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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 4

Modest neurodegeneration detected by Fluoro-Jade staining during early EAE.

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Modest neurodegeneration detected by Fluoro-Jade staining during early E...
(A and C) No evidence of Fluoro-Jade+ staining was seen in brain tissue sections from unimmunized control mice; representative images of cerebellum (A) and brainstem (C). (B and D) Fluoro-Jade+ foci (indicated with arrows) were observed in cerebellum (B) and brainstem (D) of mice at day 11 p.i. (Fluoro-Jade, green; DAPI, blue). The Fluoro-Jade+ foci consistently accompanied inflammatory foci (B and D). (E) Quantification of fluorescence intensity of the tissue section showed an increasing accumulation of Fluoro-Jade staining by day 11 p.i. (arbitrary units) (n = 15).

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