What is the recommended treatment for an acute multiple sclerosis relapse (flare‑up)?

Treatment of Acute Multiple Sclerosis Relapse

High-dose corticosteroids—either oral or intravenous methylprednisolone at 1000 mg daily for 3-5 days—are the standard treatment for acute MS relapses, with oral administration being non-inferior to intravenous and preferred for patient convenience, safety, and cost. 1, 2

First-Line Corticosteroid Therapy

Route of Administration

• Oral methylprednisolone (1000-1250 mg daily) is equally effective as intravenous administration and should be the preferred route when feasible 3, 2
• The COPOUSEP trial demonstrated non-inferiority of oral versus intravenous methylprednisolone, with 81% of oral patients versus 80% of intravenous patients achieving improvement at 28 days (absolute difference 0.5%, 90% CI -9.5 to 10.4) 2
• Oral therapy eliminates hospitalization costs, infusion requirements, and allows patients to maintain daily responsibilities 3, 4
• Patient compliance with high-dose oral prednisone (1250 mg daily) is excellent at 94.3%, with two-thirds of patients preferring oral therapy for future relapses 5

Dosing Regimens

• Standard dose: 1000 mg methylprednisolone daily for 3 days is the evidence-based regimen 2
• Alternative FDA-approved regimen: 160 mg methylprednisolone daily for 7 days, followed by 64 mg every other day for 1 month 1
• Lower doses (625 mg daily for 3 days) may be non-inferior at 30 days but show inferior EDSS improvement at day 7, making standard dosing preferable for moderate-to-severe relapses 6

Administration Details

• Initiate treatment within 15 days of relapse onset for optimal benefit 2
• For oral administration: 1000 mg requires twenty 50-mg tablets daily, which patients tolerate well 5
• For intravenous administration: can be given as injection over several minutes or as infusion in 5% dextrose or isotonic saline 1
• Reconstituted IV solution stable for 48 hours at room temperature; further diluted solution stable 4 hours at <25°C or 24 hours at 2-8°C 1

Expected Outcomes and Monitoring

Clinical Response

• Primary goal: improvement of at least one point on the Kurtzke Functional System Scale by 28 days 2
• Most patients achieve clinical improvement within 4 weeks, with no significant difference between oral and intravenous routes 3, 4
• EDSS improvement occurs progressively, with maximal benefit typically seen by 4 weeks 6, 2

MRI Monitoring

• New T2 lesions on 6-12 month follow-up MRI do not necessarily indicate treatment failure or suboptimal response 7
• Gadolinium-enhanced T1 lesions and new/enlarged T2 lesions show similar reduction with both standard and lower corticosteroid doses 6

Management of Common Side Effects

Anticipated Adverse Events

• Insomnia is the most common side effect, occurring more frequently with oral administration (77%) versus intravenous (64%) 2
• Other frequent effects include mood changes, increased appetite, and gastrointestinal symptoms 5
• Only 1-2% of patients discontinue therapy due to intolerance 5

Supportive Measures

• Monitor nutritional intake and ensure adequate hydration during treatment 7
• Avoid omega-3 fatty acid supplementation as it provides no benefit for relapse severity 7
• Consider omega-6 fatty acid supplementation, which may decrease relapse severity 7
• Do not rely on vitamin D supplementation alone for relapse management due to inconsistent evidence 7

Rehabilitation During Acute Phase

Early Intervention

• Implement gentle mobilization when medically stable, adapting intensity based on clinical status 7
• Contraindicate exercise if platelet counts fall below 20 × 10⁹/L 7
• Provide respiratory support and exercises to optimize respiratory function 7
• Manage spasticity through proper positioning, range-of-motion exercises, and prescribed medications 7

Structured Rehabilitation Phases

• Phase 1 (Pre-treatment): Enhance neuromuscular and respiratory function through pre-habilitation 7
• Phase 2 (Weeks 0-4): Acute rehabilitation with gentle mobilization and respiratory optimization 7
• Phase 3 (Weeks 8-12): Subacute rehabilitation with more intense physical therapy when stable 7
• Phase 4 (Weeks 12-26): Community rehabilitation promoting independence and reintegration 7

Special Considerations

Pediatric Dosing

• Initial dose range: 0.11-1.6 mg/kg/day in three or four divided doses 1
• For asthma exacerbations: 1-2 mg/kg/day in single or divided doses until symptoms resolve (typically 3-10 days) 1
• Minimum dose should not be less than 0.5 mg/kg every 24 hours 1
• No evidence supports tapering after improvement to prevent relapse 1

When to Consider Alternative Therapies

• If relapses are frequent or severe despite corticosteroid treatment, consider escalation to high-efficacy disease-modifying therapies 8, 9
• For highly active relapsing-remitting MS refractory to standard DMTs in patients under 45 years with disease duration <5 years, autologous hematopoietic stem cell transplantation (AHSCT) achieves 70-83% NEDA at 2 years 8, 9

Critical Pitfalls to Avoid

• Do not delay treatment initiation—begin corticosteroids promptly when relapse is diagnosed, ideally within 15 days of symptom onset 2
• Do not assume oral therapy is inferior—multiple high-quality trials demonstrate equivalence to intravenous administration 3, 4, 2
• Do not routinely taper corticosteroids after short courses—there is no evidence this prevents subsequent relapses 1
• Do not interpret new MRI lesions at 6-12 months as treatment failure—this is common and does not necessarily indicate suboptimal response 7