Highlights
- •CP volume was 30% larger in patients with RRMS than HCs and was 20% larger in patients with IRLs than those without IRLs.
- •The enlargement of CP in RRMS had close correlations with inflammatory lesions load, especially IRLs, and deep gray matter atrophy.
- •There were no statistical correlations between CP volume and cortical lesions load and cortex volume.
- •The larger CP volume was associated with higher disability and lower cognitive scores.
Abstract
Background
Choroid plexus (CP) is considered to be linked to inflammation of multiple sclerosis
(MS), but its connection with markers of inflammation in vivo in MS is unclear, the
markers such as lesions load and brain atrophy, particularly the white matter lesions
(WMLs) edge surrounded by an iron rim, termed as iron rim lesions (IRLs).
Purpose
To investigate the association between CP volume and brain lesions load, especially
IRLs load and atrophy in MS, and its relationship with clinical characteristics.
Methods
3.0 T brain MRI images were acquired from 99 relapsing-remitting MS (RRMS) and 60
healthy controls (HCs) to obtain the volumes of CP, whole brain and lesions. Volumes
were expressed as a ratio of intracranial volume. Expanded Disability Status Scale
(EDSS), Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT)
were used to assess the severity of disability and cognitive function. Student's t-test and Multivariable regression analyses were performed to evaluate the difference
of CP volumes between RRMS and HC and the association between CP volume and lesions
load, brain volumes and clinical scale scores in RRMS.
Results
CP volume was 30% larger in patients with RRMS than HCs (p < 0.001) and was 20% larger in patients with IRLs than those without IRLs (p = 0.007). Moreover, the larger CP volume was related to greater WMLs volume in the
whole RRMS (r = 0.46, p < 0.001). Further analysis in patients with IRLs showed a positive correlation between
CP volume and WMLs volume (r = 0.45, p = 0.003), and IRLs volume (r = 0.51, p < 0.001). Meanwhile, enlarged CP was related to lower volumes in the whole brain
(r = -0.30, p = 0.006), deep gray matter (r = -0.51, p < 0.001) and most regional deep gray matter nuclei (except amygdala), but no correlation
with cortical lesions or cortex volume (both p > 0.05). In addition, CP volume was significantly higher in patients with cognitive
impairment than those with cognitive preservation by MoCA scores (p = 0.011); the larger CP volume was associated with higher EDSS scores (r = 0.25, p = 0.014) and lower SDMT Z scores in RRMS (r = -0.26, p = 0.014).
Conclusion
The enlargement of CP in RRMS had close correlations with inflammatory lesions, especially
IRLs and deep gray matter atrophy, but not the cortex. Meanwhile, the larger CP volume
was associated with higher disability and lower cognitive scores. CP volume may be
a surrogate imaging marker for MS disease activity.
Keywords
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References
- A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis[J].Nature. 2021; 597: 709-714https://doi.org/10.1038/s41586-021-03892-7
- Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis[J].Mult. Scler. 2022; 28: 2202-2211https://doi.org/10.1177/13524585221114750
- The blood cerebrospinal fluid barrier orchestrates immunosurveillance, immunoprotection, and immunopathology in the central nervous system[J].BMB Rep. 2021; 54: 196-202https://doi.org/10.5483/BMBRep.2021.54.4.205
- Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues[J].Lancet Neurol. 2020; 19: 860-871https://doi.org/10.1016/S1474-4422(20)30277-5
- Meningeal inflammation and cortical demyelination in acute multiple sclerosis[J].Ann. Neurol. 2018; 84: 829-842https://doi.org/10.1002/ana.25365
- Enlarged choroid plexus related to cortical atrophy in multiple sclerosis[J].Eur. Radiol. 2023; 33: 2916-2926https://doi.org/10.1007/s00330-022-09277-2
- Value of 3T susceptibility-weighted imaging in the diagnosis of multiple sclerosis[J].AJNR Am. J. Neuroradiol. 2020; 41: 1001-1008https://doi.org/10.3174/ajnr.A6547
- Multiple sclerosis[J].Lancet. 2008; 372: 1502-1517https://doi.org/10.1016/S0140-6736(08)61620-7
- Inflammation of the embryonic choroid plexus barrier following maternal immune activation[J].Dev. Cell. 2020; 55: 617-628https://doi.org/10.1016/j.devcel.2020.09.020
- Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging[J].Acta Neuropathol. 2017; 133: 25-42https://doi.org/10.1007/s00401-016-1636-z
- Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI[J].Brain. 2021; 144: 833-847https://doi.org/10.1093/brain/awaa436
- Dimethyl fumarate in relapsing-remitting multiple sclerosis: rationale, mechanisms of action, pharmacokinetics, efficacy and safety[J].Expert. Rev. Neurother. 2015; 15: 339-346https://doi.org/10.1586/14737175.2015.1025755
- Characterization of contrast-enhancing and non-contrast-enhancing multiple sclerosis lesions using susceptibility-weighted imaging[J].Front. Neurol. 2019; 10: 1082https://doi.org/10.3389/fneur.2019.01082
- Multiple sclerosis[J].Nat. Rev. Dis. Prim. 2018; 4: 43https://doi.org/10.1038/s41572-018-0041-4
- Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans[J].Proc. Natl. Acad. Sci. U. S. A. 2021; 118https://doi.org/10.1073/pnas.2025000118
- Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease[J].Acta Neuropathol. 2018; 135: 337-361https://doi.org/10.1007/s00401-018-1807-1
- The expansion and severity of chronic MS lesions follows a periventricular gradient[J].Mult. Scler. 2022; 28: 1504-1514https://doi.org/10.1177/13524585221080667
- Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy[J].Ann. Clin. Transl. Neurol. 2022; 9: 1528-1537https://doi.org/10.1002/acn3.51644
- The SDMT is not information processing speed[J].Mult. Scler. 2021; 27: 1806-1807https://doi.org/10.1177/1352458521988959
- Relationship between white matter lesions and gray matter atrophy in multiple sclerosis: a systematic review[J].Neurology. 2022; 98: e1562-e1573https://doi.org/10.1212/WNL.0000000000200006
- Paramagnetic rim lesions are specific to multiple sclerosis: an international multicenter 3T MRI study[J].Ann. Neurol. 2020; 88: 1034-1042https://doi.org/10.1002/ana.25877
- Choroid plexus volumetrics and brain inflammation in multiple sclerosis[J].Proc. Natl. Acad. Sci. U. S. A. 2021; 118https://doi.org/10.1073/pnas.2115221118
- Systematic literature review and validity evaluation of the expanded disability status scale (EDSS) and the multiple sclerosis functional composite (MSFC) in patients with multiple sclerosis[J].BMC Neurol. 2014; 14: 58https://doi.org/10.1186/1471-2377-14-58
- The temporal and causal relationship between inflammation and neurodegeneration in multiple sclerosis[J].Mult. Scler. 2020; 26: 876-886https://doi.org/10.1177/1352458519886943
- Choroid plexus volume in multiple sclerosis vs neuromyelitis optica spectrum disorder: a retrospective, cross-sectional analysis[J].Neurol Neuroimmunol Neuroinflamm. 2022; 9https://doi.org/10.1212/NXI.0000000000001147
- Structural and clinical correlates of a periventricular gradient of neuroinflammation in multiple sclerosis[J].Neurology. 2021; 96: e1865-e1875https://doi.org/10.1212/WNL.0000000000011700
- Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions[J].Acta Neuropathol. 2017; 134: 45-64https://doi.org/10.1007/s00401-017-1696-8
- Imaging characteristics of choroid plexuses in presymptomatic multiple sclerosis: a retrospective study[J].Neurol Neuroimmunol Neuroinflamm. 2022; 9https://doi.org/10.1212/NXI.0000000000200026
- Choroid plexus enlargement in inflammatory multiple sclerosis: 3.0-T MRI and translocator protein PET evaluation[J].Radiology. 2021; 301: 166-177https://doi.org/10.1148/radiol.2021204426
- Altered secretory and neuroprotective function of the choroid plexus in progressive multiple sclerosis[J].Acta Neuropathol Commun. 2020; 8: 35https://doi.org/10.1186/s40478-020-00903-y
- An automated tool for detection of FLAIR-hyperintense white-matter lesions in multiple sclerosis[J].Neuroimage. 2012; 59: 3774-3783https://doi.org/10.1016/j.neuroimage.2011.11.032
- Brain leukocyte infiltration initiated by peripheral inflammation or experimental autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled compartments of the forebrain and midbrain[J].J Neuroinflammation. 2012; 9: 187https://doi.org/10.1186/1742-2094-9-187
- The choroid plexus: simple structure, complex functions[J].J. Neurosci. Res. 2020; 98: 751-753https://doi.org/10.1002/jnr.24571
- Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria[J].Lancet Neurol. 2018; 17: 162-173https://doi.org/10.1016/S1474-4422(17)30470-2
- Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: a neuropathological study[J].J. Neuroimmunol. 2008; 199: 133-141https://doi.org/10.1016/j.jneuroim.2008.04.035
Article info
Publication history
Published online: April 28, 2023
Accepted:
April 28,
2023
Received in revised form:
April 24,
2023
Received:
March 21,
2023
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
