epilepsy in children

2/5/2014 Epilepsy in children

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Epilepsy in children

Katie McPeak, MD, Gloria Galloway, MD, and John B. Bodensteiner, MDRevised: 17 Jun 2010Copyright Elsevier BV. All rights reserved.

Summary

Description

Epilepsy is a chronic condition characterized by recurrent seizures

It is frequently diagnosed in childhood, and more than 75% of patients have their first seizure before theage of 18 years

Seizures involve sudden attacks of involuntary movements or convulsions, or in some cases brief losses ofawareness with or without repetitive behaviors (automatisms), such as picking at clothing or lip smacking

They occur as a result of the synchronous firing of neurons and can be caused by any number ofstructural, metabolic, or drug-induced changes

Classified as idiopathic (with no known cause) or symptomatic (causes include high fever, tumors, ormetabolic disorders)

Types of seizure include generalized convulsions (generalized tonic-clonic seizures, infantile spasms,absence seizures), and partial/focal seizures (simple or complex, depending on whether consciousness isaltered)

Epilepsy can have profound physical and psychological consequences in children, including sudden death,injuries, and mood disorders

Status epilepticus is continuous or repetitive seizure activity with failure to regain consciousness betweenconvulsions. A seizure duration of longer than 10 minutes in a child should be treated as status epilepticus

Immediate action

If a seizure occurs:

Ensure that the airway is clear

Consider administering a rectal, intranasal, or buccal benzodiazepine to stop a prolonged convulsion (>2minutes)

After seizure, a patient may be turned onto his or her side to avoid aspiration, but not while convulsions arepresent because shoulder dislocation may result

Status epilepticus:

Status epilepticus (seizure in a child lasting longer than 10 minutes) is a medical emergency that requiresimmediate attention to airway, breathing, and circulation

If the patient does not respond within a few minutes to one of the forms of benzodiazepine, an emergencyresponse team should be called, measures should be taken to lessen risk to patient before their arrival,and the patient should be transferred to an emergency department for evaluation and treatment

Urgent action

Patients with breakthrough seizures despite anticonvulsant therapy might not be complying with their medicationregimen and might require hospitalization for parenteral therapy.


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Key points

Proper seizure evaluation and classification is vital for effective management of epilepsy

In a patient with recurrent unprovoked seizures, an imaging study, electroencephalography (EEG), andpossibly a lumbar puncture typically are indicated

Remission is best achieved with monotherapy with a first-line agent

Status epilepticus is a medical emergency requiring immediate attention that includes positioning thepatient to avoid injury; checking and managing the patient's airway, breathing, and circulation;administering buccal, intranasal, or rectal benzodiazepines; and immediate transferring the patient to anemergency department

In patients on anticonvulsant therapy, the primary etiology of status epilepticus is the erroneous or abrupttapering of medications

Background

Cardinal features

Epilepsy is a chronic condition characterized by recurrent seizures

It is frequently diagnosed in childhood, and more than 75% of patients have their first seizure before theage of 18 years

Seizures are episodes of disturbed behavior caused by paroxysmal, uncontrolled hypersynchronousdischarges from an aggregate of central nervous system (CNS) neurons due to a chronic underlyingprocess

Seizures may be genetic, idiopathic, or may be attributable to systemic disorders or local brain lesions

A single seizure, or recurrent seizures due to correctable or avoidable circumstances, do not indicate thata patient has epilepsy

Patients may present with partial (focal) seizures, which originate in a localized area of the cortex, orgeneralized seizures, which involve diffuse regions of the brain

Diagnosis of epilepsy is primarily clinical, supported by EEG findings

Classification of seizures is vital because it eliminates the need for unnecessary investigations and allowsfor optimal management and treatment

Remission is best achieved by monotherapy with one of the first-line drugs (carbamazepine and valproate).The selected drug depends on seizure type, age of patient, concurrent medications, and medical illnesses

Status epilepticus is continuous or repetitive seizure activity with failure to regain consciousness betweenconvulsions. Current recommendations are that any child with a seizure duration longer than 10 minutesshould be treated as having status epilepticus (almost all self-limiting convulsions stop within 5 minutes ofonset)

Prolonged seizures are associated with significant morbidity and mortality. Status epilepticus produceshypoxia, acidosis, hypertension, a relative reduction in cerebral oxygen delivery as the seizure progresses,raised intracranial pressure, a rise in body temperature (hyperpyrexia a risk), hyperkalemia, and in a smallnumber of cases rhabdomyolysis with acute renal failure or death

Diagnosis of an epileptic syndrome may be possible after consideration of age at onset and type of seizure,cognitive development and neurologic examination, and EEG findings.

Benign partial epilepsy of childhood (benign epilepsy with centrotemporal spikes, benign rolandic epilepsy):

Onset usually is between 2 and 14 years of age


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Seizures usually are partial (may progress to secondarily generalized) and classically occur during sleep

Signs and symptoms often are confined to the face (twisting of the mouth, guttural noises, dysphagia,excessive salivation)

EEG typically shows repetitive spikes in the centrotemporal (rolandic) region with a characteristichorizontal dipole of the spikes

Childhood absence epilepsy:

Seizures are rare in children under age 5, rarely last longer than 30 seconds, and are not associated withpostictal state

Characterized by frequently recurrent absence seizures, with cessation of motor activity or speech, blankfacial expression, and flickering of eyelids

EEG shows typical 3-per-second spike and generalized wave discharge

Juvenile myoclonic epilepsy:

The leading symptoms are jerky movements occurring in the morning, occasional absence seizures, andoccasional generalized seizures often precipitated by environmental factors

Other keys to the diagnosis include normal intelligence, onset around adolescence, seizures occurringshortly after waking, and precipitating factors such as sleep deprivation and psychological stress

EEG shows an irregular spike-and-wave pattern

West syndrome (infantile spasms):

Children with infantile spasms present during the first year of life

Seizures usually consist of clusters of mixed flexor and extensor spasms of trunk and extremities,persisting for minutes, with brief intervals between each spasm

Parents will describe the child as 'falling over' with arms extending forward

EEG shows characteristic hypsarrhythmia (high-voltage slow waves, irregularly interspersed with spikesand sharp waves)

Approximately 75% of children with West syndrome have an underlying CNS disorder. Children with Downsyndrome and tuberous sclerosis complex have a higher incidence of infantile spasm

Lennox-Gastaut syndrome:

Onset is age 1 to 6 years

May evolve from infantile spasms

Seizures are frequent and vary in type among patients; they may include atonic, atypical absence,myoclonic, tonic-clonic, and partial

Most children with Lennox-Gastaut syndrome demonstrate some degree of impaired intellectual functioningor information processing, along with developmental delays and behavioral disturbances

EEG typically shows slow spike-and-wave pattern

Causes

Epilepsy is not caused by a single disorder but, rather, is caused by any cerebral pathology that results insustained synchronous discharge of groups of neurons. Seizures occur in association with a number ofsystemic disorders

No specific etiology can be found in almost two thirds of patients


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Common causes

Genetic propensity

Congenital abnormalities

Antenatal and perinatal injury, especially hypoxic ischemic encephalopathy

Central nervous infection, including parasites ( ie, cysticercosis)

Vascular causes ( ie , stroke and vascular malformations)

Cerebral tumors ( benign or malignant )

Head injury

Demyelinating diseases of the CNS

Toxic causes (drugs)

Metabolic causes ( eg , electrolyte imbalance, renal and hepatic failure)

Breath-holding spells in toddlers

Childhood febrile seizure in infants

Rare causes

Psychiatric or functional (pseudoseizures).

Serious causes

Central nervous system infection

Cerebral tumors

Metabolic disturbances

Stroke

Contributory or predisposing factors

Common precipitants of seizures include:

Waking from sleep and sleep deprivation

Toxic and metabolic factors such as drugs, hypoglycemia, and hypoxia

Reflex stimuli such as glare, flashing lights, television, reading, sounds, thinking, startle, movement;genetic generalized seizure syndromes ( eg, juvenile myoclonic epilepsy) are mainly triggered by thesefactors

Stressful events in childhood

Epidemiology

Incidence and prevalence

Epilepsy is one of the most common of the neurologic disorders.

Incidence

Annual incidence is approximately 100 cases per 100,000 persons in the first year of life. The incidence thendeclines after the first year.

Prevalence


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500 to 1,000 cases per 100,000 persons.

Frequency

Approximately 35% to 40% of children with epilepsy also have mental retardation.

