What is the procedure for a Neostigmine (acetylcholinesterase inhibitor) challenge test in diagnosing Myasthenia Gravis (MG)?

Neostigmine Challenge Test Procedure in Myasthenia Gravis

Administer neostigmine 0.5 mg intramuscularly and assess clinical response at 30-45 minutes, with atropine immediately available to counteract potential muscarinic side effects including bradycardia, bronchospasm, and excessive salivation. 1, 2

Pre-Test Preparation

• Ensure atropine is drawn up and immediately available before administering neostigmine, as muscarinic side effects (excess tearing, salivation, sweating, abdominal cramping, bradycardia, bronchospasm, hypotension) can occur 3
• Perform baseline clinical assessment using objective measures such as ptosis measurement, extraocular movement range, or limb strength testing 2
• Consider baseline neurophysiological testing with CN-SFEMG if available for more objective documentation 2
• The test should be performed in a monitored setting by practitioners experienced with proper administration 3

Administration Protocol

• Administer neostigmine 0.5 mg intramuscularly 1, 2
• Alternative intranasal route: 2-4 puffs (one puff = 4.6 mg) can provide faster onset within 3 minutes, peaking at 18-33 minutes 4
• The intramuscular route is standard for diagnostic testing, while intranasal may be useful when rapid effect is needed 5, 4

Assessment Timeline and Response Evaluation

• Peak clinical response occurs at 30-45 minutes post-injection for intramuscular administration 2
• For intranasal administration, effect is evident within 3 minutes and peaks at 18-33 minutes 4
• Document improvement in specific clinical parameters:
  • Reduction in ptosis (measure in millimeters) 3
  • Improvement in extraocular movements and diplopia 3
  • Increased limb strength 2
  • Improvement in bulbar symptoms if present 5

Interpreting Test Results

• The neostigmine test demonstrates 93.4% positivity in ocular myasthenia and 97.92% positivity in generalized myasthenia, making it more sensitive than anti-AChR antibodies (57.36% and 93.77% respectively) or repetitive nerve stimulation (51.78% and 82.35% respectively) 1
• A positive test shows clear clinical improvement in weakness, ptosis, or diplopia within the expected timeframe 1, 2
• CN-SFEMG recordings, if performed, will show significant improvement in mean consecutive differences, single-pair jitter, and blocks even when clinical improvement is subtle 2

Critical Safety Considerations

• Monitor for muscarinic side effects throughout the test period, particularly bradycardia and bronchospasm 3
• Have atropine ready for immediate administration if severe muscarinic effects occur 3
• Avoid this test in patients currently taking cholinesterase inhibitors like pyridostigmine, as they already have reduced plasma cholinesterase activity and are at risk for prolonged effects 3
• If the patient is on pyridostigmine, consider holding the morning dose before testing or use the edrophonium (Tensilon) test instead, which has a shorter duration of action 3

Comparison to Edrophonium (Tensilon) Test

The neostigmine test offers advantages over edrophonium testing in certain contexts:

• Longer duration of action allows for more thorough clinical assessment 2
• Higher sensitivity, particularly in ocular myasthenia (93.4% vs 86% for edrophonium) 3, 1
• However, edrophonium has faster onset (seconds to minutes) and shorter duration, making it preferable when rapid confirmation is needed 3

Post-Test Management

• Effects last 1-2 hours for intramuscular administration and over 2 hours for intranasal administration 4, 2
• Document all clinical changes objectively using standardized scales like the MG Composite (MGC) scale when possible 2
• A positive test supports the diagnosis but should be confirmed with anti-AChR antibodies, anti-MuSK antibodies if seronegative, and electrodiagnostic studies 6, 7