Left Internuclear Ophthalmoplegia: Mechanism and Site of Lesion
Left internuclear ophthalmoplegia (INO) is caused by a lesion in the left medial longitudinal fasciculus (MLF) in the brainstem, most commonly due to demyelination in young adults and ischemic stroke in older adults.
Anatomical Mechanism
The medial longitudinal fasciculus (MLF) is a heavily myelinated fiber tract that connects the abducens nucleus (CN VI) in the pons to the contralateral oculomotor nucleus (CN III) in the midbrain. This connection is critical for conjugate horizontal eye movements:
When looking to the right:
- The right abducens nucleus activates the right lateral rectus muscle
- Signals travel via the left MLF to the left oculomotor nucleus to activate the left medial rectus muscle
- This creates conjugate rightward gaze
In left INO:
- The left MLF is damaged
- When attempting to look right, the right eye abducts normally
- The left eye fails to adduct properly due to interrupted signals from the right abducens nucleus to the left oculomotor nucleus
- Characteristic finding: impaired left eye adduction with nystagmus in the abducting right eye 1
Site of Lesion
The lesion in left INO specifically affects the left MLF, which is located in the dorsomedial pontine or midbrain tegmentum. The precise location varies based on etiology:
In multiple sclerosis (MS):
- Lesions often occur at multiple levels of the MLF
- More commonly found in the ponto-medullary junction, mid-pons, and upper pons 2
- Often bilateral (wall-eyed bilateral INO or WEBINO)
In ischemic stroke:
- Lesions more frequently occur at the level of the mesencephalon (midbrain) 2
- Usually unilateral
- Associated with vascular territories of the paramedian branches of the basilar artery
Diagnostic Imaging
MRI is the preferred imaging modality for evaluating INO:
- MRI brain with and without contrast is recommended, including high-resolution T2-weighted images of the brainstem 3
- Lesions may not always be visible despite clinical INO (sensitivity ~75% in demyelinating disease and ~67% in ischemic cases) 4
- Review by a fellowship-trained neuroradiologist increases detection rate 4
Clinical Presentation
Classic features of left INO include:
- Impaired adduction of the left eye on rightward gaze
- Nystagmus in the abducting right eye
- Normal convergence (typically preserved)
- Diplopia, especially on lateral gaze
- May be associated with other neurological symptoms depending on etiology
Differential Diagnosis and Etiologies
Multiple sclerosis: Most common cause in young adults 3, 5
- Often bilateral INO
- Associated with other demyelinating lesions
Ischemic stroke: Most common cause in older adults 3, 6
- Usually unilateral INO
- Associated with vascular risk factors
Other less common causes:
- Brainstem tumors
- Trauma
- Infection
- Hydrocephalus
- Systemic lupus erythematosus
- Subdural hematoma with transtentorial herniation 7
Clinical Implications
The presence of INO should prompt:
- Complete neuro-ophthalmologic examination
- Evaluation for other brainstem signs (nystagmus, skew deviation, cranial nerve palsies)
- MRI brain imaging
- In young adults, consideration of MS workup
- In older adults, assessment of stroke risk factors and vascular imaging
Management
Treatment is directed at the underlying cause:
- For MS: disease-modifying therapies
- For stroke: acute management and secondary prevention
- Symptomatic management of diplopia may include prisms or occlusion therapy
Conclusion
Left INO results from a lesion in the left MLF, disrupting the neural pathway that coordinates conjugate horizontal gaze. The specific location in the dorsomedial pons or midbrain varies by etiology, with MS and stroke being the most common causes. MRI is the preferred diagnostic modality, though lesions may not always be visible despite clear clinical findings.