into the floor of the orbit or when frontal sinus or frontal lobe tumors invade through the roof of the orbit.

Less commonly, tumors invade the lateral aspect of the orbit. Tumors can also spread to the pterygopalatine fossa and retromaxillary fat through the posterior wall of the maxillary sinus or sphenopalatine foramen [2–5]. The pterygopalatine fossa also houses the pterygopalatine ganglion, which is a major junction for tumors spreading along the V2 division of the fifth cranial nerve. Upward spread through the inferior orbital foramen allows tumors direct access to the inferior extraconal space and apex of the orbit. Certain malignant tumors transgressing and particularly those extending into the orbital apex may require orbital exenteration [10] because tumors in the orbital apex can easily spread into the middle cranial fossa. Additionally, sinonasal tumors that result in perineural spread may require orbital exenteration to prevent the tumor from reaching the intracranial structures, e.g., the cavernous sinus (V1 and V2) or gasserian ganglion (V3). The floor of the anterior and middle cranial fossa, orbits, pterygopalatine fossa, and palate are critical areas of tumor extension that alter surgical and radiation treatments and thus should be given special attention [2–4].

30.4 Skull Base Tumors and Neuro-ophthalmic Correlations

30.4.1 Esthesioneuroblastoma

Esthesioneuroblastoma, also known as olfactory neuroblastoma, is an uncommon malignant tumor arising from the olfactory epithelium in the nasal cavity. It can grow superiorly to involve the anterior cranial fossa through the cribriform plate and the adjacent orbits laterally. Esthesioneuroblastoma has a peak incidence of presentation in the second to fifth decades, with a slightly higher preponderance in males [12]. However, this tumor has been reported in 1- and 2-year-old children who experienced sudden blindness in one eye [13]. Patients may present with general symptoms of nasal obstruction or congestion, epistaxis, anosmia, or headache; when orbital involvement occurs, patients may manifest diplopia, proptosis, epiphora, or blindness. Motility may be compromised, depending on the extent of orbital involvement. If the tumor has involved the anterior skull base, including the planum sphenoidale, the optic nerve can be compressed on one or both sides, giving rise to blindness and optic atrophy. Rarely, the tumor can also cause leptomeningeal disease, with raised intracranial pressure manifesting as papilledema.

CT and MRI are good techniques for delineating areas of intraorbital and intracranial spread. Esthesioneuroblastoma, like other neuroectodermal tumors, expresses somatostatin receptors; hence, octreotide radionuclide scanning can also be used for imaging [14]. Definitive diagnosis requires biopsy and immunohistochemical analysis of markers specific for tissues of neural origin, such as neuron-specific enolase, synaptophysin, and chromogranin [15].

Management of esthesioneuroblastoma includes anterior craniofacial surgery with partial orbital resection as indicated, followed by radiation therapy. Orbital exenteration may be required. Chemotherapy is generally used either as an induction therapy or combined with radiation therapy following surgery; chemotherapy is rarely used alone. Follow-up after definitive treatment is essential in managing postsurgical ocular motility defects as well as effects of chemotherapy and radiation therapy. Optic nerve injury can occur during surgery or as a result of radiation therapy. Radiation-induced optic neuropathy can be diagnosed by gadolinium enhancement of the affected nerve on gadolinium-enhanced MRI [16].

30.4.2 Chordoma

Chordoma is a slow-growing tumor of notochordal origin commonly found at either end of the axial skeleton—50% of chordomas are found at the sacrum and 35% at the clivus. Chordomas, which are known to recur and cause local invasion, are primarily extradural in origin, but dural invasion can occur. Chordomas can occur at any age, though one study reported a mean age at presentation of 46 years [17].

An intracranial chordoma is most often located in the clivus, where tumors can cause significant symptoms. As the tumor erodes through the bone, it can cause simultaneous or consecutive bilateral sixth cranial nerve palsies, compression of the brain stem, and affect structures in the cavernous sinus laterally. The tumor may grow antero-superiorly to cause chiasmal compression or pituitary disturbances [18]. It may even erode inferiorly through the sphenoid sinus and present as a nasopharyngeal mass or through the foramen magnum and present with late signs of long-tract palsy and palsies of cranial nerves VIII–XII. Metastasis of sacral chordoma to lungs, skin [19], and even to the orbit has been reported [20].

