Ice Pack Test for Myasthenia Gravis
How to Perform the Test
Apply an ice pack over the closed eyelids for 2 minutes when evaluating ptosis, or for 5 minutes when evaluating strabismus or ophthalmoplegia. 1, 2
Step-by-Step Technique
Measure baseline findings before applying ice: document the degree of ptosis using marginal reflex distance (MRD) and measure any ocular misalignment in prism diopters using cover testing 1, 3
Place the ice pack directly over both closed eyelids, ensuring good contact with the skin 1, 2
Time the application precisely: 2 minutes for isolated ptosis, 5 minutes for diplopia or strabismus 1, 2, 3
Immediately reassess after removing the ice pack: remeasure MRD for ptosis and repeat cover testing for strabismus 1, 3
Enhanced Technique for Mild Ptosis
In patients with subtle ptosis (common in Asian populations with low or absent eyelid folds), perform sustained upgaze for 2 minutes immediately before applying the ice pack to accentuate fatigable weakness 4
This modification increases sensitivity from 27.8% to 72.2% in patients with mild ptosis, while maintaining 96.7% specificity 4
Interpretation Criteria
A positive test requires improvement of ptosis by at least 2 mm or reduction in ocular deviation by 50% (or by ≥10 prism diopters if the baseline deviation exceeds 20 PD). 1, 2, 3
Diagnostic Performance
For ptosis: sensitivity 89-95%, specificity 100%, positive predictive value 100% 2, 5, 6
For diplopia/ophthalmoplegia: sensitivity 76.9-83%, specificity 98.3-100%, positive predictive value 100% 2, 5, 3
The test demonstrates higher sensitivity for ptosis than for ophthalmoplegia, so a partial response (50% improvement rather than complete resolution) should still be considered positive for myasthenic diplopia 3
Single-fiber EMG remains the gold standard with >90% sensitivity, but the ice pack test offers immediate bedside diagnostic information 2
Physiologic Basis
Cooling slows acetylcholine breakdown at the neuromuscular junction, allowing the limited acetylcholine to remain in the synaptic cleft longer and partially compensate for the reduced receptor availability caused by autoantibodies. 7
This mechanism explains why the test is highly specific for myasthenia gravis rather than other causes of ptosis or ophthalmoplegia 1, 7
The test does not affect pupillary function because myasthenia targets nicotinic receptors at skeletal muscle junctions, not autonomic receptors 7
Clinical Context and Pitfalls
When to Use the Test
Apply the ice pack test in any patient presenting with variable or fatigable ptosis, fluctuating diplopia, or strabismus that changes over the course of examination 1, 2
The test is particularly valuable as an immediate screening tool while awaiting serologic testing (AChR antibodies) and electrodiagnostic studies 2, 8
Critical Distinguishing Features
Pupils must be normal in myasthenia gravis; abnormal pupils should immediately redirect evaluation toward third nerve palsy, Horner syndrome, or other neurologic causes 2, 7
Patients with oculomotor nerve paresis and Horner syndrome are invariably nonresponsive to the ice pack test, providing useful differential diagnostic information 3
The test maintains high specificity even in patients with coexisting myasthenic and thyroid eye disease, though thyroid ophthalmopathy shows mechanical restriction on forced duction testing rather than fatigable weakness 2, 3
Alternative Bedside Test
- A rest test without ice (having the patient close their eyes for several minutes) can also demonstrate improvement in ptosis and strabismus, though this is less well-standardized than the ice pack test 1, 2
Prognostic Implications
50-80% of patients presenting with isolated ocular symptoms will progress to generalized myasthenia within a few years, most commonly within the first two years 1, 2
A positive ice pack test should prompt immediate workup including AChR antibodies, consideration of anti-MuSK and anti-LRP4 antibodies if seronegative, electrodiagnostic studies, and chest imaging to evaluate for thymoma 2
Regular pulmonary function monitoring is essential given the risk of respiratory compromise, particularly in patients with bulbar symptoms such as dysphagia, which precedes myasthenic crisis in >50% of cases 2