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

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 9

Time-series analysis of ventricle volume changes in MS.

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Time-series analysis of ventricle volume changes in MS. (A) For each ind...
(A) For each individual patient with ventricle volume contractions > 6% (n = 24), we calculated the cross-correlation function (CCF) between the time series of ventricle volume (as the X variable) and the time series of the other 8 MRI and 4 clinical measures (as the Y variables). The CCF yielded 25 significant cross-correlation coefficients, within a time lag of ± 2 months, after FDR correction for multiple comparisons. The significant coefficients are depicted as lollipops in the 3D plot; color is scaled to the magnitude of the coefficient. Individual patients are arranged on the x axis; the MRI and clinical parameters are arranged on the y axis. The absolute values of the time lags are shown on the z axis, and size of the lollipop is scaled to the time lag (lag 0, largest). (B) Using the time series of CEL volume as the X variable and the other MRI and clinical parameters (including ventricle volume) as the Y variables, the CCF analysis yielded 23 significant cross-correlation coefficients after correction for multiple comparisons. Of these, 9 of 23 were correlations between CEL volume and CEL count at 0 time lags. (C) Repeating the analysis using the time series of performance in the 9-hole peg test as the X variable yielded 5 significant cross correlation coefficients after correction for multiple comparisons.