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.)
- Brain stem hemorrhage
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
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)
- Gait instability
Diagnosis and Management
- Clinical: The diagnosis is mainly clinical, based on the assessment of the patient’s ability to perform conjugate eye movements.
- 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
- 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.
- Rubin, M. (2020). Internuclear ophthalmoplegia. Merck Manual Professional Version. Retrieved May 28, 2021, from https://www.merckmanuals.com/professional/neurologic-disorders/neuro-ophthalmologic-and-cranial-nerve-disorders/internuclear-ophthalmoplegia
- Swisher, J., Kini, A., Lee, A.G. (2020). Internuclear ophthalmoplegia. American Academy of Ophthalmology. Retrieved May 28, 2021, from https://eyewiki.aao.org/Internuclear_Ophthalmoplegia