Skew Deviation

Key points at a glance

Key Points at a Glance

• Skew deviation is an acquired vertical ocular misalignment due to an imbalance in vestibular input from supranuclear otolith-ocular pathways, distinct from single muscle or cranial nerve abnormalities.
• It is a sign of posterior fossa lesions requiring urgent attention, such as stroke (most common), multiple sclerosis, and tumors.
• The triad of skew deviation, binocular torsion, and head tilt is called the ocular tilt reaction (OTR) and aids in lesion localization.
• The most important differential diagnosis is trochlear nerve palsy; the direction of torsion in the hypertropic eye (intorsion vs. extorsion) is key.
• The upright-supine test (sensitivity 80%, specificity 100%) is useful for differentiation, but less reliable in acute cases within 2 months of onset.
• Most demyelinating and ischemic cases are expected to recover spontaneously, while severe ischemia or neoplastic lesions may persist long-term.

1. What is Skew Deviation?

Skew deviation is an acquired vertical ocular misalignment not due to a single muscle or ocular motor nerve abnormality. It results from damage to the otolith system, from the peripheral labyrinth to the lower brainstem and midbrain, impairing supranuclear input to ocular motor neurons. Various brainstem and cerebellar diseases in the posterior fossa disrupt gravity-sensitive pathways from the otolith organs to the vertical gaze centers and vertical extraocular muscles, causing a supranuclear vertical strabismus due to an imbalance in vestibular input.

The neural pathway runs from the vestibular nuclei, crosses, ascends via the medial longitudinal fasciculus (MLF) to the interstitial nucleus of Cajal (iC) in the rostral midbrain. Any lesion along this pathway can cause skew deviation.

First recognized by François Magendie in 1824, the term ocular tilt reaction (OTR) was coined by Westheimer and Blair in 1975. The prevalence is unknown due to diverse causes, with no age, race, or sex predilection.

Clinical subtypes include comitant, incomitant, paroxysmal (intermittent), periodic or slowly alternating, alternating, and transient neonatal skew deviation.

Q Can skew deviation occur in children?

A

In the elderly, stroke-related vascular lesions are the main cause, while in younger individuals, demyelinating diseases such as multiple sclerosis or trauma are common. Vestibular neuritis can occur at any age. Transient neonatal skew deviation has also been reported as a subtype.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

• Vertical diplopia: The most common complaint.
• Tilted visual perception (subjective visual vertical SVV tilt): Patients may not report it unless asked. Daily visual cues may help maintain true vertical.
• Blurred vision
• Associated neurological symptoms: Dizziness, vertigo, headache, weakness, dysarthria, nausea, numbness, oscillopsia, hearing loss, tinnitus, facial nerve palsy, facial numbness, etc. (present in 91 of 136 reported cases).
• Onset pattern: Almost always acute to subacute onset. More gradual if due to demyelination or slow-growing tumor.

Clinical Findings (Findings Confirmed by Physician Examination)

• Ocular tilt reaction (OTR): Triad of skew deviation + binocular torsion + head tilt. Head tilt toward the lower eye and ipsilateral ocular torsion (opposite to normal compensatory counter-roll).
• Torsion characteristics: The higher eye is incyclotorted, the lower eye is excyclotorted. In trochlear nerve palsy, the higher eye is excyclotorted, which is an important distinguishing feature from skew deviation.
• Eye misalignment: May be comitant or incomitant. Often accompanied by horizontal deviation. Right gaze may show right hypertropia, left gaze left hypertropia, with alternating hypertropia.

The correspondence between lesion location and clinical findings is shown below.

Peripheral / Caudal Brainstem Lesions

Acute labyrinth / otolith nerve disorder: OTR toward the lesioned side (ipsilateral hypotropia)

Wallenberg syndrome: OTR toward the lesioned side (ipsilateral hypotropia) (vestibular nucleus lesion)

Peripheral vestibular / medullary / caudal pontine lesions: Ipsilateral hypotropia + head tilt

Central / rostral brainstem lesions

Midbrain iC lesion: Contralateral OTR (ipsilateral hypertropia)

INO (internuclear ophthalmoplegia): Hypertropia on the affected side

Cerebellar lesion: Alternating skew deviation with hypertropia of the abducting eye, associated with downbeat nystagmus

• Associated ophthalmic findings: Nystagmus, gaze palsy, internuclear ophthalmoplegia (INO), slow saccades, visual field defect, Horner syndrome, dorsal midbrain syndrome

Q What is the symptom of "tilted vision" in skew deviation?

