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OverviewAetiologyPathophysiologyClinical features and red flagsInvestigationsDifferential diagnosisManagementComplicationsMonitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Internuclear ophthalmoplegia and gaze palsies

Neurology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

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Time-critical presentation

Any sudden internuclear ophthalmoplegia, conjugate gaze palsy or new ocular-motor syndrome with vertigo, ataxia, weakness, sensory change, dysarthria, dysphagia, headache or reduced consciousness requires immediate posterior-circulation stroke assessment; acute ophthalmoplegia with encephalopathy, areflexia, respiratory or bulbar weakness also needs urgent neurological and critical-care escalation.

Overview

Distinguish internuclear disconnection, nuclear and infranuclear ocular-motor palsy, and supranuclear gaze disorders from the pattern of saccades, pursuit, vestibulo-ocular responses and accompanying brainstem signs.

The sixth-nerve nucleus contains motor neurons to the ipsilateral lateral rectus and internuclear neurons that cross and ascend in the opposite medial longitudinal fasciculus to activate the medial rectus. A lesion of the fasciculus therefore impairs adduction ipsilateral to the lesion during conjugate gaze. The abducting nystagmus reflects network dysconjugacy rather than a primary sixth-nerve palsy in that eye. A large lesion can also disturb vertical alignment, producing skew deviation.

Horizontal gaze palsy is different from isolated abduction weakness. Damage to the paramedian pontine reticular formation or sixth nucleus prevents both eyes looking toward the lesion; damage to the sixth nerve after it leaves the brainstem impairs only abduction of the ipsilateral eye. Testing the vestibulo-ocular reflex can distinguish supranuclear from nuclear/infranuclear disease in selected patients, but cervical injury, raised intracranial pressure and lack of training are contraindications to casual head impulse or doll's-eye manoeuvres.

Aetiology

01

Brainstem demyelination

Multiple sclerosis commonly causes unilateral or bilateral internuclear ophthalmoplegia, particularly in younger adults and when other demyelinating syndromes are present.

02

Brainstem ischaemia

A sudden unilateral internuclear or conjugate gaze deficit in an older or vascular-risk person suggests a small pontine or midbrain infarct.

03

Structural and inflammatory lesions

Tumour, hydrocephalus, infection and systemic inflammation can affect gaze centres, medial longitudinal fasciculi or their connections, often with additional neurological signs.

04

Degenerative and medicine effects

Progressive supranuclear palsy and selected sedating or antiseizure medicines cause gaze slowing or nystagmus through broader network dysfunction rather than one peripheral nerve.

Pathophysiology

  1. 1
    Internuclear disconnection

    A medial longitudinal fasciculus lesion interrupts the signal from the abducens nucleus to the opposite medial-rectus subnucleus.

  2. 2
    Disconjugate horizontal gaze

    The eye on the lesion side adducts poorly while the fellow abducting eye develops corrective nystagmus; convergence may remain variably preserved.

  3. 3
    Gaze-centre failure

    Lesions of pontine or midbrain gaze generators impair both eyes in one direction, while supranuclear disease may spare vestibulo-ocular reflex movements.

Clinical features and red flags

Unilateral internuclear ophthalmoplegiaRed flag

Adduction failure on one side with abducting nystagmus of the fellow eye during horizontal gaze supports an ipsilateral medial longitudinal fasciculus lesion, often ischaemic when onset is abrupt.

Bilateral internuclear ophthalmoplegia

Bilateral adduction deficits with abducting nystagmus suggest paired medial longitudinal fasciculus lesions. Demyelination is important in younger adults, while vascular, nutritional, inflammatory and neoplastic causes remain possible.

One-and-a-half syndromeRed flag

An ipsilateral horizontal gaze palsy plus ipsilateral INO permits only contralateral-eye abduction for horizontal voluntary gaze and localises to the pontine gaze centre or sixth nucleus plus adjacent MLF.

Dorsal midbrain syndromeRed flag

Upgaze palsy, convergence–retraction movements, light–near pupillary dissociation and lid retraction points to the dorsal rostral midbrain and warrants assessment for hydrocephalus, mass, demyelination or vascular disease.

Hemispheric gaze deviationRed flag

Acute conjugate gaze preference with contralateral face-arm weakness, aphasia or neglect supports a cerebral hemispheric lesion. Deviation and ability to cross midline should be recorded before reperfusion treatment.

