How should sudden onset diplopia be urgently evaluated and managed?

Urgent Evaluation and Management of Sudden Diplopia

Sudden onset diplopia requires immediate assessment to exclude life-threatening causes, particularly posterior communicating artery aneurysm in pupil-involving third nerve palsy, and should prompt urgent neuroimaging with MRI/MRA or CT/CTA in most cases. 1, 2

Immediate Triage: Critical Red Flags

Pupil-Involving Third Nerve Palsy (NEUROSURGICAL EMERGENCY)

• Any pupil involvement with third nerve palsy (anisocoria with ptosis and ophthalmoplegia) mandates immediate MRA or CTA to exclude posterior communicating artery aneurysm. 1, 2
• If initial MRA/CTA is negative but suspicion remains high, proceed to catheter angiography after brain MRI with and without gadolinium contrast. 1, 2
• Even mild pupil involvement in vasculopathic-appearing third nerve palsy cannot exclude compression and requires imaging. 1

Other Urgent Scenarios Requiring Immediate Imaging

• Multiple ipsilateral cranial nerve palsies (III, IV, VI) suggest cavernous sinus or orbital apex pathology. 2
• Bilateral sixth nerve involvement may indicate clival chordoma, increased intracranial pressure, or meningeal process. 1
• Associated neurological symptoms including ataxia, hemiparesis, sensory loss, Horner's syndrome, or internuclear ophthalmoplegia indicate brainstem or cerebellar pathology. 3, 4
• Diplopia with vomiting suggests posterior fossa involvement (vestibular pathways in brainstem/cerebellum). 3
• Elderly patients with scalp/temporal tenderness or jaw claudication require immediate ESR/CRP to exclude giant cell arteritis, which can cause permanent vision loss. 1, 5

Essential History Elements

Characterize the Diplopia

• First, determine if diplopia is monocular or binocular by having the patient cover each eye separately—monocular diplopia is almost always optical in nature, while binocular diplopia indicates misalignment of visual axes. 6
• Onset pattern: Sudden onset suggests vascular (stroke, aneurysm) or traumatic causes; gradual onset suggests compressive lesions (tumor) or thyroid eye disease. 2
• Direction of diplopia: Horizontal diplopia worse at distance suggests sixth nerve palsy; vertical/torsional diplopia suggests fourth nerve or skew deviation. 1

Associated Symptoms

• Ptosis suggests third nerve involvement. 1, 2
• Facial numbness suggests cavernous sinus pathology. 2
• Vision loss suggests concurrent optic neuropathy or retinal artery occlusion. 1, 2
• Headache, nausea, vomiting suggest increased intracranial pressure or posterior fossa pathology. 3, 4

Risk Factors

• Vascular risk factors (diabetes, hypertension, hyperlipidemia) suggest microvascular ischemic palsy, which typically resolves within 6 months. 1, 3, 4
• Trauma history (even occult fractures can present without recalled trauma). 2
• Age >60 years increases risk of giant cell arteritis and vasculopathic palsies. 1, 5

Focused Physical Examination

Pupillary Assessment (CRITICAL)

• Anisocoria with third nerve palsy is an emergency until proven otherwise. 1, 2
• Check for relative afferent pupillary defect (suggests optic nerve involvement). 2
• Assess accommodation deficit (common in third nerve palsy). 1

Extraocular Motility Testing

• Evaluate versions (both eyes together), ductions (each eye separately), saccades, smooth pursuit, and vergence. 2
• Perform three-step test for vertical diplopia to localize fourth nerve palsy versus skew deviation. 1
• Check for internuclear ophthalmoplegia (impaired adduction with contralateral abducting nystagmus suggests brainstem lesion). 1

Additional Neuro-Ophthalmic Signs

• Fundus examination for papilledema (increased intracranial pressure) or optic atrophy. 1
• Check for Horner's syndrome (ptosis, miosis, anhidrosis suggests carotid dissection or brainstem lesion). 1
• Assess for nystagmus (suggests brainstem or cerebellar pathology). 1
• Visual field testing may provide additional localization information. 1

Neuroimaging Strategy

First-Line Imaging

• Brain MRI with and without gadolinium plus MRA or CTA is the preferred initial study for all cranial nerve palsies, especially third nerve palsy (pupil-involved or not if incomplete ptosis/partial muscle involvement). 1, 2, 4
• Unenhanced CT of the head or orbits is not useful in the workup of diplopia and should be avoided. 2, 5

Specific Scenarios

• Pupil-involving third nerve palsy: Immediate CT/CTA if MRI unavailable, followed by catheter angiography if negative but high suspicion persists. 1, 2
• Suspected orbital apex syndrome or retro-orbital mass: Contrast-enhanced CT of brain and orbits. 5
• Suspected cavernous sinus thrombosis: CT and CT venogram. 5
• Thyroid eye disease or ocular trauma: Contrast-enhanced CT of orbits. 5

