Paraneoplastic syndromes involving the nervous system.

N Engl J Med 2003;349:1543-54. Copyright © 2003 Massachusetts Medical Society. he term “paraneoplastic syndromes” refers to symptoms or signs resulting from damage to organs or tissues that are remote from the site of a malignant neoplasm or its metastases. Paraneoplastic syndromes can affect most organs and tissues. Widely known examples include cancer cachexia, 1 hypercalcemia, 2 Cushing’s syndrome, 3 and Trousseau’s syndrome. 4 Most of these paraneoplastic syndromes occur because the tumor secretes substances that mimic normal hormones or that interfere with circulating proteins. A few paraneoplastic neurologic disorders are caused by similar mechanisms (e.g., carcinoid myopathy and encephalopathy). 5 However, most or all paraneoplastic neurologic disorders are immune-mediated. (We do not consider damage to the nervous system by cancer-induced coagulopathies or opportunistic infections to be paraneoplastic neurologic disorders.) The cancers causing paraneoplastic neurologic disorders are often asymptomatic and sometimes occult; it is the neurologic symptoms that take the patient to the doctor. The combination of an indolent tumor and severe neurologic disability suggests effective antitumor immunity coupled with autoimmune brain degeneration. This review describes paraneoplastic neurologic disorders believed to be immune-mediated and discusses our current understanding of their mechanisms.