| Title: |
Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis |
| Authors: |
Lazzarotto, Andrea; Hamzaoui, Mariem; Tonietto, Matteo; Dubessy, Anne-Laure; Khalil, Michael; Pirpamer, Lukas; Ropele, Stefan; Enzinger, Christian; Battaglini, Marco; Stromillo, Maria Laura; De Stefano, Nicola; Filippi, Massimo; Rocca, Maria Assunta; Gallo, Paolo; Gasperini, Claudio; Stankoff, Bruno; Bodini, Benedetta; MAGNIMS Study Group |
| Contributors: |
Lazzarotto, Andrea; Hamzaoui, Mariem; Tonietto, Matteo; Dubessy, Anne-Laure; Khalil, Michael; Pirpamer, Luka; Ropele, Stefan; Enzinger, Christian; Battaglini, Marco; Stromillo, Maria Laura; De Stefano, Nicola; Filippi, Massimo; Rocca, Maria Assunta; Gallo, Paolo; Gasperini, Claudio; Stankoff, Bruno; Bodini, Benedetta; Magnims Study, Group |
| Publication Year: |
2024 |
| Subject Terms: |
imaging; multiple sclerosis; myelin; neurodegeneration; neuroprotection; remyelination |
| Description: |
Cortical myelin loss and repair in multiple sclerosis (MS) have been explored in neuropathological studies, but the impact of these processes on neurodegeneration and the irreversible clinical progression of the disease remains unknown. Here, we evaluated in-vivo cortical demyelination and remyelination in a large cohort of people with all clinical phenotypes of MS followed-up for 5 years using magnetization transfer imaging (MTI), a technique that has been shown to be sensitive to myelin content changes in the cortex. We investigated 140 people with MS (37 clinically isolated syndromes, 71 relapsing-MS, 32 progressive-MS), who were clinically assessed at baseline and after 5 years and, along with 84 healthy controls, underwent a 3T-MRI protocol including MTI at baseline and after one year. Changes in cortical volume over the radiological follow-up were computed with a Jacobian integration method. Magnetization transfer ratio was employed to calculate for each patient an index of cortical demyelination at baseline, and of dynamic cortical demyelination and remyelination over the follow-up. The three indices of cortical myelin content change were heterogeneous across patients but did not significantly differ across clinical phenotypes or treatment groups. Cortical remyelination, which tended to fail in the regions closer to cerebrospinal fluid (-11%, p < 0.001), was extensive in half of the cohort, and occurred independently of age, disease duration, and clinical phenotype. Higher indices of cortical dynamic demyelination (β=0.23, p = 0.024) and lower indices of cortical remyelination (β=-0.18, p = 0.03) were significantly associated with greater cortical atrophy after one year, independently of age and MS phenotype. While the extent of cortical demyelination predicted a higher probability of clinical progression after five years in the entire cohort (OR = 1.2; p = 0.043), the impact of cortical remyelination in reducing the risk of accumulating clinical disability after five years was significant only in ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38267729; info:eu-repo/semantics/altIdentifier/wos/WOS:001191884000001; volume:147; issue:4; firstpage:1331; lastpage:1343; numberofpages:13; journal:BRAIN; https://hdl.handle.net/20.500.11768/156237 |
| DOI: |
10.1093/brain/awae024 |
| DOI: |
10.1093/brain/awae024/7588717?login=true |
| Availability: |
https://hdl.handle.net/20.500.11768/156237; https://doi.org/10.1093/brain/awae024; https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awae024/7588717?login=true |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.60ECDE93 |
| Database: |
BASE |