Patient information: Meningioma

MENINGIOMA OVERVIEW

Meningiomas are brain tumors that develop in the tissue that surrounds and protects the outer surface of the brain and spinal cord (the meninges). Meningiomas account for about 15 to 30 percent of all tumors that originate in the brain. They are seen most frequently after age 40, and are more common in women than men [1].

Meningiomas can occur in any part of the lining over the brain or spinal cord (figure 1). About 90 percent occur within the head: around the cerebral hemispheres (just inside the skull), on the under surface of the brain (at the base of the skull), or in the lower part of the brain (the brainstem, which is located just above the spinal cord). Most of the remaining meningiomas arise in the optic nerve sheath (which protects the nerve connecting the eye to the brain) and around the spinal cord.

CLASSIFICATION OF MENINGIOMA

Meningiomas are classified according to their appearance when examined under the microscope and their position in the brain. Microscopic examination provides information about the cells comprising the meningioma, including how rapidly the cells are dividing (referred to as the "mitotic index") and whether the meningioma cells are growing into or invading the adjacent normal brain. Classification provides valuable information about the likelihood of meningioma returning ("recurring") after treatment.

The most widely used classification system is that of the World Health Organization (WHO), which separates meningiomas into three categories:

Grade I or benign meningiomas — Benign meningiomas are slow-growing tumors that have well-defined borders and do not appear to invade the adjacent normal brain. Few meningioma cells are actively dividing (ie, the tumor has a low mitotic index). Approximately 90 percent of all meningiomas fall into this category.

Grade II or atypical meningiomas — Atypical meningiomas contain more cells that are actively dividing (ie, they have a higher mitotic index) than benign meningiomas. In addition, grade II tumors have other features that suggest that they are growing more rapidly than benign meningiomas. These lesions are more likely to recur than benign tumors. Atypical meningiomas constitute about 5 to 7 percent of all meningiomas.

Grade III or malignant meningiomas — Malignant meningiomas, which are sometimes referred to as anaplastic meningiomas, have the highest mitotic index. Malignant meningiomas are likely to recur after treatment. These comprise 1 to 3 percent of all meningiomas.

A higher grade correlates with a worse prognosis. Patients with benign (grade I) meningiomas generally do well, with 80 percent or more remaining free of progression or recurrence after their initial treatment. In contrast, patients with atypical (grade II) and malignant (grade III) meningiomas are at much higher risk for recurrence. In one report, patients with atypical meningiomas had recurrence within an average of five years, while patients with malignant meningiomas had recurrence within an average of only two years [2].

MENINGIOMA RISK FACTORS

The cause of meningiomas is not well understood, but may include both genetic (inherited) and environmental factors. Several conditions have been associated with an increased risk for the development of a meningioma [1]:

• Neurofibromatosis - Neurofibromatosis type 2 is a rare inherited disease that usually appears first during childhood. This disorder affects the skin and the nervous system, and increases the risk of meningiomas as well as other brain tumors. Affected patients may develop multiple meningiomas.
• Previous radiation therapy treatment - Patients who have had radiation exposure to the head have an increased risk for developing a meningioma, especially 10 to 20 years after treatment. Individuals who underwent irradiation of the brain and spinal cord during treatment for childhood leukemia are at a particularly high risk.
• History of head trauma — Magnetic resonance imaging (MRI) or computed tomography (CT scan) are frequently performed after a head injury. These tests do not increase the risk of developing meningiomas, but instead increases the chance of finding a meningioma that is not causing any symptoms.
• Exposure to female hormones and breast cancer — Several observations support a link between exposure to female hormones and the risk of meningioma. Meningiomas are more common in women overall, particularly in those who use postmenopausal hormone replacement therapy [3]. In addition, meningiomas may increase in size during pregnancy, a time when female hormones are at their highest levels. There is also a well-described relationship between breast cancer (a tumor that is dependent upon female hormones for growth) and meningioma.

Women with a history of breast cancer have a higher incidence of meningiomas, and women with a history of a meningioma have a greater likelihood of developing breast cancer [4]. Although not proven, these data suggest a shared underlying cause for both tumors.

