Epilepsy Information

List of each individual AED and the potential effect on the baby

Pregnancy Category: Guidelines established by the FDA outlining the affects of drugs on reproduction and pregnancy. This assists physicians and patients in making the best treatment choices while planning a family and during pregnancy. 

Epilepsy in children

Children with epilepsy struggle to engage in a healthy life…..mind and body.  From glancing at the frightened faces of parents to glaring at the expressions of peers who have just seen them seize, to juggling medications, doctor visits and learning difficulties, the fight to simply “maintain” is a constant series of battles to win a faceless war.  As parents, you want to make it all better; see your child healthy and thriving. But how? The best answer to that question is that you need to be “armed” for combat…armed with information.  The following section has been written to fortify you with the ammunition you need to make wise choices in the very best interest of your child.

Classifying Epilepsy Syndromes

Epilepsy syndrome classification is very important in the management of infants, children, and adolescents with epilepsy.  By understanding if your child's epilepsy fits any of the well understood patterns of a specific epilepsy syndrome, the doctor can provide you with important information about your child's condition.  For example, some types of epilepsy may be out grown, whereas other epilepsy syndromes may very likely last a lifetime.  Some epilepsy syndromes may not necessarily require medication as seizures are likely to occur infrequently and not put the child at significant risk.  Other epilepsy types may have a high risk of frequent, poorly controlled seizures and may even put the child at risk for new learning problems or developmental delay. Determining what type of epilepsy (epilepsy syndrome) your child has can help your doctor determine what treatment options are most likely to control your child's seizures without exposing them to additional risks. 

There are many epilepsy syndromes known to present in childhood.  Some present in otherwise healthy neurologically normal children.  Others epilepsy syndromes present in children with developmental delay or other associated neurological and medical problems.  For some children it may be difficult to identify a specific epilepsy syndrome following the initial seizure or during the first several months or years after the initial diagnosis.  Over time new symptoms (learning problems, speech delay, new or different types of seizures) or signs (stiffness on one side of the body or weakness, seizures brought on by heavy breathing or overheating) may develop.  Additional tests like prolonged or overnight video EEG recordings, MRI or genetic tests may reveal new information that can eventually help classify your child's type of epilepsy.  In the following section we will review several well understood epilepsy syndromes that effect infants, children, and adolescents.  These syndromes will be presented according to the typical age when the children presents with symptoms and will be organized from infancy to adulthood.   

Epilepsy syndromes are often grouped by the age when seizures first occur.  A child's age plays an important role in their risk for seizures. The brain in infants and young children can more easily be provoked to have a seizure.  This is because the brain is rapidly growing and making new connections between brain cells. This process of rapid growth is what allows the infant to rapidly learn new skills like sitting, walking and talking.  However, this process also makes the brain very excited.  Very little may be needed to tip this excited state into a seizure. This is especially true if an additional irritant or provocation like fever, infection or injury occurs.  Additionally, a baby's brain is more at risk for specific types of seizures which cannot occur in the brain of an older child or adult.  Finally, the EEG findings (brain waves) are highly influenced by age. Normal EEG patterns change rapidly over the first few weeks of life and continue to make dramatic changes over the first 3 years of life.  Similarly, abnormal EEG patterns seen in infants and children with epilepsy may change over time.  This changing information can provide additional clues and help provide your child with an accurate epilepsy syndrome diagnosis.


NEWBORN PERIOD

Neonatal seizures can take many forms from clonic seizures (repeated rhythmic jerking of one or more limb), tonic seizures (sudden stiff posture), or subtle (staring, repeated non-purposeful movement like sucking or bicycling foot movements).  The causes can include benign (non-serious) causes described below as well as serious or symptomatic causes including stroke, asphyxia (inability to breathe), genetic or metabolic disorders, infection, as well as brain malformation and even withdrawal from in utero exposure to certain illicit drugs.

