epilepsy%20(pediatric)
EPILEPSY (PEDIATRIC)
Epileptic seizure is a transient occurrence of signs or symptoms that is due to abnormal excessive or synchronous neuronal activity in the brain.
Epilepsy is a disorder that is characterized by a persistent predisposition of the brain to generate epileptic seizures.
This condition may cause neurobiologic, cognitive, psychological and social disturbances.
It is recommended that all patients having a first seizure be referred to a specialist as soon as possible.

Epilepsy%20(pediatric) Treatment

Principles of Therapy

In most clinical settings, seizures are not treated unless ≥2 unprovoked seizures are demonstrated within a 6-month period

Patient Experiences a Single Seizure

  • Detailed history needs to be taken to rule out any previous absence, myoclonic, or partial seizures because patients with undiagnosed epilepsy may present with a single generalized tonic-clonic seizure

Decision to Treat Single Seizure

  • Whether or not to treat a single seizure will be based upon the estimates of risk recurrence which vary
    • Highest recurrence risk rates (up to 90%) are seen in patients who demonstrate epileptic discharges on EEG or have congenital neurological deficits
    • Lowest recurrence risk rates (13-40%) are in patients who experience acute symptomatic seizures (provoked) or those with a normal EEG and no identifiable cause for seizure
  • Treatment with anticonvulsants can reduce the risk of recurrence by half
    • Early treatment has not shown to alter the prognosis of epilepsy
  • Consultation with epilepsy specialist will be needed to decide whether or not to treat a single seizure

Single Generalized Tonic-Clonic Seizure

  • Patient could be given anticonvulsant therapy if:
    • History of previous myoclonic, absence or focal seizures
    • EEG shows unquestionable epileptic discharges
    • Structural abnormalities are present in brain imaging
    • Patient has congenital neurological deficit
    • Patient decides the risk of recurrence is not acceptable

Pharmacological Therapy

  • Treatment initiation using a single antiepileptic drug is recommended
  • Shifting to another monotherapy may be done if initial treatment is unsuccessful
  • If with continued treatment failure, may add a 2nd drug and gradually increase to maximum tolerated dose while simultaneously tapering dose of 1st drug
  • Combination therapy may be considered if removal of the initial or 2nd drug is still ineffective
    • Consider combination therapy if patient has substantial seizure control with 1st-line agent but still experiences seizures at maximum dose
    • If various combinations fail to confer seizure freedom, return to the combination with the best control of seizures and best tolerability
    • Drugs used in combination should be matched to patient’s seizure type
    • Maximum 3 drugs can be combined; better if only 2 are used
      • Combined antiepileptic drugs should have different mechanisms of action

Pharmacotherapy

Anticonvulsants (1st-Line Anticonvulsants)

Choice of anticonvulsant drugs will be based on their indications, adverse effects and interaction profiles

Carbamazepine

  • Used as 1st-line therapy for newly diagnosed focal seizures and 1st-line therapy option for patients with primary generalized tonic-clonic seizures unresponsive or with contraindications to Valproate therapy
  • Also used as 1st-line treatment for patients with benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Also used as adjunctive treatment for focal seizures and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type) 
  • Should be avoided in absence, myoclonic, tonic and atonic seizures, idiopathic generalized epilepsy, juvenile myoclonic epilepsy and Lennox-Gastaut syndrome
  • Classification: Dibenzazepine derivative

Ethosuximide

  • Used as first-line therapy to treat absence seizures
  • Also used in childhood or juvenile absence epilepsy in combination with Lamotrigine or Valproate if unresponsive to 2 1st-line antiepileptic drugs
    • Use of Valproate for girls with childbearing potential should be avoided
  • Classification: Succinimide compound

