Internuclear ophthalmoplegia is characterized by paresis of eye adduction in horizontal gaze but not in convergence. It can be unilateral or bilateral.

During horizontal gaze, the medial longitudinal fasciculus (MLF) on each side of the brain stem enables abduction of one eye to be coordinated with adduction of the other. The MLF connects the following structures:

6th cranial nerve nucleus (which controls the lateral rectus, responsible for abduction)

Adjacent horizontal gaze center (paramedian pontine reticular formation)

Contralateral 3rd cranial nerve nucleus (which controls the medial rectus, responsible for adduction)

The MLF also connects the vestibular nuclei with the 3rd cranial nerve nuclei.

Internuclear ophthalmoplegia results from a lesion in the MLF. In young people, the disorder is commonly caused by multiple sclerosis and may be bilateral. In the elderly, internuclear ophthalmoplegia is typically caused by stroke and is unilateral. Occasionally, the cause is Arnold-Chiari malformation, neurosyphilis, Lyme disease, tumor, head trauma, nutritional disorders (eg, Wernicke encephalopathy, pernicious anemia), or drug intoxication (eg, with tricyclic antidepressants or opioids).

If a lesion in the MLF blocks signals from the horizontal gaze center to the 3rd cranial nerve, the eye on the affected side cannot adduct (or adducts weakly) past the midline. The affected eye adducts normally in convergence because convergence does not require signals from the horizontal gaze center. This finding distinguishes internuclear ophthalmoplegia from 3rd cranial nerve palsy, which impairs adduction in convergence (this palsy also differs because it causes limited vertical eye movement, ptosis, and pupillary abnormalities).

During horizontal gaze to the side opposite the affected eye, images are horizontally displaced, causing diplopia; nystagmus often occurs in the abducting eye. Sometimes vertical bilateral nystagmus occurs during attempted upward gaze.

Treatment is directed at the underlying disorder.

One-and-a-half syndrome: This uncommon syndrome occurs if a lesion affects the horizontal gaze center and the MLF on the same side. The eyes cannot move horizontally to either side, but the eye on the side opposite the lesion can abduct; convergence is unaffected. Causes include multiple sclerosis, infarction, hemorrhage, and tumor.

With treatment (eg, radiation therapy for a tumor, treatment of multiple sclerosis), improvement may occur but is often limited after infarction.