AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Brain tumors may originate from neural elements within the brain, or they may represent spread of distant cancers. Primary brain tumors arise from CNS tissue and account for roughly half of all cases of intracranial neoplasms. The remainder of brain neoplasms are caused by metastatic lesions. In adults, two thirds of primary brain tumors arise from structures above the tentorium (supratentorial), whereas in children, two thirds of brain tumors arise from structures below the tentorium (infratentorial). Gliomas, metastases, meningiomas, pituitary adenomas, and acoustic neuromas account for 95% of all brain tumors. Classification by tumor cell type is irrelevant to the emergency physician because emergent treatment is the same regardless of the tumor type.

Pathophysiology

Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, strategically located tumors may damage vital neurologic pathways traversing the brain. Tumors can invade, infiltrate, and supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the relatively restricted repository of the cranial vault, growth of intracranial tumors with accompanying edema compresses some normal tissue. Tumors proximal to the third and fourth ventricles may obstruct the flow of cerebrospinal fluid, leading to hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema.

The cumulative effects of tumor invasion, peritumor edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

Slow-growing tumors, particularly tumors expanding in the so-called silent areas of the brain, such as the frontal lobe, may be associated with a more insidious course. These tumors tend to be larger at detection.

Most primary brain tumors do not metastasize. Of those neural element tumors that do, intraparenchymal metastasis generally precedes distant hematogenous dissemination via the arterial system.

Metastatic brain tumors from non-CNS primary tumors may be the first sign of malignancy, or they may herald a relapse. Nonetheless, the signs and symptoms of brain metastases simulate those of primary brain tumors.

Frequency

United States

Estimates of the annual incidence rate of primary brain tumors range from 7-19.1 cases per 100,000 population.^{1, 2} Metastatic tumors to the brain are more common with more than 100,000 patients per year in the United States dying with symptomatic intracranial metastases.² An increase in the prevalence of HIV infection corresponds to an increase in the occurrence of primary CNS lymphoma. Pituitary adenomas are exceptionally common, and they are frequent incidental findings on autopsy. Autopsy series of patients with systemic cancer show that intracranial metastases are present in 18-24% of patients.³

International

The international incidence is not known, but it is thought to parallel that of the United States.

Mortality/Morbidity

• In the United States in 1999, primary cancers of the central nervous system were the cause of death in approximately 13,100 people.²
• Brain tumors are the second most common cancer in children, comprising 15-25% of all pediatric malignancies.¹ 
• Perhaps no other cancer is as feared as brain tumor since severe disability, including paralysis, seizures, gait disturbances, and impairment of intellectual capacity may occur.

Race

Differences are seen between ethnic groups within the same country, and a 3-fold difference in incidence has been reported between countries worldwide. Developed countries appear to have the highest rates, but this may reflect better registration systems.¹

Sex

• Meningiomas and pituitary adenomas are slightly more common in women than in men.
• Males are more likely to be diagnosed with brain tumors than females, with a male-to-female ratio of 1.5:1.¹

Age

• Tumors in the posterior fossa predominate in preadolescent children, with the incidence of supratentorial tumors increasing from adolescence to adulthood.
• Low-grade gliomas, such as astrocytomas, are more common in younger people than in older people. High-grade gliomas, such as anaplastic astrocytoma and glioblastoma multiforme, tend to originate in older persons in the fourth or fifth decade or beyond.
• In children, brain tumors are the most prevalent solid tumor, second only to leukemia as a cause of pediatric cancer. The incidence rate of primary CNS neoplasms is 3.6 cases per 100,000 children each year. 

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Presenting complaints of patients with an intracranial neoplasm tend to be similar for primary brain tumors and intracranial metastases. Manifestations depend on the cause of the symptoms: an increase in ICP, direct compression of essential gray or white matter, shifting of intracranial contents, or secondary cerebral ischemia.

Symptoms may be nonspecific and include headache, altered mental status, ataxia, nausea, vomiting, weakness, and gait disturbance. CNS neoplasms also may manifest as focal seizures, fixed visual changes, speech deficits, or focused sensory abnormalities. The onset of symptoms usually is insidious, but an acute episode may transpire when bleeding into the tumor occurs or when an intraventricular tumor suddenly occludes the third ventricle by means of a ball valve mechanism.

