Cancer and the Nervous System: Clinical Features and Complications

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Chapter 52C Cancer and the Nervous System

Clinical Features and Complications

Brain tumors are termed primary when they arise from the brain parenchyma or the cranial meninges. In contrast, metastatic brain tumors arise from a systemic cancer that spreads, typically via the hematogenous route, to the brain or meninges. The nature of tumor can often be suggested on brain imaging, because the majority of primary brain tumors are single, whereas as many as 50% of metastatic brain tumors are multiple. The location and the tempo of neurological symptoms and signs associated with primary or metastatic brain tumors depend upon the location of the tumor(s) and the rate of tumor growth. Most cerebral symptoms are subacute in onset and progress gradually, typically over weeks to months. In rare instances, the onset of symptoms is sudden. Causes of the sudden onset of symptoms include intratumoral hemorrhage, tumor cyst expansion, and obstruction of the ventricular system by tumor.

Focal signs of a brain tumor result from neural tissue invasion or compression by the tumor or its associated vasogenic edema. Common examples of focal symptoms/signs are hemiparesis, language disturbance, partial seizures, visual dysfunction, and ataxia. Multifocal cerebral lesions and increased intracranial pressure (ICP) cause generalized clinical features such as headache, confusion or somnolence, blurred or double vision, and nausea with vomiting. The neurological examination may reveal altered cognition or alertness, papilledema, and/or lateral rectus palsy and also focal signs such as hemiparesis.

Patient age is an important factor in the type of neurological symptoms associated with a brain tumor because tumor location varies with age. Pediatric brain tumors most commonly arise in the posterior fossa and therefore result in cerebellar and cranial nerve signs. These are often accompanied by signs of increased ICP due to early compression of the fourth ventricle with resultant hydrocephalus. Conversely, adult brain tumors more commonly arise in the cerebral hemispheres and result in unilateral limb paresis, cognitive impairment, language disturbance, and seizures.

When primary or metastatic tumors spread to the leptomeninges, multifocal and/or diffuse cerebral and cranial nerve signs may result. In addition, because of the associated spread of tumor to the spinal leptomeningeal compartment, features of spinal nerve root or spinal cord dysfunction may occur. Spinal symptoms will not be referred to in this chapter, which focuses on the cerebral manifestations of primary and metastatic brain tumors.

This chapter reviews the most common clinical features of brain tumors and the mechanisms underlying them, the methods of clinical evaluation, and their management. Nonmetastatic neurological complications of cancer, such as those induced by cancer treatment or paraneoplastic disorders, are outside the scope of this chapter.


Headache is a common initial symptom of a brain tumor but rarely occurs in isolation. In the majority of patients, headache as a presenting sign of a brain tumor occurs in association with focal or generalized neurological symptoms and signs. Brain tumors, similar to other mass lesions in the brain, can result in the classical symptoms of increased ICP, including onset of the headache at night or upon waking in the morning. The headache usually resolves shortly after rising. It may worsen with Valsalva maneuvers. Unless the underlying tumor is treated, the headache becomes constant and usually associated with other features of increased ICP such as nausea and vomiting, reduced level of alertness, visual disturbance, and possibly focal signs. However, less than half of patients with brain tumors present with these typical clinical features, and the headache pattern may be indistinguishable from other common headache types such as migraine, cluster, or tension headaches. In the patient with a known brain tumor, a headache that develops late in the clinical course should alert the clinician to the possibility of tumor recurrence or structural changes within the tumor, such as intratumoral hemorrhage or cyst expansion.

When headache in adults or children is accompanied by other neurological symptoms as the presenting symptom of a brain tumor, the likelihood of a primary brain tumor is higher than for metastatic brain or leptomeningeal tumors, which more commonly present with isolated headaches. The brain parenchyma does not contain nociceptive receptors, so headache associated with a brain tumor results from direct impingement or traction on pain-sensitive structures including portions of the meninges (e.g., basal dura and the venous sinuses and their tributaries), neural structures (e.g., glossopharyngeal, vagus, and trigeminal cranial nerves, as well as the upper cervical spinal nerves), and vascular structures (e.g., dural arteries; carotid, vertebral, and basilar arteries; circle of Willis; and proximal portions of cerebral, vertebral, and basilar branches).

Because it is not possible to predict with certainty which patients with systemic cancer and a new or changing headache pattern have brain metastasis, a careful neurological examination that includes tests of cognitive function is prudent, as it will often disclose findings additional to the complaints reported by the patient. Even in the presence of a normal examination, brain imaging is recommended.

Contrast-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) brain magnetic resonance imaging (MRI) sequences are the most useful methods to identify tumor, vasogenic edema, mass effect, and patency of the ventricular system. Unenhanced T1-weighted images are useful in identifying intratumoral bleeding if such bleeding is a consideration. Lumbar puncture for cytological examination or flow cytometry may be indicated if leptomeningeal tumor is suspected, but MRI findings are nondiagnostic.

Simple analgesics are usually adequate to treat headache related to impingement on pain-sensitive structures in the brain, but in rare circumstances, opioid analgesics may be required. In general, attempts should be made to treat the underlying tumor and associated vasogenic edema in order to relieve the headache. In patients without hydrocephalus, this treatment typically includes surgical resection and may include radiation and/or chemotherapy as well as the use of corticosteroids to treat vasogenic edema (see Cerebral Edema

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