Pathophysiology of the choroid plexus in brain diseases

Parratt

et al. 2022

Ann Clin Transl Neurol

Objectives Recent studies suggested that the expansion of long‐standing multiple sclerosis (MS) lesions and an enlargement of choroid plexus may be linked to chronic inflammation and microglial activation. We investigated the potential association between plexus volume and subsequent lesion expansion in patients with relapsing‐remitting MS. Methods Pre‐ and post‐gadolinium 3D‐T1, 3D FLAIR and diffusion tensor images were acquired from 49 patients. Choroid plexus (CP) volume (normalised by Total Intracranial Volume, TIV) and lesion activity were analysed between baseline and 48 months. In addition, plexus volume was measured in 40 healthy controls of similar age and gender. Results Baseline CP/TIV ratio was significantly larger in RRMS patients compared to normal controls (p < 0.001). CP/TIV ratio remained stable in RRMS patients during follow‐up period. There was a strong correlation between baseline CP/TIV ratio and subsequent rate of chronic lesion expansion (p < 0.001), which was stronger in close proximity to CSF. A cut‐off of 98 × 10−5 CP/TIV ratio predicted future lesion expansion with a sensitivity of 85% and specificity of 76%. CP/TIV ratio larger than a cut‐off was associated with >8‐fold increased risk of chronic lesion expansion. Baseline CP/TIV ratio was also associated with change in Mean Diffusivity (MD) inside of chronic lesions. Furthermore, baseline CP/TIV ratio significantly correlated with central brain atrophy. There was, however, no correlation between CP/TIV ratio and volume of new lesions. Interpretation Our data demonstrate that baseline CP/TIV ratio predicts subsequent expansion of chronic periventricular MS lesions and associated tissue damage within and outside of chronic lesions.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Parratt

et al. 2022

Ann Clin Transl Neurol

“…1,2,3,4 We recently demonstrated that lesion expansion is most noticeable in close proximity to ventricles, suggesting a link between slow burning inflammation and cerebrospinal fluid (CSF). 5 It is well established that the choroid plexus, located within the ventricular system of the central nervous system (CNS), plays an important role in the implementation of the immune response within the CNS 6 . The plexus is essential for the production of cerebrospinal fluid (CSF) 7 , but also responsible for regulating entry of immune cells and specific molecules to the brain parenchyma, providing a gateway for antigen trafficking between the CSF and the vascular circulation.…”

Section: Introductionmentioning

confidence: 99%

Choroid plexus volume predicts expansion of chronic lesions and brain atrophy

klistorner

et al. 2022

Preprint

Background and Objectives: The expansion of long-standing multiple sclerosis (MS) lesions and an enlargement of choroid plexus are linked to chronic inflammation and microglial activation. In the current study, we investigated the association between plexus volume and subsequent lesion expansion in patients with relapsing remitting MS. Methods: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 49 patients with relapsing-remitting MS. Choroid plexus volume and lesion activity were analysed between baseline and 48 months. Results: Plexus volume remained stable during follow-up period. There was a strong correlation between baseline plexus volume and subsequent rate of chronic lesion expansion (r=0.77, p<0.001), which was stronger in close proximity to CSF. Furthermore, baseline plexus volume was also associated with change of Mean Diffusivity (MD) inside expanding area (r=0.55, p<0.001). There was, however, no correlation between baseline plexus volume and volume of new lesions. A cut-off of 98 x 10-5 plexus/TIV ratio predicted future lesion expansion with a sensitivity of 85% and specificity of 76%. Plexus volume larger than a cut-off was associated with >8-fold increased risk of chronic lesion expansion. Furthermore, baseline plexus volume significantly correlated with change of MD in lesional core during the study period (r=0.67, p<0.001) and with central brain atrophy (r=0.57, p<0.001). Conclusion. Our data demonstrate that baseline plexus volume predicts subsequent expansion of chronic periventricular MS lesions and associated tissue damage.

“…The choroid plexus (CP), located within the brain's ventricular system, plays an important role in the implementation of the immune response within the central nervous system (CNS) (Mihaljevic et al 2021). The CP is essential for the production of cerebrospinal fluid (CSF) (Hofman and Chen 2016); and critically determines brain homeostasis by regulating the entry of immune cells and specific molecules into the brain parenchyma.…”

Section: Introductionmentioning

confidence: 99%

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

Walt

et al. 2022

Preprint

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.