• Although headache is the symptom customarily associated with an intracranial neoplasm, it often is a late complaint. Usually, headache is not an isolated finding.
• • Headache is the worst symptom in only one half of patients.
  • Classically, textbooks relate onset of headache to an increase in ICP.
  • Prevailing inaccurate portrayals of a tumor headache include pain that is worse in the early morning than at other times; vomiting (with or without nausea); and exacerbation with Valsalva maneuvers, bending over, or rising from a recumbent position.
  • Most headaches in patients with brain tumors are nonspecific and resemble tension-type headaches.
  • A change in any patient's headache pattern may be cause for concern.
  • New onset of headaches in middle-aged or older patients is worrisome.
  • The location of the headache reliably indicates the side of the head affected, but it does not indicate the precise site of the tumor.
  • Headaches are more common with posterior fossa tumors.
  • Headache is a more frequent symptom of intracranial tumor in pediatric patients.
• Mental status changes, especially memory loss and decreased alertness, may be subtle clues of a frontal lobe tumor. Complaints may be as mundane as sleeping longer, appearing preoccupied while awake, and apathy.
• • Temporal lobe neoplasms may lead to depersonalization, emotional changes, and behavioral disturbances.
  • Vision, smell, and other sensory disturbances may be caused by a brain tumor.
  • An acoustic neuroma may present as intermittent (then progressive) hearing loss, disequilibrium, and tinnitus.
  • Symptoms of pediatric posterior fossa tumors include increased irritability, unsteadiness, ataxia, headache, vomiting, and progressive obtundation.
  • Supratentorial tumors in children are more commonly associated with seizures, hemiparesis, visual field cuts, speech difficulties, and intellectual disturbance.
  • Pituitary adenomas may be divided into 2 broad categories: nonfunctional and hypersecretory. Nonfunctional pituitary adenomas remain asymptomatic until they are large enough to encroach the optic chiasm and disturb normal vision. Most hypersecretory pituitary adenomas secrete prolactin, with affected women noting an amenorrhea-galactorrhea syndrome. Men with prolactin pituitary adenomas more commonly complain of headache, visual problems, and impotence.
• Seizures, focal or generalized, may be the earliest expression of a brain tumor.
• • A Jacksonian pattern, ie, one in which a focal seizure begins in one extremity and then progresses until it becomes generalized, is distinctive in suggesting a focal structural lesion of the cortex.
  • Depending on the rate of growth of the tumor, seizures may be present for months to years before a brain tumor is diagnosed.
  • Any middle-aged or elderly patients presenting with a first seizure should have CNS tumor high in the differential diagnosis.
  • Patients with a brain tumor may present with acute neurologic changes mimicking those associated with stroke.

Physical

No physical finding or pattern of findings unmistakably identifies a patient with a CNS neoplasm.

• Based on their location, intracranial tumors may produce a focal or generalized deficit, but signs may be lacking (especially if the tumor is confined to the frontal lobe) or even falsely localizing.
• Papilledema, which is more prevalent with pediatric brain tumors, reflects an increase in ICP, probably lasting several days or longer. Papilledema usually does not cause visual loss. Not all patients with CNS tumors develop papilledema. 
• Diplopia may result from displacement or compression of the sixth cranial nerve at the base of the brain.
• Impaired upward gaze, called Parinaud syndrome, occurs with pineal tumors.
• Tumors of the occipital lobe specifically may produce homonymous hemianopia or partial visual field deficits.
• Anosmia may occur with frontal lobe tumors.
• Brainstem and cerebellar tumors induce cranial nerve palsies, ataxia, incoordination, nystagmus, pyramidal signs, and sensory deficits on one or both sides of the body. 
• • Three cranial nerves run through the cerebellopontine angle: facial, cochlear, and vestibular. Masses in these regions may impair the functions of these nerves.
  • Acoustic neuromas most commonly originate from the vestibular nerve (part of cranial nerve VIII).

Causes

Although few factors are unequivocally associated with an increased risk of brain cancer, some are consequential.