Skew deviationRed flag

Vertical ocular misalignment from imbalance in central otolith pathways can accompany brainstem or cerebellar disease and may change with gaze or head position; sudden skew within acute vestibular syndrome is a central warning.

Investigations

  1. 01
    Bedside ocular alignment, saccade and pursuit examinationFirst step
    Why
    Define conjugacy, direction, speed, range and nystagmus to separate internuclear, gaze-centre, nerve and junctional patterns.
    Interpretation and limitations
    Test one task at a time with an adequate target and corrected vision. Poor attention, sedation and visual loss can mimic slow or limited gaze and should be documented.
  2. 02
    Cover testing and vestibulo-ocular assessment
    Why
    Identify tropia or skew and determine whether reflex eye movement overcomes a voluntary gaze limitation.
    Interpretation and limitations
    Vestibular manoeuvres are context- and operator-dependent and may be unsafe with neck trauma. Preserved reflex range supports supranuclear dysfunction but does not name the cause.
  3. 03
    Emergency CT and CT angiography
    Why
    Assess haemorrhage, large vascular lesions and reperfusion targets when ocular-motor signs begin suddenly as a stroke syndrome.
    Interpretation and limitations
    Small pontine and midbrain infarcts can be occult on non-contrast CT. CTA and clinical severity guide acute treatment while MRI is arranged where needed.
  4. 04
    MRI brain with thin brainstem and diffusion sequences
    Why
    Detect small infarction, demyelination, tumour, inflammation, hydrocephalus and strategically placed gaze-pathway lesions.
    Interpretation and limitations

Differential diagnosis

01

Third-nerve palsy

Ptosis, pupillary change and impaired vertical movement accompany oculomotor palsy, whereas isolated internuclear disease primarily disrupts adduction during conjugate gaze.

02

Sixth-nerve palsy

One eye cannot abduct in sixth-nerve disease; a gaze-centre lesion restricts conjugate movement of both eyes towards the affected side.

03

Ocular myasthenia

Variable fatigable ptosis and anatomically inconsistent diplopia support myasthenia, which can mimic almost any ocular-motor palsy without a tract lesion.

04

Orbital or muscle restriction

Pain, proptosis, inflammation or mechanical restriction on forced movement suggests orbital disease rather than central internuclear disconnection.

Additional chapter-specific clues

Neuromuscular-junction mimicRed flag

Variable ophthalmoplegia and ptosis changing with effort or time, without a stable tract pattern, can reflect myasthenia. Pupils and sensation remain normal, but bulbar and respiratory risk must be assessed.

Management

01Sudden INO or gaze palsyActivate posterior stroke careFirst stepA conjugate gaze abnormality or internuclear pattern starts abruptly, especially with vertigo, ataxia, dysarthria, weakness or sensory change.+
  1. 1Establish last known well, perform ABCDE and glucose and document pupils, eye positions, horizontal and vertical range, nystagmus, face, bulbar function, limbs, sensation and coordination.
  2. 2Contact the stroke service for urgent CT, vascular imaging and MRI planning; do not dismiss disabling diplopia because FAST is negative or non-contrast CT appears normal.
  3. 3Follow specialist reperfusion, swallowing and observation decisions and repeat the ocular-motor map after treatment or deterioration to identify evolving brainstem involvement.
02Subacute bilateral INOInvestigate multifocal central diseaseAdduction deficits and abducting nystagmus affect both sides or occur with other episodes over days to months.+

Complications

01

Diplopia and falls

Persistent eye misalignment impairs depth perception, reading and mobility, increasing falls and driving risk during everyday activities.

02

Associated stroke disability

A small gaze sign may accompany dysphagia, ataxia, long-tract weakness or basilar disease requiring urgent stroke management.

03

Recurrent demyelinating disease

An internuclear syndrome may be the first clinical event of multiple sclerosis, with future inflammatory attacks and accumulating disability.

04

Missed pressure or structural disease

Attributing a gaze palsy to a microvascular nerve lesion can delay diagnosis of hydrocephalus, tumour or brainstem inflammation.

