Etiology

Optic nerve sheath meningioma rises in the arachnoid of the optic nerve sheath and enlarges within the subarachnoid space.

Epidemiology

Optic nerve sheath meningioma accounts for 2% of orbital tumors, 1% of central nervous system meningiomas, and 40% of optic nerve tumors.

Pediatric (< 20 years old) primary optic nerve sheath meningioma represents less than 5% of cases and can be more aggressive with high recurrence rates and intracranial extension even after surgical resection.

• About a third of these cases are associated with neurofibromatosis type 2 (Surv Ophthalmol 2008; 53:543).

There is a spectrum of growth rate (WHO classification grade I = 80%, grade II = 10%–15%, grade III = 2%–5%) from extremely slow growth to malignant meningioma, which is invasive and grows rapidly.

Extracranial metastases develop in 0.1% of meningiomas overall and meningioma is the most common extra-axial primary intracranial tumor in adults.

• The lung is the most common site of metastasis.

History

• Gradual, painless, unilateral loss of vision
• Axial proptosis but not usually severe
• Decreased vision and APD
• Vision loss can be recognized incidentally, when covering one eye.

Clinical features

• Primary tumors arise from the intraorbital or intracanalicular segments of the nerve; secondary tumors can arise from the middle cranial fossa and spread through the optic canal.
• Can cause a classic triad of visual loss, optic nerve atrophy, and optociliary shunt vessels (30% of cases) and also optic nerve swelling
• Bilateral cases should be evaluated for neurofibromatosis.
• Pain and diplopia are unusual features of this tumor.

Testing

• Neuroimaging (MRI or CT) usually obviates the need for biopsy.
• Biopsy carries a relatively high risk of visual loss.
• Enlargement of the optic nerve with perineural enhancement results in the classic tram-track sign.
• Incisional biopsy might be warranted in atypical cases.
• Automated perimetry

Testing for staging, fundamental impairment

Subtyping according to Schick includes

• Type I: orbital tumors, subtyped as
• Type Ia: flat tumor limited to the intraorbital nerve
• Type Ib: a bulbous tumor limited to the intraorbital nerve
• Type II: extension into the optic canal
• Type III: intracranial extension

Prior radiation exposure is a risk factor for intracranial meningioma, with a delay of up to 20 years or more, described in a number of case reports (BMJ, 2013:2013; J Ped Hematol Oncol 2014; 36:148).

• Radiation-induced meningioma is the most common form of radiation induced neoplasm (J Clinical Neuroscience 2012; 19:1627).
• Repeated dental x-rays have been raised as a particular concern (J Dent Res, 2013; 92:397).
• However, this association is not specific to optic nerve sheath tumors.
• The association does not suggest a primary risk factor.
• In a study of 433 intracranial meningiomas only 8 (2%) patients had a history of high-dose radiotherapy for malignancy.
• Mean onset was 24 years after treatment (Neurol Neurochirurg Polska 2012; 46:542).
• The use of cellular phones does not seem to increase the risk of intracranial malignancy, including meningioma (Bioelectromagnetics 2012; 33:187).

Hormonal risk factors can also be found in men.

• Androgen deprivation therapy with luteinizing hormone-releasing hormone analogs in the treatment of prostate cancer seems to increase the risk of meningioma in males, but this is not specifically a concern with optic nerve sheath tumors (Prostate Cancer Prostate Diseases 2013; 16:387).

Some hormonal factors in women, such as postmenopausal hormone replacement therapy and fertility medication, have proven not to be risk factors in large epidemiologic studies (J Neurosurg 2013; 118:649).

Women who report breastfeeding for more than 6 months are at decreased risk of meningioma (J Neurosurg 2013; 118:649).

Reproductive factors such as age at menarche, age at menopause, and parity have not been found to increase risk, despite the known increase in tumor growth during pregnancy (J Neurosurg 2013; 118:649).

Meningiomas frequently express progesterone and androgen receptors (both about 70%) and prolactin receptors (about 60%), but less commonly estrogen receptors (about 30% or less).

Smoking cigarettes has been suggested as a risk factor for meningioma, but this has not proven true with large epidemiologic analysis (Cancer Epidemiol 2013; 37:39).

• The association might be gender specific: Smoking might increase the risk in men, but decrease the risk in women (Cancer Epidemiol Biomarker Prev 2012; 21:943).

In a study of 203 meningiomas increased body mass index was a risk factor and this has proven true in other epidemiologic studies (Cancer Prevention Res 2011; 4:1385).

Neurofibromatosis‑2 (NF‑2):

• In 30 consecutive patients evaluated for neurofibromatosis‑2 at the University of Zurich in 1991–2003, 6 had unilateral and 2 had bilateral optic nerve sheath meningiomas (Arch Ophthalmol 2006; 124:379).
• NF-2 is primarily associated with bilateral vestibular schwannomas with a penetrance of 95%, but also optic nerve gliomas, spinal and intracranial schwannomas and meningiomas, and is caused by mutations in a tumor suppressor gene on chromosome 22q12.
• Ophthalmologic stigmata include juvenile cataracts, epiretinal membranes, and hamartomas of the retina and pigment epithelium.
• Neurofibromatosis-1 causes neurofibromas, and is distinct from NF‑2 with a different chromosomal abnormality.

