What are the typical symptoms and diagnostic approaches for myasthenia gravis (MG)?

Diagnosing Myasthenia Gravis: Symptoms and Diagnostic Approach

Myasthenia gravis presents with fatigable muscle weakness that worsens with repeated use and improves with rest, and diagnosis is confirmed through anti-acetylcholine receptor antibody testing, bedside ice pack testing, and electrodiagnostic studies when antibodies are negative. 1, 2

Clinical Symptoms

Ocular Manifestations

• Ptosis that worsens with sustained upward gaze is one of the most common presenting symptoms 1, 2
• Diplopia from asymmetric extraocular muscle weakness occurs frequently, with the ice pack test (applying ice over closed eyes for 2 minutes) being highly specific for ocular myasthenia 1, 2
• Pupils are characteristically spared in myasthenia gravis—pupillary involvement should immediately prompt consideration of alternative diagnoses such as third nerve palsy 1, 2

Bulbar and Facial Involvement

• Dysarthria, dysphagia, and facial muscle weakness indicate bulbar involvement 1, 2
• Hoarseness and drooling may occur with disease progression 1
• These symptoms fluctuate throughout the day and worsen with sustained activity 3, 4

Limb and Respiratory Weakness

• Proximal muscle weakness predominates over distal weakness, with difficulty climbing stairs being a common complaint 1, 2
• Shortness of breath with light activity requires urgent evaluation for respiratory muscle involvement, as this can progress to myasthenic crisis 1, 2
• The fatigable pattern is key: weakness increases with repeated muscle use and improves after rest 3, 4

Diagnostic Algorithm

First-Line Testing

• Order anti-acetylcholine receptor (AChR) antibodies first, as they are present in 80-85% of generalized myasthenia gravis cases but only 50% of purely ocular cases 2
• Perform the bedside ice pack test for patients with ptosis—this is highly specific and can provide immediate clinical confirmation 1, 2

Second-Line Antibody Testing

• Test for anti-MuSK (muscle-specific kinase) antibodies when AChR antibodies are negative, as approximately one-third of seronegative patients will be MuSK-positive 2
• Consider anti-LRP4 (lipoprotein-related protein 4) antibodies in double-seronegative patients 5, 4
• Anti-striated muscle antibodies should also be measured, particularly when evaluating for thymoma 1

Electrodiagnostic Studies

• Single-fiber EMG (SFEMG) is the gold standard for ocular myasthenia, with >90% sensitivity 1, 2
• Repetitive nerve stimulation showing decremental response confirms neuromuscular junction dysfunction 1
• Standard EMG and nerve conduction studies may be normal early in disease, so specialized testing is required 1

Additional Diagnostic Considerations

• Edrophonium (Tensilon) testing can provide rapid diagnostic confirmation through temporary improvement in weakness 6, 7
• Pulmonary function testing with negative inspiratory force and vital capacity is critical for patients with respiratory symptoms 5
• Thymic imaging (CT chest) should be performed to evaluate for thymoma, as approximately 30-50% of thymoma patients have myasthenia gravis 1

Critical Diagnostic Pitfalls

Distinguishing from Other Conditions

• Third nerve palsy presents with pupillary abnormalities, unlike myasthenia gravis which spares the pupils—this distinction is crucial and requires immediate neuroimaging if pupils are involved 1
• Thyroid eye disease causes restrictive myopathy with proptosis and eyelid retraction, with forced duction testing showing mechanical restriction rather than fatigable weakness 1
• Lambert-Eaton syndrome, botulism, and chronic progressive external ophthalmoplegia must be considered in the differential, with botulism showing symmetric cranial nerve palsies and gastrointestinal symptoms 1

Timing and Progression

• 50-80% of patients with initial ocular symptoms will develop generalized myasthenia within a few years, making accurate early diagnosis essential for preventing life-threatening respiratory failure 1, 2
• Regular neurological follow-up is mandatory even in patients with isolated ocular symptoms 5

Preoperative Considerations

• Any patient with suspected myasthenia gravis requiring surgery must have serum anti-AChR antibody levels measured preoperatively to avoid respiratory failure during anesthesia 1
• This is particularly critical in patients with thymomas, where approximately 20% of mortality is related to myasthenia gravis 1