other neuroectodermal tumors, such as neuroblastomas, medulloblastomas, and pinealoblastomas. They are uncommon and occur most often in children under 5 years of age. In general, the duration of symptoms to diagnosis is short, with an average of 3 months.325,874

PNETs are sharply delineated from surrounding brain tissue and are cystic, with hemorrhagic features on gross inspection. Microscopically, they are highly cellular tumors composed of very poorly differentiated small cells (90–95%) with a high nuclear-to-cytoplasmic ratio. Focal areas of differentiation along neural or glial lines and a prominent mesenchymal component may be present. Their cell of origin is impossible to identify with certainty, but ultrastructural studies show resemblance to the developing cortical plate of the fetus, suggesting an origin from primitive undifferentiated neuroectoderm of the cerebrum.

The clinical presentation depends upon the location and growth rate of the tumor. The most common presentations include signs and symptoms of increased intracranial pressure, seizures, and long tract signs. Strikingly, some children may be relatively asymptomatic despite a huge tumor mass and may be spared severe neurological symptoms and signs (with the exception of papilledema and an inappropriate affect) until death.194 Motor deficits such as hemiparesis or paraparesis are common. Visual field abnormalities and papilledema are the most common neuro-ophthalmologic findings.

MR imaging reveals a sharply defined tumor due to relative lack of edema and the presence of enhancement.306 Because the tumors sometimes show extensive calcification, CT scanning without contrast may be a useful adjunct to MR imaging.

Although aggressive treatment with surgery, radiation, and chemotherapy has been attempted, the prognosis remains poor irrespective of treatment modality. The average 5-year survival is, at best, 20%.

Posterior Fossa Tumors

Medulloblastoma

Medulloblastomas are otherwise known as the PNETs of the posterior fossa.318 They are the most common posterior fossa tumor in childhood, comprising approximately 40% of all such tumors.170,395 The incidence peaks around 5 years of age. Boys are affected somewhat more frequently than girls in most series. Children are usually diagnosed shortly after the onset of symptoms. Cushing’s217 description of the clinical course of a child with cerebellar medulloblastoma provides a graphic portrait of this disease: “A pre-adolescent child

previously in good health begins to complain of headaches or of suboccipital discomfort and to have occasional attacks of vomiting without preliminary nausea, usually on first arising in the morning. Attendance at school meanwhile may continue, but the teacher soon notices that the child is listless, inattentive, and the character of his work noticeably falls off. Ere long it is apparent that there is some unwanted clumsiness in movement and awkwardness in gait. The mother may find that the child quickly outgrows its caps and she thinks the head enlarges unduly fast. In course of time it is noticed, at home or in school, that the child’s sight is impaired; or a beginning squint of one eye may be detected, even in the absence of any complaint of double vision. The family doctor, who has previously suspected some gastrointestinal disorder, may then have the eye grounds examined and, to the surprise and shock of everyone, a choked disc is found. Three or four months, on the average, have elapsed, and at about this stage of the malady, many cases come under hospital care.”

The most common presenting symptoms are nausea, vomiting, and headaches due to increased intracranial pressure.675 This arises as the tumor grows and impinges on the roof of the fourth ventricle, causing obstruction to CSF flow. Vomiting is the most common presenting sign of cerebellar tumors and may also arise independently of intracranial pressure by direct tumor pressure on the area postrema (vomiting center), located near the inferior aspect of the fourth ventricle. Other abnormalities include papilledema, diplopia, and nystagmus. Unilateral and bilateral internuclear ophthalmoplegia have been reported, arising either from brainstem neoplastic infiltration or compression.26 In addition, older children and adults may initially present with ataxia, while infants may initially present with increasing head size due to hydrocephalus.

Most medulloblastomas are located in the midline of the cerebellum. They are considered to be congenital in nature, deriving from remnants of the fetal external granular layer of the cerebellum or the medullary velum. Medulloblastomas are highly cellular tumors composed of primitive, undifferentiated, small, round cells with abundant mitoses. Homer– Wright pseudorosettes are typically found. They are highly malignant tumors, showing local invasiveness as well as a high tendency, perhaps more than any other tumor, to seed the subarachnoid space. Extraneural metastasis to bone, lymph nodes, or viscera may arise as a result of tumor manipulation or shunting. The putative congenital origin of medulloblastoma has led some authors to use Collins’ rule to predict its course.94 This rule predicts that the period of risk for recurrence of a tumor of embryonal origin after treatment is the patient’s age at the time of diagnosis plus 9 months.

