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Acute Multiple Sclerosis Relapse

High EvidenceUpdated: 2025-12-25

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Red Flags

  • Severe neurological deficit
  • Signs of infection (fever, urinary symptoms)
  • Signs of spinal cord compression
  • Rapidly progressive symptoms
  • Altered mental status
  • Signs of optic neuritis (severe vision loss)
Overview

Acute Multiple Sclerosis Relapse

1. Clinical Overview

Summary

An acute multiple sclerosis (MS) relapse (also called an exacerbation or flare) is a sudden worsening of neurological symptoms in someone with MS, caused by new inflammation and damage to the myelin sheath (the protective covering around nerves) in the brain or spinal cord. Think of MS as your nervous system's wiring—the myelin is like insulation around electrical wires. When MS flares, the insulation gets damaged, causing electrical signals to misfire, leading to symptoms like weakness, numbness, vision problems, or balance issues. Relapses are a hallmark of relapsing-remitting MS (the most common type), where symptoms come and go. The severity ranges from mild (slight numbness) to severe (paralysis, vision loss). The key to management is recognizing a true relapse (not a pseudo-relapse from infection or heat), providing high-dose steroids to reduce inflammation, managing symptoms, and preventing future relapses with disease-modifying therapies (DMTs). Most relapses improve significantly with treatment, but some symptoms may persist.

Key Facts

  • Definition: Acute worsening of neurological symptoms due to new MS inflammation
  • Incidence: Common in relapsing-remitting MS (1-2 relapses/year average)
  • Mortality: Very low (relapses themselves), but MS can affect life expectancy
  • Peak age: Adults (20-50 years, typical MS age)
  • Critical feature: New or worsening neurological symptoms lasting >24 hours
  • Key investigation: Clinical diagnosis (usually), MRI if needed
  • First-line treatment: High-dose steroids (methylprednisolone), DMTs for prevention

Clinical Pearls

"Not all symptom worsening is a relapse" — Pseudo-relapses (worsening from infection, heat, stress) are common. Always check for infection (especially UTI) before treating as relapse.

"Relapses need to last >24 hours" — Brief symptom fluctuations (hours) are usually not true relapses. True relapses last at least 24 hours and are separated by at least 30 days from previous relapse.

"Steroids speed recovery but don't change long-term outcome" — High-dose steroids (methylprednisolone) help relapses recover faster, but don't prevent future relapses or change long-term disability. DMTs prevent relapses.

"Infection can trigger relapses" — Infections (especially UTIs) can trigger pseudo-relapses or true relapses. Always check for and treat infections.

Why This Matters Clinically

MS relapses are common and can cause significant disability and distress. Early recognition and treatment (steroids) can speed recovery and reduce disability. Preventing relapses with DMTs is crucial for long-term outcomes. This is a condition that neurologists and primary care clinicians manage, and prompt treatment can make a significant difference in recovery.


2. Epidemiology

Incidence & Prevalence

  • Overall: Common in relapsing-remitting MS
  • Relapse rate: 1-2 relapses/year average (varies widely)
  • Trend: Decreasing with DMT use
  • Peak age: Adults (20-50 years, typical MS age)

Demographics

FactorDetails
AgeAdults (20-50 years, typical MS age)
SexFemale predominance (MS is more common in women)
EthnicityHigher in certain populations (Caucasian, Northern European)
GeographyHigher in temperate climates
SettingNeurology clinics, general practice

Risk Factors

Non-Modifiable:

  • MS diagnosis (relapsing-remitting type)
  • Genetic factors

Modifiable:

Risk FactorRelative RiskMechanism
Infection2-3xTriggers inflammation
Stress1.5-2xMay trigger relapses
Heat1.5-2xWorsens symptoms (pseudo-relapse)
Stopping DMT2-5xRemoves protection
Pregnancy (postpartum)2-3xHormonal changes

Common Triggers

TriggerFrequencyTypical Patient
Infection30-40%UTI, respiratory infection
Stress20-30%Life stress, physical stress
No obvious trigger30-40%Spontaneous
Heat10-20%Hot weather, fever
Stopping DMT5-10%Non-compliance, side effects

3. Pathophysiology

The Relapse Mechanism

Step 1: Immune Activation

  • T-cells: Activated, cross blood-brain barrier
  • Inflammation: Inflammatory cells enter CNS
  • Result: Immune system attacks myelin

Step 2: Demyelination

  • Myelin damage: Immune attack damages myelin sheath
  • Axon exposure: Nerves become exposed
  • Result: Nerve signals disrupted