• Most CNS neoplasms are thought to arise from individual cell mutations.
• A prior history of irradiation to the head for reasons other than treatment of the present tumor may increase the chance of primary brain tumor.
• A few inherited diseases, such as neurofibromatosis, tuberous sclerosis, multiple endocrine neoplasia (type 1), and retinoblastoma, increase the predilection to develop CNS tumors.
• The most common tumors originating from the cerebellopontine angle are acoustic neuroma and meningioma.
• Primary CNS lymphoma is a relatively frequent occurrence in HIV patients.
• Metastatic tumors reach the brain via hematogenous dissemination through the arterial system.
• • Lung cancer is by far the most common solid tumor disseminating to the brain, followed by breast, melanoma, and colon cancer.³
  • Less common sources of metastasis are malignant melanoma, testicular cancer, and renal cell cancer.
  • Prostate, uterine, and ovarian cancers are unlikely sources of brain metastasis.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Patients with cancer are predisposed to medical complications, including bleeding disturbances (hyperviscosity), metabolic disorders (hypercalcemia), and production of excessive hormones (syndrome of inappropriate antidiuretic hormone secretion).
• With clinical suspicion of cancer, obtain routine laboratory studies on admission, including a CBC, coagulation studies, and analysis of electrolytes and comprehensive metabolic panel.

Imaging Studies

• Obtain neuroimaging studies in patients with symptoms suggestive of an intracranial neoplasm (eg, acute mental status changes; new-onset seizures; focal, motor, or sensory deficits, including gait disturbance; suspicious headache; signs of elevated ICP, such as papilledema).
• Although some tumors exhibit a characteristic appearance, do not make an unequivocal diagnosis based solely on radiologic findings.
• Generally, CT is the imaging modality of choice for the ED physician.
• • Intravenous contrast material assists in tumor identification. Most tumors demonstrate enhancement with contrast material administration.
  • Tumors may appear hypodense, isodense, or hyperdense, or they may have mixed density.
  • Metastases to the brain tend to be multiple, but certain tumors, such as renal cell carcinomas, tend to be solitary metastatic brain lesions.
• With increasing availability, MRIs may supplant CTs as the imaging procedures of choice.
• • An MRI is most helpful for identifying tumors in the posterior fossa (including acoustic neuromas), hemorrhagic lesions. It is useful in patients with an allergy to iodinated contrast material or renal insufficiency.
  • Drawbacks to MRI include incompatibility with certain medical equipment, longer imaging times (increased risk of motion artifact), and poor visualization of the subarachnoid space.
  • Neither CT nor MRI can be used to differentiate tumor recurrence from radionecrosis.
• On plain skull radiographs, large pituitary adenomas are associated with a large sella turcica.

Procedures

• Lumbar puncture is not indicated in the ED in the patient with suspected CNS neoplasms.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Prehospital Care

Prehospital care is supportive and directed to the presenting symptom complex. For example, treat seizures in the usual manner. Airway disturbance, breathing difficulty, signs of pronounced elevation in ICP, and notable impairment of consciousness may necessitate definitive airway control with endotracheal intubation and, possibly, hyperventilation.

Emergency Department Care

ED treatment of the patient with an intracerebral neoplasm depends on both the nature of the tumor and the general condition of the patient. Decisions regarding surgical resection, initiation of radiation treatment, and chemotherapy are beyond the scope of practice of the ED physician. However, general principles are germane.

• Corticosteroids may dramatically reduce signs and symptoms related to cerebral edema. Affected patients may experience relief within the first few hours of steroid therapy.
• • Dexamethasone is the agent of choice because of its minimal salt-retaining properties. Recommended doses generally range from 4-24 mg daily.³ For patients with impaired consciousness or signs of increased intracranial pressure, 10 mg IV⁴ or 10-24 mg IV³ are recommended as the first dose. Side effects, notably proximal muscle weakness, are dose-dependent. Often, corticosteroids can be tapered or discontinued after definitive therapy. The final dose of steroids should be the lowest necessary to control the patient's neurologic symptoms.³
• For patients with signs or symptoms of impending herniation and airway compromise, consider use of adjunctive medications for rapid sequence intubation. These might include lidocaine and medication for rapid-onset neuromuscular blockade, with precautions to diminish fasciculations. Induction agents, such as thiopental, may be used.
• After definitive control of the airway, consider gentle hyperventilation.
• Discuss the use of mannitol with the appropriate consultant. Although mannitol may reduce transiently lower ICP, concern about rebound increases in ICP makes its use problematic.

