What are the differential diagnoses for a 12-year-old patient with sudden onset diplopia (double vision), followed by vomiting and headache, with normal MRI findings and decreased nausea after administering medications, including antiemetics (e.g. metoclopramide) and pain relief medications (e.g. ibuprofen)?

Differential Diagnoses for Acute Diplopia with Headache and Vomiting in a 12-Year-Old

The most likely diagnosis in this 12-year-old with sudden diplopia, headache, and vomiting with normal MRI is post-viral cranial nerve VI palsy, though cerebral venous thrombosis and spontaneous intracranial hypotension must be urgently excluded despite the normal initial MRI. 1, 2

Primary Differential Diagnoses

Post-Viral Cranial Nerve VI Palsy (Most Likely)

• Cranial nerve VI (abducens) is the most common isolated nerve palsy in post-viral cases in children 2
• Presents with acute onset horizontal double vision, worse at distance than near, with worsening diplopia on lateral gaze toward the affected side 2
• Most vasculopathic and presumed post-viral palsies resolve within 6 months 2
• The improvement in nausea after antiemetics supports a benign, self-limited process 2

Cerebral Venous Thrombosis (Must Exclude Urgently)

• CVT can present with headache (90% of cases), vomiting, and diplopia from sixth nerve palsy due to increased intracranial pressure, even with initially normal imaging 1
• Headache in CVT typically progresses over days to weeks and is diffuse 1
• Isolated headache with diplopia (caused by sixth nerve palsy) without other focal signs can mimic idiopathic intracranial hypertension but represents CVT 1
• Focal or generalized seizures occur in 40% of CVT patients, distinguishing it from other cerebrovascular disease 1
• Standard MRI may miss early CVT; dedicated MR venography or CT venography is required for definitive exclusion 1

Spontaneous Intracranial Hypotension (Critical to Consider)

• Can present with sudden headache, nausea, vomiting, and diplopia from cranial nerve VI palsy 1, 3
• MRI findings may show diffuse dural enhancement, but absence of "brain sag" or tonsillar herniation does not exclude the diagnosis 1
• Diplopia may develop or persist even after headache improves with conservative management 3
• SIH can precipitate life-threatening cerebral venous thrombosis as a complication 1

Complicated Migraine (Stroke Mimic)

• Complicated migraine is a common stroke mimic in children presenting with acute neurologic deficits 1
• Can present with headache, vomiting, and visual disturbances including diplopia 1
• However, true diplopia from cranial nerve palsy is uncommon in migraine and should prompt imaging to exclude structural causes 1

Critical Diagnostic Steps Required

Immediate Imaging Protocol

• MRI brain with and without gadolinium contrast plus MRA or CTA is mandatory for acute diplopia to exclude serious pathology 1, 2, 4
• Dedicated MR venography or CT venography must be added to exclude cerebral venous thrombosis, as standard MRI sequences may miss early CVT 1
• High-resolution sequences of the pituitary and cranial nerves III-VI should be included 4

Characterize the Diplopia Pattern

• Horizontal diplopia worse at distance suggests sixth nerve palsy 2, 4
• Vertical diplopia with ptosis suggests third nerve palsy, requiring urgent aneurysm exclusion 4, 5
• Perform detailed cranial nerve examination to localize the lesion (cavernous sinus, orbital apex, brainstem, or isolated nerve) 1

Additional Workup if Initial Imaging Normal

• If MRI/MRA/MRV are normal but clinical suspicion remains high, consider lumbar puncture to assess opening pressure and CSF analysis 1
• Elevated opening pressure suggests CVT or idiopathic intracranial hypertension 1
• Low opening pressure with orthostatic headache pattern suggests spontaneous intracranial hypotension 1, 3

Less Likely but Important Differentials

Demyelinating Disease (Multiple Sclerosis)

• Brainstem lesions affecting the medial longitudinal fasciculus or cranial nerve nuclei are primary considerations in younger patients with acute diplopia 1
• Internuclear ophthalmoplegia from demyelinating plaques should be suspected if examination shows impaired adduction with contralateral abducting nystagmus 1

Posterior Circulation Stroke

• Patients with acute onset diplopia may be presenting with deficits related to posterior circulation stroke 1
• However, this is uncommon in a 12-year-old without vascular risk factors 1

Infectious/Inflammatory Causes

• Multiple ipsilateral cranial nerve palsies suggest infectious meningitis (TB, fungal, Lyme) or noninfectious causes (sarcoid, neoplasm) 1
• Infection-related CVT is more common in children (40% in one U.S. series) than adults 1

Management Approach While Awaiting Diagnosis

Symptomatic Management

• Continue antiemetics for nausea control 2
• Eye patching or occlusion therapy can temporize diplopia 2
• Prism glasses may be considered if diplopia persists 2, 4

Monitoring for Red Flags

• Watch for progression of neurological deficits, altered consciousness, or seizures suggesting CVT with venous infarction 1
• Monitor for worsening headache or new focal signs 1

Critical Pitfalls to Avoid

• Do not assume normal initial MRI excludes cerebral venous thrombosis; dedicated venography is required 1
• Do not delay vascular imaging if any concern for third nerve palsy with pupil involvement, as aneurysm must be excluded urgently 1, 4, 5
• Do not attribute all symptoms to benign post-viral palsy without excluding increased intracranial pressure from CVT or mass lesion 1
• If no recovery by 6 months, further evaluation for underlying pathology is warranted 2