A. About 20% of cancer patients develop metastases to the CNS, but only one half are symptomatic. Metastases are the most common CNS tumors (approximately 170,000 per year).

1. Seventy-five percent of brain metastasis are from lung (50%), breast (15%), and melanoma (10%); gastrointestinal, gynecologic, urologic, and cancers of unknown primary cause another 10%.

2. Twenty-five percent of metastatic lesions are single; about 20% of patients have two metastatic lesions.

3. Patients with gastrointestinal, gynecologic, or urologic tumors tend to have single brain lesions; approximately 50% are to the posterior fossa. Only 10% of other tumors metastasize to the posterior fossa.

4. Patients with lung cancer, melanoma, and tumors of unidentified origin usually have multiple metastatic lesions.

5. Most metastases localize to the frontal and parietal lobes (because of their relative mass and higher blood flow) and a few (1%) to the brainstem. Metastases lodge at the arterial border zones of the major cerebral vessels because of decreased vascular caliber and flow; hence, their preference for the gray-white junction.

6. The tumors most likely to bleed are melanoma, renal, and thyroid—the most vascular.

B. In up to 10%, an intracranial mass in patients with cancer is not a metastasis. The differential diagnosis includes:

1. Primary CNS tumor.

2. Brain abscess.

3. Demyelinating plaque.

4. Arteriovenous malformation.

1. Increased intracranial pressure (ICP) from a metastasis is usually managed with a bolus of dexamethasone 10 mg intravenously (IV) followed by 16 mg IV or orally in divided doses for maintenance.

2. For patients with minimal neurologic deficit no bolus is needed

3. If needed, dexamethasone is increased by 8 or more mg IV or orally four times a day.

4. Clinical improvement should be apparent within 24 to 48 hours of treatment, continue for several days, and then plateau.

5. Dexamethasone is tapered as tolerated after the patient’s condition is stable and more definitive therapy has started. The goal is to maintain optimal neurologic function on the lowest steroid dose due to the large number of side effects.

6. A proton pump inhibitor or H2 blocker may be started as prophylaxis against gastric bleeding, ulceration, or perforation.

D. Patients in extremis from increased ICP may need an osmotic diuretic, e.g., mannitol 20% solution 1 g per kg IV.

1. Smaller doses of mannitol (0.25 to 0.5 g per kg) can be repeated, but ICP must be monitored.

2. Only short-term hyperosmolar therapy is useful because:

3. Patients given osmotic diuretics need bladder catheterization.

E. Hyperventilation and osmotic diuretics are used only if a definitive end point is first established, because beneficial effects are temporary. The target of hyperventilation is a pCO₂ of 30 to 35 mm Hg (see Chapter 58).

1. Between 15% and 30% of patients with brain metastases have seizures.

2. Status epilepticus is managed in the standard manner (see Chapters 38 and 39).

3. Prophylactic antiepileptic drugs (AEDs) can be considered for patients with melanoma (50% of whom have seizures); otherwise there is no role for them. Posterior fossa metastases are not epileptogenic.

4. When phenytoin, dexamethasone, and whole-brain irradiation are used concurrently, the risk of erythema multiforme and erythema multiforme bullosa (Stevens-Johnson syndrome) increases.

5. Given the frequency of drug-drug interactions with older AEDs, newer agents should be considered first.

1. The ideal candidate has minimal disability, a single, circumscribed, accessible lesion, and controlled systemic disease.

2. A shunt is indicated for obstructive hydrocephalus.

3. Current areas of controversy include:

1. RT is the primary therapy for brain metastasis.

2. Prophylactic cranial irradiation is standard of care for limited stage small-cell lung cancer (SCLC); although it decreases the incidence of subsequent brain metastasis, it does not significantly affect patient survival.

3. Stereotactic radiosurgery (SR) or Gamma Knife delivers a single large or several smaller RT fractions to a well-defined, limited intracranial target with a sharp peripheral dose fall-off and minimal exposure to normal surrounding brain.

4. A patient with radiation necrosis has acute or subacute neurologic deterioration and signs and symptoms of a mass lesion.

1. As most tumors are drug-resistant, chemotherapy is not routinely indicated for management of CNS metastasis.

2. Chemotherapy may be considered in

1. Common symptoms include: gait or limb ataxia, nystagmus, papilledema, headache, dizziness, vomiting, and double vision.

2. Initial treatments are the same as for supratentorial metastases: dexamethasone and RT.

3. Acute complications of RT are more common with cerebellar than with supratentorial metastases. Therefore, dexamethasone is started 48 hours prior to RT.

4. The risk of brain herniation after lumbar puncture (LP) is greater in patients with posterior fossa masses.

5. The indications for resection are the same as for supratentorial metastases, but any sign of clinical instability or deterioration, an expanding mass, hydrocephalus, or lack of response to dexamethasone should prompt consideration of immediate neurosurgical intervention except in brain stem lesions.

6. After resection of a cerebellar metastasis, patients have a higher incidence of developing leptomeningeal dissemination due to the proximity of the tumor to CSF spaces.

A. Pituitary apoplexy is an emergency. Acute panhypopituitarism occurs when a metastasis in the sella turcica or the pituitary gland necroses or hemorrhages—causing headache, ophthalmoplegia, bitemporal hemianopsia, blindness, encephalopathy, coma, hypotension and signs of meningeal irritation.

B. Treatment is with high IV doses of corticosteroids; surgical decompression may be needed.

C. Complete endocrine work up is indicated as hormone replacement will be needed.

The hallmark of metastasis to the skull base is involvement of the cranial nerves (CN). Most tumors arise from the breast, lung, or prostate. Five major syndromes have been recognized.