DemographicsAge

More than 75% of patients have their first seizure before age 18 years

Incidence of new cases is biphasic, the highest being in early infancy and rising again in the elderlypopulation

Simple absence (petit mal) seizures are uncommon before age 5 years

Benign partial epilepsy with centrotemporal spikes (rolandic epilepsy) occurs between the ages of 2 and 14years with a peak age of onset of 9 to 10 years, but usually does not persist into adulthood

Juvenile myoclonic epilepsy usually begins between the ages of 12 and 16 years and is lifelong

Infantile spasms (West syndrome) occur during the first year of life

Age of onset of Lennox-Gastaut syndrome is 1 to 6 years

Gender

Slightly higher prevalence in males (male-to-female ratio of 1.2:1)

Simple absence seizures are more prevalent in girls

Race

There is a higher risk of childhood epilepsy in black children than in white children

Cumulative incidence per 1,000 persons aged 15 years or younger is 19.63 in black boys, 19.51 in blackgirls, 9.53 in white boys, and 9.10 in white girls

Incidence in children is lowest in the UK and Canada, intermediate in the U.S. and Japan, and generallyhigh in Scandinavia and Italy. Incidence may be 20% to 50% higher in developing countries

Genetics

Genetic factors influence certain childhood epilepsies

Inherited primary epilepsies account for approximately 30% of chronic epilepsies

Family history of seizure is statistically more likely to be found in patients with epilepsy beginning inchildhood (7.5%) than in adulthood (1.5%)

Many of the neurologic structural lesions that increase susceptibility to seizures are caused by inheriteddisorders (structural and metabolic)

Epilepsy is associated with many mental retardation syndromes, such as Down syndrome

Autosomal genetic factors form the basis of abnormal EEG pattern observed in absence and rolandic(derived from the sylvian fissure) epilepsy

The juvenile myoclonic epilepsy gene locus has been identified on chromosome 6p21

Geography

Incidence and prevalence of seizures are higher in less-developed countries


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Parasites ( eg, neurocysticercosis) are the most common cause of seizures worldwide and account for theincreased prevalence of seizures in underdeveloped countries; however, the cause of increased seizures inAmerican underprivileged children is unknown

Prevalence is highest in parts of the world with the greatest risk for brain injuries ( eg, from birth trauma,infections, poor perinatal care, head trauma)

Socioeconomic status

Prevalence is higher in patients from lower socioeconomic groups, who are more likely to suffer frominfections, poor perinatal care, and head trauma

There is a higher risk of epilepsy in young, poor black patients

At least part of the burden of epilepsy can be solved by use of preventive methods to improve social health

Codes

ICD-9 code

345 Epilepsy

345.0 Generalized nonconvulsive epilepsy

345.1 Generalized convulsive epilepsy

345.2 Petit mal status

345.3 Grand mal status

345.4 Partial epilepsy, with impairment of consciousness

345.5 Partial epilepsy, without mention of impairment of consciousness

345.6 Infantile spasms

345.7 Epilepsia partialis continua

345.8 Other forms of epilepsy

345.9 Epilepsy, unspecified

780.3 Convulsions

Diagnosis

Clinical presentation

Children most commonly present after the seizure event and often have no signs and report few symptoms.Because of the impaired consciousness in complex partial seizures and loss of consciousness in generalizedseizures, patients usually are amnestic for the ictal event. Parent or witness description of the seizure is veryhelpful.

Symptoms

There may be no symptoms if the patient presents postseizure. Symptoms before, during, and after the seizuremay be described or witnessed.

Prior to seizure (preictal):

Aura (subjective sensations) leading up to the event

Mood or behavioral changes before the seizure

During seizure (ictal):


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Vocal: crying or gasping, slurring of words, garbled speech

Motor: head or eye turning, eye deviation, posturing, jerking (rhythmic), stiffening, automatisms(purposeless repetitive movements such as picking at clothing, lip smacking); generalized or focalmovements

Respiration: change in breathing pattern, cessation of breathing, cyanosis

Autonomic: pupillary dilatation, drooling, change in respiratory or heart rate, incontinence, pallor, vomiting

Loss of consciousness or inability to understand or speak

Immediately after seizure (postictal):

Amnesia of seizure event

Confusion

Lethargy

Sleepiness

Headaches and muscle aches

Transient focal weakness (Todd's paresis, almost diagnostic for a focal onset seizure)

Symptoms and signs vary depending on the type of seizure.

Generalized seizures:

Absence: the child or parent is usually unaware of a lapse in concentration or awareness

Myoclonic: the child or parent describes single, rapidly recurrent, bilaterally synchronous shock-like jerksof face, trunk, and extremities if there is no loss of consciousness

Tonic-clonic: vague premonitory symptoms (dizziness, irritability, or anxiety) may be described leading upto the event; painful tongue may be reported after a generalized tonic-clonic seizure, secondary to tonguebiting

Postictal symptoms may include headache, confusion, generalized muscle ache, drowsiness,incontinence

Partial seizures:

Simple: depending on site of onset, symptoms include jerking of limbs, head turning, nausea,lightheadedness, vertiginous attacks, sometimes complex movements

Complex: unresponsiveness to stimuli usually preceded by aura that can manifest as altered states ofemotion, memory, cognition, sensation, or movement

Signs

There may be no signs if the patient presents postseizure.


Absence: an observed loss of consciousness for 10 to 30 seconds without loss of postural tone. Rarely,patients may present with a drop attack. Especially in children, blank stare and subtle clonic movementsof eyelids and face may be observed. No postictal confusion is present, which helps differentiate absencefrom complex partial seizure

Myoclonic: seizures demonstrate repetitive muscle contractions. Single, rapidly recurrent, bilaterallysynchronous shock-like jerks of face, trunk, and extremities occur


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Tonic-clonic: seizures display sustained contractions followed by rhythmic contractions of all fourextremities. Disordered muscle contraction, chest contraction, rigidity, and cyanosis may be observed

Partial seizures:

Simple: focal seizures (signs vary according to site and may include jerking of limbs or head turning)without alteration of awareness/consciousness

Complex: focal seizures with alteration of awareness or consciousness

Patient may appear to be in a trance for 2 to 3 minutes, and may be unresponsive to commands with afixed motionless stare and subsequent automatisms including fidgeting, repetitive hand movements, orchewing or swallowing movements of mouth and face

Associated disorders

Systemic lupus erythematosus and other autoimmune disorders

Cerebrovascular malformations

Damaged neural tissue due to stroke , trauma , surgery, or tumor

Heterotopias (areas of abnormal migration of gray matter in brain development)

Neurocutaneous disorders: approximately 80% of children with tuberous sclerosis have some form ofepileptic seizures. In Sturge-Weber syndrome, the brain damage responsible for the seizure disorderresults from chronic cortical ischemia secondary to venous vascular malformations on the meninges. Thisangiomatosis is usually in the same side as the facial angiomatosis and rarely occurs on the opposite sideor bilaterally. Neurofibromatosis type 1 is associated with epileptic seizures in 3% to 5% of patients

Cerebral palsy : the most severe convulsive disorders can be seen in those children who develop epilepsyat an early age and in those with cerebral palsy

Mental retardation: approximately 20% to 30% of children and adolescents with autism develop some formof epileptic disorder. The seizures are observed more frequently in those patients with more severe mentalretardation

In some children, Lennox-Gastaut syndrome emerges, characterized by a combination of tonic-axial,atonic, atypical absences, and myoclonic seizures

Differential diagnosis

SyncopePseudoseizuresFebrile seizuresMigraineSleep disordersNarcolepsyNight tremorsBreath-holding spells

Workup

Diagnostic decision

Diagnosis of epilepsy is a three-step process, involving clinical identification of possible seizure,consideration of differential diagnoses, and classification of seizure

Cause can be identified in many patients but is not required for the diagnosis of epilepsy. Cause may beidentified as idiopathic

Diagnosis of an epileptic syndrome may be possible after consideration of age at onset and type ofseizure, cognitive development and neurologic examination, and EEG findings


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The Commission on Classification and Terminology of the International League Against Epilepsy has proposed thefollowing classification of seizures and epileptic syndromes:

I - Partial (focal) seizures

A - simple partial seizures (consciousness not impaired)

B - complex partial seizures (consciousness impaired)

C - partial seizures evolving to secondarily generalized seizures

II - Generalized seizures of nonfocal origin

A - absence seizures (petit mal)

B - myoclonic seizures; myoclonic jerks (single or multiple)

C - tonic-clonic seizures (grand mal)

D - tonic seizures

E - atonic seizures

Generalized seizures may be further subdivided into convulsive and nonconvulsive seizures:

Nonconvulsive seizures include absence, myoclonic, tonic, and atonic seizures

Convulsive seizures include tonic-clonic, clonic, and tonic seizures

III - Unclassified epileptic seizures

I - Idiopathic epilepsy syndromes (focal or generalized):

A - benign neonatal convulsions

B - benign partial epilepsy of childhood

C - childhood absence epilepsy

D - juvenile myoclonic epilepsy

E - idiopathic epilepsy, otherwise unspecified

II - Cryptogenic or symptomatic epilepsy syndromes (focal or generalized):

A - West syndrome (infantile spasms)

B - Lennox-Gastaut syndrome

C - epilepsia partialis continua

D - temporal lobe epilepsy

E - frontal lobe epilepsy

F - posttraumatic epilepsy

G - other symptomatic epilepsies, otherwise unspecified

III - Other epilepsy syndromes of uncertain or mixed classification:

A - neonatal seizures

B - febrile seizures

C - reflex epilepsy


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D - other unspecified

Guidelines

The American Academy of Neurology , Child Neurology Society , and the American Epilepsy Society haveproduced the following:

Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile seizure in children .Report of the Quality Standards Subcommittee of the American Academy of Neurology, the ChildNeurology Society, and the American Epilepsy Society. Neurology. 2000;55:616-23

The American Academy of Neurology has produced the following:

Chen DK, So YT, Fisher RS. Use of serum prolactin in diagnosing epileptic seizures . Report of theTherapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.Neurology. 2005;65:668-75

The National Collaborating Centre for Primary Care has produced the following:

Stokes T, Shaw EJ, Juarez-Garcia A, Camosso-Stefinovic J, Baker R. Clinical Guidelines and EvidenceReview for the Epilepsies: diagnosis and management in adults and children in primary and secondary care. London: Royal College of General Practitioners; 2004

The Scottish Intercollegiate Guidelines Network has produced the following:

Diagnosis and management of epilepsies in children and young people: a national clinical guideline .Edinburgh, Scotland: Scottish Intercollegiate Guidelines Network; 2005

Don't miss!

