In an adult or adolescent presenting with fluctuating weakness, ptosis, diplopia, or dysphagia, how is the repetitive nerve stimulation test performed and interpreted for diagnosing myasthenia gravis?

Repetitive Nerve Stimulation Test for Myasthenia Gravis

Repetitive nerve stimulation (RNS) testing should be performed at 3 Hz as the standard frequency, with additional testing at 7 Hz to maximize diagnostic sensitivity, particularly in patients with mild generalized myasthenia gravis. 1

Test Performance Technique

Standard Protocol

• Apply low-rate stimulation at 3 Hz (3 stimuli per second) as the conventional frequency, delivering a short train of repetitive stimuli to the tested muscle 2
• Add testing at 7 Hz to augment sensitivity, as decremental responses are detected more frequently at this frequency than at the standard 3 Hz 1
• Test multiple muscle groups to increase diagnostic yield, as combining results from three muscles significantly increases sensitivity, especially in mild generalized MG 3

Muscle Selection Strategy

• Proximal muscles demonstrate higher sensitivity than distal muscles, with the accessory nerve (trapezius) showing superior diagnostic yield compared to ulnar nerve testing of hand muscles 3
• Test the accessory nerve (trapezius) as a valuable second-line test when initial distal muscle testing is negative, particularly in mild generalized MG 3
• Include facial muscles when bulbar symptoms are present, as these may show abnormalities when limb muscles are normal 2

Interpretation Criteria

Positive Test Definition

• A decrement of ≥10% in compound muscle action potential (CMAP) amplitude between the first and fourth or fifth stimulus indicates neuromuscular junction dysfunction consistent with myasthenia gravis 4, 5
• The decremental response corresponds to clinical muscle fatigability and confirms impaired neuromuscular transmission 6

Expected Sensitivity by Disease Subtype

• Generalized MG: 71.6% sensitivity when testing multiple muscles 6
• Ocular MG: only 38.5% sensitivity, making RNS positive in only one-third of purely ocular cases 2, 6
• Myasthenic crisis: 92% sensitivity, as severe weakness increases the likelihood of detecting decrements 4
• Inpatient setting: 83.3% sensitivity with 96.2% specificity, making RNS highly reliable for rapid diagnosis in hospitalized patients with higher grades of weakness 5

Clinical Context and Limitations

When RNS is Most Useful

• RNS serves as a rapid diagnostic tool in myasthenic crisis, providing results within hours compared to days for antibody testing 4, 5
• The test is more sensitive in AChR-antibody positive patients (present in 80% of generalized MG) than in seronegative cases 6
• Hospitalized patients with more severe weakness show higher RNS sensitivity than outpatients with milder symptoms 5

Critical Pitfall: Poor Sensitivity in Ocular MG

• Single-fiber EMG remains the gold standard for ocular myasthenia, with >90% sensitivity compared to RNS's 38.5% sensitivity in this population 2, 7
• A negative RNS does not exclude myasthenia gravis, particularly in purely ocular presentations where the majority of patients will have normal RNS 2, 6
• When clinical suspicion for ocular MG is high despite negative RNS, proceed directly to single-fiber EMG rather than repeating RNS 2, 7

Prognostic Limitations

• CMAP decrement does not correlate with long-term clinical outcomes or predict disease severity at follow-up, limiting RNS utility for prognosis 6
• There is no significant correlation between decrement magnitude and acetylcholine receptor antibody titers 6
• However, decrement does correlate with the worst recorded clinical status on a group level, suggesting some relationship to peak disease severity 6

Complementary Diagnostic Approach

When to Use Alternative Tests

• Order single-fiber EMG when RNS is negative but clinical features strongly suggest myasthenia (variable ptosis, fatigable diplopia, fluctuating weakness) 2, 7
• Perform ice pack test immediately at bedside (2 minutes for ptosis, 5 minutes for strabismus) as a highly specific screening tool while awaiting electrodiagnostic confirmation 2, 7
• Check AChR antibodies first as they confirm diagnosis in 80% of generalized MG and 50% of ocular MG 7, 8
• Test anti-MuSK antibodies when AChR is negative, as approximately one-third of seronegative patients are MuSK-positive 2, 7, 8

Pattern Recognition During Testing

• Standard MG pattern: decrement at low-rate stimulation (3 Hz) without post-exercise facilitation 4
• Lambert-Eaton pattern: low baseline CMAP amplitude with >100% increment after brief exercise or high-frequency stimulation, which may rarely appear in MG crisis 4
• Cholinergic crisis pattern: paradoxical findings that may occur with acetylcholinesterase inhibitor overdose 4