What is the appropriate workup and treatment for a patient with suspected myasthenia gravis?

Myasthenia Gravis Workup and Treatment

The comprehensive workup for suspected myasthenia gravis should include acetylcholine receptor antibodies, anti-striated muscle antibodies, muscle-specific kinase and lipoprotein-related 4 antibodies (if AChR negative), electrodiagnostic studies, and respiratory assessment, followed by treatment with pyridostigmine as first-line therapy and immunosuppression for more severe cases. 1

Diagnostic Workup

Clinical Evaluation

• Identify characteristic symptoms:
  • Variable incomitant strabismus with diplopia
  • Fluctuating ptosis that worsens with fatigue
  • Cogan lid-twitch sign (eyelid twitch when looking down then up)
  • Slow ocular saccades
  • Contralateral ptosis worsening with manual elevation of more involved eyelid 2
  • Bulbar symptoms (difficulty chewing, swallowing, slurred speech)
  • Limb weakness that worsens with repetitive use 1

Bedside Tests

• Ice pack test: Apply ice over closed eyes for 2 minutes (ptosis) or 5 minutes (strabismus) - highly specific for MG 1, 2
• Fatigue testing: Prolonged upgaze to demonstrate worsening ptosis

Laboratory Tests

1. Antibody testing:

   • Acetylcholine receptor (AChR) antibodies (positive in 80-85% of cases)
   • Anti-striated muscle antibodies (especially if thymoma suspected)
   • Muscle-specific kinase (MuSK) antibodies (if AChR negative)
   • Lipoprotein-related 4 (LRP4) antibodies (if other antibodies negative) 1, 3

2. Additional laboratory tests:

   • Creatine phosphokinase (CPK) and aldolase (to evaluate for concurrent myositis)
   • ESR and CRP (inflammatory markers)
   • Cardiac markers (troponin) if respiratory compromise or elevated CPK 2, 1

Electrodiagnostic Studies

• Repetitive nerve stimulation (RNS) - look for decremental response
• Single-fiber electromyography (SFEMG) - most sensitive test for MG 4
• Nerve conduction studies to exclude neuropathy 2

Imaging

• Chest CT or MRI to evaluate for thymoma (present in 10-20% of AChR-positive MG patients) 3
• MRI of brain/spine if symptoms suggest CNS involvement or to rule out alternative diagnoses 2

Respiratory Assessment

• Negative inspiratory force (NIF)
• Vital capacity (VC)
• Pulmonary function tests 1, 2

Cardiac Evaluation

• ECG and transthoracic echocardiogram if respiratory insufficiency or elevated CPK/troponin (to evaluate for myocarditis) 2

Treatment Approach

First-Line Treatment

• Pyridostigmine (acetylcholinesterase inhibitor): Start at 30 mg PO TID and gradually increase to maximum of 120 mg QID as tolerated 1, 5, 2

Immunosuppressive Therapy

• Corticosteroids: Prednisone 1-1.5 mg/kg PO daily for moderate to severe cases 2, 1
• Steroid-sparing agents:
  • Azathioprine as a corticosteroid-sparing agent 1
  • Consider other immunosuppressants for refractory cases 6

Acute Management of MG Crisis

1. Hospital admission with capability for ICU transfer
2. Respiratory support if needed (maintain low threshold for intubation)
3. IVIG (2 g/kg over 5 days) OR plasmapheresis for 5 days 1, 2
4. IV methylprednisolone 2-4 mg/kg/day 1
5. Frequent neurological and respiratory assessments 2

Surgical Management

• Thymectomy indicated for:
  • Patients with thymoma
  • AChR antibody-positive generalized MG patients up to age 65 1, 6

Important Considerations

Medications to Avoid

• β-blockers
• IV magnesium
• Fluoroquinolones
• Aminoglycosides
• Macrolide antibiotics 2, 1

Monitoring

• Regular neurologic evaluation
• Pulmonary function assessment in moderate to severe cases
• Prompt treatment of infections (can trigger MG flares) 1

Prognosis

• Approximately 50% of patients with ocular MG develop generalized symptoms within a few years 2
• Remission or stabilization often possible after 2-3 years of treatment 1
• Treatment response should be monitored closely, as approximately half of patients with ocular MG may not respond adequately to pyridostigmine alone 1