Idiopathic Neonatal convulsions: occur in otherwise healthy newborns in the first two weeks of life.  The EEG patterns (brain waves) remain normal or relatively normal between seizures and overall prognosis including development and seizure control is good. Typically a diagnosis is made by ruling out other possibilities, unless there is a strong family history of benign neonatal convulsions.  Tests to rule out infection of the brain, stroke, or other brain injury or metabolic cause must be performed as these causes may be life threatening and require immediate intervention.  If no cause can be found despite a complete evaluation, the seizures are classified into one of the two epilepsy syndromes below.

Benign Familial Neonatal Convulsions:

• Presentation:
  - Age: typically occur in first 2-15 days of life
    * Seizure types: Seizures are generally clonic (rhythmic jerking of one or both arms and legs) but may start with more subtle staring, chewing movements or an unusual cry. 
    * Seizures start from either side of the brain, often alternating from the left to the right on subsequent seizures.

• Diagnosis:
  - This diagnosis is made in children who have a family history of infants who developed seizures in the newborn period but outgrow seizures and develop normally.
 
• Causes:
  - Genetic causes: Typically there is a history of seizures in either the mother or the father which occurred during their first two weeks of life.  Rarely a history of newborn seizures affecting only a grandparent but not the parent can be obtained. 

• Triggers: Seizures typically occur immediately after waking from sleep.

• Prognosis:
  - Although these infants may have many seizures per day (as many as several per hour) the prognosis is good. 
  - Despite the frequency of seizures these infants continue to develop normally (eat appropriately, spend an appropriate amount of time asleep and awake as other newborns do, and are appropriately alert when awake).

• Treatment: no medications are needed

Benign Idiopathic Neonatal Convulsions (also called Fifth Day Fits):

• Presentation:
  - Age: Seizures often occur on or close to the fifth day after birth.
Seizure types: Seizures are usually clonic (rhythmic jerking of one or more arm and or leg) or apneic (the baby briefly stops breathing). The second seizure type is often associated with a dramatic color change where the infant becomes very pale or even looks bluish in color.

• Diagnosis:
  - The criteria for appropriate diagnosis of this disorder include the baby being born at full-term, there should be no history of complications during the pregnancy or delivery, and a normal neurological exam should be found before and between seizures.

• Prognosis:
  - In general there is the expectation that the child will outgrow the seizures and have normal development and intelligence in the future.
  - However rarely, some infants diagnosed as having benign Idiopathic Neonatal Convulsions have gone on to have developmental delay.

• Treatment: no medications are needed

Symptomatic seizures in the newborn period may be temporary or may be the first sign of a serious epilepsy syndrome.  Seizures following birth asphyxia or following a bleed or stroke in the brain often present within a few hours after delivery or after a bleed or stroke occur.  These seizures may be difficult to control during the first hours to days, but are often well controlled within a few days after the initial seizure occurs.  Prognosis is often based on the degree of brain injury seen on imaging (MRI/CT-scan), the baby's overall appearance and neurological exam, as well as how normal the EEG looks before, between and after seizures are controlled.  For many babies after a brief period of treatment ranging from a few days to a few months, a decision to stop seizure medications may be made by your child's neurologist.  However, a history of symptomatic seizures in the new born may be a risk factor to developing other types of epilepsy later in infancy or in early childhood.  

Some newborns develop hard to control seizures in the first few days of life that last into infancy and early childhood. These infants are often found to have seizures caused by large malformations of the brain or a genetic or metabolic disorder.  Seizures due to these causes usually carry a poor prognosis not only because the seizures are so hard to control but also because the underlying cause is associated with impairment of brain development or function. For these infants seizures may be very difficult or even impossible to control with medications and in some cases where one injured or malformed area of brain is found, epilepsy surgery may be recommended. For other babies found to have a metabolic disorder, certain dietary restrictions may be indicated. Seizures are often very different from those seen in newborns with other causes of seizures. Tonic (sudden sustained stiffening and posturing of the arms and body) or myoclonic (sudden quick random jerks of different limbs), can be seen and almost always these seizure types are associated with very serious forms of epilepsy. EEG monitoring often shows very abnormal brain waves between seizures which demonstrate how badly the brain is functioning.  
 

