Porth's Essentials of Pathophysiology, 4e

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Disorders of Brain Function

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presenting symptoms, occur in about 65% of patients; hemiparesis, aphasia, and visual field deficits in about 50%; and seizures in 15% to 20%. MetastaticTumors Metastatic tumors, mostly carcinomas, affect approxi- mately 20% to 40% of persons with cancer. 50 The five most common sites for metastasis are the lung, breast, skin (melanoma), kidney, and gastrointestinal tract. 1,52,53 Within the brain there is regional selectiv- ity for growth metastasis from the different primary types of cancer: melanoma is more typically found in the frontal and temporal lobes, breast cancer in the cerebellum and basal ganglia, and non–small cell lung cancer in the occipital lobe. Thus, it appears that tumor-specific interactions with brain tissue mediate the establishment and proliferation of brain metas- tasis. Recent investigations have begun to elucidate the mechanisms of such molecular mechanisms. For women with breast cancer, hormone receptor and human epidermal growth factor receptor-2 status is predictive of brain metastasis risk. 50 Clinically evident brain metastases present with signs of increased ICP, mental status changes, seizures, and focal neurologic deficits. Management of persons with CNS metastasis consists of symptomatic and definitive therapies. The mainstays of symptomatic control are corticosteroids for tumor-related edema, antiepileptic drugs for seizure control, and multidisciplinary inter- ventions aimed at minimizing neurologic disability. 50–52 Manifestations The clinical manifestations of brain tumors depend on the size and location of the tumor. General signs and symptoms include headache, nausea, vomiting, mental changes, papilledema, visual disturbances (e.g., dip- lopia), alterations in sensory and motor function, and seizures. 7,47 Because the volume of the intracranial cav- ity is fixed, brain tumors cause a generalized increase in ICP when they reach sufficient size or produce edema. Cerebral edema usually is of the vasogenic type, which develops around the tumors and is characterized by an increased extracellular fluid volume. The edema is thought to result from increased permeability of tumor capillary endothelial cells. Tumors can also obstruct the flow of CSF in the ventricular cavities and produce hydrocephalic dilation of the proximal ventricles and atrophy of the cerebral hemispheres. With very slow- growing tumors, complete compensation of ventricular volumes can occur, but with rapidly growing tumors, increased ICP is an early sign. The brain itself is insensitive to pain. The headache that accompanies brain tumors results from compres- sion or distortion of pain-sensitive dural or vascular structures. It may be felt on the same side of the head as the tumor, but more commonly is diffuse. In the early stages, the headache is mild and occurs in the morning on awakening and improves with head elevation. The headache becomes more constant as the tumor enlarges

It depends on the histologic grade of the tumor, its loca- tion, and, more recently, recognition of molecular fea- tures that can be linked to chemosensitivity. 50 Due to their delicate vasculature, the oligodendroglial tumors are prone to spontaneous hemorrhage. Ependymomas. Ependymomas are derived from the single layer of epithelium that lines the ventricles and spinal canal. Although they can occur at any age, they are most likely to occur in the first two decades of life and most frequently affect the fourth ventricle; they con- stitute 5% to 10% of brain tumors in this age group. 1 In adults, the spinal cord is the most common location. The clinical features depend on the location of the neo- plasm. Intracranial tumors are often associated with hydrocephalus and evidence of increased ICP. Medulloblastomas Tumors of neuronal origin (e.g., medulloblastomas) usually occur during infancy and childhood. 48 This is in accord with the principle that a cell must be capable of replication to undergo neoplastic transformation. Medulloblastoma is thought to originate from a primi- tive cell type in the cerebellum arising from one of two cerebellar germinal zones: the ventricular zone that forms the outermost boundary, or the external germinal layer that lines the outside of the cerebellum. Medulloblastomas have a bimodal distribution, peak- ing at 3 or 4 years of age and then again at 8 or 9 years of age. 48 Children usually present with signs and symp- toms of increased ICP (i.e., headache, nausea, vomiting, mental status changes, hypertension) and cerebellar dys- function (i.e., ataxia, balance problems, movement disor- ders). The tumor is highly malignant, and the prognosis for untreated children is dismal. However, the tumor is highly radiosensitive; with total excision and irradiation, the 5-year survival rate is as high as 75%. Meningiomas Meningiomas develop from the meningothelial cells of the arachnoid and are outside the brain. They usually have their onset in the middle or later years of life and constitute approximately 20% of primary brain tumors in this age group. 1 Meningiomas are slow-growing, well- circumscribed, and often highly vascular tumors. They usually are benign, and complete removal is possible if the tumor does not involve vital structures. Primary Central Nervous System Lymphomas Primary CNS lymphomas have increased in incidence by a factor of 10 in the past several decades. 1,4 These deep, periventricular, and diffuse tumors are especially com- mon in immunocompromised persons, including those with acquired immunodeficiency syndrome (AIDS) and immunosuppression after transplantation. Most primary brain lymphomas are of B-cell origin. Primary lymphomas of the CNS are highly aggressive, and recurrence is common despite treatment. Behavioral and cognitive changes, which are the most common