Internuclear ophthalmoplegia (INO)

David Goldemund M.D.
Updated on 03/06/2024, published on 03/06/2024

Anatomic and physiologic notes

Conjugate eye movements

  • positioning and stabilizing the image of an object exactly on the fovea of both eyes at the same time requires precisely coordinated activity of the eye muscles
  • the agonist and antagonist muscles of the two eyes are always simultaneously innervated (Hering’s law), and each contraction of an agonist occurs in conjunction
    with relaxation of the corresponding antagonist (Sherrington’s law)
  • conjugate movements of both eyes in the same direction are called versive movements (from the Latin for “turning”), while movements of the two eyes in opposite
    directions are vergence movements (either convergence or divergence)
  • movements of a single eye are called either duction or torsion (rotatory movement)

Conjugate horizontal gaze regulation

  • the central relay nucleus of the oculomotor system is located in the paramedian pontine reticular formation (PPRF or “pontine gaze center”), which is adjacent to the nucleus of the abducens nerve
  • PPRF is where all the neural connections for coordinating horizontal eye movements originate. This includes the fibers that link the abducens nucleus on one side of the brain to the part of the oculomotor nucleus on the opposite side that controls the medial rectus muscle
  • these fibers run in the medial longitudinal fasciculus (MLF), a white-matter tract that ascends and descends the brainstem on both sides near the midline. The MLF extends from the midbrain all the way to the cervical spinal cord and serves to interconnect all of the individual nuclei that innervate the eye muscles
  • it also transmits impulses to and from the cervical spinal cord, the vestibular nuclei, the basal ganglia, and the cerebral cortex
Conjugate horizontal gaze regulation


  • multiple sclerosis is the most common cause
  • small infarct (older patients)
  • pontine glioma  (Wiest, 1999)
  • encephalitis
  • post-surgical/-procedural
  • small brainstem hemorrhage

Clinical presentation

Anterior internuclear ophthalmoplegia (INO)

  • internuclear ophthalmoplegia (INO) is caused by a lesion in the medial longitudinal fasciculus (MLF) affecting the connection of the paramedian pontine reticular formation (PPRF) with oculomotor nuclei
  • if the left-sided MLF is damaged, the patient’s left medial rectus muscle is no longer activated during horizontal gaze to the right ⇒ the ipsilateral eye is unable to adduct and remains in the midline
  • at the same time, monocular nystagmus is seen in the contralateral abducting eye (right eye in this case)
    • this nystagmus is absent in the paretic eye (dissociated nystagmus)
  • INO involves neither a nuclear nor a peripheral palsy of the oculomotor nerves; convergence is typically preserved
  • the MLF lies near the midline, and both fasciculi may be damaged due to a single lesion
    • adduction is impaired bilaterally, and nystagmus is present in both abducting eyes.
Internuclear ophthalmoplegia (INO)

Posterior internuclear ophthalmoplegia (INO)

  • also called Lutz posterior INO, internuclear ophthalmoplegia of abduction, or reverse INO
    • first described by Lutz in 1923
  • a rare condition, clinically presenting as a mirror image of anterior INO: deficit of abduction + nystagmus in the contralateral adducting eye
  • convergence may be preserved or impaired depending on the location of the lesion
  • the location of the lesion is debated; cases of reverse INO have been localized to the PPRF, pre-nuclear rostral pons, abducens fasciculus, pontine MLF, and midbrain
  • the response to caloric stimulation of the peripheral vestibular system is preserved

Differential diagnosis

  • one-and-half syndrome
    • ipsilateral lesion of the MLF and PPRF
    • presents with a combination of ipsilateral horizontal gaze palsy and INO (internuclear ophthalmoplegia) – the ipsilateral eye is immobile in the horizontal plane, and the movement of the contralateral eye is limited to abduction, sometimes accompanied by nystagmus
  • peripheral lesions of the ocular motor nerves, neuromuscular transmission, or ocular muscles may mimic INO (pseudo-INO)
    • most commonly, pseudoINO is caused by myasthenia gravis, where, unlike INO, adduction is impaired even during near-gaze  (Zheng, 2019)
    • partial lesion of the oculomotor nerve
    • Miller-Fisher syndrome
    • orbital tumor
    • thyroid eye disease (thyroid-associated ophthalmopathy)

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Internuclear ophthalmoplegia (INO)