3. Introduction
The third cranial nerve is also known as oculomotor nerve and has 2 major components:
◦ Outer parasympathetic fibers that supply the ciliary muscles and the sphincter pupillae
◦ Inner somatic fibers that supply the levator palpebrae superioris in the eyelid (which retracts the upper eyelid)
and the 4 extraocular muscles (superior, middle, inferior recti, and inferior oblique).
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
4. Epidemiology
◦ Female = male
◦ Less frequent in children and young adults
◦ Pupil involvement was seen in 43% of patients on presentation, however, 86% of patients presented with
ptosis on the first visit.
◦ The incidence of acquired third-nerve palsy in the US population-based survey by Chengbo et al. was noted
to be 4.0 per 100 000
◦ 10 % due to intracranial aneurysms that could be life threatening
Keane JR. Third nerve palsy: analysis of 1400 personally-examined inpatients. Can J Neurol Sci. 2010 Sep;37(5):662-70.
Fang C, Leavitt JA, Hodge DO, Holmes JM, Mohney BG, Chen JJ. Incidence and Etiologies of Acquired Third Nerve Palsy Using a Population-Based Method. JAMA Ophthalmol. 2017 Jan 01;135(1):23-28.
5. Pathophysiology
◦ An interesting point to note is that before the 3rd nerve reaches the orbit, the fibers innervating the pupillary
muscles (pupillomotor fibers) are located superficially in the nerve trunk. The pial blood vessels supply these
fibers. In contrast, the main trunk of the fibers is supplied by the vasa vasorum
◦ Lesions such as an aneurysm, uncal herniation, or tumor, which compress the nerve from outside will involve
the superficial pupillomotor fibers and their blood supply. On the other hand, medical lesion such as diabetes
mellitus or hypertension microangiopathy will affect the vasa vasorum and thus spare the pupillary fibers
◦ Aberrant regeneration of third-nerve may follow compressive or traumatic lesions but not vascular lesions
like diabetes. This is because of the endoneurial sheath which is damaged only by compression and trauma
and not by vascular lesions. This aberrant regeneration phenomenon can cause lid gaze dyskinesis (eyelid
retraction with depression of the eye ) or pupil-gaze dyskinesis (the pupil constricts on down-gaze or
adduction).
Flanders M, Hasan J, Al-Mujaini A. Partial third cranial nerve palsy: clinical characteristics and surgical management. Can. J. Ophthalmol. 2012 Jun;47(3):321-5.
Motoyama Y, Nonaka J, Hironaka Y, Park YS, Nakase H. Pupil-sparing oculomotor nerve palsy caused by upward compression of a large posterior communicating artery aneurysm. Case report. Neurol. Med. Chir. (Tokyo).2012;52(4):202-5.
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
6. Etiology
◦ Vascular ischemia
◦ Trauma
◦ Intracranial neoplasm
◦ Hemorrhage
◦ Congenital
◦ Idiopathic
The most common causes: diabetes mellitus and hypertension
Kim K, Noh SR, Kang MS, Jin KH. Clinical Course and Prognostic Factors of Acquired Third, Fourth, and Sixth Cranial Nerve Palsy in Korean Patients. Korean J Ophthalmol. 2018 Jun;32(3):221-227.
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
7. Etiology
◦ Supranuclear lesions: Lesions at the level of the cerebral cortex or the supranuclear pathway cause conjugate
paresis of both the eyes.
◦ Nuclear lesions: Vascular diseases, demyelination, and tumors are the main cause of third-nerve palsy.
◦ Fascicular lesions: The etiology is similar to the nuclear lesions.
◦ Intracavernous portion: As there are other nerves present in the vicinity of the third-nerve, any lesion in the
cavernous sinus will result in multiple nerve palsies of the cranial nerve IV, cranial nerve VI, and the first
division of cranial nerve V. The common etiology is diabetes, pituitary apoplexy, aneurysm, or carotid-
cavernous fistula.
◦ Intraorbital portion: Trauma, tumors, and Tolosa-Hunt syndrome are the main causes of intraorbital third-nerve
palsy.
Singh A, Bahuguna C, Nagpal R, Kumar B. Surgical management of third nerve palsy. Oman J Ophthalmol. 2016 May-Aug;9(2):80-6.
8. Etiology
◦ Basilar portion: In this region, isolated third-nerve palsy is very common. The primary causes of isolated palsy
include aneurysms, diabetes mellitus, and extradural hematoma. Third-nerve palsy from a posterior
communicating artery, posterior cerebral artery, or superior cerebellar artery aneurysm has been
recorded. The palsy results from either direct compression of the nerve by an aneurysm or due to
subarachnoid hemorrhage in the vicinity of an aneurysm. This causes isolated and painful third-nerve palsy.
Extradural hematoma results in tentorial pressure cone and herniation of the temporal lobe. The third nerve
gets compressed by the herniation as it passes over the tentorial edge, leading to third-nerve palsy.
