Mixed Cerebrovascular Disease and the Future of Stroke Prevention
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REVIEW ARTICLE
Mixed Cerebrovascular Disease and the Future of Stroke Prevention Mark Fisher & Vitaly Vasilevko & David H. Cribbs
Received: 1 March 2012 / Revised: 17 April 2012 / Accepted: 19 April 2012 # Springer Science+Business Media, LLC 2012
Abstract Stroke prevention efforts typically focus on either ischemic or hemorrhagic stroke. This approach is overly simplistic due to the frequent coexistence of ischemic and hemorrhagic cerebrovascular disease. This coexistence, termed “mixed cerebrovascular disease”, offers a conceptual framework that appears useful for stroke prevention strategies. Mixed cerebrovascular disease incorporates clinical and subclinical syndromes, including ischemic stroke, subclinical infarct, white matter disease of aging (leukoaraiosis), intracerebral hemorrhage, and cerebral microbleeds. Reliance on mixed cerebrovascular disease as a diagnostic entity may assist in stratifying risk of hemorrhagic stroke associated with platelet therapy and anticoagulants. Animal models of hemorrhagic cerebrovascular disease, particularly models of M. Fisher : D. H. Cribbs Department of Neurology, University of California at Irvine, Irvine, CA, USA e-mail: [email protected]
cerebral amyloid angiopathy and hypertension, offer novel means for identifying underlying mechanisms and developing focused therapy. Phosphodiesterase (PDE) inhibitors represent a class of agents that, by targeting both platelets and vessel wall, provide the kind of dual actions necessary for stroke prevention, given the spectrum of disorders that characterizes mixed cerebrovascular disease. Keywords Stroke . Cerebrovascular . Hemorrhage . Hemorrhagic transformation . Microbleeds . Leukoaraiosis . Amyloid . Hypertension . Phosphodiesterase inhibitor “The way out is through the door. Why is it that no one will use this method?” Confucius
Introduction M. Fisher Department of Anatomy & Neurobiology, University of California at Irvine, Irvine, CA, USA M. Fisher Department of Pathology & Laboratory Medicine, University of California at Irvine, Irvine, CA, USA V. Vasilevko : D. H. Cribbs UCI MIND, University of California at Irvine, Irvine, CA, USA e-mail: [email protected] M. Fisher (*) UC Irvine Medical Center, 101 The City Drive South, Shanbrom Hall Room 121, Orange, CA 92868, USA e-mail: [email protected]
Stroke prevention efforts typically focus on either ischemic stroke or hemorrhagic stroke. It is understood that ischemic stroke prevention requires a comprehensive approach for the variety of stroke risk factors that a patient may encounter. Similarly, patients who have sustained hemorrhagic stroke will have targeted efforts directed against the vascular risk factor(s) thought to be most significant in the etiology of the hemorrhage, with hypertension being the typical culprit. A principal focus for attention in stroke prevention involves medications that target various elements of coagulation pathways. For prevention of ischemic stroke, platelet anti-aggregant medications are a prime issue, as well as use of anticoagulants. Some de
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