Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

What it is

MOG is a protein expressed on the outer surface of central nervous system oligodendrocytes — the same cells whose myelin sheaths are destroyed in MS and other demyelinating diseases. Antibodies against MOG were detected in some patients with MS for years, but it became clear in the mid-2010s that these patients differed clinically, on imaging and in outcome from typical MS or AQP4-positive NMOSD. The 2023 International MOGAD Panel formalised this as a distinct disease entity with diagnostic criteria.

Because MOG-IgG can also be detected at low titre in healthy controls and in some other diseases, accurate diagnosis requires a cell-based assay (CBA) against full-length human MOG — older fixed-cell ELISA assays have unacceptable false-positive rates and are no longer recommended.

How it presents

MOGAD has the broadest phenotype of any demyelinating disease. In children, the commonest presentations are:

• Acute disseminated encephalomyelitis (ADEM) — encephalopathy + multifocal CNS involvement, often after a viral illness; about 50% of paediatric ADEM is MOGAD
• ADEM-ON — ADEM followed by recurrent optic neuritis
• Recurrent or bilateral optic neuritis — severe, often with very poor initial vision but excellent recovery, and contrast-enhancement of one or both optic nerves
• Transverse myelitis — usually longitudinally extensive (>3 vertebral segments) but often with much better recovery than aquaporin-4-positive NMOSD
• Brainstem or cerebellar syndrome — ataxia, oculomotor disturbances
• Cortical encephalitis with seizures — unique to MOGAD: T2/FLAIR hyperintensity of one cerebral cortical region, with leptomeningeal enhancement, often presenting with focal seizures and headache
• In older adults: severe optic neuritis or transverse myelitis with a more relapsing course

Diagnosis

The 2023 MOGAD criteria require: (1) a typical clinical syndrome; (2) MOG-IgG positivity by cell-based assay at clearly positive titre (low-positive titres need supporting clinical-MRI features); (3) exclusion of better-fitting alternative diagnoses (notably MS, AQP4-NMOSD, ADEM not otherwise specified).

MRI features support diagnosis: large, fluffy, sometimes 'comet' or 'tumefactive' lesions with poorly defined edges; subcortical white matter and grey-white junction involvement; longitudinally extensive transverse myelitis (LETM) or short myelitis; conus involvement; bilateral or chiasmal optic nerve enhancement; reversibility of lesions on follow-up MRI.

CSF: often mild pleocytosis (median 20–60 cells); oligoclonal bands less common than in MS (about 10–20%).

Treatment

Acute attack:

• IV methylprednisolone 30 mg/kg/day (children, max 1 g/day) for 5 days, followed by a slow oral prednisolone taper over 3–6 months (this is unlike MS, where taper is short — long taper reduces early relapse risk in MOGAD)
• Plasma exchange or IVIG when steroid response is incomplete or contraindicated, particularly in severe optic neuritis or transverse myelitis
• MS disease-modifying treatments (interferons, glatiramer acetate, fingolimod, teriflunomide) are generally ineffective and should be avoided after confirmed MOGAD diagnosis

Maintenance treatment for relapsing MOGAD

About half of patients have a single attack and never relapse; the other half follow a relapsing course. For relapsing disease, maintenance immunotherapy reduces relapse risk:

• Rituximab — most evidence; observational studies show 50–80% reduction in relapse rate. Monthly serum B-cell monitoring guides re-dosing
• IVIG — increasingly first-line maintenance in children (monthly), with good tolerability and good evidence in paediatric MOGAD
• Mycophenolate mofetil — useful particularly in those intolerant to rituximab
• Azathioprine — alternative
• Long-term oral low-dose prednisolone — used in some centres, especially when other agents not available
• Several B-cell-targeted (e.g. inebilizumab) and complement-targeted (e.g. ravulizumab) treatments are in trials following positive AQP4-NMOSD results; full results expected 2025–2026

Prognosis

Outcomes in MOGAD are generally better than in either MS or AQP4-NMOSD — particularly in children, where visual and motor recovery from individual attacks tends to be very good. However, in patients with a relapsing course, persistent visual impairment, fatigue and cognitive symptoms can accumulate, and long-term immunotherapy is now standard.

How an educational review can help

MOGAD is a young diagnosis and the literature is changing rapidly. An educational review can confirm whether a child's presentation fits the 2023 criteria, place the MRI and laboratory findings in context, summarise the current evidence for maintenance treatment options, and help you prepare focused questions for your treating team — particularly the steroid taper plan and whether and when to start a maintenance immunotherapy.

It is an educational second opinion — not a diagnosis, treatment or prescription — and it does not replace the care of your child's own clinicians.