Ординатура / Офтальмология / Английские материалы / Neuro-Ophthalmology_Kidd, Newman, Biousse_2008

by rapidly progressive visual loss, neurologic deficits, and, eventually, death.14 Unlike low-grade gliomas of the anterior visual system that occur in children, malignant gliomas almost always occur in adults.14 The age range is broad, ranging from the second to the eighth decade of life. Some reports suggested that these tumors occur primarily in men, whereas others report an equal incidence in men and women.

The specific pattern of visual loss that occurs in patients with malignant gliomas of the optic nerve appears to depend on the site of origin of the tumor. Tumors that originate in the proximal portion of the nerve produce a characteristic syndrome.14 The initial symptoms are monocular blurring of vision and retrobulbar pain simulating optic neuritis. The fundus of the affected eye initially may appear normal, but most patients rapidly develop evidence of occlusive vascular disease involving the optic disc, including venous stasis and edema (Fig. 9–5A). There may be extensive hemorrhage in the posterior pole, and the appearance of the fundus may thus resemble the ischemic form of central retinal vein occlusion (CRVO), and neovascular glaucoma may develop. This does not remain, however, a monocular disease. Within 5 to 6 weeks, both eyes become affected, and the patient soon becomes completely blind. Hypothalamic dysfunction, hemiparesis, and other neurologic deficits develop in the latter stages of the disease, and death usually occurs in less than 1 year.15

Malignant optic gliomas that originate in the distal portion of the optic nerve produce a similar syndrome of progressive unilateral visual loss, neurologic symptoms, and death; however, the visual loss in these patients is associated with a normal appearing optic disc that eventually becomes pale.15

The neuroimaging appearance of a malignant glioma of the optic nerve is nonspecific. In some cases, the optic nerve appears diffusely thickened, and MRI after intravenous injection of a paramagnetic contrast agent may show

marked enhancement of the nerve with inhomogeneity and cystic-appearing areas15,16 (Fig. 9–5B).

The pathologic features of a malignant optic nerve glioma are characteristic.14–16 The vascular and partially necrotic tumor occupies most of the nerve. In the orbit, it usually infiltrates the meninges of the nerve and the surrounding soft tissue, whereas intracranially, it eventually infiltrates the optic chiasm, hypothalamus, and adjacent parts of the brain. The histopathology of this tumor is completely different from that of the typical optic nerve glioma, being characterized by extreme cellular pleomorphism, nuclear hyperchromaticity, and scattered mitoses (Fig. 9–5C). There are often numerous areas of vascular endothelial proliferation, necrosis, and hemorrhage, similar to those seen in glioblastomas.

There is no satisfactory treatment for a malignant optic nerve glioma, and death is the result in most cases. Short-term success occasionally follows treatment with combined radiotherapy and chemotherapy.

GANGLIOGLIOMA

In rare instances, ganglion cell tumors originate within the substance of the optic nerve.17–19 Such a tumor may be thought to be an optic glioma until an

exploration is performed and the nerve is removed or a biopsy of the lesion is obtained. The presentation of these tumors as well as their imaging characteristics are similar to those of optic nerve gliomas (Fig. 9–6A), although the visual

Figure 9–5 Malignant optic nerve glioma. A, Fundus showing appearance of a severe central retinal vein occlusion. B, Magnetic resonance imaging of lesion. C, Histopathology.

loss may be more rapidly progressive; however, their pathology is quite different.

The tumor is composed of numerous ganglion cells, separated by connective tissue that is abundant in some areas and sparse in others.17–19 Microscopic find-

ings show neoplastic astrocytic nuclei throughout a hypercellular nerve associated with small numbers of randomly distributed, well-differentiated ganglionic elements as well as binucleate ganglion cells (Fig. 9–6B). These tumors also show immunoreactivity to synaptophysin and neurofilament protein.19

MEDULLOEPITHELIOMAS

Medulloepitheliomas most commonly arise in the brain and spinal cord; however, they also may arise from the optic nerve.20–22 This is not surprising when

one considers that the embryonic neuroepithelium that lines the invaginated

Primary Tumors of the Optic Nerve Sheath

The most common tumor of the optic nerve sheath is the meningioma; however, a few rare tumors of the sheath have also been described, including one case of a hemangiopericytoma and several cases of schwannomas.

OPTIC NERVE SHEATH MENINGIOMA

Primary optic nerve sheath meningiomas (ONSMs) account for one third of primary optic nerve tumors, are the second most common optic nerve tumors after glioma, and are the most common tumors of the optic nerve sheath.24 Although ONSMs are said to comprise 1% to 2% of all meningiomas, their reported incidence has increased since the development of more advanced neuroimaging techniques, which have also significantly contributed to earlier recognition of the disease.

