Cerebral blood flow dependency on systemic arterial circulation in progressive multiple sclerosis

Abstract

Objectives: To determine the relationship between systemic arterial blood flow (SABF) and cerebral perfusion measures in multiple sclerosis (MS) patients.

Methods: Cerebral perfusion and SABF were assessed in 118 patients (75 clinically isolated syndrome (CIS)/relapsing-remitting MS and 43 progressive MS) through MRI examination with dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) and Doppler ultrasound, respectively. Measures of mean transit time (MTT) and time-to-peak (TTP), measured in seconds, of the normal-appearing whole brain (NAWB) and gray matter (GM) were calculated. Blood flow through the bilateral common carotid and vertebral arteries (in mL/min) represents the SABF. Whole brain volume (WBV) and body mass index (BMI) were used as additional covariates.

Results: Higher systolic blood pressure was associated with lower SABF (-0.256, p = 0.006). In the total MS sample, higher SABF was associated with shorter MTT and TTP of the NAWB (r = -0.256, p = 0.007 and r = -0.307, p = 0.001) and GM (r = -0.239, p = 0.012 and r = -0.3, p = 0.001). The SABF and TTP associations were driven by the PMS patients (r = -0.451, p = 0.004 and r = -0.451, p = 0.011). Only in PMS, SABF remained a significant predictor of NAWB (standardized β = -0.394, p = 0.022) and GM TTP (standardized β = -0.351, p = 0.037). MTT and TTP were significantly lower in patients within lower SABF quartiles when compared to the higher quartiles (age-, sex-, BMI-, and WBV-adjusted ANCOVA p < 0.025).

Conclusions: The direct relationship between systemic and cerebral blood flow seen in PMS patients may suggest failure in cerebrovascular reactivity mechanisms and insufficient perfusion control. Cerebral blood flow in PMS may be increasingly dependent on the SABF.

Key points: • In progressive multiple sclerosis (MS) patients, the systemic arterial blood flow (SABF) is associated with perfusion-based measure of time-to-peak (TTP) of the normal-appearing whole brain (r = -0.451, p = 0.004) and gray matter (r = -0.451, p = 0.004). • Cerebral blood flow in progressive MS is directly dependent on systemic arterial blood flow and may be influenced by blood pressure changes. • Neurovascular unit impairment may play an important role in MS pathophysiology and contribute towards greater clinical disability.

Keywords: Blood circulation; Multiple sclerosis; Perfusion.