The most common symptom of chordoma is diplopia due to sixth nerve palsy; other symptoms include increasing in frequency or intensity the following: headaches, visual disturbances (including bitemporal hemianopsia), ataxia, and persistent pain [21]. Signs of ischemia may be seen in the brain stem due to basilar artery compression at the clivus [18]. When the tumor compresses the brain stem, several critical structures of the oculomotor pathway are affected including nuclei of cranial nerve VI and VII, the pontine paramedian reticular formation, and medial longitudinal fasciculus in the pons. When the cavernous sinus is involved, the third, fourth, fifth, and sixth cranial nerves can become involved by tumor, and when in this location, this usually is a contraindication to extensive surgery. The presence of diplopia in patients with chordoma was associated with longer survival [17], probably because of the earlier time of diagnosis as well as the anterior location of the tumor [21]. As this tumor often involves the bone, appropriate thin-cut CT scans through the skull base and contrast-enhanced dynamic MRI are useful [22].

The primary treatment for chordoma is surgical resection, which is often difficult and incomplete due to the location and involvement of adjacent critical structures. In patients with significant cavernous sinus involvement, an aggressive surgical

approach is contraindicated because of the procedure’s related morbidity [21]. New endoscopic approaches are achieving high rates of success and this approach may be less invasive compared with intracranial surgery [23, 24]. Different approaches for management of residual chordoma include stereotactic radiosurgery and proton beam (charged-particle) radiation therapy.

30.4.3 Craniopharyngioma

Craniopharyngiomas account for 2–4% of all intracranial tumors [25]. There is a bimodal incidence peak—tumors are most often diagnosed in patients 5- to 14-years-old and patients 50to 60-years-old. The most common location for these tumors is the suprasellar region, where they grow from the squamous epithelium derived from the Rathke pouch on the undersurface of the brain. Craniopharyngiomas are mostly slow-growing tumors that are usually both calcified and cystic in nature. In children, craniopharyngiomas are the most common tumors in the suprasellar area (54% of suprasellar tumors in children are craniopharyngiomas); in adults, craniopharyngiomas are the second most common suprasellar tumor after pituitary adenoma [26].

Because of their close proximity to the optic nerves, optic chiasm, and optic tract, craniopharyngiomas cause compression of the visual apparatus leading to visual field defects in 40–70% of patients. The classical visual field defect caused by craniopharyngioma is bitemporal hemianopia or inferior bitemporal quadrantanopia. This may be accompanied by central scotoma if optic nerve compression is also present. Other presentations of craniopharyngioma include homonymous hemianopia, unilateral temporal field defects, generalized constriction, or normal fields. Pleomorphism (defined as change from one type of visual field defect to another) may occur with time. This has been attributed to intermittent emptying of cyst fluid into the ventricular system but may be a sign of recurrence, too [25, 27]. Improvement in visual fields following treatment is seen in one-third of patients [25].

The clinical presentation is usually insidious, and visual symptoms are often preceded by neuropsychological symptoms, headache, and/or endocrine dysfunction. In children, the extent of visual loss is often not appreciated until systemic symptoms become apparent. Blurred vision is the most common visual symptom, and headache is the most common systemic complaint. Headaches and visual disturbances are more common in children than in adults. Children under the age of 6 years presenting with visual symptoms have an unfavorable visual prognosis due to a late diagnosis [25]. Visual deterioration resulting in frequent falls may be attributed to clumsiness and ignored by parents. Headache may be due to raised intracranial pressure secondary to hydrocephalus or compression of sellar dura mater. About 66–90% of patients have some degree of endocrine dysfunction; hypothyroidism is the most common. Funduscopy demonstrates optic nerve involvement in the form of optic atrophy accompanied by relative afferent pupillary defect

and deterioration in color vision. Papilledema is more common in children due to hydrocephalus [26]. Chiasmal compression may lead to bow–tie atrophy due to loss of nasal maculopapular bundle fibers and nasal retinal fibers. If raised intracranial pressure occurs following the presence of bow–tie atrophy, edema of the remaining fibers in the superior and inferior poles of the optic dis results in “twin-peak papilledema,” [28]. Occasionally the tumor may start in the suprasellar region but grow posterior to the sella and down the brainstem leading to diplopia as well as other posterior fossa signs.

