Ice Test for Myasthenia Gravis

The ice test is a simple, non-invasive bedside test that can help diagnose myasthenia gravis in patients with ptosis (droopy eyelid). By applying cold to the eyelid, the test temporarily improves myasthenic weakness, providing a rapid and cost-free clue to the diagnosis.

Why the Ice Test Works

Mechanism

In myasthenia gravis, antibodies block acetylcholine receptors at the neuromuscular junction, preventing normal muscle activation. When ice is applied:

1. Cold temperature reduces the activity of acetylcholinesterase (the enzyme that breaks down acetylcholine)
2. More acetylcholine accumulates at the neuromuscular junction
3. This overcomes some of the receptor blockade
4. Muscle function temporarily improves

This effect is specific to myasthenic weakness. Other causes of ptosis (such as third nerve palsy or Horner syndrome) do not improve with cooling.

Why It's Specific

• Cold affects the enzyme that degrades acetylcholine
• It doesn't strengthen normal muscles
• It doesn't fix nerve problems (like sixth nerve palsy or fourth nerve palsy)
• Only helps when the problem is at the neuromuscular junction

When to Use the Ice Test

Indications

• Ptosis (droopy eyelid) of unknown cause
• Suspected myasthenia gravis
• Ptosis that varies during the day (worse with fatigue)
• Ptosis associated with fatigable double vision
• When rapid bedside assessment is needed
• When serology results are pending

Not Useful For

• Double vision without ptosis (ice doesn't help eye alignment)
• Known non-myasthenic ptosis
• Ruling out myasthenia completely (negative test doesn't exclude it)

How the Test Is Done

Materials Needed

• Ice pack, ice in a glove, or ice wrapped in a cloth
• Ruler or ptosis measurements (for before/after comparison)
• Timer

Procedure

1. Measure baseline ptosis

   • Measure margin-reflex distance (MRD1): distance from upper lid margin to corneal light reflex
   • Or simply note the width of the palpebral fissure
   • Document which lid(s) are droopy and by how much

2. Apply cold

   • Place ice pack (or ice in surgical glove) on the closed eyelid
   • Apply gentle pressure to ensure contact
   • Hold for 2 minutes (some protocols use up to 5 minutes)
   • Patient should keep eye closed during application

3. Remove ice immediately and measure

   • Remove the ice pack
   • Have patient open eyes immediately
   • Measure ptosis again right away (effect is temporary)
   • Compare to baseline

What to Look For

Positive test:

• Improvement of ≥2 mm in eyelid position is typically considered positive
• The lid opens wider, showing more of the eye
• Patient may notice they can see better out of that eye

Negative test:

• No improvement or <2mm change
• Lid position unchanged after ice application

Interpreting Results

Positive Ice Test

Suggests myasthenia gravis—but confirmatory testing is needed:

• Acetylcholine receptor (AChR) antibody blood test
• MuSK antibody test (if AChR negative)
• LRP4 antibody test (if both negative)
• Repetitive nerve stimulation (EMG study)
• Single fiber EMG (most sensitive)
• CT chest to evaluate for thymoma

Negative Ice Test

Does not rule out myasthenia:

• Sensitivity is ~80-90%, not 100%
• Some patients with myasthenia will have a negative ice test
• Other diagnostic tests should still be pursued if clinical suspicion is high

False Positives

Rare, but possible if:

• Ptosis has other causes that coincidentally improve
• Measurement error
• Patient cooperation issues

False Negatives

May occur if:

• Very severe myasthenia (poor baseline function)
• Myasthenia with predominant diplopia rather than ptosis
• Ice not applied long enough or with poor contact
• Ptosis from non-myasthenic cause

Test Performance

Sensitivity and Specificity

Study	Sensitivity	Specificity
Pooled data	80-90%	95-100%

• High specificity: If positive, likely myasthenia
• Moderate sensitivity: Negative test doesn't exclude myasthenia

Advantages

• Zero cost—just need ice
• No side effects
• Immediate results
• Can be done anywhere—bedside, office, even at home as a screening tool
• No special equipment needed
• High specificity (few false positives)

Limitations

• Only works for ptosis (not double vision alone)
• Not 100% sensitive (negative doesn't exclude myasthenia)
• Requires measurable ptosis at time of test
• Effect is temporary—must measure immediately
• Results can vary with technique

Differential Diagnosis of Ptosis

When considering the ice test, remember other causes of ptosis:

Condition	Ice Test	Other Features
Myasthenia gravis	Positive	Fatigable, variable, diplopia
Third nerve palsy	Negative	Pupil may be involved, eye turned out/down
Horner syndrome	Negative	Mild ptosis, small pupil, anhidrosis
Aponeurotic ptosis (aging)	Negative	High lid crease, common in elderly
Congenital ptosis	Negative	Present from birth, lid lag
Chronic progressive external ophthalmoplegia	Negative	Bilateral, progressive, limited eye movements

What Happens After a Positive Ice Test

Confirm the Diagnosis

1. Blood tests

   • AChR binding antibodies (positive in ~85% of generalized MG, ~50% of ocular MG)
   • MuSK antibodies (if AChR negative)
   • LRP4 antibodies (emerging)

2. Electrophysiology (if serology negative)

   • Repetitive nerve stimulation
   • Single fiber EMG (most sensitive)

3. Imaging

   • CT chest to look for thymoma
   • MRI brain only if other neurological signs

Begin Treatment Discussion

If myasthenia confirmed:

• Pyridostigmine (cholinesterase inhibitor)
• Immunosuppression considerations
• Thymectomy evaluation
• Monitoring for generalization (spread beyond eyes)

Frequently Asked Questions

Does the ice test hurt?

No. It's just cold. You may feel mild discomfort from the cold temperature, but it's not painful.

How long does the improvement last?

The effect is temporary—typically only a few minutes. That's why measurements must be taken immediately after removing the ice.

Can I do this test at home?

Yes, as a preliminary check. If applying ice to your droopy eyelid makes it open better, this is worth mentioning to your doctor who can perform a formal evaluation.

If my ice test is positive, do I definitely have myasthenia?

A positive ice test strongly suggests myasthenia gravis, but confirmatory blood tests and sometimes EMG studies are needed to confirm the diagnosis.

Why didn't my doctor do more testing if my ice test was positive?

The ice test is a screening tool. Your doctor likely ordered blood tests for myasthenia antibodies and possibly other studies to confirm the diagnosis before starting treatment.

Can the ice test help with double vision?

The ice test is designed for ptosis (droopy eyelid). It doesn't reliably improve eye alignment or double vision in myasthenia, so it's less useful when diplopia is the main symptom.

My ptosis varies throughout the day—when should I be tested?

Ideally when your ptosis is present and noticeable. If your eyelid is not droopy at the time of testing, there's nothing to measure improvement against.

References