TSC and

Introduction Although most epilepsy in TSC starts in children, Epilepsy is the tendency to have recurrent it can also begin in adults. The most common unprovoked . types in adults are focal (partial) seizures Unprovoked means that the seizures occur 'out of and tonic-clonic seizures. the blue' for no obvious reason such as following a head or meningitis or low blood sugar. Many children who have TSC and epilepsy also An epileptic seizure is caused by a sudden and have learning difficulties and behavioural abnormal burst of electrical activity from nerve (psychiatric) problems, including autism. The cells (neurons) in the . Billions of nerve earlier the epilepsy starts and the harder the cells makeup what is called the 'cerebral cortex'. seizures are to control with medication, the more The cerebral cortex makes up the two sides of likely the child will have learning difficulties and the brain, which are called the 'cerebral often more severe learning difficulties. hemispheres'. Each cerebral hemisphere is made up of four areas of the brain - called the Diagnosis 'lobes'. These four lobes are the frontal, The diagnosis of epilepsy depends on an temporal, parietal and occipital lobes. eyewitness, someone who has actually seen the child have the episodes - their seizures. The An epileptic seizure may come from any part eyewitness is usually the child's family who will (lobe) of the cerebral hemispheres. If the tell the doctor about what happens in the child's epileptic seizure comes from one part of the seizures. This is what doctors call the 'history'. brain it is called a 'focal' or 'partial seizure'. If the The history or description of the child's episodes or seizures is very important when making a seizure comes from both sides of the brain at the diagnosis of epilepsy. If the history is unclear same time, it is called a 'generalised' seizure. then the doctor will ask the family to try and video the child's episodes. This can be with a Epilepsy is very common in video-camera, camcorder or even a mobile complex (TSC). About 65-75% of children with phone. When the doctor looks at the video- TSC will develop epilepsy. The reason why recordings they will usually be able to make an epilepsy occurs in TSC is because of the tubers instant diagnosis of epilepsy. and areas of abnormal brain development in the of children Once the doctor has diagnosed epilepsy the and adults with TSC. The tubers and abnormal child will have a test called the electroen - areas of brain development (which are known cephalogram (EEG or brain wave test). medically as 'cortical dysplasia') contain The EEG may be undertaken with the child abnormal nerve cells - which have abnormal awake or, occasionally, when asleep. The EEG is bursts of activity and which cause the seizures. an important test because it will help to tell the doctor what type of epilepsy the child has The earliest type of epilepsy occurs in the first - the type of epilepsy is called the 'epilepsy syndrome'. year of life and the type of seizure is called infantile spasms, also known as West syndrome. Nearly all people with TSC have abnormalities In fact the diagnosis of TSC may only be made on CT (computerised tomography) or MRI after the infant has come to medical attention (magnetic resonance imaging) brain scans. with infantile spasms. Usually these are nodules (little lumps) under the lining of the brain called subependymal The other most common seizure type in children nodules. Less commonly a slow growing brain are focal, also called partial seizures and tonic- tumour (called a subependymal giant cell clonic seizures. astrocytoma - 'SEGA') may be seen on the scan. They are not usually operated on unless they Most children with TSC will have different types cause pressure on the brain causing of epileptic seizure. hydrocephalus (increased fluid in the brain). A SEGA does not usually cause seizures. TSC and Epilepsy

