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PupillaEye Exam Lab

Internuclear ophthalmoplegia (INO), one-and-a-half syndrome and gaze palsies

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Quick answer

Internuclear ophthalmoplegia (INO) is caused by a lesion of the medial longitudinal fasciculus (MLF). On side gaze, the eye on the side of the lesion fails to adduct or adducts slowly, while the other eye abducts with nystagmus; convergence is often preserved. A lesion of the abducens nucleus or the paramedian pontine reticular formation (PPRF) causes a horizontal gaze palsy toward that side, and when it also involves the neighboring MLF the result is one-and-a-half syndrome: the only horizontal movement left is abduction of the opposite eye.

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How horizontal gaze is wired

Voluntary horizontal saccades start in the frontal eye field, which drives the PPRF on the opposite side. The PPRF activates the abducens nucleus on its own side. The abducens nucleus has two outputs: motor neurons to the lateral rectus on the same side, and interneurons that cross the midline and travel up the medial longitudinal fasciculus (MLF) to the medial rectus subnucleus of the opposite third nerve. That is how both eyes turn together.

Internuclear ophthalmoplegia (INO)

  • An INO is named after the side of the MLF lesion, which is the side of the eye with the adduction deficit or slowed adducting saccades.
  • The opposite eye shows abducting nystagmus when the patient looks away from the lesion side.
  • Convergence is often preserved, showing that the medial rectus and the third nerve themselves work.
  • Common causes are multiple sclerosis in young adults (often bilateral) and brainstem stroke in older adults (usually unilateral).
  • A bilateral INO with a large exotropia is called WEBINO (wall-eyed bilateral INO).

A mild INO may show only slow adduction. Ask the patient to make quick saccades between two targets to the side and compare the speed of the two eyes.

One-and-a-half syndrome

A single lesion of the abducens nucleus or PPRF together with the adjacent MLF causes a horizontal gaze palsy toward the side of the lesion (the "one") plus an INO on the same side (the "half"). The only horizontal movement left is abduction of the opposite eye, usually with nystagmus. Causes include multiple sclerosis and pontine stroke.

Horizontal gaze palsy and frontal eye field lesions

  • Abducens nucleus lesion: neither eye can look toward the side of the lesion, and the doll's head (oculocephalic) maneuver cannot overcome the palsy, because the final common pathway for horizontal gaze is damaged.
  • PPRF lesion: saccades toward the side of the lesion are lost, but reflex movements from the doll's head maneuver may still be possible.
  • Acute frontal eye field lesion (for example a large hemispheric stroke): the eyes look toward the side of the lesion and voluntary gaze to the other side is poor, but the doll's head maneuver moves the eyes fully, because the brainstem pathway is intact. It usually recovers within days to weeks.

Parinaud (dorsal midbrain) syndrome

  • Upgaze palsy, especially of upward saccades, with the vestibulo-ocular reflex and Bell phenomenon often preserved.
  • Convergence–retraction nystagmus on attempted upward saccades.
  • Light–near dissociation of the pupils.
  • Upper eyelid retraction (Collier sign).
  • Causes include pineal region tumors in children and young adults, hydrocephalus, and midbrain stroke or multiple sclerosis.

Practice it on the virtual patient

  1. Open a right INO, look to the left and watch the right eye lag while the left eye abducts.
  2. Compare with a bilateral INO (WEBINO) and a one-and-a-half syndrome.
  3. Open a horizontal gaze palsy and a frontal eye field lesion to see how they differ.
  4. Finish with Parinaud syndrome and test upgaze and the pupils.
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Frequently asked questions

Which side is the lesion in an INO?

The lesion is in the MLF on the same side as the eye that fails to adduct. A right INO means a right MLF lesion: the right eye adducts poorly when the patient looks to the left.

Why is convergence preserved in an INO?

Convergence reaches the medial rectus subnucleus through midbrain pathways that do not use the MLF. Normal convergence shows that the medial rectus and third nerve are intact, which separates an INO from a medial rectus or third nerve palsy.

What is the most common cause of an INO?

In young adults, especially with a bilateral INO, the most common cause is multiple sclerosis. In older adults a unilateral INO is more often caused by a brainstem stroke.

What is WEBINO?

WEBINO stands for wall-eyed bilateral internuclear ophthalmoplegia: a bilateral INO with a large exotropia in primary position, usually from a midbrain lesion affecting both MLFs.