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Unilateral ptosis not corrected with ucepack test RNS negative

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ptosis ice pack test myasthenia gravis negative

This set of six clinical photographs (A-F) illustrates the variability of the ice test in a patient with myasthenia gravis presenting with bilateral asymmetric ptosis. The images are arranged in pairs representing three different days, showing the patient's eyes before and after a 2-minute ice application. Frames A, C, and E show baseline bilateral blepharoptosis with varying degrees of upper eyelid drooping obscuring the pupil and iris. Frames B, D, and F show the post-intervention state. The series demonstrates three distinct clinical responses in the right eye: (B) a negative result with no significant change, (D) an equivocal result showing subtle 1.0 mm elevation, and (F) a positive result with a marked 2.0 mm increase in the palpebral fissure. This comparison serves as an educational tool for neurology and ophthalmology students to understand the fluctuating nature of neuromuscular junction disorders and the diagnostic utility (and inconsistency) of the ice pack test, which temporarily improves ptosis by inhibiting acetylcholinesterase at the motor endplate.

This set of six clinical photographs (A-F) illustrates the variability of the ice test in a patient with myasthenia gravis presenting with bilateral asymmetric ptosis. The images are arranged in pairs representing three different days, showing the patient's eyes before and after a 2-minute ice application. Frames A, C, and E show baseline bilateral blepharoptosis with varying degrees of upper eyelid drooping obscuring the pupil and iris. Frames B, D, and F show the post-intervention state. The series demonstrates three distinct clinical responses in the right eye: (B) a negative result with no significant change, (D) an equivocal result showing subtle 1.0 mm elevation, and (F) a positive result with a marked 2.0 mm increase in the palpebral fissure. This comparison serves as an educational tool for neurology and ophthalmology students to understand the fluctuating nature of neuromuscular junction disorders and the diagnostic utility (and inconsistency) of the ice pack test, which temporarily improves ptosis by inhibiting acetylcholinesterase at the motor endplate.

Two side-by-side clinical photographs labeled A and B demonstrate a bedside ice pack test in a patient with suspected myasthenia gravis. Image A (Before Ice Pack Test) shows significant left-sided blepharoptosis, with the upper eyelid drooping to partially cover the pupil (indicated by a black arrow). Image B (After Ice Pack Test) demonstrates a positive result, where the left eyelid shows temporary elevation and resolution of ptosis (indicated by a blue arrow) following local cooling. The patient is shown in a clinical setting wearing a blue surgical cap, a nasal cannula for oxygen delivery, and an adhesive nasal strip for stabilization. This comparative series illustrates the clinical utility of the ice pack test, which inhibits acetylcholinesterase activity at the neuromuscular junction to temporarily improve muscle strength in myasthenic patients. The images highlight key diagnostic physical exam findings in neuro-ophthalmology and neuromuscular medicine.

Two side-by-side clinical photographs labeled A and B demonstrate a bedside ice pack test in a patient with suspected myasthenia gravis. Image A (Before Ice Pack Test) shows significant left-sided blepharoptosis, with the upper eyelid drooping to partially cover the pupil (indicated by a black arrow). Image B (After Ice Pack Test) demonstrates a positive result, where the left eyelid shows temporary elevation and resolution of ptosis (indicated by a blue arrow) following local cooling. The patient is shown in a clinical setting wearing a blue surgical cap, a nasal cannula for oxygen delivery, and an adhesive nasal strip for stabilization. This comparative series illustrates the clinical utility of the ice pack test, which inhibits acetylcholinesterase activity at the neuromuscular junction to temporarily improve muscle strength in myasthenic patients. The images highlight key diagnostic physical exam findings in neuro-ophthalmology and neuromuscular medicine.

A clinical photograph focused on the periocular region of a 59-year-old female patient, demonstrating bilateral ptosis (upper eyelid drooping). The presentation is asymmetrical, with the right upper eyelid showing a more pronounced descent, covering a larger superior portion of the iris compared to the left eye. A vertical ruler is positioned on the left side of the frame as a measuring tool to quantify the palpebral fissure height or marginal reflex distance. This image represents the baseline state 'before ice test' in a clinical evaluation for neuromuscular junction disorders, such as ocular myasthenia gravis or Lambert-Eaton myasthenic syndrome (LEMS). The surrounding skin appears normal without visible inflammation or edema. This visual material is used to teach diagnostic bedside maneuvers for evaluating fatiguable ptosis and distinguishing between various causes of blepharoptosis in an ophthalmological or neurological context.

