brain

Almost all people with TSC have some signs of TSC in their brain. These signs may cause only mild symptoms in some people and severe symptoms in others.

A term used by health professionals for things to do with the brain is neurology. Doctors who specialize in the brain are called neurologists. Epileptologists are a special kind of neurologist who specialises in treating Epilepsy. A neurosurgeon may be involved to determine if brain surgery is a possible treatment for an individual with TSC.

Signs and Symptoms

TSC can cause the following changes in the brain:

  • Cortical and subcortical tubers
  • Subpendymal nodules (SENs)
  • Subpendymal giant cell astrocytomas (SEGAs)

Although these changes can be called tumours, they are not cancerous.

The following topics are covered separately:

Cortical and subcortical tubers

These are found in the upper part of the brain and appear as an abnormal mass of tissue within the brain. They can also calcify or become hard. These may be large and distort the normal brain tissue. Tubers are best seen by magnetic resonance imaging (MRI).

It is thought that tubers develop along with the rest of the brain, so that the number of tubers in the brain of most individuals with TSC stays approximately the same throughout their life. This also means that tubers can be seen as early as 20 weeks’ gestation on a fetal MRI.
Tubers and the area of the brain around them, play a role in the development of seizures in TSC.

These tumours are the reason for the name Tuberous Sclerosis. “Tuber” is latin for swelling and “skleros” is greek for hard.

Subpendymal nodules (SENs)

SENs are found in about 80% of people with TSC and they are believed to not cause any symptoms. SENS are usually less than 1cm in diameter. SENs develop along with the rest of the brain but they may calcify or become hard.
If they have calcified, then SENS are visible on a Computerised Topography (CT) scan. If they have not, they may not be seen on CT images but will be seen on Magnetic Resonance Imaging (MRI).
Over time some SENs can grow to form SEGAs.

Subpendymal giant cell astrocytomas (SEGAs)

Subpendymal giant cell astrocytomas (SEGAs) are also called Subpendymal giant cell tumours (SGCTs).

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.

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).
Even though they are not cancerous, SEGAs can be problematic because they 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). This build up of pressure can result in symptoms such as vomiting, nausea, headache and changes in appetite, behavior and mood.
Up to 15% of individuals with TSC will develop a SEGA. SEGAs mostly grow from late childhood and the chance for growth greatly decreases after the mid-20s.

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 subependymal nodules (SENs) grow and become SEGAs.

Surveillance

Surveillance is important because it can lead to early detection and treatment. Each person with TSC should have an individual management plan developed with their medical team that uses these guidelines as a starting point.

  • An MRI study should be performed on diagnosis of TSC to get a baseline image of the brain.
  • An MRI should be repeated every 1 to 3 years
  • If a SEGA is found, an MRI should be repeated every 3 to 6 months to monitor growth and decide if any treatment is required.

Treatment

Tubers are sometimes treated as a part of epilepsy treatment. More information is provided here. SENs do not cause symptoms and require no treatment.

Subpendymal giant cell astrocytomas (SEGAs)  require treatment when they grow large enough to potentially block the flow of fluid inside the ventricles of the brain. The main treatment options are:

  • Surgery
  • mTOR inhibitor medicines

Because SEGAs are a benign tumour, radiation should never be used to treat this type of brain tumour.

Surgery

There are different philosophies on when to perform surgery to remove a SEGA, many doctors will recommend 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 tumour.

mTOR inihibtor medicines

In 2012, the mTOR inhibitor medicine everolimus was approved by the Therapeutic Goods Administration(TGA) in Australia for treatment of SEGAs. This was after approval in the USA in 2010. Approval in New Zealand is expected soon.

Everolimus is marketed in Australia as Afinitor® and referred to in medical literature as RAD001. The approval by the TGA was to treat SEGAs 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.

Because Afinitor® is not yet listed on the Pharmaceutical Benefits Scheme (PBS), funding arrangements will differ between health services. You should also discuss this with your doctor. Please contact ATSS if you need any more information.

Do SEGAs grow back after treatment?

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 treatment at some point in the future.

Early medical reports and the initial prospective clinical trial showed that SEGAs do regrow if mTOR inhibitor medicine 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.

 

About this article

Prepared by: Clare Stuart, The Australasian Tuberous Sclerosis Society

Reviewed by: Dr John Lawson, Paediatric Neurologist, Sydney Children’s Hospital

References:

  1. Kwiatkowski D.J., Whittemore V.H. & Thiele E.A. (2010) Tuberous Sclerosis Complex: Genes, Clinical Features, and Therapeutics. Weinheim: Wiley-Blackwell
  2. Subpendymal Giant Cell Astrocytoma (SEGA) or Subpendymal Giant Cell Tumor (SGCT), Tuberous Sclerosis Alliance, viewed 6th April 2012, http://tsalliance.org/pages.aspx?content=602

Parts of this web page have been adapted with permission from copyrighted content developed by the Tuberous Sclerosis Alliance (www.tsalliance.org)