What is the treatment for longitudinally extensive transverse myelitis (LETM)?

Treatment for Longitudinally Extensive Transverse Myelitis (LETM)

High-dose intravenous methylprednisolone (1g daily for 3-5 days) combined with intravenous immunoglobulin (IVIG) 2g/kg over 5 days is the recommended first-line treatment for LETM. 1, 2

Diagnostic Approach

Before initiating treatment, confirm the diagnosis with:

• Neurologic consultation to guide diagnosis and management 3
• MRI of the spine with thin axial cuts showing T2-weighted hyperintense lesions extending across three or more vertebral segments (defining feature of LETM) 3, 4
• Lumbar puncture to analyze:
  • Cell count (often shows pleocytosis)
  • Protein (typically elevated)
  • Glucose
  • Oligoclonal bands
  • Viral PCRs
  • Onconeural antibodies 1, 3
• Blood tests including:
  • Aquaporin-4 IgG antibodies (to evaluate for neuromyelitis optica)
  • MOG-IgG antibodies
  • Autoimmune panel (ANA, Ro/La, antiphospholipid antibodies)
  • Infectious disease screening (HIV, RPR)
  • Vitamin B12 and thyroid function tests 1, 3

Treatment Algorithm

First-Line Treatment

1. Immediately discontinue any potential causative agents (such as immune checkpoint inhibitors if applicable) 5, 1

2. Administer high-dose intravenous methylprednisolone:

   • Dosage: 1g daily for 3-5 days 1, 6
   • This should be initiated as soon as possible after diagnosis to reduce harmful inflammation 7

3. Combine corticosteroids with IVIG:

   • Dosage: 2g/kg over 5 days 1, 2
   • Particularly important for moderate to severe cases with significant weakness or sensory changes 5

Second-Line Treatment (for refractory cases)

1. Plasma exchange therapy:

   • Consider for patients who do not respond adequately to corticosteroids and IVIG within 7-10 days 1, 7
   • Typically 5-7 exchanges over 10-14 days 7

2. Rituximab:

   • Beneficial in cases with positive autoimmune antibodies or inadequate response to other therapies 1
   • Particularly important for NMOSD-associated LETM (positive aquaporin-4 IgG) 3

Maintenance Therapy

• After acute treatment, consider maintenance immunosuppressive therapy (such as azathioprine) to prevent relapses, which occur in 50-60% of cases during corticosteroid dose reduction 1

Special Considerations

• For LETM associated with neuromyelitis optica spectrum disorder (NMOSD), more aggressive immunosuppression may be required 1, 4

• For immune checkpoint inhibitor-related LETM, permanently discontinue the immune checkpoint inhibitor in addition to the above treatments 5

• Evaluate for and manage urinary retention and constipation, which are common autonomic manifestations 3, 2

Prognostic Factors

• Factors associated with poor prognosis include:
  • Extensive spinal cord MRI lesions (especially affecting ≥3 vertebral segments) 1, 4
  • Reduced muscle strength or sphincter dysfunction at presentation 1
  • Delay (>2 weeks) in the initiation of therapy 1, 7

Clinical Pearls and Pitfalls

• The presence of increased deep tendon reflexes is a key distinguishing feature of LETM compared to conditions with flaccid paralysis like Guillain-Barré syndrome 2

• Early and aggressive immunomodulatory therapy is crucial for faster recovery and improved outcomes 6, 7

• LETM is not exclusively associated with neuromyelitis optica; it can occur in various other autoimmune, inflammatory, infectious, or neoplastic conditions 4, 8

• Physical therapy plays a crucial role in managing LETM, focusing on improving functional abilities, mobility, and quality of life 9