Juvenile myoclonic epilepsy often is misdiagnosed until the patient is asked specifically about the leadingsymptomjerky movements occurring in the morning.

Questions to askPresenting condition

Was this the child's first attack or has the child complained previously about these symptoms?It isimportant to establish if this was a one-time event brought on by a precipitating factor, or if the patient hasa pattern of recurrent seizures

Describe the seizure. Did the child complain of headache, confusion, or feeling strange before,during, or after the seizure?A satisfactory clinical description of the seizure is the most importantfeature in diagnosing epilepsy. The patient may have experienced an aura before the event or postictalsymptoms including drowsiness, muscle aches, headache, or confusion. It may be difficult to find outpreseizure symptoms from young patients. Witness accounts may be useful to describe events during theseizure

Before the seizure (preictal):

Can you describe the events leading up to the child's attack? Describe any activity immediatelybefore event.These need to be determined to establish if the seizure occurred with or without warning andwhether it was preceded by symptoms characteristic of an aura of a partial seizure or symptoms typical offaintness and syncope. It may also help to determine any precipitating factors

Did the child describe any symptoms before the onset of the seizure?The child may experience aurain complex partial seizures that can manifest as altered states of emotion, memory, cognition, sensation,or movement. Vague premonitory symptoms ( eg , dizziness, irritability, or anxiety) leading up to the eventare sometimes experienced in children with generalized tonic-clonic seizures

Was the child under stress before the seizure?Seizures may be brought on by stressful situations,such as severe emotional trauma


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Has the child's sleep routine changed? Is the child sleeping normally?Sleep deprivation can be aprovoking factor

Has the child had a recent illness or fever?Febrile illness is the most common precipitant of seizurebecause it lowers seizure threshold. Hypoglycemia also can cause seizure

Were there any unusual stimuli preceding the seizure?Certain stimuli, such as flickering lights andstrobe lighting, can precipitate an attack

Is the child using any medications or drugs? Has the child had a change in medication?Certaindrugs are common precipitants of seizures. Drug and alcohol withdrawal can cause seizures

Is the child on medication for seizures? Has the medication been changed or stopped?Changes inmedication can precipitate seizures. In patients with a history of anticonvulsant use, the primary etiology ofstatus epilepticus is the erroneous or abrupt tapering of medication

Was there a breath-holding event before the seizure (in a younger child)?Breath-holding spells area common cause of seizure activity in toddlers

During the seizure (ictal):

Did anyone witness the attack?Most eyewitnesses will be able to give a reasonable description of atonic-clonic seizure. This is particularly important if the patient lost consciousness. A physical portrayalmay be more accurate than a verbal description

What was the child doing at the onset of the seizure? Did the event begin with arrested speech,odd behavior, or repetitive actions?Any focal rhythmic behavior of the face or extremities at the onsetsuggests partial epilepsy. Complex partial seizures usually begin with arrest of motion and a blank stare.Automatisms ( eg, simple hand movements), oroalimentary behavior ( eg , tasting movements orswallowing), or verbal utterances may occur either initially or during the seizure

At what time of the day did the seizure occur?The seizure may be related to sleep or occurring onawakening. There is evidence that seizures are more likely to recur if the first occurred between midnightand 9:00AM( ie , seizures arising from sleep)

Did the child describe any symptoms at onset?Patients may experience aura prior to onset of partialseizure. Vague premonitory symptoms (dizziness, irritability, or anxiety) may be described leading up tothe event in generalized tonic-clonic seizure.

Was the child able to talk and respond appropriately?Partial seizures are categorized as simple ifconsciousness remains intact or complex if consciousness is impaired during the seizure

Were there any abnormal movements of the eyes, mouth, face, head, arms, and legs?Head or eyeturning, eye deviation, posturing, rhythmic jerking, muscle spasms, stiffening, and automatisms(purposeless repetitive movements such as picking at clothing, lip smacking) may be seen in epilepticseizures. Pelvic thrusting, rocking, arm or leg movements that alternate between sides, and generalizedshaking without disturbance of consciousness do not occur in epileptic seizures but may be observed inpseudoseizures

Does the child have jerky movements occurring in the morning?This is strongly suggestive ofjuvenile myoclonic epilepsy

Did the child experience bowel or bladder incontinence?May occur during or after generalizedseizure

Immediately after the seizure (postictal):

Do you know what happened to the child when the attack finished? How did the child feel?Symptoms recorded after an attack are important. If the patient reports waking up in a wet bed with a bittentongue, suffering from a headache and muscular aches or pains, then a presumptive diagnosis of a seizurecan be made


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Contributory or predisposing factors

What was the child doing before the attack?It is important to determine if there were precipitatingfactors, such as watching television, playing computer games, bright flashing lights, sleep deprivation, orstressful life events

Does the child have autism , cerebral palsy , or another form of mental retardation?There is a highincidence of occurrence of these disorders in children with epilepsy

Does the child have any other disease or condition?A thorough medical history may help to find thecause of the seizure. A history of meningitis, encephalitis, head trauma, cancer, or cerebrovasculardisease suggests the cause of epilepsy focus. In diabetic patients, hypoglycemia may precipitateseizures; therefore, hypoglycemia should be considered in patients with diabetes before epilepsy isdiagnosed. Other metabolic disturbances may rarely cause seizures. Symptoms of other causes ofseizure disorders should be reviewed ( eg , headaches, weakness)

Is the child receiving medication? At the time of the attack was the child taking any prescriptiondrugs? Has the child had a change in medication?The patient's medications should be reviewed.Certain drugs are common precipitants of seizures

Do you know if the child is taking any nonprescription drugs or has been drinking heavily?Drugand alcohol withdrawal can cause seizures

What medications do you keep in the home?The child may have access to medications in the home.Salicylates, beta-blockers, and hypoglycemic agents all can cause hypoglycemic seizures in children

Was the child menstruating at the time of the seizure?There is evidence that girls are moresusceptible to seizures at certain times during the menstrual cycle

Has the child's sleep routine changed? Was there a breath-holding event before the seizure (in ayounger child)?Sleep deprivation may precipitate seizure. Breath-holding is a common cause of seizurein toddlers

Has the child been ill or had a fever?Fever is the most common cause of seizures in children

Family history

Is there a family history of epilepsy or seizures?Importance of genetics should not be underestimated inepilepsy. Inherited primary epilepsies account for approximately 30% of chronic clinical epilepsies. Inheritedstructural lesions ( eg , neurofibromatosis) are much less likely.

Examination

Examination findings in a patient with epilepsy usually are normal (epilepsy is idiopathic in 70% of patients).Physical signs may point to an underlying neurologic or systemic disorder of which seizures are a part.

Assess the vital signs.Ensure that the airway has been protected. Fever may be present after a seizure orthere may be evidence of a precipitating CNS infection

Do a general inspection.The child may look unwell if infection or metabolic disorder is present. Examinefor signs of trauma. Perform a Wood's lamp examination of the skin and examine for signs ofneurocutaneous syndromes commonly associated with seizures such as caf-au-lait spots, facialangioma, hypopigmented macules, maxillary freckling, and shagreen patches. Asymmetry of hands, feet,or face may indicate an abnormality of the cerebral hemisphere. Evidence of failure to thrive, a peculiarbody odor, or abnormal hair pigmentation may suggest a metabolic disorder

Do a neurologic examination.Focal neurologic signs indicate localized cerebral pathology. Check forpostictal manifestations ( eg , Todd's paralysis, which is a temporary weakness of the affected limb after aconvulsion). Check also for any neck stiffness associated with meningitis and for signs of raisedintracranial pressure (eye movement abnormality, pupil asymmetry, papilledema). Assess gait in allpatients who can walk


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Assess the patient's mental status.Confusion and memory disturbance may follow a seizure

Summary of tests

The diagnosis of epilepsy is primarily clinical, but EEG is used to help classify the event as generalized orlocalization-related epilepsy and determine appropriate therapy

All patients with possible seizure disorders should be evaluated with EEG as soon as possible

EEG helps to establish diagnosis and classify seizure type, but can rarely exclude or prove diagnosissince an EEG may be abnormal in a patient without seizures, and the interictal EEG can be normal in apatient with epilepsy

EEG rarely is indicated in the acute setting unless nonconvulsive status epilepticus is suspected, which iscommon in patients after trauma-induced seizures when altered consciousness is prolonged

Video monitoring with EEG provides accurate recording of seizures and seizure type, and is indicatedwhen there is doubt about the diagnosis after initial evaluation

Magnetic resonance imaging (MRI) is indicated for most patients with seizures, although the chance offinding a structural lesion is very low in a young person with generalized epilepsy and normal physicalexamination findings

Computed tomography (CT) should be done in patients in whom CNS infection or mass lesions aresuspected when MRI is not immediately available

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) areordered by the neurologist to evaluate patients with medically refractory seizures and candidates forsurgery

