Initial Workup and Treatment for Suspected Myasthenia Gravis
The initial workup for suspected myasthenia gravis should include acetylcholine receptor (AChR) antibodies, anti-striated muscle antibodies, and if AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies, followed by treatment with pyridostigmine as first-line therapy. 1, 2
Diagnostic Workup
Clinical Presentation Assessment
- Look for fatigable or fluctuating muscle weakness, typically more proximal than distal, with possible ocular and/or bulbar involvement (ptosis, diplopia, dysphagia, dysarthria) 2, 3
- Perform the ice test for ocular symptoms: apply ice pack over closed eyes for 2 minutes - highly specific for myasthenia gravis 2
Laboratory Testing
- Order acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies 1, 4
- If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1, 4
- Consider measuring CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 4
Electrodiagnostic Studies
- Perform single-fiber electromyography (SFEMG) - considered the gold standard with >90% sensitivity in ocular myasthenia 1, 3
- Conduct repetitive nerve stimulation testing, though it's positive in only about one-third of patients with ocular myasthenia 1
Respiratory Function Assessment
- Assess pulmonary function with negative inspiratory force (NIF) and vital capacity (VC) measurements 4
- Apply the "20/30/40 rule" to identify patients at risk of respiratory failure: vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 4
- Perform single breath count test (counting at two numbers per second while exhaling) - counting to ≥25 correlates with normal respiratory function 4
Treatment Approach
First-Line Treatment
- Start pyridostigmine (acetylcholinesterase inhibitor) at 30 mg orally three times daily 1, 2, 5
- Gradually increase dose as needed for symptom control, up to maximum of 120 mg four times daily 1, 2
- Be aware that approximately 50% of patients with ocular myasthenia may show minimal response to pyridostigmine alone 1, 2
Second-Line Treatment
- For patients with Grade 2 or higher symptoms or inadequate response to pyridostigmine, add corticosteroids (prednisone 1-1.5 mg/kg/day) 1, 2
- Corticosteroids are effective in approximately 66-85% of patients 1, 2
- Gradually taper corticosteroid dose as symptoms improve 1
Third-Line/Additional Treatment Options
- Consider azathioprine as an immunosuppressant for long-term treatment 1, 6
- For moderate to severe symptoms not responding to initial therapy, consider plasmapheresis or IVIG (2 g/kg over 5 days) 2
- Evaluate for thymectomy in appropriate patients 2
Management of Myasthenic Crisis
- Immediately hospitalize with ICU-level monitoring 4
- Continue corticosteroids and initiate either IVIG (2 g/kg over 5 days) or plasmapheresis (5 sessions over 5 days) 4
- Perform daily neurological evaluations and frequent respiratory function assessments 4
Important Precautions
- IMMEDIATELY discontinue medications that can worsen myasthenia gravis: 1, 4, 2
- Beta-blockers
- IV magnesium (absolutely contraindicated)
- Fluoroquinolones
- Aminoglycosides
- Macrolide antibiotics
Follow-up and Monitoring
- Regular assessment of respiratory function, especially in patients with generalized weakness 1, 4
- Consider polysomnography when concerned about hypoventilation not captured by standard pulmonary function tests 4
- Collaborative management between neurologist and ophthalmologist, particularly for patients with ocular involvement 1, 2