Assessment of the choroid plexuses volume in radiologically isolated syndrome

Objective: to investigate the volume of the choroid plexuses (ChP) in individuals with radiologically isolated syndrome (RIS) and its impact on conversion to multiple sclerosis (MS), and to assess the level of neuroinflammation in individuals with RIS.

Material and methods. A prospective observational study was conducted at the Federal Centre for Brain and Neurotechnologies, in which data from two groups of participants were analysed: individuals with RIS (n=32) and healthy volunteers (control group; n=30). The diagnosis of RIS was established in accordance with the 2017 McDonald criteria. All examinations were performed on a single MRI scanner with a magnetic field strength of 1.5 T. MRI morphometry of the cerebellum was performed on T1-weighted images using manual segmentation in the 3D Slicer software. Intracranial volume was determined using the automated web-based volBrain system. Statistical analysis was performed for both the absolute value of the ChP volume and the value normalized to intracranial volume.

Results. No statistically significant differences in age or sex were found between the RIS and control groups (p=0.21 and p=0.20, respectively). No differences in age or sex were observed either among individuals with RIS who subsequently converted and those who did not (p=0.67 and p=0.44, respectively). However, in patients with subsequent conversion, the ChP volume was already higher at baseline. The normalized ChP volume was higher in patients with conversion compared with those without conversion (1.435 [1.188; 1.715] mm3 versus 1.003 [0.918; 1.325] mm3; p=0.015), and the absolute ChP volume was also higher in the conversion group (1,878 [1,724; 2,333] versus 1,368 [1,163; 1,770]; p=0.024). According to the results of logistic regression, the normalized ChP volume was a significant predictor of conversion to MS (odds ratio 18.5; 95% CI 1.67–369.6), and the model’s diagnostic performance was satisfactory (AUC=0.78; 95% CI 0.62–0.94; p=0.016).

Conclusion. An increase in ChP volume, as measured by MRI morphometry, may be regarded as a non-invasive marker of neuroinflammation in the central nervous system and a potential predictor of disease progression, detectable in the early stages of the pathological process using standard MRI sequences.

1. Haki M, Al-Biati HA, Al-Tameemi ZS, et al. Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment. Medicine (Baltimore). 2024;103(8):e37297. doi: 10.1097/MD.0000000000037297

2. Andravizou A, Stavropoulou De Lorenzo S, Kesidou E, et al. The time trajectory of choroid plexus enlargement in multiple sclerosis. Healthcare (Basel). 2024 Apr 1;12(7):768. doi: 10.3390/healthcare12070768

3. Damkier HH, Brown PD, Praetorius J. Cerebrospinal fluid secretion by the choroid plexus. Physiol Rev. 2013;93(4):1847-92. doi: 10.1152/physrev.00004.2013

4. Ghersi-Egea JF, Strazielle N, Catala M, et al. Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease. Acta Neuropathol. 2018;135(3):337-61. doi: 10.1007/s00401-018-1807-1

5. Mapunda JA, Tibar H, Regragui W, Engelhardt B. How does the immune system enter the brain? Front Immunol. 2022;13:805657. doi: 10.3389/fimmu.2022.805657

6. Lun MP, Monuki ES, Lehtinen MK. Development and functions of the choroid plexus-cerebrospinal fluid system. Nat Rev Neurosci. 2015 Aug;16(8):445-57. doi: 10.1038/nrn3921

7. Balusu S, Van Wonterghem E, De Rycke R, et al. Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol Med. 2016;8(10):1162-83. doi: 10.15252/emmm.201606271

8. Benarroch EE. Choroid plexus-CSF system: Recent developments and clinical correlations. Neurology. 2016;86(3):286-96. doi: 10.1212/WNL.0000000000002298

9. Lazarevic I, Soldati S, Mapunda JA, et al. The choroid plexus acts as an immune cell reservoir and brain entry site in experimental autoimmune encephalomyelitis. Fluids Barriers CNS. 2023;20(1):39. doi: 10.1186/s12987-023-00431-6

10. Kivisäkk P, Mahad DJ, Callahan MK, et al. Human cerebrospinal fluid central memory CD4+ T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A. 2003;100(14):8389- 94. doi: 10.1073/pnas.1433000100

11. Yang AC, Kern F, Losada PM, et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature. 2021;595(7868):565-71. doi: 10.1038/s41586-021-03710-0

12. Vercellino M, Votta B, Condello C, et al. Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: A neuropathological study. J Neuroimmunol. 2008;199(1-2):133-41. doi: 10.1016/j.jneuroim.2008.04.035

13. Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: Pathology and pathogenesis. Nat Rev Neurol. 2012;8(11):647-56. doi: 10.1038/nrneurol.2012.168