A

It manifests as a tilt of the subjective visual vertical (SVV). Patients experience the sensation that the horizontal ground or vertical walls appear tilted, but if everyday visual cues (buildings, horizon, etc.) are present, the brain compensates, and the patient may not notice it.

3. Causes and risk factors

The main causes of skew deviation are listed below.

• Stroke (most common): Predilection sites are thalamus, brainstem, and cerebellum. Approximately 52% of 157 cases were due to stroke.
• Demyelinating disease of the brainstem: Multiple sclerosis (MS), etc. Lesions of the vestibular nucleus, medial longitudinal fasciculus, and interstitial nucleus of Cajal.
• Tumor
• Acute vestibular neuritis: May resolve spontaneously.
• Trauma (reported onset after blunt trauma)
• Inflammation, abscess, lesions associated with surgical procedures
• Other rare causes: Arnold-Chiari malformation, Creutzfeldt-Jakob disease

Risk factors vary by age group.

Risk factor	Older adults	Younger adults
Main underlying diseases	Stroke	Multiple sclerosis, trauma
Main risk factors	Hypertension, diabetes, hyperlipidemia, smoking	Demyelinating diseases (more common in women), trauma

Vestibular neuritis can occur at any age.

When to see a doctor

If you experience sudden vertical double vision, a sensation that your field of vision is tilted, or unsteadiness, seek medical attention promptly. Especially for those at risk of stroke, urgent evaluation may be necessary.

4. Diagnosis and testing methods

The diagnosis of skew deviation is one of exclusion. It is considered when ocular findings are inconsistent with cranial nerve palsy or when brainstem or cerebellar injury is suspected.

Differentiation from trochlear nerve palsy (most important)

Because skew deviation can be caused by conditions requiring urgent management such as stroke or demyelination, differentiation is clinically very important.

Finding	Skew deviation	Trochlear nerve palsy
Direction of torsion in the elevated eye	Incyclotorsion	Excyclotorsion
Upright-supine test	Deviation decreases by ≥50% in supine position	No decrease
Associated neurological signs	Present (nystagmus, INO, Horner syndrome, etc.)	Usually absent

Wong’s diagnostic algorithm (2010)

1. Exclude pseudostrabismus, dissociated vertical deviation (DVD), and restrictive causes (corneal light reflex, cover-uncover test)
2. Parks three-step test → localization other than superior oblique → consider skew deviation, thyroid eye disease, myasthenia gravis → contrast MRI
3. Upright-supine test: Vertical deviation decreases by ≥50% in supine position → suggests skew deviation
4. Check for other neurological signs → contrast MRI

Upright-supine test

Sensitivity 80%, specificity 100% (negative in trochlear nerve palsy). However, in acute onset (within 2 months) of skew deviation, dependence on gravity is reduced, making it less reliable. Particularly useful in chronic cases.

Other tests

• Double Maddox rod test: Quantification of ocular torsion. Used to differentiate skew deviation from trochlear nerve palsy.
• Fundus examination: Assessment of torsion (confirm incyclotorsion of the hypertropic eye), check for papilledema and optic atrophy.
• Visual field testing: Additional information on etiology.
• Neuroradiological diagnosis (contrast MRI): Evaluate for demyelination, stroke, tumor. If vertical strabismus is accompanied by ataxia, it suggests brainstem (pons/medulla) lesion, increasing likelihood of skew deviation.
• Other checks: Horner syndrome, cranial nerve palsy, INO, nystagmus, hearing loss

Differential diagnosis

• Trochlear nerve palsy (most important)
• Thyroid eye disease
• Myasthenia gravis

Q How to differentiate skew deviation from trochlear nerve palsy?

A

The most important distinguishing feature is the direction of torsion of the hypertropic eye. In skew deviation, the hypertropic eye intorts (incyclotorsion), whereas in trochlear nerve palsy, it extorts (excyclotorsion). Additionally, the upright-supine test (sensitivity 80%, specificity 100%) is useful for differentiation; a reduction of vertical deviation by 50% or more in the supine position suggests skew deviation. However, it is less reliable within 2 months of acute onset.

5. Standard Treatment

Basic Principles

Treatment of the underlying disease is fundamental. Many demyelinating and ischemic cases are transient and can be expected to recover spontaneously. Vestibular neuritis may also resolve spontaneously. More severe ischemic damage or neoplastic lesions tend to cause persistent symptoms.

