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. 2025 Apr 10;96(5):443-452.
doi: 10.1136/jnnp-2024-334913.

Dynamics of choroid plexus volume is associated with the presence and development of fatigue in multiple sclerosis

Martina Rubin  1   2   3 , Paolo Preziosa  1   2   3 , Monica Margoni  1   2   4 , Alessandro Meani  1 , Elisabetta Pagani  1 , Gianluca Corazzolla  1   3 , Loredana Storelli  1 , Damiano Mistri  1 , Massimo Filippi  1   2   3   4   5 , Maria A Rocca  6   2   3
Affiliations

Dynamics of choroid plexus volume is associated with the presence and development of fatigue in multiple sclerosis

Martina Rubin et al. J Neurol Neurosurg Psychiatry. .

Abstract

Background: Immune-mediated processes are implicated in the pathogenesis of fatigue, a common symptom in multiple sclerosis (MS). The choroid plexus (CP) regulates central nervous system (CNS) immune homeostasis and undergoes volumetric modifications possibly contributing to MS-related fatigue. We explored the association between MS-related CP volume changes and fatigue dynamics.

Method: Eighty-five patients with MS and 68 healthy controls (HC) underwent brain 3T MRI, neurological evaluation and Modified Fatigue Impact Scale (MFIS) at two timepoints (median follow-up=1.4 years). Normalised brain and regional grey matter (GM) volumes were obtained using FSL-SIENAx, FIRST, SIENA and tensor-based morphometry. CP volumes were quantified with in-house methods, and longitudinal changes were analysed using linear mixed models.

Results: At baseline, 25 (29%) patients with MS had fatigue (f-MS) (MFIS ≥38). Compared with HC, patients with MS had significantly higher brain T2-lesion volume, lower brain, deep GM, cortical volumes and higher CP volume (false discovery rate (FDR)-p ≤0.024). Compared with non-fatigued (nf-MS) patients, f-MS were older, more disabled (FDR-p ≤0.002) and showed numerically higher CP volume (FDR-p=0.076). At follow-up, 41 (68%) nf-MS remained non-fatigued (nf-FU-MS) and 19 (32%) developed fatigue (f-FU-MS). Patients with MS showed higher brain and deep GM atrophy rates versus HC (FDR-p ≤0.048), whereas clinical, lesional and brain volumetric changes were not significantly different among MS groups (FDR-p ≥0.287). CP volume significantly increased in all MS groups compared with HC (FDR-p ≤0.043), with greater enlargement in f-FU-MS versus nf-FU-MS (FDR-p=0.048).

Conclusions: Larger CP and greater enlargement are associated with the presence and development of fatigue in MS, likely reflecting dynamic inflammatory states within the CNS, supporting the immunological contribution to MS-related fatigue.

Keywords: MRI; MULTIPLE SCLEROSIS.

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Conflict of interest statement

Competing interests: MR has nothing to disclose. PP received speaker honoraria from Roche, Biogen, Novartis, Merck, Bristol Myers Squibb, Genzyme, Horizon and Sanofi, he has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. MM reports grants and personal fees from Sanofi Genzyme, Merck Serono, Novartis and Almiral. AM has nothing to disclose. EP has nothing to disclose. GC has nothing to disclose. LS has nothing to disclose. DM has nothing to disclose. MF 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, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. MAR 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, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla, she is Associate Editor for Multiple Sclerosis and Related Disorders.

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