Additional tests:

Experts disagree over value of routine blood studies because they yield very little clinically usefulinformation

Routine blood tests, including blood urea nitrogen (BUN) , creatinine , glucose , and serum chemistries ,are indicated to identify more common metabolic causes of seizures (electrolyte imbalance and evidenceof renal disease)

Hypocalcemia should be considered in neonates and infants ( ie , 22q11 deletion); however, it is very rarelya cause for seizure in older children

Complete blood count (CBC) and blood culture may identify infection

Screening for toxins in blood or urine is indicated in certain risk groups, especially those in whom a clearprecipitating factor has been identified

Anticonvulsant drug levels should be assessed if there is suspicion of breakthrough seizures

Lumbar puncture is indicated if there is suspicion of meningitis or encephalitis, and is mandatory in allpatients with human immunodeficiency virus (HIV) infection, even in the absence of symptoms or signssuggesting infection. This is always done in the hospital setting after a CT scan

Order of tests

EEG

Video monitoring with EEG

MRI

CT

Blood glucose


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Serum chemistries

BUN

Creatinine

Toxicology screen

CBC

Blood culture

Lumbar puncture

SPECT

PET

TestsBody fluidsBlood glucoseSerum chemistriesBUNCreatinineToxicology screenCBCBlood cultureTests of functionEEGImagingMRICTSPECTPETSpecial testsVideo monitoring with EEGOther testsLumbar puncture

Clinical pearls

Firsthand reports from parents or other observers are often essential for diagnosis

If diagnostic doubt remains, a policy of watchful waiting must be adopted. Patients and caregivers shouldbe asked to make a written record of any subsequent episodes

Video recording is very useful in diagnosing epilepsy when inadequate or inaccurate histories are availablefrom eyewitnesses

Consider consult

Patients should be referred to a neurologist to confirm the diagnosis; ensure that optimal treatment isgiven; and provide counseling if there is any question regarding the diagnosis, response to therapy, orprognosis

Status epilepticus is a medical emergency and requires immediate transport to the emergency department

Treatment

Goals


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Prevent seizures without causing adverse events, preferably using monotherapy and a dosing schedule thatis easy for the parent to administer

Treat the underlying disorder (if known)

Avoid precipitating factors

Withdraw antiepileptic therapy without causing seizure recurrence

Address psychological and social issues

Immediate action

Ensure that airways are clear during and after a seizure

If seizures are prolonged, a benzodiazepine or other agent may be required to immediately stop the seizure

Prompt intervention is important in patients with status epilepticus ; prolonged seizures are associated withsignificant morbidity and mortality

Therapeutic options

Summary of therapies

Treatment of epilepsy involves three important steps:

Establish the diagnosis of epilepsy and the syndrome/seizure type

Decide if medical management with anticonvulsants is necessary

Select the anticonvulsant, if required

Antiepileptic agents are the mainstay of treatment and should be started in any patient with recurrentseizures of unknown etiology or known cause that cannot be reversed. Children with epilepsy shouldalways be referred to a pediatric neurologist for initial medication recommendations

Treatment should always be started with a single agent; duration of therapy depends on the diagnosis,response, and age at onset

The selection of anticonvulsant is complex and depends on the type of epilepsy/seizure, relativeconvenience of dosing schedule, and potential adverse events

Use of anticonvulsant therapy in patients who have had a single seizure is controversial

Advice on lifestyle changes should be given to all parents and children to help reduce risk of injury duringseizures and avoid precipitating factors

Preventive measures, including stress reduction, modification of activities to decrease potential injury risk,and avoidance of sleep deprivation and prolonged fasting, should be taken to minimize the impact ofepilepsy

Partial-onset seizures:

Carbamazepine and oxcarbazepine are first-line therapy. Carbamazepine is usually the agent of choice inpatients with idiopathic benign partial seizures

Use of phenytoin is declining, as it is not well absorbed in infants and has a poor adverse effect profile.Phenobarbital may be of use in neonates and young children

Lamotrigine , levetiracetam , rufinamide , and lacosamide are used as adjuvant therapies and asmonotherapies in some circumstances. Oxcarbazepine is the only agent that is approved for monotherapyand adjunctive therapy in children


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Topiramate (as monotherapy or adjunctive therapy) and zonisamide (as adjunctive therapy only) may beused in patients with medication-resistant partial epilepsy. Zonisamide should be prescribed only by apediatric neurologist

Valproic acid can be used for secondary generalized seizures


Valproic acid has been the first choice for generalized tonic-clonic seizures and is particularly effective inpatients with atypical absence, myoclonic, and atonic seizures. It is the medication of choice for patientswith juvenile myoclonic epilepsy with mixed seizure types. However, concerns regarding the side effects ofvalproic acid have led many physicians to use levetiracetam or topiramate as first-line therapy forgeneralized seizures

Phenytoin and carbamazepine are alternative first-line options and are available in sustained-releaseformulations for maintenance therapy

Second-generation anticonvulsants, such as topiramate, lamotrigine, or levetiracetam, are occasionallyused for primary generalized seizures, although these should always be prescribed by a pediatricneurologist

Ethosuximide is used for absence seizures; valproic acid is a good alternative

Clonazepam is an alternative for myoclonic, atonic, and absence seizures

Lamotrigine may be effective in patients with juvenile myoclonic epilepsy and Lennox-Gastaut syndrome,but the risk of Stevens-Johnson syndrome is high, especially in young children or when combined withvalproic acid. Levetiracetam is also approved for use in patients with juvenile myoclonic epilepsy, andtopiramate is approved for use in patients with Lennox-Gastaut syndrome

Vigabatrin and adrenocorticotropic hormone have been used to treat idiopathic infantile spasms, andvigabatrin is the first choice for treatment of spasms in infants with tuberous sclerosis

Children with Lennox-Gastaut syndrome should be managed by a neurologist with special training inpediatric epilepsy

Refractory epilepsy:

There are no clear guidelines on the selection of combination therapy, which should be determined by theneurologist. Options include first- and second-generation anticonvulsants

Felbamate may be beneficial as an adjunctive therapy for Lennox-Gastaut syndrome and various otherrefractory epilepsies. Felbamate is a powerful medication with a significant risk of adverse effects, makingit the last-line therapy for most types of epilepsy; it should be prescribed only by a neurologist orepileptologist

Dietary manipulation , especially the use of a ketogenic diet, may be recommended by the pediatricneurologist for selected patients. Eating a high-fat/protein and low-carbohydrate diet will induce ketosis,which is believed to have a direct anticonvulsant effect. Such diets must only be used in the setting of avery experienced epilepsy center

Surgery should be considered in children with persistent, frequent seizures that are not controlled with twotrials of high-dose monotherapy and one trial of combination therapy and that have an adverse impact onthe patients' lives and/or cognitive and psychosocial development. The selection of surgical proceduredepends on the type and location of the seizures

Temporal lobectomy is the most commonly performed invasive surgical procedure and should beconsidered for patients with medically refractory epilepsy in the temporal lobe

Vagal nerve stimulator implantation may be used as adjunctive therapy for reducing the frequency ofseizures in patients over age 12 with medically intractable and inoperable seizures


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In children with extensive hemispheric lesions, surgery is the best treatment option. Hemispherectomyshould be done early in life to improve seizure control and halt the intellectual deterioration that isassociated with intractable seizure disorder

Corpus callosotomy is a palliative procedure that may be considered for children with Lennox-Gastautsyndrome and other patients with intractable atonic seizures

Status epilepticus :

Prompt intervention is important, as prolonged seizures are associated with significant morbidity andmortality

Many of these epilepsies will continue into adulthood. Patients should be transitioned to a neurologist specializingin care of adult patients with seizures. For more information, see Epilepsy in adults .

Guidelines

The American Academy of Neurology and the Child Neurology Society have produced the following:

Hirtz D, Berg A, Bettis D, et al. Practice parameter: treatment of the child with a first unprovoked seizure .Report of the Quality Standards Subcommittee of the American Academy of Neurology and the PracticeCommittee of the Child Neurology Society. Neurology. 2003;60:166-75

Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantilespasms . Report of the American Academy of Neurology and the Child Neurology Society. Neurology.2004;62:1668-81

The American Academy of Neurology and the American Epilepsy Society have produced the following:

French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs I: treatmentof new onset epilepsy . Report of the Therapeutics and Technology Assessment Subcommittee andQuality Standards Subcommittee of the American Academy of Neurology and the American EpilepsySociety. Neurology. 2004;62:1252-60

French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs II:treatment of refractory epilepsy . Report of the Therapeutics and Technology Assessment Subcommitteeand Quality Standards Subcommittee of the American Academy of Neurology and the American EpilepsySociety. Neurology. 2004;62:1261-73

French J, Smith M, Faught E, Brown L. Practice advisory: the use of felbamate in the treatment of patientswith intractable epilepsy . Report of the Quality Standards Subcommittee of the American Academy ofNeurology and the American Epilepsy Society. Neurology. 1999;52:1540-5

The American Academy of Neurology, American Epilepsy Society, and the American Association of NeurologicalSurgeons have produced the following:

Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocorticalresections for epilepsy . Report of the Quality Standards Subcommittee of the American Academy ofNeurology, in association with the American Epilepsy Society and the American Association ofNeurological Surgeons. Neurology. 2003;60:538-47

