Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging.
ABSTRACT Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra-arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion-weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8-38 cm3) and decreased to 10 cm3 (95% CI, 3-17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2-16 cm3) at baseline to 1 cm3 (95% CI, 0.4-2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality.
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ABSTRACT: Study objectives: Thrombolytic therapy has been advocated as an effective treatment for acute ischemic stroke. In an attempt to promote maximum benefit while reducing the risk of hemorrhagic complications, numerous exclusions to the use of thrombolytic therapy for acute ischemic stroke have been promulgated. This study was conducted to identify the number of acute ischemic stroke patients eligible for thrombolytic therapy and to determine the reasons those deemed ineligible were excluded. This observational study was conducted from September 15, 1996, to May 1, 1997, at an emergency department with an annual census of 70,000. Patients with a chief complaint suggestive of acute ischemic stroke were categorized as "eligible" if thrombolytic therapy was not contraindicated and could be initiated within 3 hours of symptom onset. Patients were deemed "ineligible" if the time to thrombolytic therapy would have exceeded 3 hours, or if other specific contraindications to thrombolytic therapy were present. For all categories, 95% confidence intervals (95% CI) were determined. Of the 214 patients with acute ischemic stroke who were screened, 6 (2.8%+/-2.2%) were eligible. Ninety-five patients (44%+/-7%) were excluded solely on the basis of the time interval from onset of symptoms to eligibility for thrombolytic therapy exceeding 3 hours. Other common reasons for exclusion included resolution of symptoms in 31 patients (14%+/-4%), intracranial hemorrhage as determined by head computed tomography in 22 (10%+/-4%), and minor symptoms in 20 (9%+/-4%). The majority of acute ischemic stroke patients do not meet accepted criteria for thrombolytic therapy. Most are ineligible because of delays in obtaining treatment. Strategies should be devised to reduce the time to treatment if thrombolytic therapy is to achieve widespread use in the treatment of acute ischemic stroke.Annals of Emergency Medicine 02/1999; 33(1):9-14. · 4.29 Impact Factor
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ABSTRACT: Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed. To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion. PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998. Fifty-four centers in the United States and Canada. A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan. Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59). The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality. For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06). Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.JAMA The Journal of the American Medical Association 01/2000; 282(21):2003-11. · 29.98 Impact Factor
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ABSTRACT: Our purpose was to use whole brain echo planar magnetic resonance imaging (MRI) to identify and characterize diffusion abnormalities in acute cerebral ischemia. We studied 40 patients as early as 3 hours after onset of signs and symptoms of cerebral ischemia. Diffusion-weighted imaging (DWI) of the entire brain could be completed in 3 seconds or, using seven different diffusion sensitivities (maximum b = 1,271 sec/mm2), in 48 seconds. Measurements and synthetic maps were made of apparent diffusion coefficients (ADC), a physiological parameter that characterizes the self-diffusion of water in tissue. Early ischemic lesions were identified with DWI as hyperintense regions of decreased ADC in all patients who subsequently developed infarction, before changes were evident on conventional MRI in cases studied earlier than 6 hours after onset of ischemic symptoms. Lesions as small as 4 mm in diameter were identified. The extent of lesions within white matter was best defined by controlling for the anisotropic effect of axonal orientation. The mean ADC (+/- SD) for control regions in the 36 patients was 9.15 (+/- 2.91) x 10(-4) mm2/sec. Mean ADC of ischemic regions was 56% of control values at 6 hours or less and stayed significantly reduced for 3 to 4 days after onset of ischemia. The relative ADC increased progressively over time to be pseudonormalized at 5 to 10 days and elevated in the chronic state, making the distinction of acute lesions adjacent to chronic infarcts readily apparent. DWI with echo planar imaging measures a unique physiological parameter that is sensitive to ischemic changes before conventional MRI. Its potential role in the quantitative study of human stroke pathophysiology and therapeutics is the subject of further investigation.Annals of Neurology 03/1995; 37(2):231-41. · 11.19 Impact Factor