brain

Epilepsy is a neurological condition that makes people susceptible to seizures. A seizure is a change in sensation, awareness or behaviour brought about by a brief electrical disturbance in the brain. Seizures are sometimes also called convulsions or fits. Another word for epilepsy is a seizure disorder.

Approximately 75% – 90% of individuals with TSC will have Epilepsy at some point in their life. Epilepsy can start at any age but many babies with TSC have a seizure during the first year of life.

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. An epilepsy nurse may also assist with epilepsy treatment and education

A neurosurgeon may be involved to determine if brain surgery is a possible treatment for an individual with TSC.

Signs and Symptoms

Epilepsy occurs in TSC is because the areas of abnormal brain development contain abnormal nerve cells. These nerve cells have abnormal bursts of electrical activity which cause the seizures.

Researchers are not sure which changes in the brain lead to seizures and why. The number and size of cortical tubers is thought to play a big part. The exact gene change that has caused TSC in the individual may also play a part. Because this is unknown, it is not possible to predict whether an individual with TSC will have seizures, what type they will be and how they should be treated.

Types of seizures may also change throughout the life of someone with TSC and epilepsy.

The different changes that occur in the brain due to TSC are covered on a separate page. Impacts of TSC and epilepsy on learning, behaviour and mental health is covered on a separate page.

Focal, partial, generalised – what is the difference?

The different lobes of the brain

Billions of nerve cells makeup the part of the brain called the cerebral cortex. The cerebral cortex makes up the two sides of the brain, which are called the cerebral hemispheres. Each hemisphere is made up of four areas of the brain -called the lobes. These four lobes are the frontal, temporal, parietal and occipital lobes.

An epileptic seizure may come from any part (lobe) of the cerebral hemispheres. If the epileptic seizure comes from one part of the brain it is called a focal or partial seizure. If the seizure comes from both sides of the brain at the same time, it is called a generalised seizure.

Some seizures start in one part of the brain and then move to involve other parts of the brain. These are sometimes called secondary generalized seizures.

Infantile spasms

Approximately one third of babies with TSC will develop infantile spasms. For many of them, this will be the first symptom that leads doctors to a diagnosis of Tuberous Sclerosis.

Infantile spasms are clusters of brief stiffening movements that typically start between 3 and 18 months of age and almost always occur before 2 years of age.

The most frequent and common characteristic is a sudden flexion of the neck (head nod) and all four extremities accompanied by adduction of the arms (movement of the arms towards midline as if the infant is hugging him/herself). Extensor type spasms are less common and are characterized by sudden extension of the neck and lower extremities with extension and abduction (movement of the arms away from midline to the sides).

In other cases, the spasms may be subtle, and only abrupt head nods occurring in clusters are noticed. In many cases, infantile spasms are a mix of characteristics.

At the end of a cluster the baby will often be very upset and will then be irritable for some time. Spasms often occur soon after the baby has woken from a sleep.

Sometimes infantile spasms are mistaken for normal body movements, colic/gastroesophageal reflux or startle reflex.

Other types of seizures

Some of the more common types of seizures experienced by people with TSC are listed below. For more information on seizures types, see these resources:

Focal or Partial Seizures:

  • Simple Partial seizures have a diverse range of presentations that include but are not limited to:
    • Involuntary jerking of one part of the body (“focal motor” signs).
    • Behaving out of character because the individual is hearing or seeing things that are not there; feeling unexplained fear, sadness, or joy; feeling tingling sensations; feeling nauseous; looking pale and sweating; appearing to be “drugged” because of pupillary dilatation. Jerking may begin in one area of body, arm, leg, or face. The seizure can’t be stopped, but the person stays awake and aware. Jerking may proceed from one area of the body to another and sometimes spreads to become a convulsive seizure.
  • Complex Partial seizures usually start with blank stare, followed by chewing (or lip smacking, swallowing), then random activity. The person appears unaware of surroundings; they may seem dazed and mumble; they may be unresponsive; their actions may be clumsy, not directed. The person may pick at their clothing, pick up objects, or even try to take clothes off. They may run, appear afraid, and may struggle or flail at restraint. Once a pattern is established, same set of actions usually occur with each seizure. Lasts a few minutes, but post-seizure confusion can last substantially longer. The individual will have no memory of what happened during seizure period.

At times partial seizures can progress to secondarily generalized seizures.

