Dynamics of choroid plexus volume is associated with the presence and development of fatigue in multiple sclerosis, 2024, Rubin et al.

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Dynamics of choroid plexus volume is associated with the presence and development of fatigue in multiple sclerosis
Martina Rubin; Paolo Preziosa; Monica Margoni; Alessandro Meani; Elisabetta Pagani; Gianluca Corazzolla; Loredana Storelli; Damiano Mistri; Massimo Filippi; Maria A Rocca

BACKGROUND
Immune-mediated processes are implicated in the pathogenesis of fatigue, a common symptom in multiple sclerosis (MS). The choroid plexus (CP) regulates central nervous system (CNS) immune homeostasis and undergoes volumetric modifications possibly contributing to MS-related fatigue. We explored the association between MS-related CP volume changes and fatigue dynamics.

METHODS
Eighty-five patients with MS and 68 healthy controls (HC) underwent brain 3T MRI, neurological evaluation and Modified Fatigue

IMPACT
Scale (MFIS) at two timepoints (median follow-up=1.4 years). Normalised brain and regional grey matter (GM) volumes were obtained using FSL-SIENAx, FIRST, SIENA and tensor-based morphometry. CP volumes were quantified with in-house methods, and longitudinal changes were analysed using linear mixed models.

RESULTS
At baseline, 25 (29%) patients with MS had fatigue (f-MS) (MFIS ≥38). Compared with HC, patients with MS had significantly higher brain T2-lesion volume, lower brain, deep GM, cortical volumes and higher CP volume (false discovery rate (FDR)-p ≤0.024). Compared with non-fatigued (nf-MS) patients, f-MS were older, more disabled (FDR-p ≤0.002) and showed numerically higher CP volume (FDR-p=0.076). At follow-up, 41 (68%) nf-MS remained non-fatigued (nf-FU-MS) and 19 (32%) developed fatigue (f-FU-MS).

Patients with MS showed higher brain and deep GM atrophy rates versus HC (FDR-p ≤0.048), whereas clinical, lesional and brain volumetric changes were not significantly different among MS groups (FDR-p ≥0.287). CP volume significantly increased in all MS groups compared with HC (FDR-p ≤0.043), with greater enlargement in f-FU-MS versus nf-FU-MS (FDR-p=0.048).

CONCLUSIONS
Larger CP and greater enlargement are associated with the presence and development of fatigue in MS, likely reflecting dynamic inflammatory states within the CNS, supporting the immunological contribution to MS-related fatigue.


Link | PDF (Journal of Neurology, Neurosurgery & Psychiatry)

 

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WHAT IS ALREADY KNOWN ON THIS TOPIC

⇒ Fatigue is a highly prevalent symptom in patients with multiple sclerosis (MS). Although fatigue has always been linked to structural and functional brain abnormalities in corticosubcortical circuits, the role of a dynamic proinflammatory state within the central nervous system (CNS) has been recently recognised.

⇒ The choroid plexus (CP) forms an interface between systemic immune system and CNS, acting as an immune reservoir and regulating the trafficking between peripheral circulation and cerebrospinal fluid.

⇒ Recent cross-sectional MRI studies have shown a significant CP enlargement in patients with MS already from the early stages of the disease, correlating with MRI markers of chronic-active inflammation, while longitudinal studies on the topic have provided conflicting results.

WHAT THIS STUDY ADDS

⇒ In this study, we showed a trend of association between fatigue presence and larger CP volume in patients with MS in a cross-sectional setting. ⇒ Longitudinally, we investigated whether patients with MS who developed fatigue during follow-up showed significant CP enlargement compared with both healthy controls (HC) and patients with MS who did not develop fatigue. We demonstrated a significant CP volume increase in all MS groups compared with HC, with a greater enlargement in patients developing fatigue.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

⇒ Our study may provide further insight into the dynamism of immunological processes possibly contributing to the development of fatigue in patients with MS, as reflected by the cross-sectional and longitudinal volume changes of the CP.