Internuclear ophthalmoplegia is characterized by paresis of ipsilateral eye adduction in horizontal gaze but not in convergence. It can be unilateral or bilateral.
(See also Overview of Neuro-ophthalmologic and Cranial Nerve Disorders.)
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 and 4th cranial nerve nuclei.
Internuclear ophthalmoplegia results from a lesion in the MLF:
In young people, commonly caused by multiple sclerosis and often bilateral
In older people, typically caused by stroke and is unilateral
Rarely, 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, phenothiazines, 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 (3rd cranial nerve 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 of internuclear ophthalmoplegia 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 eye affected by the lesion cannot move horizontally to either side, but the eye on the side opposite the lesion can abduct; convergence is unaffected.
Causes of one-and-a-half syndrome 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.
Key Points
Internuclear ophthalmoplegia results from a lesion in the medial longitudinal fasciculus, which coordinates abduction of one eye with adduction of the other.
Common causes are multiple sclerosis in young people (often bilateral) and stroke in older people (typically unilateral).
Distinguish internuclear ophthalmoplegia (which impairs adduction of the ipsilateral eye but not convergence) from 3rd cranial nerve palsy (which impairs adduction and convergence of the ipsilateral eye).
One-and-a-half syndrome is a rare disorder in which a lesion affects the horizontal gaze center and the medial longitudinal fasciculus on the same side; the eye on the affected side cannot move horizontally to either side, but the other eye can abduct; convergence is unaffected.
