Internuclear Ophthalmoplegia: Symptoms, Types, Causes and Treatment

Internuclear ophthalmoplegia (INO) is a fascinating yet disabling neurological eye movement disorder. It occurs when there is a disruption in the communication pathway between certain cranial nerve nuclei in the brainstem, specifically the medial longitudinal fasciculus (MLF). This disruption leads to distinctive abnormalities in how the eyes move, most notably a problem with moving one eye inward (adduction) and the appearance of involuntary, jerky movements (nystagmus) in the outward-moving (abducting) eye. INO can be a window into underlying neurological diseases and requires a nuanced understanding for effective diagnosis and management.

Symptoms of Internuclear Ophthalmoplegia

Recognizing the symptoms of INO is key for early diagnosis and appropriate management. Patients often present with a unique set of eye movement abnormalities, sometimes accompanied by other neurological symptoms.

Symptom	Description	Frequency/Context	Sources
Adduction Failure	One eye fails to move inward during horizontal gaze	Most common and defining	2 3 4 5
Abducting Nystagmus	Outward-moving eye exhibits jerky movements	Often accompanies adduction deficit	2 3 4 7 14
Diplopia	Double vision, especially when looking to the sides	Common in both unilateral & bilateral INO	5 15 16
Gaze Paresis	Weakness or limited movement in horizontal gaze	Occasionally seen	1 4 12
Ataxia	Loss of coordination (in some cases)	When nearby brainstem areas are affected	8

Table 1: Key Symptoms

Core Clinical Features

The hallmark symptom of INO is the inability of one eye to adduct (move toward the nose) when the patient tries to look to the opposite side. For example, if the left MLF is affected, the left eye cannot move inward when looking right, while the right eye (the abducting eye) will often show a coarse, jerky nystagmus as it moves outward 2 3 4.

Diplopia (Double Vision)

Patients frequently report double vision, especially when trying to look to the side opposite the lesion. The double vision can be quite debilitating, affecting daily activities such as reading or driving 5 15 16.

Abducting Nystagmus

A distinctive feature is the nystagmus of the outward-moving eye. This is thought to be an adaptive response, where the brain attempts to compensate for the weak inward movement by increasing the neural drive to both eyes, resulting in overshoot and nystagmus in the abducting eye 14. There are even more complex patterns, such as torsional–vertical nystagmus, seen in some cases 7.

Gaze Paresis and Ataxia

Some patients, especially those with larger or more strategically placed lesions, may exhibit gaze paresis (difficulty moving both eyes in a particular direction) or ataxia (loss of coordination), indicating involvement of adjacent brainstem structures 1 8 12.

Subtle and Additional Signs

• Optokinetic nystagmus abnormalities and ocular dysmetria may be present in subtle or partial forms of INO 2.
• In bilateral cases, symptoms are more severe, and patients may also experience problems with convergence (eyes coming together for near vision) 5 16.

Types of Internuclear Ophthalmoplegia

INO is not a one-size-fits-all disorder; it presents in several forms depending on the location and extent of the underlying lesion. Understanding these types guides both diagnosis and prognosis.

Type	Key Features	Typical Cause/Context	Sources
Unilateral INO	One eye affected, adduction deficit on one side	Stroke, trauma, SLE	3 5 6 9 13
Bilateral INO	Both eyes affected, often severe exotropia	Multiple sclerosis	3 5 10 12 16
INO-Plus Syndromes	INO combined with other deficits (e.g. ataxia, gaze palsy)	Larger or specific brainstem lesions	4 8 12
Exotropic INO	INO with outward deviation of eyes (exotropia)	Bilateral INO/MS	16

Table 2: Variants of INO

Unilateral Internuclear Ophthalmoplegia

Most commonly caused by a small, localized lesion (often a stroke) affecting one MLF, unilateral INO presents with adduction weakness in one eye and abducting nystagmus in the opposite eye. Trauma and autoimmune diseases like systemic lupus erythematosus (SLE) can also cause unilateral INO 3 5 6 9 13.

Bilateral Internuclear Ophthalmoplegia

When both MLFs are affected, as in many cases of multiple sclerosis (MS), the result is bilateral INO. Patients experience adduction deficits in both eyes, often leading to severe double vision and sometimes an outward deviation of the eyes (exotropia) 3 5 10 12 16.

INO-Plus Syndromes

Some patients exhibit INO in combination with other neurological findings, known as INO-plus syndromes:

• INO plus ataxia: Indicates a lesion at the pontomesencephalic junction, affecting both the MLF and cerebellar connections 8.
• One-and-a-half syndrome: INO combined with horizontal gaze palsy, usually due to a larger lesion involving both the MLF and the adjacent horizontal gaze center 12.

Exotropic INO (Wall-Eyed Bilateral INO)

Seen in severe bilateral INO, especially in MS, patients develop a pronounced outward deviation of the eyes. This form is particularly disabling and often requires surgical intervention 16.

Causes of Internuclear Ophthalmoplegia

Determining the cause of INO is crucial, as it often points to significant underlying neurological disease. While some causes are common, others are rare but clinically significant.