EARLY INFANCY:

Infantile Spasms (West Syndrome)

• Presentation:
  - Age of onset
    * Most commonly in the first year of life, typically between 4 and 8 months
  - Seizure types
    * Spasms (infantile spasms, epileptic spasms) are very brief seizures which consist of dramatic, rapid bending forward or backward of the neck, trunk, and/or arms and legs.  Spasms can also be more subtle and consist of a sudden, brief head drop.  
    * Spasms typically occur in clusters.

• Diagnosis:
  - Infantile spasms can have a profoundly negative influence on a child’s development.  Early recognition, diagnostic evaluation, and medical intervention are essential to minimize, or even reverse, the devastating impact of the seizures.
  - On EEG between events, there is a very characteristic brain wave patterns called hypsarrhythmia, which consists of much larger and disorganized brain activity with scattered spikes.  During infantile spasms, there is a sudden flattening of the EEG called an electrodecremental response.
  - There are numerous possible causes of IS, and an extensive imaging and laboratory evaluation is frequently necessary to identify a cause.  If the underlying cause can be identified, then at times, treatment can be targeted towards reversing this abnormality, and may result in a better outcome.
    * In seventy percent of cases a cause is identifiable.  These cases are called symptomatic.  (See causes below.)
    * Cases where no cause is identified are called cryptogenic.
    * A good physical exam including the skin is very important.  Some causes like Tuberous Sclerosis and Neurofibromatosis can be identified by hallmark signs on the skin.

• Causes: 
  - Structural abnormalities of the brain:
    * Lissencephaly (smooth brain)
    * Cortical Dysplasia (cortex malformation)
    * Porencephaly (abnormal fluid space)
  - Genetic causes
    * Chromosomal causes: Down Syndrome
    * Genetic: Tuberous Sclerosis
  - Metabolic Causes
    * Pyrodoxine (Vitamin B6) Deficiency
       - This can be a reversible cause of IS by replacing the missing vitamin
  - Infectious Causes
    * Infection in the womb or after birth affecting the brain fluid (meningitis) or brain tissue (encephalitis) by a bacteria or virus
  - Birth Injury
    * Lack of blood and oxygen to the brain

• Prognosis:
  - Overall prognosis is highly dependent on the underlying cause.  For example, a patient who experienced significantly long periods of oxygen deprivation at birth will have severe, irreversible brain injury and not be expected to improve with treatment of the IS.  On the other hand, children without any identifiable cause are more likely to have a good outcome.
    * Risk of intellectual disability
       - Nearly 45% will have significant intellectual disabilities.
       - A small percentage has no identifiable cause (idiopathic) and will be intellectually normal.
    * Risk of persistent epilepsy into adulthood
       - IS progresses to Lennox Gastaut Syndrome (see chapter) in approximately one third of cases.
  - Risk of death
    * In some series (series??), the risk of death was a high as one-third of patients

• Treatment:
  - Dependent on the underlying cause.  For example, if a reversible cause such as pyridoxine deficiency is identified, the first step is to treat this.
  - Cases due to an isolated structural abnormality such as cortical dysplasia may be successfully treated surgically.
  - Tuberous Scerosis has been shown to respond particularly well to vigabatrin.
  - ACTH  or corticosteroids are commonly used as well.
    * There is little scientific data to guide the dose and duration of therapy.
    * Side effects (list here?)??
    * ACTH is effective at controlling seizures but it remains unknown if it will improve the child’s long term cognitive outcome.
  - Anticonvulsant medications are used if IS occurs with other seizure types.
  - Ketogenic Diet has recently been shown also to be effective in many cases. 
  - More study remains to be completed  to discover the most effective treatment for eachcase of IS.

