What is the likely diagnosis for a 50-year-old female (F) patient presenting with sudden severe headache, left eye ptosis, and a mid-dilated non-reactive pupil?

Likely Diagnosis: Third Nerve Palsy with Pupillary Involvement - Posterior Communicating Artery Aneurysm Until Proven Otherwise

This 50-year-old woman presenting with sudden severe headache, left eye ptosis, and a mid-dilated non-reactive pupil most likely has a third nerve palsy with pupillary involvement, which represents a neurosurgical emergency requiring immediate neuroimaging to rule out a posterior communicating artery aneurysm. 1, 2

Critical Immediate Assessment

The presence of a dilated pupil with ptosis indicates third nerve palsy with pupillary involvement and requires urgent neuroimaging (MRI with gadolinium and MR angiography or CT angiography) to rule out compressive lesions, especially aneurysms. 1, 2

Why This is an Emergency

• The combination of sudden severe ("thunderclap") headache with pupil-involving third nerve palsy strongly suggests aneurysmal subarachnoid hemorrhage, particularly from a posterior communicating artery aneurysm 3
• The pupillary fibers of the third nerve run superficially and are compressed first by external masses like aneurysms, making pupil involvement a critical distinguishing feature 2
• Bilateral third nerve palsy from mirror aneurysms has been reported, though unilateral presentation is more common 3

Differential Diagnosis (In Order of Urgency)

1. Posterior Communicating Artery Aneurysm (Most Urgent)

• This is the diagnosis that must be ruled out first because it is immediately life-threatening 1, 2
• Presents with sudden severe headache, complete or partial ptosis, and dilated non-reactive pupil 3
• The presence of third cranial nerve palsy should always raise suspicion of an aneurysm 3

2. Internal Carotid Artery Dissection

• Can cause complete ophthalmoplegia, complete ptosis, and dilated pupil when dissection occurs within the cavernous sinus 4
• Internal carotid artery dissection should be considered in third, fourth, or sixth cranial nerve palsies, especially when associated with headache 4
• May result from compression, stretching, and ischemia from occlusion of nutritional arteries 4

3. Pituitary Apoplexy

• Can present as acute painful isolated unilateral third cranial nerve palsy with sudden severe headache and complete ptosis 5
• Occurs when pituitary tumor undergoes infarction with invasion into the cavernous sinus 5

4. Other Intracranial Hemorrhage or Mass

• Intracranial hemorrhage can cause pupillary dilation through decreased brainstem blood flow and ischemia, rather than just mechanical compression 6
• Unilateral fixed pupil dilation can occasionally be a false-localizing sign, though this is rare 7

Immediate Diagnostic Workup

Urgent Neuroimaging (Do Not Delay)

• MRI with gadolinium and MR angiography OR CT angiography immediately 1, 2
• If MRI unavailable, start with non-contrast CT to evaluate for subarachnoid hemorrhage, then proceed to CT angiography 8
• The sensitivity of CT for acute subarachnoid hemorrhage is 98% with specificity of 99% 8

Complete Neuro-Ophthalmologic Examination

• Evaluate extraocular movements in all directions to determine extent of third nerve involvement 1, 2
• Assess for other cranial nerve involvement (fourth, sixth nerves) which might suggest cavernous sinus pathology 4
• Fundoscopic examination to evaluate for papilledema or optic atrophy 1, 2

Critical Clinical Pearls

Pupil-Sparing vs. Pupil-Involving: The Key Distinction

• Pupil-involving third nerve palsy = compressive lesion (aneurysm) until proven otherwise 1, 2
• Pupil-sparing third nerve palsy = almost always microvascular (diabetes, hypertension, hyperlipidemia) and does not require urgent imaging 1
• This patient has pupil involvement, making urgent imaging mandatory 1, 2

Common Pitfall to Avoid

• Do not assume this is a "microvascular" third nerve palsy based on age alone - the presence of pupillary involvement overrides all other considerations and mandates urgent aneurysm workup 1, 2
• Do not delay imaging to obtain laboratory studies first 1, 2
• The sudden severe headache ("thunderclap") combined with pupil involvement makes aneurysmal subarachnoid hemorrhage the primary concern 8, 3

Management Pending Imaging

• Maintain blood pressure control to prevent aneurysm rerupture if present 8
• Neurosurgical consultation should be obtained immediately 1, 2
• Keep patient NPO in case emergency surgical intervention is needed 2