What are the diagnostic criteria and treatment options for myasthenia gravis?

Diagnosis of Myasthenia Gravis

Clinical Presentation

Myasthenia gravis diagnosis begins with recognizing the hallmark pattern of fatigable or fluctuating muscle weakness that worsens with activity and improves with rest, typically affecting proximal muscles more than distal ones. 1

Key clinical features to identify include:

• Ocular symptoms: Ptosis and extraocular movement abnormalities that fluctuate throughout the day 1
• Bulbar involvement: Dysphagia, dysarthria, facial muscle weakness, and drooling 1, 2
• Generalized weakness: Difficulty climbing stairs and proximal muscle fatigue 1
• Respiratory symptoms: Shortness of breath with light activity in more severe cases 1

A critical distinguishing feature is that pupils are characteristically NOT affected in myasthenia gravis - pupillary involvement should immediately redirect you toward third nerve palsy or other etiologies rather than MG. 1 This occurs because MG affects nicotinic receptors at the neuromuscular junction of voluntary skeletal muscles, not the autonomic nervous system controlling pupillary function. 1

Diagnostic Testing Algorithm

First-Line Serological Testing

Measure acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood as your initial laboratory confirmation. 1 The American Academy of Neurology recommends this as standard diagnostic testing. 1

• If AChR antibodies are negative, proceed to test for muscle-specific kinase (MuSK) antibodies and lipoprotein-related protein 4 (LRP4) antibodies 1, 2, 3
• Note that anti-AChR antibodies are present in only 40-77% of ocular myasthenia cases, so negative antibodies do not exclude the diagnosis 1

Bedside Clinical Tests

The ice test is highly specific for myasthenia gravis, particularly for ocular symptoms - apply an ice pack over closed eyes for 2 minutes and observe for improvement in ptosis. 1 This simple bedside test can provide immediate diagnostic support.

The Tensilon (edrophonium) test is usually negative in patients with botulism but may show minimal responses in MG, helping differentiate these conditions. 4

Electrodiagnostic Studies

Single-fiber electromyography (EMG) is the gold standard diagnostic test with >90% sensitivity for ocular myasthenia. 1, 2, 5

• Repetitive nerve stimulation (RNS) at 2-5 Hz can demonstrate decremental response, though it is positive in only one-third of patients with ocular myasthenia 2
• Standard EMG and nerve conduction studies may be normal early in disease course 4

Important caveat: Electrodiagnostic studies are operator-dependent, require specialized equipment and expertise, can take 2 hours to complete, and may be normal early in the disease. 4 Do not rely solely on these tests if clinical suspicion is high.

Ancillary Testing

• Cerebrospinal fluid examination: Typically normal in MG (mild protein elevation is uncommon), which helps distinguish from Guillain-Barré syndrome where CSF protein is often elevated by week 2 4
• Brain imaging: May help exclude brainstem strokes that can mimic MG 4
• Pulmonary function testing: Measure negative inspiratory force and vital capacity, especially crucial in generalized MG to monitor for respiratory compromise 1, 6

Critical Differential Diagnoses to Exclude

When evaluating suspected MG, actively exclude:

• Third nerve palsy: Look for pupillary abnormalities (which MG lacks); requires immediate neuroimaging for aneurysm risk 1
• Thyroid eye disease: Check for proptosis, eyelid retraction, and mechanical restriction on forced duction testing; orbital imaging shows tendon-sparing muscle enlargement 1
• Botulism: Consider when MG or Guillain-Barré are suspected; look for symmetric cranial nerve palsies and gastrointestinal symptoms 4
• Lambert-Eaton syndrome, chronic progressive external ophthalmoplegia, brainstem lesions: All can mimic MG presentation 1

Preoperative Considerations

Any patient with suspected myasthenia gravis requiring surgery MUST have serum anti-acetylcholine receptor antibody levels measured preoperatively to avoid respiratory failure during anesthesia. 1 This is particularly critical since approximately 30-50% of patients with thymomas have MG, and in 20% of thymoma patients, mortality is related to myasthenia complications. 1

Prognostic Information

Approximately 50-80% of patients presenting with isolated ocular symptoms will develop generalized myasthenia within a few years, making accurate early diagnosis essential for preventing life-threatening respiratory failure. 1 Regular respiratory function assessment and close neurological follow-up are mandatory. 1, 6