Ischemic White Matter Disease may Predispose to Intracerebral Hemorrhage
September 1, 2002 3 minutes read
Abstract & Commentary
Source: Smith EE, et al. Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke. Neurology. 2002;59:193-197.
Ischemic white matter disease, also referred to as leukoaraiosis, is found commonly and often incidentally on CT and MRI scans. While leukoaraiosis may have significant overlap with important clinical syndromes such as multi-infarct dementia and symptomatic lacunar-type stroke, it may just as often be completely asymptomatic. These data from Smith and colleagues indicate that leukoaraiosis may be a predictor of an additional and very important clinical phenomenon; it may contribute to the occurrence of intracerebral hemorrhage (ICH) among patients anticoagulated with warfarin.
Smith et al studied 26 cases of ICH and a history of prior symptomatic ischemic stroke and compared them to patients who had a prior stroke but no ICH. All patients were maintained on warfarin anticoagulation. Both the presence and severity of leukoaraiosis on CT scanning correlated with the likelihood of ICH. Leukoaraiosis was seen in 24 of 26 ICH cases (92%) compared with 27 of 56 controls (48%), a highly statistically significant result with an odds ratio (OR) of 13. Severe leukoaraiosis conferred an OR of 25. These relationships were independent of other predictors of ICH that included a history of multiple previous strokes, an INR of > 3.0, and the presence of carotid stenosis.
Leukoaraiosis increased the risk of ICH in both superficial and deep locations. This indicates a possible interaction between leukoaraiosis and a variety of vascular pathologies such as cerebral amyloid angiopathy (producing lobar bleeds) and hypertensive fibrinoid necrosis (producing basal ganglia hemorrhage). ICH did not generally occur at the site of the previous stroke, indicating that prior infarction was not the cause of bleeding. Rather it was more likely chronic diffuse ischemia (of which leukoaraiosis is the radiographic marker) that led to the hemorrhages.
Commentary
These data raise the question of whether leukoaraiosis should be taken into account when deciding to anticoagulate patients at risk for stroke. This applies in particular to elderly patients with atrial fibrillation. As Smith et al point out, leukoaraiosis may simultaneously mark the patient who, on one hand, has a high ischemic stroke risk, but at the same time is at an increased risk for a complicating hemorrhage. Among patients without a prior stroke, and, thus, at lower risk for ischemic than hemorrhagic disease, it is possible that the presence of severe leukoaraiosis should preclude warfarin use. These data further hold implications not only for warfarin therapy, but also for the even more common use of antiplatelet drugs. While patients with leukoaraiosis are generally considered to have small vessel ischemic disease mandating agents such as aspirin, this likely narrow and largely theoretical therapeutic benefit may be counteracted by a significant risk of hemorrhage. Finally, leukoaraiosis as defined by CT may not be directly equated with MRI findings such as diffuse hyperintensities on fluid-attenuated (FLAIR) sequences. Further work using MRI data rather than CT may help to better understand this process. —Alan Z. Segal
Dr. Segal, Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital, is Assistant Editor of Neurology Alert.
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