Monitoring and follow-up

  • Record ocular movement diagrams or structured descriptions of each eye in primary position and gaze directions, because 'diplopia better' does not show neurological evolution.
  • Repeat pupils, consciousness, swallowing and limb findings during any acute brainstem presentation and escalate newly crossed or long-tract signs.
  • In demyelinating disease, track new neurological episodes and objective examination rather than attributing every transient visual symptom to a prior lesion.
  • Assess diplopia's effect on reading, mobility, driving and work and use orthoptic occlusion or prism strategies only through appropriate professional advice.
  • For variable ocular weakness, monitor voice, swallowing, cough and ventilation because limb power and oxygen saturation may remain deceptively preserved.
  • Ensure final MRI and neurophysiology results are reviewed by the responsible clinician and that an early negative scan does not end follow-up of persistent signs.

Special situations

INO is named by weak adduction

A left INO means the left eye fails to adduct on right gaze because the lesion lies in the left medial longitudinal fasciculus, not the side with abducting nystagmus.

Convergence has limits

Preserved convergence can support an internuclear rather than third-nerve pattern, but lesion location, attention and age affect the response. It is not an obligatory diagnostic criterion.

Sixth nucleus differs from nerve

A sixth-nerve lesion weakens one lateral rectus; a sixth-nucleus lesion disrupts coordinated gaze of both eyes toward that side because internuclear neurons originate there.

Abducting nystagmus is secondary

The fellow eye's oscillation reflects increased conjugate drive and network imbalance. It does not mean that eye has a separate primary vestibular disorder.

Vertical saccades reveal PSP

Early slowing of vertical saccades can precede complete range loss in progressive supranuclear palsy. Voluntary and reflex movement should be distinguished by experienced examination.

Tiny lesions can disable

The MLF and gaze centres are compact, so a small pontine or midbrain infarct can cause striking diplopia with little limb weakness and be subtle on early imaging.

Common pitfalls

  1. 01

    Naming the INO from the eye with abducting nystagmus rather than the side with weak adduction.

  2. 02

    Calling a sixth-nerve palsy a gaze palsy without checking the fellow eye's movement.

  3. 03

    Excluding stroke because an acute ocular-motor syndrome has no arm weakness or facial droop.

  4. 04

    Forcing a vestibulo-ocular manoeuvre in a patient with possible cervical injury.

  5. 05

    Diagnosing multiple sclerosis from one bilateral INO without applying current clinical and MRI criteria.

  6. 06

    Attributing inconsistent ocular movements to poor effort before considering myasthenia or visual and cognitive limitations.

  7. 07

    Treating a normal early CT as exclusion of a small brainstem infarct.

Practice

Two practice questions

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Question 1 of 2
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NeurologyOriginal SBA

Localising an internuclear ophthalmoplegia

On attempted right gaze, a patient's left eye fails to adduct and the right eye abducts with nystagmus. Convergence is relatively preserved. Which localisation best fits?

Choose one answer, then submit
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Sources and review status4 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Apply principles in context and verify current guidance when a decision affects care. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • NICE NG220 multiple sclerosis recommendationsCurrent diagnostic, relapse and specialist-management framework for demyelinating ocular-motor syndromes.
  • NICE NG128 acute stroke recommendationsEmergency imaging and treatment pathway for sudden brainstem and gaze-network dysfunction.
  • NICE NG127 neurological referral guidanceRecognition and referral for sudden diplopia, progressive weakness and associated adult neurological symptoms.
  • National Clinical Guideline for StrokeUK and Ireland evidence standard for posterior-circulation stroke assessment and rehabilitation.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom
Vertical gaze depends on rostral midbrain nuclei and posterior commissural pathways. Dorsal midbrain syndrome can combine upgaze palsy, convergence–retraction nystagmus, light–near dissociation and lid retraction, associated with hydrocephalus, pineal-region lesions, demyelination or stroke. Progressive supranuclear palsy often impairs vertical saccades and postural stability, whereas sedatives and poor attention can create apparent gaze limitation without a focal ocular-motor lesion.

Examination should separate saccades, smooth pursuit, vestibular responses and vergence. Ask the patient to move eyes between fixed targets for saccades, then follow a slow target for pursuit. Note speed, range, conjugacy and nystagmus. Check pupils, ptosis, visual acuity and fields and map the rest of the brainstem and long tracts. A label such as INO should end with a side, tempo and accompanying syndrome, not stand alone.

