Brain Neoplasms

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Practice Essentials

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. See the image below.



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Neoplasms, brain. CT images of several tumor types. Slide courtesy of UMASS Continuing Education Office.

Signs and Symptoms

Presenting complaints of patients with an intracranial neoplasm tend to be similar for primary brain tumors and intracranial metastases. The onset of symptoms usually is insidious, but an acute episode may occur with bleeding into the tumor, or when an intraventricular tumor suddenly occludes the third ventricle.

Manifestations may be nonspecific and include the following:

CNS neoplasms also may manifest as follows:

Headache associated with intracranial neoplasms have the following characteristics:

Although often described as characteristic of tumor headaches, the following clincial features are not commonly present:

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. Findings may include the following:

See Clinical Presentation for more detail.

Diagnosis

With clinical suspicion of cancer, obtain routine laboratory studies on admission, including the following:

Obtain neuroimaging studies in patients with symptoms suggestive of an intracranial neoplasm, such as the following:

Although some tumors exhibit a characteristic appearance, do not make an unequivocal diagnosis based solely on radiologic findings. Generally, computed tomography (CT) is the imaging modality of choice for the emergency department physician. CT findings are as follows:

As magnetic resonance imaging (MRI) becomes increasingly available, it may supplant CT as the imaging procedure of choice. Features of MRI for imaging intracranial neoplasms are as follows:

See Workup for more detail.

Management

Acute treatment for cerebral edema from intracranial neoplasms is as follows:

Definitive treatment is as follows:

See Treatment and Medication for more detail.

For patient education resources, see the Cancer Center, as well as Brain Cancer.

Pathophysiology

Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema.



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Neoplasms, brain. Colloid cyst of the third ventricle with obstructive hydrocephalus. Image courtesy of Peter Ferrera, MD.

The cumulative effects of tumor invasion, 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 clinical course. These tumors tend to be larger at detection.

Most primary brain tumors do not metastasize, but if they do metastasize, intracranial spread generally precedes distant dissemination.

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.

Leptomeningeal infiltration may present with dysfunction of multiple cranial nerves.

Etiology

Although few factors are unequivocally associated with an increased risk of brain cancer, most CNS neoplasms are thought to arise from individual cell mutations. A few inherited diseases, such as neurofibromatosis, tuberous sclerosis, multiple endocrine neoplasia (type 1), and retinoblastoma, increase the predilection to develop CNS tumors. Primary CNS lymphoma is a relatively frequent occurrence in HIV patients. 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.

The most common tumors originating from the cerebellopontine angle are acoustic neuroma and meningioma.

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. 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.

Epidemiology

The American Cancer Society estimates that 23,880 brain and other nervous system cancers will be diagnosed in 2018.[4]  Estimates of the annual incidence rate of primary brain tumors range from 7-19.1 cases per 100,000 population. Metastatic tumors to the brain are more common, with more than 200,000 patients per year in the United States with a new diagnosis of intracranial metastases. 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.

The International Agency for Research on Cancer of the World Health Organization estimates that in 2012, brain and nervous system cancers occurred in 139,608 men and 116,605 women worldwide.[5]  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.

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.

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. 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 the fourth or fifth decade or beyond.

Prognosis

Prognostic features include the following:

In a study of 69 pediatric brain tumor survivors, the patients showed deficits in executive function, memory, and attention. Whole-brain radiation therapy, tumor size, young age at diagnosis, and male gender were risk factors for late cognitive sequelae.[6]  Adult survivors of pediatric brain tumors have an increased risk of psychiatric illnesses, including depression, anxiety, suicidal ideation, schizophrenia and related psychoses, and behavioral problems.[7]

In the United States, brain and other nervous system cancers are expected to cause approximately 16,830 deaths in 2018.[4]  Brain tumors are the second most common cancer in children, comprising 15-25% of all pediatric malignancies. 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.

