Review articleBrain metastases
Section snippets
Brain anatomy
Before discussing “brain metastases,” it is important to define the CNS compartments. The cerebral cortex forms the outer brain layer and consists of neuronal cell bodies (gray matter) that communicate synaptically with deeper structures. White-matter tracts are myelinated axons that carry information between the cortex and the deep gray structures, such as the basal ganglia and thalami. At the base of the brain, the brain stem is divided into three parts: the midbrain, pons (from Latin for
Epidemiology
Brain metastases are the most common cerebral tumors [2]. Although any primary systemic tumor may metastasize to the brain, several large clinical and autopsy series have identified the common malignancies (Table 1) [3], [4], [5], [6], [7], [8], [9], [10], [11], [12].
Posner and Chernik produced the largest and most comprehensive autopsy series; they studied 3219 patients at Memorial Sloan-Kettering Cancer Center from 1970 to 1976 [9]. Of the 2375 cases that included an autopsy of the brain,
Biology
Brain metastases occur most commonly in the setting of widely disseminated cancer. In particular, lung metastases are often present when brain metastases are discovered from nonpulmonary primary tumors. For example, one series documented primary or metastatic cancer in the lung in 99.5% (199 of 200) of patients with brain metastases in an autopsy study of 1096 patients with various carcinomas [7]. In another series, 79% of patients with brain metastases suffered from either lung cancer or lung
Symptoms and signs
The presenting symptoms and signs depend on the neuroanatomic structures disrupted by the metastasis. Some lesions present slowly, with progressive headache or cognitive dysfunction. Others present acutely with seizures. Hemorrhage into metastases may produce sudden severe headache, coma, or stroke-like focal neurologic findings; however, in an older clinicopathologic series of 15 patients with hemorrhagic metastases, the presentation was acute in only three (20%), whereas the onset was gradual
Methods of detection
At present, contrast-enhanced MRI is the best noninvasive test for evaluating the presence of brain metastases and their response to treatment. Although MR scanning is almost ubiquitous, there are occasions when it is unavailable or contraindicated (as for patients with pacemakers). In these patients, CT scanning usually delineates the lesions. Small metastases or lesions in the posterior fossa may be missed on CT, however [29], [30], [31], [32].
Contrast enhancement on MRI or CT scanning
Therapy
Infrequently, patients may be “cured” of their brain metastases and survive many years with good neurologic function. Without treatment, however, most patients succumb quickly. Clinical prognostic factors include performance status, systemic disease burden, age, response to treatment, interval from primary diagnosis until brain metastases, and cognitive function [10], [11]. The Karnofsky Performance Status (KPS) was introduced more than 50 years ago [39], [40] and remains one of the most
Chemotherapy
Currently, chemotherapy also has a limited role in treating most brain metastases. One difficulty is choosing drugs or doses that penetrate the blood–brain barrier (BBB) [96]. The intact BBB excludes agents that are hydrophilic or large, although this may be less of an issue in patients with brain metastases that have a significant amount of contrast enhancement on CT or MR scanning indicating disruption of the BBB. Nonetheless, an intact BBB creates a “sanctuary site” in the brain, and brain
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