What is the recommended IV (intravenous) steroid treatment for a multiple sclerosis (MS) flare?

IV Steroid Treatment for Multiple Sclerosis Flare

The standard treatment for an MS relapse is methylprednisolone 1000 mg intravenously once daily for 3-5 days, though oral administration at the same dose is equally effective and should be considered first for patient convenience, safety, and cost. 1, 2, 3

Dosing Regimen

Methylprednisolone 1000 mg daily for 3 days is the evidence-based standard dose for MS relapses. 1, 2

• The FDA-approved regimen specifically states 160 mg daily for 7 days followed by 64 mg every other day for 1 month has been shown effective, though this lower-dose prolonged regimen is less commonly used in current practice 1
• Administration should occur over several minutes when given as IV push, or can be infused over 30 minutes to 2 hours 1
• A 5-day course (rather than 3 days) may be used for more severe relapses, though 3 days is typically sufficient 1, 4

Route of Administration: Oral vs IV

Oral methylprednisolone 1000 mg daily is non-inferior to IV administration and should be the preferred route unless the patient cannot tolerate oral intake. 2, 3

• A high-quality 2015 randomized controlled trial (COPOUSEP) demonstrated that oral methylprednisolone 1000 mg daily for 3 days was non-inferior to IV administration, with 81% of oral patients vs 80% of IV patients achieving improvement at 28 days 2
• An earlier 1997 trial showed no significant difference between routes, with mean EDSS difference of only 0.07 grades (95% CI -0.46 to 0.60) favoring oral therapy 3
• Oral administration offers advantages in patient convenience, safety (no IV line complications), and substantially lower cost 2, 3
• The main disadvantage of oral therapy is higher rates of insomnia (77% vs 64% with IV) 2

Alternative Dosing Considerations

Lower doses of 625 mg daily may be considered for moderate relapses, though standard 1000-1250 mg provides faster initial recovery. 5

• A 2019 pilot trial comparing 1250 mg vs 625 mg daily (both for 3 days) showed non-inferiority at 30 days, but the higher dose produced superior EDSS improvement at day 7 5
• By day 90, no differences existed between doses 5
• For severe or disabling relapses, the standard 1000 mg dose should be used to maximize speed of recovery 5

Dexamethasone as Alternative

Dexamethasone may be considered specifically when brainstem or cerebellar involvement is prominent, as it crosses the blood-brain barrier more effectively than methylprednisolone. 6

• This consideration is particularly relevant for relapses involving cranial nerves, ataxia, or other posterior fossa symptoms 6
• However, methylprednisolone remains the standard and most extensively studied corticosteroid for MS relapses 1, 2, 3

Clinical Outcomes and Expectations

Corticosteroids accelerate recovery from relapses but do not influence long-term disability or prevent future relapses. 4

• Treatment speeds functional recovery, with most improvement occurring within the first 4 weeks 2, 3
• No evidence exists that corticosteroid treatment of relapses affects the natural history of MS or reduces long-term disability accumulation 4
• The decision to treat should be based on the severity of functional impairment, not simply the presence of new symptoms 4

Administration Practicalities

For IV administration, methylprednisolone can be given as direct IV push over several minutes or diluted in 50-250 mL of normal saline or D5W and infused over 30 minutes to 2 hours. 1

• Reconstituted solution is stable for 48 hours at room temperature 1
• Further diluted solutions are stable for 4 hours at room temperature or 24 hours refrigerated 1
• Rapid administration (>0.5 grams in <10 minutes) has been associated with cardiac arrhythmias and should be avoided 1

Common Pitfalls

• Do not taper corticosteroids after a 3-5 day pulse for MS relapse - tapering is unnecessary and not supported by evidence for short courses 2, 3
• Do not assume IV is superior to oral - this outdated practice persists despite clear evidence of equivalence 2, 3
• Do not treat mild relapses that don't impair function - treatment should be reserved for relapses causing meaningful disability 4
• Do not expect long-term disease modification - corticosteroids only accelerate recovery from the current relapse 4

Special Populations

Breastfeeding mothers can continue nursing after IV methylprednisolone, as relative infant dose is only 1.15-1.45%. 7

• Waiting 2-4 hours after infusion further minimizes infant exposure 7
• Estimated infant exposure (0.164-0.207 mg/kg/day) is below therapeutic doses used in neonates 7