25th June 2023

CN VI – Abducens nerve

The abducens nerve is a motor nerve that innervates the lateral rectus muscle of the eye. Due to its length and course, it is most vulnerable to damage from raised intracranial pressure, such as idiopathic intracranial hypertension and is prone to producing a false localising sign. Palsy of the abducens nerve causes loss of function of the lateral rectus resulting in the inability to look laterally. This nerve is associated with CN 3 and 4 at points of its course and can be associated with painful ophthalmoplegia.

Internuclear Ophthalmoplegia

Internuclear ophthalmoplegia (INO) is the failure of adduction of the ipsilateral eye towards the midline and nystagmus in the contralateral eye as it looks away from the midline.

Schematic of right internuclear ophthalmoplegia.

Image Source: Wikimedia Commons (2006). Internuclear ophthalmoplegia, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Internuclear_ophthalmoplegia.jpg (Accessed on: 11 January 2023).

INO results from a lesion in the median longitudinal fasciculus (MLF) which coordinates the oculomotor nerve of the ipsilateral eye with the contralateral trochlear and abducens nerves via the paramedian pontine reticular formation (PPRF). The PPRF is a supranuclear centre close to the ipsilateral abducens nucleus which controls horizontal conjugate movements.

An INO manifests as an inability to adduct the eye ipsilateral to the lesion of the MLF. A right INO is a disorder of the right MLF leading to an inability to adduct the right eye. Midbrain and pontine demyelinating lesions can cause a unilateral or bilateral INO.

Bilateral INO is very characteristic of multiple sclerosis and causes an inability to adduct either eye with resultant bilateral abduction nystagmus. If the ipsilateral PPRF or abducens nuclei are affected in addition to the ipsilateral MLF, this can cause a ‘One and a Half’ spectrum of syndromes, where an ipsilateral conjugate horizontal gaze palsy with an ipsilateral INO results in the ipsilateral eye being incapable of horizontal movement with varying degrees of response to horizontal vestibular reflexes depending on where the lesion is, while the contralateral eye also experiences the conjugate horizontal gaze palsy resulting inability to adduct the contralateral eye.

Vertical gaze palsy

A vertical gaze palsy, also known as a supranuclear gaze palsy, is a bilateral inability to make voluntary eye movements in the vertical plane, i.e. upward or downward gaze movements. Involuntary vertical eye movements would still be preserved, e.g. in reflex conjugate eye movements such as the vestibulo-ocular reflex, which can be demonstrated when an examiner passively moves the patient’s head up and down, leading to correction of the vertical paresis. On moving the head up while the patient’s gaze is fixed on a point, the eyes would reflexively move down as the head is moved up, a movement they would not be able to voluntarily do in a vertical gaze palsy.

This is a classic symptom in progressive supranuclear palsy and corticobasal degeneration but can also result from a vascular or infective insult to the structures involved – the interstitial nucleus of Cajal, rostral interstitial nucleus of medial longitudinal fasciculus, and cranial nerve 3 and 4 nuclei, and from mechanical causes like hydrocephalus or tumour. A caveat to this is if there is a bilateral infranuclear lesion, e.g. a neuromuscular junction or muscle lesion such as in myasthenia gravis, which would result in a gaze palsy that cannot be overcome by conjugate gaze testing.

Parinaud Syndrome

Parinaud syndrome, also known as dorsal midbrain syndrome, is a combination of a vertical gaze palsy with an Argyll-Robertson pupil with bilateral lid retraction (Collier sign). An Argyll-Robertson pupil is the manifestation of bilaterally small pupils that are not reactive to light but have a preserved accommodation reflex – i.e. are able to constrict when looking at near objects but not to light.

This sign is suggestive of damage to the midbrain involving damage of the pretectal nucleus or Edinger-Westphal nuclei, which results in loss of parasympathetic innervation to the iris sphincter muscles and an inability to constrict the pupil in response to light and is associated with diabetic neuropathy and neurosyphilis. As a component of Parinaud syndrome, dorsal midbrain lesions can result from a variety of aetiologies, including:

• vascular lesions, e.g. infarction, haemorrhage, arteriovenous malformations
• mechanical, e.g. tumours, hydrocephalus, trauma
• demyelinating and inflammatory conditions, e.g. neurosyphilis, multiple sclerosis and infection

The most common causes are pineal region tumours, and brainstem haemorrhage or infarction.

Kearns-Sayre syndrome

Kearns-Sayre syndrome, also known as oculocraniosomatic neuromuscular disorder with ragged red fibres, is a rare syndrome caused by mitochondrial DNA deletions resulting in defective oxidative phosphorylation and subsequent mitochondrial myopathy.

It manifests as a tetrad of:

• Chronic progressive external ophthalmoplegia – weakness and paralysis of eye muscles
• Pigmentary retinopathy leading to vision loss and night blindness
• Cardiomyopathy and cardiac conduction defects
• Cerebral folate deficiency leading to ataxia, sensorineural hearing loss, and cognitive impairment

It typically manifests before the age of 20 and has no specific gender predilection. Treatment is supportive, including Co-enzyme Q supplementation and consideration of prophylactic pacemaker implantation.