Internuclear Ophthalmoplegia


Article Author:
Kaberi Feroze


Article Editor:
Jim Wang


Editors In Chief:
Sherri Murrell


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/28/2019 11:35:48 AM

Introduction

Internuclear ophthalmoplegia is an ocular movement disorder caused by a lesion of the medial longitudinal fasciculus. [1]It is characterized by impaired adduction of the ipsilateral eye with nystagmus of the abducting eye. Although the medial longitudinal fasciculus was identified in the 1870s, internuclear ophthalmoplegia was first described in 1903.

Etiology

Internuclear ophthalmoplegia is a condition caused by a lesion of the medial longitudinal fasciculus (MLF), a fiber tract responsible for transmitting information that is vital for coordination of different eye movements. It is a paired white matter tract passing close to the midline, through the brainstem lying ventral to the cerebral aqueduct in the midbrain and the fourth ventricle in the pons and medulla. It is the final common pathway for different types of conjugate eye movements like saccades, smooth pursuit, vestibulocochlear reflex, and forms a communication between all the ocular motor nuclei.[2] A lesion of the medial longitudinal fasciculus can produce impaired horizontal conjugate eye movements.

Epidemiology

About a third of the cases of internuclear ophthalmoplegia are caused by infarctions and are commonly unilateral and seen in older individuals. Demyelinating disorders like multiple sclerosis (MS) account for another third of cases and are mostly bilateral and seen in young adults and adolescents. Some studies have shown that internuclear ophthalmoplegia is seen in about 23% of MS patients. Other causes of internuclear ophthalmoplegia include trauma, tentorial herniation, infections (like HIV, syphilis, cysticercosis, herpes zoster, tuberculoma), tumors (medulloblastoma, glioma, lymphoma, metastases), vasculitis (systemic lupus erythematosus (SLE), Sjogren syndrome), iatrogenic injury, and brainstem hemorrhage. The incidence of internuclear ophthalmoplegia in males and females is almost equal. Nearly half of all cases of internuclear ophthalmoplegia resolve within one year. Internuclear ophthalmoplegia is extremely rare in the pediatric population. Tumors like medulloblastoma and Pontine gliomas are important causes besides trauma, vasculitis, infarction, and hemorrhage.

Pathophysiology

Internuclear ophthalmoplegia occurs due to a lesion in the medial longitudinal fasciculus (MLF) by blocking the connection between contralateral sixth nerve nucleus and the ipsilateral third nerve nucleus, thus affecting horizontal gaze. One of the most important functions of the medial longitudinal fasciculus is its role in saccadic eye movements. Saccades are initiated by the frontal eye field (FEF), which sends signals to the contralateral paramedian pontine reticular formation (PPRF) for horizontal saccades and the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) for vertical saccades. [3]The paramedian pontine reticular formation activates the ipsilateral abducens nucleus which sends signals to the Lateral rectus muscle of the same side and via abducent excitatory interneurons (after decussation) to the contralateral medial rectus subnucleus of the oculomotor nucleus through the medial longitudinal fasciculus, thus resulting in horizontal gaze opposite to the initiating frontal eye field. The cardinal sign of internuclear ophthalmoplegia is slowing or impaired adduction on the same side as the medial longitudinal fasciculus lesion. The cause is because the abducent excitatory interneurons fail to reach the medial rectus subnucleus.

The contralateral abducting eye may demonstrate a dissociated horizontal nystagmus. This is thought to be a compensatory response to overcome the weakness of the adducting eye explained by Herring’s law of equal innervation. Increased innervations to the medial rectus muscle are accompanied by an increase in innervation to its yoke muscle, the contralateral lateral rectus, resulting in nystagmus.

