Disease Entity

Strabismus/ocular misalignment

Disease
Abducens nerve palsy is the most common ocular motor paralysis. The abducens (sixth) cranial
nerve controls the lateral rectus muscle, which abducts the eye. Abducens nerve palsy causes an
esotropia due to the unopposed action of the antagonistic medial rectus muscle. The affected eye
turns in toward the nose and is unable to abduct properly. The deviation is constant and is usually
greater at distance fixation than at near. The esotropia is also worse when the patient is looking
toward the affected side.

Etiology

In pediatrics

 Congenital.
 Palsies can occur, albeit rare. They can sometimes be associated with birth trauma
and with neurological conditions such as hydrocephalus and cerebral palsy.
 Acquired.
 Acquired abducens nerve palsies in childhood can be due to neoplasm, trauma,
inflammation, and idiopathic etiologies. Nontraumatic acquired sixth nerve palsies may be due to
benign recurrent sixth nerve palsy, elevated or low intracranial pressure, or pontine gliomas.
Benign isolated abducens nerve palsy can occur in childhood following ear or throat infections or
viral illness.
 Trauma, secondary to open or closed head injuries
 Trauma causes indirect pressure on the nerve, to which it is very susceptible to
trauma as it passes over the apex of the petrous temporal bone to the cavernous sinus . In
addition, traumatic abducens nerve palsy can occur secondary to bruising and/or hemorrhage
causing pressure on the nerve. Closed head trauma may cause elevated intracranial pressure and
secondarily produce a non-localizing sixth nerve palsy.

 Pontine glioma.
 Brainstem gliomas are one of the common tumors seen in the pediatric
population, and more than 80% arise from the pons with the peak age of onset between 5-8 years
of age. Presenting symptoms include ataxia, disturbance of gait, and unilateral or bilateral
abducens nerve palsy.

 Elevated or low intracranial pressure

 Elevated intracranial pressure can cause stretching of the sixth cranial nerves
which are tethered in Dorello’s canal. Their steep course over the petrous apex and the tethering
make the sixth nerve susceptible to injury. The same mechanism can explain the reason for the
non-localizing sixth nerve palsy that can be seen with either elevated or reduced intracranial
pressures [7]. Elevated intracranial pressure can occur secondary to a variety of different causes,
 including shunt failure, pseudotumor cerebri, posterior fossa tumors, neurosurgical trauma,
venous sinus thrombosis, meningitis, or Lyme disease.

 Intracranial tumor
 Posterior fossa tumors, such as pontine glioma, medulloblastoma, ependymoma,
or cystic cerebellar astrocytoma can produce unilateral or bilateral abducens nerve palsies in
children. Skull base tumors (meningioma, chordoma, nasopharyngeal carcinoma, metastasis)
predominate in the adult population. Abducens nerve palsy can also present as a postoperative
complication after resection of posterior fossa tumors in the pediatric population.

 Meningitis
 Hanna et al found abducens nerve palsy in 16.5% of patients with acute bacterial
meningitis. Cranial nerve palsies in this setting tend to be multiple and bilateral.

In adults

 Microvascular ischemia.
 Trauma.
 Idiopathic.
 Less likely:
 Multiple sclerosis.
 Neoplasm.
 Stroke.
 Sarcoidosis/vasculitis.
 Increased intracranial pressure.
 Giant cell arteritis.
 Lesions causing abducens nerve palsy are usually classified by the location of the lesion.
 Fascicular.
 Demyelination, vascular disease and metastatic tumors are likely causes of
fascicular damage. Lesions in this area can cause Foville’s syndrome (damage to the pontine
tegmentum) which is classified by partial sixth nerve palsy, ipsilateral facial weakness, loss of
taste in the anterior portion of the tongue, ipsilateral Horner’s syndrome, ipsilateral facial
sensory loss and ipsilateral peripheral deafness. Lesions in the fascicular area can also cause
Millard-Gubler syndrome, which is a result of damage to the ventral pons, is characterized by
sixth nerve palsy and contralateral hemiplegia, and may or may not also have ipsilateral facial
paralysis.
 Peripheral.
 Causes of peripheral nerve damage include closed head injury,
compression, and bacterial infection of the inner ear. Localized compression can be caused by a
primary pituitary tumor, craniopharyngioma or meningioma. Metastatic tumors and aneurysms
involving the basilar artery can also cause an abducens nerve palsy.

Risk Factors
Inflammatory and microvascular conditions are risk factors for abducens nerve palsy. Other risk
factors include multiple sclerosis, encephalitis, meningitis, cavernous sinus thrombosis,
hypertension, hypercholesterolemia, aneurysm, diabetes, arteriosclerosis, and birth trauma.

Diagnosis

History
The pattern of onset and associated symptoms can be very important in determining the etiology
of an abducens nerve palsy. Sudden onset suggests a vascular etiology, while slowly progressive
onset suggests a compressive etiology. Subacute onset suggests a demyelinating process.