Cause	Description	Frequency/Association	Sources
Multiple Sclerosis (MS)	Demyelination of MLF, often bilateral	Most common in young adults	3 5 10 12 16
Brainstem Infarct	Small stroke affecting MLF	Common in older adults	3 6 10 12
Trauma	Head injury causing brainstem damage	Less common	9 10
Tumors	Brainstem or fourth ventricular neoplasms	Uncommon	5 9 10
Infection	E.g., syphilis, other CNS infections	Rare	5 9 10
Autoimmune Diseases	Lupus, vasculitis, post-infectious	Rare, but important	5 10 13
Drug-Induced	Anti-TNFα medications causing demyelination	Very rare	17
Congenital, Miscellaneous	Arnold-Chiari, hydrocephalus, iatrogenic	Rare	5 10

Table 3: Major Causes of INO

Multiple Sclerosis

• Pathophysiology: Demyelination of the MLF is the most frequent cause of INO in young and middle-aged adults, especially in women 3 5 10 12 16.
• Features: Often bilateral, may be the first sign of MS, and can fluctuate with disease activity.

Brainstem Infarction (Stroke)

• Pathophysiology: Small vessel ischemic strokes affecting the dorsal brainstem are the leading cause of INO in older adults 3 6 10 12.
• Features: Usually unilateral, but bilateral cases occur, especially with larger or multiple infarcts.

Trauma

• Mechanism: Direct injury to the brainstem, often from head trauma, can disrupt the MLF and cause INO, sometimes transiently 9 10.

Tumors and Infections

• Tumors: Brainstem and fourth ventricular tumors can compress or infiltrate the MLF, leading to INO 5 9 10.
• Infections: Syphilis and other rare infections may affect the brainstem and produce INO 5 9 10.

Autoimmune and Drug-Induced Causes

• Autoimmune: Systemic lupus erythematosus and vasculitis have been documented as rare causes, especially in young women 5 10 13.
• Drug-Induced: Rarely, medications such as anti-TNFα agents (used in autoimmune diseases) can result in demyelination and INO 17.

Other Causes

• Congenital: Conditions like Arnold-Chiari malformation, hydrocephalus, or even iatrogenic injury (e.g., after neurosurgery) can cause INO 5 10.
• Miscellaneous: Vasculitis, hemorrhage, and even metabolic causes fall into this category 10.

Treatment of Internuclear Ophthalmoplegia

Treatment of INO varies according to the underlying cause, severity, and persistence of symptoms. Managing INO often involves a combination of treating the root cause and addressing symptoms to improve quality of life.

Approach	Specifics/Target	Effectiveness/Notes	Sources
Treat Underlying Disease	MS (immunomodulation), stroke (supportive), infection (antibiotics), autoimmune (steroids)	Often leads to recovery	6 13 17
Symptomatic Relief	Prisms, occlusion therapy, botulinum toxin injections	Reduces diplopia, improves comfort	15 16
Surgery	Strabismus correction for severe exotropia	Beneficial in selected cases	16
Rehabilitation	Orthoptic exercises, visual therapy	Supportive, variable benefit	15 16

Table 4: Treatment Options in INO

Treating the Underlying Cause

• Multiple Sclerosis: Immunomodulatory therapies (such as corticosteroids or disease-modifying agents) can reduce inflammation and promote recovery 13 17.
• Ischemic Stroke: Supportive and secondary prevention therapies are indicated. INO due to stroke often recovers spontaneously, though it may take weeks to months 6.
• Autoimmune & Drug-Induced: Corticosteroids are often effective, especially for lupus-related INO. Discontinuing offending medications, such as anti-TNFα agents, may lead to improvement 13 17.
• Infectious and Tumoral Causes: Directed therapy (antibiotics, antivirals, or oncological treatment) is necessary.

Symptomatic Management

• Prisms and Occlusion: Prism glasses or patching can help alleviate diplopia in patients with persistent symptoms 15 16.
• Botulinum Toxin: Injection into extraocular muscles can provide temporary relief from double vision and abnormal eye positioning, though effects are temporary and repeat injections may be necessary 15.
• Orthoptic Therapy: Vision therapy and exercises may provide some improvement for mild cases.

Surgical Intervention

• Strabismus Surgery: For patients with severe, stable, and persistent exotropia (especially in bilateral INO caused by MS), surgical correction of eye alignment can significantly improve quality of life 16.
• Patient Selection: Surgery is reserved for those with stable neurological disease and persistent misalignment that does not respond to other therapies.

Prognosis and Recovery

• Many cases of INO, especially those due to stroke, resolve spontaneously over weeks to months 6.
• The prognosis is excellent for isolated INO, though persistent or recurrent cases may require ongoing management for diplopia and ocular misalignment 6 15 16.

Conclusion

Internuclear ophthalmoplegia is a distinctive disorder of eye movement that, while rare, holds immense diagnostic value for neurologists and ophthalmologists alike. Its presence often signals a serious underlying neurological disorder, and understanding its nuances is essential for effective treatment.

Key Takeaways:

• INO is characterized by impaired adduction of one or both eyes and abducting nystagmus, leading to diplopia and gaze abnormalities.
• Types of INO include unilateral, bilateral, and INO-plus syndromes, with bilateral INO often associated with multiple sclerosis.
• The main causes are multiple sclerosis and brainstem infarction; however, trauma, tumors, infections, autoimmune diseases, and medications can also be responsible.
• Treatment targets both the underlying disease and symptomatic relief, with options ranging from medical therapy to surgery for persistent or severe cases.
• Prognosis is generally good, especially when the underlying cause is treatable and with timely intervention.

By recognizing the pattern of symptoms and understanding the pathophysiology, clinicians can identify the root cause and tailor treatment to restore function and improve quality of life for patients with INO.