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.

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 & 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 treatment with anticonvulsant if:
    • History of previous myoclonic, absence or focalseizures
    • 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

Pharmacotherapy

Anticonvulsants (First-Line Anticonvulsants)

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

Carbamazepine

  • Used to treat focal to bilateral tonic-clonic seizure & primary generalized tonic-clonic seizures
  • Also used as first-line treatment for patients with benign epilepsy associated w/ centrotemporal spikes, Panayiotopoulos syndrome, or late-onset childhood occipital epilepsy (Gastaut type)
  • Should be avoided in absence, myoclonic, tonic & atonic seizures
  • Classification: Dibenzazepine derivative

Ethosuximide

  • Used as first-line therapy to treat absence seizures
  • Classification: Succinimide compound

Lamotrigine

  • Used as first-line therapy for focal to bilateral tonic-clonic seizure, & primary generalized tonic-clonic, & absence seizures
  • Used to treat  focal to bilateral tonic-clonic seizure & primary generalized tonic-clonic seizures
  • Also used as adjunctive treatment for generalized tonic or atonic seizure, Lennox-Gastaut syndrome, & as tertiary therapy for myoclonic seizures
  • May also be used as 1st-line treatment for idiopathic generalized onset epilepsy if Valproate is ineffective or not tolerated
  • Classification: Phenyltriazine compound

Levetiracetam

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

Oxcarbazepine

  • Used as 1st-line monotherapy for focal to bilateral tonic-clonic seizure, & for primary generalized tonic-clonic seizures
    • At 2,400 mg/day, was shown to be effective in monotherapy for refractory focal epilepsy
  • Recommended as adjunctive treatment for patients w/ benign epilepsy associated w/ 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 & less physician monitoring is required
  • Should be avoided in absence & 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 focal to bilateral tonic-clonic seizure, generalized tonic-clonic seizures, & Lennox-Gastaut syndrome
    • Also used as tertiary treatment for patients with generalized absence & tonic or atonic seizures
    • In some countries, Topiramate is only approved as adjunctive treatment
  • May also be used as 1st-line treatment for myoclonic epilepsy of infancy, juvenile myoclonic epilepsy, & patients with Dravet syndrome
  • Classification: Sulfamate-substituted monosaccharide

Valproate (Divalproex, Sodium Valproate, Valproic Acid)

  • Used as 1st-line therapy to treat focal to bilateral tonic-clonic seizure, all generalized seizures, & idiopathic generalized epilepsy
  • May also be used as 1st-line therapy for juvenile myoclonic epilepsy, Dravet syndrome, & Lennox-Gastaut syndrome
  • Reasonable evidence supports the use of Valproic acid along with Lamotrigine & Ethosuximide for childhood absence epilepsy
  • Important adverse effect is weight gain
  • Classification: Carboxylic acid derivative

Anticonvulsants (Adjunctive/Tertiary Anticonvulsants)

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

Eslicarbazepine acetate

  • Used as tertiary treatment for refractory focal to bilateral tonic-clonic seizure if adjunctive therapies are ineffective or not tolerated
  • Classification: Carboxamide derivative

Felbamate

  • Used as adjunctive treatment for seizure associated with Lennox-Gastaut syndrome

Gabapentin

  • Used as adjunctive treatment for focal to bilateral tonic-clonic seizure
  • Should be avoided in absence & myoclonic seizures
  • Classification: Gamma-aminobutyric acid (GABA) analogue

Lacosamide

  • Used as tertiary treatment for refractory focal to bilateral tonic-clonic seizure

Phenobarbital (Phenobarbitone)

  • Treats focal onset seizures, generalized tonic-clonic, tonic & atonic seizures, & status epilepticus
  • Consider as a last-line agent; May have adverse effect on patient’s cognition
  • Classification: Barbiturate

Phenytoin

  • Used to treat focal onset seizures, generalized tonic-clonic seizures & status epilepticus
    • Valproate & Carbamazepine may be preferred since they tend to have fewer adverse effects
  • Classification: Hydantoin compound
  • Associated w/ gum hypertrophy

Pregabalin

  • Used as tertiary treatment for patients w/ refractory focal onset seizures
  • Classification: Gamma-aminobutyric acid (GABA) analogue

Primidone

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

Rufinamide

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

Tiagabine

  • Used as tertiary therapy for focal to bilateral tonic-clonic seizure
  • Should be avoided in generalized tonic-clonic, absence & myoclonic seizures
  • Classification: Nipecotic acid derivative

Vigabatrin

  • Used as tertiary therapy for refractory focal to bilateral tonic-clonic seizure
    • Should be reserved for patients not adequately controlled by other agents
  • First-line treatment for patients w/ infantile spasms secondary to tuberous sclerosis
    • May also be offered as 1st-line therapy for non-tuberous sclerosis & infantile spasms
  • Should be avoided in generalized tonic-clonic, absence & myoclonic seizures
  • Associated w/ visual field impairment in adults but few data exist in pediatric patients
  • Classification: GABA analogue

Zonisamide

  • Used as tertiary treatment for focal to bilateral tonic-clonic seizures, generalized absence & myoclonic seizures
  • Also used as adjunctive treatment for juvenile myoclonic epilepsy
  • Actions: Benzisoxazole derivative

Benzodiazepines

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

Clobazam

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

Clonazepam

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

Diazepam

  • Used as an adjunctive treatment for all types of seizures & 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 w/ similar actions to Diazepam

Midazolam

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

Nitrazepam

  • Used as tertiary treatment for patients w/ generalized myoclonic seizures, & to treat epilepsy especially infantile spasm
  • Actions: Intermediate-acting benzodiazepine w/ similar actions to Diazepam

Pinazepam

  • Used as adjunctive treatment for epilepsy
  • Actions: Long-acting benzodiazepine w/ similar actions to Diazepam

Others

Acetazolamide

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

Flunarizine

  • Used as adjunctive treatment for focal seizures resistant to conventional treatment
  • Actions: Difluorinated derivative of Cinnarizine, antihistamine, sedative & Calcium antagonist activity

 Paraldehyde

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

Combination Therapy

  • Consider combination therapy if:
    • Patient has substantial seizure control with 1st-line agent but still experiences seizures at maximum dose
  • Drugs used in combination should be matched to patient’s seizure type
  • Max 3 drugs can be combined; better if only 2 are used
  • Combination therapy should be administered as such:
    • Administer the best monotherapy option at optimal dose with no side effects
    • Administer the subsequent drugs after that, increase dose of each slowly to obtain max response with minimal toxicity

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

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 & history
  • Withdraw treatment gradually, over a few months, to prevent recurrent seizures
  • Patients already receiving anticonvulsant drugs who present w/ an unexplained seizure should have an anticonvulsant level checked
  • Withdraw 1 drug at a time in combination therapy
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