Consultations

Local practice patterns govern requests for consultations.

• Generally, care of patients with a brain tumor is multidisciplinary, requiring assistance from a neurosurgeon, an oncologist, a radiologist, and an expert in radiation therapy.
• Management varies greatly depending on tumor location, tissue type, and comorbid conditions.
• Surgical treatment options may include tumor removal or debulking, installation of a ventricular shunt, and placement of radioactive implants.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Practice parameters from the American Academy of Neurology discourage prophylactic use of anticonvulsants for seizures in patients with newly diagnosed brain tumors and suggest that it is appropriate to taper and discontinue anticonvulsant use postoperatively in patients without seizures.⁵ Anticonvulsant use may be reserved for patients with clinical seizures, but some physicians prescribe prophylactic anticonvulsants in patients with cortical tumors.

Drug Category: Corticosteroids

Steroids are thought to stabilize cell membranes and diminish the vasogenic edema associated with tumors.

Drug Category: Hyperosmolar agents

These agents may reduce ICP and cerebral edema by creating an osmotic gradient across an intact blood-brain barrier. As water diffuses from the brain into the intravascular compartment, ICP decreases.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Further inpatient care is complex and may involve multiple consultants, depending on the tumor type and overall prognosis.
• Definitive diagnosis requires tissue biopsy performed by a qualified neurosurgeon.
• Additional neurosurgical options include resection or debulking and placement of a ventricular shunt with obstructive hydrocephalus.
• The admitting physician should coordinate oncologic or radiation oncology consultations.

Further Outpatient Care

• The patient's primary physician best manages coordination of consultants, but the responsible neurosurgeon should direct the treatment of specific postoperative complications or care.
• A common problem confronting the ED physician is a patient with a known brain neoplasm complaining of a headache or worsening other symptoms. This scenario always raises the possibility of tumor recurrence or worsening cerebral edema. Obtain a CT scan or MRI to rule out life-threatening events, such as hemorrhage or herniation.
• Radiation therapy for gliomas usually is performed on an outpatient basis.

In/Out Patient Meds

• Steroids or anticonvulsants may be used.
• Provide medications for patient comfort and pain control.

Transfer

• New occurrence of CNS tumor may require transfer to a facility with appropriate neurosurgical staff.
• Speak directly to the consultant prior to transfer to address initiation of steroid or anticonvulsant treatment.

Complications

• Acute symptoms in a patient with a brain tumor, particularly when signs and symptoms simulate the presentation of a cerebrovascular accident, suggest the possibility of acute hemorrhage into a tumor. Brain neoplasms predisposed to hemorrhage include lung cancer, melanoma, and choriocarcinoma.
• Lesions near the third ventricle can cause paroxysmal symptoms of headache, syncope, or mental status change. Additionally, vomiting, ataxia, memory changes, visual disturbances, or personality changes may occur.
• • Episodic increases in ICP secondary to pressure arising from blockage of cerebrospinal fluid outflow cause transient symptoms.
  • Sudden death is a reported complication from obstruction of outflow drainage from the third ventricle.
• Sudden increases in ICP may lead to life-threatening brain herniation, which shifts the brain parenchyma in the direction of least resistance: caudally through the foramen magnum (posterior fossa tumors) or transtentorial apertures.
• Some pituitary tumors are hormonally active and capable of producing acromegaly or galactorrhea. Pituitary apoplexy, an unusual complication arising from pituitary adenomas, describes hemorrhage into the tumor, leading to headache, deterioration of vision, oculomotor palsies, and shock secondary to acute adrenal insufficiency.
• Although radiation therapy rarely causes acute toxicity with modern dosing schedules and concomitant use of steroids, subacute or chronic effects may occur.
• • Subacute encephalopathy occurs 6-16 weeks after radiation therapy and is characterized by somnolence and headaches.
  • Chronic effects of prolonged radiation treatment tend to be more serious and range from impairment of intellectual capacity to complete incapacity.

