International Panel of Experts Proposes New Diagnostic Criteria for MOG Antibody Associated Disease

Brenda Banwell, MD

Published in The Lancet Neurology, a convened panel of pediatric and adult neurologists, neuroimmunologists, and researchers have proposed a new diagnostic criteria for myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) that includes the presence of MOG-IgG as a core criterion.¹

Although the availability of cell-based assays to detect serum antibodies has expanded in recent years, there have been several patients who have been previously classified as having aquaporin-4 (AQP4)-seronegative neuromyelitis optica spectrum disorder (NMOSD). While the diseases may present similarly, patients with MOGAD can have either a monophasic or relapsing course, contrary to those with multiple sclerosis (MS) or AQP4-IgG-seronegative NMOSD.

Lead author Brenda Banwell, MD, chief of neurology and codirector of the neuroscience Center at the Children’s Hospital of Philadelphia, and others, reviewed the clinical features of reported cohorts of patients with central nervous system (CNS) demyelination and serological evidence of MOG-IgG. The proposed criteria, which the authors noted will require validation, may have the potential to improve identification of individuals with MOGAD, thus improving the definition of long-term clinical outcomes, refining inclusion criteria for clinical trials, and identifying predictors of a relapsing vs monophasic disease course.

Amongst clinical features for patients with MOG-IgG, optic neuritis is the most common onset feature, particularly among adults, along with transverse myelitis, and other less common presentations. Unlike MS or AQP4-seropositive NMOSD, sex or racial predominance has not been found in MOGAD. Patients who experience optic neuritis can also have central acuity loss, retro-orbital pain, color vision loss, and an afferent pupillary defect.

Previous research on patients with optic neuritis and serum MOG-IgG has indicated that optic disc swelling is common, occurring between 45% and 95% of patients.² "Tools that quantify visual impairment would be valuable in MOGAD, given the predilection for the optic nerve," Banwell et al wrote. "The opticospinal impairment scale might prove useful in this regard. Prospective longitudinal OCT studies might further inform our understanding of the effect of MOGAD on the optic pathway and differences between MOGAD, multiple sclerosis, and AQP4-IgG-seropositive NMOSD."

Other differences from MS, AQP4-IgG-seropositive NMOSD, and serum MOG-IgG include the clinical and imaging features of transverse myelitis. For those with demyelination and serological evidence of MOG-IgG, transverse myelitis can occur in isolation, as a component of ADEM, or concurrent with optic neuritis. Most patients with transverse myelitis associated with MOG-IgG have T2-hyperintense lesions on spinal MRI, are typically located on axial imaging, and can be restricted to the grey matter, producing the H-sign. Notably, research has shown that between 20% to 25% of spinal cord lesions in patients with MOG-IgG do not involve spinal gray matter.³

In terms of laboratory examinations, the investigators noted that serum is the preferred specimen type for MOG-IgG testing, as well as strongly endorsed serum testing using cell-based assays that use full-length human MOG. Additionally, the panel recommended clinicians include qualitative results that show negative, low positive, and clear positive findings, and semiquantitative results that highlight titers, flow cytometry ratio, or visual scores. The reason for an emphasis on clear positivity vs low positivity was influenced by evidence that higher titers are more reproducible than lower titers.⁴

READ MORE: Argentinean-Based Study Highlights International Barriers to Access and Utilization of NMOSD Care

Fundamental to the principles of MOG-IgG testing is the patient selection, Banwell et al noted, or understanding the most positive predictive value (PPV) of a patient for the disease. This type of testing was not recommended to screen all patients with central nervous system demyelination, and caution was advised when interpreting positive serum or cerebrospinal fluid (CSF) MOG-IgG results in patients who demonstrate clinical or radiological features atypical for MOGAD.

The investigators detailed a few caveats to MOG-IgG testing. MOG-IgG may be common in children with optic neuritis or acute disseminated encephalomyelitis, and thus screening these groups was recommended. In contrast, the frequency of MOG-IgG in adults with clinical, radiological, and CSF findings diagnostic of MS is low, and thus screening these individuals may yield a high false-positive rate and is not recommended.⁵

Although there is a substantially higher frequency of MOG-IgG in adults with optic neuritis with severe optic disc edema than those with retrobulbar optic neuritis, limiting preselection to this group would exclude almost half of the patients with optic neuritis who have MOG-IgG. Testing for MOG-IgG in patients with optic neuritis who also have longitudinally extensive optic nerve lesions, bilateral simultaneous optic nerve involvement, or perineuritic optic neuritis lesions on MRI will increase diagnostic yield without sacrificing PPV," the authors wrote.

REFERENCES
1. Banwell B, Bennett JL, Marignier R, et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed critieria. Lancet Neurol. Published online January 24, 2023. doi:10.1016/S1474-4422(22)00431-8.
2. Chen JJ, Flanagan EP, Jitprapaikulsan J, et al. Myelin oligodendrocyte glycoprotein antibody-positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Opthalmol. 2018;195:8-15.
3. Mariano R, Messina S, Kumar K, et al. Comparison of clinical outcomes of transverse myelitis among adults with myelin oligodendrocyte glycoprotein antibody vs aquaporin-4 antibody disease. JAMA New Open. 2019(2):e1912732
4. Reindl M, Schanda K, Woodhall M, et al. International multi center examination of MOG antibody assays. Neurol Neuroimmunol Neuroinflam. 2020;7(2):e674. doi:10.1212/NXI.0000000000000674
5. Sechi E, Buciuc M, Pittock SJ, et al. Positive predictive value of myelin oligodendrocyte glycoprotein autoantibody testing. JAMA Neurol. 2021;78(6):741-746. Doi:10.1001/jamaneurol.2021.0912.