Longitudinal enlargement of choroid plexus is associated with chronic lesion expansion and neurodegeneration in RRMS patients

Abstract

Background and Objective: We explored dynamic changes in the choroid plexus (CP) in patients with relapsing-remitting multiple sclerosis (RRMS) and assessed its relationship with chronic lesion expansion and atrophy in various brain compartments. Methods: Fifty-seven RRMS patients were annually assessed for a minimum of 48 months with 3D FLAIR, pre- and post-contrast 3D T1 and diffusion-weighted magnetic resonance imaging (MRI). The CP was manually segmented at baseline and last follow-up. Results: The volume of CP significantly increased by 1.4% annually. However, the extent of CP enlargement varied considerably among individuals (ranging from −3.6 to 150.8 mm3 or −0.2% to 6.3%). The magnitude of CP enlargement significantly correlated with central ( r = 0.70, p < 0.001) and total brain atrophy ( r = −0.57, p < 0.001), white ( r = −0.61, p < 0.001) and deep grey matter atrophy ( r = −0.60, p < 0.001). Progressive CP enlargement was significantly associated with the volume and extent of chronic lesion expansion ( r = 0.60, p < 0.001), but not with the number or volume of new lesions. Conclusion: This study provides evidence of progressive CP enlargement in patients with RRMS. Our findings also demonstrate that enlargement of the CP volume is linked to the expansion of chronic lesions and neurodegeneration of periventricular white and grey matter in RRMS patients.

The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis

“…Although some studies provided evidence favoring an association between CP/TIV ratio and neurodegenerative changes, such as cortical thinning or deep GM atrophy in MS, other studies suggested that CP inflammation may not be the primary cause of neurodegeneration [19,33,39].…”

“…According to Klistorner and co-workers, normalized CPV was robustly associated with deep gray matter (GM) volume loss (as measured by ventricular enlargement) and only slightly with cortical or whole brain atrophy. Furthermore, the progressive plexus enlargement was associated with the volume of chronic lesion expansion, but not with the number or volume of new lesion load [31,33]. These associations imply that the CP could be involved in (the beginning or sustaining) the low-grade inflammatory process at the edges of chronic periventricular MS lesions [20,[33][34][35].…”

“…Furthermore, the progressive plexus enlargement was associated with the volume of chronic lesion expansion, but not with the number or volume of new lesion load [31,33]. These associations imply that the CP could be involved in (the beginning or sustaining) the low-grade inflammatory process at the edges of chronic periventricular MS lesions [20,[33][34][35]. The expansion of chronic MS lesions has been implied as one of the main forces that drive MS progression [36].…”

“…The expansion of chronic MS lesions has been implied as one of the main forces that drive MS progression [36]. Therefore, CP enlargement could contribute to the ongoing neurodegenerative component in longstanding MS [26,33,35]. Potential mechanisms of CP involvement in the neurodegenerative processes of MS are depicted in Figure 3.…”

“…number or volume of new lesion load [31,33]. These associations imply that the CP could be involved in (the beginning or sustaining) the low-grade inflammatory process at the edges of chronic periventricular MS lesions [20,[33][34][35].…”