Generalised Seizures:

  • Myoclonic seizures involve a sudden, involuntary, brief shock-like muscle contraction that usually involves both sides of the body, with synchronous jerks most often affecting the neck, shoulders, upper arms, body, and upper legs. May cause person to spill what they were holding or fall off a chair.
  • In Atonic seizures, the individual suddenly loses postural tone, which may result in a head nod or jaw drops (milder form), or falling to the ground (stronger form). Consciousness is usually impaired. The individual usually recovers after a few seconds to a minute.
  • Absence seizures involve a stare that may begin and end gradually, usually lasts 5-30 seconds and is not generally provoked by hyperventilation. Child may be partially responsive during episode. Eye-blinking or slight twitching movements of the lips may be seen. Children with this type of seizure often have global cognitive impairment; therefore, it may be difficult to distinguish a seizure from the child’s usual behavior.

Febrile Seizures:

A febrile seizure is a convulsion associated with a significant rise in body temperature. The incidence of febrile seizures is higher in TSC affected people (approximately 10%) than in the general population (5%). Read more about febrile seizures.

Epilepsy syndromes

Another way of describing the epilepsy that an individual has is through a syndrome. The two main types of syndromes diagnosed in individuals with TSC and epilepsy are:

  • West syndrome: this is diagnosed on the basis of infantile spasms, the age at onset of spasms (under 12 months of age) and a typical EEG appearance – called hypsarrhythmia.
  • Lennox-Gastaut syndrome: this is diagnosed on the basis of different seizure types that occur in a child (particularly tonic, tonic-clonic and partial seizures), the age at onset of the different types of seizures (between 1 and 6 years of age) and a typical EEG appearance (called slow spike and slow wave activity).
The link between seizures and developmental delay

There have been many different studies into understanding the link between epilepsy and other symptoms of TSC such as intellectual impairment, autism and mental health issues.

Some research has suggested that epilepsy starting early in life, infantile spasms and epilepsy that cannot be controlled may all increase the chance of intellectual impairment and autism.

Although more research is needed to understand this better, it does suggest that controlling seizures as early as possible may help to improve neurological outcomes. This is why many doctors will be aggressive in treating seizures, especially during the first 2 years of life.

Status epilepticus

Anyone with epilepsy and TSC is at risk of status epilepticus. Possible triggers for this include an illness that results in a high temperature (fever) or missing doses of anticonvulsant medications.

Convulsive status epilepticus can be defined by the following:

A tonic-clonic seizure that lasts longer than 30 minutes or, repeated tonic-clonic seizures, each lasting less than 5 minutes with the child not recovering fully between each seizure and these seizures continue for at least minutes.

Convulsive status epilepcticus can also be called tonic-clonic status epilepticus.

Status epilepticus is a medical emergency and needs emergency treatment. If it is not treated urgently and successfully, then the person may suffer brain damage and, rarely, may die.

There are different types of status epilepticus and the other most common type which also occurs commonly in children with TSC is non-convulsive status epilepticus.

In non-convulsive status epilepticus the children become quieter than usual, may stop talking, drool excessively and appear to not to be aware of their surroundings. They may also have subtle head nods (atonic) or myoclonic seizures. Non-convulsive status epilepticus is common in children who have Lennox-Gastaut syndrome.

Parents are usually the first to recognise that their child has changed or is different. The EEG is very important in making a diagnosis of non-convulsive status epilepticus. Although it is not as severe a medical emergency as convulsive status epilepticus, it does require urgent treatment.

Monitoring, Tests and Diagnosis

The most common type of test done to diagnose epilepsy and to understand the type of epilepsy is an EEG. EEG stands for electroencephalogram and it is a painless test that records the brain’s electrical activity, sometimes called brain waves.

For more information on EEG and the different types of EEGs:

http://www.rch.org.au/cep/tests/index.cfm?doc_id=3174

Some parents who notice a change in their child’s behavior or seizure types find it useful to videotape the behavior or seizure. This may help a doctor make a diagnosis or decide which tests should be done and can be much easier than waiting in a hospital for the child to repeat the behavior or seizure.

Some individuals who have regular seizures, or their parents, find it helpful to track seizures on a computer or mobile phone. Seizure Tracker (link to resource to be added), developed by a TSC family in the USA, is one tool that can be used for this.

Treatment

There are several different ways to treat epilepsy in individuals with Tuberous Sclerosis:

  • Anticonvulsant medicines
  • A special epilepsy diet
  • Vagal Nerve stimulation
  • Surgery
  • mTOR inhibitor medicines

Treatment may often be a case of trial and error and doctors rely on their own experiences, the experiences of their colleagues and published research to decide which treatment option to recommend in an individual with TSC and epilepsy.

Anticonvulsant medicines

The majority of people who have epilepsy will take anti-epileptic drugs (AEDs) also known as anticonvulsant medications.

It may take a while to find the right medicine or amount (dose) of a medicine that works best for the person, whether a child or adult. Sometimes children and even some adults will need to take a combination of two or more AEDs.