Seizure types In a complex partial seizure almost anything can The following gives a short description of the happen. What exactly does happen will depend most common types of seizures that occur in which part of the brain (which lobe) the seizure children with TSC. is coming from. The seizure may start first with an before the child (or adult) then starts to Infantile spasms (also called 'salaam show abnormal behaviour. This abnormal attacks'): behaviour may range from a slight dreaminess to This is often the first type of seizure to occur in complete unresponsiveness and lack of TSC. It usually starts between 4 and 9 months of awareness. The child may show 'automatisms' age, but sometimes as early as a few weeks of which means that the child does semi-purposeful age and as late as 12 months of age. Spasms actions such as fiddling with their clothes or that start after the age of 18 months are called buttons, lip-smacking, swallowing repeatedly or ''. A spasm involves a sudden mumbling incoherently. Their eyes or head may jerk - usually forwards but less commonly also repeatedly turn to one side. A complex backwards - with the arms thrown outwards and partial seizure may last for seconds the knees either coming up towards the chest or to many minutes. Two things may then happen at extending out in front of the infant. The spasm the end of a complex partial seizure. Either, the may involve both sides of the body at the same seizure will stop and then the person will be time or one side may be particularly involved. confused and may sleep. Or, the seizure may Each spasm lasts 1 to 3 seconds and may occur spread and progress into what is called a singly or in clusters. A cluster may last from a 'secondary generalised tonic-clonic' seizure'. minute to over 20 minutes. Between 5 and 50 spasms may occur in a cluster. At the end of a Tonic-clonic seizure: cluster the infant will often be very upset and This is the most common and also the most well- will then be irritable for some time. Spasms recognised type of epileptic seizure. It is also usually occur soon after the infant has woken called a 'grand mal' attack. The seizure involves from sleep (a day-time nap or night's sleep). If two phases - the tonic and the clonic phase. The the spasms have been occurring for some weeks seizure often starts with a sudden cry or grunt. the infant's development may slow down and Within a second or two, the person stiffens and if they may even be thought to not see properly. standing will fall. The jaw is often clenched and Their sleep and feeding pattern may also be the tongue may be bitten. The eyes are turned disrupted. upwards. If the bladder is full, there may be urinary incontinence (the person 'wets Focal (partial) seizures: themselves'). This stiffening or tonic phase These are common in TSC. They are sometimes usually lasts 20 to 30 seconds after which the divided up into 'simple' and 'complex' partial clonic (or jerking) part occurs. In the clonic part, seizures. Simple means that the child remains the jerks increase in frequency, reach a peak and fully conscious and complex means that the then start to slow down before then stopping. child's consciousness is impaired but mot Over 90% of tonic-clonic seizures last 2 completely lost. to 3 minutes but rarely they may last longer than 5 minutes. If the seizure last longer than 5 In a simple seizure the child (or adult) may minutes this is often called 'convulsive status complain of an abnormal sensation or feeling. epilepticus'. This can be an unpleasant feeling in the stomach, an unpleasant smell or taste, sudden 'Drop attacks' or 'drop seizures': fear or episode of deja vu. This is called an Different types of seizures may cause the child to 'aura'. A simple partial seizure may also cause suddenly 'drop' and either stumble or actually jerking of one side of the face, arm or leg whilst fall down. There are three types of seizures that the person is still able to talk and interact with cause 'drop attacks'. These are 'tonic' or their surroundings. stiffening seizures (as if a tree has been felled), TSC and Epilepsy

'atonic' (as if a puppet's strings have been suddenly cut) and 'myoclonic' (as if someone has Convulsive, also called tonic-clonic status been suddenly shocked or startled).Sometimes epilepticus can be defined by the following: two of these seizures may occur together, and this is often called a 'myoclonic-atonic' seizure. a tonic-clonic seizure that lasts longer than 30 minutes Myoclonic seizure: or, These are quite common in children with TSC. repeated tonic-clonic seizures, each lasting The seizure looks like a sudden shock or startle less than 5 minutes with the child not and can involve the whole body, one side of the recovering fully between each seizure and body, the face or just one arm or leg. Myoclonic these seizures continue for at least minutes. seizures may be focal (coming from one part or lobe of the brain - usually the frontal lobe) or Status epilepticus is a medical emergency and generalised. needs emergency treatment. If it is not treated urgently and successfully, then the child may Absence seizures: suffer brain damage and, rarely, may die. The child's consciousness is lost during this type There are different types of status epilepticus of seizure but there are no abnormal movements. and the other most common type which also They used to be called 'petit mal' attacks but this occurs commonly in children with TSC is 'non- term is no longer used. Absence seizures are convulsive status epilepticus'. very rare in children with TSC. Some children In 'non-convulsive status epilepticus' the children with TSC can have seizures in which they appear become quieter than usual, may stop talking, to be unresponsive and 'blank' and fidget with drool excessively and appear to not to be aware their clothes for a minute or so - but these will be of their surroundings. They may also have subtle focal and not absence seizures. head nods (atonic) or myoclonic seizures. Non- convulsive status epilepticus is common in Epilepsy syndrome children who have Lennox-Gastaut syndrome. Different types of epilepsy - called the 'epilepsy Parents are usually the first to recognise that syndrome' - can occur in children with TSC. The their child 'has changed' or is 'different'. The EEG two most common epilepsy syndromes are: is very important in making a diagnosis of non- convulsive status epilepticus. Although it is not 1. West syndrome: this is diagnosed on the basis as severe a medical emergency as convulsive of infantile spasms, the age at onset of spasms status epilepticus, it does require urgent (under 12 months of age) and a typical EEG treatment. appearance - called . Treatment 2. Lennox-Gastaut syndrome: this is diagnosed In general the same medicines which are used to on the basis of different that occur treat any type of epilepsy are used to control the in a child (particularly tonic, tonic-clonic and seizures occurring in TSC. Particularly helpful partial seizures), the age at onset of the different types of seizures (between 1 and 6 years of age) drugs include carbamazepine, vigabatrin (for and a typical EEG appearance (called slow spike infantile spasms), sodium valproate, , and slow wave activity). levetiracetam, rufinamide and topiramate. Other drugs that may be used include corticosteroids It is important to understand that a child with and nitrazepam for the treatment of infantile TSC may start with West syndrome in the first spasms (West syndrome). Treatment tends to be year of life and then evolve (change) into less effective in those with severe learning Lennox-Gastaut syndrome in the second or third difficulties, than in those who do not have year of life. learning difficulties. One drug in the lowest effective dose should be used if possible. The recognition of un-wanted side-effects from TSC and Epilepsy

