Introduction
Brain metastases are neoplasms that originate in tissues outside the brain and spread secondarily to involve the brain. Of cancer patients, 25% develop brain metastases. As such, cerebral metastases are the most common type of brain tumor in adults.
There are more than 100,000 brain metastases annually in the United States. Of these metastases, 80% are supratentorial, 15% are cerebellar, and 5%
are located in the brainstem or spinal cord. In addition, 25% of metastases are discovered before or at the time of diagnosis of primary tumor; 60%
develop in the next 1 to 6 months, and 10% in months 7 to 12. About 5% develop more than 1 year after the primary tumor is diagnosed.
152 FUNDAMENTALS OF NEUROLOGIC DISEASE
Figure 14-4 Magnetic resonance imaging scan of pitu-itary adenoma. (Courtesy of Blaine Hart, MD)
145-154_Davis14 3/2/05 4:30 PM Page 152
The most common sources of intracranial metastases are the lung, breast, GI or genitourinary tracts, skin (melanoma), and leukemia. For unknown reasons, a few cancers, such as prostate, uterine, and ovarian, seldom metastasize to the brain. At the time of diagnosis, 1/3 of metastases are single and 2/3 are multiple. However, only 1%
of cerebral metastases that are solitary have not metastasized elsewhere in the body. In addition, it is common for a patient with an initial single metastasis subsequently to develop other cerebral metastases.
Pathophysiology
Most metastases arrive via the blood stream and commonly lodge at the gray–white matter junction, particularly in watershed areas of the cerebral hemi-spheres. A few metastases reach the spinal cord via retrograde flow via the veins in Batson’s plexus or by extension into the brain from dural or skull metas-tases. The tumor embolus begins to grow and pro-duces angiogenesis factors that stimulate new vessel formation to supply blood to the tumor bed. These new blood vessels lack a blood–brain barrier. Brain metastases cause considerable vasogenic edema sur-rounding the tumor that may exceed the size of the tumor. Thus the mass effect of even small metas-tases may be considerable.
Metastases produce clinical symptoms through several mechanisms. The most common is dis-placement of brain tissue by the rapidly growing tumor and the adjacent cerebral edema. The dis-placement causes vessel compression and ischemia, alterations in normal anatomy, and dis-ruption of extracellular fluid spaces. If the tumor is located in the eloquent cortex, the tumor itself may destroy critical neurons and cause symptoms.
A metastasis may suddenly become necrotic, hem-orrhage, rapidly expand in size, and produce an abrupt increase of symptoms. The tumor may
“irritate” adjacent cerebral cortex neurons, trigger-ing focal seizures. Finally, the mass effect of the tumor and cerebral edema may trigger brain her-niation (see “Overview”).
Cerebral metastases must be distinguished from other brain lesions such as a primary brain tumor, cerebral hemorrhage, cerebral infarction, and brain abscess. In autopsy series, 5% to 10% of lesions thought to be a solitary metastasis had another etiology.
Major Clinical Features
Cerebral metastases are usually symptomatic, but a few are discovered at autopsy. Over 2/3 of patients have neurologic signs and symptoms that are sim-ilar to other mass lesions (Table 14-4). Seizures are usually focal motor, some of which become sec-ondarily generalized. As metastases expand and produce increased ICP, deterioration of mental status develops and brain herniation may occur.
Major Laboratory Findings
MRI with gadolinium enhancement is the best diagnostic test. A negative test essentially rules out cerebral metastases. T1-weighted images may not show a small lesion unless there is hemorrhage, but areas of low intensity from the edema may be seen. T2-weighted images show areas of increased intensity that encompass both the tumor and sur-rounding edema. T1-weighted images with gadolinium show a heterogenous or ring-enhanc-ing lesion, usually with surroundring-enhanc-ing edema. Shift-ing of brain structures from the tumor mass effect commonly are seen on all images. A careful search for other metastases should be made, as all lesions are not the same size.
Principles of Management and Prognosis Surgical removal of the metastasis only occasion-ally is helpful in markedly prolonging life. Surgery should be considered when the diagnosis is in
CHAPTER 14—Brain Tumors 153
Table 14-4 Presenting Signs of Brain Metastases
Sign Percent
Impaired Cognition 60%
Hemiparesis 60%
Headache 50%
Aphasia 20%
Hemisensory Loss 20%
Seizures 20%
Papilledema 20%
Visual Field Cut 10%
Stupor or Coma 5%
145-154_Davis14 3/2/05 4:30 PM Page 153
doubt or when the patient is in good overall health, the primary tumor is small and responding to treatment, and there are no other critical sys-temic metastases.
Dexamethasone reduces the cerebral edema and often dramatically improves the patient’s symptoms for 1 to 2 months. The addition of whole-brain or localized radiation therapy to the metastases adds a few more months of survival, but the patient must undergo the complications of radiation and a month of therapy. Chemotherapy appears to add little to survival, but the patient often receives systemic chemotherapy for the pri-mary tumor.
In summary, the median survival without any treatment is 1 to 2 months from the discovery of the brain tumor. With corticosteroids, the survival extends to 2 to 4 months. The median survival with steroids plus radiostherapy is between 3 and 6 months, with 10% surviving 1 year.
RECOMMENDED READING
Arnold SM, Patchell RA. Diagnosis and manage-ment of brain metastases. Hematol Oncol Clin N Amer 2001;6:1985–1107. (Good brief review of brain metastases and treatment options).
Black PM. Benign brain tumors: meningiomas, pituitary tumors and acoustic neuromas. Neu-rol Clin 1995;13:927–952. (Review of clinical, neuroimaging, and treatments of these tumors).
Ciric I. Long-term management and outcome for pituitary tumors. Neurosurg Clin N Am 2003;14:167–171. (Entire issue is devoted to clin-ical, pathologic, and medical/surgical manage-ment of pituitary tumors).
DeAngelis LM. Brain tumors. N Engl J Med 2001;344:114–123. (Excellent overall review).
Fishman RA. Brain edema. N Engl J Med 1975;293:
706–711. (Classic review of types of cerebral edema and their treatments).
Posner JB. Neurologic Complications of Cancer.
Philadelphia: FA Davis; 1995. (Excellent prehensive review of all types of CNS cancer com-plications, including metastases to the brain and leptomeninges, CNS infections, paraneoplastic syndromes, and side effects of chemotherapy and radiation).
154 FUNDAMENTALS OF NEUROLOGIC DISEASE 145-154_Davis14 3/2/05 4:30 PM Page 154
Overview
Single seizures occur in about 5% of the popula-tion. Nearly 2 million individuals in the United States (~1%) have epilepsy; 100,000 new cases of epilepsy are diagnosed annually. An epileptic seizure is the behavioral manifestation of abnormal brain neuronal activity. Recurrent seizures second-ary to brain disease or dysfunction define epilepsy, which is characterized by recurrent, usually tran-sient, abrupt episodes of disturbed brain function with combinations of loss of consciousness, altered psychic function, and convulsive movements.