White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis

Abstract

Background: Hypoperfusion has been reported in lesions, normal-appearing white (NAWM) and gray matter (NAGM) of patients with clinically definite multiple sclerosis (MS) by using perfusion MRI. However, it is still unknown how early such changes in perfusion occur. The aim of our study was to assess the presence of hemodynamic changes in the NAWM and subcortical NAGM of patients with clinically isolated syndrome (CIS) in comparison to healthy controls and to patients with early relapsing-remitting (RR) MS.

Methods: Absolute cerebral blood flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the periventricular and frontal NAWM, thalamus and putamen nuclei of 12 patients with CIS, 12 with early RR-MS and 12 healthy controls using dynamic susceptibility contrast enhanced (DSC) T2*-weighted MRI.

Results: Compared to controls, CBF was significantly decreased in the periventricular NAWM of CIS patients and in the periventricular NAWM and putamen of RR-MS patients. Compared to CIS, RR-MS patients showed a significant CBF decrease in the putamen.

Conclusions: CBF was decreased in the NAWM of both CIS and RR-MS patients and in the subcortical NAGM of RR-MS patients suggesting a continuum of tissue perfusion decreases beginning in white matter and spreading to gray matter, as the disease progresses.

Figures

Figure 1

Selected axial gradient-echo echo-planar magnetic resonance images (A, C), and color-coded cerebral blood flow (CBF) map (B, D) from a patient with clinically isolated syndrome. Circular regions of interest were placed on the frontal and periventricular NAWM and on the thalamus and putamen nuclei bilaterally. The color bars indicate the CBF values (in milliliters per 100 grams per minute).

Figure 2

Box plots display the 25% to 75% values (boxes) ± 95% values (whiskers), median values (horizontal lines within boxes) of mean absolute cerebral blood flow (CBF) value distribution in the putamen nucleus (A) and in the periventricular NAWM (B) among healthy controls (CTRL) (empty box), patients with clinically isolated syndrome (CIS) (hatched box) and patients with relapsing-remitting multiple sclerosis (RR-MS) (crosshatched box). Only significant P values are reported. Note significantly lower CBF values in the periventricular NAWM and putamen of patients with RR-MS and in the periventricular NAWM of patients with CIS.