What is the diagnostic and treatment approach for Multiple Sclerosis (MS) vs Neuromyelitis Optica Spectrum Disorder (NMOSD) vs Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)?

Diagnostic and Treatment Approach for MS vs NMOSD vs MOGAD

Accurate antibody testing is essential for differentiating MS, NMOSD, and MOGAD as these conditions require distinct treatment approaches, with inappropriate therapy potentially worsening outcomes and promoting disability. 1

Diagnostic Approach

Clinical and Laboratory Features

Multiple Sclerosis (MS)

• Clinical presentation: Typically relapsing-remitting course with dissemination in space and time
• CSF findings:
  • Oligoclonal bands present in up to 98% of patients in Central/Northern Europe 2
  • Positive OCBs in 84-98% of cases (may be lower in Asian populations: 40-80%) 2
  • Rarely shows neutrophilic pleocytosis (≤2% of cases) 2

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• Clinical presentation: Optic neuritis, myelitis, area postrema syndrome, brainstem syndromes 2
• Laboratory findings:
  • AQP4-IgG antibody positive (primary biomarker)
  • Frequent neutrophilic pleocytosis 2
  • Higher rates of elevated serum ANA (66.7%) and ENA (42.9%) 3

MOGAD (MOG Antibody-Associated Disease)

• Clinical presentation:
  • Predominantly monofocal attacks (91%), typically optic neuritis (>70%) 3
  • May present as ADEM-like syndrome, especially in children 2
  • Symptoms often flare after tapering oral steroids 2
• Laboratory findings:
  • MOG-IgG antibody positive (using cell-based assays) 4
  • OCBs present in only 12-13% of cases 2
  • Lymphomonocytic pleocytosis with neutrophils (in 43% of cases) 2
  • Lower rates of elevated serum ANA (21.7%) and ENA (5.0%) 3

MRI Characteristics

MS

• Brain MRI:
  • Periventricular, juxtacortical, infratentorial lesions
  • Dawson's finger-type lesions (present in 98.6% of MS cases) 2
  • Juxtacortical U-fiber lesions
  • Ovoid lesions adjacent to lateral ventricles 2

NMOSD

• Brain MRI:
  • Up to 70% have brain lesions at onset 2
  • Peri-ependymal lesions around third ventricle and cerebral aqueduct
  • Dorsal medulla/area postrema lesions 2
• Spinal MRI:
  • Longitudinally extensive transverse myelitis (LETM) extending ≥3 segments 2

MOGAD

• Brain MRI:
  • May have normal supratentorial MRI 4
  • ADEM-like presentation with large white matter lesions 2
  • Absence of Dawson's finger lesions (98.6% of cases) 2
  • Absence of U-fiber lesions (94.2% of cases) 2
• Spinal MRI:
  • May show both short and longitudinally extensive lesions 2
• Optic nerve:
  • Often bilateral involvement 2
  • May involve optic chiasm 2

Treatment Approach

Multiple Sclerosis

• Acute attacks: High-dose corticosteroids
• Disease-modifying therapies:
  • First-line: Interferon-beta, glatiramer acetate, dimethyl fumarate, teriflunomide
  • Second-line: Natalizumab, fingolimod, ocrelizumab, alemtuzumab

NMOSD

• Acute attacks:
  • High-dose IV methylprednisolone
  • Plasma exchange for severe attacks or inadequate steroid response 5
• Maintenance therapy:
  • Rituximab
  • Eculizumab
  • Satralizumab
  • Inebilizumab
  • Traditional immunosuppressants: Azathioprine, mycophenolate mofetil 5
• Important: MS therapies like interferon-beta and natalizumab may worsen NMOSD 4

MOGAD

• Acute attacks:
  • High-dose IV methylprednisolone followed by slow oral steroid taper 4
  • Plasma exchange or IVIG for severe attacks or inadequate steroid response 4
• Maintenance therapy:
  • IVIG (1-2 g/kg ideal body weight, usually given over 2 consecutive days monthly) 4
  • Consider rituximab, mycophenolate mofetil, or azathioprine for relapsing disease 4
• Important:
  • High risk of flare-ups after steroid cessation - slow tapering critical 4
  • Avoid MS-specific treatments like interferon-beta or natalizumab 4
  • Despite anti-CD20 therapy (rituximab), 28.6% of MOGAD patients may continue to have relapses 3

Clinical Pearls and Pitfalls

Diagnostic Pitfalls

• Some patients diagnosed with "pattern II MS" lesions may actually have MOGAD 2
• MOG-IgG serum concentrations depend on disease activity and treatment status 4
• If initially negative but MOGAD is still suspected, consider retesting during:
  • Acute attacks
  • Treatment-free intervals
  • 1-3 months after plasma exchange or IVIG 4

Treatment Considerations

• MOGAD: Do not discontinue maintenance therapy too early, as relapses can occur even after prolonged periods of stability 4
• NMOSD and MOGAD: Consider that some patients may have co-existing autoantibodies (e.g., NMDAR antibodies) that might require additional treatment considerations 2, 4
• MOGAD: Check serum IgA level before administering IVIG to prevent severe reactions in patients with IgA deficiency 4

Monitoring

• Monitor response to therapy through:
  • Improvement in neurological symptoms
  • Assessment for adverse reactions
  • Clinical reassessment after 3-4 months of therapy 4
• Some MOGAD patients may convert to antibody-negative status, with no attacks occurring after conversion 3