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, which may comprise any of the following:

Symptoms may be nonspecific and include any of the following:

Central nervous system (CNS) neoplasms also may manifest as follows:

Onset of symptoms usually is insidious. However, an acute episode may occur with bleeding into the tumor, or when an intraventricular tumor suddenly occludes the third ventricle.

In a United Kingdom study of 139 children with brain tumors, the median time from symptom onset to diagnosis of a brain tumor was 3.3 months. Head tilt, cranial nerve palsies, endocrine and growth abnormalities, and reduced visual acuity were associated with a longer delay in diagnosis. Headache was the most common initial manifestation, occurring in 55 patients (40%). By the time of diagnosis, patients had a median of six signs and/or symptoms.[8]

In a study from the United States, the mean time to diagnosis in the emergency department from onset of any symptom was 86.3 days, and 104.5 days for headache. Approximately 91% of cases were diagnosed by computed tomography scan, with 48% of tumors located in the posterior fossa. Headache, nausea/vomitting, and gait disturbance were the most common presenting symptoms.[9]

Although headache is the symptom customarily associated with an intracranial neoplasm, it often is a late complaint. In addition, headache usually is not an isolated finding, and headache is the worst symptom in only one half of patients.

Other features of headache from brain tumors are as follows:

Prevailing portrayals of tumor headache that are in fact inaccurate include the following:

Manifestations of brain tumor may reflect the tumor site, as follows:

Pituitary adenomas may be divided into two 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-secreting pituitary adenomas more commonly complain of headache, visual problems, and impotence.

Seizures, focal or generalized, may be the earliest expression of a brain tumor. Depending on the rate of growth of the tumor, seizures may be present for months to years before a brain tumor is diagnosed. Seizures are common in patients with supratentorial meningioma, affecting anywhere from 10% to 50% of individuals with these lesions, and are frequently the presenting symptom.[10]   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. 

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. Findings in these patients may include the following:

Laboratory 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). Therefore, with clinical suspicion of cancer, obtain routine laboratory studies on admission, including the following:

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.

Diagnosis of a suspected brain tumor is dependent on appropriate brain imaging and histopathology. Gadolinium-enhanced magnetic resonance imaging (MRI) is the preferred modality because of its resolution and enhancement with contrast agents. If MRI cannot be performed (e.g., in patients with metallic implants, embedded devices, or claustrophobia), head and spine computed tomography (CT) is acceptable, although the resolution is not as high as MRI and it cannot adequately assess lesions in the posterior fossa and spine.[11]   

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.

Additional imaging such as magnetic resonance perfusion, magnetic resonance spectroscopy, or fluorodeoxyglucose positron emission tomography may be necessary for diagnosis and staging, and should be ordered only under the direction of the treating physician.[11]

Approach Considerations

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. The patient's primary physician best manages coordination of consultants, but the responsible neurosurgeon should direct the treatment of specific postoperative complications or care. New occurrence of CNS tumor may require transfer to a facility with appropriate neurosurgical staff. 

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.

 

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 intracranial pressure (ICP), and notable impairment of consciousness may necessitate definitive airway control with endotracheal intubation and, possibly, hyperventilation.

Emergency Department Care

Emergency department (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.

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.

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. For patients with impaired consciousness or signs of increased intracranial pressure (ICP), 10 mg IV[12] or 10-24 mg IV 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.

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.

Medical Care

Further inpatient care is complex and may involve multiple consultants, depending on the tumor type and overall prognosis. The admitting physician should coordinate oncologic or radiation oncology consultations. Radiation therapy for gliomas usually is performed on an outpatient basis.

Surgical Care

Definitive diagnosis requires tissue biopsy performed by a qualified neurosurgeon. Neurosurgical options include resection or debulking and placement of a ventricular shunt with obstructive hydrocephalus.

Complications

Acute symptoms in a patient with a brain tumor, particularly when signs and symptoms resemble stroke, 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, as follows:

Dexamethasone (Decadron)

Clinical Context:  Used in treatment of vasogenic cerebral edema; improves endothelial integrity.

