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Multicenter Study
. 2025 May 8;22(1):47.
doi: 10.1186/s12987-025-00656-7.

Relevance of choroid plexus volumes in multiple sclerosis

Britta Krieger  1 , Barbara Bellenberg  1 , Anna Katharina Roenneke  1 , Ruth Schneider  2 , Theodoros Ladopoulos  2 , Zainab Abbas  2 , Rebekka Rust  3 , Tanja Schmitz-Hübsch  3 , Claudia Chien  4 , Ralf Gold  2 , Friedemann Paul  3 , Carsten Lukas  5
Affiliations
Multicenter Study

Relevance of choroid plexus volumes in multiple sclerosis

Britta Krieger et al. Fluids Barriers CNS. .

Abstract

Background: The choroid plexus (ChP) plays a pivotal role in inflammatory processes that occur in multiple sclerosis (MS). The enlargement of the ChP in relapsing-remitting multiple sclerosis (RRMS) is considered to be an indication of disease activity and has been associated with periventricular remyelination failure. This cross-sectional study aimed to identify the relationship between ChP and periventricular tissue damage which occurs in MS, and to elucidate the role of neuroinflammation in primary progressive multiple sclerosis (PPMS).

Methods: ChP volume was assessed by a novel deep learning segmentation method based on structural MRI data acquired from two centers. In total, 141 RRMS and 64 PPMS patients were included, along with 75 healthy control subjects. In addition, T1w/FLAIR ratios were calculated within periventricular bands to quantify microstructural tissue damage and to assess its relationship to ChP volume.

Results: When compared to healthy controls, ChP volumes were significantly increased in RRMS, but not in patients with PPMS. T1w/FLAIR ratios in the normal appearing white matter (NAWM) showing periventricular gradients were decreased in patients with multiple sclerosis when compared to healthy control subjects and lower T1w/FLAIR ratios radiating out from the lateral ventricles were found in patients with PPMS. A relationship between ChP volume and T1w/FLAIR ratio in NAWM was found within the inner periventricular bands in RRMS patients. A longer duration of disease was associated with larger ChP volumes only in RRMS patients. Enlarged ChP volumes were also significantly associated with reduced cortex volumes and increased lesion volumes in RRMS.

Conclusions: Our analysis confirmed that the ChP was significantly enlarged in patients with RRMS, which was related to brain lesion volumes and which suggested a dynamic development as it was associated with disease duration. Plexus enlargement was further associated with periventricular demyelination or tissue damage assessed by T1w/FLAIR ratios in RRMS. Furthermore, we did not find an enlargement of the ChP in patients with PPMS, possibly indicating the reduced involvement of inflammatory processes in the progressive phase of MS. The association between enlarged ChP volumes and cortical atrophy in RRMS highlighted the vulnerability of structures close to the CSF.

