• Clinical science

Generalized epilepsy in childhood

Abstract

Pediatric generalized epilepsy syndromes are a diverse group of conditions with onset in infancy or childhood. The International League Against Epilepsy (ILAE) classifies generalized epilepsy syndromes according to the etiology as either idiopathic, symptomatic, or cryptogenic. In idiopathic generalized epilepsy syndromes, the most common form of childhood epilepsy, genetic causes are suspected. The symptomatic forms are associated with metabolic or structural abnormalities, while the etiology of cryptogenic epilepsies is unknown. The syndromes are further classified according to the patient's age at onset, as well as clinical and EEG characteristics. A detailed patient history, including a description of seizures, offers vital diagnostic clues. The diagnosis may be confirmed with an EEG. With adequate treatment, idiopathic epilepsy syndromes have a good prognosis. In comparison, symptomatic epilepsy syndromes do not respond well to treatment and have a relatively poor prognosis, often resulting in developmental delays and cognitive impairments.

Etiology

Etiology of seizures according to age

  • Infants
    • Congenital (idiopathic; genetic association)
    • Secondary to
      • Perinatal or postnatal infections
      • Head trauma
      • Metabolic disorders
  • Children
    • Idiopathic (genetic association suspected)
    • Secondary to
      • Metabolic disorders
      • Structural abnormalities of the cerebrum
      • Infections
      • Head trauma
      • Febrile seizures

References:[1][2][3][4]

Idiopathic generalized epilepsy syndromes

Idiopathic generalized epilepsy syndromes are the most common forms of epilepsy in children (25%). Genetic causes are suspected and, in some cases, have been identified. The majority of these syndromes occur in otherwise healthy individuals.

Age at disease onset Clinical findings and characteristics Ictal EEG Treatment Prognosis

Childhood absence epilepsy

(pyknolepsy)

  • 6–7 years
  • Sex: <
  • Absence seizures lasting 5–10 seconds up to 100x/day
    • Brief unresponsiveness without convulsions
    • Amnestic during seizures; children appear to be staring or daydreaming
    • Lip smacking, eye fluttering or head nodding are common
    • No postictal phase
  • Atypical absence seizure: more gradual onset and ending, duration of > 30 seconds.
  • Triggers: hyperventilation, lights
  • 3 Hz spikes and waves in all regions of the brain
  • 80% of children are seizure-free with treatment
  • Usually subsides before adulthood

Juvenile absence epilepsy

  • 9–13 years
  • Sex: =
  • Regular 3–4 Hz spikes and waves in all regions of the brain
  • 1st-line: valproic acid
  • Avoid triggers: sleep deprivation, alcohol, drugs, flickering lights

Juvenile myoclonic epilepsy

(Janz syndrome)

  • 12–20 years
  • Triad of seizures :
    • Bilateral symmetrical myoclonic jerks, primarily after awakening, without impaired consciousness
    • Generalized tonic-clonic seizures
    • Absence seizures with impaired consciousness
    • Triggers: sleep deprivation, alcohol consumption, flickering lights
  • Irregular 3–5 Hz polyspikes and waves with frontocentral predominance
  • Interictal EEG: 4–6 Hz bilateral polyspike and slow wave
  • Responds well to antiseizure drug therapy; seizures become less frequent in adulthood
  • Life-long treatment usually required (high risk of recurrence)
  • Increased risk of psychiatric comorbidities

Epilepsy with tonic-clonic seizures alone

  • 14–20 years
  • Fast spikes during tonic phase; bursts of spikes and slow waves during clonic phase
  • 70% are seizure-free under treatment
  • In some cases, no medical therapy is necessary → avoid triggers

Epilepsy with myoclonic-atonic seizures

(Doose syndrome)

  • 2–6 years
  • Sex: >
  • Bursts of 2–5 Hz spikes and waves or polyspikes; slow waves synchronous to atonic phase

  • Background slowing with theta rhythm

  • ∼ 70% remission with normal development and cognition
  • ∼ 30% have an unfavorable prognosis (status epilepticus, cognitive impairment)

References:[1][5][6][7][8][9][10][11][12]

Symptomatic or cryptogenic generalized epilepsy syndromes

Symptomatic generalized epilepsy syndromes typically occur in association with structural or metabolic abnormalities, whereas cryptogenic generalized epilepsy syndromes describe seizures of unknown etiology. These syndromes do not respond well to antiseizure drug therapy and are commonly associated with developmental delays, as well as motor and cognitive impairments.

Age at disease onset Etiology Clinical findings and characteristics EEG Treatment Prognosis

Infantile spasms

(West syndrome)

  • 3–7 months
  • Sex: >
  • Sudden symmetric, synchronous spasms, usually in clusters of 5–10
  • Jerking flexion (jackknife movement) or extension of the neck, torso, and extremities
  • Followed by a tonic phase
  • Hypsarrhythmia: characteristic finding in interictal EEG; high-voltage delta waves with irregular multifocal spikes and slow waves
  • Ictal EEG: very heterogeneous
  • Poor; increased mortality
  • Neurodevelopmental delay, regression of psychomotor abilities in > 85% of cases
  • In ∼ 50% of cases spasms cease before age 5 years
  • Most cases develop other forms of epilepsy )
Lennox-Gastaut syndrome
  • 3–5 years
  • Sex: >
  • Majority of cases due to structural brain abnormalities
  • 40% of cases are cryptogenic
  • Multifocal sharp and slow waves
  • Abnormal interictal EEG: slow spike-wave pattern
  • Poor; only 10% are seizure-free under treatment
  • Developmental delay, cognitive impairment, and psychotic symptoms
  • Mortality rate of 3–7%

Progressive myoclonic epilepsy

Type: Unverricht-Lundborg disease

  • 6–15 years
  • Generalized spike wave paroxysms
  • Photosensitivity
  • Severe physical disability and cognitive decline
  • Fatal within 5–20 years after disease onset

References:[1][2][9][11][12][13][14][15]

Diagnostics

  • Seizure history (see diagnosis of epilepsy)
  • EEG: abnormal electrical discharges
  • Laboratory analysis
    • Rule out metabolic abnormalities (e.g., hypoglycemia, electrolyte abnormalities)
    • Toxicology screening; determine anticonvulsant plasma levels in previously diagnosed patients receiving medical treatment
    • Blood cultures and lumbar puncture in febrile patients
  • Cranial MRI and CT scan: rule out structural brain abnormalities (e.g., tumors)

References:[16]