Oculomotor Synkinesis

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 by Bayan Al Othman, MD on June 30, 2020.


Disease Entity

Disease

Oculomotor Synkinesis (also known as aberrant regeneration of the third cranial nerve or oculomotor nerve misdirection) refers to the abnormal response to firing of the oculomotor nerve causing paradoxical co-contraction (i.e., synkinesis) of muscles. It is a result of persistent partial oculomotor nerve dysfunction after failure to completely recover from disruption of the nerve due to any cause. The term “synkinesis” refers to involuntary muscular movements that accompany voluntary movements. The third cranial nerve (oculomotor nerve) supplies the inferior oblique, medial rectus, superior rectus, inferior rectus, the parasympathetically innervated pupil sphincter, and levator palpebrae muscles. In aberrant regeneration after injury to the oculomotor nerve, fibers grow to supply muscles other than their original terminal muscle, leading to co-contraction of these muscles (lid, extraocular muscles, or pupil) on firing of the nerve.

Etiology

This phenomenon can occur with (secondary) or without (primary) preceding oculomotor nerve dysfunction. The primary oculomotor synkinessis is typically secondary to slow growing intracavernous lesions (e.g., meningioma, intracavernous aneurysm, or schwannoma). [1] However, secondary oculomotor synkinesis most commonly results weeks to months following an acquired third cranial nerve palsy (e.g., trauma, surgery, tumor, posterior communicating artery aneurysm). [2] When associated with trauma, it is more commonly the indirect effects such as hematoma formation, rather than the direct trauma which damages the nerve. [3] The incidence of aberrant regeneration of the third nerve after acute oculomotor nerve injury is about 15%. [4]

Rare reports have been documented showing ophthalmoplegic migraine as a cause of oculomotor synkinesis, likely secondary to major ischemic damage to peripheral nerve. [5][6] One unique report discusses a case of oculomotor misdirection secondary to aytpical Tolosa Hunt Syndrome causing inflammation of the nerve, seen clinically and proven by enhancement on magnetic resonance imaging (MRI).[6] Another case report documents a patient with oculomotor synkinesis following an episode of Miller-Fisher Syndrome.[6]

Epidemiology

This phenomenon has been reported in a wide range of ages from infants to elderly patients, and does not appear to be limited to a specific demographic. [4][6][7]

General Pathology

Oculomotor nerve injury is categorized as follows by Seddon’s Peripheral Nerve Injury Classification: [8][9]

First Degree/Neurapraxia: Conduction block, continuity of axon is maintained. Most commonly microvascular in origin such as from diabetes or hypertension. Explains why aberrancy does not usually result from ischemic injury of nerve.

Second Degree/Axonotmesis: Crush injury, disruption of axon while endoneurial tubes are preserved. Nerve regeneration is confined to original architecture so aberrancy does not occur.

Third Degree/Neurotmesis: Nerve and endoneurium are disrupted, may regenerate in aberrant pathway.

Pathophysiology

Oculomotor synkinesis most commonly occurs in the process of regeneration after acute cranial nerve injury. Historical laboratory studies have provided evidence of this mechanism. In 1928, an experiment severing the sciatic nerve of a cat showed fibers originating from the proximal end of the two trunks aberrantly regenerating without concern for their original pathways. [9] In 1935 the German ophthalmogist, Bielschowsky stated that “in the course of healing….the nerve fibers prefer certain ‘routes’ for growing in the wrong sheaths,” leading to the synkinesis or paradoxical co-contraction of extraocular muscles. [9]

This phenomenon can occur rarely without preceding oculomotor nerve palsy. One controversial theory for this is ephaptic transmission, or pre-existing links between axons, as a sequel to nerve injury. This theory suggests that when associated with slow-growing parasellar or cavernous sinus meningiomas, subclinical oculomotor nerve disruption and regeneration occur concomitantly, which may allow for electrical cross-talk between individual fibers whose myelin sheaths have been damaged by slow compression. [6][9]

Diagnosis

The diagnosis of oculomotor synkinesis is clinical, based on history and physical exam, and can be confirmed by neuroimaging demonstrating causative lesion of cranial nerve damage.

History

Patients may report history of oculomotor nerve damage, possibly due to traumatic brain injury or neurosurgery, weeks to months before onset of current symptoms. This may be reported as history of acute onset of double vision or ptosis that may have partially resolved or have been treated with patch or prism.

