Table 1.

Disease Characteristics that Distinguish MOGAD, MS, and NMOSD [2–6, 11–17]

	Patient Profile	Clinical Features	Serum autoantibody	Radiology	Long-term Treatment
MOGAD	Less race or sex predilection than MS or NMOSD	Recurrent or isolated attacks of ON, myelitis, ADEM, cerebral monofocal or multifocal deficits, brainstem or cerebellar deficits, cerebral cortical encephalitis often with seizures. Disability is driven by attacks without a progressive phase	Serum MOG-IgG targets the MOG protein located on the outermost myelin sheath layers and oligodendrocyte cell surface	MOGAD is often associated with large or longitudinally extensive lesions of the brain, spine, or optic nerve. Cranial lesions are sometimes called “fluffy” because the margins are poorly defined compared to the well circumscribed lesions seen in MS. Longitudinal intra-orbital optic nerve lesions are seen with T2, STIR, and gadolinium enhanced T1-weighted MRI, often with perineural enhancement. Myelitis cases demonstrate more frequent involvement of the lower cord (including the conus) than NMOSD and often involve the central gray matter causing the so-called “H-sign”. Cerebellar peduncle involvement is a helpful distinguishing feature of MOGAD. MOGAD MRI lesions tend to resolve over time	Off label immunotherapies for relapsing cases
MS	Mean age of onset is 32 years. More common in patients of white European descent with a female to male ratio of 3:1	ON, myelitis, brainstem syndromes, cerebellar dysfunction with relapsing and progressive components of disability accrual	There is no serum autoantibody	MS lesions are often hyper-intense on T2 and FLAIR MRI involving the periventricular, juxta-cortical, infra-tentorial and spine regions. Gadolinium enhancement indicates active disease. Relative to MOGAD and NMOSD, ON lesions tend to be shorter and unilateral, often affecting the intra-orbital optic nerve segments. Spinal lesions are also shorter and affect peripheral regions of the cord with nodular enhancement. The so-called “central vein” sign, a brain lesion characterized by a central area (dot or line) of hypo-intensity with T2 hyper-reflective white matter lesions (in 2 planes), is helpful in distinguishing MS cases from MOGAD	Approved MS disease modifying therapies
NMOSD	Mean age of onset is 40 years. More common in patients of Asian, Afro-Caribbean descent. Female-to-male ratio is 9:1 for AQP4-IgG seropositive cases	Recurrent ON, myelitis, area postrema syndrome, cerebral syndromes, narcolepsy and diencephalic syndromes, acute brainstem syndromes. Disability is driven by attacks without a progressive phase	AQP4-IgG binds to AQP4 on astrocytic foot processes	Brain MRI often shows normal findings or nonspecific white matter lesions. ON may manifest with a T2-hyperintense lesion or T1-weighted gadolinium-enhancing lesion extending over more than half the optic nerve length, involving the intracranial optic nerve segments and optic chiasm. Acute myelitis may be associated with LETM on MRI (lesions that extend over 3 contiguous segments) or 3 contiguous segments of focal spinal cord atrophy. Area postrema syndrome may show associated dorsal medulla/area postrema lesions. Acute brainstem syndromes may associate with peri-ependymal lesions	Relapses are common and long-term immunosuppression is required. Previously off label use of many agents was the mainstay of therapy, but targeted therapies approved for use in seropositive NMOSD include eculizumab, satralizumab, and inebilizumab

ON  optic neuritis, ADEM  acute disseminated encephalomyelitis, STIR short tau inversion recovery, MRI magnetic resonance imaging, FLAIR fluid-attenuated inversion recovery, LETM longitudinal extensive transverse myelitis