How is a fatiguability test performed in a patient suspected of having myasthenia gravis (Muscle Gravis)?

How to Perform a Fatiguability Test in Myasthenia Gravis

The fatiguability test in myasthenia gravis involves observing for worsening muscle weakness with repeated or sustained muscle activity, most commonly assessed through clinical examination of ocular muscles (sustained upgaze for ptosis), repetitive nerve stimulation showing decremental response, or standardized physical performance tests like the arm movement test. 1, 2

Clinical Bedside Fatiguability Testing

Ocular Muscle Fatiguability

• Sustained upgaze test: Have the patient look upward continuously for 30-60 seconds and observe for progressive worsening of ptosis or development of diplopia, which indicates fatigable weakness characteristic of myasthenia gravis 1, 2
• Repeated eye movement: Ask the patient to perform rapid saccadic eye movements repeatedly and assess for increasing ophthalmoplegia or diplopia 1
• The ocular muscles are particularly susceptible to fatigue due to the high proportion of twitch fibers and fewer acetylcholine receptors in these muscles 1

Ice Pack Test (Diagnostic Adjunct)

• Apply an ice pack over closed eyes for 2 minutes for ptosis assessment or 5 minutes for strabismus evaluation 2, 3
• Expect approximately 2mm reduction in ptosis if myasthenia gravis is present 2, 3
• This test has 92% sensitivity and high specificity for myasthenia gravis, particularly for ocular symptoms 2, 3
• The cooling slows acetylcholine breakdown at the neuromuscular junction, temporarily compensating for reduced receptor availability 3

Bulbar and Limb Muscle Fatiguability

• Sustained arm abduction: Have the patient hold arms extended at 90 degrees and observe for progressive weakness over 1-2 minutes 1, 2
• Repetitive counting: Ask the patient to count aloud from 1 to 100 and listen for progressive dysarthria or hypophonia indicating bulbar muscle fatigue 1, 2
• Repeated swallowing: Observe for increasing dysphagia with repeated swallowing attempts 1

Electrodiagnostic Fatiguability Testing

Repetitive Nerve Stimulation (RNS)

• Perform slow-frequency (2-3 Hz) repetitive stimulation of a motor nerve while recording compound muscle action potentials (CMAP) from the corresponding muscle 1, 2, 4
• A decremental response of >10% between the first and fourth CMAP is considered positive for neuromuscular junction dysfunction 4
• Sensitivity is 71.6% in generalized myasthenia gravis but only 38.5% in purely ocular disease, making it less reliable for ocular-only presentations 4
• Test multiple muscles if initial testing is negative, as sensitivity increases with testing of clinically affected muscles 5, 4

Single-Fiber Electromyography (SFEMG)

• SFEMG is the gold standard with >90% sensitivity for ocular myasthenia gravis, far superior to repetitive nerve stimulation 2, 6
• Measures "jitter" (variability in time interval between two muscle fiber action potentials from the same motor unit) which increases with neuromuscular junction dysfunction 1, 2
• Requires specialized equipment and expertise, limiting widespread availability 6

Quantitative Physical Performance Tests

Arm Movement Test (AMT)

• Measure the number of arm movements performed in consecutive time intervals (e.g., 30-second intervals over several minutes) 7
• Calculate linear trend (LT) reflecting dynamic performance decline over time 7
• Myasthenia gravis patients show negative LT (declining performance) even when routine testing appears normal 7
• This correlates with acetylcholine receptor antibody elevation (r = -0.59, P < 0.005) but not with subjective fatigue perception 7

Six-Minute Walk Test (6MWT)

• Measure distance walked in consecutive 1-minute intervals over 6 minutes 7
• Calculate LT to quantify progressive decline in walking speed, which differs significantly from stable performance in healthy controls 7
• Useful for detecting fatigability even in patients with low quantitative MG scores and no pathologic decrement on RNS 7

Critical Diagnostic Workup After Positive Fatiguability Testing

Essential Laboratory Tests

• Anti-acetylcholine receptor (AChR) antibodies should be tested first, present in 80% of generalized myasthenia gravis but only 50% of ocular cases 2, 6
• Anti-muscle-specific kinase (MuSK) antibodies if AChR antibodies are negative, as one-third of seronegative patients are MuSK-positive 2
• Anti-striated muscle antibodies should be included in initial workup 1, 2

Respiratory Assessment

• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 1, 2
• This is critical as fatigability can progress to respiratory compromise 1

Evaluation for Concurrent Conditions

• CPK, aldolase, ESR, CRP to evaluate for concurrent myositis 1, 2
• Troponin T and ECG (consider echocardiogram) if respiratory insufficiency or elevated CPK to rule out myocarditis 1, 2
• CT chest with contrast after diagnosis confirmation to evaluate for thymoma, present in 10-20% of AChR-positive patients 2

Important Caveats

• Pupils are characteristically spared in myasthenia gravis; pupillary involvement should prompt immediate consideration of third nerve palsy or other diagnoses 6
• Fatiguability testing may be normal early in disease or in well-controlled patients, requiring repeat testing or more sensitive methods like SFEMG 5, 4
• Physical fatigability does not correlate with subjective fatigue perception, which is influenced by depression and sleep disturbance rather than objective muscle weakness 8, 7
• 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years, necessitating ongoing monitoring even with isolated ocular fatiguability 2, 6