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

Initial Workup and Treatment Approach for Suspected Myasthenia Gravis

The initial workup for suspected myasthenia gravis should include acetylcholine receptor antibody testing, electrodiagnostic studies, and pulmonary function assessment, followed by first-line treatment with pyridostigmine. 1, 2

Diagnostic Workup

Laboratory Testing

• Test for acetylcholine receptor (AChR) and antistriated muscle antibodies in blood 1, 2
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1, 2, 3
• Check creatine phosphokinase (CPK), aldolase, ESR, and CRP to evaluate for possible concurrent myositis 1
• If respiratory insufficiency or elevated CPK/troponin T is present, perform cardiac evaluation with ECG and echocardiogram to rule out concomitant myocarditis 1

Neurophysiological Testing

• Perform electrodiagnostic studies, including neuromuscular junction testing with repetitive stimulation and/or jitter studies 1, 2
• Conduct nerve conduction studies to exclude neuropathy 1
• Perform needle EMG to evaluate for myositis 1

Functional Assessment

• Conduct pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) measurements 1, 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

Additional Testing

• Consider MRI of brain and/or spine depending on symptoms to rule out CNS involvement or alternative diagnoses 1
• The ice test (applying an ice pack over closed eyes for 2 minutes) is highly specific for ocular myasthenia gravis 2
• Obtain neurology consultation 1, 2

Treatment Approach

First-Line Treatment

• Start pyridostigmine (acetylcholinesterase inhibitor) at 30 mg PO three times daily 1, 2, 5
• Gradually increase pyridostigmine to a maximum of 120 mg orally four times daily as tolerated and based on symptoms 1, 2

Second-Line Treatment

• For patients with Grade 2 or higher symptoms, consider corticosteroids (prednisone 1 to 1.5 mg/kg PO daily) 1, 2
• Wean corticosteroids based on symptom improvement 1

For Severe Disease (Grade 3-4)

• Consider hospital admission, possibly requiring intensive care unit monitoring 1
• Continue corticosteroids and initiate IVIG 2 g/kg over 5 days or plasmapheresis for 5 days 1
• Perform frequent pulmonary function assessments 1, 4
• Conduct daily neurological evaluations 1

Long-term Management

• Consider immunosuppressive therapy with azathioprine, cyclosporine, or mycophenolate mofetil for moderate to severe disease 2, 3
• Thymectomy may be beneficial, particularly in patients with thymoma 6, 3

Important Considerations and Pitfalls

• Avoid medications that can worsen myasthenia gravis, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, macrolides, and butalbital-containing products like Firocet 1, 2, 7
• Monitor for signs of impending myasthenic crisis requiring immediate intervention, including difficulty holding up the head, slurred speech, trouble with chewing or swallowing 4
• Watch for respiratory compromise even when patients don't show obvious symptoms of dyspnea 4
• Recognize that ocular weakness with asymmetric ptosis and binocular diplopia is the most typical initial presentation, while early or isolated oropharyngeal or limb weakness is less common 8
• Be aware that most patients with initial ocular weakness develop bulbar or limb weakness within three years of symptom onset 8