Step 3: Clinical Manifestation

  • Symptoms: Depend on location of damage
  • Weakness: If motor pathways affected
  • Numbness: If sensory pathways affected
  • Vision problems: If optic nerve affected
  • Balance problems: If cerebellum affected

Step 4: Recovery (Partial)

  • Remyelination: Some myelin repair
  • Compensation: Brain adapts
  • Result: Symptoms improve, but may not fully recover

Classification by Type

TypeMechanismClinical Features
Relapsing-remittingRelapses with recoveryMost common, relapses come and go
Secondary progressiveRelapses become less frequent, disability accumulatesProgressive after initial relapsing phase
Primary progressiveNo relapses, gradual progressionLess common, gradual decline

Anatomical Considerations

Common Sites of Relapse:

  • Optic nerve: Vision problems (optic neuritis)
  • Spinal cord: Weakness, numbness, bladder problems
  • Brainstem: Double vision, balance problems
  • Cerebellum: Balance, coordination problems
  • Brain: Various symptoms depending on location

Why These Areas:

  • High myelin content: More myelin = more vulnerable
  • Blood-brain barrier: May be more permeable in these areas

4. Clinical Presentation

Symptoms: The Patient's Story

Typical Presentation:

Common Relapse Presentations:

Optic Neuritis:

Spinal Cord Relapse:

Brainstem Relapse:

Cerebellar Relapse:

Signs: What You See

Vital Signs (Usually Normal):

SignFindingSignificance
TemperatureUsually normal (may be elevated if infection)Fever suggests infection (pseudo-relapse)
Heart rateUsually normalUsually normal
Blood pressureUsually normalUsually normal

Neurological Examination:

FindingWhat It MeansFrequency
WeaknessMotor pathway affected50-60%
NumbnessSensory pathway affected40-50%
Vision problemsOptic nerve affected20-30%
Balance problemsCerebellum/brainstem affected30-40%
Bladder problemsSpinal cord affected20-30%

Signs of Pseudo-Relapse (Infection):

Red Flags

[!CAUTION] Red Flags — Immediate Escalation Required:

  • Severe neurological deficit — May need urgent steroids, hospital admission
  • Signs of infection (fever, urinary symptoms) — May be pseudo-relapse, needs treatment
  • Signs of spinal cord compression — Medical emergency, needs urgent imaging
  • Rapidly progressive symptoms — May need urgent treatment
  • Altered mental status — May indicate other cause
  • Signs of optic neuritis (severe vision loss) — May need urgent steroids

New or worsening symptoms
Lasting >24 hours
Weakness
In limbs, face
Numbness
In limbs, face, trunk
Vision problems
Blurred vision, double vision, vision loss
Balance problems
Unsteadiness, falls
Bladder problems
Urgency, frequency, retention
Fatigue
Increased fatigue
5. Clinical Examination

Structured Approach: ABCDE

A - Airway

  • Assessment: Usually patent
  • Action: Secure if compromised

B - Breathing

  • Look: Usually normal
  • Listen: Usually normal
  • Measure: SpO2 (usually normal)
  • Action: Support if needed

C - Circulation

  • Look: Usually normal
  • Feel: Pulse (usually normal), BP (usually normal)
  • Listen: Heart sounds (usually normal)
  • Measure: BP (usually normal), HR
  • Action: Monitor if severe

D - Disability

  • Assessment: Neurological examination
  • Action: Assess function, disability

E - Exposure

  • Look: Neurological examination
  • Feel: Strength, sensation
  • Action: Complete neurological examination

Specific Examination Findings

Neurological Examination:

  • Cranial nerves: May show abnormalities (optic neuritis, facial weakness)
  • Motor: May show weakness
  • Sensory: May show numbness
  • Reflexes: May be increased (upper motor neuron signs)
  • Coordination: May show problems (if cerebellar)
  • Gait: May show problems (if balance affected)

Signs of Pseudo-Relapse:

  • Fever: Infection
  • UTI signs: Frequency, urgency, dysuria
  • Other: As appropriate

Special Tests

TestTechniquePositive FindingClinical Use
Neurological examinationFull neurological examAbnormalities consistent with MSConfirms relapse
Urine dipstickCheck for UTIPositive (infection)Identifies pseudo-relapse
EDSS scoreDisability scaleIncreased scoreQuantifies disability

6. Investigations

First-Line (Bedside) - Do Immediately

1. Clinical Diagnosis (Usually Sufficient)

  • History: New or worsening symptoms, >24 hours, separated by >30 days
  • Examination: Neurological abnormalities consistent with MS
  • Action: Usually sufficient for diagnosis

