Asymptomatic optic nerve enhancement between optic neuritis (ON) attacks occurs predominantly at the site of previous lesions in 17% of patients with aquaporin-4 (AQP4) immunoglobulin G (IgG) neuromyelitis optica spectrum disorder (NMOSD), according to findings published in Neurology.

Researchers conducted a retrospective cohort study from 2009 to 2019 at Mayo Clinic to assess optic nerve enhancement incidence between optic neuritis (ON) attacks in 100 patients with AQP4-IgG positive NMOSD.

Patients underwent a total of 198 magnetic resonance imaging (MRI) scans with 107 scans performed between NMOSD attacks and 91 scans performed during attacks. Asymptomatic optic nerve enhancement presented in 18 of 107 (17%) MRI scans 30 days following an ON attack. After 60 days and 90 days following ON attacks, 16 of 107 (15%) and 13 of 107 (12%) cases of optic nerve enhancement remained, respectively.

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On 15 of the 18 MRI scans, optic nerve enhancement shortened the length of lesions at sites of previous optic neuritis attacks. Optic nerve enhancement in new asymptomatic lesions occurred in 2 patients and 1 patient experienced orbital pain without changes in visual acuity or fields until 15 days after enhancement was seen on MRI scan.

Since most locations of optic nerve enhancement occurred at sites of previous lesions, the researchers suggested that persistent or intermittent blood-brain barrier breakdown accounted for these findings, although they did not discount subclinical disease activity.

After analyzing potential confounding factors, the investigators discovered that younger age increased likelihood of asymptomatic optic nerve enhancement. They also found that administration rates of plasmapheresis and intravenous steroids did not significantly impact number of patients with enhancement scans.

“This study demonstrates that patients with AQP4-IgG positive NMOSD can have asymptomatic optic nerve enhancement on MRI,” the authors said. “This holds clinical and research related implications and prompts several questions regarding treatment efficacy as well as assessment of outcomes and adjudication of clinical ON attacks and subsequent treatment decisions in clinical trials.”


Shah S, Morris P, Buciuc M, et al. Frequency of asymptomatic optic nerve enhancement in a large retrospective cohort of patients with aquaporin-4+ NMOSD. Neurology. Published online June 13, 2022. doi:10.1212/WNL.0000000000200838