Aberrant regeneration of the third cranial nerve

Aberrant regeneration (reinnervation) is a misdirection of axons that occurs in the process of repair following conditions that cause mechanical disruption of a nerve. Axons that originally innervated one muscle are mistakenly routed to a different muscle. Following a command to the original muscle to contract, the aberrantly reinnervated muscle contracts in addition to, or instead of, the agonist.

In aberrant regeneration of CN III, fibers originally destined to innervate the medial rectus may reinnervate the levator palpebrae or other extraocular muscles.(1,2) The lid elevates on adduction because of synkinesis between the medial rectus and the levator. Attempted upgaze may cause adduction because of misdirection of superior rectus fibers into the medial rectus. The upper lid may elevate on downgaze due to inferior rectus fibers aberrantly innervating the levator.

The video, courtesy of Dr. Daniel Gold and the Neuro-ophthalmology Virtual Education Library (NOVEL) at the University of Utah, shows a woman with a traumatic left CN III palsy.(3) In response to an OKN stimulus, there is left eyelid elevation on attempted adduction because fibers that originally innervated the left MR became misrouted to the levator. Compare with the normal responses occurring in the right eye. Adduction occurs in the left eye with attempted upward and downward saccades because some fibers that should have reinnervated the left SR and IR were misrouted to the left MR.

Aberrant regeneration of CN III, also referred to as misdirection syndrome or oculomotor synkinesia, is a helpful clinical feature distinguishing ischemic from mechanical, compressive lesions. The common causes are posterior communicating artery aneurysm and head trauma. Vasculopathic injury, such as diabetic CN III palsy, does not cause aberrant reinnervation.

Video legend. Aberrant regeneration of the third cranial nerve after a traumatic injury. Video courtesy of Dr. Daniel Gold and the Neuro-ophthalmology Virtual Education Library (NOVEL).


1. Miller NR. Walsh and Hoyt's clinical neuro-ophthalmology: the essentials. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2008

2. Campbell WW. Clinical signs in neurology: a compendium. Philadelphia: Wolters Kluwer Health, 2016.

3. Gold DR. Aberrant Regeneration of the 3rd Nerve. Neuro-ophthalmology Virtual Education Library, Daniel Gold Collection. http://NOVEL.utah.edu