The American Academy of Pediatrics has produced the following:

Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrileseizures: clinical practice guideline for the long-term management of the child with simple febrile seizures .Pediatrics. 2008;121:1281-6

The Canadian Paediatric Society has produced the following:


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Emergency Paediatrics Section, Canadian Paediatric Society. Management of the paediatric patient withgeneralized convulsive status epilepticus in the emergency department . Paediatr Child Health. 1996;1:151-5

The National Collaborating Centre for Primary Care has produced the following:

Stokes T, Shaw EJ, Juarez-Garcia A, Camosso-Stefinovic J, Baker R. Clinical Guidelines and EvidenceReview for the Epilepsies: diagnosis and management in adults and children in primary and secondary care. London: Royal College of General Practitioners; 2004

The National Institute for Health and Clinical Excellence has produced the following:

Newer drugs for epilepsy in children . London: National Institute of Clinical Excellence; 2004

The Scottish Intercollegiate Guidelines Network has produced the following:

Diagnosis and management of epilepsies in children and young people: a national clinical guideline .Edinburgh, Scotland: Scottish Intercollegiate Guidelines Network; 2005

Order of therapies

Carbamazepine

Valproic acid

Phenytoin

Phenobarbital

Lamotrigine

Oxcarbazepine

Topiramate

Ethosuximide

Clonazepam

Levetiracetam

Zonisamide

Lacosamide

Rufinamide

Vigabatrin

Adrenocorticotropic hormone

Temporal lobectomy

Vagal nerve stimulator implantation

Hemispherectomy

Corpus callosotomy

Lifestyle changes

Dietary manipulation

Efficacy of therapies


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Approximately 60% to 70% of all children with epilepsy enter prolonged remission (>5 years) withmonotherapy. Approximately half of these patients eventually become seizure free

Approximately 30% of patients, usually those with severe epilepsy starting in early childhood, continue tohave seizures and never achieve remission

Surgical resection of epileptogenic tissue in patients with complex partial seizures of temporal lobe originhas success rates (defined as no seizures for 5 years after surgery; some auras may be present) of 55%to 70%, with a mortality rate of less than 5%

Medications and other therapiesMedicationsCarbamazepineValproic acidPhenytoinPhenobarbitalLamotrigineOxcarbazepineTopiramateEthosuximideClonazepamLevetiracetamZonisamideLacosamideRufinamideVigabatrinAdrenocorticotropic hormoneSurgical therapyTemporal lobectomyVagal nerve stimulator implantationHemispherectomyCorpus callosotomyOther therapiesDietary manipulationLifestyleLifestyle changes

Clinical pearls

Most patients can be managed with monotherapy

The second- and third-generation anticonvulsants are as effective as the first-generation anticonvulsants,but they do not have as long a track record of use, especially in patients with generalized epilepsy

Lifestyle suggestions are given to all patients with seizures, whether solitary or repeated

Never

Never prescribe felbamate without consulting an epilepsy expert

Never start an anticonvulsant medication following a solitary seizure when there is a clear reversibleprecipitating factor

Management in special circumstances

Coexisting disease

Renal insufficiency may alter drug selection.

Coexisting medication


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Concurrent medications alter drug selection, especially oral contraceptives and other anticonvulsants.

Patient satisfaction/lifestyle priorities

Epilepsy can have profound practical and psychological implications. Children may feel uncomfortable andself-conscious about their friends or other children seeing them having a seizure; other children may lackunderstanding or bully them

Patients with epilepsy are at risk of developing a range of psychiatric problems

Many commonly used antiepileptic drugs cause sedation at therapeutic doses and ataxia and diplopiawhen taken in excess

Patient and caregiver issues

Impact on career, dependents, family, and friends

Parents of children with epilepsy should not hide the diagnosis. Other family members and friends shouldbe aware of the potential for seizures and how to deal with them

Patients should carry some sort of identification on their person stating that they have epilepsy and,preferably, listing current medications and medication allergies

Questions parents ask

How will I be able to cope when the seizures happen?Parents may find it very frightening to see theirchild having what appears to be a seizure. Advise them to keep calm so that they can describe exactlywhat happened. Tell them to contact the physician if the child collapses for any reason at all, and explainthat children, like adults, can have either generalized or partial seizures. Explain that other conditions cansometimes be mistaken for epilepsy, such as febrile convulsions and breath-holding spells, and that it isimportant for the physician to exclude these

Will the treatment work? How long will my child have to take the medication?Patients usuallyneed to continue taking antiepileptic drugs until they are free from seizures for at least 2 years, and somepatients may need to remain on antiepileptic therapy indefinitely

Will my child be able to go to school?Federal and state legislation is designed to prevent schools fromdiscriminating against patients with epilepsy

Can my child still play games and participate in other physical activities?Most children withstraightforward epilepsy have a perfectly normal, active childhood and, with a few sensible safetyprecautions, are able to enjoy doing all of the things their friends do, like swimming, sports, and games

How will the condition affect my child's ability to communicate, make friends, and lead a normallife?Support groups are available for parents and caregivers that will help them understand the disease sothat they can encourage the child to grow into a happy, independent individual. Parents may fear thatfriends, neighbors, and relatives will react badly to the news that their child has epilepsy. Negativereactions are most likely when people are afraid or do not understand the condition. Explain the value ofopenness and honesty as the best ways to combat any stigma surrounding epilepsy, and assure parentsthat most people are sympathetic and supportive if they know how they can help

Will epilepsy cause other problems, such as behavioral difficulties?Some children's seizures aremade worse by stress, emotional upset, or boredom, and certain antiepileptic drugs can cause behavioralproblems. Sometimes, simply missing out on information during an absence seizure or having to miss anouting because of an attack can leave the child feeling frustrated or confused, leading to behavioralproblems. It is important to avoid factors that may precipitate seizures and to adhere to the medicationregimen

Is it my fault that my child has epilepsy?Many parents wonder whether something they did or failed todo triggered their child's epilepsy. Reassure the parents that they are not responsible for causing thecondition, and explain that, in many cases, the cause of epilepsy is a mystery


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Health-seeking behavior

If a seizure precipitant is identified ( eg, sleep derivation, flashing lights, television, computer games), askthe parent if the child has avoided these triggers

Ask if the child has had a traumatizing or upsetting experience for which the parents may have soughtcounseling, as some types of seizures are associated with stress

Follow-up

Patients taking antiepileptic drugs require regular long-term follow-up because efficacy and toxicity variesamong patients, and establishing the optimal therapeutic dose, which can take many months, is largelytrial and error

Monitoring of serum drug levels may be useful in establishing the dosing schedule

If seizures continue despite administration of the maximal tolerated dose and documented compliance,different medication(s) should be introduced

Plan for review

Patients or their guardians should be asked to keep a written account of subsequent seizures

Parents must be educated about the risk of subsequent seizures

Patients should be monitored closely in the first months of therapy until the optimal therapeutic dose isreached; regular monitoring for adverse effects is also necessary during therapy

Breakthrough seizures suggest noncompliance, infections, medication interactions, or inappropriate dosingand may require hospitalization for further monitoring and treatment

Information for patient or caregiver

Parents of children with epilepsy should receive advice/counseling regarding:

Implications of the diagnosis ( eg , going to school)

Aims of treatment

Prognosis

Expected duration of treatment; there is no medication or dose that is appropriate for all children withepilepsy

Importance of compliance

Adverse events

Patient and caregiver organizations, where to go for help

Parents should be given a written medication information sheet providing:

Details of treatment

When to administer the medication

What to do if a dose is missed

Which other drugs (including over-the-counter preparations) can be safely administered in conjunction withantiepileptic drugs

What to do if the child experiences adverse events

What to do for recurrent or prolonged seizures


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Ask for advice

Question 1

How should I decide whether to initiate treatment in a patient with a solitary seizure?

Answer 1

This is a difficult question, even for a neurologist. Whether to initiate treatment after a first seizure is dependent onthe consequences of treating versus not treating and the likelihood of future seizures. If it is clear that the patienthas a seizure disorder (lateral tongue biting, prolonged postictal confusion, suggestive EEG findings), theninitiating treatment is the safest option. If it is unclear whether the seizure was situational or psychogenic, and asecond seizure would not endanger the patient, then it is probably best to wait. The safest option is to consult aneurologist in all cases of new-onset seizure with an unknown source.

Question 2

For how long should patients take antiepileptic drugs? Do the benefits of long-term treatment outweigh the risks?

Answer 2

If a patient has been seizure free for 2 years, it is generally accepted that medications can be graduallywithdrawn, unless the EEG findings remain abnormal.

Question 3

How do I select the optimal monotherapy or combination therapy from the many antiepileptic drugs available?

Answer 3

This is a difficult decision to make and is dependent on factors such as the patient's age, IQ (some medicationsdecrease cognitive ability, which is not acceptable to highly intelligent patients), and others. Consultation with aneurologist is essential for diagnosis and to determine appropriate treatment. Monotherapy is preferable tocombination therapy, and maximal doses of alternative single agents should be tried before combination therapyis attempted. Only a small proportion of patients who experience no improvement with a properly administeredantiepileptic drug will experience improvement with another drug. Many patients with refractory seizures neverbecome completely seizure free.

Question 4

What is the role of surgery in the treatment of epilepsy, and in which patients is it recommended?