When Imaging Can Be Deferred

• Isolated sixth nerve palsy in patients with vascular risk factors (diabetes, hypertension) without other neurological signs can be referred to neurology/ophthalmology for outpatient workup rather than immediate ED imaging. 5
• However, isolated sixth nerve palsy should not be discharged without considering increased intracranial pressure, as it may occur with elevated ICP without direct nerve compression. 2

Etiology-Based Management

Microvascular Ischemic Palsies (Most Common in Adults)

• Typically associated with diabetes, hypertension, hyperlipidemia; onset is acute, may be accompanied by pain, without other neurological findings. 1, 3, 4
• Most resolve within 6 months (one-third within 8 weeks). 1
• If no recovery by 6 months, approximately 40% have serious underlying pathology warranting further evaluation. 1, 3
• Management: Optimize vascular risk factors (diabetes, hypertension, hyperlipidemia control). 3, 4

Aneurysm (Neurosurgical Emergency)

• Requires urgent neurosurgical consultation. 3, 4
• Do not delay imaging or consultation. 1, 2

Giant Cell Arteritis

• High-dose corticosteroids immediately to prevent permanent vision loss. 3
• Obtain ESR/CRP in all patients >60 years with recent diplopia. 5

Stroke/TIA

• Patients with acute retinal artery occlusion (which may present with transient diplopia) should be referred immediately to emergency department or stroke center because risk of ischemic stroke is 3-6% in first 1-4 weeks, and 20-24% have concurrent stroke. 1
• Silent brain infarction is present in 19% of CRAO and 25% of BRAO patients, and these patients should undergo prompt referral to stroke center. 1

Trauma

• Usually self-evident with history of head injury, basilar skull fracture, or acute rise in intracranial pressure from intracranial bleed. 1

Neoplasm

• May be insidious or acute; neurologic changes include other motor deficits depending on location. 1
• Evaluate for facial/extremity motor weakness, other cranial nerve involvement, visual field defects, optic nerve involvement, elevated IOP, proptosis. 1

Demyelinating Disease (Multiple Sclerosis)

• Sixth nerve palsy with demyelinating disease typically involves pons with other neurological findings (most notably facial palsy). 1
• However, isolated cranial nerve VI palsy is most common in adults. 1

Myasthenia Gravis

• Consider in patients with fluctuating diplopia, ptosis, or fatigable weakness. 7
• Edrophonium (Tensilon) test: 2 mg IV initially, then 8 mg if no reaction after 45 seconds; positive test shows increased muscle strength. 8

Symptomatic Management While Awaiting Diagnosis

Immediate Relief Options

• Eye patching or occlusion (eye patch, occlusive contact lens, Bangerter foil, or MIN lens) for immediate relief. 1, 3, 2, 4
• Prism correction (press-on Fresnel or ground-in prisms) can provide temporary relief, though effectiveness is limited in incomitant deviations. 1, 2, 4
• Botulinum toxin of antagonist extraocular muscle or levator can temporize while waiting for recovery. 1

Special Considerations

• With complete ptosis, many patients are not troubled by diplopia until lid is elevated. 1
• Accommodation deficit may cause reading difficulty: Prescribe uniocular progressive lenses or bifocals with high bifocal segment placement when infraduction is compromised. 1

Disposition and Referral

Immediate Ophthalmology/Neurosurgery Consultation

• Pupil-involving third nerve palsy. 1, 2, 4
• Signs of increased intracranial pressure (papilledema, bilateral sixth nerve palsy). 2, 4
• Multiple cranial nerve palsies. 2, 4
• Associated neurological deficits (ataxia, hemiparesis, sensory loss, Horner's syndrome, internuclear ophthalmoplegia). 3, 4

Urgent Neurology/Ophthalmology Referral (Within 1 Week)

• Isolated fourth or sixth nerve palsies without other neurological signs can be referred for outpatient workup. 1, 5
• Skew deviation requires referral to neurology, otolaryngology, or neuro-otology based on likely cause. 1

Follow-Up Protocol

• Reassess at 6 months: If no recovery by 6 months in presumed microvascular palsy, further evaluation for underlying pathology is warranted. 1, 3, 4
• Control vascular risk factors: Optimize diabetes, hypertension, hyperlipidemia management. 3, 4

Common Pitfalls to Avoid

• Do not assume pupil-sparing third nerve palsy is benign if ptosis is incomplete or muscle involvement is partial—these patients still require neuroimaging. 1
• Do not order unenhanced CT of head/orbits—it is not useful for diplopia workup. 2, 5
• Do not discharge isolated sixth nerve palsy without considering increased intracranial pressure. 2
• Do not miss bilateral sixth nerve involvement—it suggests serious pathology (clival chordoma, increased ICP, meningeal process). 1, 2
• Do not forget to check ESR/CRP in patients >60 years—giant cell arteritis can cause permanent vision loss if not promptly treated. 1, 5