MENINGIOMA SYMPTOMS

As noted above, meningiomas may be identified after the patient has an MRI or CT scan for some other reason, such as a head injury. Meningiomas may also be discovered when a person seeks medical attention because he or she is experiencing neurologic symptoms [5]. A variety of symptoms are possible, depending primarily on the location of the meningioma.

Seizures — Seizures (sometimes called "fits") are the result of disorganized electrical activity in the brain. They can cause a person to pass out, involuntarily move the arms and legs, and/or lose muscle control throughout the body. Seizures are also seen in patients with epilepsy and other neurologic disorders. Among patients with meningioma, seizures are the most common presenting symptom and occur in 30 to 40 percent of patients [6].

Neurologic symptoms — Symptoms of a meningioma develop as a result of abnormal functioning of a specific area of the brain. This usually occurs when the tumor presses on normal brain tissue. The symptoms depend upon the location of the meningioma within the brain and the function of that particular area (eg, movement, vision, hearing, sense of balance).

A wide range of symptoms can be seen in patients with meningiomas. Some examples include:

• Visual changes - Individuals with a meningioma may experience a variety of visual difficulties such as loss of vision in one eye, blind spots, or blurred or double vision. Visual changes may not be noticed by the patient, and may only be noticed as a result of detailed testing.
• Hearing loss - Meningiomas can cause hearing loss by damaging or compressing the cochlear nerve, which transmits nerve impulses from the ear to the brain.
• Mental status changes - Patients with large meningiomas on the undersurface of the brain may have subtle changes in their personality or mental status, causing the person to appear that they are not paying attention or are forgetful.
• Arm and/or leg weakness - A meningioma can cause different patterns of weakness in the arms and legs, depending upon the location of the tumor. As an example, parasagittal meningiomas (ie, tumors located along the separation of the right and left halves of the brain, (figure 1) may cause weakness in both legs. In contrast, tumors arising at the foramen magnum (ie, the location where the base of the brain connects to the spinal cord) may produce a progressive weakness first in the arm and then progresses to involve the leg on the same side, followed by similar changes on the other side of the body.

Obstructive hydrocephalus — As meningiomas grow, they may block the flow of spinal fluid (referred to as obstructive hydrocephalus). Spinal fluid is a clear liquid that is produced within the brain; it functions to fill and protect spaces within and around the brain and spinal cord. If the flow of spinal fluid is blocked, pressure within the head increases. As the pressure on the brain increases, a person may experience headaches (particularly in the morning), nausea, and vomiting. If the condition is untreated, the person may become unable to respond to those around him or her (called a coma).

MENINGIOMA TESTS

If a meningioma is suspected, the clinician will want to obtain a detailed scan of the brain, using either MRI or CT. Both give a detailed image of the brain's structure, and both can show a tumor and its location.

CT scans are generally more readily available and less expensive than MRI, so a brain CT is often the first test that is ordered. However, MRI is the preferred test if a brain tumor is suspected because it can define more precisely the location and extent of a tumor in the brain or spinal cord (including the meninges), allowing for better treatment planning. Furthermore, the appearance of meningiomas on MRI scanning is unique, meaning that few other types of tumors have a similar appearance. As a result of this unique appearance, a biopsy to confirm that a tumor is a meningioma may not be needed.

In some cases, other disorders need to be ruled out to make a definite diagnosis. As examples, infections (such as tuberculosis), cancers other than meningiomas, and inflammatory diseases (such as sarcoidosis) can cause similar neurologic signs and/or symptoms and thickening of the meninges, making it difficult to determine if a meningioma or another problem is the cause.

MENINGIOMA TREATMENT

The initial treatment of a meningioma may include surgery, radiation therapy, or careful observation without treatment (sometimes referred to as "conservative management"). (See "Treatment of meningiomas".)

Risks versus benefits of treatment — The best approach requires a balance between the potential benefits of treatment (ie, alleviating symptoms and preventing further tumor growth) and the potential side effects and risks of treatment.