2. Check for Infection (Important)

  • Urine dipstick: Check for UTI
  • Other tests: As appropriate
  • Action: Rule out pseudo-relapse

Laboratory Tests

TestExpected FindingPurpose
Urine dipstickMay show infection (if pseudo-relapse)Rules out pseudo-relapse
Full Blood CountUsually normalBaseline
CRPMay be elevated (if infection)Identifies infection

Imaging

MRI Brain/Spine (If Needed):

IndicationFindingClinical Note
Uncertain diagnosisNew lesions, enhancing lesionsConfirms relapse
Severe relapseNew lesions, enhancing lesionsAssesses severity
Differential diagnosisRules out other causesImportant

Findings:

  • New lesions: New areas of demyelination
  • Enhancing lesions: Active inflammation (gadolinium enhancement)
  • Old lesions: Previous damage

Diagnostic Criteria

Clinical Diagnosis:

  • New or worsening symptoms + >24 hours duration + separated by >30 days + neurological abnormalities = MS relapse

Pseudo-Relapse vs True Relapse:

  • Pseudo-relapse: Symptoms worsen from infection, heat, stress (not new inflammation)
  • True relapse: New inflammation causing new or worsening symptoms

Severity Assessment:

  • Mild: Minimal disability, can function
  • Moderate: Significant disability, affects function
  • Severe: Severe disability, may need hospital admission

7. Management

Management Algorithm

        SUSPECTED MS RELAPSE
    (New/worsening symptoms >24h)
                    ↓
┌─────────────────────────────────────────────────┐
│         CHECK FOR INFECTION                      │
│  • Urine dipstick (UTI)                          │
│  • Other tests as needed                         │
│  • If infection: Treat infection first         │
│  • If symptoms persist: True relapse             │
└─────────────────────────────────────────────────┘
                    ↓
┌─────────────────────────────────────────────────┐
│         ASSESS SEVERITY                          │
├─────────────────────────────────────────────────┤
│  SEVERE (severe disability, hospital needed)    │
│  → Hospital admission                             │
│  → IV steroids                                    │
│  → Supportive care                                │
│                                                  │
│  MILD-MODERATE                                   │
│  → Outpatient management                          │
│  → Oral steroids (if indicated)                  │
│  → Supportive care                                │
└─────────────────────────────────────────────────┘
                    ↓
┌─────────────────────────────────────────────────┐
│         STEROID TREATMENT                         │
│  • High-dose steroids (methylprednisolone)       │
│  • Duration: 3-5 days                             │
│  • Taper: Usually not needed (short course)       │
│  • Mechanism: Reduces inflammation                │
└─────────────────────────────────────────────────┘
                    ↓
┌─────────────────────────────────────────────────┐
│         SYMPTOM MANAGEMENT                       │
│  • Pain: Analgesia                                │
│  • Spasticity: Muscle relaxants                   │
│  • Bladder: As needed                             │
│  • Fatigue: Rest, pacing                         │
└─────────────────────────────────────────────────┘
                    ↓
┌─────────────────────────────────────────────────┐
│         PREVENT FUTURE RELAPSES                   │
│  • Review DMT (disease-modifying therapy)        │
│  • Ensure compliance                              │
│  • Consider switching DMT if frequent relapses   │
│  • Lifestyle: Avoid triggers (infection, stress) │
└─────────────────────────────────────────────────┘
                    ↓
┌─────────────────────────────────────────────────┐
│         MONITOR & FOLLOW-UP                      │
│  • Symptoms should improve within days to weeks  │
│  • If not improving: Reassess                     │
│  • Long-term: DMT for prevention                 │
└─────────────────────────────────────────────────┘

Acute/Emergency Management - The First Hour

Immediate Actions (Do Simultaneously):

  1. Check for Infection

    • Urine dipstick: Check for UTI
    • Other tests: As appropriate
    • Action: Treat infection if present (may be pseudo-relapse)
  2. Assess Severity

    • Disability: How much function affected
    • Function: Can patient function independently?
    • Action: Determine if hospital admission needed
  3. Start Steroids (If True Relapse)

    • Methylprednisolone: High dose (500mg-1g IV or 500mg-1g oral)
    • Mechanism: Reduces inflammation
    • Duration: 3-5 days
  4. Supportive Care

    • Symptom management: Pain, spasticity, bladder
    • Rest: Important for recovery
    • Rehabilitation: As needed

Medical Management

High-Dose Steroids (First-Line):

DrugDoseRouteDurationNotes
Methylprednisolone500mg-1gIVOD3-5 days
Methylprednisolone500mg-1gOralOD3-5 days (if IV not needed)