Prognosis

• Tumor resectability, tumor location, age of the patient, and tumor histology are the primary determinants of survival.
• Without radiation therapy, the mean life expectancy of a patient with brain metastases is 1 month. Radiation therapy may extend survival to 4-6 months.
• Patients with seizures secondary to a brain tumor generally experience obvious neurologic deterioration over a 6-month course.
• Most patients with brain metastases die from progression of their systemic disease rather than from brain damage.

Patient Education

• For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education article Brain Cancer.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Consider a brain tumor in any adult patient with new-onset seizures.
• Temporal herniation may cause compression of the contralateral cerebral peduncle, resulting in false lateralizing signs.
• Patients with a brain tumor, especially a tumor in the frontal or temporal lobe, may present with behavioral and subtle mental status changes that can be mistaken for depression or other psychiatric illness.
• Delay in diagnosis of a brain tumor may expose the patient to deterioration and the physician to liability.
• Liberal use of imaging, based primarily on the history of new or changing headache types probably allows detection of most lesions.
• Wrongly diagnosing multiple CT-enhancing lesions as metastatic lesions when the patient has a treatable CNS infectious lesion is another pitfall. This is one argument for biopsy confirmation of all tumors.
• Neither CT nor MRI can be used to differentiate a tumor from radionecrosis in patients who have already undergone radiation therapy.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Neoplasms, brain. CT images of several tumor types. Slide courtesy of UMASS Continuing Education Office.
	View Full Size Image
Media type:  CT

Media file 2:  Neoplasms, brain. Colloid cyst of the third ventricle with obstructive hydrocephalus. Image courtesy of Peter Ferrera, MD.
	View Full Size Image
Media type:  CT

Media file 3:  Neoplasms, brain. Occipital lobe glioblastoma with surrounding edema.
	View Full Size Image
Media type:  CT

Media file 4:  Neoplasms, brain. Noncontrast CT scan of a tumor in the region of the posterior corpus callosum.
	View Full Size Image
Media type:  CT

Media file 5:  Neoplasms, brain. Contrast CT scan of the same patient as in media file4. Notice that contrast enhancement brings out detail.
	View Full Size Image
Media type:  CT

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. McKinney PA. Brain tumours: incidence, survival, and aetiology. J Neurol Neurosurg Psychiatry. Jun 2004;75 Suppl 2:ii12-7. [Medline].
2. DeAngelis LM. Brain tumors. N Engl J Med. Jan 11 2001;344(2):114-23. [Medline].
3. Lassman AB, DeAngelis LM. Brain metastases. Neurol Clin. Feb 2003;21(1):1-23, vii. [Medline].
4. Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol. Nov 2004;16(6):593-600. [Medline].
5. Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. May 23 2000;54(10):1886-93. [Medline].
6. Collins VP. Brain tumours: classification and genes. J Neurol Neurosurg Psychiatry. Jun 2004;75 Suppl 2:ii2-11. [Medline].
7. Ferrera PC, Kass LE. Third ventricle colloid cyst. Am J Emerg Med. Mar 1997;15(2):145-7. [Medline].
8. Fisher PG, Carson BS. Childhood brain tumors. Curr Ther Neruol Dis. 1997;239-245.
9. Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology. Sep 1993;43(9):1678-83. [Medline].
10. Grant R. Overview: Brain tumour diagnosis and management/Royal College of Physicians guidelines. J Neurol Neurosurg Psychiatry. Jun 2004;75 Suppl 2:ii18-23. [Medline].
11. Purdy RA, Kirby S. Headaches and brain tumors. Neurol Clin. Feb 2004;22(1):39-53. [Medline].
12. Shemie S, Jay V, Rutka J, Armstrong D. Acute obstructive hydrocephalus and sudden death in children. Ann Emerg Med. Apr 1997;29(4):524-8. [Medline].
13. Snyder H, Robinson K, Shah D, Brennan R, Handrigan M. Signs and symptoms of patients with brain tumors presenting to the emergency department. J Emerg Med. May-Jun 1993;11(3):253-8. [Medline].

Article Last Updated: Sep 20, 2007