What are the top causes of abducens (sixth cranial nerve) palsy?

Top 10 Causes of Abducens Palsy

The most common cause of abducens (sixth cranial nerve) palsy in adults is microvascular ischemia (approximately 37% of cases), particularly in patients over 50 years with diabetes and hypertension, while in children, neoplasms predominate. 1, 2, 3

Ranked Etiologies by Frequency

1. Microvascular/Vasculopathic (36.7-37%)

• Most common in adults over 50 years with diabetes mellitus, hypertension, or hyperlipidemia as risk factors 1, 2, 3
• Presents with acute onset horizontal diplopia, may be accompanied by pain, typically resolves within 6 months (one-third resolve within 8 weeks) 1
• If no recovery by 6 months, approximately 40% demonstrate serious underlying pathology requiring further evaluation 1

2. Idiopathic (17.7%)

• Diagnosis of exclusion after comprehensive workup 3
• More common in young adults between 20-40 years of age 4
• Generally has good prognosis with spontaneous recovery 4

3. Neoplastic (10.9-14.3%)

• Most frequent cause in pediatric populations (50% in children presenting to emergency departments) 5, 6
• Includes brain metastases, meningiomas, glioblastomas, medulloblastomas, nasopharyngeal carcinomas, pituitary tumors, and clival chordomas 1, 7, 4, 3
• May present insidiously or acutely with associated neurologic deficits including facial/extremity motor weakness, other cranial nerve involvement, visual field defects, papilledema, or proptosis 1, 2
• Bilateral sixth nerve involvement suggests clival chordoma, increased intracranial pressure, or meningeal process 1

4. Vascular Anomalies (10.2%)

• Includes aneurysms (4.2%), most frequently located in the intracavernous region of the internal carotid artery 4, 3
• Carotid artery aneurysms in cavernous sinus may present with concomitant Horner's syndrome, CN III/IV palsies, or facial pain 2
• Dural sinus thrombosis is another vascular cause, particularly in pediatric populations 6

5. Inflammatory/Infectious (9.4-19.4%)

• Multiple sclerosis is the most common demyelinating cause; pontine lesions typically produce ipsilateral facial palsy alongside sixth nerve palsy 1, 2, 4
• Viral meningoencephalitis and systemic viral infections account for significant proportion 4
• Postviral sixth nerve palsy (including post-COVID-19 infection and post-vaccination) is a diagnosis of exclusion 2
• Guillain-Barré syndrome accounts for 14.2% in pediatric emergency presentations 6
• Meningitis (infectious, inflammatory, or carcinomatous) requires lumbar puncture following neuroimaging 1

6. Traumatic (3.1-4.3%)

• Usually self-evident with history of head injury, typically involving basilar skull fracture or acute rise in intracranial pressure from intracranial bleed 1, 2, 3
• Patients with trauma-related palsies are less likely to recover compared to vascular causes 2
• Pathological findings on neuroimaging are rare despite clinical presentation 4

7. Giant Cell Arteritis (GCA)

• Medical emergency in elderly patients presenting with scalp/temporal tenderness, jaw claudication, or pain 1, 2
• Can cause permanent visual loss if untreated 2
• Requires immediate checking of erythrocyte sedimentation rate and C-reactive protein, with temporal artery biopsy if results indicate possible GCA 1

8. Increased Intracranial Pressure

• Presents with papilledema, bilateral sixth nerve palsy, or meningeal signs (stiff neck with headache) 1
• Requires lumbar puncture following neuroimaging to measure intracranial pressure 1
• Pseudotumor cerebri and hydrocephalus are specific causes 7, 6

9. Congenital

• Accounts for small proportion of cases 5
• Requires extraocular muscle surgery with 80.9% success rate 2
• May present with spontaneous recovery in some cases 5

10. Other Rare Causes

• Sphenoid sinus mucocele, petrosal nerve schwannoma at petrous apex, hypertensive intraventricular hemorrhage 7
• Parotid tumor with skull base/brainstem invasion (nuclear damage shows no improvement) 7
• Lyme disease and syphilis (require systemic serology testing) 1

Critical Clinical Pearls

Bilateral sixth nerve palsy is never a benign vasculopathic finding and requires immediate investigation for increased intracranial pressure or structural lesion. 8

• Left-sided involvement (52%) is more frequent than right-sided (38%), with bilateral involvement in 10% of cases 4
• The proportion of etiology significantly differs according to age, sex, and the medical specialty managing the patient 3
• In elderly patients with vasculopathic risk factors and no temporal tenderness/jaw claudication, evaluation may be limited to blood pressure, serum glucose, and hemoglobin A1c, with follow-up to determine spontaneous resolution 1
• Neuroimaging should be considered in all young patients or any patient with other cranial neuropathies, neurologic changes, elevated intraocular pressure, or absence of compelling vasculopathic risk factors 1