A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis

Abstract

The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR-based approach. Using a 3 Tesla scanner, dual-echo, 3D fast-field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel-based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical-subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto-occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2-visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology.

Thalamic Damage Predicts the Evolution of Primary-Progressive Multiple Sclerosis at 5 Years

“…Similar to our findings, an increased thalamic MD in patients with MS with different clinical disease phenotypes in comparison with healthy controls was found in these studies, on average. 9,16,17,31 However, contrary to our results, an increased thalamic FA has been described. 17,31 Several factors might contribute to explaining the discrepancy between ours and previous findings concerning baseline thalamic FA abnormalities, including the fact that previous studies recruited patients with different MS phenotypes, predominantly relapsing-onset MS, whereas we enrolled patients with PPMS only.…”

“…Previous studies in patients with early PPMS (within 5 years of symptom onset) have reported that thalamic atrophy 9,23,30 and thalamic microscopic damage, quantified by using magnetization transfer imaging 30 and DTI, 9 are early features of PPMS. However, little is known about the temporal pattern of the evolution of these abnormalities and their relationship with disability accumulation.…”

“…[3][4][5][6][7][8] Several studies have emphasized the role of GM abnormalities and their relationship to clinical disability in PPMS. [5][6][7]9 However, only a few studies identified MR imaging markers of GM damage with the potential to predict subsequent disability accumulation. [10][11][12] In addition, most of these studies assessed whole GM damage, by using either a histogram-based or a voxelwise approach.…”

Effects of disease modifying therapies on brain and grey matter atrophy in relapsing remitting multiple sclerosis

“…Moreover, deep GM nuclei are site of relevant atrophy as well, i.e., compared to matched healthy subjects, up to 25% loss of the thalamus volume has been demonstrated in RRMS [24][25][26][27][28]. GM atrophy becomes more widespread and severe in secondary (SPMS) and primary progressive MS (PPMS) [29][30][31][32][33][34][35][36][37] and, in some patients, may undertake a dramatic acceleration, i.e., up to 14-fold compared to age-matched healthy individual [16,36]. Although PPMS and SPMS show similar extent of total GM atrophy, different regional atrophy distribution was described in these two types of MS [34][35][36][37] and some correlations between regional WM lesion load and GM atrophy were more often observed in SPMS compared to PPMS, a finding somehow expected given the differences in the WM lesion load that characterize these two MS types.…”

MR Imaging of Gray Matter Involvement in Multiple Sclerosis: Implications for Understanding Disease Pathophysiology and Monitoring Treatment Efficacy

“…64 With a voxel-based approach, a significant correlation was found in PPMS between a regional decrease of MTR values of cortical areas of the motor network and the EDSS scores as well as between MTR values in cortical areas of the cognitive network and the Paced Auditory Serial Addition Test scores. 65 Ceccarelli et al 66 showed DTI abnormalities in brain areas associated with motor and cognitive functions in PPMS (Fig 3). Bodini et al 67 found 11 brain regions with an anatomic corre- spondence between reduced NAWM FA values and GM atrophy in patients with early PPMS.…”