More information on the different medicines used to treat epilepsy in TSC is available here:

http://www.tuberous-sclerosis.org/publications/pub_anti-epileptic_drugs_how_they_treat_seizures_and_their_unwanted_side-effects.pdf

Ketogenic diet

If medication does not successfully control the seizures in an individual with TSC, the ketogenic diet may be an option especially in young children.

The ketogenic diet is a diet that is high in fat content and low in carbohydrates that has been effective in treating epilepsy in some individuals with or without TSC. This diet is usually used for children rather than adults due to its restrictiveness, although there have been a few individuals with TSC continuing on the diet successfully into adulthood.

This diet is a medical regime and requires the help of an experienced dietician. When a neurologist recommends the ketogenic diet, they will usually refer the family to a dietician if one is not already a part of the clinic team.

The low glycemic index diet (LGIT) and modified Atkin’s diet are modifications of the ketogenic diet that are more palatable for some individuals. These epilepsy diets should never be tried without the help of a health professional as there are dangerous short and long-term side effects.

Vagal nerve stimulator

If medication does not successfully control the seizures in an individual with TSC, the vagal nerve stimulator (VNS) may be an option.

It involves insertion of a device, similar to a cardiac pacemaker, under the skin on the chest that will send intermittent electrical signals to the brain by stimulating the left vagus nerve in the neck. It is not fully understood how VNS works, but the theory is that the stimulation alters nerve pathways that lead to a seizure.

VNS has provided improved seizure control for some individuals with TSC. It is not possible to determine before implanting the device who will and will not respond.

More information about VNS is available here: http://www.rch.org.au/cep/treatments/index.cfm?doc_id=3245

Surgery

If medication does not successfully control the seizures in an individual with TSC, epilepsy surgery may be an option.

Although surgery has many risks and no guarantees, it can be successful in controlling seizures in individuals w are candidates for surgery. There are many TSC families in Australia that have been through brain surgery for epilepsy.

It is difficult to decide whether an individual is a candidate for epilepsy surgery. Different neurologists and neurosurgeons will have different opinions. The ideal candidate for surgery is an individual with only one seizure type and only one area of their brain that is the focus of the seizure. It is also ideal if that area of the brain can be safely removed without causing significant loss of function.

The pre-surgical stage involves a series of tests to better understand the types of seizures that an individual is having and what is happening inside the brain. This will usually involve a stay in the hospital and monitoring with a video EEG. This may be followed with a series of other tests to understand the structure of the brain of that individual.

The pre-surgical stage will result in a recommendation on whether surgery is an option and if it is, what type of surgery is recommended.

Most individuals with TSC will not fit the criteria for an ideal surgery candidate and the decision of whether to operate will be very difficult. It is important that a team of experienced health care professionals work together with the family in this process.

mTOR inihibtor medicines

There is some evidence from clinical trials that these new medicines may help to control seizures in some individuals with TSC.

This research in a very early stage and it will be some time before it is known if these medicines will become a real option for treating epilepsy.

 

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. Anti-epileptic drugs: how they treat seizures and their unwanted side-effects, Tuberous Sclerosis Association, viewed 9th April 2012, http://www.tuberous-sclerosis.org/publications/pub_anti-epileptic_drugs_how_they_treat_seizures_and_their_unwanted_side-effects.pdf
  3. Epilepsy in Adults with TSC, Tuberous Sclerosis Alliance, viewed 9th April 2012, http://tsalliance.org/pages.aspx?content=585
  4. Epilepsy Surgery for Individuals with TSC, Tuberous Sclerosis Alliance, viewed 9th April 2012, http://tsalliance.org/pages.aspx?content=586
  5. Infantile Spasms and TSC, Tuberous Sclerosis Alliance, viewed 9th April 2012, http://tsalliance.org/pages.aspx?content=592
  6. Types of Seixures Affecting Individuals with TSC, Tuberous Sclerosis Alliance, viewed 29th April 2012, http://tsalliance.org/pages.aspx?content=606
  7. Epilepsy Explained, Epilepsy Australia, viewed 29th April 2012, http://www.epilepsyaustralia.net/Epilepsy_Information/Epilepsy_explained/Epilepsy_explained.aspx#types
  8. Vagal Nerve Stimulation, The Royal Children’s Hospital Melbourne, viewed 9th April 2012, http://www.rch.org.au/cep/treatments/index.cfm?doc_id=3245
Parts of this web page have been adapted with permission from copyrighted content developed by the Tuberous Sclerosis Alliance (www.tsalliance.org) and the Tuberous Sclerosis Association (www.tuberous-sclerosis.org)