Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy

Klistorner, Samuel; Barnett, Michael; Parratt, John; Yiannikas, Con; Graham, Stuart L.; Klistorner, Alexander

doi:10.1002/acn3.51644

Cited by 30 publications

(27 citation statements)

References 60 publications

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“…First, our finding of overall annual choroid plexus enlargement was novel in the context of neurodegenerative diseases. The volume increase was in contrast to previous longitudinal studies on CP volume in stroke and multiple sclerosis ( 30 , 32 ), where no change in time was observed. However, this could be attributed to both differing study population as well as lower number of subjects and shorter follow-up in the cited studies.…”

Section: Discussioncontrasting

confidence: 99%

Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status

Martínková

Ferretti²,

Ferrari³

et al. 2023

Front. Psychiatry

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IntroductionChoroid plexus (CP)-related mechanisms have been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. In this pilot study, we aimed to elucidate the association between longitudinal changes in CP volume, sex and cognitive impairment.MethodsWe assessed longitudinal changes in CP volume in a cohort of n = 613 subjects across n = 2,334 datapoints from ADNI 2 and ADNI-GO, belonging to cognitively unimpaired (CN), stable mild cognitive impairment (MCI), clinically diagnosed Alzheimer’s disease dementia (AD) or convertor (to either AD or MCI) subgroups. CP volume was automatically segmented and used as a response variable in linear mixed effect models with random intercept clustered by patient identity. Temporal effects of select variables were assessed by interactions and subgroup analyses.ResultsWe found an overall significant increase of CP volume in time (14.92 mm3 per year, 95% confidence interval, CI (11.05, 18.77), p < 0.001). Sex-disaggregated results showed an annual rate of increase 9.48 mm3 in males [95% CI (4.08, 14.87), p < 0.001], and 20.43 mm3 in females [95% CI (14.91, 25.93), p < 0.001], indicating more than double the rate of increase in females, which appeared independent of other temporal variables. The only diagnostic group with a significant CP increase as compared to CN was the convertors group, with an increase of 24.88 mm3/year [95% CI (14, 35.82), p < 0.001]. ApoE exhibited a significant temporal effect, with the E4 homozygote group’s CP increasing at more than triple the rate of non-carrier or heterozygote groups [40.72, 95% CI (25.97, 55.46), p < 0.001 vs. 12.52, 95% CI (8.02, 17.02), p < 0.001 for ApoE E4 homozygotes and E4 non-carriers, respectively], and may have modified the diagnostic group relationship.ConclusionOur results contribute to potential mechanisms for sex differences in cognitive impairment with a novel finding of twice the annual choroid plexus enlargement in females and provide putative support for CP-related mechanisms of cognitive deterioration and its relationship to ApoE E4.

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Section: Discussioncontrasting

confidence: 99%

Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status

Martínková

Ferretti²,

Ferrari³

et al. 2023

Front. Psychiatry

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“…(Fleischer et al 2021) (Manouchehri and Stüve 2021) (V. A. Ricigliano et al 2021) (S. Klistorner et al 2022). We recently reported that the volume of CP predicts subsequent expansion of chronic periventricular MS lesions and is associated with tissue damage within and outside of chronic lesions.…”

Section: Discussionmentioning

confidence: 91%

“…(Fleischer et al 2021) (Manouchehri and Stüve 2021) (V. A. Ricigliano et al 2021) (S. Klistorner et al 2022).…”

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Choroid plexus volume is enlarged in clinically isolated syndrome patients with optic neuritis

Klistorner

Walt

Barnett

et al. 2022

Preprint

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Objectives: People with Multiple Sclerosis (MS) have a larger choroid plexus (CP) volume than healthy controls. We investigated CP volume in early MS by quantitatively assessing brain MRI scans in patients presenting with optic neuritis (ON) as a clinically isolated syndrome (CIS), compared to a cohort with established Relapsing Remitting Multiple Sclerosis (RRMS) and healthy controls. Methods: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 44 CIS ON patients at baseline, 1, 3, 6 and 12 months after the onset of ON. Fifty RRMS patients and 50 healthy controls were also included for comparison. Results: ANOVA revealed significantly larger CP volumes in both ON CIS and RRMS groups compared to healthy controls (p<0.001 for both), but no difference between ON CIS and RRMS patients (p=0.9) Twenty-three ON CIS patients who converted to CDMS during 10 years of follow-up demonstrated CP volume similar to RRMS patients, but significantly larger compared to healthy controls (p<0.001). Increased CP volume was identified even in a sub-group of patients without MS-like lesions at baseline (p<0.001). A significant (~6%) transient increase of CP volume was observed following a new bout of inflammation, which, however, returned to pre-inflammatory state few months later. CP volume was not associated with the severity of acute inflammation of the optic nerve or long-term optic nerve axonal loss, not with brain lesion load or severity of tissue damage within lesions. Interpretation: Our data demonstrate that enlarged CP can be observe very early in a disease, transiently reacts to acute inflammation, but not associated with the degree of tissue destruction.

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“…7 Most recently, CP enlargement in MS was associated with the expansion of chronic lesions and lesion severity measured with diffusion MRI 8 and with remyelination failure in periventricular areas quantified with 11 C-PiB-PET. 9…”

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Understanding the Role of the Choroid Plexus in Multiple Sclerosis as an MRI Biomarker of Disease Activity

et al. 2023

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The choroid plexus (CP) is an organoid structure located in the ventricles of the brain that produces CSF and serves as a port of entry for lymphocytes into the CNS. In multiple sclerosis (MS), the CP acts as an important modulator and target of inflammatory activity, as shown in postmortem studies.1-3 Recently, new evidence has emerged highlighting the importance of in vivo CP measurements for understanding MS pathogenesis. The first study, published in 2020, showed gadolinium enhancement in the CP of patients with MS who had recently experienced a clinical relapse.4 Subsequent work demonstrated that CP volume was larger in patients with RRMS than in healthy controls, particularly in those with radiologically active disease, in whom it also correlated with clinical relapses.5 Clinical relevance of the finding was suggested when it was shown that CP volume correlated with the expanded disability status scale (EDSS).6 CP volume also predicted future EDSS development over a follow-up of 4 years, more than conventional MRI markers, such as the number of T2 or gadolinium-enhancing lesions at baseline. The enlargement of the CP is MS-specific because it was not observed in patients with neuromyelitis optica spectrum disorder or migraine.7 Most recently, CP enlargement in MS was associated with the expansion of chronic lesions and lesion severity measured with diffusion MRI8 and with remyelination failure in periventricular areas quantified with 11C-PiB-PET.9

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Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy

Cited by 30 publications

References 60 publications

Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status

Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status

Choroid plexus volume is enlarged in clinically isolated syndrome patients with optic neuritis

Understanding the Role of the Choroid Plexus in Multiple Sclerosis as an MRI Biomarker of Disease Activity

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