How do I distinguish Internuclear Ophthalmoplegia (INO) from 6th cranial nerve palsy on physical exam?

Distinguishing INO from 6th Nerve Palsy on Physical Exam

The key distinguishing feature is that INO produces impaired adduction of the ipsilateral eye with abduction nystagmus in the contralateral eye, while 6th nerve palsy produces impaired abduction of the affected eye with esotropia that worsens in the direction of the paretic muscle. 1, 2

Critical Examination Findings

Internuclear Ophthalmoplegia (INO)

• Adduction weakness on the side of the MLF lesion during conjugate horizontal gaze (but adduction is preserved during convergence testing) 2, 3
• Abduction nystagmus in the contralateral eye (the eye that can still abduct) 2, 3
• Skew deviation may be present, typically with the eye higher on the side of the lesion 2, 4
• Dissociated vertical-torsional nystagmus with the eye beating down on the side of the lesion 2
• Bilateral INO shows impaired adduction in both eyes with bilateral abduction nystagmus and impaired vertical gaze-holding 2

6th Nerve Palsy

• Abduction deficit of the affected eye (cannot move laterally past midline) 1
• Incomitant esotropia that increases when looking toward the side of the paretic lateral rectus muscle 1, 5
• Compensatory head turn toward the side of the palsy to maintain fusion 1
• No abduction nystagmus in the contralateral eye (this is the critical negative finding) 1
• Vertical deviation in peripheral 6th nerve palsy is typically ≤5 PD and within normal range; vertical deviation >5 PD suggests central pathology or skew deviation 5

Specific Testing Maneuvers

Convergence Testing (Critical Differentiator)

• INO: Adduction is preserved during convergence because convergence pathways bypass the MLF 2, 3
• 6th nerve palsy: Convergence is normal (both eyes adduct normally) 1

Vestibulo-Ocular Reflex (VOR) Testing

• INO: VOR testing (head rotation with fixation) will still show impaired adduction on the affected side 6, 4
• 6th nerve palsy: VOR may help distinguish nuclear from supranuclear gaze palsy 6

Static Head Tilt Testing

• Peripheral 6th nerve palsy: Head tilt to either side induces hyperdeviation in the eye on the side of the head tilt (alternating pattern) 5
• Central 6th nerve palsy (brainstem lesion): Hyperdeviation remains on the same side regardless of head tilt direction 5
• INO with OTR: May show consistent skew deviation with head tilt toward the lesion side 4

Associated Neurological Signs

INO Red Flags

• Gaze-evoked nystagmus in multiple directions suggests brainstem or cerebellar pathology (common in MS) 7
• Multiple cranial nerve involvement (5th, 7th nerve palsies) suggests pontine pathology 4
• Bilateral INO is highly suggestive of multiple sclerosis in younger patients 3

6th Nerve Palsy Red Flags

• Other cranial neuropathies (3rd, 4th nerve involvement) suggest cavernous sinus or brainstem pathology 1
• Papilledema suggests elevated intracranial pressure 1
• Bilateral 6th nerve palsy suggests increased ICP, meningeal process, or clival chordoma 1

Common Pitfalls to Avoid

• Do not confuse partial INO with 6th nerve palsy: In partial INO, there is slowed adduction rather than complete failure, and abduction nystagmus in the contralateral eye is the giveaway 2, 3
• Do not miss convergence testing: This single maneuver definitively distinguishes INO (convergence preserved) from medial rectus palsy 2, 3
• Do not overlook vertical deviations: Small vertical deviations (≤5 PD) are normal in 6th nerve palsy; larger deviations suggest additional pathology like skew deviation or INO 5
• Do not assume isolated findings: Central 6th nerve palsy from brainstem lesions often has associated INO, facial palsy, or contralateral hemiparesis requiring urgent neuroimaging 6, 4

Neuroimaging Indications

• INO: MRI brain with contrast is the gold standard to identify MLF lesions from MS, stroke, or tumor 3, 4
• 6th nerve palsy: Neuroimaging indicated for young patients, those without vasculopathic risk factors, bilateral involvement, other cranial neuropathies, or signs of elevated ICP 1
• Vasculopathic 6th nerve palsy in elderly with diabetes/hypertension may be observed for 6 months before imaging if isolated and no red flags 1