Epidemiology
Meningiomas typically arise in adults in their fourth to sixth decades of life and are rare in children. They are more common in African Americans and in females, with a 2 : 1 female/male ratio in intracranial meningiomas; in Africans, there seem to be a gender-equal distribution.
ONSMs occur more commonly in middle-aged women, but reports of the female/male distribution vary widely in the literature; ratios as high as a 5 : 1 female predilection have been cited.
Approximately 4% to 7% of ONSMs occur in childhood. Unlike those in adults, childhood ONSMs display no gender predilection, and they are often associated with NF-2. The prognosis for childhood orbital meningioma is poor compared with that in older patients. In addition to producing visual impairment, the tumor may extend to adjacent areas such as the cavernous sinus, sella turcica, annulus of Zinn, pterygomaxillary fossa, and medial sphenoid wing.19–23
Clinical Features
The most common symptom of ONSM is visual deterioration (80%). Proptosis is observed in 30% of patients and is generally small, with a mean increase on exophthalmometry of 3.2 (range, 0–13) mm. Optic disk changes are observed in 97%: disk swelling is the most frequent change, followed by atrophy and optociliary shunts. Although visual loss, optic atrophy, and optociliary shunt vessels are characteristic signs of ONSM, this triad may be seen in as few as 25% of patients. Presenting visual acuity is a broad prognostic factor: patients with better than 20/50 visual acuity tend to retain good acuity for some time.19
Investigations
Imaging
Magnetic resonance imaging (MRI) is the technique of choice for evaluating optic nerve tumors, including ONSMs (Fig.18.2). CT with contrast is more sensitive in identifying calcification in these vascular tumors (Fig. 18.3). On T1-weighted images, ONSMs are typically isointense or slightly hypointense to brain and optic nerve tissue. T1-weighted images with gadolinium enhancement and fat suppression typically provide recognition and good definition of meningiomas, both intracranially and within the orbit and optic canal.20–23
The diagnosis of ONSM relies heavily on radiographic growth patterns that can be described in four imaging categories:
1. Tubular with diffuse expansion growth patterns, apical expansion toward the orbital apex, or anterior nerve expansion toward the globe
2. Globular growth pattern caused by exophytic expansion outside the nerve sheath
3. Spindle-shaped fusiform pattern which tapers at the proximal and distal ends
Calcification is observed in 31% of ONSMs. The presence of dense calcification indicates slow tumor growth.20–23
A radiographic study of ONSM found that among the 8% of cases confined to the optic canal, bilaterality was higher (38%) than in intraorbital ONSMs. Half the patients with bilateral ONSMs had tumors along the planum sphenoidale, continuous with the lesions in both optic canals. Thus, it appears that some cases of apparently bilateral ONSMs were truly bilateral, whereas others represent either the spread of a planum sphenoidale meningioma to both optic canals or a unilateral ONSM across the planum to the contralateral optic canal.19
Somatostatin Receptor Scintigraphy
Imaging may not always definitively distinguish ONSM from other optic nerve pathology. Accurate diagnosis is aided by the clinical pattern and occasionally surgical biopsy (Fig. 18.4). However, biopsies are associated with a high risk of visual loss and the spread of the tumor within the orbit, particularly in the case of ONSMs. Thus, a less invasive diagnostic procedure is desirable.
In vitro and in vivo studies have demonstrated that meningiomas have a dense, homogeneous distribution of somatostatin receptors (SSRs) and that somatostatin receptor scintigraphy (SSRS) can be used in vivo to identify SSR-positive tumors. However, several other neoplasms such as neuroendocrine tumors and non-Hodgkin lymphoma (NHL) also show increased somatostatin receptor expression. SSR uptake ratio in meningiomas is significantly higher than in other orbital tumor subgroups, with the exception of adenocarcinoma. Using a threshold uptake ratio of 5.9, the sensitivity of SSRS for ONSM is as high as 100% and the specificity up to 97.2%. SSRS can be used for the differential diagnosis of ONSM, vascular lesions, NHLs, optic nerve gliomas, idiopathic orbital inflammation, and sarcoid, and the procedure potentially reduces the need for an intraorbital biopsy (Fig. 18.5). However, SSRS cannot completely replace histopathologic diagnosis because, despite the risks, atypical cases may still require biopsy.24
Management
Treatment of ONSM has changed substantially over recent decades. Twenty years ago, most clinicians considered optic nerve meningioma to be untreatable. Patients were monitored clinically and with imaging, and surgical resection of the nerve was only offered when the tumor threatened the optic chiasm.