A clinical photograph focused on the periocular region of a 59-year-old female patient, demonstrating bilateral ptosis (upper eyelid drooping). The presentation is asymmetrical, with the right upper eyelid showing a more pronounced descent, covering a larger superior portion of the iris compared to the left eye. A vertical ruler is positioned on the left side of the frame as a measuring tool to quantify the palpebral fissure height or marginal reflex distance. This image represents the baseline state 'before ice test' in a clinical evaluation for neuromuscular junction disorders, such as ocular myasthenia gravis or Lambert-Eaton myasthenic syndrome (LEMS). The surrounding skin appears normal without visible inflammation or edema. This visual material is used to teach diagnostic bedside maneuvers for evaluating fatiguable ptosis and distinguishing between various causes of blepharoptosis in an ophthalmological or neurological context.

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Here is a thorough analysis of this clinical scenario:

Unilateral Ptosis: Ice Pack Test Negative + RNS Negative

What These Two Negative Tests Mean

Ice Pack Test (negative): The ice pack test works by local cooling of the ptotic eyelid, which inhibits acetylcholinesterase at the neuromuscular junction (NMJ) and temporarily increases available acetylcholine - improving ptosis in myasthenia gravis (MG). A negative ice pack test (no improvement in ptosis after 2 minutes of ice application) makes MG unlikely as the cause of ptosis.
As stated in Bradley and Daroff's Neurology: "a negative ice-pack test in a ptotic lid makes MG unlikely" (Fakiri et al., 2013).
RNS Negative: Repetitive nerve stimulation detects a decremental response to slow stimulation, confirming impaired NMJ transmission. However, this test has a critical limitation:
"RNS confirms impaired NMT but is frequently normal in mild or purely ocular disease."
  • Bradley and Daroff's Neurology in Clinical Practice
So a negative RNS does NOT rule out ocular MG - it is commonly false-negative in isolated ocular involvement. But taken together with a negative ice pack test, MG becomes much less likely.

Differential Diagnosis: If Not MG, Then What?

CauseKey Features
Horner SyndromeMild unilateral ptosis (2-3 mm), miosis (small pupil), anhidrosis, lower lid elevation (upside-down ptosis); no EOM involvement
CN III (Oculomotor) PalsyComplete ptosis, eye deviated "down and out," dilated pupil (if compressive - e.g. aneurysm), or pupil-sparing (if ischemic - diabetes/HTN)
Aponeurotic/Involutional PtosisMost common in elderly, elevated superior eyelid crease, good levator function, no neurological signs
CPEO (Mitochondrial)Bilateral (often asymmetric) slowly progressive ptosis + ophthalmoplegia; Kearns-Sayre syndrome if + retinopathy + cardiac conduction defects
Oculopharyngeal Muscular DystrophyBilateral ptosis + dysphagia, late-onset (>50 years), autosomal dominant, GCG repeat in PABPN1 gene
Myotonic DystrophyBilateral ptosis + facial weakness, myotonia, systemic features
Mechanical ptosisLid mass, inflammation, infiltration
Cerebral (Supranuclear) ptosisRight hemispheric lesion, gaze deviation, upgaze paresis

How to Differentiate Further

For Horner Syndrome (most common cause of mild unilateral ptosis):
  • Look for miosis (anisocoria greater in dim light)
  • Apraclonidine 1% eye drop test (reversal of anisocoria confirms Horner)
  • Cocaine 4-10% test (pupil fails to dilate on affected side)
  • Hydroxyamphetamine test localizes to preganglionic vs postganglionic
For CN III Palsy:
  • Is there EOM restriction (adduction, elevation, depression)?
  • Is the pupil dilated? - if yes, urgent neuroimaging to rule out posterior communicating artery aneurysm
  • Pupil-sparing CN III palsy in a diabetic/hypertensive patient = microvascular
If MG is still suspected (seronegative):
  • Even with negative RNS and negative ice pack test, MG is not fully excluded
  • Proceed to Single-Fiber EMG (SFEMG) - the most sensitive test for NMJ dysfunction, showing increased jitter in almost all MG patients, even those with purely ocular disease (60% show abnormal jitter even in a limb muscle)
  • Check AChR antibodies and anti-MuSK antibodies (AChR Ab negative does not exclude MG)
  • Consider a tensilon/edrophonium test if SFEMG not available

Bottom Line

TestResultImplication
Ice Pack TestNegativeMG unlikely but not excluded
RNSNegativeCommon in ocular MG; does NOT rule it out
Next stepSFEMGMost sensitive - abnormal in ~98% of MG; can confirm or exclude
If SFEMG also negativeConsider non-MG causesHorner, CN III palsy, aponeurotic, myogenic
The most important next steps are:
  1. SFEMG (if MG still clinically suspected)
  2. Pupil examination - miosis = Horner; mydriasis + EOM palsy = CN III
  3. AChR / anti-MuSK antibodies
  4. Neuroimaging (MRI brain/orbits, MRA if CN III palsy with pupil involvement)
  • Bradley and Daroff's Neurology in Clinical Practice (p. 2776)
  • Bradley and Daroff's Neurology in Clinical Practice (p. 2770, Table 17.2)
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