Keywords: Choroid plexus; MRI; Multiple sclerosis; Neuroinflammation.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the local ethics committees of the Ruhr-University Bochum (Approval No. 20–7054-BR) and of the LAGeSo Berlin (No. ZS EK 10 407/08, new: 08/0407-EK 15 and No. 06/0510 ZS EK 15). It was conducted according to the Declaration of Helsinki in its applicable version. Every participant provided written informed consent before screening. Consent for publication: Not applicable. Competing interests: R. Schneider has received consulting and speakers’ honoraria from Roche Pharma AG, Novartis Pharma, Merck KGaA and Alexion Pharma & has received research scientific grant support from Novartis Pharma, all not related to this work; T. Ladopoulos has received a research grant from Novartis Pharma, unrelated to this project; R. Rust has received speaking honoraria from Roche, unrelated to this project; C. Chien received writing honoraria from the British Society for Immunology, is a Standing Committee on Science Member for the CIHR, and has received research support from Novartis and Alexion, and is part of a consortium project funded by the US Department of Defense, unrelated to this project; R. Gold has received research support and speaker’s honoraria from Bayer-Schering, Biogen Idec, BMS, Chugai, Eisai, Genesis, Janssen, Merck Serono, Nikkiso Pharma, Novartis, Roche, Sanofi-Genzyme, Sandoz, and Teva, consulting honoraria from ZLB Behring, Baxter, Roche, and Talecris, and personal stock options in Bayer, Merck, and Roche; F. Paul received support from NeuroCure Clinical Research Center for the present manuscript, has received research support from German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Einstein Foundation, Guthy Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck Serono, Novartis, Bayer, Roche, consulting fees from Alexion, Roche, Horizon, Neuraxpharm, has received honoraria for lectures, presentations, speakers bureaus from Almirall, Bayer, Biogen, GlaxoSmithKline, Hexal, Merck, Sanofi Genzyme, Novartis, Viela Bio, UCB, Mitsubishi Tanable, Celgene, Guthy Jackson Foundation, Serono, support for attending meetings or travel from Merck, Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Alexion, Viela Bio, Roche, UCB, Mitsubishi Tanable, Celgene, participated on a data safety monitoring board or advisory board for Celgene AdBoard, Roche AdBoard, USB AdBoard, Merck AdBoard, is an associatee editor with Neurology, Neuroimmunology, and Neuroinflammation and academic editor with PloS One; C. Lukas received a research grant by the German Federal Ministry for Education and Research, BMBF, German Competence Network Multiple Sclerosis (KKNMS), grant no.01GI1601I, and received consulting and speaker’s honoraria from Biogen Idec, Bayer Schering, BMS, Daiichi Sankyo, Merck Serono, Novartis, Sanofi, Genzyme and TEVA. B. Krieger reports no disclosures relevant to the manuscript. B. Bellenberg reports no disclosures relevant to the manuscript. Z. Abbas reports no disclosures relevant to the manuscript. T. Schmitz-Hübsch reports no disclosures relevant to the manuscript. A.K. Roenneke reports no disclosures relevant to the manuscript. Clinical trial number: Not applicable.

Figures

Fig. 1
Fig. 1
Choroid Plexus volumes in control subjects, relapsing-remitting, and primary progressive multiple sclerosis. Comparison of choroid plexus (ChP) volumes normalized for intracranial volumes between control subjects (CS) and patients with relapsing-remitting (RRMS) and primary progressive multiple sclerosis (PPMS). Values from the two centers are coloured in blue (Berlin) and yellow (Bochum). P-values were obtained from pairwise Tukey post-hoc tests following the analysis of covariance with age, sex, and center as covariates
Fig. 2
Fig. 2
Relationship between choroid plexus volumes and disease duration. Relationship between choroid plexus (ChP) volumes normalized for intracranial volume and disease duration for patients with relapsing-remitting (RRMS) and primary progressive multiple sclerosis (PPMS). Blue lines represent fitted linear regression lines. P-values (for ChP vs. disease duration) and adjusted R2 were obtained from linear regression analyses with age and sex as covariates
Fig. 3
Fig. 3
Relationship between choroid plexus volumes and brain volumes. Relationship between choroid plexus (ChP) volumes normalized to intracranial volume and cortical gray matter volume, white matter volume, lesion volume, or lateral ventricle volume for patients with relapsing-remitting (RRMS) and primary progressive multiple sclerosis (PPMS). P-values (for ChP vs. volumes) and adjusted R2 were obtained from linear (or non-linear for lateral ventricle volume) regression analyses with age and sex as covariates
Fig. 4
Fig. 4
T1w/FLAIR ratios within periventricular bands. Mean T1w/FLAIR ratios of normal-appearing white matter in each periventricular band (band b2 to band b10) for control subjects (CS), patients with primary progressive MS (PPMS), and patients with relapsing-remitting MS (RRMS). Error bars represent standard errors
Fig. 5
Fig. 5
T1w/FLAIR ratios versus ChP volumes for each periventricular band. Relationship between T1w/FLAIR ratios and ChP volumes normalized to intracranial volume in each periventricular band (band b2 to band b10) for relapsing-remitting MS (RRMS,blue) and primary progressive MS (PPMS, green) patients. P-values (for ratios vs. ChP volumes) and adjusted R2 were obtained from linear regression analyses with age, sex, and center as covariates. P-values were corrected for multiple comparisons using Benjamini-Hochberg procedure
Fig. 6
Fig. 6
T1w/FLAIR ratios for long and short disease durations. Mean T1w/FLAIR ratios in each periventricular band (band b2 to band b10) for relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) patients divided into long (>10 years) and short (<10 years) disease durations. Error bars represent standard errors
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