Mechanism: Reduces inflammation → speeds recovery

Note: Steroids speed recovery but don't change long-term outcome or prevent future relapses

Symptom Management:

SymptomTreatmentNotes
PainAnalgesia (paracetamol, NSAIDs)As needed
SpasticityBaclofen, tizanidineIf spasticity
BladderAs neededIf bladder problems
FatigueRest, pacingImportant

Disease-Modifying Therapies (DMTs) - For Prevention:

DMTTypeNotes
Interferon betaInjectableFirst-line
GlatiramerInjectableFirst-line
FingolimodOralSecond-line
NatalizumabIVSecond-line
OcrelizumabIVSecond-line

Mechanism: Prevents relapses, reduces inflammation

Note: DMTs prevent relapses but don't treat acute relapses

Disposition

Admit to Hospital If:

  • Severe disability: Unable to function independently
  • IV steroids needed: If severe or can't take oral
  • Supportive care needed: Needs monitoring, rehabilitation

Outpatient Management:

  • Mild-moderate cases: Can be managed outpatient
  • Regular follow-up: Monitor recovery, DMT review

Discharge Criteria:

  • Stable: No complications
  • Can take oral: Oral intake OK
  • Clear plan: For treatment, follow-up

Follow-Up:

  • Symptoms: Should improve within days to weeks
  • If not improving: Reassess, consider further investigation
  • DMT review: Ensure on appropriate DMT, compliance
  • Long-term: Ongoing MS management

8. Complications

Immediate (Days-Weeks)

ComplicationIncidencePresentationManagement
Persistent symptoms20-30%Symptoms don't fully recoverOngoing management, rehabilitation
Infection (from steroids)5-10%Increased infection riskTreat infections
Steroid side effects10-20%Insomnia, mood changes, GI upsetUsually self-limiting

Persistent Symptoms:

  • Mechanism: Incomplete recovery, permanent damage
  • Management: Ongoing management, rehabilitation
  • Prevention: Early treatment, prevent relapses

Early (Weeks-Months)

1. Further Relapses (If Not on DMT)

  • Mechanism: Ongoing MS activity
  • Management: DMT to prevent relapses
  • Prevention: DMT compliance

2. Disability Accumulation

  • Mechanism: Each relapse may cause some permanent damage
  • Management: DMT to prevent relapses, rehabilitation
  • Prevention: Prevent relapses with DMT

Late (Months-Years)

1. Secondary Progressive MS (20-30% over time)

  • Mechanism: Relapses become less frequent, disability accumulates
  • Management: Ongoing management, may need different DMT
  • Prevention: Early DMT, prevent relapses

9. Prognosis & Outcomes

Natural History (Without Treatment)

Untreated MS Relapse:

  • Most cases: Improve over weeks to months
  • Some cases: May not fully recover
  • Disability: May accumulate with each relapse

Outcomes with Treatment

VariableOutcomeNotes
Recovery70-80%Most recover significantly
Persistent symptoms20-30%Some symptoms may persist
Time to recoveryDays to weeksWith steroids
MortalityVery lowRelapses themselves don't cause death

Factors Affecting Outcomes:

Good Prognosis:

  • Early treatment: Better outcomes
  • Mild relapses: Usually recover well
  • On DMT: Prevents future relapses
  • Younger age: Better recovery

Poor Prognosis:

  • Severe relapses: May not fully recover
  • Not on DMT: Higher risk of further relapses
  • Older age: May recover less well
  • Multiple relapses: Disability accumulates

Prognostic Factors

FactorImpact on PrognosisEvidence Level
Early treatmentBetter recoveryHigh
SeverityMore severe = worseModerate
DMT compliancePrevents future relapsesHigh
AgeYounger = better recoveryModerate

10. Evidence & Guidelines

Key Guidelines

1. NICE Guidelines (2019) — Multiple sclerosis in adults: management. National Institute for Health and Care Excellence

Key Recommendations:

  • High-dose steroids for relapses
  • DMTs for prevention
  • Evidence Level: 1A

2. AAN Guidelines (2018) — Disease-modifying therapies for MS. American Academy of Neurology

Key Recommendations:

  • DMTs for relapsing-remitting MS
  • Evidence Level: 1A

Landmark Trials

Multiple studies on steroid treatment, DMT efficacy.

Evidence Strength

InterventionLevelKey EvidenceClinical Recommendation
High-dose steroids1AMultiple RCTsFirst-line for relapses
DMTs1AMultiple RCTsPrevent relapses

11. Patient/Layperson Explanation

What is an MS Relapse?

