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Research Article
Elisabeth Solana
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
Corresponding Author
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The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a surface-based diffusion MRI processing tool to investigate regional modifications of microstructure and volume loss in GM at different time-points of the disease, and their relationship to disability. We studied 54 healthy controls and 247 MS patients classified according to disease duration: MS1 (less than 5 years, n=67); MS2 (5-15 years, n=107); and MS3 (more than15 years, n=73). We compared GM mean diffusivity (MD) and volume between groups, and estimated their clinical correlations. Regional modifications in MD and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in right putamen. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes extended to more than 80% of regions in MS3 group. Clinical disability was correlated with GM changes. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.
Keywords
grey matter, DTI, volume, disease course, multiple sclerosis
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Competing interest reported. E.M.-H., V.M., E.V., J.R., C.M., J.B. and F.P. have nothing to disclose. E.S and E.L.-S received travel reimbursement from Sanofi; N.S.-V. received compensation for consulting services and speaker honoraria from Genzyme-Sanofi, Novartis, Roche and Almirall; Y.B. received speaking honoraria from Biogen, Novartis and Genzyme; I.P.-V. received travel reimbursement from Roche and Genzyme, and she holds stock options in Aura Innovative Robotics. Currently, she is an employee at UCB Pharma, her contribution to this work is associated with her previous work at IDIBAPS; M.S. received speaker honoraria from Genzyme, Novartis and Biogen; M.A. holds equity shares of Bionure, S.L. and Goodgut S.L. and stock options of Attune Neurosciences Inc. He is currently an employee of Roche, although his contribution to this work is associated with his previous work at IDIBAPS; E.H.M.-L. received travel support for international and national meetings from Roche and Sanofi-Genzyme, and honoraria for consultancies from Novartis, Roche and Sanofi. She is currently employed by the European Medicines Agency (Human Medicines) since 16 April 2019. This article is related with her activity under Hospital Clinic of Barcelona/IDIBAPS affiliation and consequently, as external activity, it does not represent the views of the Agency or its Committees. She is a member of the International Multiple Sclerosis Visual System (IMSVISUAL) Consortium; A.S. received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, TEVA, Novartis and Roche; J.F. has received compensation for consultancies to Novartis, Lündbeck and AC Immune; S.L. received compensation for consulting services and speaker honoraria from Biogen Idec, Novartis, TEVA, Genzyme, Sanofi and Merck.
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Elisabeth Solana
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 13 Apr, 2021
No community comments so far
Editorial decision: Major revision
On 14 Jun, 2021
Reviews received
Received 10 Jun, 2021
Reviewers agreed
On 02 Jun, 2021
Reviewers agreed
On 30 May, 2021
Reviews received
Received 27 May, 2021
Reviewers agreed
On 27 May, 2021
Reviewers agreed
On 27 May, 2021
Reviews received
Received 06 May, 2021
Reviewers agreed
On 03 May, 2021
Reviewers agreed
On 30 Apr, 2021
Reviewers invited
Invitations sent on 30 Apr, 2021
Editor assigned
On 30 Apr, 2021
Editor invited
On 12 Apr, 2021
Submission checks complete
On 09 Apr, 2021
First submitted
On 09 Apr, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a surface-based diffusion MRI processing tool to investigate regional modifications of microstructure and volume loss in GM at different time-points of the disease, and their relationship to disability. We studied 54 healthy controls and 247 MS patients classified according to disease duration: MS1 (less than 5 years, n=67); MS2 (5-15 years, n=107); and MS3 (more than15 years, n=73). We compared GM mean diffusivity (MD) and volume between groups, and estimated their clinical correlations. Regional modifications in MD and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in right putamen. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes extended to more than 80% of regions in MS3 group. Clinical disability was correlated with GM changes. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.
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