The expansion and severity of chronic MS lesions follows a periventricular gradient

Abstract

Background and Objectives: Expansion of chronic lesions in MS patients and recently described CSF-related gradient of tissue damage are linked to microglial activation. The aim of the current study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces. Methods: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 36 RRMS patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1-mm thick concentric rings radiating from the ventricles. Results: Voxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue distraction at baseline that significantly increased during follow-up in rings close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone. Discussion: Our data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.

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

“…Thus, for instance, it is feasible that soluble cytotoxic factors and/or inflammatory mediators produced by long-standing intrathecal inflammation (including choroid plexus, but also meningeal infiltrates and interstitial fluid 9 ) could diffuse from CSF into the periventricular white matter, forming /sustaining a permanent inflammatory environment in and around the ventricles, thereby driving slow-burning inflammation at the rim of chronic periventricular lesions. [39][40][41] This concept is supported by the recently described periventricular gradient of chronic lesion expansion, which demonstrated a decrease in a rate of chronic lesion enlargement as distance from the CSF (and plexus) increases 5 ; and by the observation reported in this study that the association between baseline plexus volume and lesion expansion is stronger in close proximity to the CSF. Notably, the periventricular gradient of lesion expansion is strikingly similar to the pattern of microstructural damage in the white matter described near the ventricles and in the most external cortical layers (i.e.…”

“…[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 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.…”

Choroid plexus volume predicts expansion of chronic lesions and brain atrophy

“…Thus, for instance, it is feasible that soluble cytotoxic factors and/or inflammatory mediators produced by longstanding intrathecal inflammation (including choroid plexus, but also meningeal infiltrates and interstitial fluid 9 ) could diffuse from CSF into the periventricular white matter, forming /sustaining a permanent inflammatory environment in and around the ventricles, thereby driving slow-burning inflammation at the rim of chronic periventricular lesions. 37 38 39 This concept is supported by the recently described periventricular gradient of chronic lesion expansion, which demonstrated a decrease in a rate of chronic lesion enlargement as distance from the CSF (and plexus) increases 5 ; and by the observation reported in this study that the association between baseline plexus volume and lesion expansion is stronger in close proximity to the CSF. Notably, the periventricular gradient of lesion expansion is strikingly similar to the pattern of microstructural damage in the white matter described near the ventricles and in the most external cortical layers (i.e.…”

“…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…”

“…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.…”