The suits against the makers of Vioxx, Celebrex, PPA and Ortho Evra all include claims that the medication could cause strokes. Strokes a re complicated injuries and can be very severe. The difficulty in proving such claims arises from the variety of other factoors that can lead to a stroke. Some understanding of the different knds of strokes is helpful. Strokes that involve a bleeding in the brain are called hemorhaggic and strokes where the blood flow is cut of are called ischemic.
On the macroscopic level, ischemic strokes most often are caused by extracranial embolism or intracranial thrombosis, but they may also be caused by decreases in cerebral blood flow. On the cellular level, any process that disrupts blood flow to a portion of the brain unleashes an ischemic cascade, leading to the death of neurons and cerebral infarction. Understanding this chain of events is important for understanding current therapeutic approaches.
Emboli may arise from the heart, the extracranial arteries or, rarely, the right-sided circulation (paradoxical emboli). The sources of cardiogenic emboli include valvular thrombi (e.g.: in mitral stenosis, endocarditis, prosthetic valves), mural thrombi (e.g.: in myocardial infarction [MI], atrial fibrillation, dilated cardiomyopathy, severe congestive heart failure [CHF]), and atrial myxomas. MI is associated with a 2-3% incidence of embolic stroke, of which 85% occur in the first month after MI.
Within seconds to minutes of the loss of perfusion to a portion of the brain, an ischemic cascade is unleashed that, if left unchecked, causes a central area of irreversible infarction surrounded by an area of potentially reversible ischemic tissue. The ischemic cascade offers many points at which such interventions could be attempted. Multiple strategies for blocking this cascade are currently under investigation. The timing of restoring cerebral blood flow appears to be a critical factor. Time also may prove to be a key factor in neuronal protection.
Thrombotic strokes can be divided into large vessel, including the carotid artery system, or small vessel comprising the intracerebral arteries, including the branches of the Circle of Willis and the posterior circulation. The most common sites of thrombotic occlusion are cerebral artery branch points, especially in the distribution of the internal carotid artery. Arterial stenosis (i.e.: turbulent blood flow), atherosclerosis (i.e.: ulcerated plaques), and platelet adherence cause the formation of blood clots that either embolize or occlude the artery. Less common causes of thrombosis include polycythemia, sickle cell anemia, protein C deficiency, fibromuscular dysplasia of the cerebral arteries, and prolonged vasoconstriction from migraine headache disorders. Any process that causes dissection of the cerebral arteries also can cause thrombotic stroke (e.g.: trauma, thoracic aortic dissection, arteritis). Occasionally, hypoperfusion distal to a stenotic or occluded artery or hypoperfusion of a vulnerable watershed region between 2 cerebral arterial territories can cause ischemic stroke.