Although there is impaired adduction in the ipsilateral eye, some patients may have normal convergence. This is called dissociation of convergence and is an important sign which helps distinguish internuclear ophthalmoplegia from pseudo internuclear ophthalmoplegia (e.g., myasthenia gravis, third nerve palsy). It was initially thought that patients with medial longitudinal fasciculus lesion below the level of the oculomotor nucleus (posterior internuclear ophthalmoplegia of Cogan) had retained convergence and lesions above the oculomotor nucleus level (anterior internuclear ophthalmoplegia of Cogan) had absent convergence. However, recent studies have disproved this theory and retained convergence is thought to reflect the innate ability to converge to near targets.

History and Physical

Patients with internuclear ophthalmoplegia report symptoms of varying severity. Some patients may report blurry vision or diplopia or dizziness on lateral gaze. Surprisingly, some patients may complain of vertical diplopia. Vertical diplopia in the primary position is due to skew deviation of eyes with the weak adducting eye being hypertrophic. Skew deviation is a vertical misalignment of eyes caused by asymmetrical disruption of supranuclear input from the otolithic organs of the inner ear.

The hallmark of internuclear ophthalmoplegia is impaired adduction in the eye ipsilateral to the affected medial longitudinal fasciculus, which can range from mild limitation to severe restriction of adduction. There is a nystagmus in the abducting eye associated with this, which usually lasts for a few beats.[4] Some patients with internuclear ophthalmoplegia may converge to a near target. The dissociation of the medial rectus function during horizontal saccades and convergence helps to confirm a medial longitudinal fasciculus lesion, ruling out other causes of medial rectus weakness. In all cases of internuclear ophthalmoplegia, the physician should be on the lookout for other brainstem signs to confirm the diagnosis of internuclear ophthalmoplegia and localize the site of the medial longitudinal fasciculus lesion. Lesions of the medial longitudinal fasciculus associated with adjacent brainstem structures can produce a variety of ocular motor signs and are called internuclear ophthalmoplegia plus syndromes.

  1. A lesion involving the paramedian pontine reticular formation (horizontal gaze center) and the medial longitudinal fasciculus produces “one and a half syndrome.” This syndrome is characterized by loss of all horizontal movements except abduction in the contralateral eye.
  2. Unilateral internuclear ophthalmoplegia may be accompanied by vertical strabismus due to skew deviation or associated trochlear nerve palsy.
  3. Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) which is a rare disorder in which bilateral internuclear ophthalmoplegia is associated with bilateral exotropia.[5] Exotropia is thought to occur due to disruption of the input from otolithic organs.

Evaluation

The physical examination in most patients with internuclear ophthalmoplegia helps practitioners to arrive at a diagnosis. However, investigations like neuroimaging assist in finding the underlying cause. MRI can be a valuable tool in this regard, and up to 75% of patients may have a visible lesion. For demyelinating lesions, proton density imaging is considered to be ideal. Supplementary blood and cerebrospinal fluid (CSF) studies may be undertaken to detect uncommon causes.[6]

Treatment / Management

Treatment depends on the underlying cause. Acute strokes require hospitalization and neurological evaluation. Other pathologies require management by a physician (e.g., MS, infections, SLE). Most patients with demyelination, infectious, and traumatic etiologies show complete recovery. Patients with cerebrovascular disorders had a less favorable recovery. Recovery is said to be more likely if internuclear ophthalmoplegia is isolated than if other neurological signs accompany it. According to some studies, recovery is also said to be less likely if there was a visible lesion causing internuclear ophthalmoplegia.

The majority of the patients with persistent internuclear ophthalmoplegia have minimal symptoms. Those with diplopia may benefit from botulinum toxin injections or Fresnel prisms. Surgical correction of strabismus may be used for patients with wall-eyed bilateral internuclear ophthalmoplegia.

Pearls and Other Issues

A simple physical examination is often all that is required to diagnose a case of internuclear ophthalmoplegia. Although most cases of isolated internuclear ophthalmoplegia have a favorable prognosis, patients should be evaluated to determine the underlying cause. The medial longitudinal fasciculus with its periventricular location represents an accessible site for stem cell delivery to test newer innovative neuroprotective and restorative therapies such as stem cell remyelination.