Factors that are considered in choosing among different treatment options include:

• Location of the meningioma — The location of the meningioma determines whether or not the tumor can be removed completely and whether or not blood vessels, nerves, and the underlying brain are likely to be damaged during surgery. As an example, tumors located on the surface of the brain are easiest to remove without risking potentially serious complications.

In contrast, tumors located on the undersurface of the brain or in the groove between the right and left halves of the brain may be more difficult to remove safely. When a tumor cannot be removed with surgery, radiotherapy may be used in conjunction with partial removal of the meningioma.

• Size of the meningioma — Large tumors are more likely to compress or damage the brain, either directly or by causing swelling of the surrounding normal brain. In contrast, small tumors may not produce symptoms. Thus, patients with larger tumors are more likely to require surgery, even though the operation may be difficult.
• Symptoms — Tumors that produce symptoms generally require treatment, both to relieve symptoms and prevent their worsening. If a patient is asymptomatic and has no evidence of neurologic dysfunction, careful observation may be appropriate until it can be determined how fast the tumor is growing.
• Age — Active treatment may not be recommended for older patients with small meningiomas that do not cause symptoms because of the increased risk of serious medical complications following surgery in this age group. In addition, if an older person's tumor is growing slowly, it may never reach a size where it causes symptoms.

In contrast, surgery is more often recommended for younger patients who are less likely to have serious treatment complications. Furthermore, younger patients have a longer life expectancy, and even a slow growing tumor may have time to reach a size where it could cause symptoms.

• Overall medical condition — Surgery to remove a brain tumor is complex and can be associated with serious complications; this is more likely to occur in patients who have other serious medical conditions.

Surgery — Surgery is the preferred treatment for most meningiomas.

Extent of surgery — Total removal of a meningioma provides the best chance of avoiding a future recurrence. However, the ability to completely remove the tumor depends upon the size and location of the meningioma. Some tumors cannot be totally removed because the tumor is too close or involved with important parts of the brain or blood vessels. In such cases, the tumor may be only partially removed. For tumors near the optic nerve, a small sample of the tumor may be removed so that it can be examined more closely with a microscope.

To improve the chances of completely removing a meningioma, a procedure called embolization may be recommended before surgery. During this procedure, a catheter is carefully placed into the blood vessels leading to or "feeding" the tumor. A material is injected into the blood vessels, which blocks the blood flow. This helps to decrease the risk of serious bleeding during surgery [7].

For tumors that are incompletely removed, the likelihood of recurrence is relatively high, even for grade I tumors. As an example, of 581 patients treated with surgery alone, 75 percent of those undergoing complete removal of a meningioma were free of recurrence 10 years after surgery compared with 39 percent whose tumors had not been completely resected [8].

Following surgery, the risk of tumor recurrence depends upon how much tumor was removed and whether it was cancerous, noncancerous, or atypical. (See 'Meningioma outcomes' below.) For patients whose tumor cannot be removed completely with surgery, radiation therapy is often recommended after surgery to reduce the risk of recurrence (see 'Adjuvant radiotherapy' below.

Complications of surgery — Complications associated with surgery include damage to nearby normal brain and medical complications of major surgery (eg, bleeding, infection). Examples of potentially serious complications include:

• Accumulation of fluid in the brain (cerebral edema) is common after surgery for meningiomas. A steroid medication such as dexamethasone (Decadron) may be given before and after surgery to minimize the extent of cerebral edema.
• About 20 percent of patients without seizures prior to surgery will develop them after surgery. Thus antiseizure medication is usually recommended following surgery. The medication can usually be slowly discontinued within one week after surgery if seizures do not occur.
• Worsened or new neurologic symptoms may develop after surgery. Examples of neurologic symptoms include muscle weakness, speech problems, or difficulty with coordination. These symptoms are a result of damage to the brain or other parts of the nervous system, or they may be due to bleeding, cerebral edema, or infection.
• Medical complications of brain surgery include pneumonia, heart attack, an irregular heart rhythm, or blood clots.
• Patients who undergo brain surgery or who have brain tumors have an increased risk of blood clots in the veins (deep venous thrombosis) and movement of blood clots to the lungs (pulmonary embolism). As a result, preventive measures are recommended after surgery. This includes use of anticoagulant medications and compression boots (devices that go around the legs and inflate periodically). (See "Patient information: Deep vein thrombosis (DVT)".)