Answer 4

Surgery is reserved for patients with severe, medically intractable epilepsy. Only patients with a clearly localizableseizure focus (usually mesial temporal sclerosis) are candidates. A battery of tests, including long-term videomonitoring and the Wada test (to determine the location of the language center), are required before surgicalintervention. In children with extensive hemispheric lesions, total hemispherectomy early in life is the besttreatment option, as the procedure not only improves seizure control but also arrests the intellectual deteriorationthat is associated with the intractable seizure disorder.

Question 5

How should febrile convulsions be treated?

Answer 5

Children with febrile convulsions rarely require treatment with antiepileptic drugs, even for prolonged febrileseizures. Rectal diazepam may be prescribed for use as necessary, but a scheduled daily medication is almostnever necessary.

Consider consult


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Always refer patients to a neurologist if they do not respond to monotherapy or if there is a question aboutthe organic nature of seizures

Breakthrough seizures may indicate treatment failure or failure to adhere to the medication regimen;hospitalization for parenteral therapy may be necessary if the seizures are repeated, prolonged, orassociated with cardiorespiratory compromise. Intravenous fosphenytoin will rapidly (within 30 minutes to 2hours) restore phenytoin levels in patients on an oral phenytoin regimen

Refer patients with drug-resistant epilepsy to a pediatric neurologist or epileptologist and those who requiresurgery to a neurosurgeon

Consult with a dietitian if a ketogenic diet is being considered

If serious emotional consequences are a cause for concern, refer the child to a psychologist

Summary of evidence

Evidence

Medications:

Immediate initiation of anticonvulsant therapy following a first tonic-clonic seizure has been shown toreduce the risk of a second seizure and the time to achieve remission for 2 years. Long-term prognosisdoes not appear to be affected, however, and the risks must be weighed against the benefits [33] , [34] ,[35] Level A

Evidence supports waiting for at least 2 seizure-free years before discontinuing anticonvulsants in childrenwith partial seizures [36] Level A

Continued anticonvulsant treatment in patients who have been seizure free for 2 years or more isassociated with an increased likelihood of remaining seizure free at 2 years when compared with gradualmedication withdrawal. Age under 16 years, number of anticonvulsants, seizure control since startingmedication, and the period of remission before withdrawal was attempted were all important clinicalpredictors of relapse after medication withdrawal [37] , [38] Level A

A systematic review comparing carbamazepine versus valproate for the treatment of epilepsy in childrenand adults found some evidence to support the policy of using carbamazepine as first-line treatment forpartial seizures but no evidence to support the use of valproate over carbamazepine for the management ofgeneralized epilepsy [1] Level A

A systematic review found no overall difference between carbamazepine and phenytoin when used asmonotherapy in children and adults with partial-onset seizures or generalized-onset tonic-clonic seizures.However, the possibility of an important difference between these drugs has not been excluded, and resultswere not presented separately for patients with generalized epilepsy and those with partial epilepsy [2]Level A

A systematic review comparing carbamazepine versus phenobarbital in children and adults with epilepsyfound no overall difference between the drugs in terms of time to 12-month remission and time to firstseizure. However, subgroup analysis for time to first seizure suggested an advantage of phenobarbital forpatients with partial-onset seizures and an advantage of carbamazepine for patients with generalized-onsettonic-clonic seizures. Significantly more patients in the phenobarbital group withdrew from treatment,suggesting that carbamazepine is better tolerated than phenobarbital [3] Level A

An RCT in 91 children with generalized tonic-clonic seizures or partial and secondary generalized seizuresshowed that phenobarbital and carbamazepine were similarly effective and had a similar incidence ofbehavioral side effects [5] Level B


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A systematic review compared lamotrigine versus carbamazepine monotherapy in children and adults withpartial-onset seizures or generalized-onset tonic-clonic seizures with or without other generalized seizuretypes. Treatment withdrawal significantly improved with lamotrigine compared to carbamazepine, butresults for time to first seizure suggested that carbamazepine was superior in terms of seizure control,although the findings did not reach statistical significance [4] Level A

A systematic review found no overall difference between phenytoin and valproate monotherapy for thetreatment of partial-onset seizures or generalized-onset tonic-clonic seizures in children and adults [6]Level A

A systematic review comparing monotherapy with phenobarbital versus phenytoin in children and adultswith partial-onset seizures or generalized-onset tonic-clonic seizures found no significant differencebetween the medications in terms of seizure control, but phenytoin was significantly less likely to bewithdrawn (presumably because of fewer side effects) [10] Level A

A systematic review comparing different anticonvulsants administered to neonates for the treatment ofestablished seizures found that phenytoin and phenobarbital were similarly effective, controlling seizures inless than 50% of infants. Mortality and neurodevelopmental outcomes were not reported [11] Level A

A systematic review found that adjunctive treatment with lamotrigine was significantly more effective thanplacebo in reducing seizure frequency in patients with drug-resistant partial epilepsy. However, only one ofthe included RCTs recruited children, and there is insufficient evidence to determine whether lamotrigine ismore or less effective in the pediatric population [12] Level A

In a systematic review assessing the efficacy of lamotrigine, valproate, and ethosuximide in the treatmentof absence seizures in children and adolescents, the included trials were of poor methodologic quality,leading the reviewers to conclude that there was insufficient evidence to guide clinical practice [7] Level B

One small RCT included in the aforementioned review compared lamotrigine versus placebo for 4 weeks inchildren and adolescents with newly diagnosed typical absence seizures. Lamotrigine significantlyincreased the number of children who remained seizure free over 4 weeks [13] Level B

Another small RCT comparing lamotrigine versus valproate in children with newly diagnosed typicalabsence seizures found that lamotrigine was less effective than valproate in preventing seizures at 1, 3,and 12 months [8] Level B

A double-blind RCT involving 453 children with absence epilepsy showed that ethosuximide and valproicacid were more effective than lamotrigine in treating childhood absence seizures. Ethosuximide wasassociation with fewer adverse effects, although the rates of discontinuation were similar across the threetreatment groups [9] Level A

A systematic review compared oxcarbazepine versus phenytoin monotherapy in adults and children withepilepsy and reviewed data on an individual basis. Results from patients with partial-onset seizures showedthat oxcarbazepine was significantly less likely to be withdrawn than phenytoin, but there was no overalldifference between the two agents in terms of seizure control [14] Level A

A systematic review found that adjunctive treatment with oxcarbazepine was significantly more effectivethan placebo in reducing seizure frequency in adults and children with drug-resistant partial epilepsy [15]Level A

A systematic review found that topiramate reduces the frequency of seizures compared with placebo whenused as an adjunctive treatment for drug-resistant partial epilepsy in the short term [16] Level A

A systematic review found insufficient evidence to determine the optimal treatment for Lennox-Gastautsyndrome but noted that topiramate, felbamate, and lamotrigine may be beneficial as adjunctive therapies[17] Level B


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A systematic review comparing anticonvulsant drugs used for the treatment of acute tonic-clonicconvulsions in children identified only one RCT, which compared lorazepam versus diazepam. Intravenouslorazepam was not found to be more effective than intravenous diazepam, and no evidence was found tosupport the use of lorazepam over diazepam as first-line therapy in children with acute tonic-clonicconvulsions. However, limited evidence suggested that rectal lorazepam may be more effective and saferthan rectal diazepam, although the data were insufficient to recommend that lorazepam replace diazepamas the first-choice rectal agent for the treatment of acute tonic-clonic convulsions in children [18] Level A

A systematic review found that adjunctive levetiracetam therapy significantly reduced the frequency ofseizures in adolescents with drug-resistant partial epilepsy compared with placebo [19] Level A

A multicenter RCT in 122 patients, including adolescents, with idiopathic generalized epilepsy withmyoclonic seizures despite adequate antiepileptic monotherapy showed that adjunctive therapy withlevetiracetam was effective and well tolerated compared with placebo [20] Level A

A multicenter RCT in 229 patients aged 4 to 65 with uncontrolled generalized tonic-clonic seizures despitestable doses of one or two antiepileptic drugs found that adjunctive treatment with levetiracetam resulted ina higher number of seizure-free patients compared with placebo [21] Level A

A systematic review including four 12-week trials of adjunctive therapy with zonisamide in patients withdrug-resistant partial epilepsy found that adjunctive zonisamide reduced seizure frequency compared withplacebo. However, it was uncertain whether zonisamide can provide longer periods of effective seizurecontrol, and adverse effects were noted [22] Level A

An RCT involving 139 patients with Lennox-Gastaut syndrome characterized by multiple types of seizuresresistant to treatment showed that rufinamide was effective in decreasing seizure frequency and severity[23] Level A

In the UK Infantile Spasms Study, 107 infants with spasms were randomly assigned to either hormonetreatment or vigabatrin and followed up until clinical assessment at 12 to 14 months of age. Bothtreatments were effective in reducing infantile spasms. Hormone treatment controlled spasms betterinitially in patients with no identifiable etiology but not at 12 to 14 months of age. Neurologic developmentwas similar in both groups [24] Level A

A 2-week, multicenter RCT and a 3-year follow-up study involving 32 patients with infantile spasms showedthat vigabatrin was effective in treating the disorder. The time to response was shorter in patients withtuberous sclerosis and in those receiving high-dose vigabatrin as opposed to lower-dose vigabatrin [25]Level B

