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Subependymal giant cell astrocytoma (SEGA) occurs in up to 20% 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 noncancerous 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 25 years in individuals with TSC.
First, the word subependymal refers to the area below the ependymal lining, a membrane that surrounds the cerebrospinal fluid-filled spaces within 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, since the cells in the tumor are not just astrocytic but as well neuronal in origin, the term subependymal giant cell tumor or SGCT has been suggested. At the International TSC Consensus Conference in June 2012 experts recommended to continue using the term SEGA nonetheless for consistency.
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 noncancerous 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 spaces (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), may eventually grow and become SEGAs.
Individuals with TSC should receive regular brain imaging, at least until adulthood. If regular scanning is performed, a SEGA can usually be noted at an early stage so that appropriate follow-up and/or treatment can be initiated.
New SEGAs seem to very rarely arise after 20-25 years of age. Brain imaging, preferably MRI with and without contrast, should be performed every 1 to 3 years until the age of 25 years. Beyond 25 years of age screening brain MRI may not be needed and follow-up intervals may be prolonged thereafter if a SEGA has remained stable. 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. CSF now accumulates and causes increased pressure in the brain. 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.
In the past surgery has been the sole treatment strategy for growing and/or symptomatic SEGAs.
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. Approval was based on the very positive results of an important clinical trial in 2010 and subsequently confirmed by a larger, more detailed phase 3 clinical trial in 2013 documenting successful shrinkage in TSC associated SEGAs.
There are advantages and disadvantages of surgical and medical treatment, which should be reviewed with physicians familiar with TSC and SEGA. Aspects that help in decisionmaking are summarized by the expert recommendations from the International Tuberous Sclerosis Complex Consensus Conference in 2012 (to be published in Pediatric Neurology).
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 repeat surgery or medical treatment at some point in the future.
Medical reports and prospective clinical trials showed that SEGAs do regrow if treatment with a mTOR inhibitor is stopped. It is not yet known if and when long-term treatment with an mTOR inhibitor will eventually avert the risk of re-growth.
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 headaches, nausea, and vomiting. Increased frequency and/or severity of seizures, neurological and behavioral changes, clumsiness, visual disturbance and even loss of vision may be associated. Hydrocephalus caused by the SEGA can be life threatening and necessitates treatment.
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, neuro-oncologist 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 in children 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 a mTOR inhibitor an option?
- What are the side effects of treatment with a mTOR inhibitor?
Franz DN, Belousova E, Sparagana S, et al. (2013) Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 381: 125-132.
Franz DN, Krueger DA, Balko MG (2010) Subependymal giant cell astrocytomas, In Tuberous Sclerosis Complex: Genes, Clincal Features, and Therapeutics, DJ Kwiatkowski, VHWhittemore, 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.
Roth J, Roach SE, MD; Bartels U, Jóźwiak S, Koenig MK, Weiner HL, Franz DN, Wang HZ (2013) Subependymal giant cell astrocytoma: diagnosis, screening, and treatment.
Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012. Accepted by Pediatric Neurology (publication pending)
American Brain Tumor Association
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Children's Brain Tumor Foundation
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The Childhood Brain Tumor Foundation
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National Brain Tumor Society
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National Cancer Institute, National Institutes of Health
Cancer Topics / “What you need to know about brain tumors”
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
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Telephone: 1-800-352-9424 or 1-301-496-5751
For access to free Telecommunications Relay Services (TRS) for people with hearing or speech impairment dial 7-1-1 on your telephone.
Pediatric Brain Tumor Foundation
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Telephone: 1-828-665-6891 or 1-800-253-6530 (8:30 am – 5:00 pm Eastern Time)
Reviewed and updated by Darcy Krueger, MD, and David Franz, MD, February 2011; by TS Alliance Ute Bartels, MD, August 2013
**This information from the Tuberous Sclerosis Alliance is intended to provide basic information about TSC. It is not intended to, nor does it, 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.