What is the treatment approach for a patient with low neurofilament light chain (NfL), high myelin oligodendrocyte glycoprotein (MOG) glial fibrillary acidic protein (GFAP), and elevated tumor necrosis factor superfamily member 13B (TNFSF13B), C-type lectin domain-containing protein 1 (CDCP1), and interleukin 12B (IL-12B) levels, indicating high cytokine activity?

Treatment Approach for MOG Antibody-Associated Disease with Low NfL and High Cytokine Activity

For a patient with low neurofilament light chain (NfL), high myelin oligodendrocyte glycoprotein (MOG) glial fibrillary acidic protein (GFAP), and elevated cytokine activity (TNFSF13B, CDCP1, IL-12B), high-dose intravenous methylprednisolone (1000 mg daily for 3-5 days) followed by a slow oral prednisone taper over 2-3 months is the recommended first-line treatment. 1

Diagnostic Interpretation

• The biomarker profile with low NfL suggests limited neuronal damage despite active inflammation, which is characteristic of MOG antibody-associated disease (MOGAD) 2, 3
• High MOG-GFAP levels indicate active inflammatory demyelination with astrocytic involvement 4
• Elevated cytokines (TNFSF13B, CDCP1, IL-12B) reflect high inflammatory activity, supporting the diagnosis of an active MOGAD episode 5
• The sGFAP/sNfL ratio has demonstrated utility in discriminating MOGAD from other autoimmune demyelinating diseases 4

Treatment Algorithm

Acute Treatment Phase:

1. Immediate intervention with high-dose corticosteroids:

   • Administer intravenous methylprednisolone 1000 mg daily for 3-5 days 6, 1
   • Follow with oral prednisone starting at 1 mg/kg/day with slow taper over 2-3 months to prevent early relapses 1

2. For severe attacks or inadequate response to steroids:

   • Implement plasma exchange (5-7 exchanges) or immunoadsorption early 1
   • Alternative: intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days for patients who cannot undergo plasma exchange 1

Maintenance/Prevention Phase:

• Regular clinical assessments every 3-6 months to evaluate treatment response and detect early signs of relapse 1
• Monitor MOG-IgG serum concentrations, as they vary with disease activity (higher during attacks) and treatment status (lower during immunosuppression) 1

Important Clinical Considerations

• Avoid treating as multiple sclerosis, as some MS disease-modifying therapies might be ineffective or potentially harmful in MOGAD 6, 1
• Be cautious about stopping steroids too quickly, as MOGAD has a high risk of flare-ups after steroid cessation 1
• The low NfL level in this case suggests limited neuronal damage despite active inflammation, which may indicate a better prognosis for recovery if treated promptly 3
• The high cytokine profile (TNFSF13B, CDCP1, IL-12B) suggests active inflammation that requires aggressive immunosuppression 5

Monitoring Recommendations

• Track sNfL and sGFAP levels as they correlate with disease activity - sNfL levels are typically higher during attacks than in remission 7, 3
• If MOG-IgG testing is negative but MOGAD is still suspected, consider re-testing during acute attacks, treatment-free intervals, or 1-3 months after plasma exchange/IVIG 1
• Monitor for common MOGAD presentations including optic neuritis, transverse myelitis, and brainstem encephalitis 8
• Be vigilant for steroid-dependent course characterized by frequent flare-ups after intravenous methylprednisolone withdrawal 8

Treatment Pitfalls to Avoid

• Do not use mainstay MS treatments as they can worsen outcomes in MOGAD 6, 1
• Avoid stopping steroids too quickly as this can lead to disease reactivation 1
• Do not overlook the possibility of neutrophilic pleocytosis in CSF, which can mimic CNS infection but is actually characteristic of MOGAD 8, 1