CT scanning classically reveals a well-defined, hyperdense tumor of the vermis. Isolated hemispheric involvement is rare in children.774 The hyperdensity of the tumor arises from its

Fig. 11.16  Cerebellar medulloblastoma. (a) Sagittal T1-weighted MR image shows mass with lower intensity than brain parenchyma (arrowheads). Mass occupies fourth ventricle. (b) Axial T1-weighted image shows mass filling of fourth ventricle (arrowheads). (c) Coronal

T1-weighted MR image shows uniform tumor enhancement (arrows). (d) Sagittal T1-weighted MR image of same patient after treatment consisting of surgical excision, radiation, and chemotherapy

composition by small, round cells with a high nuclear-to-cyto- plasmic ratio. The tumor enhances diffusely with contrast. Unlike cerebellar astrocytomas, cysts are uncommonly seen, and unlike cerebellar ependymomas, calcification is seen in less than 10% of cases. The MR appearance is variable and nonspecific (Fig. 11.16). The T2-weighted are hypointense or isointense to gray matter,595 which reflects the tumor composition of increased nuclear-to-cytoplasmic ratio and, hence, reduced water content. The heterogeneity of the MR signal results from cysts and calcification within the tumor mass.

The management is complex and includes various combinations of surgical excision, irradiation, and chemotherapy.285 However, in comparison with all malignant brain tumors, the outlook has improved most dramatically for children with medulloblastomas. This is largely due to the use of craniospinal rather than local radiotherapy, with the addition of

chemotherapy in selected patients. Because leptomeningeal dissemination is common, a staging workup of the neuroaxis is now advocated for guiding postoperative management.241 Through continued refinement in chemotherapy and radiotherapy, both progression-free survival and overall survival have improved to 80%.675

Cerebellar Astrocytoma

Astrocytomas are the most common brain tumors in children. They tend to occur in various locations, both infratentorially and supratentorially. Cerebellar astrocytomas may occur anywhere in the cerebellum, including the vermis, the hemispheres, or both. Cerebellar astrocytomas show no gender predilection and tend to develop in a slightly older age group than medulloblastomas,

generally peaking in incidence in the latter half of the first decade.227,328

The early presentation of affected children consists of early morning headaches and vomiting due to increased intracranial pressure. Vomiting generally occurs in the morning and may occur without nausea. After vomiting, the child may feel well for the rest of the day, with a repeat performance the following morning. Because the symptoms are recurrent, the child may undergo gastrointestinal evaluation before a correct diagnosis is finally made. As the tumor enlarges, the headaches become persistent. Neurologic symptoms may help predict the location of the tumor. The child with a midline cerebellar tumor presents with truncal ataxia, whereas the child with cerebellar hemispheric tumor shows appendicular signs (e.g., dysdiadochokinesia, dysmetria). Children may show apathy, irritability, and neck stiffness and pain and may develop attacks of unconsciousness (so-called “cerebellar fits”). Because of the insidious nature of the symptoms, some children have few or no complaints until late in the disease, despite the presence of a large tumor, with papilledema as the only abnormal finding. The average duration of symptoms before diagnosis is approximately 18 months, compared with only 5 months in medulloblastoma.

The most common neuro-ophthalmologic abnormalities are papilledema, diplopia, and nystagmus. Coarse nystagmus to the side of the lesion is of localizing value and should be distinguished from vestibular nystagmus, which is directed to the side opposite the lesion. The presence of a sixth nerve palsy may be a false localizing sign indicating increased intracranial pressure or may signal neoplastic invasion of the brainstem, the latter usually accompanied by hyperreflexia and Babinski responses. Children may have torticollis if brainstem involvement results in fourth nerve palsy.

Cerebellar astrocytomas are generally noninvasive, welldemarcated tumors.790 Mitoses are conspicuously absent and, when present, suggest a malignant astrocytoma. Approxi­ mately 80% of cerebellar astrocytomas are cystic, showing either a large cyst with a solid mural nodule or multiple smaller cysts. Microscopic or gross calcification is present in up to 25% of cases. At least two histologic types exist. The most common form (termed the juvenile variety) consists of areas of compact, fibrillated cells with abundant Rosenthal fibers alternating with loose spongy areas composed of microcysts. Rosenthal fibers are eosinophilic, beaded, or cigarshaped swellings of astrocytes that represent a benign degenerative process. The second type is a diffuse form, consisting of fibrillated stellate or piloid cells, identical to that encountered in cerebral astrocytomas. The juvenile form has a considerably better prognosis than the diffuse form. Early recurrence and poor survival is also associated with brainstem invasion and onset before 4 years of age.

The presence on CT scanning of a low-density mass, typically within the cerebellar hemispheres, often with a cystic component, is suggestive of a cerebellar astrocytoma. The presence of an enhancing nodule on CT scanning adjacent to the cyst is a compelling evidence of the diagnosis. On MR imaging, the tumor signal is nearly always hypointense to the surrounding cerebellum on T1-weighted imaging and hyperintense and generally homogenous in appearance on proton density and T2-weighted imaging (Fig. 11.17).

