Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Neuro-Ophthalmology_Wright, Spiegel, Thompson_2006

CHAPTER 8: BRAIN LESIONS WITH OPHTHALMOLOGIC MANIFESTATIONS 271

Many patients will complain of headache, particularly if there is increased intracranial pressure. This sign is of no localizing value. Ophthalmologic signs specific for a tumor are rare. Acquired nystagmus, diplopia, ocular motor dysfunction, and papilledema are suggestive of progressive intracranial neoplasm and demand emergent evaluation. These symptoms may be of nontumor etiology.

This survey is divided into tumors of glial origin, neural origin, meningeal origin, and congenital origin.

Tumors of Glial Origin

Gliomas are tumors that arise from neuroglial cells. These cells provide support for neural tissue. In childhood, gliomas comprise 75% or more of primary intracranial tumors.35 Gliomas include astrocytomas, oligodendrogliomas, ependymomas, choroid plexus papillomas, and colloid cysts.

Astrocytomas develop in several areas of the brain: the brainstem, cerebrum, optic pathway, and cerebellum. The tumors in each of these areas have specific biological behaviors. In addition to topographic nomenclature based on the site of origin, astrocytomas have also been divided on the basis of histological differences. The most common type of tumor is a fibrillary astrocytoma. A grading system with the three levels is commonly employed to describe the histological characteristics of fibrillary astrocytomas. Grade 1 is a well-differentiated astrocytoma, grade 2 is an anaplastic, more cellular astrocytoma, and grade 3 is glioblastoma multiforme, which is the most aggressive form with the worst prognosis.7

Most fibrillary astrocytomas during childhood occur in the cerebellum, brainstem, or hypothalamus. These tumors as a rule infiltrate normal brain tissue, preserving functions until late in the disease course. This tendency frequently leads to a delay in diagnosis.

Some fibrillary astrocytomas assume an appearance of parallel tumor cell growth and orientation termed pilocytic. The juvenile form of the pilocytic astrocytoma occurs in children and has a very benign prognosis. This tumor type is particularly common in the optic pathway.

Astrocytoma of the cerebellum is one of the most common childhood brain tumors. These tumors arise from either the vermis or the lateral lobes of the cerebellum. They are well circumscribed and often develop a large cyst. Often the tumor is

CHAPTER 8: BRAIN LESIONS WITH OPHTHALMOLOGIC MANIFESTATIONS 273

FIGURE 8-10. Sagittal MRI of a 4-year-old boy who presented with a left esotropia. Within 2 weeks, he began to have difficulty walking. Note the diffuse enlargement of the pons from a fibrillary astrocytoma. The tumor extends from the thalamus to the medulla.

radiation therapy of 8000 cGy consisting of divided doses delivered twice daily. Chemotherapy has been disappointing. The prognosis is usually quite poor, with a 5-year survival rate of only 20%.39 Typical ophthalmologic signs and symptoms are a horizontal gaze paresis, horizontal nystagmus, trigeminal nerve paresis, and double vision, occurring in approximately 50% of the affected patients.

Astrocytoma of the cerebrum may arise in any portion of any hemisphere. These tumors are often infiltrative so that complete surgical resection is usually impossible. These patients are usually treated with surgical excision, followed in some cases by radiation therapy. Chemotherapy has generally been disappointing. Survival may vary from excellent for patients with benign pilocytic astrocytomas to poor for those patients with glioblastoma. Cerebral astrocytomas, although common in adults, are relatively rare in children. Ophthalmologic signs of

these tumors may include visual field defects and increased intracranial pressure (Fig. 8-11). The most common nonophthalmologic symptom is a seizure disorder.

Astrocytoma of the hypothalamus—in the region of the third ventricle—are quite common in childhood. These children present with hypothalamic dysfunction, visual loss, or both. Clinically, one suspects a primary origin in the hypothalamus when the visual loss is minimal compared to the level of hypothalamic or pituitary axis dysfunction. These tumors are usually of the juvenile pilocytic type. Treatment is usually radiation therapy unless the third ventricle is compromised. A ventricular peritoneal shunting or a surgical debulking of the tumor is needed. A biopsy has been desirable in the past, but modern imaging has made this test no longer mandatory.

Astrocytoma of the optic nerve is one of the most frequent tumors affecting children with ophthalmologic signs and symptoms. These tumors, whether they involve the optic nerve, the optic chiasm, or optic tract, are termed optic gliomas. These tumors are usually of very benign histological appearance (juvenile pilocytic astrocytoma).

