Neurologic Complications of Systemic Cancer

American Family Physician,  Feb 15, 1999  by M.D. Newton, Herbert B.

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Neurologic complications occur frequently in patients with cancer. After routine chemotherapy, these complications are the most common reason for hospitalization of these patients. Brain metastases are the most prevalent complication, affecting 20 to 40 percent of cancer patients and typically presenting as headache, altered mental status or focal weakness. Other common metastatic complications are epidural spinal cord compression and leptomeningeal metastases. Cord compression can be a medical emergency, and the rapid institution of high-dose corticosteroid therapy, radiation therapy or surgical decompression is often necessary to preserve neurologic function. Leptomeningeal metastases should be suspected when a patient presents with neurologic dysfunction in more than one site. Metabolic encephalopathy is the common nonmetastatic cause of altered mental status in cancer patients. Cerebrovascular complications such as stroke or hemorrhage can occur in a variety of tumor-related conditions, including direct invasion, coagulation disorders, chemotherapy side effects and nonbacterial thrombotic endocarditis. Radiation therapy is the most commonly employed palliative measure for metastases. Chemotherapy or surgical removal of tumors is used in selected patients.

Family physicians often perform the initial evaluation of patients with neurologic complications of systemic cancer.1-4 These complications are diverse and can affect any level of the central and peripheral nervous system. The most frequently implicated tumors are those from the lung, breast, colon, rectum, prostate gland, head and neck, as well as tumors related to leukemia and lymphoma.1,4 Direct involvement of the nervous system includes brain metastases, epidural spinal cord compression, leptomeningeal metastases and various neuropathies (e.g., cranial or peripheral). Indirect effects of systemic cancer include vascular disorders, infections, metabolic abnormalities and paraneoplastic syndromes.

An estimated 15 to 20 percent of cancer patients have symptomatic neurologic complications during the course of their illness.4 The most common complaints are back pain, mental status changes, headache, limb pain and leg weakness. Other than routine chemotherapy, neurologic problems are the most common reason for the hospitalization of patients with systemic cancer.4 Because of improved cancer treatments and longer survival in more patients, neurologic problems will continue to increase in frequency.1,2 Neurologic complications in cancer patients may be even more common than estimates indicate. Investigators at the Johns Hopkins Oncology Center reported that 46 percent of patients admitted to their solid tumor service over a three-month period required either evaluation or treatment of a neurologic problem.1 Another study found that approximately 30 percent of patients with small-cell lung cancer had serious neurologic complications during the course of their disease.2

Patients with neurologic complications of systemic cancer can experience severe weakness, dementia, seizure activity, loss of ambulation, pain and incontinence. Any of these problems can be devastating to functional ability and quality of life. Early recognition and accurate diagnosis, followed by appropriate therapy, often result in pain relief, improved neurologic function, enhanced quality of life and, possibly, prolonged survival.1

Brain Metastases

Brain metastases are the most common neurologic complication of systemic cancer in adult patients.5,6 In the United States, these metastases occur in 20 to 40 percent of cancer patients who are over 20 years of age.6 Metastatic brain tumors are almost 10 times more common than primary brain tumors.7

Although metastases to the brain can be generated by primary tumors in a variety of sites (Table 1),5,6,8 more than 60 percent derive from tumors of the lung and breast. Although malignant melanoma represents only 1 percent of all systemic malignancies, it has the highest propensity for spread to the brain.5

Most systemic tumor cells reach the brain by hematogenous spread through the arterial circulation.5,6,8 Occasionally, these cells can reach the brain by way of Batson's plexus (a venous system that drains the base of the skull, spinal column and pelvis) or by direct extension from adjacent structures such as the sinuses or skull.

Brain metastases disrupt the function of adjacent neural tissue by a number of mechanisms, including direct displacement of brain structures by the enlarging tumor, perilesional edema, irritation of overlying gray matter and compression of arterial and venous vasculature.

Patients with brain metastases may have a variety of neurologic signs and symptoms (Table 2).5,6,8,9 The most common symptoms are headache, altered mental status and focal weakness. The headaches are usually generalized, often occur during sleep and become progressively more severe. Mental status changes may initially be subtle, with patients exhibiting lethargy, loss of interest in activities, irritability or memory loss. The type and degree of weakness depends on the location of the tumor, but a hemiparetic pattern is most common. Seizures are another commonly encountered symptom of brain metastases.