What are the differential diagnoses and urgent work‑up for a patient presenting with upward gaze deviation (upward rolling of the eyes)?

Differential Diagnoses for Upward Gaze Deviation

Upward rolling of the eyes demands immediate distinction between benign syncope-related movements versus life-threatening posterior fossa pathology, with urgent neuroimaging required for any persistent deviation or accompanying neurological symptoms. 1

Immediate Triage Based on Clinical Context

Transient Upward Gaze During Syncope (Benign)

• Brief upward eye deviation during witnessed loss of consciousness with rapid, complete recovery requires no neurological workup 1
• Transient upward gaze, myoclonic jerks, and automatisms result from global cerebral hypoperfusion and resolve immediately once perfusion restores 1
• Do not pursue extensive neuroimaging for transient movements during syncope with rapid recovery 1

Persistent or Recurrent Upward Gaze Deviation (Urgent Evaluation Required)

Proceed immediately to emergency neurological assessment if upward gaze persists beyond syncope recovery or occurs without syncope 1

Critical Differential Diagnoses Requiring Urgent Recognition

1. Skew Deviation (Posterior Fossa Emergency)

This is the most critical diagnosis to identify, as it indicates stroke, demyelination, or mass lesion requiring immediate intervention 2, 3, 4

Clinical features distinguishing skew deviation:

• Vertical strabismus with diplopia and blurred vision 3
• Ocular tilt reaction: head tilt toward the hypotropic (lower) eye with both eyes rotating in the same direction 2, 4
• Hypertropic eye shows fundus incyclotorsion; hypotropic eye shows fundus excyclotorsion (this pattern distinguishes it from 4th nerve palsy where the hypertropic eye is excyclotorted) 2, 4
• Vertical visual field tilt in the same direction as head tilt 2, 4
• May be comitant or incomitant 2

Urgent workup for skew deviation:

• Obtain brain and brainstem MRI with and without contrast immediately to evaluate for stroke, demyelination, or mass lesion 2, 3, 1, 4
• Complete neuro-ophthalmic examination checking for Horner's syndrome, cranial nerve palsies, internuclear ophthalmoplegia, nystagmus, and hearing loss 2, 3
• Fundus examination for papilledema or optic atrophy 2
• Upright-supine test: hypertropia reducing >50% in supine position suggests skew deviation (80% sensitivity, 100% specificity), though unreliable in acute presentations within 2 months 2, 4

Common etiologies:

• Acute vestibular neuronitis 2, 4
• Posterior circulation stroke 3, 1, 5
• Demyelinating disease 2, 4
• Cerebellar or brainstem lesions 2, 4

Referral pathway:

• Immediate neuro-ophthalmology and neurology consultation 3, 4
• Consider otolaryngology if peripheral vestibular pathology suspected 4

2. Parinaud Syndrome (Dorsal Midbrain Lesion)

Conjugate upward gaze palsy from midbrain or thalamic infarction 5

Key features:

• Bilateral upward gaze palsy with preserved horizontal gaze 5
• May result from unilateral thalamic infarction, not just midbrain lesions 5
• Obtain brain MRI with diffusion-weighted imaging within 24 hours 1

3. Superior Oblique Palsy (4th Nerve Palsy)

New-onset vertical diplopia with upward deviation may represent superior oblique palsy, but neuroimaging is mandatory if not isolated 2, 1

Diagnostic features:

• Parks-Bielschowsky three-step test: hypertropia greatest in opposite lateral gaze and head tilt to same side 2, 1
• Excyclotorsion of the hypertropic eye (opposite pattern from skew deviation) 2
• Head tilt away from hypertropic side 2

When to image:

• If not isolated or associated with other neurological symptoms, obtain neuroimaging immediately 2, 1
• Small vertical fusional amplitudes without trauma history indicate acquired cause requiring neuroimaging to exclude trochlear schwannoma 2, 1
• In patients >50 years, urgently obtain ESR and CRP to evaluate for giant cell arteritis 1
• If GCA suspected, initiate IV methylprednisolone 1g daily for 3 days immediately before diagnostic confirmation 1

4. Oculogyric Crisis (Drug-Induced)

Sustained upward eye deviation with thought disorder from dopamine antagonists or dopamine depletion 6

Clinical presentation:

• Upward eye deviation with pathological fixation of thought and attention disorder 6
• All functional conjugate eye movements present in upper gaze field, suggesting vertical gaze-holding mechanism imbalance 6
• Eyes driven down only by combined blink and downward saccade 6

Management:

• Responds promptly to anticholinergic agents 6
• Review medication history for antipsychotics, antiemetics (metoclopramide), or dopamine-depleting drugs 6

5. Post-Hypoxic Encephalopathy

Sustained upgaze in coma following cardiac arrest or prolonged hypotension indicates severe hypoxic brain injury 7

Distinguishing features:

• Occurs in comatose patients after cardiac arrest or systemic hypotension 7
• May develop slow downward-beating nystagmus as forced upgaze resolves 7
• Synchronous upward gaze movements with facial myoclonic jerks 7
• Does NOT indicate structural pretectal or midbrain lesion; results from diffuse cerebral and cerebellar damage with brainstem sparing 7

6. Benign Paroxysmal Tonic Upgaze (Pediatric)

Rare condition in infants presenting with episodic upward gaze deviation 8, 9

Clinical features:

• Onset during first year of life 8
• Episodes of sustained upward eye deviation with neck hyperextension 8
• Vertical nystagmus of fixation, increased by nervousness or fever 8
• Normal horizontal gaze and ataxia 9
• Benign course with spontaneous remission by age 4 years 8
• Not responsive to L-Dopa 8

Urgent Workup Algorithm

For ANY persistent upward gaze deviation:

1. Determine if transient during witnessed syncope with rapid recovery:

   • If YES: Evaluate for cardiac causes per standard syncope protocol; no neuroimaging needed 1
   • If NO: Proceed to step 2

2. Assess for red flags requiring immediate neuroimaging:

   • Diplopia, limb weakness, sensory deficits, or speech difficulties 1
   • Syncope occurring in supine position 1
   • Confusion or amnesia following episode 1
   • Headache or signs of increased intracranial pressure 1
   • Any persistent upward gaze deviation 1

3. If red flags present, obtain urgent MRI brain and brainstem with and without contrast 2, 3, 1, 4

4. Complete neuro-ophthalmic examination:

   • Three-step test and upright-supine test 2
   • Fundus examination for torsion pattern 2, 4
   • Check for ocular tilt reaction 2, 4
   • Assess for other cranial nerve palsies, INO, nystagmus 2, 3

5. Age-specific considerations:

   • Patients >50 years: Urgently obtain ESR and CRP for giant cell arteritis 1
   • Infants <1 year: Consider benign paroxysmal tonic upgaze if episodic with normal development 8, 9

6. Medication review for oculogyric crisis:

   • Check for antipsychotics, antiemetics, or recent medication changes 6
   • Trial anticholinergic agents if drug-induced suspected 6

Critical Pitfalls to Avoid

• Do not delay neuroimaging for persistent upward gaze assuming benign syncope-related movement 1
• Do not miss giant cell arteritis in elderly patients; delaying corticosteroids is the strongest risk factor for permanent blindness 1
• Do not assume benign etiology even with isolated vertical diplopia, as 11% of skew deviation cases have no other neurologic signs 4
• Do not rely solely on three-step test to exclude skew deviation, as it can mimic 4th nerve palsy 4
• Do not overlook posterior circulation stroke in patients with isolated vertical gaze palsy 1