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Unraveling the heterogeneous pathological substrates of relapse-onset multiple sclerosis: a multiparametric voxel-wise 3 T MRI study

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Abstract

Background

In multiple sclerosis (MS), pathological processes affecting brain gray (GM) and white matter (WM) are heterogeneous.

Objective

To apply a multimodal MRI approach to investigate the regional distribution of the different pathological processes occurring in the brain WM and GM of relapse-onset MS patients.

Methods

Fifty-seven MS patients (forty-two relapsing remitting [RR], fifteen secondary progressive [SP]) and forty-seven age- and sex-matched healthy controls (HC) underwent a multimodal 3 T MRI acquisition. Between-group voxel-wise differences of brain WM and GM volumes, magnetization transfer ratio (MTR), T1-weighted(w)/T2w ratio, intracellular volume fraction (ICV_f), and quantitative susceptibility mapping (QSM) maps were investigated.

Results

Compared to HC, RRMS showed significant WM, deep GM and cortical atrophy, significantly lower MTR and T1w/T2w ratio of periventricular and infratentorial WM, deep GM and several cortical areas, lower ICV_f in supratentorial and cerebellar WM and in some cortical areas, and lower QSM values in bilateral periventricular WM (p < 0.001). Compared to RRMS, SPMS patients showed significant deep GM and widespread cortical atrophy, significantly lower MTR of periventricular WM, deep GM and cerebellum, lower T1w/T2w ratio of fronto-temporal WM regions, lower ICV_f of some fronto-tempo-occipital WM and cortical areas. They also had increased QSM and T1w/T2w ratio in the pallidum, bilaterally (p < 0.001).

Conclusion

A periventricular pattern of demyelination and widespread GM and WM neuro-axonal loss are detectable in RRMS and are more severe in SPMS. Higher T1w/T2w ratio and QSM in the pallidum, possibly reflecting iron accumulation and neurodegeneration, may represent a relevant MRI marker to differentiate SPMS from RRMS.

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Data availability

The data sets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

This study did not receive any funding.

Author information

Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy

    Monica Margoni, Elisabetta Pagani, Paolo Preziosa, Mor Gueye, Matteo Azzimonti, Maria A. Rocca & Massimo Filippi

  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Monica Margoni, Paolo Preziosa, Mor Gueye, Matteo Azzimonti, Maria A. Rocca & Massimo Filippi

  3. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Monica Margoni & Massimo Filippi

  4. Vita-Salute San Raffaele University, Milan, Italy

    Paolo Preziosa, Maria A. Rocca & Massimo Filippi

  5. Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

Authors
  1. Monica Margoni
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  2. Elisabetta Pagani
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  7. Massimo Filippi
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Corresponding author

Correspondence to Massimo Filippi.

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Conflicts of interest

M. Margoni reports grants and personal fees from Almirall. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020. E. Pagani received speakers’ honoraria from Biogen Idec. P. Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. M. Gueye and M. Azzimonti have nothing to disclose. M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; and speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. She receives research support from the MS Society of Canada, the Italian Ministry of Health, and Fondazione Italiana Sclerosi Multipla. She is the Associate Editor for Multiple Sclerosis and Related Disorders. Prof. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, and Fondazione Italiana Sclerosi Multipla.

Ethical approval

Approval was received from the institutional ethical standards committee on human experimentation of IRCCS Ospedale San Raffaele for any experiments using human subjects (Protocol N° 2009-74). Written informed consent was obtained from all subjects prior to study participation according to the Declaration of Helsinki.

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Margoni, M., Pagani, E., Preziosa, P. et al. Unraveling the heterogeneous pathological substrates of relapse-onset multiple sclerosis: a multiparametric voxel-wise 3 T MRI study. J Neurol 270, 3839–3850 (2023). https://doi.org/10.1007/s00415-023-11736-9

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  • DOI: https://doi.org/10.1007/s00415-023-11736-9

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