In Reply We appreciate the comments by De Bonis and Zamboni regarding our article,1 in which we identified cerebrovascular reactivity (CVR) impairment in patients with multiple sclerosis (MS). We agree that such a finding of impairment in cerebral blood flow (CBF) regulation in MS presents new questions regarding its causes and, more importantly, its detrimental effects on healthy neurons that lead to neurodegeneration. As our study clearly indicated, the CVR deficit is likely due to chronically high nitric oxide (NO) concentrations formed secondary to repetitive vascular inflammatory cascades in MS.2 Prolonged exposure to NO, a potent vasodilator, may desensitize endothelial and smooth-muscle function through vascular habituation, thus decreasing vasodilatory capacity. This capacity, measured as CVR, is related to neurovascular coupling, an important brain feature of modulating blood flow in response to neuronal activity. Therefore, CVR deficit will primarily affect the healthy neurons as a result of an activity-induced hypoxia due to disrupted neurovascular coupling. We believe this is the main contributor of CVR impairment; however, we agree that other possible causes of this deficit must be explored because it may be an important underlying mechanism of neurodegeneration in MS.
Ge Y, Marshall O, Lu H. Intracranial Relationship Between Arterioles and Venules Size–Reply. JAMA Neurol. 2015;72(1):124-125. doi:10.1001/jamaneurol.2014.3517