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A variety of nonmetastatic neurologic complications of malignant disease can be recognized. Metabolic encephalopathy due to electrolyte abnormalities, infections, drug overdose, or the failure of some vital organ may be reflected by drowsiness, lethargy, restlessness, insomnia, agitation, confusion, stupor, or coma. The mental changes are usually associated with tremor, asterixis, and multifocal myoclonus. The electroencephalogram is generally diffusely slowed. Laboratory studies are necessary to detect the cause of the encephalopathy, which must then be treated appropriately.

Immune suppression resulting from either the malignant disease or its treatment (eg, by chemotherapy) predisposes patients to brain abscess, progressive multifocal leukoencephalopathy, meningitis, herpes zoster infection, and other opportunistic infectious diseases. Moreover, an overt or occult cerebrospinal fluid fistula, as occurs with some tumors, may also increase the risk of infection. MRI or CT scanning aids in the early recognition of a brain abscess, but metastatic brain tumors may have a similar appearance. Examination of the cerebrospinal fluid is essential in the evaluation of patients with meningitis and encephalitis but is of no help in the diagnosis of brain abscess.

Cerebrovascular disorders that cause neurologic complications in patients with systemic cancer include nonbacterial thrombotic endocarditis, septic embolization, and cerebral infarcts due to malignancy-induced hypercoagulability. Cerebral, subarachnoid, or subdural hemorrhages may occur in patients with myelogenous leukemia and may be found in association with metastatic tumors, especially melanoma. Spinal subdural hemorrhage sometimes occurs after lumbar puncture in patients with marked thrombocytopenia.

Disseminated intravascular coagulation occurs most commonly in patients with acute promyelocytic leukemia or with some adenocarcinomas and is characterized by a fluctuating encephalopathy, often with associated seizures, that frequently progresses to coma or death. There may be few accompanying neurologic signs. Venous sinus thrombosis, which usually presents with convulsions and headaches, may also occur in patients with leukemia or lymphoma. Examination commonly reveals papilledema and focal or diffuse neurologic signs. Anticonvulsants, anticoagulants, and medications to lower the intracranial pressure may be of value.

Autoimmune paraneoplastic disorders occur when the immune system reacts against neuronal antigens expressed by tumor cells. The clinical manifestations depend on the autoantibody. Symptoms may precede those due to the neoplasm itself. Several distinct syndromes are common, each associated with specific antibodies and tumors (Table 24–5). Identification of an antibody is not always possible in a suspected autoimmune paraneoplastic condition, and a search for an underlying neoplasm should be undertaken. Treatment of the neoplasm offers the best hope for stabilization or improvement of the neurologic symptoms, which often are not completely reversible. Specific treatment of the antibody-mediated symptoms by intravenous immunoglobulin (IVIG) administration, plasmapheresis, corticosteroids, or other immunosuppressive regimens is frequently attempted despite limited evidence of efficacy. Many of the disorders listed in Table 24–5 can occur either as paraneoplastic phenomena or in isolation; when they occur in the absence of a tumor, the response to immunotherapy is typically more favorable.

Table 24–5.Autoimmune paraneoplastic disorders and ...

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