Abducens nerve palsy

From EyeWiki


Abducens nerve palsy


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, developmental neuronal migration defects,[1] and with neurological conditions such as hydrocephalus and cerebral palsy.
  • Acquired.
    • Acquired abducens nerve palsies in childhood can be due to neoplasm, trauma, infection, inflammation, and idiopathic etiologies. Nontraumatic acquired sixth nerve palsies may be due to benign recurrent sixth nerve palsy, elevated or low intracranial pressure, pontine gliomas, and in rare cases, acute lymphoblastic leukemia.[2] Benign isolated abducens nerve palsy can occur in childhood during an episode of sinusitis,[3] or following an ear, throat, or viral infection. Rarely, isolated abducens nerve palsy has even presented in children with Kawasaki disease after IVIG therapy.[4]
  • Trauma, secondary to open or closed head injuries
    • Trauma causes indirect pressure on the nerve, which is very susceptible to trauma as it passes over the apex of the petrous portion of the 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 (ICP) 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. This nerve tends to run steep from the pons to Dorello’s canal and runs a long way to the lateral rectus,[5] making 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.[6] 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 gliomas, medulloblastomas, ependymomas, trigeminal schwannomas,[7] or cystic cerebellar astrocytomas 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.

Based on an retrospective study of 14 patients admitted to Hacettepe University Children’s Hospital Pediatric Emergency Department between Jan 01, 2002 and December 31, 2012.[8]

In adults

  • Microvascular ischemia.
  • Trauma.
  • Idiopathic.
  • Less likely:
    • Multiple sclerosis.
    • Neoplasm.
    • Stroke.
    • Sarcoidosis/vasculitis.
    • Increased intracranial pressure.
    • Giant cell arteritis.
    • Hypophosphatasia Syndrome (with secondary clival thickening)[9]
    • Gestational Hypertension[10]
    • Gradenigo syndrome[11]
    • Creutzfeldt-Jakob Disease[12]
  • 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.
      • Based on a retrospective study reported by the Mayo Clinic from 1950’s to 1980’s for patients of all age groups (1919 patients total)[16]
        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, schwannoma[17] 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, birth trauma, and neurosurgical intervention.[18]


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. In children, given that neoplasms and trauma are the most common etiologies of abducens nerve palsy, immediate and careful evaluations must be performed to rule out serious etiologies.[19] It is important to keep in mind the pseudo-restrictive effects of alternating monocular fixation and vergence when having both eyes open at the same time; therefore, each eye must be tested independently.[20]

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.[21] It is important to differentiate isolated sixth 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.[22]

Symptoms

Diplopia is the most common presenting 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 pulse synchronous 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.[23] 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.[24] In the event of subarachnoid hemorrhage, the patients can present with leptomeningeal irritation and present with cranial nerve palsies.[25]

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.

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.[26] 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 meningioma, and cavernous sinus B cell lymphoma. Due to the possibility 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.[27]

Laboratory test

  • Complete blood cell (CBC) count
  • Glucose levels
  • Glycosylated hemoglobin (HbA1C)
  • Erythrocyte sedimentation rate
  • 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
    • Optic nerve edema
    • 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 nerve palsy includes vasculopathy related to hypertension and diabetes mellitus, aneurysm, sphenoiditis, neoplasm,[28] 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. Thyroid eye disease, although more commonly bilateral, may present with unilateral symptoms including proptosis and symptoms of inflammation upon awakening.[29] 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. Myasthenia gravis may mimic an isolated sixth nerve palsy, but is usually accompanied by fatigability, shortness of breath and hoarseness, all of which are worse later in the day.[30] 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.

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.[31] 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 6 months.

Surgery

Strabismus surgery can be performed for persistent abducens nerve palsies that demonstrate stable measurements over a 6-month period.[32] 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 injections to the medial rectus of the affected eye 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 non-selected sixth nerve palsy cases, and a higher rate of 71% in 419 patients with diabetes mellitus, hypertension, or atherosclerosis[33].