Cerebellar astrocytomas have the best overall prognosis of any childhood brain tumor.860 The preferred treatment of cerebellar astrocytomas is complete surgical resection.514,894 If this is accomplished, the 10-year survival rate exceeds 90%. If only incomplete excision is possible due to the invasion of critical surrounding brainstem parenchyma, patients may be observed expectantly for tumor progression before radiotherapy is considered.

Ependymoma

Intracranial ependymomas, which account for about 12% of pediatric brain tumors, may arise from any region of the ventricular system, but most childhood ependymomas are located in the posterior fossa.893 The average age at diagnosis is 5 or 6 years.741 Unlike medulloblastomas, the diagnosis is usually delayed as a result of the insidious onset of symptoms.207

Posterior fossa ependymomas arise from differentiated ependymal cells that line the roof, floor, or lateral recesses of the fourth ventricle. Most are solid in nature, but some are very soft and deformable. Therefore, in contrast with most other brain tumors that grow as steadily enlarging masses, ependymomas can wrap themselves around various structures in their vicinity and become quite adherent to the adjacent brain. They also have a tendency to exit through the foramina of Magendie and Luschka into the subarachnoid space.558

In general, posterior fossa ependymomas present with signs and symptoms of increased intracranial pressure (due to obstruction of the fourth ventricle) and unsteady gait.487,893 The growth characteristics of these tumors render them more likely to present with neuro-ophthalmologic manifestations than other posterior fossa tumors. Invasion of the cerebellum, brainstem, or cerebellopontine angle produce corresponding neurological abnormalities that include nystagmus, ocular motor nerve palsies, and internuclear ophthalmoplegia. Brodsky and Boop125 described a 3-year-old boy with unilateral Duane syndrome who was found to have a large ependymoma that was compressing the floor of the fourth ventricle.

Torticollis may result from the involvement of the trochlear nerve or may accompany neck pain and stiffness from encroachment of the tumor on the upper cervical nerve roots. Spinal cord ependymomas are a well-recognized but readily overlooked cause of papilledema.578 Ependymomas are cellular tumors with a regular histologic pattern. Ependymal rosettes are diagnostic and are composed of tumor cells lined around a central lumen. Perivascular pseudorosettes are common, and cilia may be present. Two grades of ependymomas are recognized: a benign or differentiated ependymoma and a malignant or anaplastic variety. The anaplastic variety has typical features of ependymomas but also has pleomorphism, necrosis, increased cellularity, mitoses, and giant cells. Anaplastic ependymomas are more common in the supratentorial regions.

A posterior fossa ependymoma appears on CT scanning as a hyperdense or isodense fourth ventricular mass with punctate calcifications, small cysts, and moderate enhancement with contrast. Extension of the mass through the fourth ventricular foramina or the foramen magnum further supports the diagnosis. The MR imaging signals may be heterogeneous or homogenous, depending on the presence of calcification, hemorrhage, or cysts (Fig. 11.18).841

Posterior fossa ependymomas are quite difficult to surgically excise in their entirety and have a high recurrence rate after surgery.386 Although gross total resection has been widely accepted as an important prognostic factor,589 many children experience recurrence despite gross total resection,352,837 and only slightly more than half of children are

long-term survivors of this cancer. This is compounded by the tendency of the tumor to seed the CSF pathways, including the spinal subarachnoid space. While radiation therapy is standard for cases in which the tumor communicates with the ventricular system, it has deleterious effects on the developing brain, producing neurocognitive defects that may be mitigated by conformal radiotherapy.589,675

A neuro-ophthalmologic syndrome of visual impairment with mutism may follow posterior fossa surgery in children.545 Following suboccipital craniotomy (usually for removal of medulloblastoma or ependymoma), these children become withdrawn without verbal output and exhibit impaired visual behavior mimicking cortical visual loss. These children fail to blink to a threat or follow objects.545 Pupillary activity remains normal and retinal examination reveals only papilledema. Neuroimaging discloses no lesions of the retrogeniculate pathway. The prognosis for visual recovery is excellent and parallels the return of normal speech. The mechanism is unclear.545

