What is the appropriate diagnostic work‑up for a patient presenting with ptosis?

Diagnostic Work-Up for Ptosis

Begin with urgent pupillary examination in bright and dim lighting to identify third nerve palsy with pupillary involvement—a neurosurgical emergency requiring immediate neuroimaging to rule out posterior communicating artery aneurysm. 1

Step 1: Pupillary Assessment and Extraocular Motility

Pupil-Involving Ptosis (Dilated Pupil)

• Obtain urgent MRI with gadolinium plus MR angiography or CT angiography immediately to exclude compressive lesions, especially aneurysms 1, 2
• If MRI is unavailable, start with non-contrast CT to evaluate for subarachnoid hemorrhage, then proceed to CT angiography 2
• Posterior communicating artery aneurysm is the most urgent diagnosis; missing this can be fatal 3, 2

Pupil-Sparing Ptosis

• Complete ptosis with complete ophthalmoplegia and normal pupil in patients with diabetes, hypertension, or hyperlipidemia is almost always microvascular ischemic third nerve palsy 1, 2
• Incomplete ptosis or partial ophthalmoplegia with normal pupil requires neuroimaging (MRI with gadolinium and MRA or CTA) because compressive lesions can present this way 1, 3, 2
• This is the most dangerous pitfall: never assume pupil-sparing guarantees benign disease when the palsy is incomplete 3, 2

Step 2: Assess for Variability and Fatigability

Ice Pack Test

• Apply ice pack over closed eyes for 2 minutes for ptosis (5 minutes for strabismus) 4, 3
• Reduction of ptosis by approximately 2 mm is highly specific for myasthenia gravis 4, 1, 3
• This test should be performed before more invasive testing 1, 3

Clinical Signs of Myasthenia Gravis

• Variable ptosis that worsens with prolonged upgaze and improves with rest is pathognomonic 4, 3
• Cogan lid-twitch sign: brief eyelid overshoot when refixating from downgaze to primary position 4, 3
• Strabismus pattern changes during prolonged examination due to fatigability 4, 3
• Slow saccadic eye movements 4, 3
• Contralateral ptosis may worsen when manually elevating the more ptotic lid (Hering's law) 4

Laboratory Confirmation for Myasthenia

• Acetylcholine receptor antibodies (positive in 40-77% of ocular myasthenia cases) 3
• If antibodies negative, test for muscle-specific kinase (anti-MuSK) and lipoprotein-related protein 4 (LRP4) 4
• Repetitive nerve stimulation testing (positive in only one-third of patients with ocular myasthenia) 4
• Edrophonium (Tensilon) test: 0.2 mL (2 mg) IV initially, then 0.8 mL (8 mg) if no reaction after 45 seconds; 95% sensitive for generalized myasthenia, 86% sensitive for ocular myasthenia 4, 5
• Chest CT to screen for thymoma (present in 10-15% of myasthenia patients) 3

Step 3: Evaluate for Horner Syndrome

• Mild ptosis (1-2 mm) with miosis and anhidrosis indicates disruption of the oculosympathetic pathway 1
• Pharmacologic testing with apraclonidine or cocaine drops can confirm the diagnosis 6

Step 4: Complete Sensorimotor and Fundus Examination

Neurological Red Flags Requiring Imaging

• Associated sixth or fourth nerve palsies suggest cavernous sinus pathology 3, 2
• Ipsilateral cerebellar ataxia, tremor, or hemiplegia indicates midbrain/nuclear lesions 2
• Contralateral superior rectus weakness indicates nuclear third nerve involvement 2
• Papilledema or optic atrophy on fundus examination 1

Proptosis or Orbital Signs

• MRI of orbits with contrast is the optimal imaging modality for suspected orbital mass, thyroid eye disease, or vascular malformation 4, 1, 3
• CT orbits with contrast is complementary for assessing bony anatomy and orbital volumes 4

Step 5: Additional Testing When Neuroimaging is Normal

• Serological tests for infectious diseases: syphilis, Lyme disease 1, 3
• Lumbar puncture with CSF analysis: glucose, protein, cell count, cytology, and culture 1
• Consider testing for giant cell arteritis in elderly patients with scalp tenderness or jaw claudication 2

Common Pitfalls to Avoid

• Never assume pupil-sparing third nerve palsy is benign without confirming complete ptosis and complete ophthalmoplegia—partial presentations require urgent imaging 1, 3, 2
• Do not overlook myasthenia gravis due to variable presentation; perform ice test even when suspicion is moderate 3
• In children with congenital ptosis, failure to diagnose and treat early leads to amblyopia and permanently poor vision 3, 7
• Performing strabismus surgery before orbital decompression in thyroid eye disease worsens alignment 3
• 50-80% of patients with ocular myasthenia develop generalized, potentially life-threatening disease within a few years 4, 3