Physiologic studies of cerebral ischemia

Abstract

Using the technology of his day, limited to direct observation and histological techniques, Fisher conclusively established the importance of the atherosclerotic carotid plaque in stroke. Recognizing the limits of his observations, he raised a number of questions as regards the degree of carotid disease necessary to adversely affect the brain and the effects of silent carotid occlusion. He also suggested the possible beneficial effects of revascularization. These questions have been addressed and in large part answered by PET. Thresholds of electrical activity and of cellular viability have been established both for cerebral blood flow and for oxygen metabolism. The effects of severe carotid stenosis have been found to be limited to the anterior border zone, where a decreased CBF and CBF to CBV ratio is seen in association with a trend towards rising OEF and declining CMRO2. The acute effects of a stroke and the passage of ischemia to infarction have been documented as they affect CBF, OEF, and CMRO2 in densely ischemic areas and in the penumbra region. An early pattern of elevated OEF in the face of diminished CBF is recognized and evolves into a later pattern of low OEF and CMRO2 characteristic of cell death. Silent carotid occlusion has been shown to produce widespread hypoperfusion and metabolic depression, the former improved by bypass, the latter not. Finally, the CBF to CBV ratio does not appear to be adequate in identifying patients who would benefit from EC-IC bypass, while an elevated preoperative OEF, an unusual event, does not clearly guarantee improved postoperative oxygen metabolism or the prevention of an ipsilateral stroke. Because the anterior border zone is selectively vulnerable to cerebral ischemia in patients with carotid stenosis, and since irreversible oxygen hypometabolism ensues once occlusion occurs, PET may be useful in identifying patients who may be at risk of further ischemic events should stenosis progress to occlusion. PET may also prove to be helpful in understanding the pathophysiology of ischemic complications associated with cerebral aneurysms and AVMs and may be a useful tool for deciding the timing of therapeutic intervention in these conditions.