Knowledge of the basic topographic and functional anatomy of the brain is critical for tumor localization and delineation of regions that need to be spared during treatment. Generally, the brain consists of three major divisions: The cerebrum, cerebellum, and brainstem. The cerebral hemispheres and midline structures are supratentorial, and the cerebellum and lower brainstem are infratentorial. The longitudinal cerebral fissure divides the cerebrum into two hemispheres. Each hemisphere is divided by the major sulci into six lobes: Frontal, parietal, occipital and temporal, and the midline central and limbic lobes. The central sulcus (of Rolando) separates the frontal lobe from the parietal lobe. The parietal-occipital fissure separates the parietal lobe from the occipital lobe. The lateral fissure (of Sylvius) defines the temporal lobe boundaries. The cerebral hemispheres are connected by the corpus callosum, beneath which are located the midline structures (third ventricle, pineal body, and midbrain) and the deep paramedian structures (lateral ventricles, caudate nucleus, lentiform nucleus, thalamus, and hypothalamus).

There are three historic approaches to defining the functional anatomy of the cerebral hemispheres. Brodmann’s schema numbers 52 areas of structural specialization to provide both anatomic and functional “road map” of the brain by which tumor location can be described (1,2). Another approach is a regional (lobe) division of function. The occipital lobe is primarily involved with vision and its dependent functions. The temporal lobe processes sound, vestibular sensations, sights, smells, and other perceptions into complex “experiences” important for memory. Wernicke’s area is located on the posterior portion of the superior temporal gyrus and plays a critical role in receptive speech. The parietal lobe, specifically the postcentral gyrus, is involved in somatosensory function, sensory integration (body image), and Gnostic (perceptive) functions. The frontal lobe is associated with higher level cognitive functions, such as reasoning and judgment. The frontal lobe contains the primary motor cortex (precentral gyrus) and Broca’s area (inferior third of the frontal gyrus), which is important in expressive speech. The limbic lobe mediates memories, drives, and stimuli. It affects visceral functions central to emotional expression, including sexual drive. Finally, the central lobe (insula) is important in visceral sensation and motility. The most modern method to describe functional neuroanatomy is through various techniques of functional mapping. Classic mapping utilizes microelectrode stimulation of the cortical surface directly. Newer noninvasive techniques such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and magnetoencephalography (MEG) are increasingly being integrated into clinical practice (3,4,5). Together, these procedures allow for precise mapping of function in an individual and can accurately predict deficits related to injury of a given area by tumor or therapy.

Annually, an estimated 63,000 new cases of primary nonmalignant and malignant CNS tumors are diagnosed in the United States with an estimated 13,000 deaths (6,7). The incidence of all primary nonmalignant and malignant brain and CNS tumors is 18.71 cases per 100,000 person-years. In the United States, the rate is slightly higher in females (19.88 per 100,000 person-years) than males (17.44 per 100,000 person-years) (7). The incidence rates are higher in more developed countries than in less-developed countries (8). The incidence rate of childhood primary nonmalignant and malignant brain and CNS tumors is 4.7 cases per 100,000 person-years. The rate is (4.75 per 100,000 person-years in males and 4.66 per 100,000 person-years in females) (7).

Most of the primary CNS tumors are located within the frontal, temporal, parietal, and occipital lobes of the brain.
Sixty-one percent of gliomas occur in the frontal, temporal, parietal, and occipital lobes. Tumors in other locations in the cerebrum account for another 3%. Of all tumors, 2%, 4%, and 2% are found in the ventricles, cerebellum, and brainstem, respectively. The pituitary and pineal gland account for ∼7% of tumors. Tumors of the meninges represent 24% of all tumors (7).

The overall incidence of primary spinal cord tumors is approximately 10% to 19% of all primary brain tumors (9). Schwannomas and meningiomas account for ∼60% of primary spinal tumors, with schwannomas being slightly more frequent; both types occur primarily in adults. Most primary spinal gliomas are ependymomas with a predilection for the cauda equina. The frequency of individual spinal cord tumors is quite different from that of their histopathologic counterparts in the brain. Gliomas constitute 46% of primary intracranial tumors but only 23% of spinal tumors. The incidence ratios of intracranial to intraspinal astrocytomas, ependymomas, and meningiomas are approximately 10:1, 3:1, and 18:1, respectively (10). Finally, the incidence ratio of intracranial to intraspinal tumors is higher up to four times in pediatric patients than in adults.

Table 31.1 shows the current WHO pathologic classification system of common primary CNS tumors (11). The most frequently reported histology is meningioma, which accounts for over 29% of all tumors, followed closely by glioblastoma and astrocytoma. The predominately benign nerve sheath tumors account for 8% of all tumors, of which 54% are acoustic neuromas. Pituitary tumors compose 6% of these lesions. Tumors of the glial cell origin represent about a half of all tumors. These include astrocytomas, glioblastomas, oligodendrocytomas, ependymomas, mixed gliomas, and neuroepithelial tumors. Astrocytomas and glioblastomas account for three-quarters of gliomas—the majority being glioblastomas (7). The most common spinal cord intramedullary tumors are those that are derived from glial precursors (astrocytes, ependymocytes, and oligodendrocytes) (12).

Metastatic brain tumors are the most common intracranial neoplasms in adults and it is about 10 times more common than primary intracranial tumors. In two cohorts of patients diagnosed with colorectal, lung, breast, or kidney carcinoma or melanoma, brain metastases were diagnosed in 8.5% to 9.6% (13,14). The cumulative incidence was estimated between 16% and 20% in patients with lung carcinoma, 7% in patients with renal carcinoma, 7% in patients with melanoma, 5% in patients with breast carcinoma, and 1% to 2% in patients with colorectal carcinoma.

