What is the initial workup and treatment for myasthenia (myasthenia gravis)?

Initial Workup and Treatment for Myasthenia Gravis

The initial workup for myasthenia gravis should include acetylcholine receptor (AChR) antibodies, anti-striated muscle antibodies, and muscle-specific kinase (MuSK) and lipoprotein-related 4 (LRP4) antibodies if AChR antibodies are negative, followed by first-line treatment with pyridostigmine. 1

Clinical Presentation

Myasthenia gravis (MG) is a B-cell mediated autoimmune disorder affecting the neuromuscular junction, characterized by:

• Variable skeletal muscle weakness that worsens with fatigue
• Ocular symptoms (present in 50% of patients initially): ptosis and variable strabismus/diplopia 2
• Bulbar symptoms: facial weakness, difficulty swallowing, speaking
• Limb weakness
• Respiratory muscle weakness (in severe cases)

Key clinical findings include:

• Ptosis that worsens with prolonged upgaze
• Cogan lid-twitch sign (brief overshoot of eyelid when looking from down to primary position)
• Slow ocular saccades
• Variable and incomitant strabismus that changes pattern with fatigue
• Improvement of symptoms after rest or ice pack test

Diagnostic Workup

1. Laboratory tests:

   • Acetylcholine receptor (AChR) antibodies (positive in 80-85% of patients) 3
   • If AChR antibodies negative, test for:
     • Muscle-specific kinase (MuSK) antibodies (5-8% of patients)
     • Lipoprotein-related 4 (LRP4) antibodies (<1% of patients)
   • Anti-striated muscle antibodies (associated with thymoma)
   • Cardiac markers (troponin) if respiratory compromise present 1

2. Electrophysiologic testing:

   • Repetitive nerve stimulation (shows decremental response)
   • Single-fiber electromyography (increased jitter)
   • Nerve conduction studies to exclude neuropathy 1

3. Imaging:

   • Chest CT or MRI to evaluate for thymoma (present in 10-20% of AChR-positive MG patients)
   • Brain/spine MRI to assess for alternative diagnoses if presentation is atypical 1

4. Pulmonary function tests:

   • Negative inspiratory force and vital capacity to assess respiratory function 1

Treatment Algorithm

1. Symptomatic Treatment

• Pyridostigmine (acetylcholinesterase inhibitor) 4
  • Start at 30 mg orally three times daily
  • Gradually increase to maximum of 120 mg orally four times daily based on symptom response 1
  • Useful for initial symptom control in all forms of MG

2. Immunosuppressive Treatment

For patients with more than mild symptoms or inadequate response to pyridostigmine:

• Corticosteroids:

  • Prednisone 0.5-1.5 mg/kg orally daily
  • 66-85% of patients show positive response 1
  • Monitor for steroid side effects

• Steroid-sparing agents (often added to reduce steroid requirements):

  • Azathioprine
  • Mycophenolate mofetil
  • Tacrolimus 5

3. Surgical Treatment

• Thymectomy:
  • Indicated for all patients with thymoma
  • Beneficial in AChR antibody-positive generalized MG patients up to age 65 6
  • Consider minimally invasive or robotic-assisted approaches

4. Treatment for MG Flares/Crisis

• Hospital admission with capability for ICU transfer
• Neurology consultation
• Frequent neurological assessments and pulmonary function monitoring
• Treatment options:
  • Intravenous immunoglobulin (IVIG): 2 g/kg over 5 days
  • Plasmapheresis for 5 days
  • Corticosteroids: prednisone 1-1.5 mg/kg PO daily 1
  • Low threshold for intubation if respiratory parameters deteriorate

Important Considerations and Pitfalls

• Medication precautions:

  • Avoid medications that can exacerbate MG: aminoglycosides, β-blockers, IV magnesium, fluoroquinolones, macrolides, and daptomycin 1
  • Safer antibiotics include penicillins, cephalosporins, and tetracyclines
  • For MRSA infections, consider linezolid (with monitoring) or vancomycin 1

• Disease progression:

  • 50-80% of patients with initial ocular symptoms develop generalized MG within a few years 2
  • Monitor closely for signs of generalization, especially respiratory involvement

• Special populations:

  • Elderly patients: Start medications at lower doses and titrate more slowly
  • Surgical patients: Continue pyridostigmine until surgery 1
  • Persistent strabismus: Consider surgical intervention after disease stabilization (typically 2-3 years) 1

• Infections:

  • Treat infections promptly and aggressively as they can trigger MG flares
  • Use penicillins, cephalosporins, or tetracyclines as first-line antibiotics 1

By following this systematic approach to diagnosis and treatment, clinicians can effectively manage patients with myasthenia gravis and minimize morbidity and mortality associated with this condition.