Examination in Myasthenia Gravis
A thorough examination in myasthenia gravis must systematically assess for fatigable weakness in ocular, bulbar, respiratory, and limb muscles, with particular attention to pupil-sparing ptosis and ophthalmoplegia, while documenting objective improvement with rest or ice application. 1
Essential Clinical History Components
- Fluctuating muscle weakness that worsens with repetitive use and improves with rest, particularly affecting proximal more than distal muscles 1, 2
- Ocular symptoms including ptosis and diplopia, present in the majority of patients at onset 1, 3
- Bulbar manifestations such as dysarthria (speech becoming unintelligible during prolonged speaking), dysphagia (food remaining in mouth after swallowing), and facial weakness 1, 4
- Respiratory symptoms including shortness of breath with light activity, which requires urgent assessment 1
- Temporal pattern with symptoms typically worse later in the day or after sustained activity 2, 3
- Associated autoimmune conditions including thyroid disease (hyperthyroidism, Hashimoto's disease) 3
Critical pitfall: A history of "speech becoming unintelligible during prolonged speaking" has a likelihood ratio of 4.5 for myasthenia gravis, making this a particularly valuable historical feature 4.
Physical Examination Findings
Ocular Examination
- Ptosis assessment with sustained upgaze for 60 seconds to demonstrate fatigability 1
- Extraocular movements testing for diplopia and ophthalmoplegia, noting that pupils are characteristically not affected in myasthenia gravis 1
- Peek sign (eyelid elevation when attempting to close eyes tightly), which has a likelihood ratio of 30.0 when present 4
- Quiver eye movements may be observed 4
Critical distinction: Pupillary involvement should immediately alert you to consider alternative diagnoses such as third nerve palsy, as myasthenia affects nicotinic receptors at the neuromuscular junction but not the autonomic nervous system controlling pupillary function 1.
Bulbar and Facial Examination
- Facial muscle strength testing, including assessment for facial weakness 1, 2
- Speech evaluation during prolonged conversation to detect dysarthria 1, 4
- Swallowing assessment for dysphagia 1
- Jaw strength testing for masseter weakness 2
Respiratory Assessment
- Pulmonary function testing is crucial in generalized myasthenia gravis to monitor for respiratory compromise 1
- Assessment of respiratory muscle strength particularly in patients with bulbar symptoms or generalized weakness 5
- Diaphragmatic function evaluation, as diaphragmatic compound muscle action potentials may be low-amplitude in severe cases 5
Limb Examination
- Proximal muscle strength testing in upper and lower extremities, as weakness is typically more proximal than distal 1, 2
- Fatigability testing with repetitive movements (e.g., sustained arm abduction, repeated squatting) 2, 3
- Deep tendon reflexes which are typically normal 2
Bedside Diagnostic Tests
Ice Pack Test
- Apply ice pack over closed eyes for 2 minutes and measure improvement in ptosis 1, 6
- Highly specific for myasthenia gravis, particularly for ocular symptoms 1
- Positive test: Likelihood ratio of 24.0; Negative test: Likelihood ratio of 0.16 4
Rest Test
- Have patient rest in a dark, quiet room for 30 minutes with eyes closed 4
- Measure improvement in ptosis or other fatigable symptoms 4
- Negative test makes myasthenia unlikely (likelihood ratio 0.52) 4
Sleep Test
- Abnormal result has a likelihood ratio of 53.0 for confirming diagnosis 4
- Normal result makes myasthenia very unlikely (likelihood ratio 0.01) 4
Neostigmine Challenge Test
- Pre-test preparation: Ensure atropine is drawn up and immediately available before administering neostigmine 6
- Document improvement in specific clinical parameters including reduction in ptosis, improvement in extraocular movements and diplopia 6
- Monitor for muscarinic side effects throughout the test period, particularly bradycardia and bronchospasm 6
- Positive response: Likelihood ratio of 15.0; Negative response: Likelihood ratio of 0.11 4
- Avoid in patients currently taking pyridostigmine due to risk of prolonged effects 6
Important note: The neostigmine test offers higher sensitivity than edrophonium testing, particularly in ocular myasthenia 6.
Laboratory and Electrodiagnostic Studies
Serologic Testing
- Acetylcholine receptor (AChR) antibodies present in 80-85% of patients, though only 40-77% in ocular myasthenia 1, 2, 3
- Anti-MuSK antibodies if seronegative for AChR, found in 5-8% of patients 2, 3
- Anti-striated muscle antibodies particularly in patients with suspected thymoma 1
Critical consideration: Approximately 10% of patients are seronegative for all known antibodies, so negative antibody testing does not exclude myasthenia gravis 2, 3.
Electrodiagnostic Studies
- Repetitive nerve stimulation showing >10% decremental response 1, 5
- Single-fiber EMG with >90% sensitivity for ocular myasthenia 1
Important pitfall: Decremental responses may be absent during periods of severe weakness, particularly in patients with isolated bulbar and respiratory muscle involvement, and may only become positive after treatment initiation 5.
Imaging Studies
- Chest CT or MRI to evaluate for thymoma, present in 10-20% of AChR-positive patients 2, 3
- Brain imaging may help exclude brainstem strokes that can mimic myasthenia gravis 1
Key Differential Diagnoses to Exclude
- Third nerve palsy: Distinguished by pupillary abnormalities (unlike myasthenia) and requires immediate neuroimaging 1
- Thyroid eye disease: Shows proptosis, eyelid retraction, and mechanical restriction on forced duction testing rather than fatigable weakness 7, 1
- Botulism: Presents with symmetric cranial nerve palsies and gastrointestinal symptoms 1
- Lambert-Eaton syndrome: Distinguished by autonomic symptoms and post-exercise facilitation 1
Critical warning: Approximately 50-80% of patients presenting with isolated ocular symptoms will develop generalized myasthenia within a few years, making accurate diagnosis essential for preventing life-threatening respiratory failure 1.