A systematic review of 14 studies evaluating nine different agents in a total of 681 patients with infantilespasms found that high-dose hormonal treatment may act faster and be more effective in preventing long-term developmental outcomes in patients without an underlying cause. Vigabatrin may be more effective inpatients with tuberous sclerosis [26] Level A

A practice parameter from the American Academy of Neurology and the Child Neurology Societyconcluded on the basis of less than optimal evidence that adrenocorticotropic hormone is probably effectiveand vigabatrin is possibly effective in the short-term treatment of infantile spasms [27] Level C

Surgical therapies:

A systematic review identified one RCT that compared temporal lobectomy versus medical treatment for 1year in patients with poorly controlled temporal lobe epilepsy. The trial found that temporal lobectomysignificantly increased the likelihood of being completely seizure free and of being free of seizures with orwithout auras, improved quality of life, and increased the proportion of patients who were employed orattending school compared with medical treatment [28] Level A

A systematic review comparing vagal nerve stimulation using a high-level model versus a low-level model inadults and children with drug-resistant partial seizures found that the high-stimulation model wassignificantly better than the low-stimulation model with regard to overall efficacy. Vagal nerve stimulationwas well tolerated despite adverse effects of hoarseness, cough, pain, paresthesias, and dyspnea;withdrawal from treatment was rare in both groups [29] Level A


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Dietary manipulation:

A systematic review found no RCT evidence to support the use of a ketogenic diet in children with epilepsy.However, the reviewers noted that there is observational evidence of an effect on seizures and concludedthat ketogenic diets may be a possible treatment option for patients with poorly controlled epilepsy [30]Level A

A systematic review evaluating the use of vitamin supplements in conjunction with anticonvulsants inpatients with epilepsy identified 15 small trials, all of low methodologic quality, and found no reliableevidence to support the routine use of vitamins in patients with epilepsy [31] Level A

Self-management education programs:

A systematic review that examined the effect of self-management education programs for children andadolescents on seizure control and other health outcomes identified only one trial. Although the trial wasnot of high quality, the reviewers concluded on the basis of the evidence that a child-centered model ofeducation may improve knowledge about epilepsy and behavioral outcomes and may reduce seizurefrequency. However, the reviewers could not determine the size of the effect or what the key components ofthe program should be [32] Level B

References[1] Marson AG, Williamson PR, Hutton JL, Clough HE, Chadwick DW. Carbamazepine versus valproatemonotherapy for epilepsy. Cochrane Database Syst Rev. 2000:CD001030CrossRef[2] Tudur Smith C, Marson AG, Clough HE, Williamson PR. Carbamazepine versus phenytoin monotherapy forepilepsy. Cochrane Database Syst Rev. 2002:CD001911CrossRef[3] Tudur Smith C, Marson AG, Williamson PR. Carbamazepine versus phenobarbitone monotherapy for epilepsy.Cochrane Database Syst Rev. 2003:CD001904CrossRef[4] Gamble CL, Williamson PR, Marson AG. Lamotrigine versus carbamazepine monotherapy for epilepsy.Cochrane Database Syst Rev. 2006:CD001031CrossRef[5] Banu SH, Jahan M, Koli UK, Ferdousi S, Khan NZ, Neville B. Side effects of phenobarbital and carbamazepinein childhood epilepsy: randomised controlled trial. BMJ. 2007;334:1207CrossRef[6] Tudur Smith C, Marson AG, Williamson PR. Phenytoin versus valproate monotherapy for partial onset seizuresand generalized onset tonic-clonic seizures. Cochrane Database Syst Rev. 2001:CD001769CrossRef[7] Posner EB, Mohamed K, Marson AG. Ethosuximide, sodium valproate or lamotrigine for absence seizures inchildren and adolescents. Cochrane Database Syst Rev. 2005:CD003032[8] Coppola G, Auricchio G, Frederico R, et al. Lamotrigine versus valproic acid as first-line monotherapy in newlydiagnosed typical absence seizures: an open-label, randomized, parallel-group study. Epilepsia 2004;45:1049-53CrossRef[9] Glauser TA, Cnann A, Shinnar S, et al. Ethosuximide, valproic acid and lamotrigine in childhood absenceepilepsy. N Eng J Med. 2010;362:790-9[10] Taylor S, Tudur Smith C, Williamson PR, Marson AG. Phenobarbitone versus phenytoin monotherapy forpartial onset seizures and generalized onset tonic-clonic seizures. Cochrane Database Syst Rev. 2001:CD002217CrossRef[11] Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev.2004:CD004218CrossRef[12] Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant partial epilepsy. CochraneDatabase Syst Rev. 2001:CD001909CrossRef[13] Frank LM, Enlow T, Holmes GL, et al. Lamictal (lamotrigine) monotherapy for typical absence seizures inchildren. Epilepsia. 1999;40:973-9CrossRef


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[14] Muller M, Marson AG, Williamson PR. Oxcarbazepine versus phenytoin monotherapy for epilepsy. CochraneDatabase Syst Rev. 2006:CD003615CrossRef[15] Castillo S, Schmidt DB, White S. Oxcarbazepine add-on for drug-resistant partial epilepsy. CochraneDatabase Syst Rev. 2000:CD002028CrossRef[16] Jette N, Hemming K, Hutton JL, Marson AG. Topiramate add-on for drug-resistant partial epilepsy. CochraneDatabase Syst Rev. 2008:CD001417CrossRef[17] Hancock EC, Cross HH. Treatment of Lennox-Gastaut syndrome. Cochrane Database Syst Rev.2009:CD003277CrossRef[18] Appleton R, Macleod S, Martland T. Drug management for acute tonic-clonic convulsions including convulsivestatus epilepticus in children. Cochrane Database Syst Rev. 2008:CD001905CrossRef[19] Chaisewikul R, Privitera MD, Hutton JL, Marson AG. Levetiracetam add-on for drug-resistant localizationrelated (partial) epilepsy. Cochrane Database Syst Rev. 2001:CD001901CrossRef[20] Nobachtar S, Andermann E, Meyvisch P, et al. Levetiracetam for the treatment of idiopathic generalizedepilepsy with myoclonic seizures. Neurology. 2008;70:607-16CrossRef[21] Berkovic SFT, Knowlton RC, Leroy RF, et al. Placebo-controlled study of levetiracetam in idiopathicgeneralized epilepsy. Neurology. 2007;69:1751-60CrossRef[22] Chadwick DW, Marson AG. Zonisamide add-on for drug-resistant partial epilepsy. Cochrane Database SystRev. 2005:CD001416CrossRef[23] Glauer T, Kluger G, Sachdeo R, et al. Rufinamide for generalized seizures associated with Lennox-Gastautsyndrome. Neurology. 2008;70:1950-8CrossRef[24] Lux AL, Edwards SW, Hancock E, et al. The United Kingdome Infantile Spasms Study (UKISS) comparinghormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentrerandomized trial. Lancet Neurol. 2005;4:712-7CrossRef[25] Elterman RD, Shields WD, Mansfield KA, et al. Randomized trial of vigabatrin in patients with infantilespasms. Neurology. 2001;57:1416-21[26] Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev.2008:CD001770CrossRef[27] Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms:report of the American Academy of Neurology and Child Neurology Society. Neurology. 2004;62:1668-81[28] Cucherat M. Meta-analysis of surgery trials in refractory epilepsy [in French]. Rev Neurol (Paris).2004;160:5S232-40[29] Privitera MD, Welty TE, Ficker DM, Welge J. Vagus nerve stimulation for partial seizures. CochraneDatabase Syst Rev. 2002:CD002896CrossRef[30] Levy R, Cooper P. Ketogenic diet for epilepsy. Cochrane Database Syst Rev. 2003:CD001903CrossRef[31] Ranganathan LN, Ramaratnam S. Vitamins for epilepsy. Cochrane Database Syst Rev. 2005:CD004304CrossRef[32] Stokes T, Shaw EJ, Camosso-Stefinovic J, Baker R, Baker GA, Jacoby A. Self-management education forchildren with epilepsy. Cochrane Database Syst Rev. 2007:CD004724CrossRef[33] Camfield P, Camfield C, Dooley J, et al. A randomized study of carbamazepine versus no medication after afirst unprovoked seizure in childhood. Neurology. 1989;39:851-2[34] Marson A, Jacoby A, Johnson A, et al. Immediate versus deferred antiepileptic drug treatment for earlyepilepsy and single seizures: a randomized controlled trial. Lancet. 2005;365:2007-13


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CrossRef[35] Musicco M, Beghi E, Solari A, Viani F. Treatment of first tonic-clonic seizure does not improve the prognosisof epilepsy. First Seizure Trial Group (FIRST Group). Neurology. 1997;49:991-8[36] Sirven JI, Sperling M, Wingerchuk DM. Early versus late antiepileptic drug withdrawal for people with epilepsyin remission. Cochrane Database Syst Rev. 2001:CD001902CrossRef[37] Medical Research Council Antiepileptic Drug Withdrawal Study Group. Prognostic index for recurrence ofseizures after remission of epilepsy. BMJ. 1993;306:1374-8[38] Medical Research Council Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepilepticdrug withdrawal in patients in remission. Lancet. 1991;337:1175-80

Outcomes

Prognosis

Overall, the prognosis is good, with approximately 70% of patients achieving protracted remission