Radiation therapy — Radiation therapy uses high energy x-rays to damage tumor cells. The x-rays are carefully aimed at the area of the brain affected by the tumor. Unlike normal cells, tumor cells are less able to repair the damage caused by exposure to x-radiation, particularly when the radiation is administered over several days.

Radiation treatment is given in frequent low doses (usually daily treatment, five days per week for 5 to 6 weeks). The total radiation dose is based upon the number of treatments and the amount of radiation administered per treatment. The area of the area of the brain treated is called the treatment field. The total radiation dose and the treatment field are carefully calculated to maximize radiation exposure of tumor cells and minimize damage to the normal brain tissue.

The standard way to deliver radiation is by external beam radiation therapy (EBRT). During EBRT, the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient as he or she lies on a table underneath the machine. The high energy beams are targeted to the area of the brain where the meningioma is located.

Radiation therapy is used for patients who have had partial removal of their meningioma. In addition, radiation may be recommended when surgery is not possible or if surgery has more risks than benefits. As an example, radiation therapy has become the preferred treatment for optic nerve sheath meningiomas (ie, tumors arising in the lining around the nerve to the eye), since there is a lower risk of vision loss after radiation compared to surgery.

Side effects of radiotherapy — A common concern of patients who undergo radiation therapy is treatment-related side effects. Radiation kills both tumor and normal cells, although tumor cells are somewhat more sensitive to the effects of radiation. Nevertheless, radiation therapy cannot kill all tumor cells without damaging nearby normal brain tissue. Side effects of radiotherapy to the brain can be divided into short term and long term effects.

• Short term effects — During radiation treatment, hair loss will occur, typically starting around the third or fourth week of therapy. Hair loss is limited to the areas where treatment occurs; this may be temporary or permanent. Regrowth typically begins two to three months after treatment ends. Mild fatigue is common and often does not develop until the last few weeks of radiation treatment. Mild skin redness or irritation may occur and is temporary. Headaches or nausea occur less frequently and can be treated so that they are not persistent.
• Long term effects — Potential long term effects of RT are more concerning but fortunately less common than short term side effects, especially when modern dosing and treatment plans are used. The most serious long term effect of RT is death of a large number of normal brain cells; this is called radiation necrosis. This may occur many months after the radiation therapy is completed, particularly if high doses are used [6].

Most patients have no symptoms of radiation necrosis. However, patients who have symptoms may have difficulties with short term memory, planning and reaching goals, controlling behavior, paying attention, and organizing thoughts [9]. The risk of these effects depends upon the location and size of the tumor being irradiated and the radiation techniques used; high doses of radiation to a small area are thought to pose a greater risk than lower doses of radiation to larger areas of the brain.

Adjuvant radiotherapy — Use of radiation therapy after partial surgical removal of meningioma is called adjuvant radiotherapy. Adjuvant radiotherapy appears to reduce the risk of recurrence substantially. In one analysis, 77 percent of patients who received adjuvant radiotherapy after a partial surgical removal of a noncancerous meningioma had no recurrence after 10 years [10]. This outcome is similar to that of people who have complete removal of a noncancerous meningioma.

Stereotactic radiosurgery — Stereotactic radiosurgery is an alternative to external beam radiation therapy. This does not actually involve performing surgery, but instead uses narrow beams of radiation that are delivered from multiple angles. This allows a very high dose of radiation to be delivered to a narrow area. This approach may offer substantial advantages to a person with a meningioma because it is able to deliver more radiation to the tumor while minimizing the amount of normal brain that is affected. In contrast to conventional external beam radiation therapy, stereotactic radiosurgery is given as a single treatment.

Stereotactic radiosurgery has been used to deliver adjuvant radiation therapy following partial removal of a meningioma. It has also been used as an alternative to surgery for patients with relatively small meningiomas that cannot be completely removed with surgery. Stereotactic radiosurgery and surgical removal have similar long-term outcomes for patients with small meningiomas [11].

