Subependymal giant cell astrocytoma (SEGA) occurs in up to 15% of individuals with tuberous sclerosis complex (TSC) and is more likely to develop during childhood and adolescence. SEGA is a type of brain tumor that occurs in individuals with TSC that is non-cancerous and is not malignant but can still be very problematic. It is important to monitor for the occurrence of this brain tumor during childhood and until approximately the age of 21 years in individuals with TSC.
First, the word subependymal refers to the area below the ependyma (the membrane that lines the ventricles, or cerebrospinal fluid-filled spaces) of the brain. Giant cell refers to the very large, abnormal cells that are found with microscopic examination of the tumor. Astrocytoma refers to the type of tumor based on the most prevalent cell type. Historically, this tumor type has been classified as a slow-growing astrocytoma. However, a more appropriate term for this type of tumor may be subependymal giant cell tumor, or SGCT, since the cells in the tumor are of mixed types (not just astrocytes). You will see both terms used in the medical literature. We will use the term SEGA in this TSC Information Sheet.
SEGAs are usually found in the ventricles in the brain. Ventricles are natural spaces deep inside the brain filled with a clear fluid called cerebrospinal fluid (CSF). SEGAs are non-cancerous tumors, meaning they do not metastasize (spread to other parts of the brain or the body). However, the tumor can be problematic because it may grow sufficiently large to block the flow of CSF within the brain, causing an increase in the pressure within the head and enlargement of the fluid-filled ventricles (a process known as hydrocephalus).
Typically, SEGAs are very slow growing, but occasionally they may begin to grow more rapidly. It is not known what triggers the growth of a SEGA or why some individuals with TSC have a SEGA, whereas others do not. It is also not known why only some of the small nodules found on the surface of the ventricles, referred to as subependymal nodules (SENs), grow and become SEGAs.
Individuals with TSC should receive regular brain imaging, at least until adulthood and beyond that if medically necessary. If regular scanning is performed, changes in the size of a SEN indicating presence of a SEGA can usually be noted at an early stage so that appropriate follow-up and/or treatment can be initiated. SEGA can be observed on either MRI or CT scanning, and often a contrast agent will be used to better visualize the tumor. Some individuals with TSC have been diagnosed with the disease only after they were diagnosed with a symptomatic SEGA.
An individual with TSC who has a SEGA may initially have no signs or symptoms of having a brain tumor, only to develop symptoms when the tumor has grown large enough to block the flow of CSF and cause increased pressure. At this stage, some common signs are headaches, nausea, vomiting, clumsiness or inability to walk, increased frequency and/or severity of seizures, behavioral changes, and/or visual problems (blurred or double vision). The changes may be subtle, so it is important to be vigilant if an individual with TSC is known to have a SEGA. Signs of increased pressure may also be noted by a physician performing a detailed neurological assessment which includes examining the appearance of the nerves in the back of the eyes.
Typically, any SEGA that is either causing symptoms and/or enlarging requires surgical removal. Although there are different philosophies on when to perform surgery to remove a SEGA, the NIH Consensus Conference report (Roach et al., 1999) recommends that any SEGA that is increasing in size or causing symptoms should be surgically removed. There are several different surgical approaches used by neurosurgeons to successfully remove this type of tumor, but radiation therapy should not be used to treat a SEGA (there are examples of radiation therapy given for a SEGA actually made the tumor grow and transform into a cancerous tumor).
In 2010, the mTOR inhibitor everolimus (marketed in the United States as Afinitor® and referred to in medical literature as RAD001) was approved by the Federal Drug Administration (FDA) to treat SEGA associated with TSC in individuals for which surgery is not an option. Approval was based on the very positive results of a small but important clinical trial in 2010 that showed dramatic reduction in the size of the SEGA in those individuals who received the medication. A larger, more detailed Phase 3 clinical trial was completed in 2011 that confirmed the earlier study’s findings.
If a SEGA is completely surgically removed, that SEGA will not regrow. However, there have been numerous cases in which neurosurgeons are unsuccessful in the complete removal of a SEGA or in which another SEGA began to grow at a different location after the initial SEGA was removed. In such instances, the remaining or new SEGA will require some intervention (repeat surgery or medical treatment) at some point in the future.
Early medical reports and the initial prospective clinical trial showed that SEGAs do regrow if everolimus treatment is stopped. It is not known if long-term treatment with an mTOR inhibitor will eventually result in the complete reduction in the SEGA or prevent future regrowth.
