What is the appropriate diagnosis and treatment approach for a 16-year-old male presenting with acute onset ptosis?

Acute Onset Ptosis in a 16-Year-Old Male

In a 16-year-old male with acute onset ptosis, myasthenia gravis is the primary concern and requires immediate assessment for respiratory compromise, followed by urgent evaluation to rule out life-threatening third nerve palsy from posterior communicating artery aneurysm. 1, 2

Immediate Life-Threatening Conditions to Rule Out

Assess for Myasthenia Gravis with Respiratory Involvement

• Check for neck drop, dysphagia, dysarthria, or difficulty breathing—these indicate generalized myasthenia gravis requiring ICU-level monitoring for impending respiratory failure. 1
• Measure vital capacity and negative inspiratory force immediately if any bulbar or respiratory symptoms are present. 1
• Look for fatigable weakness that worsens with sustained activity and improves with rest—this pattern is highly specific for neuromuscular junction pathology. 1, 3
• Assess whether ptosis is bilateral and worsens by evening or with prolonged upgaze. 3
• Check for Cogan lid-twitch sign (brief overshoot of the eyelid when looking down then quickly up). 1

Rule Out Third Nerve Palsy from Aneurysm

• Examine pupils in bright and dim illumination—anisocoria or mydriasis with ptosis indicates pupil-involving third nerve palsy requiring urgent MRA or CTA to rule out posterior communicating artery aneurysm. 4, 5
• Even if the pupil appears normal initially, aneurysms can present this way, so maintain high suspicion. 4
• Assess for complete versus partial ptosis and extraocular muscle involvement—partial ptosis with incomplete extraocular muscle dysfunction cannot be assumed to be microvascular and requires neuroimaging. 4
• Check for associated sixth or fourth nerve palsy, which would localize to the cavernous sinus. 4

Evaluate for Horner Syndrome

• Look for miosis (not mydriasis) with ptosis—this suggests Horner syndrome from internal carotid dissection until proven otherwise. 2
• Assess for anhidrosis and facial flushing asymmetry. 2

Diagnostic Algorithm After Excluding Emergencies

Bedside Testing

• Perform the ice pack test: apply ice pack over closed eyes for 2 minutes—reduction of ptosis by ≥2mm is highly specific for myasthenia gravis. 1, 3, 5
• Test for fatigability with sustained upgaze for 60 seconds—worsening ptosis confirms myasthenia. 1
• Assess reflexes (should be preserved in myasthenia, unlike neuropathy). 3
• Check for muscle wasting (absent in myasthenia, present in muscular dystrophy). 3

Laboratory Testing

• Order acetylcholine receptor antibody (AChR-Ab) testing—this has 80-88% sensitivity for generalized myasthenia gravis and 98-100% specificity, making it the gold standard serological test. 3, 5
• If AChR-Ab is negative, order anti-MuSK antibody (positive in one-third of seronegative patients) and anti-LRP4 antibody. 3, 5
• Check creatine kinase—it should be normal in myasthenia (elevated CK suggests muscular dystrophy or inflammatory myopathy). 3
• Consider blood glucose and HbA1c if there are vascular risk factors, as diabetic third nerve palsy can present with isolated ptosis. 6

Neuroimaging Indications

• Obtain urgent MRA or CTA if pupil is involved or if there is any third nerve palsy with extraocular muscle dysfunction. 4, 5
• Order MRI with gadolinium if partial third nerve palsy with incomplete ptosis or partial extraocular muscle involvement is present. 4, 5
• If high suspicion for aneurysm persists despite normal MRA/CTA, proceed to catheter angiogram after brain MRI. 4
• Consider orbital CT or MRI if sinusitis symptoms are present (rare cause of isolated ptosis from inflammation of oculomotor nerve's distal branch). 7

Electrophysiological Testing

• Single-fiber EMG has >90% sensitivity and is the gold standard electrophysiological test for myasthenia, but is technically demanding and not first-line. 3
• Repetitive nerve stimulation is positive in only one-third of ocular myasthenia cases, making it less useful. 3, 5

Management Based on Etiology

If Myasthenia Gravis Confirmed

• Admit for monitoring if any signs of generalized disease (neck drop, bulbar symptoms, respiratory symptoms). 1
• Order chest CT to screen for thymoma (present in 10-15% of myasthenia patients). 3
• Initiate treatment with acetylcholinesterase inhibitors and consider immunosuppression in consultation with neurology. 3

If Pupil-Sparing Third Nerve Palsy with Complete Ptosis and Complete Motility Dysfunction

• This classic presentation is almost always secondary to microvascular disease (diabetes, hypertension, hyperlipidemia). 4
• Manage vascular risk factors and observe for spontaneous recovery over 3 months. 4

If Pupil-Involving Third Nerve Palsy

• Urgent neuroimaging and neurosurgical consultation for possible aneurysm, tumor (meningioma, schwannoma, metastatic lesion), or other compressive lesion. 4

Critical Pitfalls to Avoid

• Do not dismiss ptosis with normal pupil as benign—partial third nerve palsy or seronegative myasthenia can present this way. 4, 3
• Do not overlook variable ptosis that worsens with fatigue—this is pathognomonic for myasthenia gravis. 5
• Do not delay respiratory assessment in patients with neck drop or bulbar symptoms—myasthenic crisis can be life-threatening. 1
• Do not assume microvascular etiology if ptosis is incomplete or extraocular muscle involvement is partial—these require neuroimaging. 4
• In a 16-year-old, congenital ptosis is unlikely with acute onset, but acquired causes including myasthenia, third nerve palsy, and rarely sinusitis-related inflammation must be systematically excluded. 2, 8