Stereotactic radiotherapy — Stereotactic radiotherapy is slightly different than stereotactic radiosurgery, although both use multiple narrow beams of radiation directed from different angles. However, stereotactic radiotherapy divides the dose into several treatments rather than giving the dose in one single treatment. The intent of stereotactic radiotherapy is to reduce radiation injury to nearby brain structures while maintaining tumor control.

This technique has been particularly useful in meningiomas of the optic nerve sheath, as well as those arising at the base of the skull.

Watchful waiting versus treatment — If a meningioma is small and does not cause symptoms, it may be possible to postpone surgery and/or radiation therapy. The decision to delay treatment is also influenced by the location and size of the tumor, as well as the person's overall medical condition. Treatment is usually considered if there is evidence of tumor growth or if the person develops symptoms.

Watchful waiting requires periodic physical examination along with an imaging test (MRI or CT scan of the head). This is usually recommended every three months for one year, then once per year, assuming that the meningioma does not grow or cause symptoms during this time.

Outcomes do not appear to be worse in patients who are closely monitored. In a review of 60 patients who were diagnosed with small, asymptomatic meningiomas, none developed symptoms during an average of 32 months [12]. Of the 45 patients who had a repeat MRI or CT, 35 had no increase in the size of their tumor, while the remaining 10 showed slow tumor growth, even over the course of up to 15 years.

Systemic therapy — Several treatments, including chemotherapy, hormone therapy, and immunotherapy, have been studied in patients whose tumor recurs after surgery and/or radiation therapy. These treatments are referred to as systemic treatments because they are given by mouth or into a vein and can affect the entire body. The goal of systemic therapy is to slow the growth of the meningioma. The benefits of systemic therapy are usually limited and the treatment is not intended to cure the condition. If possible, re-irradiation or repeat surgery should be considered.

Systemic treatments have been used for patients with malignant meningiomas in an attempt to prevent recurrence. Although initial reports were positive, subsequent studies have not confirmed a benefit. Thus, systemic therapy is usually reserved for treatment of meningiomas that recur after surgery or radiotherapy.

MENINGIOMA OUTCOMES

The long-term outcome of people with meningioma depends upon several factors. For patients who require treatment of symptomatic or large meningiomas, the outcome depends upon the completeness of surgery and the meningioma type (ie, benign, atypical, or malignant). It is important to remember that discussions of outcomes are based upon averages; these averages do not necessarily predict how long an individual patient will survive.

• Small meningiomas that cause no symptoms and do not require treatment do not usually shorten a person's life.
• Complete resection of the tumor is possible in about 80 percent of patients with benign meningiomas, approximately 70 to 80 percent of whom survive at least ten years without a recurrence.
• For patients whose tumors cannot be completely removed and those with cancerous tumors, the rate of recurrence is markedly increased. However, the use of radiation therapy after surgery has improved outcomes, and the risk of recurrence may be similar to patients whose tumor is completely resected.
• Cancerous (malignant) meningiomas are much more likely to recur, even after complete surgical removal.
• Recurrence rates are somewhat lower after removal of atypical meningiomas, although recurrence is more frequent than in people who have surgical removal of a benign meningioma. The benefit of postoperative radiation is controversial in these patients.

CLINICAL TRIALS

Progress in treating meningioma requires that better treatments be identified through clinical trials. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Clinical trials are conducted in many countries around the world. Ask for more information about clinical trials, or read about clinical trials at:

       www.cancer.gov/clinical_trials/learning/

       www.cancer.gov/clinical_trials/

       http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Deep vein thrombosis (DVT)

Professional Level Information:
Biology and clinical features of meningioma
Classification of brain tumors
Risk factors for brain tumors
Spinal cord tumors
Treatment of meningiomas

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• American Brain Tumor Association

      (www.abta.org)

• American Cancer Society

      (www.cancer.org)

• National Cancer Institute

      (www.cancer.gov)

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• OncoLink

       (www.oncolink.com/index.cfm)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

      (http://cancer.about.com/forum)