Table 2.

Major red flags for false MOG-IgG positivity in patients with suspected CNS demyelinating syndromes.

Clinical features and disease course	- Progressive disease course, either from onset (primary progressive course) or after an initial period of relapsing disease activity (secondary progressive course). Consider MS, spinal cord sarcoidosis, metabolic, or genetic etiologies (e.g., B12 deficiency, adrenoleukodystrophy). - Hyperacute severe presentation (<12 h). Consider stroke/ischemic damage (e.g., spinal cord infarction, ischemic optic neuropathy). - Concomitant peripheral neuropathy. Can rarely be found in patients with MOGAD but its significance is unclear. Consider other causes of myeloneuropathy or encephalomyeloneuropathy (e.g., other autoimmune/paraneoplastic neurologic disorders, metabolic or genetic conditions).
CSF findings	- Oligoclonal bands or elevated IgG-Index. Consider MS or sarcoidosis.
MRI	- Brain abnormalities typical of MS: Ovoid periventricular lesions in the hemispheric white matter (perpendicularly oriented to the main ventricle axis), brainstem, or cerebellar hemispheres; linear or S-shaped juxtacortical lesions. Ring or open-ring enhancement. - Spinal cord abnormalities typical of MS: Multiple, short (<3 contiguous vertebral body segments) lesions peripherally located on axial images (commonly along the dorsal-lateral columns), often accompanied by focal atrophy. Ring or open-ring enhancement. - Lesion persistence, or development of new asymptomatic brain/spine lesions over time. Consider MS. - Central vein sign. Consider MS.
Serology	- Borderline or low MOG-IgG titer. These should be interpreted based on the clinical-MRI phenotype. Consider repeat testing, preferably with a more accurate assay (e.g., live vs. fixed CBA). Consider CSF testing when the diagnostic suspicion is high.* - Coexistence of neural autoantibodies other than MOG-IgG. In these patients the contribution of MOG-IgG to the neurological syndrome is generally poor and the clinical-MRI phenotype is mostly driven by the accompanying antibody.
Other	- Other clinical-MRI findings suggestive of alternative diagnosis (e.g., blood or microhemorrhages on MRI, positive screening for infections on serum and/or CSF).

CBA, cell-based assays; CSF, cerebrospinal fluid; MOGAD, myelin oligodendrocyte glycoprotein-IgG associated disease; MS, multiple sclerosis.

^*The validity of CSF-exclusive MOG-IgG positivity in conferring a diagnosis of MOGAD is still pending validation.