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Updated: Dec 2, 2025
Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007
Transient enlargement of brain ventricles during relapsing-remitting multiple sclerosis and experimental autoimmune
Jason M Millward1,2, Paula Ramos Delgado1, Alina Smorodchenko3
1Experimental Ultrahigh Field Magnetic Resonance, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Abstract:
The brain ventricles are part of the fluid compartments bridging the CNS with the periphery. Using MRI, we previously observed a pronounced increase in ventricle volume (VV) in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Here, we examined VV changes in EAE and MS patients in longitudinal studies with frequent serial MRI scans. EAE mice underwent serial MRI for up to 2 months, with gadolinium contrast as a proxy of inflammation, confirmed by histopathology. We performed a time-series analysis of clinical and MRI data from a prior clinical trial in which RRMS patients underwent monthly MRI scans over 1 year. VV increased dramatically during preonset EAE, resolving upon clinical remission. VV changes coincided with blood-brain barrier disruption and inflammation. VV was normal at the termination of the experiment, when mice were still symptomatic. The majority of relapsing-remitting MS (RRMS) patients showed dynamic VV fluctuations. Patients with contracting VV had lower disease severity and a shorter duration. These changes demonstrate that VV does not necessarily expand irreversibly in MS but, over short time scales, can expand and contract. Frequent monitoring of VV in patients will be essential to disentangle the disease-related processes driving short-term VV oscillations from persistent expansion resulting from atrophy.
Insights
Brain ventricle volume (VV) fluctuates dynamically in multiple sclerosis (MS) models and patients. Frequent MRI monitoring is crucial for understanding these short-term changes and their relation to disease progression.
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Brain ventricles are fluid compartments connecting the central nervous system (CNS) and periphery.
- Previous MRI studies showed increased ventricle volume (VV) in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS).
Purpose of the Study:
- To investigate dynamic changes in ventricle volume (VV) during the course of EAE in mice and in patients with relapsing-remitting MS (RRMS).
- To correlate VV fluctuations with disease activity, inflammation, and blood-brain barrier integrity.
Main Methods:
- Longitudinal serial MRI scans were performed on EAE mice for up to 2 months, with gadolinium contrast used to assess inflammation.
- Time-series analysis of monthly MRI data from RRMS patients over 1 year was conducted.
- Histopathology confirmed inflammation in EAE mice.
Main Results:
- In EAE mice, VV increased significantly before clinical onset and resolved with remission, coinciding with blood-brain barrier disruption.
- Despite symptom persistence, VV normalized in EAE mice by the study's end.
- Most RRMS patients exhibited dynamic VV fluctuations; contracting VV correlated with lower disease severity and shorter disease duration.
Conclusions:
- Ventricle volume (VV) changes in MS are not always irreversible and can exhibit short-term expansion and contraction.
- Frequent VV monitoring is essential to differentiate disease-related oscillations from permanent atrophy in MS.
- Understanding these dynamic VV changes may offer new insights into MS pathophysiology and progression.
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