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Optic nerve enhancement can occur in some cases of NMOSD. This study analyzes its frequency, and what its consequences are for clinical trial design.

Neuromyelitis optica spectrum disorder (NMOSD) can involve a variety of symptoms related to the optic nerve. Asymptomatic or persistent optic nerve enhancement is rare in cases of aquaporin-4-immunoglobulin G-positive (AQP4-IgG+) NMOSD. Understanding cases of asymptomatic or persistent nerve enhancement in these cases can have important implications for understanding treatment efficacy in clinical trials and practice. This study, published in Neurology, provides a characterization of NMOSD interattack optic nerve enhancement. The study used a retrospective cohort design with data from 2000 to 2019.

All patients whose data was used had AQP4-IgG+ optic neuritis and were evaluated at Mayo Clinic. MRI orbits were reviewed by a neuroradiologist, neuro-ophthalmologist, and neuroimmunologist, and all were blinded to clinical history. Interattack optic nerve enhancement more than 30 days after attack was measured, and correlation between interattack enhancement and Snellen visual acuity at attack and follow-up were assessed. A total of 198 MRI scans from 100 patients were identified, with 107 interattack MRIs from 78 patients. Optic nerve enhancement was exhibited on 18 out of 107 interattack scans, with a median of 192.5 days from attack. On 15 of these scans, enhancement occurred at the attack site. 

Overall, asymptomatic nerve enhancement was found in 17% of patients with NMOSD, and most of these cases were at the site of prior optic nerve attacks. They may represent intermittent blood–brain barrier breakdown. New asymptomatic enhancement was found in only 2% of patients. The study demonstrated that MRI can reveal asymptomatic optic nerve enhancement in patients with AQP4-IgG+ NMOSD. This is most likely due to breakdown of the blood–brain barrier, though subclinical disease activity may also contribute.


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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