Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease

Abstract

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and pediatric-onset multiple sclerosis (POMS) share clinical and magnetic resonance imaging (MRI) features but differ in prognosis and management. Early POMS diagnosis is essential to avoid disability accumulation. Central vein sign (CVS), paramagnetic rim lesions (PRLs), and central core lesions (CCLs) are susceptibility-based imaging (SbI)-related signs understudied in pediatric populations that may help discerning POMS from MOGAD.

Methods: T2-FLAIR and SbI (three-dimensional echoplanar imaging (3D-EPI)/susceptibility-weighted imaging (SWI) or similar) were acquired on 1.5T/3T scanners. Two readers assessed CVS-positive rate (%CVS+), and their average score was used to build a receiver operator curve (ROC) assessing the ability to discriminate disease type. PRLs and CCLs were identified using a consensual approach.

Results: The %CVS+ distinguished 26 POMS cases (mean age 13.7 years, 63% females, median EDSS 1.5) from 14 MOGAD cases (10.8 years, 35% females, EDSS 1.0) with ROC = 1, p < 0.0001, (cutoff 41%). PRLs were only detectable in POMS participants (mean 2.1±2.3, range 1-10), discriminating the two conditions with a sensitivity of 69% and a specificity of 100%. CCLs were more sensitive (81%) but less specific (71.43%).

Conclusion: The %CVS+ and PRLs are highly specific markers of POMS. After proper validation on larger multicenter cohorts, consideration should be given to including such imaging markers for diagnosing POMS at disease onset.

Keywords: 3D-EPI; CVS; MOGAD; POMS; PRLs; SWI.

Figure 1.

CVS assessment on 3D-EPI in a POMS subject. 3D-EPI in one of the POMS participants reveals positive central vessel signs in at least three of the four lesions included in this axial brain section (shown by arrows).

Figure 2.

CVS assessment on SWI. CVS assessment on SWI sequences was performed (a) after linear registration of the T2-FLAIR (b) in the SWI space. This post-processing allowed the (c) overlying of the two images for optimal detection of the central vein (arrows). (a), (b), and (c) are images of a POMS participant.

Figure 3.

PRL assessment on phase images from SWI and phase images from 3D-EPI. Phase images derived from (a) SWI and (b) 3D-EPI similarly reveal PRLs (arrows) in subcortical and periventricular white matter in two of the POMS participants.

Figure 4.

CCL in POMS and MOGAD. Phase images derived from 3D-EPI shows CCL (arrows) in a (a) POMS and (b) MOGAD participant.

Figure 5.

Chart representing the algorithm for participants’ selection. Here depicted is a flow chart for POMS and MOGAD participants’ selection. Seven out of 21 MOGAD participants initially identified were excluded for lack of brain lesions adequate for CVS assessment. Three out of these seven MOGAD participants excluded had a monophasic course of diseases, whereas the additional four participants had a multiphasic course of disease. Three out of the 29 POMS participants initially identified were excluded for lack of brain lesions adequate for CVS assessment, 2 had only extensive confluent WM lesions and 1 did not have brain lesions greater than 3 mm.

Figure 6.

CVS and PRL by disease group. (a) Boxplots for CVS+ rate (%CVS+) by disease type visually demonstrate distinction between MOGAD and POMS. (b) Scatterplot for both %CVS+ and PRLs presence by disease type show how the presence of PRLs may suggest a diagnosis of POMS even in POMS subjects with a %CVS+ rate close to the 41% threshold.

Figure 7.

Lack of CVS in MOGAD. None of the lesions (arrows) in these two 3D-EPI axial sections of the brain of a MOGAD participant show positive central vessel sign.