What is the management of Lambert-Eaton Myasthenic Syndrome (LEMS)?

Management of Lambert-Eaton Myasthenic Syndrome (LEMS)

The first-line treatment for Lambert-Eaton Myasthenic Syndrome is amifampridine (Firdapse), a potassium channel blocker that improves neuromuscular transmission, with additional immunotherapy for patients with persistent symptoms despite symptomatic treatment. 1, 2

Diagnostic Workup

• Screen all LEMS patients for small cell lung cancer (SCLC), especially older patients with smoking history, as approximately 50% of LEMS cases are paraneoplastic 1, 3
• Diagnostic confirmation includes clinical features (proximal muscle weakness, reduced reflexes, autonomic symptoms), electromyography, and anti-voltage-gated calcium channel antibody testing 3, 4
• Perform pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) to evaluate respiratory function 5

Treatment Algorithm

First-Line Symptomatic Treatment

• Amifampridine (Firdapse, 3,4-diaminopyridine) is FDA-approved for LEMS in adults and pediatric patients 6 years and older 2
• Dosing recommendations:
  • Adults and pediatric patients ≥45 kg: Start with 15-30 mg daily in 3-5 divided doses 2
  • Pediatric patients <45 kg: Start with 5-15 mg daily in divided doses 2
  • Increase dose gradually (5 mg daily every 3-4 days for adults; 2.5 mg daily every 3-4 days for children <45 kg) 2
  • Maximum single dose: 20 mg for adults/pediatric patients ≥45 kg; 10 mg for pediatric patients <45 kg 2
  • Maximum daily dose: 100 mg for adults/pediatric patients ≥45 kg; 50 mg for pediatric patients <45 kg 2
• Patients with renal impairment, hepatic impairment, or known N-acetyltransferase 2 poor metabolizers should start at the lowest recommended initial daily dosage 2

Second-Line and Adjunctive Treatments

• Intravenous Immunoglobulin (IVIg) for patients with severe weakness despite amifampridine:

  • Provides transient improvement in muscle strength for up to eight weeks 1, 6
  • Typically administered as 2 g/kg over 5 days (0.4 g/kg/day) 5

• Plasma Exchange:

  • May induce transient improvement but rarely normalizes function 1
  • Consider for patients who don't respond to or cannot tolerate other therapies 6

• Immunosuppressive Therapy:

  • Consider for patients with persistent symptoms despite amifampridine 1
  • Options include combinations of prednisone (1-1.5 mg/kg orally daily), azathioprine, or cyclosporine 1, 5
  • Improvement may take months and requires chronic administration 1

Treatment of Underlying Malignancy

• For paraneoplastic LEMS (SCLC-LEMS), oncological treatment should take priority 3, 7
• Treating the underlying cancer often improves LEMS symptoms 7

Important Considerations and Precautions

• Monitor for seizures, as amifampridine can cause seizures; do not use in patients with history of seizures 2
• Watch for hypersensitivity reactions including anaphylaxis 2
• Avoid medications that can worsen neuromuscular weakness:
  • β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 8, 5
• For patients requiring magnesium repletion, consult neurology before administration 8
• Prognosis differs between forms:
  • Non-tumor LEMS has normal life expectancy, though complete remission is uncommon 4
  • In tumor-associated LEMS, prognosis is determined by cancer progression 4

Monitoring and Follow-up

• Regular assessment of muscle strength and functional status 5
• Pulmonary function testing for patients with respiratory symptoms 5
• Continued surveillance for malignancy in initially negative cancer screenings, particularly in the first few years after diagnosis 3