Twenty-five percent to 30% of patients continue to have seizures despite optimal drug therapy

The prognosis is dependent on the underlying syndrome

Excellent in 20% to 30% of all patients. Includes benign epilepsy syndromes, childhood febrileconvulsions, and most asymptomatic seizures

Good in 40% of all patients; seizures are controlled with medication. Includes primary generalized epilepsyand some localization-related epilepsies

Uncertain in 10% to 20% of all patients; drug therapy is suppressive rather than curative, but surgicaltherapy may result in cure. Includes severe idiopathic epilepsy

Poor in approximately 20% of all patients developing seizures; drug treatment is largely unsuccessful, andsurgery is often not possible. Includes severe childhood epilepsy syndromes; epilepsies due to congenitalor inherited disorders; and many localization-related epilepsies due to gross structural lesions and earliertrauma, abscess, or encephalitis

Factors affecting prognosis

The prognosis for patients with long-standing epilepsy is very different from that for patients in whom thecondition is newly diagnosed. Surgical intervention may be most effective if undertaken early in the diseasecourse, once drug resistance has been established

Left temporal lobe epilepsy may affect long-term memory, and patients with seizures originating on the leftside of the brain may have less well developed language skills than those with right-sided seizures

The younger the child is when seizures begin and the more extensive the area affected, the poorer theoutcome

Children with poorly controlled seizures are at higher risk for intellectual decline

Clinical pearls

Monotherapy should be used in most patients

Patients who fail to respond to two or more single antiepileptic agents should be referred to a pediatricneurologist or epileptologist

Progression of disease

Therapeutic failure


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Misdiagnosis ( ie , the patient does not have epilepsy) is one of the most common reasons fortreatment failure. Alternatively, the patient may have both epileptic and nonepileptic attacks, andambulatory monitoring or telemetry may be necessary to determine the diagnosis

If a first-line antiepileptic medication is unsuccessful in controlling symptoms, second-line therapyshould be instituted

Recurrence

Monotherapy results in satisfactory control of seizures in approximately 60% of patients. Of patientsin whom the first antiepileptic drug tried is ineffective, approximately half respond to an alternativedrug. Of the remaining patients, less than 50% experience improved seizure control with theaddition of a second drug (combination therapy)

Patients with focal epilepsy related to an underlying structural lesion and those with multiple seizuretypes and developmental delay are particularly likely to require combination therapy

No clear guidelines exist for combination therapy. In most cases, the initial regimen consists of oneof three first-line agents ( carbamazepine , phenytoin , or valproic acid ) plus an adjunctivemedication. If unsuccessful, newer drugs, such as lamotrigine , oxcarbazepine , levetiracetam ,vigabatrin , and tiagabine , are indicated

Surgery is indicated in 20% of patients with epilepsy resistant to medical therapy, includingcombination therapy

Deterioration

Acute repetitive seizures, which are distinguishable from status epilepticus in that recovery occursbetween seizures, should be anticipated in patients with epilepsy. The management plan should bediscussed with the child's parents ( eg, rescue therapy with an oral, sublingual, intranasal, or rectalbenzodiazepine). Intramuscular or intravenous fosphenytoin may also be given when appropriate

Breakthrough seizures indicate noncompliance with the antiepileptic medication regimen, treatmentfailure, an acute infection (especially febrile illnesses), or inappropriate or inadequate dosing ofmedication. If oral therapy is not an option, hospitalization for parenteral therapy may be necessary;intramuscular or intravenous fosphenytoin will rapidly (within 30 minutes to 2 hours) restorephenytoin levels in patients on an oral phenytoin regimen

Clinical complications

Children with epilepsy are at risk of developing a variety of psychiatric problems as they get older

Patients with seizures secondary to developmental abnormalities or acquired brain injury may haveimpaired cognitive function and other neurologic defects

Patients with epilepsy often develop short-term memory loss that may progress over time

Abnormal personality traits ('interictal personality') generally are believed to be due to underlying structurallesions, effects of antiepileptic drugs, or psychosocial factors

Patients may injure themselves during a generalized tonic-clonic seizure; lacerations, shoulderdislocations, and even fractures may result

Consider consult

Refer all children with epilepsy to a neurologist. Patients with a poor response to monotherapy should bereassessed by the neurologist and alternative monotherapy or combination therapy considered

Hospitalization for parenteral therapy may be necessary in patients with breakthrough seizures if oraltherapy is not an option. Intravenous fosphenytoin will rapidly (within 30 minutes to 2 hours) restorephenytoin levels in patients on an oral phenytoin regimen

Refer patients with drug-resistant epilepsy to a pediatric neurologist or epileptologist and those who requiresurgery to a neurosurgeon


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Prevention

Primary prevention

Numerous diseases or types of brain damage can cause epilepsy, including developmental abnormalities,skull trauma, infections, and poor perinatal care

Epilepsy is more common in less developed countries and lower socioeconomic groups, suggesting thatimprovements in social health can reduce the incidence

Improved perinatal care, better control of infections, and a reduction in the incidence of childhood headtrauma will reduce the incidence of epilepsy

There is some evidence of a higher incidence of epilepsy in children delivered breech (3.8%) compared withchildren delivered vertex (2.2%)

At least part of the burden of epilepsy can be alleviated by the use of preventive methods to improve socialhealth

Modifiable risk factorsAlcohol and drugs

Alcohol and drug abuse are known causes of seizures and should be avoided.

Medication history

Poor compliance with the antiepileptic drug regimen can result in breakthrough seizures

Reassess antidiabetic therapy in patients with epilepsy caused by hypoglycemia

In patients with metabolic causes, reassess medication(s)

Immunization

There is some evidence that immunization ( eg , with pertussis vaccine) may cause epilepsy in susceptibleindividuals. The decision to immunize children with a strong family history of pertussis-induced seizures should bediscussed. The new acellular pertussis vaccine is unlikely to put the child at risk for epilepsy.

Other

Inherited primary epilepsies account for approximately 30% of chronic clinical epilepsies observed. Families inwhich there is a history of epilepsy should be advised to help affected children avoid known precipitating factorswhen possible.

Secondary prevention

Risk of recurrence is minimized by the following:

Ensuring good compliance with medication

Ensuring therapeutic serum levels of antiepileptic medication

Using an alternative agent if no response is seen with the initial agent

Starting combination therapy in patients with seizures refractory to monotherapy

Considering surgery in suitable patients if medical treatment is ineffective

Resources

References

Evidence references


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[1] Marson AG, Williamson PR, Hutton JL, Clough HE, Chadwick DW. Carbamazepine versus valproatemonotherapy for epilepsy. Cochrane Database Syst Rev. 2000:CD001030CrossRef[2] Tudur Smith C, Marson AG, Clough HE, Williamson PR. Carbamazepine versus phenytoin monotherapy forepilepsy. Cochrane Database Syst Rev. 2002:CD001911CrossRef[3] Tudur Smith C, Marson AG, Williamson PR. Carbamazepine versus phenobarbitone monotherapy for epilepsy.Cochrane Database Syst Rev. 2003:CD001904CrossRef[4] Gamble CL, Williamson PR, Marson AG. Lamotrigine versus carbamazepine monotherapy for epilepsy.Cochrane Database Syst Rev. 2006:CD001031CrossRef[5] Banu SH, Jahan M, Koli UK, Ferdousi S, Khan NZ, Neville B. Side effects of phenobarbital and carbamazepinein childhood epilepsy: randomised controlled trial. BMJ. 2007;334:1207CrossRef[6] Tudur Smith C, Marson AG, Williamson PR. Phenytoin versus valproate monotherapy for partial onset seizuresand generalized onset tonic-clonic seizures. Cochrane Database Syst Rev. 2001:CD001769CrossRef[7] Posner EB, Mohamed K, Marson AG. Ethosuximide, sodium valproate or lamotrigine for absence seizures inchildren and adolescents. Cochrane Database Syst Rev. 2005:CD003032[8] Coppola G, Auricchio G, Frederico R, et al. Lamotrigine versus valproic acid as first-line monotherapy in newlydiagnosed typical absence seizures: an open-label, randomized, parallel-group study. Epilepsia 2004;45:1049-53CrossRef[9] Glauser TA, Cnann A, Shinnar S, et al. Ethosuximide, valproic acid and lamotrigine in childhood absenceepilepsy. N Eng J Med. 2010;362:790-9[10] Taylor S, Tudur Smith C, Williamson PR, Marson AG. Phenobarbitone versus phenytoin monotherapy forpartial onset seizures and generalized onset tonic-clonic seizures. Cochrane Database Syst Rev. 2001:CD002217CrossRef[11] Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev.2004:CD004218CrossRef[12] Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant partial epilepsy. CochraneDatabase Syst Rev. 2001:CD001909CrossRef[13] Frank LM, Enlow T, Holmes GL, et al. Lamictal (lamotrigine) monotherapy for typical absence seizures inchildren. Epilepsia. 1999;40:973-9CrossRef[14] Muller M, Marson AG, Williamson PR. Oxcarbazepine versus phenytoin monotherapy for epilepsy. CochraneDatabase Syst Rev. 2006:CD003615CrossRef[15] Castillo S, Schmidt DB, White S. Oxcarbazepine add-on for drug-resistant partial epilepsy. Cochr

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