What is the differential diagnosis for an adult patient with eyelid droop (ptosis), considering potential causes such as third cranial nerve palsy, levator muscle weakness, or eyelid trauma, and taking into account past medical history, including conditions like diabetes or stroke?

Differential Diagnosis of Eyelid Droop (Ptosis) in Adults

Immediate Life-Threatening Causes to Rule Out First

Pupil-involving third nerve palsy from posterior communicating artery aneurysm is the most urgent diagnosis and requires immediate neuroimaging with MRI/gadolinium plus MRA or CTA to prevent fatal rupture. 1, 2, 3

Critical Initial Assessment

Examine pupillary responses in bright and dim lighting immediately to identify pupillary involvement, which represents a potential neurosurgical emergency. 4

• Dilated pupil with ptosis: Third nerve palsy with pupillary involvement—obtain urgent MRI with gadolinium and MRA or CTA immediately to rule out aneurysm. 1, 3
• Normal pupil with complete ptosis and complete ophthalmoplegia: Classic pupil-sparing third nerve palsy, almost always microvascular disease from diabetes, hypertension, or hyperlipidemia. 1, 2
• Mild miosis with mild ptosis: Horner syndrome from carotid dissection until proven otherwise—requires urgent vascular imaging. 4, 5

Neurogenic Causes

Third Nerve Palsy (Oculomotor Nerve)

Pupil-sparing third nerve palsy with incomplete ptosis or partial ophthalmoplegia cannot be assumed benign—compressive lesions can present this way and require neuroimaging with MRI/gadolinium and MRA or CTA. 1, 2

• Microvascular (vasculopathic): Most common in adults with diabetes, hypertension, or hyperlipidemia; presents with complete ptosis, complete motility dysfunction, and normal pupil. 1, 2
• Compressive lesions: Posterior communicating artery aneurysm (most urgent), meningioma, schwannoma, metastatic tumors—typically cause pupil involvement but may initially spare the pupil. 1, 2
• Trauma and subarachnoid hemorrhage: History of head injury or sudden severe headache. 1, 2
• Infectious causes: Syphilis, Lyme disease, viral illnesses—consider serologic testing if neuroimaging normal. 1, 2
• Demyelinating disease: Multiple sclerosis—may have other neurologic symptoms. 2
• Isolated superior division palsy: Rare presentation with ptosis alone without ophthalmoplegia, as levator is innervated by superior division. 4, 6

Horner Syndrome

• Mild ptosis with miosis and anhidrosis: Disruption of oculosympathetic pathway from carotid dissection, brainstem stroke, or apical lung tumor. 4, 5

Myogenic Causes

Myasthenia Gravis

Variable, fatigable ptosis that worsens with prolonged upgaze and improves with rest is pathognomonic for myasthenia gravis. 2

• Ice pack test: Apply ice over closed eyes for 2 minutes; reduction of ptosis by approximately 2 mm is highly specific for myasthenia gravis. 2, 4
• Cogan lid-twitch sign: Characteristic finding when eyes move from downgaze to primary position. 2
• Acetylcholine receptor antibodies: Present in 40-77% of ocular myasthenia cases. 2
• Thymoma screening: Obtain chest CT as thymoma present in 10-15% of myasthenia patients. 2
• Associated conditions: Increased risk with autoimmune thyroid disease. 2

Mechanical Causes

Eyelid and Orbital Pathology

• Giant papillary conjunctivitis: Severe cases cause lid swelling and ptosis from contact lens wear; papillae with white fibrotic centers in long-standing disease. 1
• Floppy eyelid syndrome: Upper eyelid easily everted, associated with obesity and sleep apnea. 1
• Giant fornix syndrome: Elderly women (eighth to tenth decade) with enlarged superior fornix and coagulum of mucopurulent material causing ptosis. 1
• Orbital masses: Tumors, vascular malformations, or inflammatory processes causing mechanical ptosis—MRI orbits with contrast is optimal imaging. 1

Traumatic Causes

• Direct eyelid trauma: Levator muscle or aponeurosis damage. 1, 7
• Orbital fractures: CT orbits without contrast is superior for identifying osseous integrity and fractures. 1

Aponeurotic Causes

• Involutional (age-related): Most common cause of acquired ptosis in elderly; levator aponeurosis dehiscence or disinsertion. 7, 5

Diagnostic Algorithm

Step 1: Pupillary Examination (Most Critical)

• Dilated pupil + ptosis: Urgent neuroimaging (MRI/gadolinium + MRA or CTA) for aneurysm. 1, 3
• Miosis + mild ptosis: Urgent vascular imaging for Horner syndrome/carotid dissection. 4, 5
• Normal pupil + complete ptosis + complete ophthalmoplegia: Likely microvascular; observe if diabetes/hypertension present. 1, 2
• Normal pupil + incomplete ptosis or partial ophthalmoplegia: Obtain neuroimaging—cannot assume benign. 1, 2

Step 2: Variability Assessment

• Fatigable ptosis worsening with upgaze: Perform ice pack test for myasthenia gravis. 2, 4
• Constant ptosis: Consider aponeurotic, mechanical, or neurogenic causes. 7, 5

Step 3: Associated Findings

• Ophthalmoplegia present: Evaluate for third, fourth, or sixth nerve involvement; check for cavernous sinus pathology. 1
• Proptosis present: MRI orbits with contrast for orbital mass or thyroid eye disease. 1
• Other neurologic symptoms (ataxia, tremor, hemiplegia): Localize lesion along third nerve pathway from midbrain to orbit. 1, 4

Step 4: Fundus Examination

• Papilledema or optic atrophy: Indicates potentially life-threatening intracranial pathology requiring urgent neuroimaging. 4

Critical Diagnostic Pitfalls to Avoid

• Never assume pupil-sparing indicates benign microvascular disease when ptosis is incomplete or ophthalmoplegia is partial—compressive lesions including aneurysms can present this way. 1, 2
• Missing pupil-involving third nerve palsy as a neurosurgical emergency can be fatal—always obtain urgent neuroimaging. 2, 3
• Overlooking myasthenia gravis due to variable presentation—perform ice test even when presentation is atypical. 2
• In children with congenital ptosis, failing to diagnose and treat early leads to amblyopia with permanently poor vision. 2, 7

Neuroimaging Indications

Urgent (Same Day)

• Pupil-involving ptosis: MRI with gadolinium + MRA or CTA. 1, 3
• Horner syndrome with acute onset: CTA or MRA for carotid dissection. 4, 5

Elective (Within Days)

• Pupil-sparing ptosis with incomplete presentation or partial ophthalmoplegia: MRI with gadolinium + MRA or CTA. 1, 2
• Ptosis with proptosis or other neurologic deficits: MRI head and orbits with contrast. 4

Laboratory Studies if Imaging Normal

• Serologic testing for syphilis and Lyme disease. 1
• Lumbar puncture with glucose, protein, cell count, cytology, and culture. 1
• Acetylcholine receptor antibodies for suspected myasthenia gravis. 2, 4