• Optic nerve glioma
• Inflammatory (sarcoid, granulomatosis with polyangiitis)
• Neoplastic (lymphoma, metastatic) infiltration of the optic nerve

Natural history

Observation without treatment is appropriate in some cases to confirm that the visual loss is progressive before intervening.

Among 42 patients with unilateral optic nerve sheath meningiomas treated at Massachussets Eye and Ear Infirmary from 1973 to 1999

• 16 were observed without treatment for a mean of 10.2 years from onset of symptoms
• 4 had stable visual function
• 3 showed improvement without treatment (Arch Ophthalmol 2002; 120:1505)

Medical therapy

In a 180-patient study of the progesterone receptor inhibitor, mifepristone, there was no demonstrated efficacy over placebo. (J Neurooncol 2010; 99:365).

Tamoxifen, an oral estrogen receptor inhibitor, was found not to have efficacy in a phase II.

• This was predictable because only 10%–30% of meningiomas express estrogen receptors and their functional role is not known (J Neurooncol 1993; 15:75; Current Opinion Oncol 2012; 24:666).

Interferon seems to have short-term, limited efficacy.

Hydroxyurea has been studied and seems to be ineffective (J Neurooncol 2012; 107:315).

Temozolomide is an oral alkylating agent, a prodrug of dacarbazine, used effectively for intracranial malignancy.

• However, in 16 patients with meningioma treated with temozolomide in a phase II trial, there was no radiographic response (Neurology 2004; 62:1210).

About 90% of meningiomas harbor somatostatin receptors.

• Although its role is not known, somatostatin has been found to inhibit meningioma growth in vitro (J Neuooncol 2004; 66:155).
• Octreotide is a somatostatin analogue that is metabolized more slowly and can be radiolabeled.
• Octreotide scintigraphy is used to demonstrate overexpression of somatostatin receptors in a meningioma.
• Octreotide can be administered subcutaneously and is well tolerated, but demonstrated no efficacy in a small phase II trial (Neurooncol 2011; 13:530).

Topical mitomycin-C can be applied in conjunction with surgical resection for cystic tumors (OPRS 2008; 24;235).

Radiation therapy

Stereotactic fractionated radiotherapy is the preferred modality as adjuvant treatment after surgery for meningioma in general and is the preferred primary modality of treatment for meningiomas that are in close proximity to important neurovascular structures such as the optic nerve.

The standard fractionation scheme is 1.8–2 Gy fractions, 5 days/week (Int J Rad Onc Biol Phys 2012; 82:1268).

In a study of 113 eyes with optic nerve sheath meningioma treated with stereotactic fractionated radiotherapy, tumor regression was observed in 5 eyes, progression in 4 eyes, and 104 remained stable. Visual acuity was preserved in 95% after 1 year and 91% after 5 years (Int J Rad Onc Biol Phys 2012; 82:773).

Similar results have been reported in numerous smaller studies:

• 15 patients (BJO 2002;86:1265)
• 35 patients (AJO 2006;142:343
• 25 patients (Int J Rad Onc Biol Phys 2009;75:1166)
• 11 patients (BJO 2010;94:559
• 34 patients (BJO 2010;94:564
• 30 patients (J Neurosurg 2010; 113:S28)

Surgery

Surgery is associated with a high risk of precipitating blindness secondary to optic nerve vasculature damage (Ophthalmology 2003;110:2019).

Surgery is indicated for large intraorbital tumors with no useful vision.

Tumors can be approached by pterional craniotomy, unroofing the optic canal, and decompressing the nerve (J Neurosurg 2004; 101:951).

Small feeding vessels between the carotid artery and optic nerve should be preserved.

Irrigation instead of coagulation should be used.

The dura mater around the optic canal can be resected.

The optic canal bone can be decompressed by drilling laterally until the floor of the optic canal is reached to prevent contact with the nerve.

• The optic canal is then unroofed and tumor around the optic nerve and dura mater are removed.

For tumors infiltrating the nerve, resection is limited to the exophytic part, unless the eye has no light perception, in which case the optic nerve can be transected.

As an alternative to surgical resection of the tumor, a window can be created in the dura to relieve pressure on the optic nerve (OPRS 2006; 22:278).

Complication is vision loss with either observation or surgery.

Radiation-induced optic neuropathy is dose-related and the overall complication rate, including dry eye, cataracts, radiation retinopathy, etc., is at least 10%.

Tumor growth can lead to continued loss of vision.

Posterior extension can affect the chiasm and contralateral optic nerve.

Hudson in 1912 differentiated optic nerve tumors between intraneural and nerve sheath tumors.

• He further subdivided the latter group between endotheliomas and meningiomas.

In a 1922 case report, a 20-year-old man with "Recklinhausen disease" treated at the Mayo Clinic had a swollen left eye and difficulty using his hands and walking, proptosis of 9 mm and visual loss.

