What condition is associated with a positive Neostigmine test?

Neostigmine Test is Positive in Myasthenia Gravis

The Neostigmine test is positive in myasthenia gravis, showing significant clinical improvement in muscle strength and reduction of fatigue symptoms after administration. This diagnostic test is particularly valuable in confirming myasthenia gravis when clinical presentation is suggestive but other tests may be inconclusive.

Mechanism and Diagnostic Value

Neostigmine is an acetylcholinesterase inhibitor that:

• Prevents breakdown of acetylcholine at the neuromuscular junction
• Increases availability of acetylcholine to bind with receptors
• Temporarily improves neuromuscular transmission in myasthenic patients

The test works because:

• In myasthenia gravis, there is a reduction in functional acetylcholine receptors due to autoantibodies
• Neostigmine compensates for this deficit by increasing acetylcholine concentration at the synapse
• This results in measurable improvement in muscle strength and reduction of fatigue symptoms

Test Performance Characteristics

The Neostigmine test shows excellent sensitivity in myasthenia gravis:

• 93.4% positivity in ocular myasthenia gravis 1
• 97.92% positivity in generalized myasthenia gravis 1
• Higher positivity rate than anti-acetylcholine receptor antibodies (57.36% in ocular and 93.77% in generalized MG) 1
• Higher positivity rate than repetitive nerve stimulation (51.78% in ocular and 82.35% in generalized MG) 1

Test Protocol and Evaluation

The test involves:

1. Baseline assessment of muscle strength and fatigue symptoms
2. Administration of neostigmine (typically 0.5 mg)
3. Evaluation of clinical response after 90 minutes 2

Positive response is evaluated through:

• Clinical improvement measured by MG composite scale
• Neurophysiological improvement on concentric-needle single-fiber electromyography (CN-SFEMG) 2
• Reduction in mean value of consecutive differences (MCD)
• Decrease in single-pair jitter and blocks on electromyography

Clinical Applications

The Neostigmine test is particularly valuable in:

• Confirming diagnosis when clinical presentation suggests myasthenia gravis
• Cases where antibody tests are negative (seronegative myasthenia gravis)
• Distinguishing between myasthenic and cholinergic crisis
• Evaluating treatment response

Important Precautions

When performing the Neostigmine test:

• Administer in a monitored setting with resuscitation equipment available
• Have atropine readily available to counteract muscarinic side effects
• Use with caution in patients with cardiac conditions, as neostigmine can cause bradycardia 3
• Monitor for potential adverse effects including excessive salivation, abdominal cramping, and bradycardia

Alternative Diagnostic Tests

While the Neostigmine test is highly sensitive, a comprehensive diagnostic approach may include:

• Anti-acetylcholine receptor antibody testing (positive in ~80% of generalized MG)
• Anti-MuSK and anti-LRP4 antibody testing in seronegative cases
• Repetitive nerve stimulation
• Single-fiber electromyography (considered gold standard in many centers) 4
• Ice pack test (application of ice over closed eyes for 2 minutes for ptosis or 5 minutes for strabismus) 4

The Neostigmine test remains a valuable diagnostic tool, particularly in resource-limited settings or when other tests are inconclusive, with its high sensitivity making it an important component of the diagnostic algorithm for myasthenia gravis.