Key points

  • Horizontal conjugate gaze requires coordinated activity between the pontine horizontal gaze centre, ipsilateral sixth-nerve nucleus and the contralateral third-nerve medial rectus subnucleus linked by the medial longitudinal fasciculus.
  • Internuclear ophthalmoplegia causes impaired adduction of the eye on the side of the medial longitudinal fasciculus lesion with abducting nystagmus of the other eye during horizontal gaze.
  • Convergence may be preserved in a classic posterior internuclear lesion, but variable convergence neither proves nor excludes the diagnosis and depends on lesion extent and examination technique.
  • Bilateral internuclear ophthalmoplegia in a younger adult suggests demyelination, while sudden unilateral disease in an older adult suggests brainstem ischaemia; neither age rule is absolute.
  • One-and-a-half syndrome combines an ipsilateral horizontal gaze palsy with internuclear ophthalmoplegia, leaving only abduction of the contralateral eye for horizontal voluntary gaze.
  • One-and-a-half syndrome plus an ipsilateral lower motor neurone facial palsy is often called eight-and-a-half syndrome and localises a compact dorsal pontine lesion.
  • A supranuclear gaze palsy may improve with the vestibulo-ocular reflex, whereas a nuclear or infranuclear palsy generally restricts both voluntary and reflex movement; only test the reflex safely and when neck movement is appropriate.
  • A cerebral hemispheric destructive lesion often drives the eyes toward the lesion and away from the weak limbs; an irritative seizure focus may drive gaze away, but patterns vary and must be integrated with consciousness and imaging.
  • Vertical gaze centres lie in the rostral midbrain. Upgaze or downgaze limitation with lid, pupil, convergence or consciousness changes raises midbrain, hydrocephalic, degenerative or drug causes.
  • Differentiate binocular diplopia from oscillopsia and blur, record the direction of maximal separation and inspect alignment, pupils and lids before repeating fast pursuit or saccade manoeuvres.
  • Myasthenia can mimic almost any painless ocular-motor palsy but does not cause an internuclear tract lesion; variability, fatigable ptosis and inconsistent anatomy support junctional testing.
  • MRI can miss a very small early brainstem infarct, so persistent coherent signs and vascular tempo require stroke-specialist review despite unrevealing first imaging.
Protocol should include the suspected midbrain or pons. Very early diffusion imaging can be negative; repeat assessment or imaging follows persistent focal signs.
  • 05
    Targeted demyelinating and inflammatory evaluation
    Why
    Investigate bilateral, recurrent or multifocal ocular-motor syndromes with MRI, CSF and selected blood studies.
    Interpretation and limitations
    White-matter lesions and oligoclonal bands are interpreted against current multiple-sclerosis criteria and clinical dissemination; neither an INO nor one lesion alone automatically establishes MS.
  • 06
    Myasthenia antibody and neurophysiology studies
    Why
    Assess a variable fatigable ocular syndrome that does not respect a stable central tract localisation.
    Interpretation and limitations
    Negative antibodies do not exclude ocular myasthenia. Repetitive stimulation or single-fibre EMG is selected by specialists, while urgent bulbar or respiratory weakness takes clinical priority.
    • 1
    Confirm a reproducible internuclear pattern and examine vision, pupils, sensation, long tracts, cerebellar function and bladder symptoms while reviewing previous neurological episodes.
  • 2Arrange neurology-led MRI brain and relevant cord, with CSF and targeted inflammatory, nutritional or infectious tests only when the clinical phenotype supports them.
  • 3AlternativeApply current multiple-sclerosis or alternative diagnostic criteria through specialist review and address diplopia, driving, work and rehabilitation while uncertainty is resolved.
    • 03Variable ocular weaknessTest junctional alternatives and ventilationPtosis or ophthalmoplegia fluctuates, fatigues or changes anatomy between examinations without pupillary abnormality or clear central signs.+
    1. 1Ask about chewing, speech, swallowing, neck and limb fatigue and breathlessness and assess cough and locally approved respiratory measurements when generalisation is possible.
    2. 2AlternativeSeek neurology advice for antibody and electrophysiological testing and review medicines, thymic disease and alternative orbital or mitochondrial causes.
    3. 3EscalationEscalate immediately for bulbar or respiratory decline and avoid medicines known to worsen transmission until the specialist and prescribing context are reviewed.