Cerebrovascular reactivity and implications for understanding the pathophysiology of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a severe neurological disease commonly diagnosed in young adults. Recent controversial publications attribute the inflammation, sclerosis, and degenerative lesions to venous insufficiency. We recently found characteristic reductions in cerebrovascular reactivity (CVR) in the presence of venous congestion caused by other neurological disorders. We therefore hypothesize that CVR may also be reduced in patients with MS. A computer‐controlled gas blender (RespirAct™, TRI, Canada) was used to precisely target normoxic PETCO2 changes between 40 to 50 mmHg in 7 MS subjects with varying type and severity. BOLD MRI was performed simultaneously as an indirect measure of changes in cerebral blood flow. CVR, defined on a voxel‐wise basis as %ΔBOLD signal/ΔPETCO2, was color coded and superimposed on anatomical scans to form CVR maps. Each CVR map was compared voxel‐by‐voxel with a CVR atlas generated from 37 healthy subjects. Contrary to our hypothesis, CVR in MS subjects was greater than the healthy cohort. The degree of hyper‐reactivity correlated with the severity of MS. Regions of increased CVR may reflect the confounding dependency of BOLD MRI on cerebral blood volume which could be increased due to insufficient venous drainage. However, it may actually reflect an increased flow response to hypercapnia which overwhelms the altered venous draining system leading to venous congestion.