Physical examination
All patients with presumed abducens nerve palsy need a complete ophthalmologic examination,
including visual acuity, binocular function and stereopsis, motility evaluation, strabismus
measurements at near, distance, and in the cardinal positions of gaze, measurement of fusional
amplitudes, cycloplegic refraction, and evaluation of ocular structures in the anterior and
posterior segments. Precise assessment of ductions and versions, as well as precise orthoptic
measurements in lateral gazes are helpful in determining incomitance associated with abducens
nerve palsy. Slow saccadic velocity in side gaze may be present and is helpful with the diagnosis.
If a history of trauma was reported, then forced ductions are recommended to rule out
impingement of the muscle by fractured bone (in a case of esotropia, the medial rectus should be
examined) and bone imaging recommended.

Signs
Because the greatest motility deficit occurs on attempt to abduct the palsied eye, palpebral
fissure widening upon abduction may be seen with maximal abduction effort. The patient may
also present with a head turn toward the affected eye, to keep their eye opposite the field of gaze
of the affected lateral rectus muscle and thereby avoid or minimize diplopia. It is important to
differentiate isolated 6th nerve associated abduction deficit from a gaze palsy or INO as this
would localize the lesion to the nucleus/internuclei of the 6th and 3rd nerve [8]. 

Symptoms
Diplopia is the most common symptom. Patients will have horizontal uncrossed diplopia which
is greater at distance than at near. The diplopia is also worse in the direction of the palsied
muscle and gets better in the contralateral gaze (incomitant). In recent onset palsies, the deviation
measures greater when the paretic eye is fixating and smaller when the nonparetic eye is fixing
(primary and secondary deviations).
In cases of abducens nerve palsy due to raised intracranial pressure, patients may experience
associated symptoms of headache, pain around the eyes, nausea, vomiting, or tinnitus. Low ICP
from a CSF leak can also cause abducens palsy and can present with symptoms of headache and
 can hence present clinically very similarly to raised ICP[7]. MRI brain and orbits can sometimes
help distinguish between high and low ICP. If a patient has a lesion causing the abducens nerve
palsy which affects other structures in the brain, other neurologic signs may be observed. If the
etiology of the abducens nerve palsy is a brainstem lesion affecting the sixth cranial nerve
fasciculus, there may be associated ipsilateral facial weakness, contralateral hemiparesis, or
sensory abnormalities. If the abducens nerve palsy presents together with other ipsilateral cranial
nerve palsies, etiology could be a lesion involving the meninges, superior orbital fissure, orbital
apex, or cavernous sinus. Presence of orbital signs or pulse synchronous tinnitus can suggest an
arteriovenous fistula.

Clinical diagnosis
There is a limitation to abduction in the affected eye. Abducens nerve palsy causes an esotropia
due to the unopposed action of the antagonistic medial rectus muscle. The affected eye turns in
toward the nose and is unable to abduct properly. The deviation is constant and is usually greater
at distance fixation than at near, and also greater when the patient is looking toward the affected
side.

Diagnostic procedures
There is no universal consensus about diagnostic relevance of MRI in abducens nerve palsy. In
general, if unilateral abducens nerve palsy presents acutely, MRI could be performed, especially
if there is no evidence of vasculopathic risk factors. Some clinicians may prefer to routinely
perform MRI in all patients with abducens nerve palsy, even with evidence of vasculopathy
(Bendszus et al. 2001). Another study by Murchison and others in 2011 analyzed cost-
effectiveness of MRI imaging as it related to lesions found and affected courses of treatment, and
determined that it may not be medically necessary to perform MRI on every patient with an
isolated cranial nerve palsy.
However, according to a 2017 review by Elder et al, the most recent input to the MRI debate was
a 2013 prospective study of 109 patients > 50 years old with isolated ocular motor neuropathies
who received MRI.  An etiology other than ischemia was found in 16.5% of patients, including
brainstem infarction, petroclival mass, and cavernous sinus B cell lymphoma.  Due to the
possiblility of dangerous diseases presenting with an isolated cranial motor neuropathy, the
authors recommended MR imaging even if a microvascular cause is suspected.  The authors
stress that high-resolution brain and orbital MRI with gadolinium, fat suppression, and thin
coronal and axial cuts through the orbits are necessary, as sixth nerve palsy mimics (e.g. thyroid
eye disease) may be missed by a standard MRI brain [6].

Laboratory test

 Complete blood cell (CBC) count

 Glucose levels
 Glycosylated hemoglobin (HbA1C)
 Erythrocyte sedimentation rate and/or C-reactive protein
 Fluorescent treponemal antibody-absorption test, VDRL or RPR
 Lyme titer
 Glucose tolerance test
 Antinuclear antibody test
 Rheumatoid Factor test

 MRI could be performed for the following:

 Patients younger than 45 years
 Associated pain or other neurologic abnormality
 History of cancer
 Bilateral sixth nerve palsy
 Papilledema
 If no marked improvement is seen or other nerves become involved
 An LP can be considered if MRI results are negative.