• He underwent a Kronlein operation for removal of the optic nerve and a 2 x 5‑cm optic nerve sheath meningioma (J Nerv Ment Dis 1922; 56:441).

In a 1940 case report from the Mayo Clinic, a 48-year-old woman underwent transfrontal craniotomy for proptosis and decreased visual acuity.

• A combined intraorbital and intracanalicular nerve sheath meningioma was removed by unroofing the orbit and optic canal
• The patient was febrile for 10 days and required spinal taps to remove collected blood, but final visual acuity was 20/200 with a centrocecal scotoma (Arch Ophthalmol 1940; 23:337).

1. Arena S, Barbieri F, Thellung S, et al: Expression of somatostatin receptor mRNA in human meningiomas and their implication in in vitro antiproliferative activity. J Neuooncol 2004; 66:155.
2. Bosch MM, Wichmann WW, Boltshauser E, Landau K: Optic nerve sheath meningioma in patients with neurofibromatosis 2. Arch Ophthalmol 2006; 124:379
3. Chamberlain MC: Hydroxyurea for recurrent surgery and radiation refractory high-grade meningioma. J Neurooncol 2012; 107:315.
4. Chamberlain MC, Tsao-Wei DD, Groshen S: Temozolomide for treatment-resistant recurrent meningioma. Neurology 2004; 62:1210.
5. Chourmouzi D, Papadopoulou E, Kontopoulos A, Drevelegas A: Radiation-induced intracranial meningioma and multiple cavernomas. BMJ Case Reports 2013, 2013.
6. Claus EB, Calvocoressi L, Bondy ML, et al: Exogenous hormone use, reproductive factors, and risk of intracranial meningioma in females. J Neurosurg 2013; 118:649.
7. Dirksen D, Runte C, Berghoff L, et al: Dental x-rays and risk of meningioma: anatomy of a case-control study. J Dent Res, 2013; 92:397.
8. Dutton JJ: Optic nerve sheath meningiomas. Surv Ophthalmol 1992; 37:167.
9. Egan RA, Lessell S: A contribution to the natural history of optic nerve sheath meningiomas. Arch Ophthalmol 2002; 120:1505.
10. Fan Z, Ji T, Wan S, et al: Smoking and risk of meningioma: a meta-analysis. Cancer Epidemiol 2013; 37:39.
11. Godlewski B, Drummond KJ, Kaye AH: Radiation-induced meningiomas after high-dose irradiation. J Clinical Neuroscience 2012; 19:1627.
12. Goodwin JW, Crowley J, Eyre HJ, et al: A Phase II evaluation of tamoxifen in unresectable or refractory meningiomas: a Southwest Oncology Group study. J Neurooncol 1993; 15:75.
13. Hudson, A. C.: Primary Tumors of the Optic Nerve, Roy. London Ophth. Hosp. Rep. 18:317, 1912.
14. Johnson DR, Kimmel DW, Burch PA, et al: Phase II study of subcutaneous octreotide in adults with recurrent or progressive meningioma and meningeal hemangiopericytoma. Neurooncol 2011; 13:530.
15. Kunert P, Matyla E, Prokopienko M, Marchel A: Radiation-induced tumours of meninges. Report on eight cases and review of the literature. Neurol Neurochirurg Polska 2012; 46:542
16. Li Q, Coulson H, Klaassen Z, et al: Emerging association between androgen deprivation therapy and male mengioma: significant expression of luteinizing hormone-releasing hormone receptor in male meningioma. Prostate Cancer Prostate Diseases 2013; 16:387.
17. Michaud DS, Bove G, Gallo V, et al: Anthropometric measurements, physical activity, and risk of glioma and meningioma in a large prospective cohort study. Cancer Prevention Res 2011; 4:1385.
18. Miller NR: New concepts in the diagnosis and management of optic nerve sheath meningiomas. J Neuro-Ophthalmol 2006; 26:200.
19. Parker HL: A case of Recklinghausen's disease with involvement of the peripheral nerves, optic nerve and spinal cord. J Nerv Ment Dis 1922; 56:441.
20. Repacholi MH, Lerchi A, Roosi M, et al: Systematic review of wireless phone use and brain cancer and other head tumors (Bioelectromagnetics 2012; 33:187).
21. Saeed P, Rootman J, Nugent RA, et al: Optic nerve sheath meningiomas. Ophthalmology 2003;110:2019
22. Schick U, Dott U, Hassler W: Surgical management of meningiomas involving the optic nerve sheath. J Neurosurg 2004; 101:951
23. Songdej N: Focal cranial hyperostosis from meningioma: a complication from previous radiation treatment for childhood T-cell acute lymphoblastic leukemia. J Ped Hematol Oncol 2014; 36:148.
24. Turbin RE, Wladis EJ, Frohman LP, et al: Role for surgery as adjuvant therapy in optic nerve sheath meningioma. OPRS 2006; 22:278.
25. Wen PY, Quant E, Drappatz J, Beroukhim R, Norden AD: Medical therapies for meningiomas. J Neurooncol 2010; 99:365.