Chronic neurovascular uncoupling syndrome.

O ur current understanding of the blood supply to the human brain has advanced considerably but is far from complete. Although great progress has been made in determining the relationship between neuroglial activity and blood flow, especially in animal models, this relationship is not as well defined in humans, in particular for diseases that cause chronic compromise of the cervicocerebral vasculature. There is no mystery concerning the ischemic consequences to the brain when there is an acute loss in blood flow. However, there is a major gap in our knowledge concerning the effect of chronic vascular insuf-ficiency on the integrity of the brain and the associated functional consequences. C. Miller Fisher in 1954 was the first to report an association between unilateral/bilateral carotid occlu-sion and senile dementia. 1 Interestingly, the report references a study from Freyhan et al, 2 in which a decrease in cerebral blood flow observed in patients with arteriosclerotic dementia and senile psychosis was thought to be attributable to increased vascular resistance with vascular changes preventing a "com-pensatory" increase in blood form. More recently, a study that compared the effect of increased oxygen extraction fraction and cognition in patients who were enrolled in the National Institute of Neurological Disorders and Stroke sponsored Carotid Occlusion Surgery Study 3 found a significant association between increased oxygen extraction fraction and diminished mental function once covariates, including age, education, side of occlusion, depression, and previous stroke, were controlled. 4 Therefore, it seems that a relationship between hemodynamic insufficiency and diminished brain function in the absence of clinically expressed ischemic events can occur. This raises important questions concerning the cause of the brain dysfunc-tion in these patients. Is it secondary to inadequate delivery of metabolic substrates with functional impairment alone, or does inadequate blood flow actually result in a physical degradation in the structure of the neuropil or glia, such as a reduction in the complexity of neural networks or more drastically glioneuronal loss? If physical injury occurs, then it becomes imperative that the presence of hemodynamic insufficiency is detected before significant loss in neurological function develops. The mechanism and effects of hemodynamic insufficiency can only be appreciated through assessment of neurovascu-lar coupling. During the last 20 years, the field of functional brain mapping has shown that MRI can view neural activity by measuring signal changes caused by activity-induced modulation in local blood flow. Blood flow secondary to neuronal activation can increase …