A study of the mechanisms of normal-appearing white matter damage in multiple sclerosis using diffusion tensor imaging

Abstract

Diffusion tensor imaging (DTI) investigates brain tissue microstructure in vivo. In multiple sclerosis (MS) Wallerian degeneration of axons traversing focal lesions is a potential mechanism of damage in normal-appearing white matter. In vivo evidence for this hypothesis is limited. The present study investigated the relationship between DTI-derived indices in the normal-appearing corpus callosum (CC) and the lesion loads (LLs) in connected cerebral regions. DTI was performed in 39 MS patients and in 21 age-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) were estimated in the genu, body and splenium of CC. Patients showed lower FA and higher MD in the CC than controls and both correlated with the total LL (r = -0.56 and r = 0.54, p < 0.0001). The LL of individual cerebral lobes correlated with both FA and MD in the corresponding callosal regions, with the body showing the strongest correlations with frontal and parietal LL (p < 0.0001). The strong correlations between DTI indices in the CC and the extent of lesions in connected brain regions support the hypothesis that Wallerian degeneration of axons transected by remote, but connected focal lesions, is an important pathogenic mechanism of damage in MS.

Diffusion tensor MR imaging evaluation of the corpus callosum of patients with multiple sclerosis

“…These studies have shown decrease of the FA values in the NAWM, probably secondary to myelin sheath and axonal destruction 4,[9][10][11] . These abnormalities tend to expand the extracellular space, resulting in increased diffusivity and reduced directionality (FA) 3 . Although CC is a good example of NAWM, with high concentration of white matter tracts, it was poorly studied in MS patients 1,6 .…”

“…The classic subdivision of the CC was suggested by Witelson, who tried to link the crossing fibers of the related cortical areas 2 . The callosal tracts are frequently affected in patients with multiple sclerosis (MS), which is a demyelinating disease associated with axonal destruction and Wallerian degeneration [3][4][5] . Magnetic resonance (MR) imaging is the gold standard imaging technique for the evaluation of patients with MS. however, there are microstructural pathologic alterations in MS patients that cannot be assessed with conventional MR sequences 1,6 .…”

“…It also interconnects both cerebral hemispheres, promoting functional integration of sensory and motor functions 2 . The CC is composed of many different fiber types, with varied thicknesses and myelin sheath variations 3 . The classic subdivision of the CC was suggested by Witelson, who tried to link the crossing fibers of the related cortical areas 2 .…”

“…Also, areas of normal-appearing white matter (NAWM), defined as normal signal intensity on T2-weighted images, have been shown histological abnormalities 4,5 . Advanced MR imaging techniques, such as MR spectroscopy and diffusion tensor imaging (DTI), have been employed for evaluating the NAWM in patients with MS 3,5 . The DTI is an advanced MR imaging technique that provides unique quantitative information regarding the structural and orientational features of the central nervous system.…”

Neuroimaging of corpus callosum in central nervous system demyelinating disorders

“…Acute NMO patients had significantly higher average MDs than controls in the genu of the CC and optic radiation, and significantly lower average MDs in medulla oblongata, internal capsule and thalamus. [64] CC IN SUSAC SYNDROME MRI Susac's syndrome (SS) is a clinical triad of encephalopathy, branch retinal artery occlusion and sensorineural hearing loss. It is sometimes misdiagnosed because of similarities with ADEM and MS.…”