Grand Rounds Conference Jinghua Chen, MD, PhD University of Louisville Department of Ophthalmology and Visual Sciences May 1, 2015

History CC: Double vision for two days. HPI: 12 year old boy presented with diplopia for 2 days. About 2 days ago he noticed double vision and he had problem looking to his right with his right eye. 12 year old boy presented with diplopia for 2 days. About 2 days ago he noticed double vision and he had problem looking to his right with his right eye. He denied any vision change. He denied any vision change.

Past Medical History POH: Myopia (-3.50 D OD and D OS) PMH: Asthma Allergy: Chocolate FH: None contributory Eye Medication: None

Exam ODOS ODOS BCVA: 20/20 20/20 Pupils: 4  34  3 No RAPD OU No RAPD OU IOP: 1311 EOM Limited abduction OD CVF:Full OU Anterior segment: Normal OU DFE: Normal OU

Eye Movement Exam in ED

Lab Workup in ED Hematology: Normal Hematology: Normal ICP: 26 (<25 mm Hg) ICP: 26 (<25 mm Hg) CSF: CSF: Appearance: clear Appearance: clear Color: colorless Color: colorless RBC: 10 (0/ µL) RBC: 10 (0/ µL) WBC: 138, 94% lymph (0-8/ µL) WBC: 138, 94% lymph (0-8/ µL) Glucose: 40 (50-80 mg/dL) Glucose: 40 (50-80 mg/dL) Total protein: 47 (15–45 mg/dL) Total protein: 47 (15–45 mg/dL)

MRI without and with Contrast Normal MRI T2 weighted images

Assessment Assessment 12 year old boy presented with diplopia for 2 days. LP shows elevated ICP, mild increased WBC, normal MRI 12 year old boy presented with diplopia for 2 days. LP shows elevated ICP, mild increased WBC, normal MRI Other history: Other history: One week ago patient developed high fever with some neck stiffness. One week ago patient developed high fever with some neck stiffness. He also complained eye pain and headache. He also complained eye pain and headache. Impression: Right 6 th nerve palsy due to Meningitis Impression: Right 6 th nerve palsy due to Meningitis Differential Diagnosis: Differential Diagnosis: Infection, viral illness Infection, viral illness Brain tumor: lesion of cerebellopontine angle Brain tumor: lesion of cerebellopontine angle Nucleus aplasia: Duane’s syndrome Nucleus aplasia: Duane’s syndrome Ischemic mononeuropathy: most common in adults Ischemic mononeuropathy: most common in adults Trauma Trauma Inflammation: petrous bone, facial pain, Gradenigo syndrome Inflammation: petrous bone, facial pain, Gradenigo syndrome Migraine headache Migraine headache Elevated pressure inside the brain Elevated pressure inside the brain

Management Patient received one time dose of iv Rocephin inside hospital. Patient received one time dose of iv Rocephin inside hospital. Follow up office visit 10 days later. Follow up office visit 10 days later. Patient states doing better. Patient states doing better. No diplopia, crossing or drifting. No diplopia, crossing or drifting. No blurred vision. No blurred vision.

The sixth nerve has the longest subarachnoid course of all cranial nerves Ophthalmology 2 nd. 2004: 1324

Pediatric Sixth Nerve Palsies The Rochester Epidemiology Project - Olmsted County residents The annual combined incidence of third, fourth, and sixth nerve palsies was 7.6 per 100,000 (95% confidence interval, 5.1 to 10.1). The annual combined incidence of third, fourth, and sixth nerve palsies was 7.6 per 100,000 (95% confidence interval, 5.1 to 10.1). The fourth (36%), followed by the sixth (33%), the third (22%), and multiple nerve palsies (9%). The fourth (36%), followed by the sixth (33%), the third (22%), and multiple nerve palsies (9%). American Academy of Ophthalmology; 2006:118 Am J Ophthalmol.Am J Ophthalmol Apr;127(4):

Etiologies of Acquired 6 th Nerve Palsy J Ophthalmic Vis Res Apr; 8(2): 160–171. *6% to 30% attributed to a miscellaneous group of causes that includes leukemia, migraine, pseudotumor cerebri, multiple sclerosis; the miscellaneous group of etiologies reflects the poor localizing value of sixth nerve paresis. **6% to 29%, etiology undetermined, reflecting vulnerability of the nerve to conditions which are transient, benign and unrecognizable.

Isolated Sixth Nerve Palsy The 6 th cranial nerve is the most frequently affected nerve in an isolated ocular motor palsy. The 6 th cranial nerve is the most frequently affected nerve in an isolated ocular motor palsy. Diabetes mellitus, hypertension or history of a recent viral infection. Diabetes mellitus, hypertension or history of a recent viral infection.