A. Orbital syndrome characterized by dull, continuous, progressive pain over the affected eye with proptosis, external ophthalmoplegia, and blurred vision. There is decreased sensation over the distribution of ophthalmic division of the trigeminal nerve (CN V).

B. Parasellar syndrome (cavernous sinus metastasis) manifests as unilateral frontal headache and ophthalmoplegia. Patients may have decreased sensation over the distribution of the ophthalmic division of CN. V. If cavernous sinus thrombosis occurs, there may be chemosis, edema of the eyelids and forehead, proptosis, and papilledema with retinal hemorrhages. In both the parasellar and orbital syndromes, steroids are warranted before RT to prevent acute vision loss from radiation-induced edema.

C. Middle fossa syndrome (Gasserian ganglion) is characterized by pain, numbness, or paresthesias over the distribution of the second (maxillary) or third (mandibular) divisions of CN V. The initial presentation may be a “numb chin” or a “numb lip.” Pterygoid and masseter weakness and abducens palsy occur late. About 65% of these lesions are from breast cancer and 15% from lymphomas. Approximately half the patients have mandibular metastasis, 15% have skull base lesions, and 20% carcinomatous meningitis.

D. Jugular foramen syndrome manifests as hoarseness and dysphagia (CN X) with or without pain (CN IX or X). Examination may show asymmetric palatal elevation (CN IX), weakness of the ipsilateral sternocleidomastoid and trapezius muscles (CN XI), and Horner’s syndrome (oculo-sympathetic). Weakness and atrophy of the tongue may be found if the tumor extends to the adjacent hypoglossal canal (CN XII).

E. Occipital condyle syndrome manifests as stiff neck and severe occipital pain that increases with neck flexion. Dysarthria and dysphagia from unilateral involvement of CN XII are seen in approximately 50%.

Dural metastases can cause headache or underlying venous sinus thrombosis and may invade the parenchyma. Malignant subdural effusions can also occur. Breast and prostate tumors are most commonly implicated.

A. Metastatic epidural spinal cord compression (ESCC) occurs in approximately 5% to 10% of patients with cancer. ESCC is an emergency.

B. Prognosis. The most important determinant is neurologic function at presentation.

1. Ninety percent of ambulatory patients remain so after treatment, and have a 75% probability of surviving 1 year. Fewer than 10% of nonambulatory patients survive 1 year.

2. Only 50% of paraparetic and 13% of paraplegic patients with “radiosensitive” tumors become ambulatory after treatment.

3. Once neurologic dysfunction begins, paraplegia and loss of sphincter control occur within hours and are usually irreversible.

C. ESCC must be suspected on clinical grounds and must prompt timely confirmation and treatment.

1. About 60% of epidural metastates are from prostate, lung, breast, and kidney cancer; about 15% from multiple myeloma.

2. Approximately 50% of adults with an acute transverse myelopathy have metastatic ESCC. In 50% it is the initial manifestation of cancer, and in one half of those, the primary is lung cancer.

1. About 95% of patients with epidural tumor have progressive axial pain with or without a radicular or referred component.

2. Some weakness and sensory disturbance are present in 80% of patients.

3. Almost 60% of patients have sphincter dysfunction, a poor prognostic sign that implies bilateral cord or root damage.

1. The vertebral column, and never the intervertebral disks, is involved in about 85% of epidural tumors from solid cancers.

2. About 50% to 70% of lesions involve the thoracic spine.

3. About 20% to 30% involve the lumbosacral spine.

4. About 10% to 20% involve the cervical spine.

5. At least one-third of patients with breast and prostate cancer have metastatic lesions at multiple levels.

F. There are three potential mechanisms of metastatic ESCC.

1. Most common is hematogenous spread to the vertebra.

2. The valveless veins in Batson’s plexus allow tumor seeding when the intraabdominal pressure increases.

3. Direct invasion of a paravertebral mass through the intervertebral foramen occurs in 75% of ESCC from lymphoma.

G. Diagnosis. Non-contrast-enhanced followed by contrast-enhanced MRI should be performed in all cases of suspected ESCC to establish the diagnosis and the extent of tumor invasion (Fig. 53.1). Because disease is often multifocal and discontinuous, the entire spine should be imaged. CT scan with or without myelography may be needed if an MRI is contraindicated.

1. If spinal cord compression is suspected, or upon confirmation, a 10-mg IV bolus of dexamethasone is administered and followed by 4 mg IV every 6 hours. If pain is severe, or if there is paresis or sphincter involvement, a 100-mg IV bolus of dexamethasone is administered and followed by 24 mg IV every 6 hours until more definitive treatment is started.

2. Maintenance dosage of dexamethasone (4 mg IV or orally every 6 hours) is then tapered as tolerated.

3. Steroids can promote clinical improvement and decrease pain but rarely produce a dramatic reversal of established neurologic disability. Prognosis is better when they do.

4. An indwelling bladder catheter should be inserted to check PVR and remain in.

5. Deep venous thrombosis prophylaxis and a stool-softening regimen should be started.

I. Although the intent of therapy remains palliative, several treatment options are available.

2. Decompressive laminectomy works only temporarily. It fails because

4. RT alone is the procedure of choice for radiosensitive tumors.

5. Laminectomy plus radiation. For select patients, surgery followed by RT is better than RT alone for preserving function and increasing survival.

6. Epidural tumors do not respond rapidly enough to chemotherapy to warrant its use in most acute situations.