Enhancing Healthcare Team Outcomes

Findings of internuclear ophthalmoplegia on a physical exam needs a CNS work up to determine the cause. A multidisciplinary team including nurses should be involved in the work up. The treatment depends on the cause.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Internuclear Ophthalmoplegia - Questions

Take a quiz of the questions on this article.

Take Quiz
A 28-year-old male has a 2-week history of right-sided numbness and mild headaches. Four days ago he developed double vision. Exam shows decreased sensation to pinprick and light touch on the left leg, arm and face. On left gaze, he is unable to gaze past the midline with his right eye and develops horizontal nystagmus of the left eye. Convergence and eye movement to the right are normal. Where is the lesion?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
How can bilateral internuclear ophthalmoplegia (INO) be differentiated from a bilateral medial rectus nuclear lesion?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 32-year-old female presents with complaint of diplopia. On rightward gaze, her left eye does not adduct past the midline and horizontal nystagmus is noted in the right eye. Upward and downward gaze are normal. What is the diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 68-year-old woman complains of headaches and vertigo. Gradually, the patient develops a spastic hemiplegia on the right side, with hyperactive deep tendon reflexes of the right arm and right leg. The patient complains of double vision. Examination reveals that the left eye is deviated nasally, indicating a paralysis of the left lateral rectus muscle. The patient has a paralysis of ocular adduction on attempting lateral gaze and horizontal nystagmus in the abducting eye. Pupillary reactions are normal. Where is the lesion most probably located?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 65-year-old male patient presents with a sudden onset of double vision. Ocular examination reveals the limitation of adduction in the right eye and a nystagmus in the left eye on left gaze. What is the most likely underlying cause of the patient’s ocular condition?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 25-year-old male, known to have multiple sclerosis, presents with complaints of occasional double vision for the past 5 days. Right Internuclear ophthalmoplegia is diagnosed. Which of the following ocular findings may be seen in this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 45-year-old patient comes presents with complaints of occasional blurring of vision and dizziness. On examination, there is a limitation of adduction in the right eye and a nystagmus in the left eye on attempted left gaze. Convergence is intact. What is the most likely location of the lesion causing these ophthalmic signs?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Internuclear Ophthalmoplegia - References

References

Internuclear ophthalmoplegia., Virgo JD,Plant GT,, Practical neurology, 2017 Apr     [PubMed]
Wall-eyed bilateral internuclear ophthalmoplegia in a patient with progressive supranuclear palsy., Ushio M,Iwasaki S,Chihara Y,Murofushi T,, Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, 2008 Jun     [PubMed]
Isolated medial longitudinal fasciculus syndrome: Review of imaging, anatomy, pathophysiology and differential diagnosis., Kochar PS,Kumar Y,Sharma P,Kumar V,Gupta N,Goyal P,, The neuroradiology journal, 2017 Jan 1     [PubMed]
Correlating Function and Imaging Measures of the Medial Longitudinal Fasciculus., Sakaie K,Takahashi M,Remington G,Wang X,Conger A,Conger D,Dimitrov I,Jones S,Frohman A,Frohman T,Sagiyama K,Togao O,Fox RJ,Frohman E,, PloS one, 2016     [PubMed]
Pearls & Oy-sters: The medial longitudinal fasciculus in ocular motor physiology., Frohman TC,Galetta S,Fox R,Solomon D,Straumann D,Filippi M,Zee D,Frohman EM,, Neurology, 2008 Apr 22     [PubMed]
Abducting nystagmus in the medial longitudinal fasciculus (MLF) syndrome- internuclear ophthalmoplegia (INO)., Stroud MH,Newman NM,Keltner JL,Gay AJ,, Archives of ophthalmology (Chicago, Ill. : 1960), 1974 Jul     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Nurse-Elder Adult Care. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Nurse-Elder Adult Care, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Nurse-Elder Adult Care, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Nurse-Elder Adult Care. When it is time for the Nurse-Elder Adult Care board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Nurse-Elder Adult Care.