What are the differential diagnoses for a 12-year-old student with sudden onset diplopia (double vision), headache, and initial vomiting, now resolved, with normal MRI (Magnetic Resonance Imaging) angiogram and venogram results?

Differential Diagnoses for Acute Diplopia with Headache and Vomiting in a 12-Year-Old with Normal MRI/MRA/MRV

The most likely diagnoses are post-viral sixth nerve palsy, spontaneous intracranial hypotension (SIH), or cerebral venous thrombosis (CVT) that requires dedicated venography to exclude, despite normal initial imaging. 1

Primary Differential Diagnoses to Consider

Post-Viral Sixth Nerve Palsy (Most Common in Children)

• Cranial nerve VI (abducens) palsy is the most common isolated cranial nerve palsy in post-viral cases in children, presenting with acute onset horizontal diplopia worse at distance than near, with worsening on lateral gaze toward the affected side 1, 2
• The preceding vomiting and headache may represent a viral prodrome 3
• This is a diagnosis of exclusion after ruling out more serious pathology 2
• Most vasculopathic and presumed post-viral palsies resolve within 6 months 2

Cerebral Venous Thrombosis (Critical to Exclude)

• CVT can present with headache, vomiting, and diplopia from sixth nerve palsy due to increased intracranial pressure, even with initially normal imaging 1
• Isolated sixth nerve palsy may occur with elevated ICP without direct nerve compression 4
• Normal initial MRI does NOT exclude CVT—dedicated MR venography or CT venography is required 1
• The American Heart Association emphasizes that CVT can mimic idiopathic intracranial hypertension but represents a serious, life-threatening condition 1

Spontaneous Intracranial Hypotension

• SIH should be considered in the differential diagnosis of acute diplopia with headache and vomiting in a 12-year-old, despite normal initial MRI 1
• Classic orthostatic headache may be absent in some cases 3
• Look for smooth, diffuse dural and leptomeningeal enhancement on MRI, though "brain sag" or tonsillar herniation may not always be present 3

Demyelinating Disease (Multiple Sclerosis)

• Brainstem nuclei and connecting tracts involvement suggests demyelinating disease like multiple sclerosis in younger patients presenting with acute diplopia 2
• A demyelinating plaque affecting the medial longitudinal fasciculus is a primary consideration in younger patients with internuclear ophthalmoplegia 3
• Brain stem lesions can cause skew deviation with associated neurologic features including nystagmus and ataxia 3

Critical Diagnostic Steps Required NOW

Immediate Additional Imaging

• Dedicated MR venography (MRV) with contrast or CT venography (CTV) must be performed urgently to exclude cerebral venous thrombosis 3, 1
• MRV with contrast is helpful in detecting intracranial sinovenous stenosis that can go undetected on traditional noncontrast (time-of-flight) MRV 3
• If MRV is not possible or results are ambiguous, contrast-enhanced CTV is a fast, widely accessible alternative with high sensitivity and specificity 3

Detailed Cranial Nerve Examination

• Perform a complete three-step test to localize which cranial nerve is affected 4
• Assess pupillary function carefully—pupil involvement changes the differential dramatically 3
• Check for multiple ipsilateral cranial nerve palsies (III, IV, VI) which suggest cavernous sinus or orbital apex pathology 3, 4
• Examine for other neuro-ophthalmic signs: Horner's syndrome, internuclear ophthalmoplegia, nystagmus 3
• Fundus examination to check for papilledema (suggesting increased ICP) or optic atrophy 3

Laboratory Workup

• If neuroimaging remains normal after dedicated venography, serologic testing for infectious diseases (syphilis, Lyme disease) should be considered 3
• Lumbar puncture may be indicated if imaging is negative, including glucose, protein, cell count, cytology, and culture 3

Management While Awaiting Definitive Diagnosis

Symptomatic Relief

• Eye patching or occlusion therapy (occlusive contact lens, Bangerter foil) to temporize diplopia 4, 1, 2
• Antiemetics for nausea control if vomiting recurs 1
• Press-on (Fresnel) prisms may provide temporary relief, though effectiveness is limited in incomitant deviations 4, 2

Monitoring for Red Flags

• Watch for progression of neurological deficits, altered consciousness, or seizures suggesting CVT with venous infarction 1
• Monitor for signs of increased intracranial pressure 4
• Reassess if no improvement by 6 months, as this warrants further evaluation for underlying pathology 2

Critical Pitfalls to Avoid

Do NOT Assume Normal MRI Excludes Serious Pathology

• The single most dangerous error is assuming normal initial MRI/MRA excludes cerebral venous thrombosis—dedicated venography is mandatory 1
• Isolated sixth nerve palsy should not be discharged without considering increased intracranial pressure 4

Do NOT Miss Pupil-Involving Third Nerve Palsy

• If any pupil involvement is present with diplopia, this requires immediate MRA or CTA to exclude posterior communicating artery aneurysm, which is a neurosurgical emergency 4
• Even partial extraocular muscle involvement or incomplete ptosis cannot exclude a compressive lesion 3

Do NOT Delay Vascular Imaging

• If there is any concern for third nerve palsy with pupil involvement, aneurysm must be excluded urgently 1
• If high suspicion for aneurysm persists despite normal MRA or CTA, proceed to catheter angiography after brain MRI with contrast 3, 4