Physical examination

On external exam, the patient may have ptosis of the affected eye as a sign of third cranial nerve palsy. Motility exam may show a partial or complete paresis of extraocular muscles innervated by the third nerve. The pupil may or may not be involved. Any combination of synkinetic movement of the muscles innervated by the third nerve may be present (e.g., elevation of the upper eyelid on downward gaze or adduction; adduction of the eye on attempted vertical gaze; limited elevation and depression of the eye with retraction of the globe on attempted vertical gaze; or pupillary constriction with extraocular muscle movement). In some cases the constriction to convergence may be greater than the light response producing a pseudo-Argyll Robertson pupil picture ipsilaterally. [9]

Signs

  • “Pseudo Von-Graefe Sign:” elevation of upper eyelid on downward gaze or adduction [9]
  • Adduction of the eye on attempted upward or downward gaze[9]
  • Limitation of elevation and depression of the eye with retraction of the globe on attempted vertical movement[7]
  • “Pseudo-Argyll Robertson pupil”: greater constriction of pupil to convergence than to light and gaze-evoked pupillary constriction[4][7]

Symptoms

The primary presenting symptom of oculomotor synkinesis is binocular diplopia. Patients may also report ptosis or anisocoria.

Diagnostic procedures

  • Complete Ocular and Neurological Examination
  • Imaging of brain (MRI preferred over computed tomography (CT) scan)
  • Angiography (e.g., CTA, MRA, catheter angiography) for aneurysm if necessary

Differential diagnosis

The differential diagnosis for oculomotor synkinesis includes myasthenia gravis affecting neuromuscular junctions and neurosyphillis or Adie’s pupil affecting pupillary response. The typical features of reproducible synkinetic movements would not be present in myasthenia or syphilis however.

General treatment

Treatment strategies vary depending on individual clinical manifestations in each patient. Patching, prism therapy, or strabismus surgery may be needed for symptomatic patients but the aberrancy needs to be taken into consideration for surgical planning.

Prognosis

Depends on the underlying diagnosis.

Prevention

None

References

  1. Flanders, D., Mainville, N., Dubé, P. and Flanders, M. (2019). Pediatric and Adult Strabismus- Third Nerve Palsy. [online] www..medicine.mcgill.ca. Available at: http://www2.medicine.mcgill.ca/strabismus/atlas/patients/notesAndReferences/thirdNervePalsy.php [Accessed 10 Apr. 2019].
  2. Weber E, Newman A. (2007). Aberrant Regeneration of the Oculomotor Nerve: Implications for Neurosurgeons. Neurosurg Focus. 23(5):E14.
  3. Peter W. MacIntosh & Virna Shah (2018) Steroids in the Management of Synkinesis after Traumatic Oculomotor Palsy in India, Neuro-Ophthalmology, 42:3, 135-138
  4. 4.0 4.1 4.2 Kafa A, Bir T, Aberan H, Iincii U, Rejenerasyonu S, Atalay B, Gedik A, Caner , Oto S, Bavbek M, Altinors, N. (2003). Aberrant Regeneration of the Third Cranial Nerve in a Patient with Severe Head Injury. Turkish Neurosurgery. 13.
  5. O’Day J, Billson F, King J. (1980). Opthalmoplegic Migraine and Aberrant Regeneration of the Oculomotor Nerve. British Journal of Ophthalmology. 64:534-536.
  6. 6.0 6.1 6.2 6.3 6.4 Harris G, Breazzano M, Shyu I, Donahue S, Lavin P. (2019). Oculomotor Synkinesis (Aberrant Reinnervation of the Third Cranial Nerve) Associated with Atypical Tolosa-Hunt Syndrome. Neuro-Ophthalmology, DOI: 10.1080/01658107.2019.1576738.
  7. 7.0 7.1 7.2 Shrestha UD, Adhikari S. (2012). Aberrant Regeneration of the Third Cranial Nerve. Nepal J Ophthalmology. 4(7):176-178.
  8. Seddon, HJ. (1942). A Classification of Nerve Injuries. British Medical Journal. 2(4260): 237-239.
  9. 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Weber E, Newman A. (2007). Aberrant Regeneration of the Oculomotor Nerve: Implications for Neurosurgeons. Neurosurg Focus. 23(5):E14.