Optic nerve gliomas may occur sporadically or be associated with neurofibromatosis type 1 (NF1). In a survey of patients with NF1, the incidence of optic pathway gliomas was found to be as high as 20%, with just less than half involving the optic nerve.25 The ophthalmologic findings are generally decreased visual function, optic disc swelling or pallor, strabismus, and proptosis. Visual loss or optic nerve atrophy occurs in about one-third of children with NF1.2,16,26 Visual loss is more common in the sporadic patients. Gayre and coworkers found visual loss in 63% of the children they have followed.14

A tumor involving the optic nerve usually causes a fusiform enlargement of the nerve. The tumor diffusely replaces the normal neural architecture. In a patient with neurofibromatosis type 1 and an optic nerve glioma, the nerve is enlarged, but much of the tumor is in the subarachnoid space, surrounding and compressing an apparently normal optic nerve. One of the commonly associated findings of optic nerve gliomas is meningeal vascular hyperplasia. The hyperplasia often extends well beyond the limit of the optic nerve involvement. This benign reaction makes it difficult on neuroimaging to accurately determine the true extent of nerve involvement.

Astrocytomas of the chiasm are similar to those of the optic nerve in appearance. Because they lack a meningeal covering,

CHAPTER 8: BRAIN LESIONS WITH OPHTHALMOLOGIC MANIFESTATIONS 275

A

B

FIGURE 8-11A,B. A 16-year-old boy with no visual complaints presented for ophthalmologic evaluation. (A) A coronal MRI demonstrates bilateral astrocytomas infiltrating the lateral geniculate nuclei (arrows). The left lesion has a substantial cystic component. (B) Visual acuity and pupils were normal, but an automated visual field examination demonstrated a dense right homonymous hemianopsia.

FIGURE 8-12. Coronal MRI of optic chiasmatic glioma in a 6-year-old boy. This patient was treated for 20/200 amblyopia for 1 year before his diagnosis. At that time, a right afferent pupillary defect and optic atrophy were noted. Note the compression of the midline third ventricle.

they may have a significant exophytic portion. That portion of the tumor may fill the suprasellar cistern compressing the hypothalamus and third ventricle (Fig. 8-12). These patients have optic atrophy, strabismus, and decreased vision. Six percent of patients with NF1 may harbor a chiasmatic glioma.25 These patients may also develop endocrinopathies from upward extension into the hypothalamus or symptoms of increased intracranial pressure from extension into the third ventricle with compromise of CSF flow. Such extension portends a poorer prognosis.

The diagnosis of optic gliomas involves neuroimaging, particularly magnetic resonance imaging, of the visual pathways. In addition to the optic glioma, MRI may often demonstrate “hamartomatous” lesions of the basal ganglia in patients with

CHAPTER 8: BRAIN LESIONS WITH OPHTHALMOLOGIC MANIFESTATIONS 277

neurofibromatosis. These lesions have disappeared during longterm follow-up.

The natural history of optic nerve and chiasmatic gliomas is uncertain. In some cases, the tumor remains static, in other cases there may be slow growth, while in rare cases there may be rapid growth with invasion of contiguous structures. Wright and colleagues followed 17 patients with optic nerve gliomas.44 Nine of their patients demonstrated no growth of the tumor, while 8 showed enlargement. Patients with neurofibromatosis may have had a slightly more benign prognosis. Hoyt and Baghdassarian described 18 patients with chiasmatic gliomas.16 Only eight eyes showed any deterioration of visual function, suggesting that these lesions do not grow, and may be hamartomas. Imes and Hoyt reported the long-term follow-up (median, 20 years) for 28 patients with chiasmatic glioma, including some from the initial study.18 Five had died, but four deaths were from tumor before 1969, suggesting a static course for most optic gliomas. More troublesome in the Imes and Hoyt report was the high incidence of secondary intracranial tumors, which were responsible for death in a number of patients.18 Perhaps these patients are more prone to tumor development, or did these tumors develop because of the radiotherapy they had received?

The visual prognosis is varied; some patients are unchanged whereas others show a slow loss of vision, even after an extended period of stability.2,14 More striking is a report that has shown that these tumors may even regress spontaneously and the vision improve. Parsa and colleagues presented 13 cases of spontaneous regression with no treatment.30 In many cases, the regression was associated with improvement in visual function.

