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internuclear ophthalmoplegia INO medial longitudinal fasciculus clinical features

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Internuclear Ophthalmoplegia (INO)

Anatomy & Pathophysiology

INO results from a lesion in the medial longitudinal fasciculus (MLF) — the white matter tract that ascends from the abducens nucleus (CN VI) in the pons to the oculomotor nucleus (CN III) in the midbrain. This tract coordinates horizontal conjugate gaze by relaying a signal from abducens interneurons to contralateral medial rectus motor neurons.

When the MLF is damaged, this cross-midline communication is severed, causing failure of adduction of the ipsilateral eye on attempted contralateral gaze, while the contralateral eye abducts normally (often with nystagmus).

Diagram of the horizontal gaze pathway. The red X marks the MLF lesion that produces INO — disrupting communication between the abducens and oculomotor nuclei.

Clinical Presentation

Feature	Description
Ipsilateral eye	Slowed or absent adduction on attempted lateral gaze
Contralateral eye	Full abduction, often with abducting nystagmus
Convergence	Often preserved (uses a different pathway)
Bilateral INO	Both eyes fail to adduct; strongly suggests MS

Example: A left INO = left eye fails to adduct when looking right, while the right eye abducts with nystagmus.

Causes

Cause	Notes
Multiple sclerosis	Most common; typically younger patients, often bilateral
Brainstem stroke	Most common cause in older patients; typically unilateral
Tumor	Brainstem glioma, metastasis
Trauma	Brainstem injury
Wernicke's encephalopathy	Thiamine deficiency
Other	Infection, vasculitis, anti-NMDAR encephalitis

Rule of thumb: Bilateral INO in a young person = MS until proven otherwise. Unilateral INO in an older patient = vascular (stroke).

Diagnosis

Clinical exam is key: observe for adduction lag and contralateral abducting nystagmus
MRI brain/brainstem (with DWI if acute): identifies demyelinating plaques or infarct in the MLF
Work up the underlying cause (MS panel, vascular risk factors, etc.)

Associated Syndromes

WEBINO (Wall-Eyed Bilateral INO): bilateral INO with exotropia at rest
One-and-a-half syndrome: ipsilateral gaze palsy + INO — lesion involves both the PPRF/abducens nucleus AND the MLF on the same side; only preserved movement is contralateral abduction

Management

Treatment is directed at the underlying cause:

MS: corticosteroids for acute relapse; disease-modifying therapy long-term
Stroke: standard ischemic stroke management (thrombolysis/thrombectomy if eligible, antiplatelets, risk factor control)
Symptomatic: prism glasses or patching may help with diplopia; INO from MS or stroke often improves spontaneously

(Harrison's Principles of Internal Medicine, 21st ed., p. 989)

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