What is the best next step for a 35-year-old woman with bilateral weakness, bloody vision in one eye, retro-orbital pain, and a history of bilateral hand numbness, who has focal hyperintensities in the right optic nerve and spinal cord on MRI, consistent with optic neuritis and potential multiple sclerosis (MS) relapse?

Treatment of Acute Optic Neuritis with Myelopathy in Multiple Sclerosis

Initiate high-dose intravenous methylprednisolone 1000 mg/day for 3 days immediately, followed by oral prednisone 1 mg/kg/day for 11 days with a 4-day taper. This is the gold standard treatment for acute optic neuritis with concurrent demyelinating lesions, based on the landmark Optic Neuritis Treatment Trial and supported by the American Academy of Neurology 1, 2, 3.

Immediate Treatment Protocol

• Begin IV methylprednisolone 1000 mg/day for 3 consecutive days administered over at least 30 minutes to avoid cardiac arrhythmias 1, 3.
• Follow with oral prednisone 1 mg/kg/day for 11 days, then taper over 4 days 1, 4, 5.
• Do not delay treatment beyond 2 weeks, as this is associated with significantly poorer visual outcomes and neurological recovery 1, 6, 7.

The clinical presentation—bilateral weakness, optic neuritis with retro-orbital pain, prior hand numbness, and MRI showing focal hyperintensities in the optic nerve and spinal cord with T1 hypointense lesions—strongly suggests an acute MS relapse with both optic nerve and spinal cord involvement 1, 6.

Why Glucocorticoids Over Other Options

• Plasmapheresis is reserved for second-line therapy when patients fail to respond to IV steroids within 5-7 days or have progressive worsening despite steroid treatment 1, 6.
• IVIG and ACTH are not first-line treatments for acute demyelinating optic neuritis with myelopathy in MS 1, 2.
• IV methylprednisolone accelerates recovery from acute MS relapses and reduces the rate of MS development over 2 years (7.5% vs 16.7% with placebo) 4, 8, 5.

Critical Monitoring During Treatment

• Assess for treatment response within 3-5 days—if vision continues to worsen or no improvement occurs, consider plasma exchange as second-line therapy 1, 6.
• Monitor visual acuity, visual fields, and funduscopy at baseline and every 4-6 weeks 1, 6, 2.
• Perform visual-evoked potentials to objectively assess optic nerve recovery and detect subclinical bilateral involvement 1, 6, 2.
• Watch for steroid-related complications including hyperglycemia, psychiatric symptoms (occurs in 10% at doses ≥1 mg/kg prednisone), and gastrointestinal issues 7, 3.

When to Consider Plasma Exchange

• Severe visual loss with no improvement after 3-5 days of IV methylprednisolone 1, 6.
• Progressive neurological worsening despite steroid therapy 1.
• Extensive spinal cord lesions (>3 segments) with reduced muscle strength or sphincter dysfunction 7.

The patient's left leg weakness (4/5 strength with hip flexion and knee extension) combined with optic neuritis suggests multifocal demyelination requiring aggressive initial treatment 1, 6.

Important Diagnostic Considerations

• The MRI findings (T2 hyperintensities in optic nerve and spinal cord, T1 hypointense lesions) confirm active demyelination and support the diagnosis of MS relapse 1, 6.
• Consider testing for NMO-IgG (aquaporin-4 antibodies) if the patient has longitudinally extensive transverse myelitis (>3 segments) or severe/recurrent optic neuritis, as this would change long-term management 7, 1.
• MOG-IgG testing may be warranted if the patient has bilateral optic neuritis, steroid-dependent relapses, or OCB-negative CSF 7.

Long-Term Management Considerations

• Relapses occur in 50-60% of patients during corticosteroid dose reduction, necessitating consideration of disease-modifying therapy 7, 1, 6.
• Repeat MRI at 3-6 months to assess for new demyelinating lesions and guide decisions about initiating disease-modifying therapy 1, 6.
• The presence of multiple T2 lesions on brain MRI is a strong predictor of conversion to clinically definite MS (adjusted rate ratio 5.53 for ≥3 lesions) 5.

Critical Pitfalls to Avoid

• Never use oral prednisone alone as initial treatment—the Optic Neuritis Treatment Trial showed oral prednisone alone (without IV methylprednisolone) increased the rate of recurrent optic neuritis and did not reduce MS conversion 5.
• Do not administer IV methylprednisolone faster than 30 minutes for doses ≥500 mg, as rapid infusion can cause cardiac arrhythmias and cardiac arrest 3.
• Avoid delaying treatment while awaiting additional testing—begin steroids immediately while diagnostic workup proceeds in parallel 1, 6.