Benign myoclonic epilepsy of infancy

• Presentation:
  - Age: 6 month to 3 years
    * Seizure types:
       - myoclonic seizures
       - 3 of 10 are triggered by lights or startle
       - Some happen with fever (febrile seizures)

• Diagnosis:
 - EEG:
    * Ictal EEG (during seizure): polyspike-wave
    * Interictal EEG(between seizures): normal 
    * Genetic testing. Sodium channel gene (SCN1A)

• Causes:  
 - Unknown

• Prognosis:
 - Development: normal in most cases
 - Remission with rare predisposition for grand mal seizures later in life
 
• Treatment: 
 - Only for a few years
 - Valproic acid (Depakote) 

Dravet Syndrome (severe myoclonic epilepsy of infancy)

• Presentation:
 - Age: year of age
   * Seizure types: starts with prolonged febrile seizures (status epilepticus), generalized tonic clonic seizures (GTCS), atypical absence and complex partial seizures

• Diagnosis:
 - Genetic testing
 
• Causes: 
 - Genetic causes
 - Associated problems:
   * Status epilepticus
   * SUDEP
   * Autism
   * Movement disorders
   * Upper respiratory infections
   * Sleep problems 
   * Problems with nutrition and growth

• Prognosis:
  - Seizures stabilize by age four . 85% survive to adulthood.
  - Before seizures and then regression with developmental delay (???)
   * Risk of intellectual disability
   * Risk of persistent epilepsy into adulthood
   * Risk of death

• Treatment: difficult to control.
 
 
Generalized epilepsies with febrile seizures plus

• Presentation:
  - Age
   * Seizure types presentation: many syndromes in the same family (febrile seizures extending beyond age 6, GTC, myoclonic, absence, atonic)

• Diagnosis:
  - Genetic testing

• Causes: 
  - Genetic causes: Autosomal dominant (passed down through families). Many family members affected.

• Prognosis:
  - depending on the syndrome

• Treatment: depends of the type of seizures
 

LATE INFANCY

Lennox-Gastaut syndrome

• Presentation
  - Age of onset
    * Between 2 and 8
    * One third of cases of LGS are preceded by IS
  - Seizure types
    * Tonic-Atonic
    * Myoclonic
    * Atypical Absence
    * Generalized Tonic Clonic
    * Multifocal partial
  - Prolonged seizures (status epilepticus) is common and can occur in many different forms.
    * For example, some patients with LGS will develop atypical absence status epilepticus with only subtle evidence of slowed thinking and responsiveness.
  - Intellectual Ability
    * Usually associated with intellectual disability and behavioral issues

• Diagnosis:
o The EEG classically shows what is called a slow spike and wave pattern.

• Causes:
  - Structural abnormalities of the brain:
    * Lissencephaly (smooth brain)
    * Cortical Dysplasia (cortex malformation)
    * Porencephaly (abnormal fluid space)
  - Genetic causes
    * Rare
  - Metabolic Causes
    * Variable
  - Infectious Causes
    * Infection in the womb or after birth affecting the brain fluid (meningitis) or brain tissue (encephalitis) by a bacteria or virus
  - Birth Injury
    * Lack of blood and oxygen to the brain

• Prognosis:
  - Seizures associated with LGS tend to be treatment resistant.  The likelihood of remission of epilepsy is very low.
  - Cognitive deterioration may occur.

• Treatment:
  - See section on treatment
  - Felbamate
  - Co-management by a team of specialists including behaviorists and child mental health providers can be very helpful.

CHILDHOOD

Childhood absence epilepsy

• Presentation:
  - Age: 4 to 10 years
    * Seizure types:
       - Absence seizures 
       - Very frequent and in clusters
       - Triggers:
          * Hyperventilation
          * More rarely photic stimulation

• Diagnosis:
  - On EEG: generalized 3 Hz spike-wave discharges

• Causes: 
  - Genetic causes: family history of epilepsy

• Prognosis:
  - Development: normal
  - Disappear during adolescence
  - GTC may occur later in life
  - Rare cases of intractability

• Treatment:
  - Depakote
  - Lamictal
  - Klonopin
  - Keppra
  - Diamox
 
 
Landau Kleffner Syndrome (acquired epileptic aphasia)

• Presentation:
  - Age: between 3 and 8 years
  - Seizures types: 
    * Normal speech, then a seizure may occur (GTCS and atypical absence), speech regresses 
    * Sometime mistaken with hearing loss, but the problem is the processing of information. 
    * Seizures happen in 7 out of 10 patients.