Primary radiation therapy, however, has the potential to improve or stabilize visual acuity in many patients with progressive ONSM. In one series, only 9% showed progressive visual deterioration after radiation treatment. The adverse effects of newer radiotherapy machines and delivery methods are transient or minor.24,25
Controversy: Although treatment strategy must be individualized for each patient, radiotherapy is recommended for patients with progressive visual deterioration and/or visual field constriction. External beam radiation, fractionated stereotactic radiotherapy and proton radiation should be considered for treatment, depending on the geographic region and available technologies, particularly for well-defined lesions. In 2003, radiotherapy was recommended for ONSMs that reduce visual acuity to 20/60 or less; however, based on recent efficacy of radiotherapy for ONSM, it is now recommended in all patients with progressive visual loss. Nevertheless, the optimal timing of radiotherapy for ONSMs remains controversial.24,25
Role of Surgery
Surgical excision of ONSM is technically difficult and associated with postoperative blindness; thus, in some regions it has been replaced by radiation therapy. However, surgery continues to be used for biopsies in atypical cases and in cases where visual preservation is not possible. Surgery may be indicated for orbitocranial lesions that extend to the prechiasmal and parachiasmal regions, particularly with a large intracranial component, or in cases where the planum sphenoidale is involved. Presently, vision-sparing, microsurgical dissection for primary ONSM is not feasible because of the involvement of the pial blood supply to the nerve via the meningioma.19–23
Ectopic Orbital Meningiomas
Nineteen cases of orbital meningiomas with no connection to the optic nerve sheath or intracranial meninges have been reported and are known as “ectopic” or “extradural” meningiomas. Patients ranged in age from 7 to 71 years. With the exception of one 9-year-old girl, all patients were male, in contrast to most meningioma series. The tumors were located either at the orbital rim or in the medial orbital wall, with adhesion to the periosteum; in one intraconal case, the lesion was located inferomedial to the optic nerve.
Several theories have been offered to explain the origin of ectopic meningiomas. Although no arachnoidal cells have been found outside the dural sheath of the optic nerve in the orbit, Cushing found arachnoidal cells accompanying certain cranial nerves at their sites of exit through the skull foramina. Others have suggested the presence of similar cells in the arterial sheaths where vessels pierce the skull or in the periosteum.26–31
Additional sources for orbital ectopic meningiomas have been proposed: (1) from occasional arachnoid “nests” in the orbit, (2) from the optic nerve sheath with separation before clinical evaluation, and (3) from smaller nerves endowed with arachnoid cells. It has also been proposed that almost all ectopic meningiomas originate from the same location in the superomedial part of the orbit. This location suggests that ectopic orbital meningiomas could originate from an orbital meningocele or from meningeal tissue that had been trapped outside the central nervous system (Fig. 18.6).28–31
Secondary Meningiomas of the Orbit
Thirty to forty percent of all meningiomas arise from the base of the anterior or middle fossa with the potential to involve the orbit secondarily. Spheno-orbital meningiomas (SOMs) account for half of these tumors, and olfactory groove meningiomas (OGMs) and tuberculum sella meningiomas (TSMs) account for most of the remainder. Extensions of these tumors may enter the orbits, paranasal sinuses, cavernous sinus, sella, infratemporal fossa, and posterior fossa.32–42 Visual loss is common, occurring in over 95% of patients with TSM and in over 50% of patients with OGM. Meningiomas of the medial third of the sphenoid wing (anterior clinoid meningiomas, ACM) also typically present with ipsilateral visual loss, although contralateral vision is affected in one-third of patients. The original description, in 1911, of the Foster Kennedy syndrome included the triad of optic disk pallor in one eye, optic disk edema in the fellow eye, and anosmia or hyposmia in association with anterior cranial fossa mass lesions, especially OGM and TSM. Other symptoms and signs associated with these meningiomas include headache and mental or personality changes, the latter two of which are most commonly associated with OGM.32–45
Secondary orbital meningiomas that are large and longstanding show considerable overlap in signs and symptomatology. These meningiomas invade the orbit by one of two routes. They can invade the bone and, by hyperostosis, involve the posterolateral orbit and push laterally into the temporal fossa. The other pattern of growth is seen in lesser sphenoid wing meningiomas, TSM, and OGM. Here, the tumor gains access to the orbital cavity through the superior orbital fissure, along the optic canal, or by invasion through the bone at the orbital apex.46–48
Optic Pathway Gliomas (OPGs)
Pathogenesis and Etiology
OPGs are the most common tumors of the optic nerve. They are difficult to treat because of the high risk of visual loss from intervention. OPGs comprise about 1% of all intracranial tumors and are of two different types: juvenile benign pilocytic astrocytoma and adult malignant glioblastoma.49–53
Epidemiology
The mean age of diagnosis of OPG is 8.8 years, although they may occur as late as 79 years. Additionally, patients with OPGs that invade the hypothalamus typically present at a younger age (often by 1 year) with diencephalic syndrome. The female/male ratio is roughly equal, although some data suggest that OPGs limited to the optic nerves are more common in girls.49,53
OPGs are considered benign tumors when diagnosed in pediatric patients. Reports have shown varying levels of incidence of NF-1, ranging from 10% to 70%, among patients with OPGs, whereas the incidence of OPG in patients with NF-1 varies from 8% to 31%. Optic pathway gliomas that are seen in patients with NF-1 are generally felt to have a better prognosis than those found in isolation.
