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MAJOR CATEGORIES OF NEUROLOGIC DISEASE
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but intravascular lymphoma is generally more rapidly progressive than most of these conditions Sarcomas of the Brain These are malignant tumors composed of cells derived from connective tissue elements ( broblasts, rhabdomyocytes, lipocytes, osteoblasts, smooth muscle cells) They take their names from their histogenetic derivation namely, brosarcoma, rhabdomyosarcoma, osteogenic sarcoma, chondrosarcoma and sometimes from the tissue of which the cells are a part, such as adventitial sarcomas and hemangiopericytoma All these tumors are rare They constitute from 1 to 3 percent of intracranial tumors, depending on how wide a range of neoplasms one chooses to include in this group (see below) Occasionally one or more cerebral deposits of these types of tumors will occur as a metastasis from a sarcoma in another organ Others are primary in the cranial cavity and exhibit as one of their unique properties a tendency to metastasize to nonneural tissues a decidedly rare occurrence with primary glial tumors It is a disturbing fact that a few sarcomas have developed 5 to 10 years after irradiation or, in one instance among 3000 patients of which we are aware, after proton beam irradiation of the brain Fibrosarcomas have occurred after radiation of pituitary adenomas and osteogenic sarcoma after other types of radiation, all localized to bone or meninges Our experience with hemangiopericytoma has been limited to two intracranial lesions that simulated meningiomas and two others that arose in the high cervical spinal cord and caused subacute quadriparesis initially misdiagnosed as a polyneuropathy A number of other cerebral tumors, described in the literature as sarcomas, are probably tumors of other types The rapidly growing, highly malignant monstrocellular sarcoma of Zulch or gi ant-cell brosarcoma of Kernohan and Uihlein, so named for their multinucleated giant cells, have been reinterpreted by Rubinstein as a form of giant-cell glioblastoma or mixed glioblastoma and brosarcoma The hemangiopericytoma of the leptomeninges, also classi ed by Kernohan and Uihlein as a form of cerebral sarcoma, is considered by Rubinstein to be a variant of the angioblastic meningioma of Bailey and Cushing
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Patients Who Present Primarily with Signs of Increased Intracranial Pressure
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Upon rst presentation, a number of patients show the characteristic symptoms and signs of increased intracranial pressure: periodic bifrontal and bioccipital headaches that awaken the patient during the night or are present upon awakening, projectile vomiting, mental torpor, unsteady gait, sphincteric incontinence, and papilledema Most of these symptoms and the increased ICP are the result of hydrocephalus The diagnostic problem is resolved by CT or MRI, which should be obtained in all patients with symptoms of increased intracranial pressure with or without focal signs The tumors most likely to present in this way are medulloblastoma, ependymoma of the fourth ventricle, hemangioblastoma of the cerebellum, pinealoma, colloid cyst of the third ventricle, and less often, craniopharyngioma or a high spinal cord tumor In addition, with some of the cerebral gliomas discussed in the preceding section, increased intracranial pressure may occasionally precede focal cerebral signs Medulloblastoma, Neuroblastoma, and Retinoblastoma Medulloblastoma The medulloblastoma is a rapidly growing embryonic tumor that arises in the posterior part of the cerebellar
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vermis and neuroepithelial roof of the fourth ventricle in children It accounts for 20 percent of childhood brain tumors Rarely, it presents elsewhere in the cerebellum or other parts of the brain in adults (Peterson and Walker) The origin of this tumor remained in doubt for a long time Bailey and Cushing introduced the name medulloblastoma, although medulloblasts have never been identi ed in the fetal or adult human brain; nevertheless the term is retained for no reason other than its familiarity The current view of the tumor is that it originates from stem cells that have been prevented from maturing and differentiating to their normal growth-arrested state They retain their capacity to divide ad in nitum The tumor may differentiate uni- or pluripotentially, varying from case to case This accounts for the recognized histologic variants, ranging from the undifferentiated medulloblastoma to medulloblastoma with glial, neuronal, or even myoblastic components Rosette formation, highly characteristic of the below-described neuroblastoma is seen in half of medulloblastoma cases Molecular genetic qualities relate the medulloblastoma to retinoblastomas and certain pineal cell tumors and, rarely, to certain autosomal dominant diseases such as nevoid basal cell carcinoma The most common histologic variant, recognized by Hortega in his classic work on the histology of brain tumors, is the isomorphic glioblastoma, from which both astrocytes and oliogodendrocytes are derived Studies of cell lines from human medulloblastomas reveal a loss of genetic information on the distal part of chromosome 17 distal to the p53 region Schmidek has proposed that this accounts for the neoplastic transformation of cerebellar stem cells, at various stages of their differentiation, into tumor cells It is also notable that medulloblastomas are encountered in Gorlin syndrome, caused by mutations in the gene encoding patched, the receptor for sonic hedgehog ligand, and in Turcot syndrome, due to mutations in DNA repair genes (Louis et al) Another line of research has strongly implicated the JC virus, the same agent that causes progressive multifocal leukoencephalopathy (Chap 33) Genomic sequences from this virus have been found in 72 percent of tumors in some series (Khalili et al), and an experimental transgenic model in which the JC protein is expressed is characterized by a cerebellar tumor that resembles the medulloblastoma Neuroblastomas differ from medulloblastomas when analyzed for genetic markers, as indicated below The majority of the patients are children 4 to 8 years of age, and males outnumber females 3:2 or 3:1 in the many reported series As a rule, symptoms have been present for 1 to 5 months before the diagnosis is made The clinical picture is distinctive and derives from secondary hydrocephalus and raised intracranial pressure as a result of blockage of the fourth ventricle Typically, the child becomes listless, vomits repeatedly, and has a morning headache The rst diagnosis that suggests itself may be gastrointestinal disease or abdominal migraine Soon, however, a stumbling gait, frequent falls, and diplopia as well as strabismus lead to a neurologic examination and the discovery of papilledema or sixth nerve palsies Papilledema is present in all except a small proportion of patients by the time they come to the attention of the neurologist However, when the tumor is located in the lateral cerebellum or in the cerebrum, as it usually is in adults, signs of raised intracranial pressure may be delayed Dizziness (positional) and nystagmus are frequent A small proportion of these children have a slight sensory loss on one side of the face and a mild facial weakness Head tilt, the occiput being tilted back and away from the side of the tumor, indicates a developing cerebellar-foraminal herniation Rarely, signs of spinal root and subarachnoid metastases precede cerebellar
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