An MS relapse (also called an exacerbation or flare) is a sudden worsening of neurological symptoms in someone with multiple sclerosis. It happens when new inflammation damages the protective covering around nerves (myelin), causing symptoms like weakness, numbness, vision problems, or balance issues. Think of MS as your nervous system's wiring—when MS flares, the insulation gets damaged, causing electrical signals to misfire.

In simple terms: Your MS symptoms suddenly get worse, usually lasting at least 24 hours. Most relapses improve with treatment, but some symptoms may persist.

Why does it matter?

MS relapses can cause significant disability and distress. Early treatment (steroids) can speed recovery and reduce disability. Preventing relapses with disease-modifying therapies (DMTs) is crucial for long-term outcomes. The good news? With proper treatment, most relapses improve significantly within days to weeks.

Think of it like this: It's like your MS symptoms flaring up—with the right treatment, they usually improve quickly.

How is it treated?

1. Check for Infection (Important):

  • Why: Infections (especially UTIs) can make MS symptoms worse (pseudo-relapse)
  • Treatment: If infection found, treat that first
  • If symptoms persist: Then treat as true relapse

2. Steroid Treatment:

  • High-dose steroids: Like methylprednisolone, reduce inflammation and help your symptoms recover faster
  • Duration: Usually 3-5 days
  • How to take: Usually IV in hospital if severe, or oral if mild-moderate
  • Note: Steroids speed recovery but don't prevent future relapses

3. Symptom Management:

  • Pain: Painkillers if needed
  • Spasticity: Muscle relaxants if needed
  • Bladder: As needed
  • Fatigue: Rest, pacing

4. Prevent Future Relapses:

  • DMTs: Disease-modifying therapies prevent relapses
  • Compliance: Important to take DMTs as prescribed
  • Lifestyle: Avoid triggers (infection, stress, heat)

The goal: Speed recovery from the relapse, manage symptoms, and prevent future relapses.

What to expect

Recovery:

  • Most cases: Start feeling better within days
  • Symptoms: Usually improve within days to weeks
  • Full recovery: Most people recover significantly, but some symptoms may persist

After Treatment:

  • Steroids: You'll take high-dose steroids for 3-5 days
  • Symptoms: Should improve within days to weeks
  • Follow-up: You'll need follow-up to monitor recovery and review your DMT

Recovery Time:

  • Mild relapses: Usually recover within days to weeks
  • Moderate relapses: Usually recover within weeks
  • Severe relapses: May take longer, may not fully recover

When to seek help

See your doctor if:

  • You have new or worsening MS symptoms lasting more than 24 hours
  • You have symptoms that concern you
  • You think you might be having a relapse

Call 999 (or your emergency number) immediately if:

  • You have severe neurological symptoms (severe weakness, vision loss)
  • You feel very unwell
  • You have signs of infection (fever, urinary symptoms)

Remember: If you have new or worsening MS symptoms, especially if they last more than 24 hours, see your doctor. Early treatment can speed recovery and reduce disability. Also, always check for infection (especially UTIs) as infections can make MS symptoms worse.


12. References

Primary Guidelines

  1. National Institute for Health and Care Excellence. Multiple sclerosis in adults: management. NICE guideline [NG220]. 2019.

  2. Rae-Grant A, Day GS, Marrie RA, et al. Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):789-800. PMID: 29686116

Key Trials

  1. Multiple studies on steroid treatment and DMT efficacy.

Further Resources

  • NICE Guidelines: National Institute for Health and Care Excellence
  • MS Society: Multiple Sclerosis Society

Last Reviewed: 2025-12-25 | MedVellum Editorial Team


Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists. This information is not a substitute for professional medical advice, diagnosis, or treatment.

Last updated: 2025-12-25

At a Glance

EvidenceHigh
Last Updated2025-12-25

Red Flags

  • Severe neurological deficit
  • Signs of infection (fever, urinary symptoms)
  • Signs of spinal cord compression
  • Rapidly progressive symptoms
  • Altered mental status
  • Signs of optic neuritis (severe vision loss)

Clinical Pearls

  • **"Not all symptom worsening is a relapse"** — Pseudo-relapses (worsening from infection, heat, stress) are common. Always check for infection (especially UTI) before treating as relapse.
  • **"Infection can trigger relapses"** — Infections (especially UTIs) can trigger pseudo-relapses or true relapses. Always check for and treat infections.
  • **Red Flags — Immediate Escalation Required:**
  • - **Severe neurological deficit** — May need urgent steroids, hospital admission
  • - **Signs of infection (fever, urinary symptoms)** — May be pseudo-relapse, needs treatment

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines