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Asymptomatic nerve enhancement in patients with NMOSD can make assessing clinical trial results more complicated. This article analyzes how commonly this type of enhancement occurs, and what effects that may have.

Nerve enhancement in cases of aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) is not common, but does occur in some patients. A better understanding of this unique circumstance, including how often it occurs, what is involved in such cases, and how they respond to treatment, can affect the assessment of efficacy in both clinical trials and clinical practice. The goal of this retrospective cohort study, published in Neurology, was to describe NMOSD interattack optic nerve enhancement. The study used data from between 2000 and 2019. 

The median follow-up period was 5.5 years, and all patients included had AQP4-IgG-positive optic neuritis. All patients were evaluated at the Mayo Clinic, and had MRI orbits reviewed by neuroradiologists, neuro-ophthalmologists, and neuroimmunologists who were blinded to the relevant clinical history. The researchers measured interattack optic nerve enhancement, and then assessed the relationship between interattack enhancement and Snellen visual acuity, converted to the logarithm of the minimum angle of resolution. These measures were assessed at both follow-up and attack times. A total of 198 MRI scans in 100 patients were assessed, including 107 interattack MRIs from 78 patients.

The authors found that optic nerve enhancement was present in 18 out of 107 interattack scans. Fifteen scans showed enhancement at the site of prior attacks, where the lesion location was the same, but the lesion length was shorter. Only two scans showed new asymptomatic lesions. There was no difference found in visual acuity at preceding attack nadir, as well as no difference in visual acuity between those with and without interattack optic nerve enhancement. The authors conclude by noting that asymptomatic nerve enhancement occurred in 17% of patients with NMOSD, of which the majority occurred at the site of prior attacks. They suggest that clinical trials for NMOSD require blinded relapse adjudication when assessing treatment efficacy.


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Shah, S. S., Morris, P., Buciuc, M., Tajfirouz, D., Wingerchuk, D. M., Weinshenker, B. G., Eggenberger, E. R., Di Nome, M., Pittock, S. J., Flanagan, E. P., Bhatti, M. T., & Chen, J. J. (2022). Frequency of Asymptomatic Optic Nerve Enhancement in a Large Retrospective Cohort of Patients With Aquaporin-4+ NMOSD. Neurology, 99(8), e851-e857. https://doi.org/10.1212/wnl.0000000000200838