Neuroscience Clerkship

 

 

 

 

ANISOCORIA

 

Anisocoria is defined as a difference in pupil size between the two eyes. Anisocoria is associated with a variety of neurologic conditions, some benign and other serious.


Pupil Physiology

Pupil size is controlled by two sets of antagonist muscles:

the pupillary sphincter (parasympathetic)

                          and

the pupillary dilator muscles (sympathetic)

Under normal conditions, the pupils remain equal at all levels of light.

The parasympathetic pathway (figure above) originates in the Edinger-Westphal nucleus in the dorsal mid brain and exits to run with cranial nerve III (oculomotor nerve) through the cavernous sinus to the ciliary ganglion. From the cililary ganglion, postganglionic fibers then travel to the pupilloconstrictor muscle of the iris.
 

 

The sympathetic pathway (figure above) originates in the hypothalamus to run down in the brainstem laterally to reach at spinal column at C8-T2. Fibers then run with the ventral roots to the paravertebral sympathetic chain. These fibers then pass through the stellate ganglion near the apex of the lung to run to the superior cervical ganglion. The postganglionic fibers then travel in the sheath of the internal carotid artery to innervate the pupillary dilator muscle. In addition, sympathetic fibers supply innervation to smooth muscles of the upper and lower eyelids. Lastly, sympathetic fibers also travel with the external carotid artery to supply blood vessels and sweat glands of the face. Thus, a complete Horner's syndrome (at or proximal to the internal carotid artery) will result in ptosis, miosis and anhydrosis.


Common Causes of Anisocoria

Physiologic anisocoria

Mild anisocoria (typically 1 mm or less) is common in the general population. As long as there are no other accompanying signs and symptoms (e.g., diplopia, pain, ptosis), this represents a benign, normal anatomic variant.

 

Horner's Syndrome

Horner's syndrome results from disruption of the sympathetic fibers anywhere between the hypothalamus and the eye. Thus, Horner's syndrome can be seen in primary brainstem pathology; lesions of the superior cervical ganglia and disorders of the carotid artery. Common causes include Wallenberg's syndrome (i.e., infarction of the lateral medulla), cervical cord disease (e.g., syrinx), apical lung disease (e.g., pancoast tumor), carotid artery dissection, and cavernous sinus disease (i.e., infection or neoplastic invasion).

As noted above, a full Horner's syndrome will produce miosis, anhydrosis and ptosis. As the primary problem in Horner's syndrome is a failure of pupillary dilatation, the anisocoria will be more marked in the dark than the light.

Above: Horner's syndrome is the left eye. (A) In the light; (B) In the dark; and (C) In the dark after a brief lapse of time. Note the difference in the anisocoria between light and dark. Often a subtle sign of a mild Horner's will be a dilatation lag when going from light to dark.

 

Pharmacologic testing with eye drops can be very helpful in localizing the site of the lesion in a patient with Horner's syndrome. Cocaine (a norepinephrine reuptake blocker) eye drops will fail to dilate the affected side, and can confirm the presence of a Horner's syndrome.

Hydroxyamphetamine drops are used to stimulate norepinephrine release from the postganglionic sympathetic neuron (i.e., the neuron at the superior sympathetic ganglia that then runs to the eye). If the site of the lesion is the postganglionic neuron, dilation will not occur with the use of hydroxyamphetamine, where a lesion in the brainstem or between the cord and the superior cervical ganglion will dilate normally.


Third Nerve Palsy

A cranial nerve III palsy results in a dilated, poorly reactive pupil. As the pupil is unable to constrict to light, the anisocoria is more apparent in the light than dark. As the third nerve also innervates several extraocular muscles, a third nerve palsy often results in an accompanying ptosis and diplopia (the latter from weakness of the medial rectus, inferior rectus, inferior oblique, and superior rectus muscles).

The most important causes of a third nerve palsy are external compression of an aneursym (typically one arising from the posterior communicating artery) and uncal herniation where the medial temporal lobe compresses the adjacent third nerve. Of course, third nerve palsies may occur in other conditions, including diabetes, vasculitis, and infiltrating disorders (e.g., neoplasm, sarcoid, etc.)

 

Pharmacologic

Atropine and many other drugs have anticholingeric side effects. Inadvertent or unintentional exposure to these agents may result in a dilated, fixed pupil. This can often occur in medical personnel, especially nurses who dispense medications. In contrast to a third nerve palsy, the remainder of the examination is normal (i.e., no ptosis or extrocular muscle weakness). Proving inadvertent pharmacologic administration can be performed by instilling 1% pilocarpine eye drops. In pharmocologic paralysis, no constriction will occur, where in a third nerve palsy, the pupil will quickly constrict.


• Local Damage to the Iris

Mechanical damage to the iris may result in anisocoria. This is most often seen after cataract surgery, but can also occur with trauma, and some inflammatory disorders (e.g., uveitis).