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Stroke Alert: A Review of Current Clinical Stroke Literature
By Matthew E. Fink, MD, Interim Chair and Neurologist-in-Chief, Director, Division of Stroke & Critical Care Neurology, Weill Cornell Medical College and New York Presbyterian Hospital
Risk of Thromboembolism in Patients Treated with Recombinant Factor VIIa for Warfarin- Associated Hemorrhages of the Central Nervous System
Source: Robinson MT, et al. Stroke 2010;41:1459-1463.
Intracerebral hemorrhage (ICH) associated with oral anticoagulation is a growing problem as the prevalence of atrial fibrillation increases in the aging population. The outcomes are poor due to increasing hematoma size in the first several hours, and anticoagulation should be reversed quickly. Anticoagulation is also associated with other forms of intracranial hemorrhage (subdural, epidural, and subarachnoid) that can result in catastrophic outcomes and require emergency neurosurgical intervention. In these situations, immediate reversal of anticoagulation is critical. The traditional therapy to reverse warfarin anticoagulation is the combination of fresh-frozen plasma (FFP) and vitamin K, but this protocol is slow and benefit is delayed. Recombinant Factor VIIa (rFVIIa) is a rapidly acting hemostatic agent that lowers the INR and reduces hematoma growth. The major complication of this therapy is thrombosis, and mortality has been shown to be increased from acute coronary thrombosis, as well as deep vein thromboses and pulmonary embolism.
The investigators reviewed the records of all patients at the Mayo Clinic with anticoagulation-associated hemorrhages of the central nervous system who received rFVIIa. The primary end point was the frequency of new thromboembolic events, which included myocardial infarction, deep vein thrombosis, ischemic stroke, and pulmonary embolism. One hundred and one (101) patients were identified; 54% had ICH and 30% had subdural hematomas. Thirteen patients (12.8%) had new thromboembolic events (10 deep vein thromboses and three ischemic strokes) within 90 days after treatment with rFVIIa. Eight of these events occurred within two weeks of therapy. The risk of thromboembolism in this group of patients is clinically important and should be considered when the use of rFVIIA is considered.
Microbleeds and Active Matrix Metalloproteinase-9 (MMP-9) Are Risk Factors for Deterioration after Lacunar Stroke
Source: Koh SH, et al. Eur J Neurology 2010:doi:10.1111/j.1468-1331.2010.03100.x (published online).
Brain microbleeds that are seen on t2-weighted, gradient echo MR imaging are thought to represent the result of a microangiopathic process in atherosclerosis, chronic hypertension, and amyloid angiopathy. The injured vessels are more prone to blood extravasation, resulting in small, intraparenchymal hematomas that range in size from 2 mm to 5 mm, and are clinically silent. Because brain microbleeds are a marker of significant microangiopathy, their presence might be expected to adversely effect tissue survival and alter outcome after ischemic stroke. In addition, MMP-9 is an enzyme that is normally undetectable in the central nervous system, until activated by various insults, including hemorrhage and infarction. MMP-9 plays a role in the dissolution of basement membrane proteins and blood-brain-barrier breakdown and plays an important role in tissue injury after stroke.
The investigators recruited 206 patients with a first lacunar stroke diagnosed by MRI (maximum lesion diameter of 15 mm), reviewed the MRIs for the presence of brain microbleeds, and measured venous MMP-9 levels. Neurological deterioration was defined as an increase of more than two points in the NIH Stroke Scale, 14 days after stroke onset. Seventy-nine patients (38.3%) had microbleeds and 48 (23.3%) showed neurological deterioration. Active MMP-9 levels were significantly elevated among patients with microbleeds (p < 0.001) and the presence of microbleeds and elevated MMP-9 were independent risk factors for neurological deterioration. Assessing these indicators at time of admission may be useful in identifying patients at risk for deterioration.
Transcranial Doppler Assessment of Embolic Signals and Intracranial Stenosis May Improve Selection of Patients Who May Benefit from Carotid Endarterectomy
Sources: Markus HS, et al. Lancet Neurol 2010;9:663-671; Meseguer E, et al. Ann Neurol 2010;68:9-17; Easton JD, et al. Ann Neurol 2010;68:1-2.
Several recent studies have looked at the utility of using transcranial Doppler (TCD) to identify patients with transient ischemic attacks (TIA) or asymptomatic carotid artery stenosis who would most benefit from carotid endarterectomy (CEA), by measuring the frequency of microembolic signals from the stenotic artery, and assessing for intracranial stenosis.
The Asymptomatic Carotid Emboli Study (ACES) prospectively examined 467 patients with asymptomatic carotid artery stenosis of at least 70% with repeated TCD microembolism studies over a period of two years and noted the development of any ischemic stroke or TIA. Embolic signals were present in 77 of 467 patients at baseline and the hazard ratio for risk of ipsilateral stroke or TIA over two years of follow-up was 5.57 (p < 0.007). The absolute annual risk of stroke or TIA between baseline and 2 years for those with embolic signals was 7.13% compared to 3.04% in those without embolic signals.
In a related study, Meseguer and colleagues performed TCD studies in 1,823 patients within four hours of admission to their TIA clinic. Intracranial narrowing or occlusion (TCD criteria) was found in 8.8% of patients, and was independently associated with age, hypertension, and diabetes. After one-year follow-up on best medical therapy, the incidence of recurrent vascular events (TIA recurrence, stroke, myocardial infarction, vascular death) was 7.0% in those with intracranial narrowing of occlusion and 2.4% in those without (p < 0.007).
Transcranial Doppler is a rapid, safe, and cost-effective diagnostic tool to risk-stratify patients who have carotid artery stenosis and help to select those who are most likely to benefit from surgery.