Multiple Sclerosis Research Repository

“Myelin and axon pathology in multiple sclerosis assessed by myelin water and multi-shell diffusion imaging” by Reza Rahmanzadeh et al

-neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patient cohort

-progressive patients differ from RRMS patients because of more extensive axon/myelin damage in the cortex

-myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage

-despite the applied measures demonstrating good sensitivity to pathological changes in MS patients, they lack specificity for both myelin and axonal damage

-MCMDI is an alternative technique to the NODDI model that provides estimates of intra- and extra-neurite compartments in the brain, which has been applied to MS patients

-MP2RAGE and 3D-EPI permit identification of the specific lesion subtypes such as cortical and chronic active lesions

-cortical lesions more common in PMS than RRMS

-vertex-wise analysis showed areas across NAGM in which MWF and NODDI-NDI were lower in PMS compared to RRMS

-MWF and NDI in white matter lesions did not correlate with EDSS when the entire cohort was considered

-in patients with clinical deficits (EDSS greater than 1)-NDI in white matter lesions was associated with EDSS

-MWF and NDI in white matter lesions were related to serum NfL, but this correlation was not significant after adjusting for T2 lesion volume; however, when only patients with EDSS greater than 1 were considered, white matter lesion MWF correlated with serum neurofilaments

-suggesting that axon and myelin damage are synchronized and/or driven by a common pathological event

-in a large majority of lesions-axonal damage outweighed myelin damage; may be due to a primary axonal pathology as previously suggested

-a pivotal finding of this study is the presence of axonal damage independent of demyelination in both focal white matter lesions and NAWM; these findings are also in line with previous spectroscopy studies showing a very early diffuse reduction of N-acetylaspartate in NAWM in RRMS and increase in lipid levels at the site of future MS lesions; pathologically, this may be related to primary oliogodendrocytopathy leading to axonal damage via disruption of oligodendrocyte neuron cross-talk or to direct damage to the neuroaxonal unit

-magnetization transfer ratio-another surrogate measure of both myelin and axonal damage-is mostly related to disability when measured in lesions and not in the normal-appearing tissue

-it may well be that those patients experience a higher functional reserve and more effective mechanisms compensating for structural damages, which is often the case at early disease stages

-MWF and NDI: provide surrogate-not direct-markers of myelin and axon characteristics