Syndromes of the Sixth Nerve Palsy- Localizing Signs 1. Brainstem 1. Brainstem 2. Subarachnoid space 2. Subarachnoid space 3. Petrous apex 3. Petrous apex 4. Cavernous sinus/superior orbital fissure 4. Cavernous sinus/superior orbital fissure 5. Orbit 5. Orbit

Brainstem Syndrome Brainstem Syndrome A lesion in the posterior fossa may be compressive, ischemic, inflammatory (multiple sclerosis in young adults) or degenerative and may involve the fifth, seventh and eighth cranial nerves A lesion in the posterior fossa may be compressive, ischemic, inflammatory (multiple sclerosis in young adults) or degenerative and may involve the fifth, seventh and eighth cranial nerves J Ophthalmic Vis Res Apr; 8(2): 160–171.

Subarachnoid Space - Elevated Intracranial Pressure Syndrome Downward displacement of the brainstem causing stretching of the sixth nerve as its exits the pons and inside Dorello’s canal. Downward displacement of the brainstem causing stretching of the sixth nerve as its exits the pons and inside Dorello’s canal. 30% of patients with pseudotumor cerebri have sixth nerve paresis as the only neurologic deficit 30% of patients with pseudotumor cerebri have sixth nerve paresis as the only neurologic deficit Other pathologies in the subarachnoid space include hemorrhage, meningeal infections (viral, bacterial, fungal), inflammation (sarcoidosis) or infiltrations (lymphoma, leukemia, carcinoma). Other pathologies in the subarachnoid space include hemorrhage, meningeal infections (viral, bacterial, fungal), inflammation (sarcoidosis) or infiltrations (lymphoma, leukemia, carcinoma). J Ophthalmic Vis Res Apr; 8(2): 160–171.

Petrous Apex Syndrome  Gradenigo's Syndrome  1904 the syndrome was introduced by Giuseppe Gradenigo  A complication of otitis media and mastoiditis  Triad of diplopia, facial pain and otorrhea

Cavernous Sinus Syndrome Third, fourth, fifth, sixth and sympaththetic fibers. Third, fourth, fifth, sixth and sympaththetic fibers. Internal carotid artery aneurysm Internal carotid artery aneurysm J Ophthalmic Vis Res Apr; 8(2): 160–171.

Orbital Syndrome Proptosis Proptosis Congestion of conjunctival vessels and chemosis Congestion of conjunctival vessels and chemosis Optic atrophy or papilledema. Optic atrophy or papilledema. Horner syndrome may be present Horner syndrome may be present Trigeminal signs Trigeminal signs Tumors of the orbit, orbital pseudotumor, thyroid eye disease, orbital cellulitis or myositis. Tumors of the orbit, orbital pseudotumor, thyroid eye disease, orbital cellulitis or myositis.

The Six Mimickers of Sixth Nerve Palsy Thyroid eye diseases Thyroid eye diseases Myasthenia gravis Myasthenia gravis Duane’s syndrome Duane’s syndrome Spasm of the near reflex Spasm of the near reflex Delayed break in fusion Delayed break in fusion Old blowout fracture of the orbit Old blowout fracture of the orbit

Management of Pediatric Patients Identify and treat the cause of the condition, and to relieve the symptoms. Identify and treat the cause of the condition, and to relieve the symptoms. Neoplasms, especially of the posterior fossa account for 39%. (Robertson DM, Arch Ophthalmol 1970;83: ) Neoplasms, especially of the posterior fossa account for 39%. (Robertson DM, Arch Ophthalmol 1970;83: ) Trauma accounts for 54.4%. (Abbas Bagheri, J Ophthalmic Vis Res 2010;5:32-37.) Trauma accounts for 54.4%. (Abbas Bagheri, J Ophthalmic Vis Res 2010;5:32-37.) Maintain binocular vision: Maintain binocular vision: Fresnel prisms Fresnel prisms Injection of botulinum toxin into the ipsilateral medial rectus. Injection of botulinum toxin into the ipsilateral medial rectus. Development of an abducens nerve palsy following minimal head trauma should raise the suspicion of a compressive lesion such as a tumor. Development of an abducens nerve palsy following minimal head trauma should raise the suspicion of a compressive lesion such as a tumor. Spontaneous recovery of an abducens nerve palsy may occur even with skull base tumors or leukemia, perhaps from axonal regeneration, resorption of hemorrhage in tumors or immune response to the tumor. Spontaneous recovery of an abducens nerve palsy may occur even with skull base tumors or leukemia, perhaps from axonal regeneration, resorption of hemorrhage in tumors or immune response to the tumor. Surgery: Surgery: Vertical muscle transposition procedures such as Jensen's, Hummelheim's or whole muscle transposition. Vertical muscle transposition procedures such as Jensen's, Hummelheim's or whole muscle transposition. Operation on both the lateral and medial rectii of the affected eye. Operation on both the lateral and medial rectii of the affected eye.