Lamotrigine

  • Used as 1st-line therapy for newly diagnosed focal seizures, primary generalized tonic-clonic and absence seizures, and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
    • Treatment option for patients with absence seizures unresponsive to Ethosuximide or Valproate
  • May also be used as 1st-line treatment for idiopathic generalized onset epilepsy and juvenile myoclonic epilepsy if Valproate is ineffective or not tolerated
  • Also used as adjunctive treatment for focal seizures, generalized tonic or atonic seizure, Lennox-Gastaut syndrome, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type) and as tertiary therapy for myoclonic seizures
  • Also used in childhood or juvenile absence epilepsy in combination with Ethosuximide or Valproate if unresponsive to 2 1st-line antiepileptic drugs
    • Use of Valproate for girls with childbearing potential should be avoid
  • Classification: Phenyltriazine compound

Levetiracetam

  • Used as 1st-line therapy option for newly diagnosed focal seizures, primary generalized myoclonic seizures, idiopathic generalized epilepsy, and juvenile myoclonic epilepsy
  • Also used as adjunctive treatment for focal seizures, primary generalized tonic-clonic seizures, myoclonic seizures, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type) and tertiary therapy for absence seizures
  • Also recommended as 2nd-line therapy for patients with benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type) if treatment failure with Carbamazepine or Lamotrigine occurs
  • Classification: Analogue of Piracetam which is a nootropic

Oxcarbazepine

  • Used as alternative 1st-line monotherapy for newly diagnosed focal to bilateral tonic-clonic seizure, for primary generalized tonic-clonic seizures benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
    • At 2400 mg/day, was shown to be effective in monotherapy for refractory focal epilepsy
  • Recommended as adjunctive treatment for patients with focal seizures, benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Similar efficacy to Carbamazepine
    • Additional benefits were seen when Oxcarbazepine was added to Carbamazepine therapy
  • Better tolerated than Carbamazepine, fewer drug interactions and less physician monitoring is required
  • Should be avoided in absence, tonic or atonic seizures, Lennox-Gastaut syndrome, idiopathic generalized epilepsy, juvenile myoclonic epilepsy and myoclonic seizures
  • Classification: 10-keto analogue of Carbamazepine

Topiramate

  • Used as first-line monotherapy in patients with generalized myoclonic seizures, in newly diagnosed patients with epilepsy, or conversion to monotherapy, or as adjunctive treatment for newly diagnosed focal seizure, generalized tonic-clonic seizures, myoclonic seizures, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, Lennox-Gastaut syndrome and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
    • Also used as tertiary treatment for patients with generalized absence and tonic or atonic seizures
    • In some countries, Topiramate is only approved as adjunctive treatment
  • May also be used as 1st-line treatment for idiopathic generalized epilepsy, myoclonic epilepsy of infancy, juvenile myoclonic epilepsy, and patients with Dravet syndrome
  • Classification: Sulfamate-substituted monosaccharide

Valproate (Divalproex, Sodium Valproate, Valproic Acid)

  • Used as 1st-line therapy to treat newly diagnosed focal seizures, generalized tonic-clonic seizures, absence seizures, myoclonic seizures, tonic or atonic seizures, all generalized seizures, and idiopathic generalized epilepsy
  • May also be used as 1st-line therapy for juvenile myoclonic epilepsy, Dravet syndrome, Lennox-Gastaut syndrome and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Also used as adjunctive treatment for focal seizures, generalized tonic-clonic seizures, myoclonic seizures, idiopathic generalized epilepsy, juvenile myoclonic epilepsy and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • The use of Valproic acid in combination with Lamotrigine or Ethosuximide for childhood absence epilepsy maybe considered for patients unresponsive to 2 1st-line antiepileptic drugs
  • Use of Valproate for girls with childbearing potential should be avoided
  • Important adverse effect is weight gain
  • Classification: Carboxylic acid derivative

Anticonvulsants (Adjunctive/Tertiary Anticonvulsants)

  • Recommended for patients who have not benefited from treatment with 1st-line antiepileptic medications or for whom these drugs are not suitable (eg poor tolerance, contraindications to 1st-line drugs, etc)