• Diagnosis:
  - On EEG: 
    * Spikes in temporal region 
    * More active while patient has aphasia

• Causes: 
  - Structural abnormalities of the brain:
  - Genetic causes
  - Metabolic Causes
  - Infectious Causes
  - Birth Injury

• Prognosis:
  - Seizures usually controlled 
  - Speech could improve or not.

• Treatment:
  - AEDS: valproic acid, ethosuximide, denzodiazepines
  - Steroids
  - Gamma globulin (a natural protein substance that is part of the blood) 
  - Surgical treatment: multiple subpial transections (surgery that cuts nerve fibers in the outer layers of the brain while avoiding  the vital functions concentrated in the deeper layers of brain tissue.)
 

LATE CHILDHOOD-EARLY ADOLESCENCE

Benign Rolandic epilepsy

• Presentation
  - Age: 3 to 13 years (more frequently ages 7 to 8)
  - Seizures types:
    * Mainly nocturnal seizures
    * Mouth sensation or movements
    * Speech arrest
    * Increased drooling
    * Rare tonic-clonic seizures (unilateral: one side)

• Diagnosis:
  - On EEG: centro-temporal spikes(sharp waves over the central temporal regions of the brain)

• Causes: 
  - Genetic causes: genetic component. Runs in families

• Prognosis:
  - Development: normal
  - Could have some mild cognitive problems
  - Excellent, remission by adolescence

• Treatment
  - Only when:
    * Happens during sleep
    * Affects cognition
    * Repetitive seizures
 
 
Benign childhood seizures with occipital paroxysms of early onset

• Presentation:
  - Age:5 years
  - Seizures types:
    * Eye deviation
    * Consciousness affected
    * Evolves to a generalized tonic-clonic seizure.
    * Three out of 10 patients develop partial status epilepticus.
    * Most seizures occur during sleep.
    * Vomiting during the seizure

• Diagnosis:
  - On EEG: occipital spikes

• Prognosis: excellent

• Treatment: none
 
 
Benign childhood seizures with occipital paroxysms (late onset)

• Presentation:
  - Age:  8-10 years
  - Seizures types:
    * Visual symptoms are followed by clonic seizure involving half of the body.
    * Headaches occur after the seizures.

• Diagnosis:
  - On EEG

• Causes: 
  - Genetic causes

• Prognosis
  - Not as good as the early onset type

• Treatment: needed (Carbamazepine is choice)
 

LATE ADOLESCENCE-EARLY CHILDHOOD

Juvenile absence epilepsy

• Presentation:
  - Age: around puberty
  - Seizures types:
    * Absence seizures
    * Not as frequent as childhood absence epilepsy
    * Triggers:
       - Hyperventilation
       - Less frequently: sleep deprivation and photic stimulation

• Diagnosis:
  - On EEG: 3Hz generalized spike-wave discharges

• Causes: 
  - Genetic causes: 11% family history of epilepsy

• Prognosis: 85% controlled. 15% require more than one AED
 
• Treatment: Zarontin, Depakote, Lamictal, Keppra
 

Juvenile myoclonic epilepsy

• Presentation:
  - Age: around adolescence (mainly 12 to 18 years)
  - Seizures types:
    * Myoclonic seizures (always)
    * GTC (80%)
    * Absence seizures (50%)
    * Triggers: 
       - Photic stimulation 
       - Sleep deprivation
       - Hyperventilation

• Diagnosis:
  - On EEG: generalized polyspike-wave discharges

• Causes: 
  - Genetic causes: family history of epilepsy is common (around 50%)

• Prognosis: easy to control; requires treatment for life
 
• Treatment: Depakote, Lamictal, Keppra, Topamaz, Zonegran
 
Generalized tonic clonic seizures of awakening

• Presentation:
  - Age: around adolescence
  - Seizures types
    * GTC on awakening
    * Less common absence and myoclonic seizures
    * Trigger: photic stimulation

• Diagnosis:
  - On EEG: generalized spike-wave discharges

• Causes: 
  - Genetic causes: 12% family history of epilepsy

• Prognosis: easy to control; requires treatment for life

• Treatment: Depakote