Class Summary

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

Mannitol (Osmitrol)

Clinical Context:  May reduce subarachnoid space pressure by creating osmotic gradient between cerebrospinal fluid in arachnoid space and plasma. Not for long-term use.

Class Summary

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.

Author

Bruce M Lo, MD, MBA, CPE, RDMS, FACEP, FAAEM, FACHE, Chief, Department of Emergency Medicine, Sentara Norfolk General Hospital; Medical Ditector, Sentara Transfer Center; Professor and Assistant Program Director, Core Academic Faculty, Department of Emergency Medicine, Eastern Virginia Medical School

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Sanz Laniado Medical Center, Netanya, Israel

Disclosure: Nothing to disclose.

Additional Contributors

Edmond A Hooker, II, MD, DrPH, FAAEM, Associate Professor, Department of Health Services Administration, Xavier University, Cincinnati, Ohio; Assistant Professor, Department of Emergency Medicine, University of Cincinnati College of Medicine

Disclosure: Nothing to disclose.

J Stephen Huff, MD, FACEP, Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

Disclosure: Nothing to disclose.

References

  1. Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology. 1993 Sep. 43(9):1678-83. [View Abstract]
  2. Purdy RA, Kirby S. Headaches and brain tumors. Neurol Clin. 2004 Feb. 22(1):39-53. [View Abstract]
  3. Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology. 1993 Sep. 43(9):1678-83. [View Abstract]
  4. American Cancer Society. Cancer Facts & Figures 2018. Cancer.org. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf. 2018; Accessed: March 30, 2018.
  5. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. International Agency for Research on Cancer. Available at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed: August 10, 2015.
  6. Tonning Olsson I, Perrin S, Lundgren J, Hjorth L, Johanson A. Long-term cognitive sequelae after pediatric brain tumor related to medical risk factors, age, and sex. Pediatr Neurol. 2014 Oct. 51 (4):515-21. [View Abstract]
  7. Shah SS, Dellarole A, Peterson EC, Bregy A, Komotar R, Harvey PD, et al. Long-term psychiatric outcomes in pediatric brain tumor survivors. Childs Nerv Syst. 2015 May. 31 (5):653-63. [View Abstract]
  8. Wilne S, Collier J, Kennedy C, Jenkins A, Grout J, Mackie S, et al. Progression from first symptom to diagnosis in childhood brain tumours. Eur J Pediatr. 2012 Jan. 171(1):87-93. [View Abstract]
  9. Lanphear J, Sarnaik S. Presenting symptoms of pediatric brain tumors diagnosed in the emergency department. Pediatr Emerg Care. 2014 Feb. 30 (2):77-80. [View Abstract]
  10. Englot DJ, Magill ST, Han SJ, Chang EF, Berger MS, McDermott MW. Seizures in supratentorial meningioma: a systematic review and meta-analysis. J Neurosurg. 2016 Jun. 124 (6):1552-61. [View Abstract]
  11. Perkins A, Liu G. Primary Brain Tumors in Adults: Diagnosis and Treatment. Am Fam Physician. 2016 Feb 1. 93 (3):211-7. [View Abstract]
  12. Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol. 2004 Nov. 16(6):593-600. [View Abstract]

Neoplasms, brain. CT images of several tumor types. Slide courtesy of UMASS Continuing Education Office.

Neoplasms, brain. Colloid cyst of the third ventricle with obstructive hydrocephalus. Image courtesy of Peter Ferrera, MD.

Neoplasms, brain. Occipital lobe glioblastoma with surrounding edema.

Neoplasms, brain. CT images of several tumor types. Slide courtesy of UMASS Continuing Education Office.

Neoplasms, brain. Colloid cyst of the third ventricle with obstructive hydrocephalus. Image courtesy of Peter Ferrera, MD.

Neoplasms, brain. Occipital lobe glioblastoma with surrounding edema.

Neoplasms, brain. Noncontrast CT scan of a tumor in the region of the posterior corpus callosum.

Neoplasms, brain. Contrast CT scan of the same patient as in media file4. Notice that contrast enhancement brings out detail.