Brainstem Tumors

Brainstem gliomas represent about 15% of pediatric CNS tumors.428 The mean age at diagnosis is 7–9 years, with no gender predilection.541 Diffuse gliomas are the most commonly encountered brainstem tumor, accounting for 58–75% of all tumors.9,276 Children with diffuse brainstem gliomas

invariably have a rapidly progressive course. They often present acutely with multiple cranial nerve signs, ataxia, long tract signs, and cerebellar signs. Current management options for these tumors are limited to radiotherapy, with or without adjuvant chemotherapy. Systemic chemotherapy has been used, albeit with unproven efficacy. These tumors show a variable clinical presentation but a uniformly poor outcome by virtue of their location. The pons is the most common site of origin of brainstem gliomas, followed by the midbrain and the medulla.573,659 The prognosis is dismal.675 Most children die within 18 months of diagnosis, similar to the clinical course for glioblastoma multiforme.8,541

Brainstem tumors are suggested by the triad of long tract signs, cranial neuropathies, and ataxia. In addition, brainstem gliomas should be considered in the differential diagnosis of

an infant with failure to thrive who has facial paresis, absent cough reflex during suctioning, or a depressed gag reflex. The cranial nerves most commonly affected are the sixth and seventh nerves, and the two are often present together. The most common neuro-ophthalmologic symptom is diplopia due to involvement of the ocular motor nerves.

Seesaw nystagmus in a patient with brainstem tumor localizes the tumor to the region of the diencephalon. The presence of a third or fourth cranial nerve palsy, diffuse ophthalmoplegia, the various features of Parinaud syndrome in any combination, or profound hydrocephalus suggests a mesencephalic component to the tumor. Occasionally, diffuse ophthalmoplegia due to mesencephalic involvement simulates myasthenia gravis clinically as well as by showing a false-positive response to Tensilon.123,711 Convergence palsy

may accompany midbrain tumors or tumors of the pineal region. Primary position upbeat nystagmus has been observed in tumors at the pontomesencephalic junction.884

Horizontal eye movement abnormalities (horizontal gaze paresis due to involvement of the abducens nuclei or the paramedian pontine reticular formation, internuclear ophthalmoplegia, one-and-a-half syndrome) are features of pontine involvement.192 Pontine horizontal gaze abnormalities may be associated with ipsilateral facial palsy and contralateral hemiparesis. Pontine gliomas have been reported to cause chronic isolated sixth nerve palsy.327 An associated sixth nerve palsy may also occasionally show spontaneous improvement. Asymmetry of the palate, absent gag reflex, atrophy of the tongue, and various other bulbar signs, including swallowing and feeding abnormalities, indicate medullary involvement. Vomiting, unaccompanied by headache, may occur due to direct infiltration of the emesis center in the medulla. Ataxia may result from direct cerebellar involvement or, more likely, from the compromise of cerebellar pathways passing through any of the cerebellar peduncles. Rarely, brainstem tumors have been associated with congenital ocular motor apraxia.968

In contrast with the cerebellar tumors discussed, hydrocephalus and signs and symptoms of increased intracranial pressure are quite uncommon in pontine glioma until late, despite significant enlargement of the brainstem and even bulging of the enlarged brainstem into the fourth ventricle. However, tectal and tegmental gliomas may present with headaches and increased intracranial pressure due to compression and obstruction of the sylvian aqueduct.

Duration of symptoms until diagnosis varies widely, from several weeks to several years. Biopsy is seldom necessary because MR imaging is diagnostic.675 Although the natural

history is one of inexorable progression, there are a few reports of brainstem tumors showing a remitting and exacerbating course.778 This presentation may be mistaken for a demyelinating or parainfectious disorder. Presumably, these remissions result from resolution of edema or necrosis in the area of the tumor.

Most brainstem gliomas are fibrillary astrocytomas similar to those found in the cerebral hemispheres; only a small minority are pilocytic in nature. The tumor cells are seen to intermingle with neurons and nerve fibers on histopathologic examination, infiltrating along these structures rather than destroying them. This may explain the relative preservation of various neural functions in the brainstem despite apparent diffuse involvement of the brainstem structures. It is not unusual for the child with a pontine glioma to present initially to the ophthalmologist for evaluation of a horizontally incomitant esotropia or a face turn resulting from a sixth nerve palsy. If such a child has an initially negative neuroimaging study, reimaging for a possible pontine glioma is indicated if the palsy fails to completely resolve within 6 months.

Brainstem tumors are much more easily identified with MR imaging than CT scanning (Fig. 11.19). CT scanning typically shows an expanded brainstem that is hypodense or isodense to the surrounding brainstem.87 MR imaging shows a brainstem mass that is hypointense on T1-weighted images and hyperintense on T2-weighted images. T2-weighted images are especially useful for detecting tumor infiltration into surrounding structures.307 Other characteristic findings include obscuration of the pons with no contrast enhancement, and engulfment of the basilar artery by tumor.257 Diffuse tumors enlarge the brainstem smoothly, without focal areas of exophytic growth, and have a worse prognosis.