The danger in not treating a SEGA that is increasing in size is that it will eventually block the flow of CSF and cause a significant increase in pressure in the brain, leading to severe neurological and behavioral changes. The individual may have increased frequency and severity of seizures, drastic personality and behavioral changes, and even loss of vision. Clumsiness, severe headaches, nausea, and vomiting may also be associated with a large SEGA. Before surgery to remove a SEGA was standard neurosurgical practice, many individuals with TSC died from the consequences of the hydrocephalus caused by the tumor.
You should contact your physician as soon as possible. If you are not currently under the care of a neurologist, you should contact your primary care physician. Ultimately, you will probably be referred to a neurologist or neurosurgeon who is familiar with treatment of SEGAs.
Most neurosurgeons have specialties within the field of neurosurgery, so you should look for a neurosurgeon who has training in brain tumor surgery and, if possible, surgery for SEGA. When you meet with the neurosurgeon, you might ask the following questions:
- How many times have you performed surgery to remove a SEGA from other individuals with TSC?
- What was the age range of the individuals with TSC on whom you have operated?
- What is the surgical approach you will use to remove the SEGA?
- What are the possible complications that might occur during and after the surgery?
- Once the surgery is complete, what will the recovery time be?
- What is the chance that the same SEGA will regrow?
- How will this be monitored post-surgery?
- Is treatment with Afinitor® an option?
- How effective is treatment with Afinito®r?
- What are the side effects of treatment with Afinitor®?
Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G, Dinopoulous A, Thomas G, Crone KR (2006) Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 59(3):490-8
Franz DN, Krueger DA, Balko MG (2010) Subependymal giant cell astrocytomas, In, Tuberous Sclerosis Complex: Genes, Clincal Features, and Therapeutics, DJ Kwiatkowski, VH Whittemore, EA Thiele (Editors), Weinheim: Wiley-Blackwell, pp: 211-228
Goh S, Butler W, Thiele EA (2004) Subependymal giant cell tumors in tuberous sclerosis complex. Neurology 63:1457-1461
Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 363(19):1801-11
Roach ES, DiMario FJ Jr, Kandt RS, Northrup H (1999) Tuberous Sclerosis Complex Consensus Conference: Recommendations for diagnostic evaluation. J Child Neurol 14:401-407
Torres OA, Roach ES, Delgado MR, Sparagana SP, Sheffield E, Swift D, Bruce D (1998) Early diagnosis of subependymal giant cell astrocytoma in patients with tuberous sclerosis. J Child Neurol 13(4):173-7
Afinitor®
www.afinitor.com
American Brain Tumor Association
2720 River Road, Des Plaines, IL 60018
www.abta.org
Telephone: 1-800-886-2282
Email: info@abta.org
The Childhood Brain Tumor Foundation
20312 Watkins Meadow Drive, Germantown, MD 20876
www.childhoodbraintumor.org
Toll Free: 877-217-4166
Telephone: 301-515-2900
Email: cbtf@childhoodbraintumor.org
National Brain Tumor Society
22 Battery Street, Suite 612, San Francisco, CA 94111-5520
www.braintumor.org
Telephone: 1-800-770-8287
National Cancer Institute, National Institutes of Health
Cancer Topics / “What you need to know about brain tumors”
www.cancer.gov/cancertopics/wyntk/brain
National Cancer Institute’s Cancer Information Service
NCI Public Inquiries Office, 6116 Executive Boulevard, Room 3036A,
Bethesda, MD 20892-8322
cis.nci.nih.gov/
Telephone: 1-800-422-6237
National Institute of Neurological Disorders and Stroke, National Institutes of Health
Brain and Spinal Tumor Information Page
For health or medical questions and general information:
NIH Neurological Institute, PO Box 5801, Bethesda, MD 20824
www.ninds.nih.gov/disorders/brainandspinaltumors/brainandspinaltumors.htm
Voice: (800) 352-9424 or (301) 496-5751
TTY (for people using adaptive equipment): (301) 468-5981
Pediatric Brain Tumor Foundation of the United States
302 Ridgefield Court, Asheville, NC 28806
www.pbtfus.org
Telephone: 1-828-665-6891 or 1-800-253-6530
FAX: 1-828-665-6894
Reviewed and updated by Darcy Krueger, MD, and David Franz, MD, February 2011.
**Tuberous Sclerosis Alliance Information Sheets are intended to provide basic information about TSC. They are not intended to, nor do they, constitute medical or other advice. Readers are warned not to take any action with regard to medical treatment without first consulting a physician. The TS Alliance does not promote or recommend any treatment, therapy, institution or health care plan.