What is the treatment approach for tumefactive multiple sclerosis (MS)?

Treatment Approach for Tumefactive Multiple Sclerosis

High-dose intravenous corticosteroids followed by plasmapheresis is the first-line treatment for acute tumefactive multiple sclerosis lesions, with subsequent disease-modifying therapy selection based on disease activity and risk factors. 1, 2

Acute Treatment Phase

Tumefactive multiple sclerosis (TMS) is a rare variant of MS characterized by large (>2 cm) demyelinating lesions that mimic brain tumors on imaging, with an estimated prevalence of 1-3/1000 MS cases 1.

The acute management includes:

1. High-dose intravenous methylprednisolone:

   • 1g daily for 3-5 days
   • Accelerates recovery from acute symptoms and reduces attack severity 3

2. Plasma exchange therapy (plasmapheresis):

   • Indicated for patients with severe attacks or inadequate response to steroids
   • Typically 5-7 exchanges over 10-14 days 2

3. Brain biopsy:

   • May be necessary in diagnostically challenging cases
   • Helps differentiate from neoplasms, abscesses, or other inflammatory conditions 4

Disease-Modifying Therapy Selection

After acute treatment, disease-modifying therapy (DMT) selection should follow these principles:

For Newly Diagnosed TMS:

• First-line options:

  • B-cell depleting therapies (ocrelizumab, ofatumumab)
  • Natalizumab (especially for highly active disease) 2

• Effective alternatives:

  • Glatiramer acetate
  • Dimethyl fumarate 4

Important Medication Considerations:

• Avoid fingolimod:
  • Strong evidence suggests an association between fingolimod and TMS development
  • TMS has been reported both with fingolimod initiation (median 7 months after starting) and discontinuation (median 3 months after stopping) 5, 6
  • The FDA has amended fingolimod prescribing information to include TMS in the Warnings and Precautions section 5

Monitoring and Follow-up

1. MRI surveillance:

   • Baseline MRI within 48 hours post-treatment
   • Follow-up MRI at 3-month intervals 7
   • Include T2-weighted images, T2-FLAIR, and diffusion-weighted imaging 3

2. Clinical assessment:

   • Regular neurological examinations every 3 months
   • Evaluate for new symptoms or progression 7

3. Treatment response evaluation:

   • Assess for resolution of tumefactive lesions
   • Monitor for development of new MS lesions

Special Considerations

1. Autologous Hematopoietic Stem Cell Transplantation (AHSCT):

   • May be considered for aggressive, treatment-refractory TMS
   • Best candidates are younger patients (<45 years) with short disease duration (<10 years) and evidence of inflammatory activity 7
   • Not recommended for patients with EDSS >6.0 or disease duration >20 years 7

2. Progressive TMS:

   • For patients who develop secondary progressive MS with inflammatory activity, consider B-cell depleting therapies or AHSCT in appropriate candidates 7

Pitfalls and Caveats

1. Diagnostic challenges:

   • TMS can mimic brain tumors, abscesses, or stroke on imaging
   • Detailed history, comprehensive MRI, and sometimes brain biopsy are needed for accurate diagnosis 2

2. Treatment monitoring:

   • Monitor for severe increase in disability after stopping certain DMTs, particularly fingolimod 6
   • Be vigilant for new tumefactive lesions during treatment transitions

3. Disease progression:

   • Some TMS patients may progress to clinically definite MS
   • Early aggressive treatment may delay progression or second demyelinating events 2

The management of tumefactive MS requires prompt recognition, aggressive acute treatment, and careful selection of disease-modifying therapy to prevent relapses and disease progression.