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183 TUMORS OF THE NERVOUS SYSTEM

183 TUMORS OF THE NERVOUS SYSTEM
Harrison’s Manual of Medicine

183

TUMORS OF THE NERVOUS SYSTEM

Laboratory Evaluation
Intracranial Tumors
Complications of Radiation Therapy
Bibliography

Brain tumors present with: (1) progressive focal neurologic deficits, (2) seizures, or (3) “nonfocal” neurologic disorders (headache, dementia, personality change, gait disorder). Systemic symptoms (malaise, anorexia, weight loss, fever) suggest metastatic rather than primary brain tumor.

Focal neurologic deficits—due to compression of neurons or white matter by tumor, or edema

Seizures—caused by stimulation of excitatory or loss of inhibitory cortical circuits

Nonfocal neurologic disorders—due to increased intracranial pressure (ICP), hydrocephalus, or diffuse tumor spread

Headache—caused by focal irritation/displacement of pain-sensitive structures or increased ICP. Elevated ICP suggested by papilledema, impaired lateral gaze, headache that intensifies with recumbency

Strokelike onset—may reflect hemorrhage into tumor
Brain tumors may be large at presentation if located in clinically silent region (i.e., prefrontal) or slow-growing; diencephalic, frontal, or temporal lobe tumors may present as psychiatric disorder.
Laboratory Evaluation
Primary brain tumors have no systemic features of malignancy, unlike metastases. CSF exam is limited to diagnosis of possible meningitis or meningeal metastases but may cause brain herniation in setting of a large brain mass or obstructive hydrocephalus. Neuroimaging reveals mass effect (volume of neoplasm and surrounding edema) and contrast enhancement (breakdown of blood- brain barrier permitting leakage of contrast into brain parenchyma).

TREATMENT
Symptomatic Treatment   Glucocorticoids (dexamethasone 12–20 mg/d in divided doses) to temporarily reduce edema; prophylaxis with anticonvulsants (phenytoin, carbamazepine, or valproic acid) for tumors involving cortex or hippocampus. Low-dose subcutaneous heparin for immobile patients.