Tamhankar MA, Biousse V, Ying GS, Prasad S, Subramanian PS, Lee MS, Eggenberger E, Moss HE, Pineles S, Bennett J, Osborne B, Volpe NJ, Liu GT, Bruce BB, Newman NJ, Galetta SL, Balcer LJ. Isolated third, fourth, and sixth cranial
nerve palsies from presumed microvascular versus other causes: a prospective study. Ophthalmology.2013 Nov;120(11):2264-9.
Chaudhry NS, Brunozzi D, Shakur SF, Charbel FT, Alaraj A. Ruptured posterior cerebral artery aneurysm presenting with a contralateral cranial nerve III palsy: A case report. Surg Neurol Int. 2018;9:52.
9. Etiology
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
10. Clinical Features
◦ Ptosis: Due to paralysis of LPS (levator palpebrae superioris) muscle
◦ Ocular deviation: In case of third-nerve palsy, the lateral rectus and superior oblique are spared, and their
unopposed action brings the eye in a “down and out” position.
◦ Pupil: In compressive third-nerve palsy, the pupil becomes fixed and dilated due to paralysis of sphincter
pupillae. Ciliary muscle paralysis also leads to loss of accommodation. However, in ischemic lesions, the pupil
is spared, and there is no loss of accommodation.
◦ Diplopia: This occurs due deviation of the affected eye resulting in the image falling on an extrafoveal point.
However, due to ptosis the patient usually doesn’t complain of double vision as ptosis acts as a barrier to
diplopia.
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
Komurcu HF, Ayberk G, Ozveren MF, Anlar O. Pituitary adenoma apoplexy presenting with bilateral third nerve palsy and bilateral proptosis: a case report. Med Princ Pract. 2012;21(3):285-7.
11. Four Distinct Syndromes
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
12. Evaluation
◦ Pupil-sparing third-nerve palsy
- Blood pressure recording
- Complete blood count (CBC)
- Blood sugar including Hb1AC
- Erythrocyte sedimentation rate (ESR)
◦ Non-pupil-sparing third-nerve palsy
- MRI of brain
- Cerebral CT angiography
Kim JH, Hwang JM. Imaging of Cranial Nerves III, IV, VI in Congenital Cranial Dysinnervation Disorders.Korean J Ophthalmol. 2017 Jun;31(3):183-193.
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
Tamhankar MA, Biousse V, Ying GS, Prasad S, Subramanian PS, Lee MS, Eggenberger E, Moss HE, Pineles S, Bennett J, Osborne B, Volpe NJ, Liu GT, Bruce BB, Newman NJ, Galetta SL, Balcer LJ. Isolated third, fourth, and sixth cranial
nerve palsies from presumed microvascular versus other causes: a prospective study. Ophthalmology.2013 Nov;120(11):2264-9.
13. Differential Diagnosis
◦ Ophthalmoplegic migraine
◦ Internuclear ophthalmoplegia
◦ Ptosis in adults or congenital ptosis
◦ Anisocoria
◦ Myasthenia gravis
◦ Thyroid ophthalmopathy
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
De Silva DA, Siow HC. A case report of ophthalmoplegic migraine: a differential diagnosis of third nerve palsy.Cephalalgia. 2005 Oct;25(10):827-30.
14. Management
◦ Treat underlying causes if any
◦ In cases of diplopia, the affected eye can be occluded with the help of an eye patch or opaque contact lens.
In pediatric cases, amblyopia due to ptosis or squint can be prevented by alternate patching
◦ Botulinum toxin (?)
◦ In pupil-sparing cases, surgical treatment is advised after 6 months in acquired palsies, if there is no
improvement in symptoms.
Modi P, Arsiwalla T. Cranial Nerve III Palsy. InStatPearls [Internet] 2019 Feb 1. StatPearls Publishing.
Singh A, Bahuguna C, Nagpal R, Kumar B. Surgical management of third nerve palsy. Oman J Ophthalmol. 2016 May-Aug;9(2):80-6
Talebnejad MR, Sharifi M, Nowroozzadeh MH. The role of Botulinum toxin in management of acute traumatic third-nerve palsy. J AAPOS. 2008 Oct;12(5):510-3.
Kattleman B, Flanders M, Wise J. Supramaximal horizontal rectus surgery in the management of third and sixth nerve palsy. Can. J. Ophthalmol. 1986 Oct;21(6):227-30.
Wang WX, Xu BN, Wang FY, Wu C, Sun ZH. Microsurgical management of posterior cerebral artery aneurysms: A report of thirty cases in modern era. Br J Neurosurg. 2015 Jun;29(3):406-12.
15. Prognosis
◦ The prognosis in most cases of third-nerve palsy is usually good, as spontaneous regression of the
symptoms occurs within a few months; however, the degree of recovery depends on the etiology and
management.
Kim K, Noh SR, Kang MS, Jin KH. Clinical Course and Prognostic Factors of Acquired Third, Fourth, and Sixth Cranial Nerve Palsy in Korean Patients. Korean J Ophthalmol. 2018 Jun;32(3):221-227.