Symptomatic Therapy While Awaiting Recovery

• Prism therapy: Useful as initial treatment for diplopia management. If there is gaze-dependent deviation, prism glasses are used.
• Botulinum toxin injection: For symptom relief.

Treatment for Persistent Cases

• Prism therapy: For persistent vertical diplopia.
• Botulinum toxin injection: For symptom relief.
• Vertical strabismus surgery (including vertical muscle shortening): Applied to permanent cases where treatment of the underlying disease is not indicated and vertical misalignment is fixed. Surgery can reduce vertical and torsional diplopia, reduce subjective visual vertical tilt, and in some cases improve head tilt.

The goal of surgery is customized to each patient. Priority varies depending on which symptom—diplopia, head tilt, or visual vertical tilt—bothers the patient most. Botulinum toxin injection, prisms, and surgery are effective for all symptoms of OTR, but improvement of head tilt itself is often difficult.

Coordination

Referral to neurology, otolaryngology, or neuro-otology is necessary depending on the etiology.

Q Does skew deviation resolve without treatment?

A

Most demyelinating or ischemic skew deviations are transient and spontaneous recovery can be expected. Symptomatic treatment with prism glasses is used during recovery. However, severe ischemic damage or neoplastic lesions may persist long-term, and surgery is indicated for such permanent cases.

6. Pathophysiology and Detailed Mechanism

Basic Neural Pathways

The otolith organs (utricle and saccule) detect linear motion and tilt, and transmit this information to the interstitial nucleus of Cajal (iC). The specific pathways are as follows:

• Otolith → projects to ipsilateral lateral vestibular nucleus
• After leaving the vestibular nucleus, fibers cross and ascend in the MLF
• Reach the iC and provide supranuclear control of vertical extraocular muscles

Any damage along this pathway causes an imbalance in vestibular input between the two sides, resulting in skew deviation.

Lesion Sites and Localization

Peripheral/Caudal Lesions

Acute labyrinth/otolith nerve disorder → OTR toward the lesion side (ipsilateral inferior oblique overaction)

Wallenberg syndrome → OTR toward the lesion side (vestibular nucleus involvement)

Since the lesion is before the decussation along the pathway, the effect appears on the same side.

Central/Rostral Lesion

Unilateral iC lesion → Contralateral OTR (ipsilateral hypertropia)

INO (due to crossing after MLF lesion) → Lesion side hypertropia

Cerebellar lesion → Alternating skew deviation (abducting eye hypertropia)

Pathophysiology of OTR

Normally, when the head is tilted, the otolith-ocular reflex produces ocular counter-roll (compensatory opposite rotation) opposite to the head tilt. In OTR, ocular rotation occurs in the direction of the head tilt (compensation in the opposite direction). This is interpreted as a response to a state where, due to reduced vestibular input on one side, the vestibular input on the healthy side mistakenly perceives that the head is constantly tilted.

---

8. References

• Brodsky MC, Donahue SP, Vaphiades M, Brandt T. Skew deviation revisited. Surv Ophthalmol. 2006;51(2):105-128. PMID: 16500212. https://pubmed.ncbi.nlm.nih.gov/16500212/
• Kattah JC, Talkad AV, Wang DZ, Hsieh YH, Newman-Toker DE. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke. 2009;40(11):3504-3510. PMID: 19762709. https://pubmed.ncbi.nlm.nih.gov/19762709/
• Wong AMF. Understanding skew deviation and a new clinical test to differentiate it from trochlear nerve palsy. J AAPOS. 2010;14(1):61-67. PMID: 20227626. https://pubmed.ncbi.nlm.nih.gov/20227626/
• Wong AMF, Colpa L, Chandrakumar M. Ability of an upright-supine test to differentiate skew deviation from other vertical strabismus causes. Arch Ophthalmol. 2011;129(12):1570-1575. PMID: 22159676. https://pubmed.ncbi.nlm.nih.gov/22159676/
• Hernowo A, Eggenberger E. Skew deviation: clinical updates for ophthalmologists. Curr Opin Ophthalmol. 2014;25(6):485-487. PMID: 25250734. https://pubmed.ncbi.nlm.nih.gov/25250734/
• Lemos J, Subei A, Sousa M, et al. Differentiating Acute and Subacute Vertical Strabismus Using Different Head Positions During the Upright-Supine Test. JAMA Ophthalmol. 2018;136(4):322-328. PMID: 29450486. https://pubmed.ncbi.nlm.nih.gov/29450486/
• American Academy of Ophthalmology: Adult Strabismus Preferred Practice Pattern（PPP）