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Intrathecal Inflammatory Profile and Gray Matter Damage Predict Progression Independent of Relapse Activity in Early Multiple Sclerosis
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Elisa Colato ,
Matteo Foschi ,
Agnese Tamanti ,
Stefano Ziccardi ,
Chiara Eccher,
Francesco Crescenzo ,
Albulena Bajrami,
Gian Marco Schiavi,
Valentina Camera ,
Daniela Anni ,
Federica Virla ,
Maddalena Guandalini ,
Ermanna Turano ,
Francesca Benedetta Pizzini,
Stefania Montemezzi ,
Bruno Bonetti ,
Owain Howell ,
Roberta Magliozzi ,
Richard S. Nicholas,
Antonio Scalfari ,
Cristina Granziera ,
Ludwig Kappos ,
Massimiliano Calabrese
Neurology Neuroimmunology & Neuroinflammation, Volume: 12, Issue: 4
Swansea University Author:
Owain Howell
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DOI (Published version): 10.1212/nxi.0000000000200399
Abstract
Background and ObjectivesThe objective of this study was to determine, at the time of diagnosis, a CSF and MRI profile of intrathecal compartmentalized inflammation predictive of progression independent of relapse activity (PIRA) in early relapsing-remitting multiple sclerosis (RRMS).MethodsThis fiv...
| Published in: | Neurology Neuroimmunology & Neuroinflammation |
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| ISSN: | 2332-7812 |
| Published: |
Ovid Technologies (Wolters Kluwer Health)
2025
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa69891 |
| Abstract: |
Background and ObjectivesThe objective of this study was to determine, at the time of diagnosis, a CSF and MRI profile of intrathecal compartmentalized inflammation predictive of progression independent of relapse activity (PIRA) in early relapsing-remitting multiple sclerosis (RRMS).MethodsThis five-year prospective study included 80 treatment-naïve patients with RRMS enrolled at time of diagnosis. All patients underwent a lumbar puncture, regular neurologic evaluations including an Expanded Disability Status Scale (EDSS) assessment every 6 months, and an annual 3T brain MRI. PIRA was defined as having a confirmed disability progression independent of relapse activity. CSF levels of 68 inflammatory molecules were evaluated in combination with white matter and cortical lesion number (CLn) and volume, and regional gray matter thickness and volume.ResultsDuring the follow-up, 23 patients with RRMS (28.8%) experienced PIRA. At diagnosis, participants with PIRA were older (44.0 ± 10.7 vs 37.4 ± 12.4, p = 0.017) and with more disability (median EDSS score [interquartile range] of 3 [range 2–4] for PIRA vs 1.5 [range 1–2] for no PIRA group, p < 0.001). Random forest selected LIGHT, CXCL13, sTNFR1, sTNFR2, CCL7, MIF, sIL6Rbeta, IL35, CCL2, and IFNβ as the CSF markers best associated with PIRA. sTNFR1 (hazard ratio [HR] 10.11 [2.61–39.10], p = 0.001), sTNFR2 (HR 5.05 [1.63–15.64], p = 0.005), and LIGHT (HR 1.79 [1.11–2.88], p = 0.018) were predictors of PIRA at regression analysis. Baseline thalamus volume (HR 0.98 [0.97–0.99], p = 0.005), middle frontal gyrus thickness (HR 0.05 [0.01–0.72], p = 0.028), and CLn (HR 1.15 [1.05–1.25], p = 0.003) were MRI predictors of PIRA.DiscussionA specific intrathecal inflammatory profile associated with TNF superfamily markers, CLn, and atrophy of several cortical and deep gray matter regions, assessed at time of diagnosis, is predictive of PIRA in early MS. |
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| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
D. Marastoni was supported by the GR-2021-12373041 grant from Italian Ministry of Health. M. Calabrese was supported by the RF-2021-12373319 grant from Italian Ministry of Health. R. Magliozzi was supported by grant from the Italian MS Foundation (FISM 2023/R-Single/038), #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)- A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022). |
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4 |