In most cases, the NF-1 diagnosis is based on the minimal criterion of at least six café-au-lait spots measuring at least 15 mm in diameter. The true incidence of NF-1 may be considerably higher because most studies fail to mention the presence or absence of this disease in their patients.49–54
Clinical Features
Patients with OPG may be asymptomatic or may develop symptoms, depending on tumor location. For example, patients with a tumor of the nerve within the orbit may present with proptosis, strabismus, or visual loss (Fig. 18.7A), whereas patients with intracranial OPG can present with visual loss, endocrine/hypothalamic disturbances, spasmus nutans, and obstructive hydrocephalus.
Proptosis is usually gradual and painless; however, on rare occasions, a patient may present with acute loss of vision resulting from hemorrhage into the tumor. Optic disk swelling or pallor, visual acuity loss, visual field loss, and relative afferent pupillary defects may be seen as a result of the compressive effects of the tumor (Fig. 18.7B). The tumor eventually causes optic nerve atrophy because of pressure effects on the nerve fibers and the nutrient arteries. Primary and secondary strabismus is seen, along with restriction of extraocular muscle motility. Additionally, dissociated vertical nystagmus may be observed in suprasellar extending lesions.
Bilateral visual loss is associated with chiasmal involvement causing bitemporal field defects. Proptosis is more frequent in patients with NF-1 (21.5%) than in those without (5.5%), whereas patients without NF-1 are more likely to present with nystagmus and hydrocephalus.49–54
Investigations
Imaging
CT imaging of optic nerve gliomas reveals a well-demarcated enlargement of the nerve, often with a tortuous or kinked appearance. Tumors of the chiasm exhibit various appearances, from enlargement of the chiasm to a suprasellar mass that may calcify. The tumor is usually isodense to brain, and contrast enhancement is variable. Although OPGs may be readily apparent on CT, magnetic resonance imaging (MRI) is the preferred method. Typical MRI findings include an isointense to hypointense lesion on T1-weighted images, with hyperintensity seen on T2-weighted sequences and homogeneous enhancement with gadolinium administration (Fig. 18.7C and D). Some reports have described detailed MRI findings in patients with NF-1, including bilateral tumors with circumferential growth and downward kinking of the intraorbital segment of the optic nerve (Fig. 18.8). Additionally, the double intensity or pseudo-cerebrospinal fluid signal is characteristic in NF-1. This consists of a hyperintense core on T1-weighted images surrounded by lower signal intensity. The inverse is seen on T2-weighted images.
Patients with NF-1 are more likely to demonstrate glioma extension along the optic tracts into the lateral geniculate ganglia and temporal lobes, as well as infiltrating lesions. Positron emission tomography technology has also been shown to be useful for monitoring progression and treatment response in OPGs and may reveal changes earlier compared with MRI.
Pathology
Histologically, OPGs in childhood are typically low-grade gliomas and are divided into pilocytic and fibrillary subtypes based on appearance. Pilocytic astrocytomas are more common and classically have a biphasic pattern with characteristic Rosenthal fibers and eosinophilic granular bodies (Figs. 18.7E and 18.9) In contrast, a relatively new subgroup of OPGs has been defined: the so-called pilomyxoid astrocytomas. These tumors are characterized by piloid cells in a loose fibrillary and myxoid background, are asymptomatic, and tend to be smaller. They lack Rosenthal fibers and have only rare eosinophilic granular bodies. Pilomyxoid astrocytomas were once classified with pilocytic astrocytomas, but they constitute a distinct entity with more aggressive behavior.