14. Huang H, Zheng S, Yang Z. Voxel-based morphometry and a deep learning model for the diagnosis of early Alzheimer’s disease based on cerebral gray matter changes. Cereb Cortex. 2023;33(3):754-63. doi: 10.1093/cercor/bhac099

15. Potemkina EG, Salomatina TA, Andreev EV, et al. MR morphometry in epileptology: progress and perspectives. Burdenko's Journal of Neurosurgery. 2023;87(3):113-9 (In Russ., In Engl.). doi: 10.17116/neiro202387031113

16. Agren R, Awad A, Blomstedt P, Fytagoridis A. Voxel-based morphometry of cerebellar lobules in essential tremor. Front Aging Neurosci. 2021;13:667854. doi: 10.3389/fnagi.2021.667854

17. Manouchehri N, Stüve O. Choroid plexus volumetrics and brain inflammation in multiple sclerosis. Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):e2115221118. doi: 10.1073/pnas.2115221118

18. Fleischer V, Gonzalez-Escamilla G, Ciolac D, et al. Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans. Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2025000118. doi: 10.1073/pnas.2025000118

19. Ricigliano VAG, Morena E, Colombi A, et al. Choroid plexus enlargement in inflammatory multiple sclerosis: 3.0-T MRI and translocator protein PET evaluation. Radiology. 2021;301(1):166-77. doi: 10.1148/radiol.2021204426

20. Müller J, Sinnecker T, Wendebourg MJ, et al. Choroid plexus volume in multiple sclerosis vs neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2022;9(2):e1147. doi: 10.1212/NXI.0000000000001147

21. Bergsland N, Dwyer MG, Jakimovski D, et al. Association of choroid plexus inflammation on MRI with clinical disability progression over 5 years in patients with multiple sclerosis. Neurology. 2023;100(9):e911-20. doi: 10.1212/WNL.0000000000201608

22. Margoni M, Gueye M, Meani A, et al. Choroid plexus enlargement in paediatric multiple sclerosis: Clinical relevance and effect of sex. J Neurol Neurosurg Psychiatry. 2023;94(3):181-8. doi: 10.1136/jnnp-2022-330343

23. Preziosa P, Pagani E, Meani A, et al. Chronic active lesions and larger choroid plexus explain cognition and fatigue in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024;11(2):e200205. doi: 10.1212/NXI.0000000000200205

24. Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of multiple sclerosis: The radiologically isolated syndrome. Neurology. 2009;72(9):800-5. doi: 10.1212/01.wnl.0000335764.14513.1a

25. Landes-Chateau C, Ricigliano VAG, Mondot L, et al. Choroid plexus enlargement correlates with periventricular pathology but not with disease activity in radiologically isolated syndrome. Mult Scler. 2024;30(10):1278-89. doi: 10.1177/13524585241272943

26. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-73. doi: 10.1016/S1474-4422(17)30470-2

27. Bannai D, Cao Y, Keshavan M, et al. Manual segmentation of the human choroid plexus using brain MRI. J Vis Exp. 2023;(202):e65341. doi: 10.3791/65341

28. Manjon JV, Coupe P. volBrain: An online MRI brain volumetry system. Front Neuroinform. 2016;10:30. doi: 10.3389/fninf.2016.00030

29. Stavropoulou De Lorenzo S, Bakirtzis C, Konstantinidou N, et al. How early is early multiple sclerosis? J Clin Med. 2023 Dec 29;13(1):214. doi: 10.3390/jcm13010214

30. Hochstetler A, Lehtinen MK. Choroid plexus as a mediator of CNS inflammation in multiple sclerosis. Mult Scler. 2024 Dec;30(5 Suppl):19-23. doi: 10.1177/13524585241292974

31. Krieger B, Bellenberg B, Roenneke AK, et al. Relevance of choroid plexus volumes in multiple sclerosis. Fluids Barriers CNS. 2025;22(1):47. doi: 10.1186/s12987-025-00656-7

32. Klistorner S, Barnett MH, Parratt J, et al. Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy. Ann Clin Transl Neurol. 2022 Oct;9(10):1528-37. doi: 10.1002/acn3.51644

33. Wang X, Zhu Q, Yan Z, et al. Enlarged choroid plexus related to iron rim lesions and deep gray matter atrophy in relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2023;75:104740. doi: 10.1016/j.msard.2023.104740

34. Klistorner S, Barnett MH, Wang C, et al. Longitudinal enlargement of choroid plexus is associated with chronic lesion expansion and neurodegeneration in RRMS patients. Mult Scler. 2024 Apr;30(4-5):496-504. doi: 10.1177/13524585241228423