Internuclear Ophthalmoplegia

Internuclear ophthalmoplegia (INO) is an ocular movement disorder that affects the conjugate horizontal gaze, meaning the eyes are incapable of moving in a simultaneous and coordinated manner on the horizontal plane. This disorder is usually caused by a lesion in the brain stem involving the medial longitudinal fasciculus (MLF) and is characterized by impaired adduction ipsilateral to the MLF lesion and abduction nystagmus contralateral to the MLF lesion. Internuclear ophthalmoplegia is a clinical diagnosis. However, investigations involving neuroimaging, especially MRI, help establish the diagnosis. Management of INO varies depending on the cause. The prognosis mainly depends on the etiology. For instance, trauma patients do not have a very favorable prognosis, whereas patients with ischemic and demyelinating causes have a favorable recovery.

Last update:

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp



Internuclear ophthalmoplegia (INO) is an ocular movement disorder that is due to a lesion of the medial longitudinal fasciculus (MLF), mainly in the brain stem tegmentum (dorsomedial pons or the midbrain).


  • ⅓ of cases in adolescents due to multiple sclerosis
  • ⅓ of cases in old age due to stroke/infarction
  • Rare in children


Internuclear ophthalmoplegia is mainly due to autoimmune demyelinating disorder and infarction.

  • Autoimmune INO: due to a demyelinating disorder, such as multiple sclerosis or Sjögren syndrome (bilateral)                                                                                                                           
  • Infarction INO: due to a brain stem infarction (unilateral)
  • Other causes:   
    • Head trauma
    • Tumors (medulloblastoma, glioma, lymphoma)
    • Arnold-Chiari malformation
    • Infection (HIV, syphilis, cysticercosis, etc.)
    • Hydrocephalus
    • Brain stem hemorrhage


Normal physiology

The MLF has a very important role in controlling the direction of eye movements.

  • A pair of crossed fiber tracts surrounding the paramedian area of the midbrain and pons
  • Heavily myelinated
  • Mainly controls the horizontal gaze by interconnecting the cranial nerves III (oculomotor nerve), IV (trochlear nerve), and VI (abducens nerve) via interneuronal pathways:
    • The signal for saccadic eye movements (quick simultaneous movements) initiates in the frontal eye field which, in turn, activates the contralateral paramedian pontine reticular formation (PPRF). 
    • The PPRF innervates the ipsilateral cranial nerve (CN) VI nucleus, resulting in abduction of the ipsilateral eye through the action of the lateral rectus muscle. 
    • Signals from the activated abducens nucleus are also transmitted to the contralateral CN III nucleus via the MLF, resulting in adduction of the contralateral eye through the action of the medial rectus muscle.


Internuclear ophthalmoplegia occurs because of a lesion or dysfunction of the MLF, characterized by: 

  • Defective adduction on the same side as the lesion 
  • Abducting nystagmus on the contralateral side
  • Normal convergence of the eyes due to intact medial rectus innervation
Defect of horizontal gaze in internuclear ophthalmoplegia

Defect of horizontal gaze in internuclear ophthalmoplegia:
Note the ipsilateral defective adduction, contralateral abducting nystagmus, and normal convergence.
MLF: medial longitudinal fasciculus
III: nucleus of the oculomotor cranial nerve III
VI: nucleus of the abducens cranial nerve VI
PPRF: paramedian pontine reticular formation

Image by Lecturio. License: CC BY-NC-SA 4.0

Clinical Presentation

The presentation of patients with INO can vary but includes:

  • Changes in vision and eye movements:
    • Marked limitation of adduction in eye ipsilateral to the side of MLF lesion
    • Abduction nystagmus of contralateral eye
    • Blurry vision
    • Diplopia (sometimes vertical diplopia, mainly seen in unilateral INO)
    • Oscillopsia
  • Others:
    • Dizziness
    • Gait instability
    • Weakness
    • Headache

Diagnosis and Management


  • Clinical: The diagnosis is mainly clinical, based on the assessment of the patient’s ability to perform conjugate eye movements.                  
  • Radiologic:
    • MRI and CT scans may be used (MRI is preferred).
    • Proton density imaging is also helpful for diagnosing underlying demyelinating lesions. 
    • Optokinetic tape is also highly sensitive for testing for INO.


Management depends on the underlying cause.

  • Neurologic cause: treated after detailed neurology evaluation
  • Infectious/autoimmune cause: 
    • Corticosteroids are the treatment of choice.
    • Diframpadine (potassium channel blocker) has been used in patients with demyelinating disease.
  • Diplopia: can be treated with botulinum toxin injections or Fresnel prisms
  • Strabismus: can be surgically treated in patients with wall-eyed bilateral INO

Differential Diagnosis

  • Lateral gaze palsy: due to a lesion in CN VI (abducens) resulting in impaired ipsilateral abduction. Lateral gaze palsy can be caused by trauma or microvascular ischemia or can be secondary to multiple other causes, including multiple sclerosis, stroke, or increased intracranial pressure.
  • One and a half syndrome: horizontal movement disorder of the eyes. One and a half syndrome is characterized by a conjugate horizontal gaze palsy in one direction and an internuclear ophthalmoplegia in the other. The syndrome is caused by a lesion of the PPRF and the MLF and is most commonly due to cerebrovascular diseases. 
  • Stroke: occlusion of distal penetrating arteries that leads to dorsal brain stem infarction and can present as INO, diplopia, or vision changes. Brainstem stroke can also present with diverse visual symptoms, including homonymous hemianopia or cortical blindness, skew deviation of eyes, nystagmus, and ocular or facial pain.


  1. Rubin, M. (2020). Internuclear ophthalmoplegia. Merck Manual Professional Version. Retrieved May 28, 2021, from
  2. Swisher, J., Kini, A., Lee, A.G. (2020). Internuclear ophthalmoplegia. American Academy of Ophthalmology. Retrieved May 28, 2021, from

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.