Neuroimaging by CT demonstrates a calcified cyst, a hallmark of craniopharyngioma. Contrast enhancement of the cyst helps delineate the lesion further. MRI is useful for defining the local anatomy, especially in adults (since calcification is less common in adults than in children), for surgical planning and long-term follow-up. Treatment consists of surgical resection with adjunctive radiation therapy. Children with hydrocephalus may require shunting also. The adamantinomatous type of craniopharyngioma occurs more frequently in children, while the squamous type occurs more frequently in adults; the squamous type of craniopharyngioma seems to be less aggressive and has a lesser incidence of visual field defects. Improvement in visual fields is seen following treatment in one-third of patients [25]. However, compared to pituitary adenoma, craniopharyngioma has a poorer visual outcome as a result of delayed diagnosis and long-standing compression of visual structures. Postoperative complications include hypopituitarism, seizures, and paresis of the third and fourth cranial nerves. Radiation therapy may result in visual field changes that may not be reflected on MRI. Recurrences of tumor occur more commonly in children, who may have more than one episode of recurrence, the mean period of 8 years [25]. Sometimes cystic recurrences are very difficult to treat. There has been few reports of injections within the cyst with agents as interferon with variable results. The duration of symptoms prior to recurrence may be as short as 2 weeks, and symptoms may be similar to those at the initial presentation; blurred vision is the most common symptom. Since the risk of local recurrence is high, MRI is useful for long-term monitoring, but detailed neuro-ophthalmic testing with visual fields is most important for early detection of recurrence [25].

30.4.4 Meningioma

Meningiomas are the most common nonglial primary intracranial tumors and are often discovered in adults in their fourth to sixth decades of life. The incidence is higher in older individuals, in African Americans, and in females (female to male ratio of 2:1) [29]. Ninety percent of all meningiomas occur in the supratentorial compartment, where the parasagittal region and over the convexity are the most common locations [29, 30]. The incidence of skull base meningiomas is 9.3%, according to the National Cancer Data Base (1985–1994) statistics. Meningiomas may be multiple and may be part of a familial autosomal-dominant inherited syndrome, neurofibromatosis type 2 and meningiomatosis [31–33]. Meningiomas originate from arachnoid cap cells commonly found in association with arachnoid

villi at the dural venous sinuses and veins [30, 34]. About 1–2% of meningiomas arise from extradural sites, including primary intraosseous meningioma, which arises from the bone [35]. Treatment is determined primarily by the World Health Organization classification system, a three-tiered system comprised of three grades—meningioma, atypical meningioma, and anaplastic (malignant) meningioma [29].

About 90% of meningiomas are considered histologically benign; the remaining are considered atypical or malignant [36]. The major risk factor for developing meningioma, apart from increased age, is exposure to ionizing radiation, including therapeutic radiation therapy for head and neck neoplasia. The majority of asymptomatic meningiomas can be followed safely with serial brain imaging until the tumor either enlarges significantly or becomes symptomatic [37].

Clinical presentation of a meningioma depends on the tumor’s location. Gradually evolving new-onset headache and an insidious personality change may lead to a long latency before the diagnosis is made and depicts the slow-growing nature of the tumor. Meningiomas may be associated with clinical syndromes of neuro-ophthalmic interest; depending on the size and location of the tumor, meningiomas in the posterior parasagittal region can cause homonymous hemianopia, and if there is impingement of the superior sagittal sinus, there may be raised intracranial pressure with papilledema; sphenoid wing tumors can cause visual loss, trigeminal dysfunction, and/or ophthalmoplegia; suprasellar tumors can cause bitemporal hemianopia and optic atrophy; and olfactory groove meningioma can cause FosterKennedy syndrome usually with loss of smell. Cavernous sinus meningiomas may result in proptosis, diplopia, or primary aberrant oculomotor regeneration [29, 30]. Skull base intraosseous meningiomas are usually slow growing and painless, with symptoms present for months to years prior to diagnosis. These symptoms can include cranial nerve deficits, ophthalmoplegia, visual field problems, proptosis (sometimes proptosis is present only as a result of hyperostosis of the orbital bones) and deformity [35].

Primary optic nerve sheath meningiomas (ONSMs) arise from the optic nerve sheath, intraorbital or intracanalicular optic nerve, or intracranial optic nerve. (Optic nerve tumors are covered in detail in Chapter 31.)

Secondary ONSM is an extension of intracranial meningioma into the orbit. Secondary ONSMs are much more common than primary ONSMs, but the unqualified term “optic nerve sheath meningioma” ordinarily refers to primary ONSM. ONSM is an important cause of visual loss [38]. Occasionally, bilateral or multifocal meningioma and meningiomatosis is seen, with neurofibromatosis type 2 and almost all of these patients also harbor bilateral acoustic neuromas.

Secondary ONSMs arise intracranially from the dura at locations other than the orbit, e.g., sphenoid bone (including the anterior clinoid), on or near the planum sphenoidale, olfactory groove, cavernous sinus, and other locations that spread toward the orbit and within the confines of the optic nerve sheath through the optic canal, compromising function by impairing blood supply to the nerve and interfering with axon transport [38]. The majority of secondary ONSMs are unilateral; however, bilateral cases may occur as a result of spread of a planum sphenoidale