medication is more difficult in children and Advice, information and support particularly if the child has learning difficulties. Advice on all aspects of epilepsy may be found This is because they may not be able to describe from: any side-effects. It is therefore important that those who care for the child should look out for (previously called the British any changes in their child's behaviour. Epilepsy Association) - tel 0113 210 8800 Epilepsy Helpline: freephone 0808 800 5050 A treatment called the ketogenic diet may sometimes be helpful for children with seizures E-mail address [email protected] that are difficult to control by medicine. The Website www.epilepsy.org.uk ketogenic diet is available in three types: the 'classical', the 'medium chain triglyceride (MCT)' Advice and information on the different and 'modified Atkin's'. It is important to antiepileptic drugs used to treat epilepsy can be understand that the ketogenic diet is not a found from: normal diet and children need to take vitamin www.medicinesforchildren.org.uk and mineral supplements. The diet is also difficult for the family to prepare and the child to take. Epilepsy surgery or the implantation of a vagal nerve stimulator (VNS) may be an effective treatment option for a very small number of children and adults with seizures that do not respond to antiepileptic medication.

More information on the anti-epileptic drugs (AEDs) used in people with TSC can be found in another fact sheet ('Antiepileptic drugs: how they treat seizures and their unwanted side- effects')

Prognosis (outcome) The outcome for children with TSC and epilepsy varies enormously. Most seizures will continue Author: into later life, including into adult life. Although Dr Richard E. Appleton tonic-clonic seizures may become less frequent Consultant Paediatric Neurologist with time, focal (partial) seizures usually The Roald Dahl EEG Unit continue. However, there are always exceptions Paediatric Neurosciences Foundation Alder Hey Children's Hospital to this general rule. Treatment (sometimes Liverpool including surgery for a very small group of children) will help to reduce the number or August 2011 change the pattern of seizures, but it is unlikely that the epilepsy will ever completely 'go away'. Further information on TSC and the work of the Tuberous Sclerosis Association can be obtained from our website at: Epilepsy is generally more difficult to control if www.tuberous-sclerosis.org the child has moderate or severe learning difficulties. While every effort is made to ensure that our publications are correct, please note that some information may change after the date of printing. Information in this leaflet is not intended to be a substitute for medical advice from your own doctors, who know your individual circumstances. We strongly recommend you talk to your doctor, and share the above information. The TSA cannot be held responsible for any actions taken as a result of using TSA information resources. Tuberous Sclerosis Association is a Company Limited by Guarantee Registered in and No. 2900107 English Registered Charity Number. 1039549 | Scottish Registered Charity No. SC042780 Registered Office: Abertawe House, Ystrad Road, Fforestfach, Swansea, SA5 4JB