What are the common causes of an acute unilateral third‑nerve (oculomotor) palsy, especially with pupil involvement, in an older patient with diabetes, hypertension, or hyperlipidaemia?

Causes of Unilateral Third Nerve Palsy

In older patients with diabetes, hypertension, or hyperlipidemia presenting with acute unilateral third nerve palsy, the etiology depends critically on pupillary involvement: pupil-sparing palsies are almost always due to microvascular ischemic disease, while pupil-involving palsies require urgent exclusion of posterior communicating artery aneurysm. 1

Pupil-Sparing Third Nerve Palsy

Microvascular ischemic disease is the predominant cause when the presentation includes:

• Normal pupillary function with complete ptosis and complete extraocular muscle dysfunction 1
• Associated vascular risk factors: diabetes mellitus, hypertension, or hyperlipidemia 1
• The annual incidence is approximately 4 per 100,000, with diabetic patients at significantly elevated risk 1

Critical Caveat for Pupil-Sparing Cases

Even with an apparently normal pupil, neuroimaging with MRI/gadolinium and MRA or CTA is mandatory if:

• Extraocular muscle involvement is incomplete or partial 1
• Ptosis is incomplete rather than complete 1
• Compressive lesions (including aneurysms) can occasionally present with pupil-sparing features, particularly early in their course 2

The 2012 case report demonstrates that a large posterior communicating artery aneurysm compressing the nerve from below can cause pupil-sparing palsy even after 2 weeks of symptoms 2. This underscores that pupil-sparing does not guarantee benign etiology when the clinical picture is atypical.

Pupil-Involving Third Nerve Palsy

Posterior communicating artery aneurysm is the most urgent life-threatening diagnosis that must be ruled out immediately. 3

Anatomic Basis

The third nerve passes lateral to the posterior communicating artery in the subarachnoid space, making aneurysms at this location particularly likely to compress the nerve and involve pupillary fibers 1. The pupil may appear normal at initial presentation but can dilate subsequently 1.

Other Compressive Causes Along the Nerve Pathway

Midbrain/Nuclear lesions cause:

• Ipsilateral cerebellar ataxia (superior cerebellar peduncle involvement) 1
• Ipsilateral flapping tremor and ataxia (red nucleus involvement) 1
• Ipsilateral hemiplegia or hemiparesis (cerebral peduncle involvement) 1
• Contralateral superior rectus weakness with complete third nerve palsy indicates nuclear localization 1

Subarachnoid space lesions include:

• Mass lesions or intracranial bleeding causing uncal herniation through the tentorial notch 1
• Subarachnoid hemorrhage 1
• Ectatic posterior cerebral artery causing direct vascular compression 4
• Non-aneurysmal posterior communicating artery ectasia, sometimes combined with tentorial meningioma 5

Cavernous sinus pathology may present with:

• Associated sixth and fourth nerve palsies 1
• Tumors including meningioma, schwannoma, and metastatic lesions 1

Orbital/orbital apex lesions cause:

• Divisional palsy (superior or inferior division involvement) 1
• Associated optic neuropathy and proptosis 1

Additional Etiologies

• Trauma 1
• Viral illnesses 1
• Demyelinating disease 1
• Leptomeningeal disorders 1
• Infectious diseases (syphilis, Lyme disease) 1
• Giant cell arteritis in elderly patients with scalp tenderness, temporal tenderness, or jaw claudication 1

Diagnostic Algorithm

For Pupil-Sparing Palsy with Complete Ptosis and Complete Motility Dysfunction

Assume microvascular etiology in patients with diabetes, hypertension, or hyperlipidemia. 1 Observation with optimization of vascular risk factors is appropriate, with expected recovery within 3 months 6.

For Pupil-Sparing Palsy with Incomplete Features OR Any Pupil-Involving Palsy

Urgent neuroimaging is mandatory: 1, 3

• MRI with gadolinium and MRA, or CTA 1, 3
• If MRI unavailable, start with non-contrast CT to evaluate for subarachnoid hemorrhage, then proceed to CTA 3
• If high suspicion for aneurysm persists despite normal MRA/CTA, obtain catheter angiography after brain MRI with contrast focused on the third nerve 1

If Neuroimaging is Normal

Proceed with serologic testing for infectious diseases (syphilis, Lyme), and consider lumbar puncture for glucose, protein, cell count, cytology, and culture. 1

Common Pitfalls

The most dangerous error is assuming pupil-sparing guarantees benign microvascular disease without assessing completeness of the palsy. Partial involvement or incomplete ptosis mandates imaging even with a normal pupil 1. Additionally, vasculopathic third nerve palsy can occasionally involve the pupil mildly 1, and compressive lesions can initially spare the pupil 7, 2.

Clinical features such as pain, speed of onset, and completeness of palsy are not reliable for distinguishing ischemic from compressive etiologies. 7 Only the combination of pupillary status and completeness of dysfunction provides diagnostic guidance.