Brivaracetam

  • Recently approved as monotherapy or adjunctive therapy for focal onset seizures in patients ≥4 years old as oral therapy and for patients ≥16 years old as both oral and intravenous therapy
  • Classification: 2-pyrrolidine derivative and Levetiracetam analog

Eslicarbazepine acetate

  • Used as tertiary treatment for refractory focal seizure and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type) if adjunctive therapies are ineffective or not tolerated
  • Classification: Carboxamide derivative

Felbamate

  • Used as adjunctive treatment for seizure associated with Lennox-Gastaut syndrome if all antiepileptic medications have been deemed ineffective

Gabapentin

  • Used as adjunctive treatment for focal seizure and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Should be avoided in absence and myoclonic seizures, Lennox-Gastaut syndrome, idiopathic generalized epilepsy and juvenile myoclonic epilepsy
  • Classification: Gamma-aminobutyric acid (GABA) analogue

Lacosamide

  • Used as tertiary treatment for refractory focal onset seizure and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type) if adjunctive therapies are ineffective or not tolerated

Perampanel

  • Used as adjunctive treatment for patients ≥12 years of age with generalized tonic-clonic seizures and as tertiary therapy for focal epilepsy
  • Classification: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist

Phenobarbital (Phenobarbitone)

  • Tertiary treatment option for patients with focal onset seizures, generalized tonic-clonic, tonic and atonic seizures, neonatal seizure, benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type), and status epilepticus
  • Consider as a last-line agent; may have adverse effect on patient’s cognition
  • Should be avoided in absence seizures
  • Classification: Barbiturate

Phenytoin

  • Tertiary treatment option for patients with focal onset seizures, generalized tonic-clonic seizures, benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type) and status epilepticus
    • Valproate and Carbamazepine may be preferred since they tend to have fewer adverse effects
  • Should be avoided in absence seizures, idiopathic generalized epilepsy and juvenile myoclonic epilepsy 
  • Classification: Hydantoin compound
  • Associated with gum hypertrophy

Pregabalin

  • Used as tertiary treatment for patients with refractory focal onset seizures and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Should be avoided in absence seizures, tonic or atonic seizures, idiopathic generalized epilepsy, Lennox-Gastaut syndrome and juvenile myoclonic epilepsy
  • Classification: GABA analogue

Primidone

  • Used as tertiary treatment for focal onset seizures, and generalized tonic-clonic seizures
  • Classification: Barbiturate, related to Phenobarbital and partially metabolized to Phenobarbital

Rufinamide

  • Used as tertiary treatment for generalized tonic or atonic seizures, and adjunctive therapy for Lennox-Gastaut syndrome in children ≥4 years old
  • Classification: Carboxamide derivative

Stiripentol

  • Used as adjunctive treatment for patients with Dravet syndrome
  • Classification: GABA analogue

Tiagabine

  • Used as tertiary therapy for refractory focal onset seizures and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Should be avoided in generalized tonic-clonic, absence and myoclonic seizures, idiopathic generalized epilepsy, juvenile myoclonic epilepsy and Lennox-Gastaut syndrome
  • Classification: Nipecotic acid derivative

Vigabatrin

  • Used as tertiary therapy for refractory focal seizure and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
    • Should be reserved for patients not adequately controlled by other agents
  • 1st-line treatment for patients with infantile spasms that may or may not be due to tuberous sclerosis
  • Should be avoided in generalized tonic-clonic, absence and myoclonic seizures, idiopathic generalized epilepsy and juvenile myoclonic epilepsy
  • Associated with visual field impairment in adults but few data exist in pediatric patients
  • Classification: GABA analogue

Zonisamide

  • Used as tertiary treatment for refractory focal seizure, generalized absence, myoclonic seizures and benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Also used as adjunctive treatment for juvenile myoclonic epilepsy, idiopathic generalized epilepsy and refractory focal epilepsy
  • Classification: Benzisoxazole derivative

Benzodiazepines

Use of benzodiazepines may be limited by development of tolerance and sedation; other antiepileptics are usually preferred