Intracranial Tumors
The only known risk factor is ionizing radiation. Adverse effects of primary brain tumors are caused by local growth. Biopsy is essential for tissue diagnosis.
Astrocytomas   Most common primary intracranial neoplasm. Prognosis poor if age >65 years, poor baseline functional status, high-grade tumor. Difficult to treat; infiltration along white matter pathways prevents total resection. Imaging studies fail to indicate full tumor extent. Surgery for pathologic diagnosis and to control mass effect. Survival ranges from an average of 93 months for low-grade tumors to 12 months for high-grade tumors. Radiation therapy (RT) prolongs survival and improves quality of life. Systemic chemotherapy with nitrosoureas is only marginally effective, often employed as adjunct to RT for high-grade gliomas. Role of stereotaxic radiosurgery (single dose, highly focused radiation—gamma knife) unclear; most useful for tumors ❤ cm in diameter. Interstitial brachytherapy (stereotaxic implantation of radioactive beads) reserved for tumor recurrence; associated with necrosis of normal brain tissue. For low-grade astrocytoma, optimal management is uncertain.
Oligodendrogliomas   Supratentorial; mixture of astrocytic and oligodendroglial cells. As oligodendroglial component increases, so does long-term survival; 5-year survival >50%. Total surgical resection often possible; may respond dramatically to chemotherapy if deletions of chromosomes 1p and 19q are found.
Ependymomas   Derived from ependymal cells; highly cellular. Location—spinal canal in adults. If histologically aggressive (cellular atypia, frequent mitotic figures), recurrence is certain. If total excision, 5-year disease-free survival >80%. Radiosensitive.
Germinomas   Tumors of midline brain structures; onset in second decade. Neuroimaging—uniformly enhancing mass. Treatment—complete surgical excision; 5-year survival >85%. Radiosensitive and chemosensitive.
Primitive Neuro-Ectodermal Tumors (PNET)   Half in posterior fossa; highly cellular; derived from neural precursor cells. Treatment—surgery, chemotherapy, and RT.
Primary CNS Lymphomas   B cell malignancy; most occur in immunosuppressed pts (organ transplantation, AIDS). May present as a single mass lesion (immunocompetent pts), multiple mass lesions, or meningeal disease (immunosuppressed pts). Prognosis generally poor. Dramatic, transient responses occur with glucocorticoids. In immunocompetent pts, RT and combination chemotherapy may increase survival to ³18 months; AIDS-related cases survive £3 months.
Meningiomas   Extraaxial mass attached to dura; dense and uniform contrast enhancement is diagnostic. Total surgical resection of benign meningiomas is curative. With subtotal resection, local RT reduces recurrence to <10%. Small, asymptomatic meningiomas may be followed radiologically. Rare aggressive meningiomas—treat with excision and RT.
Schwannomas   Vestibular schwannomas present as progressive, unexplained unilateral hearing loss. MRI reveals dense, uniformly enhancing tumor at the cerebellopontine angle. Surgical excision may preserve hearing.
Tumors Metastatic to Brain   Disseminate to brain by hematogenous spread. Skull metastases rarely invade CNS; may compress adjacent brain or cranial nerves or obstruct intracranial venous sinuses. Primary tumors that metastasize to the nervous system are listed in Table 183-1. Brain metastases are well demarcated by MRI and enhance with gadolinium; triple-dose contrast is most sensitive for detection; ring enhancement is nonspecific. Differential diagnosis includes brain abscess, radiation necrosis, toxoplasmosis, granulomas, demyelinating lesions, primary brain tumors, CNS lymphoma, stroke, hemorrhage, and trauma. CSF cytology is unnecessary—intraparenchymal metastases rarely shed cells into CSF. One-third of pts presenting with brain metastasis have unknown primary (ultimately small cell lung cancer, melanoma most frequent); primary tumor never identified in 30%. CXR is best screening test for occult cancer; if negative, obtain chest CT. If chest CT negative, obtain CT scan of abdomen and pelvis. Further imaging studies unhelpful if above studies negative. Biopsy of primary tumor or accessible brain metastasis is needed to plan treatment. Treatment is palliative—glucocorticoids, anticonvulsants, or RT may improve quality of life. Whole-brain RT is given, because multiple microscopic tumor deposits are likely throughout the brain. A single metastasis is often surgically excised followed by whole-brain RT. Systemic chemotherapy may produce dramatic responses in isolated cases.

Table 183-1 Frequency of Primary Tumors That Metastasize to the Nervous System

Leptomeningeal Metastases   Presents as multifocal cranial nerve or polyradicular involvement in setting of known malignancy. Diagnosis by CSF cytology, MRI (nodular meningeal tumor deposits or diffuse meningeal enhancement), or meningeal biopsy. Associated with hydrocephalus due to CSF pathway obstruction; detected by complete neuraxis MRI. Aggressive treatment (intrathecal chemotherapy, focal external beam RT) produces sustained response (~6 months) in 20% of pts.
Spinal Cord Compression from Metastases (See Chap. 194)   Expansion of vertebral body metastasis posteriorly (usually lung, breast, or prostate primary) into epidural space compresses cord. Back pain (>90%) usually precedes development of weakness, sensory level, or incontinence. Medical emergency; early recognition of impending spinal cord compression is essential to avoid permanent devastating sequelae. Diagnosis is by spine MRI. Progression may be slowed by administration of glucocorticoids while awaiting surgery or RT.
Complications of Radiation Therapy
Three patterns of radiation injury after CNS RT:

1.
Acute—headache, sleepiness, worse neurologic deficits during or immediately after RT. Self-limited and glucocorticoid-responsive.

2.
Early delayed—somnolence (children), Lhermitte’s sign; within 4 months of RT. Increased T2 signal on MRI. Also self-limited and improves with glucocorticoids.

3.
Late delayed—dementia or other progressive neurologic deficits; typically >1 year after RT. White matter abnormalities on MRI; ring-enhancing mass due to radiation necrosis. Positron emission tomography (PET) distinguishes delayed necrosis from tumor recurrence. Progressive radiation necrosis is best treated palliatively with surgical resection. Endocrine dysfunction due to hypothalamus or pituitary gland injury can be due to delayed effects of RT.
Bibliography

For a more detailed discussion, see Sagar SM, Israel MA: Primary and Metastic Tumors of the Nervous System, Chap. 370, p. 2442, in HPIM-15.

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