With the exception of a primary paraspinal or neuraxis tumor, spinal cord tumors occur most often in the setting of disseminated disease from a distant primary tumor site. The spine is overall the most common site of bony metastases, with a reported incidence of 40% in patients with cancer (15). Of those patients with spine metastases, 10% to 20% develop malignant spinal cord compression (MSCC), accounting for 14,100 to 28,200 cases annually (16,17,18). MSCC from epidural metastases occurs in 5% to 10% of all patients with cancer and in up to 40% of patients with preexisting nonspinal bone metastases (15,19,20,21). MSCC may involve the spinal cord at any level, and symptoms depend on the location of the compression. The incidence of MSCC by vertebral levels is 10% to 16% cervical, 35% to 40% in T1 to 6, 44% to 55% in T7 to 12, and 20% in the lumbar spine (22,23,24). In 10% to 38% of cases, metastatic lesions present initially at multiple, noncontiguous levels (22,25,26).

The histology of MSCC follows the incidence patterns of primary malignancies, with the most common histologic diagnoses (i.e., breast, lung, and prostate) accounting for approximately half of all cases (6,15). Approximately 25% of all patients with MSCC have breast cancer, 15% have lung cancer, and 10% have prostate carcinomas. Overall, 5.5% of patients with breast cancer, 2.6% of patients with lung cancer, 7.2% of patients with prostate cancer, and 0.8% of patients with colorectal cancer experience a MSCC (17). Other commonly reported histologic diagnoses in adults include, in the order of cumulative incidence, multiple myeloma, nasopharynx, renal cell, melanoma, small cell lung, lymphoma, and cervix (15,17,27).

Medical treatment generally consists of steroids with or without mannitol (33). Patients who present with emergent symptoms are typically treated with dexamethasone. Response to therapy is usually noted within 12 to 18 hours of administration with over 80% of patients showing dramatic improvement by 3 to 4 days after initiation of therapy (34,35). A common regimen in patients receiving radiation therapy is high dose dexamethasone (10–25 mg IV or po) followed by maintenance on oral steroids (4–6 mg three or four times a day), with tapering initiated upon stabilization of symptoms and initiation of therapy, usually over 1 to 2 months (33,36,37). In the setting of MSCC from solid tumors, dexamethasone has been shown to improve rates of surviving with intact gait function (38,39). Side effects of intermediate- to long-term steroid use may include: hyperglycemia, insomnia, emotional lability, thrush, gastric irritation, ulceration and possibly perforation, proximal muscle wasting, weight gain and adiposity (moon facies, buffalo hump, and centripetal obesity), osteoporotic compression fractures, arthralgias with withdrawal, and aseptic necrosis of the hip joints (40). Some of these side effects persist even after steroid withdrawal. Owing to the incidence of steroid-induced complications with dosing longer than 21 days in duration, higher doses and longer tapering schedules should be based on the physician’s assessment of symptom severity and response (39,41,42). Patients should be instructed during tapering to note signs of worsening headaches and/or existing neurological deficits. They should be instructed to resume a higher steroid dose should such symptoms occur and consult their physician. Asymptomatic patients generally do not require corticosteroids and routine use of corticosteroids during radiation therapy in asymptomatic patients should be avoided. Select patients with MSCC may not receive steroids during treatment if they are at high risk of complications due to underlying medical comorbidities, such as peptic ulcer disease, uncontrolled diabetes, or other medical problems that may cause severe or life-threatening problems if exacerbated by steroids (43). Dexamethasone and mannitol drugs decrease peritumoral brain edema by different mechanisms of action and mannitol is therefore often used in steroid refractory patients (44). A common regimen of mannitol is a 20% to 25% solution given intravenously over ∼30 minutes dosed at 0.5 to 2.0 g/kg (45).

Stabilization of the patient in status epilepticus to perform imaging and make management decisions is critical (46). After securing the airway and stabilizing the patient, seizure activity must be terminated as rapidly as possible, especially as failure to control seizures can potentially lead to physical injuries, airway compromise, secondary brain hypoxia/injury, or coma (45,46). Rapid onset/short acting benzodiazepines and phenytoin are commonly used. Recommended initial regimens include 0.1 mg/kg at 2 mg/min of lorazepam or diazepam at 0.2 mg/kg at 5 mg/min. Phenytoin infusion of 15 to 20 mg/kg at <50 mg/min in adults is indicated for seizure activity refractory to benzodiazepines or after truncation of seizures with diazepam (46). There is no clear evidence to support the prophylactic use of anticonvulsants in patients diagnosed with a brain tumor in the absence of documented seizures (47,48).

Surgical resection and/or placement of a shunt are often required for emergent management of brain tumors causing life-threatening hydrocephalus, mass effect, or profound neurologic impairment. This may relieve symptoms enough that other treatment modalities can be initiated. Symptoms are usually related to mass effect, so resection or debulking are often the only logical choices if medical therapy fails to provide improvement in neurologic symptoms. Rapid surgical decompression is the treatment of choice for such problems when surgery can be safely performed based on patient performance status or tumor location. If no neurosurgical team is available, transfer of the patient should be initiated while medical measures are undertaken to stabilize the patient.

Many patients with spinal cord compression are not candidates for laminectomy and are treated with steroids and radiation therapy. Most series in the literature show no difference in outcomes when comparing laminectomy-treated patients to those managed with radiation therapy alone (15,24,49,50). However, a randomized trial evaluating the
benefit of adding surgical decompression to the radiotherapeutic management of symptomatic metastatic spinal cord compression showed that patients who underwent decompressive surgery had a significantly improved median time of gait retention and ability to regain gait function albeit without affecting overall survival (51). Therefore, all patients presenting with MSCC of short duration should be evaluated by an experienced neurosurgeon for emergent decompression before initiating radiation therapy.