Combined third, fourth, and sixth nerve palsies

Heather E Moss MD PhD (Dr. Moss of Stanford University has no relevant financial relationships to disclose.)
James Goodwin MD, editor. (Dr. Goodwin of the University of Illinois at Chicago has no relevant financial relationships to disclose.)
Originally released January 8, 2003; last updated February 27, 2018; expires February 27, 2021


Diplopia is a common complaint in patients with diseases of the central nervous system and is usually helpful for localization of pathology. A minority of patients complaining of diplopia have signs that indicate involvement of multiple ocular motor nerve palsies. These must be differentiated from single ocular motor nerve palsies, neuromuscular junction, myopathic disorders, and supranuclear disorders. Their recognition is important because the differential diagnosis includes a higher frequency of mass and inflammatory lesions in the vicinity of the orbital apex or cavernous sinus, which may require urgent therapy.

Key points


Ophthalmoplegia can be caused by multiple ocular motor nerve palsies (combined third, fourth, and/or sixth nerve palsies), single ocular motor nerve palsies, supranuclear gaze disorders, neuromuscular junction disorders, and myopathy.


• Cavernous sinus lesions can affect combinations of 3 (oculomotor), 4 (trochlear), V1 (ophthalmic), V2 (maxillary), 6 (abducens), and postganglionic sympathetic nerve fibers and can cause orbital congestion.


• Orbital apex lesions can affect combinations of 2 (optic nerve), 3 (oculomotor), 4 (trochlear), V1 (ophthalmic), 6 (abducens), and postganglionic sympathetic nerve fibers and can cause orbital congestion.

Historical note and terminology

By definition, multiple ocular motor palsies are present when eye muscle weakness, with or without anisocoria and ptosis, indicates dysfunction of more than one ocular motor nerve. These may be unilateral or bilateral. They should be distinguished from supranuclear disorders of ocular motility, which often show dissociations between different types of eye movements (ie, limited saccades but full vestibuloocular range of eye movements). In contrast, the ocular defects in multiple ocular motor palsies always affect all types of eye movements. Non-selective palsies are also found with diffuse disorders of the muscle, neuromuscular junction, or nerve (eg, Graves ophthalmopathy, myasthenia gravis, and Miller-Fisher syndrome) and may be difficult to distinguish from multiple ocular motor palsies.

“Ocular motor nerves” refers to cranial nerves 3, 4, and 6. “Oculomotor nerve” refers solely to cranial nerve 3.

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