ONSMs may be primary or secondary. Secondary ONSMs arise intracranially from dura on or near the planum sphenoidale and spread anteriorly within the confines of the optic nerve sheath through the optic canal to surround the orbital portion of the nerve, whereas primary ONSMs arise from arachnoid cap cells within the dural sheath surrounding the orbital or, less commonly, the canalicular portion of the optic nerve.25,26 Independent of the primary site of origin, ONSMs usually spread around the optic nerve through the subdural

and subarachnoid spaces, following pathways of least resistance such as vessels and dural septae.25,27 As they spread, they compromise the function of

the nerve both by impairing blood supply to the nerve and by interfering with axon transport. The tumors thus are interposed between the nerve substance and its extradurally derived blood supply, making the majority of ONSMs not amenable to resection.

Some ONSMs remain localized to a small segment of the optic nerve, whereas others spread to surround the entire length of the orbital and canalicular portions of the nerve. Rarely, the tumor infiltrates the dura and spreads beyond the confines of the nerve to infiltrate adjacent orbital structures, including fat, extraocular muscles, and bone. When the tumor spreads to adjacent bone, it may enter the haversian canal system, inciting hyperostosis and bone proliferation.28

In a meta-analysis by Dutton published in 1992,24 the mean age at presentation for primary ONSMs was 41 years (age range 3 to 80), with women being affected more often than men (3:2). Patients with neurofibromatosis had a higher incidence of ONSM compared with the general population. Almost all cases (95%) were unilateral. The majority of primary ONSMs were intraorbital, with 8% confined to the optic canal. Interestingly, canalicular meningiomas had a higher incidence of bilaterality (38%) than ONSMs within the orbit. In a subsequent series,29 half of the patients with bilateral ONSMs had tumor along the planum sphenoidale in continuity with the lesions in both optic canals. Thus, it would appear that some cases of apparently bilateral ONSMs are truly bilateral, whereas others represent either spread of a primary planum sphenoidale meningioma to both optic canals or of a unilateral ONSM across the planum to the contralateral optic canal.

ONSMs have three main morphologic patterns on imaging: tubular, fusiform, and globular.29 CT scanning typically shows enlargement of the optic nerve with an increased density peripherally and decreased density centrally (the “tramtrack” sign). These changes are particularly well seen after intravenous injection of iodinated contrast material (Fig. 9–10). In addition, in some cases of ONSM, calcifications surrounding the nerve are present on CT scanning, although they may be masked by contrast enhancement and thus are best identified on precontrast soft tissue and bone-windowed images.36 The presence of such calcifications is thought to indicate slow growth.29

MRI provides somewhat better detail of ONSMs than does CT scanning34 (Fig. 9–11). In particular, the soft tissue component of the tumor is readily visible, particularly when T1-weighted are viewed after intravenous injection of a paramagnetic contrast agent and fat saturation techniques are used. The appearance of the optic nerve on coronal magnetic resonance (MR) images after gadolinium is most often that of a hypodense area (the nerve) surrounded by an

Figure 9–10 Axial non-contrast computed tomography scan demonstrates a hyperintense left optic nerve sheath with central lucency corresponding to the nerve (i.e., the “tram-track” sign).

Figure 9–11 Axial, non-contrast, T1-weighted magnetic resonance imaging in a patient with a right optic nerve sheath meningioma shows a fusiform mass surrounding the optic nerve with the lateral deviation of the nerve. Note extension of the tumor into the optic canal.

In many cases, performance of a 30-degree test reveals solid thickening of the nerve, whereas in others, the tumor is located more posteriorly, and the anterior enlargement of the nerve is the result of cerebrospinal fluid that is trapped by the tumor.35

In rare cases, small tumors located within the optic canal are impossible to detect using current neuroimaging procedures. Such lesions usually are discovered during exploratory craniotomy. The lesions may be suspected, however, in any patient with slowly progressive, unilateral loss of vision associated with signs of optic neuropathy.36 In addition, the presence of enlarged, aerated, posterior ethmoid and sphenoid sinuses, a condition known as pneumosinus dilatans, is believed by some authors to be pathognomonic of an ONSM.37

Two histologic patterns are seen in primary ONSMs.38 In the meningothelial or syncytial pattern, polygonal cells are arranged in sheets separated by vascular trabeculae. Mitoses are uncommon. In the transitional pattern, spindle or oval cells are arranged in the whorls. Psammoma bodies are common in this form and develop from hyalinization and deposition of calcium salts in the degenerated centers of the whorls.

