AUTHORS: Rahmanzadeh R, Lu PJ, Weigel M, Galbusera R, Nguyen TD, Schiavi S, Wang Y, La Rosa F, Bach Cuadra M, Radue EW, Kuhle J, Kappos L, Granziera C

Multiple Sclerosis Journal, 25(7): 682-683, June 2019

ABSTRACT

Introduction: 

The interplay between axonal and myelin damage in multiple sclerosis (MS) is poorly understood.

Objectives: 

This study aimed to evaluate the concomitant presence of axonal and myelin injury in MS by using myelin water imaging (MWI) and neurite density and orientation dispersion imaging (NODDI).

Methods: 

Thirty-two MS patients (22 relapsing-remitting MS-RRMS and 10 progressive MS-PMS) and 20 healthy controls (HC) underwent multi-parametric magnetic resonance imaging (MRI) at 3T. MRI data were reconstructed in MWI and multishell diffusion for NODDI. Mean MW fraction (MWF) and NODDI metrics (neurite density index- NDI and orientation dispersion index- ODI) were extracted in (i) white matter and cortical MS lesions (WMLs, CLs), (ii) two consecutive 2-voxel layers of NAWM around WMLs (denoted as Rim 1&2), (iii) normal appearing WM and GM (NAWM and NAGM) and (iv) WM and GM in HC (WM-HC and GM-HC). CLs were manually divided into intra-cortical and leuko-cortical lesions (ICLs and LCLs).
By using analysis of variance (Hp01-3-4) and paired t-test (Hp02) we tested the hypotheses (Hp) that myelin and axonal damage: Hp0-1 do not differ among WMLs and NAWM/WM-HC; Hp0-2 are equally extensive in WMLs; Hp0-3 are the same in WMLs, Rim 1&2 and distant NAWM; and Hp0-4 don’t differ among ICLs, LCLs, NAGM and GM-HC. To assess Hp0-2, we manually segmented the mirror normal-appearing contralateral region of 121 WMLs and evaluate the percentage of myelin (%MWF) and axonal density (%NDI) reduction in WMLs.

Results: 

We analyzed 590 lesions (WMLs: 465, ICLs: 29, LCLs: 96). In WMLs, MWF, NDI and ODI were reduced compared to NAWM and WMHC (p< 0.001). In Rim 1&2 of WMLs, MWF and NDI were significantly higher than in WMLs (p< 0.001). %MWF reduction was higher than %NDI in WMLs (p< 0.0001). ICLs exhibited lower NDI than LCLs (p< 0.05). ICLs showed also lower MWF, NDI and ODI compared to NAGM (p< 0.01) whereas LCLs had lower NDI/ODI (p< 0.001) but equal MWF to NAGM. NAWM had a higher ODI compared to WM-HC (p< 0.001). Reported differences were consistent in both RRMS and PMS subgroups.

Conclusion:

 In both RRMS and PMS patients, WMLs and CLs showed significant myelin and axonal injury compared to normal appearing and healthy tissue. In WMLs, myelin pathology outweighed axonal damage, however diffuse axonal pathology was present – though at a lower extent – in NAWM. LCLs showed more pronounced axonal than myelin pathology. Axonal damage in ICLs was higher than LCLs.

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