What is the cause of new onset diplopia (double vision) in a patient with multiple sclerosis (MS)?

New Onset Double Vision in Multiple Sclerosis

Primary Cause

In a patient with multiple sclerosis presenting with new onset diplopia, the most likely cause is internuclear ophthalmoplegia (INO) from a demyelinating lesion in the medial longitudinal fasciculus (MLF) of the brainstem, though cranial nerve palsies (particularly sixth nerve) and other brainstem lesions must also be considered. 1, 2

Pathophysiology and Clinical Presentation

Internuclear Ophthalmoplegia (Most Common MS-Related Cause)

• INO results from demyelinating plaques affecting the MLF in the brainstem, causing failure of ipsilateral eye adduction with contralateral abduction nystagmus 2, 3
• This is one of the most frequent presentations of MS-related diplopia because MS preferentially attacks heavily myelinated regions including the brainstem 2
• The diplopia is typically horizontal and worsens with lateral gaze 2

Cranial Nerve Palsies

• Sixth nerve palsy is the most common cranial neuropathy overall, presenting with horizontal diplopia worse at distance and in lateral gaze toward the affected side 4, 1
• In MS patients, sixth nerve involvement typically occurs with pontine lesions, often accompanied by facial palsy since the seventh nerve curves over the sixth nerve nucleus 4
• Third and fourth nerve palsies can also occur but are less common in MS 1
• Isolated cranial nerve VI palsy is most common in adults, though MS lesions typically involve the pons with other neurologic findings 4

Other MS-Related Causes

• Skew deviation from brainstem or cerebellar lesions affecting the vestibulocerebellum, with abnormalities in the rostral pons and midbrain resulting in contralateral hypotropia 4, 2
• Lesions in the thalamus and basal ganglia may lead to abnormalities of gaze, saccades, pursuit, and nystagmus 2

Critical Diagnostic Approach

Red Flags Requiring Urgent Evaluation

• Multiple cranial nerve palsies suggest extensive brainstem involvement 1
• Pupil-involving third nerve palsy requires urgent evaluation to exclude aneurysm or compressive lesion 1
• Progressive symptoms or failure to resolve warrant immediate neuroimaging 1
• Associated posterior circulation symptoms (vertigo, ataxia, dysarthria) suggest brainstem stroke 5

Essential Workup

• MRI brain and orbits with contrast is the examination of choice to identify demyelinating plaques and assess for acute lesions 1, 3
• MRI provides superior detection of posterior circulation and brainstem lesions compared to CT 6
• Complete motility examination including cover-uncover testing, assessment for INO pattern, and evaluation for nystagmus 4
• Testing for binocular fusion and stereopsis to assess functional impact 4

Management Strategy

Acute Phase

• High-dose corticosteroids for acute MS relapses causing diplopia, though be aware of potential adverse effects including central serous retinopathy 2, 3
• Referral to neurology or neuro-ophthalmology for comprehensive evaluation and MS disease-modifying therapy optimization 4, 3

Symptomatic Relief

• Prism glasses may provide temporary relief while awaiting recovery, typically over 6 months 4, 5
• Eye patching can eliminate diplopia but removes binocular vision 5
• Botulinum toxin or strabismus surgery may be considered for persistent cases after 6 months if no recovery occurs 4, 5

Disease-Modifying Considerations

• Nine classes of disease-modifying therapies are available for relapsing-remitting MS, reducing annualized relapse rates by 29-68% 3
• Be aware that some MS treatments (particularly fingolimod) can cause macular edema, which may worsen visual symptoms 2

Common Pitfalls to Avoid

• Do not assume vasculopathic sixth nerve palsy in MS patients without considering demyelinating etiology, as MS-related palsies require different management 4
• Failure to identify INO pattern (impaired adduction with contralateral abduction nystagmus) may delay MS diagnosis 2
• Do not rely on CT imaging for brainstem pathology—MRI is essential for detecting demyelinating lesions 6
• In MS patients under 50, if sixth nerve palsy shows no recovery by 6 months, approximately 40% demonstrate serious underlying pathology warranting further evaluation 4
• Bilateral sixth nerve involvement should raise concern for increased intracranial pressure or meningeal process, not just MS plaques 4