MRI–clinical correlations in the primary progressive course of MS: new insights into the disease pathophysiology from the application of magnetization transfer, diffusion tensor, and functional MRI

Abstract 

Despite patients with primary progressive multiple sclerosis (PPMS) experience a progressive disease course from onset, the burden and activity of lesions on conventional magnetic resonance imaging (MRI) scans of the brain are lower than in all other main clinical phenotypes of MS. This review outlines the major contributions given by magnetization transfer MRI, diffusion tensor MRI and functional MRI to the understanding of the pathophysiology of PPMS and provides evidence that, at least, three factors might explain this clinical/MRI discrepancy: (a) the presence of a diffuse tissue damage at a microscopic level; (b) a prevalent involvement of the cervical cord, and (c) an impairment of the adaptive capacity of the cortex to limit the functional consequences of subcortical structural damage.

Keywords:  Primary progressive multiple sclerosis, Magnetic resonance imaging, Magnetization transfer, Diffusion tensor, Functional magnetic resonance imaging

Abbreviations:  PPMS, primary progressive multiple sclerosis, MRI, magnetic resonance imaging, RR, relapsing remitting, SP, secondary progressive, MT, magnetization transfer, DT, diffusion tensor, NAWM, normal-appearing white matter, NAGM, normal-appearing gray matter, fMRI, functional magnetic resonance imaging, MTR, magnetization transfer ratio, ADC, apparent diffusion coefficient, D̄, mean diffusivity, FA, fractional anisotropy, ROI, region-of-interest, CSF, cerebrospinal fluid, NABT, normal-appearing brain tissue, BOLD, blood oxygenation level-dependent, CBF, cerebral blood flood, CBV, cerebral blood volume, EDSS, expanded disability status scale, SMA, supplementary motor area, SII, upper bank of the sylvian fissure, MFG, middle frontal gyrus, CMA, cingulate motor area