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Transient enlargement of brain ventricles during relapsing-remitting multiple sclerosis and experimental autoimmune encephalomyelitis
Jason M. Millward, … , Thoralf Niendorf, Sonia Waiczies
Jason M. Millward, … , Thoralf Niendorf, Sonia Waiczies
Published November 5, 2020
Citation Information: JCI Insight. 2020;5(21):e140040. https://doi.org/10.1172/jci.insight.140040.
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Research Article Inflammation

Transient enlargement of brain ventricles during relapsing-remitting multiple sclerosis and experimental autoimmune encephalomyelitis

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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.

Authors

Jason M. Millward, Paula Ramos Delgado, Alina Smorodchenko, Laura Boehmert, Joao Periquito, Henning M. Reimann, Christian Prinz, Antje Els, Michael Scheel, Judith Bellmann-Strobl, Helmar Waiczies, Jens Wuerfel, Carmen Infante-Duarte, Claudia Chien, Joseph Kuchling, Andreas Pohlmann, Frauke Zipp, Friedemann Paul, Thoralf Niendorf, Sonia Waiczies

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Figure 6

Relapsing-remitting MS patients show dynamic changes in ventricle volumes.

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Relapsing-remitting MS patients show dynamic changes in ventricle volume...
(A) Over the course of 1 year, the cohort of MS patients showed a small but significant increase in ventricle volume of +284 mm, equivalent to +0.08406% (median ± IQR, P = 0.0006, Wilcoxon signed rank test, n = 33). (B and C) Plotting the values for individual patients showed a heterogeneous picture, with some individuals showing high variability in ventricle volume (B) and others showing lower variability (C). (D) A reference cohort of healthy subjects showed no significant changes over the course of a 6-month observation period (n = 6). (E) The maximum change in ventricle volume of the healthy subjects was ± 6%. (F) The MS patient cohort showed significantly greater variability in ventricle volumes (as indicated by the coefficient of variation) compared with healthy controls (**P = 0.0065, Student’s t test).

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ISSN 2379-3708

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