Differential diagnosis
Differential diagnosis for abducens cranial nerve palsy includes Duane’s retraction syndrome
(Types 1 and 3), congenital esotropia, thyroid eye disease, spasm of the near reflex, longstanding
esotropia with medial rectus contracture, ocular neuromyotonia, and lateral rectus myositis. An
abduction deficit can be produced by orbital disease, such as a blowout fracture with entrapment
of the medial rectus muscle, or by neuromuscular disease such as ocular myasthenia gravis or
Miller-Fisher syndrome. Clinical assessment for orbital, neuromuscular, and brainstem disease is
the first step in evaluation for this condition, and after this, an abducens nerve palsy can be
diagnosed by exclusion. If the abducens palsy becomes bilateral and/or worsens in the months
after initial presentation, consider a clival tumor and imaging (CT sagittal view).

Management

General treatment
Treatment depends on etiology of the abducens nerve palsy. In general, underlying or systemic
conditions are treated primarily. Most patients with a microvascular abducens nerve palsy are
simply observed and usually recover within 3-6 months. Treatment for the diplopia associated
with abducens nerve palsy can be managed with prisms, occlusion, botulinum toxin, or surgery.
Occlusion using Bangerter filter or pirate patch can eliminate diplopia and confusion, prevent
amblyopia or suppression in younger patients, and decrease the possibility of ipsilateral medial
rectus contracture. Base-out Fresnel prisms can be used to help the patient maintain binocular
single vision in the primary position, but are not usually useful due to the incomitance of the
deviation. Botulinum toxin injections to the medial rectus of the affected eye are sometimes used
to prevent secondary contraction of the medial rectus, or during transposition procedures to
weaken the non-operative muscle. In general, surgical intervention is reserved for patients who
have had stable orthoptic measurements for at least 3-6 months. 

Surgery
Strabismus surgery can be performed for persistent abducens nerve palsies that demonstrate
stable measurements over a 6 month period. Forced duction test is performed in the office or in
the operating room in order to assist with surgical planning. Often, a resection of the affected
 lateral rectus and recession of the ipsilateral medial rectus (recess/resect or “R and R” procedure)
is performed. Alternatively, a resection of the affected lateral rectus with a recession of the
contralateral medial rectus may be performed.
Various forms of transposition surgeries can be considered (e.g., Jensen, Hummelsheim,
Augmented Hummelsheim with resections +/- Foster modifications, Knapp's procedure).
Botulism toxin can also be used as a temporizing treatment.

Surgical follow up
Patients may be managed closely postoperatively, and any residual diplopia can be managed with
prisms.

Complications
The most likely complication following surgical correction of abducens nerve palsy is the risk of
over- or under-correction, which can be managed postoperatively with prisms.

Prognosis
The prognosis for sixth nerve palsy depends on the underlying etiology. Rush and Younge
reported a recovery rate of 49.6% in 419 nonselected sixth nerve palsy cases, and a higher rate of
71% in 419 patients with diabetes mellitus, hypertension, or atherosclerosis.

References

1. Bendszus M, Beck A, Koltzenburg M, et al. MRI in isolated sixth nerve

palsies. Neuroradiology 2001;43(9):742-745.
2. Murchison AP, Gilbert ME, Savino PJ. Neuroimaging and Acute Ocular Motor
Mononeuropathies. Arch Ophthalmol. 2011;129(3):301-305.
3. Thurtell MJ, Tomsak RJ, Daroff RB. What do I do now? Neuro-ophthalmology.  Oxford,
New York;  2011.
4. Von Noorden GK. Binocular Vision and Ocular Motility: Theory and Management of
Strabismus, Third ed. 
5. Rush JA, Younge BR. Paralysis of cranial nerves III, IV, and VI. Arch Ophthalmol
1981;99:76–79  
6. Elder C, Hainline C, Galetta SL, Balcer LJ, Rucker JC. Isolated Abducens Nerve Palsy:
Update on Evaluation and Diagnosis. Curr Neurol Neurosci Rep [Internet]. 2016; 16(8):69.
Available from: http://link.springer.com/10.1007/s11910-016-0671-4  
7. Hofer JE, Scavone BM. Cranial Nerve VI Palsy After Dural-Arachnoid Puncture. Anesth
Analg [Internet]. 2015 Mar [cited 2019 Aug 22];120(3):644–6. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/25695579  
8. Virgo JD, Plant GT. Internuclear ophthalmoplegia. Pract Neurol [Internet]. 2017;
17(2):149–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27927777