The incidence of novel asymptomatic, or silent, lesions during remission are uncommon in myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD) and appear to suggest a high risk for imminent relapse, according to findings published in JAMA Network Open.

Evaluating Novel Silent Lesions

For the retrospective cohort study, researchers evaluated the occurrence of, and characteristics associated with, novel silent lesions on MRI in MOGAD and AQP4-NMOSD. The study team reviewed the frequency of new silent lesions identified during either attack MRIs during the acute clinical event or remission MRIs, those captured outside of a relapse and at least 3 months since the last attack. They also examined the median time to next relapse in the presence of definite (reference MRI performed at least 4 weeks from last attack onset), probable (reference MRI performed during last attack), and no new silent lesions captured during remission MRIs.

The study team examined clinical and MRI data from 404 patients (75% women), including 182 with MOGAD and 222 with AQP4-NMOSD, between February 1, 1994 and April 1, 2021. Patients with MOGAD were followed for a median of 52 months (range, 11-253 months) and patients with AQP4-NMOSD were followed for a median of 87.5 months (range, 11-260 months). Patients with MOGAD were younger than those with AQP4-NMOSD at the time of disease onset (28 vs 43 years).

Silent Lesions on Attack MRIs Vs Remission MRIs

In total, patients with MOGAD had 296 attack MRIs and 167 remission MRIs. The researchers detected novel attack silent lesions on 33% of attack MRIs and new remission silent lesions on 3.0% of remission MRIs. Median time between remission scan and next relapse in light of definite or probable new remission lesions was 2 months (interquartile [IQR] range, 1-6 months), compared with 73 months (IQR, 20-104 months) with no new remission lesions detected (HR, 23.86; 95% CI, 7.51-75.79).

Among patients with AQP4-NMOSD, the study team conducted 470 attack MRIs and 269 remission MRIs. New attack silent lesions were found during 18.7% of attack MRIs, and new remission silent lesions were detected in 2.6% of remission MRIs. For these patients, median time from remission scan to subsequent relapse in the setting of definite or probable new remission lesions was 5 months (IQR, 2-6 months), compared with 85 months (IQR, 29-167 months) with no new remission lesions (HR, 21.23; 95% CI, 8.05-53.65).

Many Silent Lesions Later Become Symptomatic

The investigators noted that new lesions detected during remission MRIs seemed to precede impending relapses in both cohorts, but their location determined the ensuing relapse symptoms more often in patients with AQP4-NMOSD than in those with MOGAD, a finding that they suggest indicates that many silent lesions later became symptomatic.

Because new remission silent lesions are rare, according to the investigators, long-term regular monitoring of lesion load by brain and spinal cord MRI may not be effective in clinical practice or as a surrogate biomarker of disease activity in clinical trials for MOGAD and AQP4-NMOSD. However, in MOGAD compared with MS, they also noted that consecutive follow-up scans to identify new silent lesions may be a valuable diagnostic tool to differentiate MS from MOGAD in patients with low MOG antibody titers, especially within the first year of disease onset.