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References

  1. McKay VH, Touil LL, Jenkins D, et al. Managing the child with a diagnosis of Moebius syndrome: more than meets the eye. Archives of Disease in Childhood 2016;101:843-846.
  1. Teksam O, Keser AG, Konuskan B, Haliloglu G, Oguz KK, Yalnizoglu D. Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients. Pediatr Emerg Care. 2016;32(5):307‐311. doi:10.1097/PEC.0000000000000366
  1. Emiroglu M, Alkan G, Kartal A, Cimen D. Abducens nerve palsy in a girl with incomplete Kawasaki disease. Rheumatol Int. 2016;36(8):1181‐1183. doi:10.1007/s00296-016-3515-2
  1. 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
  2. O'Connor KP, Pelargos PE, Palejwala AH, Shi H, Villeneuve L, Glenn CA. Resection of Pediatric Trigeminal Schwannoma Using Minimally Invasive Approach: Case Report, Literature Review, and Operative Video. World Neurosurg. 2019;127:518‐524. doi:10.1016/j.wneu.2019.04.113
  1. Khade N, Carrivick S, Orr C, Prentice D. Recurrent abducens nerve palsy and hypophosphatasia syndrome. BMJ Case Rep. 2019;12(4):e226895. Published 2019 Apr 11. doi:10.1136/bcr-2018-226895
  1. Nieto-Calvache AJ, Loaiza-Osorio S, Casallas-Carrillo J, Escobar-Vidarte MF. Abducens Nerve Palsy In Gestational Hypertension: A Case Report and Review of the Literature. J Obstet Gynaecol Can. 2017;39(10):890‐893. doi:10.1016/j.jogc.2017.04.031
  1. Prasad S, Volpe NJ. Paralytic strabismus: third, fourth, and sixth nerve palsy. Neurol Clin. 2010;28(3):803‐833. doi:10.1016/j.ncl.2010.04.001
  1. Anthony CM, Giles GB, Justin GA, Wedel ML, Grant AD. Creutzfeldt-Jakob Disease Presenting with Abducens Nerve Palsy. Cureus. 2019;11(9):e5564. Published 2019 Sep 4. doi:10.7759/cureus.5564
  1. Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
  1. Nakamizo A, Matsuo S, Amano T. Abducens Nerve Schwannoma: A Case Report and Literature Review. World Neurosurg. 2019;125:49‐54. doi:10.1016/j.wneu.2019.01.123
  1. Von Noorden GK. Binocular Vision and Ocular Motility: Theory and Management of Strabismus, Third ed.
  1. Virgo JD, Plant GT. Internuclear ophthalmoplegia. Pract Neurol [Internet]. 2017; 17(2):149–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27927777
  1. Thurtell MJ, Tomsak RJ, Daroff RB. What do I do now? Neuro-ophthalmology. Oxford, New York; 2011.
  1. Parr M, Carminucci A, Al-Mufti F, Roychowdhury S, Gupta G. Isolated Abducens Nerve Palsy Associated with Ruptured Posterior Inferior Cerebellar Artery Aneurysm: Rare Neurologic Finding. World Neurosurg. 2019;121:97‐99. doi:10.1016/j.wneu.2018.09.096
  1. Bendszus M, Beck A, Koltzenburg M, et al. MRI in isolated sixth nerve palsies. Neuroradiology 2001;43(9):742-745.
  1. Murchison AP, Gilbert ME, Savino PJ. Neuroimaging and Acute Ocular Motor Mononeuropathies. Arch Ophthalmol. 2011;129(3):301-305.
  1. 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
  1. Rush JA, Younge BR. Paralysis of cranial nerves III, IV, and VI. Arch Ophthalmol 1981;99:76–79
    1. # McKay VH, Touil LL, Jenkins D, et al. Managing the child with a diagnosis of Moebius syndrome: more than meets the eye. Archives of Disease in Childhood 2016;101:843-846.
    2. # Teksam O, Keser AG, Konuskan B, Haliloglu G, Oguz KK, Yalnizoglu D. Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients. Pediatr Emerg Care. 2016;32(5):307‐311. doi:10.1097/PEC.0000000000000366
    3. # Teksam O, Keser AG, Konuskan B, Haliloglu G, Oguz KK, Yalnizoglu D. Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients. Pediatr Emerg Care. 2016;32(5):307‐311. doi:10.1097/PEC.0000000000000366
    4. # Emiroglu M, Alkan G, Kartal A, Cimen D. Abducens nerve palsy in a girl with incomplete Kawasaki disease. Rheumatol Int. 2016;36(8):1181‐1183. doi:10.1007/s00296-016-3515-2
