioplasty. To our knowledge, this is the first report of hyperperfusion syndrome after intracranial angioplasty of a distal MCA branch.
OBJECTIVE: To determine the prognosis of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy. BACKGROUND: The outcome of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy is unknown. These patients may represent the target group for investigation of more aggressive therapies such as intracranial angioplasty. METHODS: The authors performed a chart review and telephone interview of patients with symptomatic intracranial atherosclerosis identified in the Stanford Stroke Center clinical database. A Cox regression model was created to identify factors predictive of failure of antithrombotic therapy. The authors generated Kaplan-Meier survival curves to determine the timing of recurrent TIA, stroke, or death after failure of antithrombotic therapy. RESULTS: Fifty-two patients had symptomatic intracranial atherosclerosis and fulfilled entry criteria. Twenty-nine of the 52 patients (55.8%) had cerebral ischemic events while receiving an antithrombotic agent (antiplatelet agents [55%], warfarin [31%], or heparin [14%]). In a Cox regression model, older age was an independent predictor of failure of antithrombotic therapy, and warfarin use was associated with a decrease in risk. Recurrent TIA (n = 7), nonfatal/fatal stroke (n = 6/1), or death (n = 1) occurred in 15 of 29 (51.7%) of the patients who failed antithrombotic therapy. The median time to recurrent TIA, stroke, or death was 36 days (95% CI 13 to 59). CONCLUSIONS: Patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy have extremely high rates of recurrent TIA/stroke or death. Recurrent ischemic events typically occur within a few months after failure of standard medical therapy. The high recurrence risk observed warrants testing of alternative treatment strategies such as intracranial angioplasty.
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