As the natural history of optic glioma is unknown, the treatment remains controversial. It is impossible with the available tests to predict which tumor will progress. For optic nerve gliomas, appropriate management should be close serial examinations of the patient for evidence of progressive visual loss or tumor enlargement. Such examinations should include neuroimaging at least every 6 months, determination of visual acuity and fields at 3-month intervals for the first year, then at 6-month intervals thereafter. If there is deterioration in visual function or enlargement of the tumor, many authors advocate removal of the optic nerve, usually using a combined orbito- tomy-craniotomy approach. However, surgical resection should be undertaken only when necessary, usually due to extreme proptosis, in light of the reports of spontaneous regression.30 If

both optic nerves or the chiasm are involved, radiation therapy is the most appropriate therapeutic approach.

For optic chiasm glioma, a biopsy is performed only when there is an atypical presentation or a need to debulk an exophytic portion of the tumor because of compression of normal structures (see Fig. 8-12). There does not seem to be a deleterious effect on visual function from removal of such an exophytic portion. These patients, like those with optic nerve tumors, are followed very carefully for radiologic enlargement or visual deterioration. If there is either radiologic expansion or visual deterioration, treatment usually consists of chemotherapy for children less than age 4 and radiotherapy for older children.29 Vincristine and carboplatin are the agents typically used.

Ependymomas are the third most frequent childhood brain tumor, with a peak incidence occurring early in life. Ependymomas arise from the ependymal cells of the lining epithelium of the ventricles, cerebral aqueduct, and spinal canal. The most common location for such a tumor in childhood is the fourth ventricle. The tumor characteristically occludes the ventricle, producing increased intracranial pressure. It may infiltrate normal tissues or extend into the cerebellopontine angle. About 11% of patients have metastasis to other parts of the craniospinal axis at the time of their presentation.31 The treatment is partial surgical resection, followed by radiation therapy to the tumor bed with additional treatment to the whole brain and spinal cord. The survival rate for this tumor is variable, depending on the histology and extent of surgical resection.

Colloid cysts of the third ventricle are also tumors of glial origin. These tumors produce symptoms of increased intracranial pressure including papilledema and abduction weakness. These tumors are benign. They may be diagnosed by MRI. The treatment is resection.

Choroid plexus tumors usually occur in the lateral ventricles of children, less frequently in the third or fourth ventricles. These tumors often secrete excess CSF, producing hydrocephalus and papilledema. Most tumors have a benign histological appearance. The mainstay of treatment is complete surgical resection. If the tumor is only partially resected, craniospinal irradiation is necessary.

Oligodendrogliomas are usually located in the cerebral hemispheres but may occur in any part of the brain. They are usually of benign histological appearance and often calcified. Due to their location in the hemispheres, the ophthalmologic

which is often calcified. A medulloblastoma may obliterate the fourth ventricle and infiltrate the cerebellum, the brainstem, and the meninges. It may also metastasize to any location bathed by CSF. There is usually a brief history of headache and vomiting from increased intracranial pressure. There may also be ocular motor signs from infiltration of the brainstem and disruption of ocular motor nuclei and their interconnections. Such signs include internuclear ophthalmoplegia, gaze palsy, and ocular motor neuropathy.

Medulloblastomas are highly malignant with a poor prognosis. Treatment consists of an aggressive resection followed by craniospinal irradiation. Chemotherapy is also employed, particularly in younger patients. The survival rate for 5 years is approximately 50%.10

Other tumors of neuronal origin include neuroblastomas, which may arise in the central nervous system but are quite rare. Most CNS neuroblastomas occur during childhood. They have a poor prognosis. Only approximately 30% of patients are alive at 5 years.4

Gangliogliomas are benign tumors, usually occurring in the third ventricle, which often present with hypothalamic dysfunction or noncommunicating hydrocephalus. Because of their location, they might be confused with optic glioma. The ophthalmologist may help in the diagnosis, because usually the visual function is better than with optic gliomas and there is little optic atrophy.

Tumors of Meningeal Origin

Tumors of the meninges are very rare in childhood and represent only a small percentage of tumors during childhood and the teenage years.35 There is no sex predilection observed for the tumors presenting in childhood, in contrast to the female predilection in adulthood. Meningiomas may have a more aggressive behavior in childhood than they have in adulthood. The tumors arise from the arachnoid layer of the meninges and may have an intracranial, intraspinal, or intraventricular location. There is a striking association with NF1. A patient with neurofibromatosis often has multiple foci of meningioma as well as other intracranial tumors such as acoustic neuromas, neurofibromas, and gliomas.

Intracranial meningiomas may produce symptoms because of mass effect, direct compression of the tumor on brain tissue