Clobazam

  • Recommended as adjunctive treatment for patients with focal seizures, generalized tonic-clonic seizures, benign epilepsy associated with centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type), and Lennox-Gastaut syndrome
  • Also used as tertiary treatment for patients with generalized absence, myoclonic seizures, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, and Dravet syndrome
  • Actions: Long-acting benzodiazepine with similar actions to Diazepam

Clonazepam

  • Also used as tertiary treatment for focal to bilateral tonic-clonic seizure, generalized absence seizures, generalized myoclonic seizures, idiopathic generalized epilepsy and juvenile myoclonic epilepsy
  • Used as an alternative to other antiepileptics in status epilepticus
  • Actions: Long-acting benzodiazepine with similar actions to Diazepam

Diazepam

  • Used as an adjunctive treatment for all types of seizures and status epilepticus
  • Actions: Long-acting benzodiazepine which acts by enhancing GABA activity in the brain

Lorazepam

  • Used as 1st-line agent in the treatment of status epilepticus
    • Advantageous to Diazepam in status epilepticus because it has a longer duration of action
    • Disadvantage: Parenteral form requires refrigeration
  • Actions: Long-acting benzodiazepine with similar actions to Diazepam

Midazolam

  • Used to treat status epilepticus resistant to treatment by Diazepam, Lorazepam and Phenytoin
  • Actions: Short-acting benzodiazepine with similar actions to Diazepam

Nitrazepam

  • Used to treat epilepsy especially infantile spasm
  • Actions: Intermediate-acting benzodiazepine with similar actions to Diazepam

Others

Acetazolamide

  • Used as adjunctive treatment for refractory focal to bilateral tonic-clonic seizure, atypical absence, tonic, atonic and myoclonic seizures resistant to conventional treatment
  • Actions: Inhibits carbonic anhydrase in glial cells in central nervous system (CNS)

Paraldehyde

  • Used to treat status epilepticus resistant to conventional treatment
    • Use is limited by the hazards associated with its administration
  • Actions: Sedative and hypnotic with antiepileptic effects

Piracetam

  • Used as tertiary treatment for patients with generalized myoclonic seizures
  • Actions: Nootropic with CNS protective properties against hypoxia

Prednisolone

  • Used as 1st-line treatment for patients with infantile spasms without tuberous sclerosis

Propofol

  • As an anesthetic, it is used in conjunction with assisted ventilation to control refractory status epilepticus
  • Actions: Short-acting anesthetic

Tetracosactide

  • Also recommended for patients with non-tuberous sclerosis-caused infantile spasms

Thiopental sodium

  • Treatment option for patients with refractory convulsive status epilepticus
  • Actions: Short-acting barbiturate anesthetic

Non-Pharmacological Therapy

Vagus Nerve Stimulation

  • Adjunctive intervention to reduce frequency of seizures in patients with focal to bilateral tonic-clonic or generalized onset seizures refractory to anticonvulsants
  • Optional treatment for patients with contraindications for surgery

Nutrition

  • A ketogenic diet may help in the management of pediatric patients
    • Studies have shown marked reduction in seizure frequency in children on high fat, low carbohydrate controlled protein (ketogenic) diet
  • Modified Atkins diet and low glycemic index treatment may also be considered as an alternative to ketogenic diet

Psychological Interventions

  • Eg relaxation techniques, cognitive behavior therapy
  • May be helpful in pediatric patients with focal epilepsy

Treatment Maintenance

  • Routine level monitoring of anti-epileptic drug is not recommended in patients but may be considered
  • Continue treatment for 2-5 years
  • If patient is seizure-free after 2-5 years, drug withdrawal may be considered based on patient preference, seizure type and history
  • Withdraw treatment gradually, over a few months, to prevent recurrent seizures
  • Patients already receiving anticonvulsant drugs who present with an unexplained seizure should have an anticonvulsant level checked
  • Withdraw 1 drug at a time in combination therapy
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