What is the treatment for Multifocal Acquired Demyelinating Sensory and Motor (MADSAM) neuropathy?

Treatment of Multifocal Acquired Demyelinating Sensory and Motor (MADSAM) Neuropathy

The first-line treatment for MADSAM neuropathy is intravenous immunoglobulin (IVIg), with corticosteroids as an alternative option, as MADSAM responds to both therapies unlike MMN which typically only responds to IVIg. 1, 2

Understanding MADSAM

MADSAM neuropathy, also known as Lewis-Sumner syndrome, is a variant of chronic acquired demyelinating polyneuropathy characterized by:

• Asymmetric, multifocal pattern of motor and sensory loss 1
• Conduction block and other features of demyelination on nerve conduction studies 2
• Prominent demyelination on sensory nerve biopsies 2
• Elevated cerebrospinal fluid protein in approximately 82% of patients 2
• Negative anti-GM1 antibody titers (unlike MMN) 2

Treatment Algorithm

First-Line Therapies:

1. Intravenous Immunoglobulin (IVIg)

   • Recommended as initial therapy due to consistent efficacy 2
   • Typical dosing: 2 g/kg divided over 2-5 days for induction, followed by maintenance therapy (0.4-1 g/kg every 2-6 weeks) 1
   • Monitor for response and adjust dosing interval based on clinical symptoms 3

2. Corticosteroids

   • Alternative first-line option, especially when IVIg is contraindicated or unavailable 2
   • Approximately 50% of MADSAM patients respond to prednisone therapy 2
   • Typical starting dose: Prednisone 1 mg/kg/day with gradual taper based on clinical response 3
   • Important distinction from MMN, which typically worsens with corticosteroid treatment 1, 2

Second-Line/Refractory Disease Options:

• Plasmapheresis

  • Consider in patients who fail to respond to IVIg and corticosteroids 3
  • Typically 5-6 exchanges over 2 weeks 3

• Immunosuppressive Agents

  • For patients with inadequate response to first-line therapies 3
  • Options include:
    • Azathioprine (2-3 mg/kg/day) 4
    • Mycophenolate mofetil 4
    • Cyclophosphamide (for severe refractory cases) 4
    • Rituximab (for severe refractory cases) 5

Monitoring and Follow-up

• Regular clinical assessment of motor and sensory function 3
• Follow-up nerve conduction studies to assess treatment response 3
• Long-term monitoring is essential as MADSAM may have a relapsing-remitting course 3

Treatment Response and Prognosis

• Approximately 41% of MADSAM patients achieve clinical remission within 5 years 3
• MADSAM patients are generally more refractory to treatment than typical CIDP patients 3
• Patients with ganglioside antibody positivity may have more sustained treatment responses 5

Special Considerations

• MADSAM has been reported following COVID-19 infection, suggesting possible post-infectious etiology in some cases 6
• MADSAM more closely resembles CIDP in its treatment response profile than MMN 1, 2
• Some patients initially diagnosed with MMN may evolve to develop sensory symptoms consistent with MADSAM, particularly those with positive ganglioside antibodies 5

Common Pitfalls to Avoid

• Misdiagnosing MADSAM as MMN can lead to inappropriate treatment choices, as corticosteroids are often effective in MADSAM but may worsen MMN 1, 2
• Inadequate treatment duration - improvement may be gradual and require prolonged therapy 3
• Failure to recognize that MADSAM is generally more treatment-resistant than typical CIDP, potentially requiring combination therapy 3