Chronic Neurovascular Uncoupling Syndrome

Abstract

Our 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 insufficiency 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 occlusion 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 compensatory 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 Study3 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 dysfunction 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 …