Abstract

Cortical demyelination occurs early in multiple sclerosis (MS) and relates to disease outcome. The brain cortex has endogenous propensity for remyelination as proven from histopathology study. In this study, we aimed at characterizing cortical microstructural abnormalities related to myelin content by applying a novel quantitative MRI technique in early MS. A combined myelin estimation (CME) cortical map was obtained from quantitative 7-Tesla (7T) T and T1 acquisitions in 25 patients with early MS and 19 healthy volunteers. Cortical lesions in MS patients were classified based on their myelin content by comparison with CME values in healthy controls as demyelinated, partially demyelinated, or non-demyelinated. At follow-up, we registered changes in cortical lesions as increased, decreased, or stable CME. Vertex-wise analysis compared cortical CME in the normal-appearing cortex in 25 MS patients vs. 19 healthy controls at baseline and investigated longitudinal changes at 1 year in 10 MS patients. Measurements from the neurite orientation dispersion and density imaging (NODDI) diffusion model were obtained to account for cortical neurite/dendrite loss at baseline and follow-up. Finally, CME maps were correlated with clinical metrics. CME was overall low in cortical lesions (p = 0.03) and several normal-appearing cortical areas (p < 0.05) in the absence of NODDI abnormalities. Individual cortical lesion analysis revealed, however, heterogeneous CME patterns from extensive to partial or absent demyelination. At follow-up, CME overall decreased in cortical lesions and non-lesioned cortex, with few areas showing an increase (p < 0.05). Cortical CME maps correlated with processing speed in several areas across the cortex. In conclusion, CME allows detection of cortical microstructural changes related to coexisting demyelination and remyelination since the early phases of MS, and shows to be more sensitive than NODDI and relates to cognitive performance.

Highlights

  • Demyelinating cortical lesions are a pathologic hallmark of multiple sclerosis (MS), which can develop from the earliest disease stages and relate to disease progression [1,2,3,4,5,6].Based on the presence of myelin degradation products inside macrophages and microglia, cortical lesions can be distinguished as actively demyelinating and postdemyelinating [4, 7]

  • We applied combined myelin estimation (CME) from quantitative 7T acquisitions to assess microstructural changes likely related to myelin content in cortical lesions and normal-appearing cortex of early MS cases

  • Mean CME was overall abnormally decreased in cortical lesions and several regions of the cortical mantle, without significant changes in diffusion metrics or cortical thinning, suggesting early cortical demyelination in the absence of decreased neuroaxonal density and overt cortical atrophy

Read more

Summary

Introduction

Demyelinating cortical lesions are a pathologic hallmark of multiple sclerosis (MS), which can develop from the earliest disease stages and relate to disease progression [1,2,3,4,5,6]. Based on the presence of myelin degradation products inside macrophages and microglia, cortical lesions can be distinguished as actively demyelinating and postdemyelinating [4, 7]. Ongoing demyelination can coexist within the same lesion with massive remyelination [8]; the efficiency of the latter seemingly changes according to disease type and anatomical location [9, 10]. Knowledge on remyelinating phenomena in the early disease is, very limited, such as the actual clinical impact of cortical demyelination and remyelination in MS patients

Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.