How do you differentiate and treat a multiple sclerosis (MS) flare from a pseudo flare?

Differentiating MS Flare from Pseudo Flare

A true multiple sclerosis (MS) flare is characterized by new or worsening neurological symptoms lasting at least 24 hours, while a pseudo flare is a temporary worsening of existing symptoms due to external factors without new inflammatory activity. 1

Definitions and Key Differences

True MS Flare (Relapse/Exacerbation)

• Involves new inflammatory demyelinating activity in the central nervous system 1
• Symptoms develop over days and last at least 24 hours 1
• Presents with new neurological symptoms or significant worsening of previous symptoms 1
• Occurs at least 30 days after a previous attack 1
• Often shows new or enhancing lesions on MRI 1

Pseudo Flare

• Temporary worsening of existing symptoms without new inflammatory activity 1
• Often triggered by external factors like infection, increased core body temperature, or stress 1
• Symptoms typically resolve when the triggering factor is addressed 1
• No new lesions or enhancement on MRI 1

Diagnostic Approach

Clinical Assessment

• Determine if symptoms are new or worsening of existing symptoms 1
• Evaluate duration of symptoms (true flare lasts at least 24 hours) 1
• Check for potential triggers of pseudo flare:
  • Infection (especially urinary tract or respiratory) 1
  • Increased body temperature 1
  • Physical or emotional stress 1

MRI Evaluation

• True flare: May show new T2 lesions or gadolinium-enhancing lesions 1
• Pseudo flare: No new lesions or enhancement 1
• Gadolinium-enhancing lesions indicate active inflammation and blood-brain barrier disruption 1
• Typical MS lesions show specific characteristics:
  • Nodular or ring enhancement 1
  • Sharp edges, often periventricular in location 1
  • Enhancement typically resolves over 1-2 months 1

Laboratory Testing

• Check for signs of infection (CBC, urinalysis, blood cultures if indicated) 1
• Consider CSF analysis in atypical presentations to confirm inflammatory activity 1

Treatment Approach

For True MS Flare

• High-dose corticosteroids (typically methylprednisolone 1000mg IV daily for 3-5 days) 2
• Plasma exchange may be considered for severe attacks unresponsive to steroids 2
• Evaluate need for adjustment of disease-modifying therapy 2

For Pseudo Flare

• Identify and treat the underlying trigger 1
• For infection: appropriate antimicrobial therapy 1
• For temperature-related symptoms: cooling strategies (cool baths, air conditioning) 1
• Symptomatic treatment as needed 2
• No need for corticosteroids or change in disease-modifying therapy 1

Common Pitfalls and Caveats

• Misdiagnosing pseudo flare as true relapse may lead to unnecessary treatment with corticosteroids and potential overtreatment 1
• Failing to recognize true flare may result in delayed appropriate treatment and disease progression 2
• Certain conditions can mimic MS symptoms and should be considered in differential diagnosis:
  • Vascular disorders (including CADASIL, phospholipid antibody syndrome) 1
  • Infections (HTLV1, Lyme disease) 1
  • Inflammatory conditions (neuromyelitis optica, acute disseminated encephalomyelitis) 1
• Careful correlation of clinical symptoms with MRI findings is essential but can be challenging when multiple lesions are present 1

Red Flags Suggesting Alternative Diagnosis

• Persistent enhancement of lesions for more than 3 months (consider sarcoidosis or vascular abnormality) 1
• Leptomeningeal enhancement (consider neurosarcoidosis or granulomatous disease) 1
• Punctate or miliary enhancement patterns (consider CLIPPERS, vasculitis, PML) 1
• Lack of response to standard MS treatments 3