Susceptibility-Based Imaging Accurately Differentiates Pediatric-Onset MS From MOGAD

Recently published in the Multiple Sclerosis Journal, a multicenter study demonstrated that susceptibility-based imaging (SbI) has a high sensitivity and specificity to differentiate pediatric-onset multiple sclerosis (POMS) from pediatric myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). These findings also suggest that central vein sign (CVS) and paramagnetic rim lesions (PRLs) in SbI are highly specific markers for POMS which may be vital for early differentiation for treatment and disability prevention.¹

Using SbI, the CVS-positive rate distinguished 26 cases of POMS (mean age, 13.7 years; women, 63%; median Expanded Disability Status Scale [EDSS], 1.5) from 14 cases of MOGAD (mean age, 10.8 years; women, 35%; mean EDSS, 1.0). Among these 40 cases of participants, investigators observed a receiver operator curve (ROC) equaled 1 (P <.0001), with a cutoff of 41% perfectly separating both groups.

“This study shows that several biomarkers using SbI can be extremely helpful to discriminate between MS and MOG associated disease in children. This is important for several reasons: first, MOG associated disease in children represent 50% of all mog associated associated cases. Second, in children, MOG associated disease mimics MS quite often. Thus, at disease onset it is often difficult to tease out which disease is occurring as we have to wait several weeks to have results from mog IgG levels which helps with diagnosis in many cases but in some other cases are misleading (ie false positives and false negatives),” senior author Emmanuelle Waubant, MD, PhD, professor of neurology at University of California, San Francisco, told NeurologyLive®. "As it’s important to start disease modifying treatment early after disease onset in MS to prevent disability accumulation, a very early diagnosis is necessary. In addition, treatments used to prevent flares have different efficacy in MS and mog associated disease. Third, the study is telling us about the underlying pathophysiology of those two disorders. This may help design new treatment strategies."

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In the study, investigators acquired T2-FLAIR and SbI (3-dimensional echoplanar imaging [3D-EPI]/susceptibility-weighted imaging [SWI] or similar) on 1.5T/3T scanners. After 2 readers assessed CVS-positive rate, theiraverage score was then used to build a ROC to assess the ability to discriminate between pediatric POMS and pediatric MOGAD disease type. Using a consensual approach, the investigators identified PRLs and CCLs among the participants.

"It is the first study to evaluate 3 SbI markers at the same time in both cohorts of pediatric MS and MOGAD. Our findings suggest that the proportion of central vein sign is an excellent discriminant between ms and MOGAD as it has been reported another smaller study in children," Waubant told. "In addition, our study also reports that paramagnetic rim lesions are also good markers of MS, but not MOGAD. Thus, these sequences could be implemented for MRI scans done at disease onset when a demyelinating disease is suspected, as they could establish more reliably a diagnosis of MS versus MOGAD, owing to the presence of at least 41% central vein sign and paramagnetic rim lesions."

In the group of participants with POMS, PRLs were the only SbI-related signs detectable (mean 2.1 [±2.3], range 1-10), discriminating the 2 conditions with a sensitivity of 69% and a specificity of 100%. Notably, the investigators observed central core lesions (CCLs) were more sensitive (81%) but less specific (71.43%).

Limitations of the study included the small sample size, especially for the MOGAD group, and therefore researchers recommended larger cohort studies to confirm the findings. The authors also noted the POMS and MOGAD groups did not differ in features with using different SbI sequences with or without contrast administration and CVS-positive rate in both groups were similar on either SWI or 3D-EPI. Also, a significant proportion of participants with MOGAD did not show any brain lesions which limited the number of patients with MOGAD that could be included in the study. This also might represent a real-world challenge to apply CVS as an imaging biomarker in pediatric demyelinating diseases, the investigators noted.

"We found it surprising and very exciting that we could discriminate with so much confidence between MS and MOGAD. These findings could mean earlier accurate diagnosis and improved management for patients," Waubant told. "As always, the first order of business is to confirm those findings in children and adults. The next steps are also to look at specific myelin markers in both disorders to understand better pathophysiology differences and sort out if central vein sign and paramagnetic rim lesions can be measured over time to monitor treatment efficacy on MS course."

REFERENCES
1. Sacco S, Virupakshaiah A, Papinutto N, et al. Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease. Mult Scler. 2023;29(14):1736-1747. doi:10.1177/13524585231204414