References BSCS Book 5, Neuro-Ophthalmology: BSCS Book 5, Neuro-Ophthalmology: Azarmina M, Azarmina H. The Six Syndromes of the Sixth Cranial Nerve J Ophthalmic Vis Res Apr; 8(2): 160–171. Azarmina M, Azarmina H. The Six Syndromes of the Sixth Cranial Nerve J Ophthalmic Vis Res Apr; 8(2): 160–171. Shrader EC, Schlezinger NS. Neuro- ophthalmologic evaluation of abducens nerve paralysis. Arch Ophthalmol. 1960;63:84–91. Shrader EC, Schlezinger NS. Neuro- ophthalmologic evaluation of abducens nerve paralysis. Arch Ophthalmol. 1960;63:84–91. Rucker CW. The causes of paralysis of the third, forth, and sixth cranial nerves. Am J Ophthalmol. 1966;61:1293–1298. Rucker CW. The causes of paralysis of the third, forth, and sixth cranial nerves. Am J Ophthalmol. 1966;61:1293–1298. Johnston AC. Etiology and treatment of abducens paralysis. Trans Pac Coast Otoophthalmol Soc Annu Meet. 1968;49:259–277. Johnston AC. Etiology and treatment of abducens paralysis. Trans Pac Coast Otoophthalmol Soc Annu Meet. 1968;49:259–277. Robertson DM, Hines JD, Rucker CW. Acquired sixth-nerve paresis in children. Arch Ophthalmol. 1970;83:574–579. Robertson DM, Hines JD, Rucker CW. Acquired sixth-nerve paresis in children. Arch Ophthalmol. 1970;83:574–579. Rush JA, Younge BR. Paralysis of cranial nerves III, IV, and VI. Cause and prognosis in 1000 cases. Arch Ophthalmol. 1981;99:76– 79. Rush JA, Younge BR. Paralysis of cranial nerves III, IV, and VI. Cause and prognosis in 1000 cases. Arch Ophthalmol. 1981;99:76– 79. Patel SV, Mutyala S, Leske DA, Hodge DO, Holmes JM. Incidence, associations, and evaluation of sixth nerve palsy using a population-based method. Ophthalmology. 2004;111:369–375. Patel SV, Mutyala S, Leske DA, Hodge DO, Holmes JM. Incidence, associations, and evaluation of sixth nerve palsy using a population-based method. Ophthalmology. 2004;111:369–375. Bagheri A, Babsharif B, Abrishami M, Salour H, Aletaha M. Outcomes of surgical and non-surgical treatment for sixth nerve palsy. J Ophthalmic Vis Res. 2010;5:32–37. Bagheri A, Babsharif B, Abrishami M, Salour H, Aletaha M. Outcomes of surgical and non-surgical treatment for sixth nerve palsy. J Ophthalmic Vis Res. 2010;5:32–37. Quah BL, Ling YL, Cheong PY, et al. A review of 5 years' experience in the use of botulinium toxin A in the treatment of sixth cranial nerve palsy at the Singapore National Eye Centre. Singapore Med J.1999 Jun;40(6): Boger WP 3 rd, Puliafito CA, Magoon EH. Recurrent isolated sixth nerve palsy in children. Ann Ophthalmol Mar;16(3):237-8, Quah BL, Ling YL, Cheong PY, et al. A review of 5 years' experience in the use of botulinium toxin A in the treatment of sixth cranial nerve palsy at the Singapore National Eye Centre. Singapore Med J.1999 Jun;40(6): Boger WP 3 rd, Puliafito CA, Magoon EH. Recurrent isolated sixth nerve palsy in children. Ann Ophthalmol Mar;16(3):237-8, Holmes JM, Mutyala S, Maus TL. Pediatric third, fourth, and sixth nerve palsies: a population-based study. Am J Ophthalmol Apr;127(4): Holmes JM, Mutyala S, Maus TL. Pediatric third, fourth, and sixth nerve palsies: a population-based study. Am J Ophthalmol Apr;127(4): Repka MX, Lam GC, Morrison NA. The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy. J Pediatr Ophthalmol Strabismus 1994;31: Repka MX, Lam GC, Morrison NA. The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy. J Pediatr Ophthalmol Strabismus 1994;31:79-83.