    5. # Teksam O, Keser AG, Konuskan B, Haliloglu G, Oguz KK, Yalnizoglu D. Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients. Pediatr Emerg Care. 2016;32(5):307‐311. doi:10.1097/PEC.0000000000000366
    6. # 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
    7. # O'Connor KP, Pelargos PE, Palejwala AH, Shi H, Villeneuve L, Glenn CA. Resection of Pediatric Trigeminal Schwannoma Using Minimally Invasive Approach: Case Report, Literature Review, and Operative Video. World Neurosurg. 2019;127:518‐524. doi:10.1016/j.wneu.2019.04.113
    8. # Teksam O, Keser AG, Konuskan B, Haliloglu G, Oguz KK, Yalnizoglu D. Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients. Pediatr Emerg Care. 2016;32(5):307‐311. doi:10.1097/PEC.0000000000000366
    9. # Khade N, Carrivick S, Orr C, Prentice D. Recurrent abducens nerve palsy and hypophosphatasia syndrome. BMJ Case Rep. 2019;12(4):e226895. Published 2019 Apr 11. doi:10.1136/bcr-2018-226895
    10. # Nieto-Calvache AJ, Loaiza-Osorio S, Casallas-Carrillo J, Escobar-Vidarte MF. Abducens Nerve Palsy In Gestational Hypertension: A Case Report and Review of the Literature. J Obstet Gynaecol Can. 2017;39(10):890‐893. doi:10.1016/j.jogc.2017.04.031
    11. # Prasad S, Volpe NJ. Paralytic strabismus: third, fourth, and sixth nerve palsy. Neurol Clin. 2010;28(3):803‐833. doi:10.1016/j.ncl.2010.04.001
    12. # Anthony CM, Giles GB, Justin GA, Wedel ML, Grant AD. Creutzfeldt-Jakob Disease Presenting with Abducens Nerve Palsy. Cureus. 2019;11(9):e5564. Published 2019 Sep 4. doi:10.7759/cureus.5564
    13. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    14. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    15. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    16. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    17. # Nakamizo A, Matsuo S, Amano T. Abducens Nerve Schwannoma: A Case Report and Literature Review. World Neurosurg. 2019;125:49‐54. doi:10.1016/j.wneu.2019.01.123
    18. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    19. # Teksam O, Keser AG, Konuskan B, Haliloglu G, Oguz KK, Yalnizoglu D. Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients. Pediatr Emerg Care. 2016;32(5):307‐311. doi:10.1097/PEC.0000000000000366
    20. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    21. # Von Noorden GK. Binocular Vision and Ocular Motility: Theory and Management of Strabismus, Third ed.
    22. # Virgo JD, Plant GT. Internuclear ophthalmoplegia. Pract Neurol [Internet]. 2017; 17(2):149–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27927777
    23. # 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
    24. # Thurtell MJ, Tomsak RJ, Daroff RB. What do I do now? Neuro-ophthalmology. Oxford, New York; 2011.
    25. # Parr M, Carminucci A, Al-Mufti F, Roychowdhury S, Gupta G. Isolated Abducens Nerve Palsy Associated with Ruptured Posterior Inferior Cerebellar Artery Aneurysm: Rare Neurologic Finding. World Neurosurg. 2019;121:97‐99. doi:10.1016/j.wneu.2018.09.096
    26. # Bendszus M, Beck A, Koltzenburg M, et al. MRI in isolated sixth nerve palsies. Neuroradiology 2001;43(9):742-745.
    27. # 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
    28. # Khade N, Carrivick S, Orr C, Prentice D. Recurrent abducens nerve palsy and hypophosphatasia syndrome. BMJ Case Rep. 2019;12(4):e226895. Published 2019 Apr 11. doi:10.1136/bcr-2018-226895
    29. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    30. # Kung NH, Van Stavern GP. Isolated Ocular Motor Nerve Palsies. Semin Neurol. 2015;35(5):539‐548. doi:10.1055/s-0035-1563568
    31. # Thurtell MJ, Tomsak RJ, Daroff RB. What do I do now? Neuro-ophthalmology. Oxford, New York; 2011.
    32. # Von Noorden GK. Binocular Vision and Ocular Motility: Theory and Management of Strabismus, Third ed.
    33. # Rush JA, Younge BR. Paralysis of cranial nerves III, IV, and VI. Arch Ophthalmol 1981;99:76–79