What is the initial treatment approach for patients presenting with Lambert-Eaton Myasthenic Syndrome (LEMS) symptoms?

Initial Treatment Approach for Lambert-Eaton Myasthenic Syndrome (LEMS)

Amifampridine (3,4-diaminopyridine) is the first-line symptomatic treatment for patients presenting with Lambert-Eaton Myasthenic Syndrome (LEMS) symptoms. 1, 2

Understanding LEMS

Lambert-Eaton myasthenic syndrome is a rare presynaptic autoimmune neuromuscular junction disorder characterized by:

• Progressive proximal muscle weakness
• Reduced or absent reflexes
• Autonomic dysfunction
• Caused by antibodies against voltage-gated calcium channels, reducing acetylcholine release

Initial Diagnostic Workup

When a patient presents with suspected LEMS symptoms:

1. Evaluate for classic triad:
   • Proximal muscle weakness
   • Autonomic dysfunction
   • Depressed tendon reflexes
2. Perform diagnostic confirmation:
   • Electromyography (repetitive nerve stimulation)
   • Anti-VGCC antibody serology
3. Screen for underlying malignancy (especially small cell lung cancer, present in up to 60% of cases) 3

First-Line Treatment: Amifampridine (Firdapse®)

Dosing Protocol

• Adults and pediatric patients ≥45 kg:

  • Starting dose: 15-30 mg daily, divided into 3-5 doses per day
  • Can increase by 5 mg daily every 3-4 days
  • Maximum single dose: 20 mg
  • Maximum daily dose: 100 mg 1

• Pediatric patients <45 kg:

  • Starting dose: 5-15 mg daily, divided into 3-5 doses
  • Can increase by 2.5 mg daily every 3-4 days
  • Maximum single dose: 10 mg
  • Maximum daily dose: 50 mg 1

• Patients with renal/hepatic impairment or known NAT2 poor metabolizers:

  • Start at the lowest recommended initial daily dosage 1

Monitoring Response

• Assess improvement in muscle strength
• Monitor for adverse effects:
  • Common side effects include paresthesia (62%), upper respiratory tract infection (33%), abdominal pain (14%), nausea (14%), headache (14%), and elevated liver enzymes (14%) 1
  • Serious adverse reactions include seizures and hypersensitivity reactions

Contraindications

• History of seizures
• Hypersensitivity to amifampridine or other aminopyridines 1

Second-Line and Adjunctive Treatments

If symptomatic treatment with amifampridine is inadequate:

1. Consider adding pyridostigmine:

   • Can be combined with amifampridine for enhanced effect 4

2. Immunomodulating therapy:

   • Intravenous immunoglobulin (IVIg) when symptomatic treatment is insufficient 5
   • Immunosuppressants (prednisone plus azathioprine) for persistent symptoms 3

3. Anti-tumor treatment:

   • For paraneoplastic LEMS (associated with cancer), oncological treatment should take priority 5, 3

Treatment Efficacy and Evidence

Multiple randomized controlled trials have demonstrated that amifampridine is effective in treating LEMS symptoms with an acceptable safety profile 6. In one pivotal study, patients receiving amifampridine showed significant improvement in muscle strength compared to placebo, with minimal side effects 6.

Important Considerations

• LEMS can be an early indicator of cancer; prompt oncological screening is essential
• Long-term treatment with amifampridine has shown continued efficacy for up to 10 years in some patients 4
• Regular monitoring for side effects is important, though serious adverse events are rare
• Avoid concomitant use of drugs that lower seizure threshold 1

By following this treatment approach, most patients with LEMS can achieve significant symptomatic improvement and enhanced quality of life.