MOGAD Clinical Guidelines

Disease Pathophysiology

MOGAD is caused by pathogenic antibodies targeting full-length MOG protein, a molecule located on the outer membrane of myelin sheaths in the brain, spinal cord, and optic nerves, demonstrating a direct pathogenic impact of MOG-IgG antibodies through immunological mechanisms 1, 2
The disease demonstrates discrete histopathological features with primary demyelination showing intralesional complement and IgG deposits, distinct from MS pathology 3, 2
MOGAD is characterized by the near-complete absence of aquaporin-4 (AQP4) antibodies, distinguishing it from neuromyelitis optica spectrum disorders 1, 2

Optic neuritis in MOGAD can present with severe visual deficit or blindness during or after acute episodes, often with bilateral involvement and prominent papilledema, papillitis, or optic disc swelling on fundoscopy 3, 4
Transverse myelitis in MOGAD is characterized by longitudinally extensive transverse myelitis (LETM) affecting ≥3 vertebral segments, with conus medullaris lesions being particularly characteristic, and may result in permanent sphincter and/or erectile disorders 5, 4
Acute disseminated encephalomyelitis (ADEM) in MOGAD presents with large, confluent T2 brain lesions, disturbance of consciousness, behavioral changes, or epileptic seizures, and can manifest as "recurrent ADEM," "multiphasic ADEM," or "ADEM-ON" (ADEM with recurrent optic neuritis) 3, 5, 4

Adults with MOGAD typically experience a relapsing course in at least 80% of cases, while children more commonly have monophasic disease, particularly with ADEM presentations 2
A significant proportion of adult patients with MOGAD meet McDonald's criteria for MS at some point during their disease course, leading to frequent historical misdiagnosis 2
There is a high risk of flare-ups after steroid cessation in MOGAD, requiring careful monitoring and slow tapering 1, 6

MOGAD is significantly more frequent in young children compared to adults, with frequency declining with age 5, 4

Cerebrospinal fluid analysis in MOGAD often shows neutrophilic CSF pleocytosis or white cell count >50/μl, and the absence of CSF-restricted oligoclonal bands 4, 5
Antibody testing for MOGAD requires cell-based assays (CBA) using full-length human MOG, with serum being the specimen of choice, and MOG-IgG titers being disease-activity dependent 2, 6

Progressive disease course is very atypical for MOGAD and should prompt consideration of alternative diagnoses, with phenotypic overlap with MS occurring in 33% of cases meeting McDonald's criteria 2, 1
Post-vaccination onset of MOGAD can occur 4 days to 4 weeks after vaccination, and co-existence with teratoma or NMDAR encephalitis is possible but rare 5, 4

High-dose intravenous methylprednisolone is first-line for acute attacks in MOGAD, with plasma exchange or immunoadsorption initiated early if steroids fail, and slow steroid taper being mandatory due to high risk of flare-ups after rapid cessation 6
Preventive therapy in MOGAD is reserved for relapsing disease only, with rituximab, IVIG, and oral immunosuppressants showing observational benefit, and beta-interferons, natalizumab, and fingolimod being contraindicated due to differences in immunopathogenesis 6, 1, 2

MOGAD has a more favorable prognosis than neuromyelitis optica spectrum disorder, with lower disability scores at follow-up even with brainstem involvement, and brainstem involvement in the first event does not indicate worse prognosis in MOGAD 6