Traditionally, ONSMs have either been observed without intervention or treated by excision of the tumor along with the nerve because of concern for intracranial extension. In such cases, the patient is blind following surgery, and disturbances of eyelid function and eye movements are often present.24 Attempts to excise these

tumors while keeping the optic nerve itself intact are usually unsuccessful, and most patients are blind in the eye following such surgery.25,29,39–41 The only excep-

tions are ONSMs that are primarily extradural.24 In such cases, the bulk of the

tumor can be excised, although rarely if ever can the entire tumor be removed,24,29,42 as at least some of the tumor remains behind in the subdural or

subarachnoid space surrounding the nerve. In other cases, particularly those with acute visual loss, some authors recommend opening the optic nerve sheath to decompress the nerve.29,43

To date, trials of medical therapy for ONSM have not been successful. Because meningioma cells often express a variety of hormone receptors, most commonly estrogen and progesterone receptors,44 it might be expected that treatment with estrogen or progesterone antagonists would result in destruction of the tumor or at least reduction in its size and extent, but this does not seem to be the case. Similarly, although hydroxyurea has been said to be helpful in some cases of intracranial meningioma, we are aware of only one case report in which the treatment of an ONSM with hydroxyurea resulted in visual improvement.45

Radiotherapy for ONSM was initially used only as an adjuvant to surgery, as meningiomas in general were once considered to be completely radioresistant. In 1981, however, Smith et al46 reported the successful treatment of five patients with ONSMs using conventional fractionated radiotherapy. These authors documented improvement in visual acuity in two of the patients, an improvement in the visual field in three, and regression of retinochoroidal shunt vessels in two patients. Kennerdell et al40 subsequently treated six patients with fractionated radiation therapy and documented improvement in visual acuity and visual fields in five patients with stabilization in one. No complications were observed during a follow-up period that ranged from 3 to 7 years.

In 2002, Turbin et al36 reported a retrospective series of 64 patients with primary ONSMs who had been managed with observation alone, surgery, surgery

with radiation, and radiation alone. The study included patients from the original paper by Kennerdell et al40 The follow-up in this study ranged from 51 to 516 months, with a mean follow-up of 150 months. Turbin et al concluded that treatment with radiation alone resulted in the best long-term visual outcome even though about one third of patients treated in this fashion developed complications from the radiation, including radiation retinopathy, retinal vascular occlusion, persistent iritis, and temporal lobe atrophy. The study does not describe which radiation technique was used, but given the era during which the study was conducted and the length of time the patients were followed, it is likely that the majority of the patients were treated with conventional treatment techniques.

The major concern with radiotherapy for ONSMs is late toxicity. Not only can radiation damage the optic nerve itself but adjacent tissues can also be damaged,

including the retina, pituitary gland, and the white-matter tracts of the brain.47 Retinal injury has been described with exposures of more than 50 Gy,48,49 but

coexistence of diabetes mellitus may lower the threshold for retinal or optic nerve damage to 45 Gy.49,50 Late pituitary dysfunction is a rare complication of

radiation as is small-vessel injury in the anterior temporal lobe after irradiation of ONSMs that extend intracranially.47,51

The threshold for radiation damage to the optic nerve, optic chiasm, or both has been estimated to be 8 to 10 Gy for a single dose.50 Because lower doses of radiation are thought to have a more uncertain effect on benign tumors such as ONSMs, and a large, single dose of radiation is associated with a high risk of tissue damage, single-dose stereotactic radiosurgery is not widely used to treat ONSMs; however, stereotactic fractionated radiotherapy (SFR) appears to offer the potential for delivering a sufficient amount of radiation to an ONSM in a manner more focused than that of conventional fractionated radiation therapy, thus minimizing the complications from exposure of the surrounding tissue to high doses of radiation.

SFR requires complex planning, which is facilitated by sophisticated software and three-dimensional imaging. The pretreatment imaging (CT and/or MRI) and radiation delivery require the patient to be repeatedly immobilized, although the newest linear accelerator (LINAC) units such as the Cyberknife use a tracking system that eliminates the need for rigid immobilization during the treatment phase. Unlike conventional radiation therapy, the LINAC system delivers the radiation in non-coplanar fields that take into account the characteristics of the surrounding tissue. Every beam is sizeand shape-adjusted by different devices, micro-leaf collimators being the most advanced way of achieving a high degree of conformality to the tumor, thus minimizing irradiation of the surrounding tissue.52

In 1996, the first case report appeared in the literature documenting improvement of vision after conformal irradiation of ONSM.53 Since then, at least seven series have been published that have documented either improvement or stabi-

lization of vision after SFR. These series are discussed in detail later.

The natural history of the ONSM is progressive loss of visual acuity.29–31,54 In one series,55 six of seven patients with initial visual acuity of 20/40 or better who were followed without intervention had nearly complete loss of vision over an average duration of 9 years. Nevertheless, observation is appropriate if there is no significant visual dysfunction, no significant progression of visual loss,