Symptoms of MS Flare and Treatment
For an acute MS relapse, treat as early as possible with high-dose corticosteroids (oral or IV methylprednisolone) as first-line therapy, and if severe deficits persist after steroid treatment, proceed to plasma exchange as rescue therapy.
Recognizing MS Relapse Symptoms
An MS relapse (also called exacerbation or flare) presents as new or worsening neurological symptoms lasting at least 24 hours in the absence of fever or infection. The most common relapse symptoms include 1, 2:
- Fatigue (most frequent)
- Weakness of lower or upper extremities
- Sensory symptoms (numbness, tingling, pain)
- Walking problems and gait disturbance
- Visual disturbances (optic neuritis with vision loss, double vision)
- Bladder/bowel dysfunction
- Cognitive changes
- Vertigo or balance problems
Critical Distinction: True Relapse vs. Pseudo-Relapse
Before treating, you must exclude pseudo-relapses—temporary worsening of old symptoms triggered by:
- Urinary tract infections or other infections
- Fever or elevated body temperature
- Metabolic derangements
- Sleep deprivation
- Heat exposure
True relapses represent new acute focal inflammatory demyelination, while pseudo-relapses reflect transient dysfunction in previously damaged areas 3, 4, 5.
Treatment Algorithm
First-Line Treatment: High-Dose Corticosteroids
Initiate treatment promptly when relapses are bothersome or impair function 3, 2, 4:
Dosing options (equivalent efficacy):
- IV methylprednisolone: 1000 mg daily for 3-5 days
- Oral methylprednisolone: 1000-1250 mg daily for 3-5 days (equally effective, more convenient, less expensive) 4
- Optional oral taper following high-dose treatment (though evidence for benefit is limited)
Mechanism: Corticosteroids reduce inflammation, restore blood-brain barrier integrity, and may have neuroprotective effects 2.
Second-Line Treatment: Plasma Exchange (PLEX)
- Severe neurological deficits persist after completing steroid treatment
- Persistent contrast-enhancement on repeat MRI of the symptomatic lesion
- Particularly severe or fulminant presentations
PLEX protocol: Typically 5-7 exchanges over 10-14 days 3
PLEX serves as acute rescue therapy and should be initiated relatively soon after failed steroid response, as earlier treatment correlates with better outcomes 3.
Third-Line Options (Exceptional Cases)
For fulminant or tumefactive disease failing steroids and PLEX 3:
- Cyclophosphamide (cytotoxic agent)
- Rituximab (B-cell depletion)
Important caveat: These agents likely accelerate remission rather than provide immediate relapse remedy due to their pharmacokinetics. Risk-benefit must be carefully weighed 3.
Alternative: ACTH
Adrenocorticotropic hormone (ACTH) provides an alternative to glucocorticoids but is:
- Currently much more expensive
- Not proven superior to corticosteroids
- May be considered when corticosteroids are contraindicated 3
Adjunctive Management
Rehabilitation and Symptom Management
- Neurorehabilitation is an essential component of relapse care 3, 4
- Address specific symptoms (spasticity, bladder dysfunction, fatigue, pain)
- Physical and occupational therapy to maximize functional recovery
Diagnostic Confirmation
While MS relapse remains primarily a clinical diagnosis, MRI may be useful for 3, 2:
- Confirmation of new inflammatory activity
- Evaluation for multifocal disease
- Guiding treatment decisions in ambiguous cases
Common Pitfalls to Avoid
Treating pseudo-relapses with corticosteroids: Always exclude infection, fever, and metabolic issues first 4, 5
Delaying treatment: Early treatment (within 12 hours of symptom onset when possible) improves outcomes 3, 2
Inadequate follow-up: 30% of patients report lack of relapse treatment efficacy at one and three months, indicating need for close monitoring 1
Ignoring residual deficits: Even with prompt treatment, clinical or subclinical sequelae frequently remain and contribute to stepwise disability progression 2, 4
Impact and Prognosis
Relapses have significant socioeconomic impact 1:
- Average loss of 12.7 work/school days per relapse
- 68% report impact on household tasks
- 20% require emergency room or hospital care
Relapses serve as indicators of disease activity and should prompt consideration of escalating to more effective disease-modifying therapy to target freedom from disease activity 3, 5.