Management
The natural history of childhood OPG is almost always benign; most tumors grow slowly in a self-limited manner, and some even regress spontaneously. Some long-term studies indicate that patients who are not treated may retain stable visual function. It has been recommended that most patients with unilateral optic nerve gliomas, particularly those with NF-1, be followed up at regular intervals, both clinically and with neuroimaging, without intervention unless there is documented visual deterioration. Once significant visual deterioration occurs or cosmesis or discomfort becomes troubling, treatment may be considered (Fig. 18.7F).
Radiotherapy
Historically, radiation therapy was the treatment of choice for OPGs, but use of this approach in young children has fallen out of favor because of possible cognitive and endocrine disturbances, as well as radiation-induced complications such as secondary tumors and occlusive vascular disease. Currently, despite the lack of randomized trials comparing radiation therapy with other treatment modalities, radiation therapy is reserved for the treatment of progressive OPG in children older than 5 to 7 years of age.53,55,56
Controversy: Authors of many studies have demonstrated no benefit of radiation therapy over observation or surgery in terms of 10-year progression rates, long-term survival, or preservation of sight. New techniques of delivering radiation, including stereotactic radiosurgery and proton beam radiotherapy, have been developed. Stereotactic conformal radiotherapy has a 5-year survival rate of 79% without the cognitive or endocrine disturbances associated with traditional external-beam radiation therapy.57 Proton beam therapy is an attractive option for radiation therapy in that it can provide high doses of radiation to the lesion with steep attenuation and minimal collateral damage.
Chemotherapy
Although no single chemotherapeutic agent has been identified as a primary treatment, chemotherapy is considered first-line therapy for OPGs that cause visual loss or pituitary or hypothalamic dysfunction. It can treat tumors that have gone beyond the observation stage, even in young children, without the long-term cognitive and neuroendocrine sequelae seen with surgery and radiation therapy. Because of this, chemotherapy is now the primary treatment modality in children younger than 3 years of age with progressive or symptomatic disease. Carboplatin, cisplatin, vincristine, vinblastine, actinomycin D, lomustine, thioguanine, procarbazine, etoposide, tamoxifen, and temozolomide are some of the agents that have been used as first-line therapies. However, the most widely used regimen is a combination of carboplatin and vincristine in a 10-week induction phase, followed by 48 weeks of maintenance carboplatin/vincristine.
In summary, observation is recommended for newly diagnosed OPG and resection for progressive, large intraorbital tumors associated with blindness, cosmetic deformity, or discomfort. Surgery may also be indicated in some exophytic chiasmatic tumors. Radiotherapy is preferred for progressive chiasmatic tumors in older children, and chemotherapy for those in children younger than 3 years with progressive disease.
Natural History and Clinical Course
Overall, OPGs tend to be low-grade and slow growing with long patient survival. Additionally, the presence of NF-1 and an anterior location are associated with a more favorable prognosis, whereas younger age at presentation is associated with a poorer prognosis; progression has been documented in 15% to 30% of OPG cases and leads to visual impairment in approximately 30%. Worsening vision or involvement of the contralateral field has been attributed to an increase in the pressure of a pre-existing lesion on nearby axons, rather than evidence of “true” extension into previously uninvolved chiasmic tissue.
Chiasm involvement and hypothalamic involvement are associated with a decreased rate of survival, although survival is still greater than 90% for treated and untreated tumors.
A retrospective series of OPG by Dutton studied findings in optic pathway gliomas based on location.53 Table 18.1 summarizes presenting findings and outcomes in those restricted to the optic nerve, and Table 18.2 summarizes prognosis based on regions involved. The subgroup of patients with pilomyxoid astrocytoma typically demonstrates a higher rate of local tumor recurrence (75% vs. 50%) and cerebrospinal fluid dissemination (see Tables 18.1 and 18.2).
Table 18.1
Anterior Optic Pathway Gliomas: Presentation and Prognosis
| Anterior Optic Pathway Gliomas | |
| Progression/recurrence | 40% |
| Presenting vision ≥20/40 | 21% |
| Presenting vision ≥20/200 | 45% |
| Progressive visual loss | 21% |
| Tumor-related mortality | <5% |
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