6th Nerve Palsy

The sixth cranial nerve has the longest intracranial course of any cranial nerve, making it vulnerable to a wide range of pathologies at multiple anatomical sites (brainstem, subarachnoid space, Dorello's canal, cavernous sinus, and orbit).

• Microvascular ischemia (diabetes mellitus, hypertension, atherosclerosis) — the most common cause in adults, accounting for ~37–46% of cases. Typically presents as an acute, isolated palsy that resolves spontaneously over 8–12 weeks
• Brainstem infarction (pontine stroke)

• Primary brain tumors (pontine glioma, [meningioma](/rare-disease/meningioma), schwannoma)
• Clivus tumors (chordoma, chondrosarcoma)
• Cerebellopontine angle tumors
• Metastatic disease / leptomeningeal carcinomatosis
• Nasopharyngeal carcinoma with skull base invasion

• Space-occupying lesions (tumor, hemorrhage, abscess)
• Hydrocephalus
• Idiopathic intracranial hypertension (pseudotumor cerebri)
• Cerebral venous sinus thrombosis
• Meningeal infiltration

• Post–lumbar puncture
• Spontaneous intracranial hypotension (CSF leak)

• Head trauma / skull base fracture (~4–7% of cases)

• Neurosarcoidosis
• Granulomatosis with polyangiitis (Wegener)
• IgG4-related disease
• Tolosa-Hunt syndrome (painful ophthalmoplegia)
• Giant cell arteritis
• Systemic lupus erythematosus
• Sjögren syndrome
• Neuro-Behçet syndrome

• Multiple sclerosis (demyelinating plaque in pons or medial longitudinal fasciculus)

• Bacterial meningitis
• Tuberculous meningitis
• Neurosyphilis
• Lyme disease
• HIV
• Cryptococcal meningitis
• Varicella-zoster virus
• Aspergillus

• Cavernous sinus thrombosis
• Cavernous sinus infection
• Cavernous sinus tumors (meningioma, pituitary adenoma, metastasis)
• Carotid-cavernous fistula

• Aneurysm (posterior circulation)
• Dural arteriovenous fistula
• Vascular malformation / hemorrhage

• Myasthenia gravis (may mimic CN VI palsy)
• Thyroid eye disease (restrictive myopathy)
• Miller Fisher syndrome (anti-GQ1b antibody)

• Wernicke encephalopathy
• Post-surgical (e.g., after neurosurgical procedures)
• Idiopathic (~18–23% of cases)

The etiologic spectrum in children differs significantly from adults. Microvascular ischemia is rare; neoplasia and raised intracranial pressure are proportionally more common.

• Posterior fossa tumors (medulloblastoma, ependymoma, brainstem glioma)
• Pontine glioma (diffuse intrinsic pontine glioma)
• [Acute lymphoblastic leukemia](/rare-disease/acute-lymphoblastic-leukemia) (CNS involvement)
• Other CNS tumors
• ~10% of isolated acquired pediatric CN6 palsies are associated with a newly diagnosed brain tumor

• Brain tumors (secondary effect)
• Hydrocephalus
• Idiopathic intracranial hypertension (pseudotumor cerebri)
• Dural sinus thrombosis

• Anti-GQ1b syndrome (Miller Fisher spectrum)
• Guillain-Barré syndrome
• Post-viral (following upper respiratory infection or other viral illness)
• Post-vaccination
• These account for ~50% of isolated cases in children

• Bacterial meningitis
• Lyme disease
• Mycoplasma infection
• Viral infections

• Multiple sclerosis
• MOG antibody–associated disease

• Neurosarcoidosis
• Other granulomatous disease

• Head trauma / skull base fracture

• No identifiable cause in ~5–30% of pediatric cases
• Recurrent isolated sixth nerve palsy — rare; young females with left-sided palsy and recent immunization are at higher risk of recurrence. Complete recovery is typical

1. Oh SY. Clinical Outcomes and Etiology of Acquired Sixth Cranial Nerve Palsy. Medicine (Baltimore). 2022
2. Kim HJ, Kim HJ, Choi JY, et al. Etiologic Distribution of Isolated Abducens Nerve Palsy: Analysis of 807 Patients and Literature Review. Eur J Neurol. 2023
3. Hörner S, et al. Sixth Cranial Nerve Palsy: Etiology and Outcome. J Neurol. 2022
4. Meyer C, Wynn DP, Pulst SM, Chen R, Digre K. Clinical Reasoning: A 22-Year-Old Man With Diplopia. Neurology. 2017
5. Buracchio T, Rucker JC. Pearls and Oy-Sters of Localization in Ophthalmoparesis. Neurology. 2007
6. Giacobbe A, et al. Clinical Reasoning: Sixth Nerve Palsy. Neurology. 2023
7. Munro NA, Fernandez RL. Clinical Reasoning: Cranial Nerve Palsies. Neurology. 2018
8. Chang MY, Borchert MS. Etiology and Outcomes of Acquired Pediatric Sixth Nerve Palsies. J Neuroophthalmol. 2022
9. Park KA, Oh SY, Min JH, Kim BJ, Kim Y. Acquired Onset of Third, Fourth, and Sixth Cranial Nerve Palsies in Children and Adolescents. Eye (Lond). 2019
10. Hanna FA, Jabaly-Habib H, Halachmi-Eyal O, et al. Sixth Nerve Palsy in Children: Etiology, Long-Term Course, and a Diagnostic Algorithm. J Child Neurol. 2022
11. Teksam O, et al. Sixth Cranial Nerve Palsy in Children. J Pediatr Ophthalmol Strabismus. 2016
12. Kingma HJ, Ceulemans B. Recurrent Isolated Sixth Nerve Palsy in Children. Eur J Paediatr Neurol. 2022