Seizure Disorder, Absence

Description

An absence seizure is a generalized epileptic seizure characterized by a brief lapse of awareness.

Absence seizure types according to the International League Again Epilepsy (ILAE) 2010 classification include (1):

• Typical absence
  • Formerly called petit mal seizures
  • Abrupt-onset behavioral arrest, loss of awareness, and blank staring, sometimes with mild upward eye deviation, repetitive blinking
  • May include automatisms, tonic or atonic features, eyelid or facial clonus, autonomic features
  • Lasts 5 to 30 seconds
  • Immediate return to normal consciousness
  • Associated with genetic generalized epilepsies, namely, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), and juvenile myoclonic epilepsy
• Atypical absence
  • Onset and offset less abrupt than typical absence seizures
  • Lasts 10 to 45 seconds
  • Impairment of consciousness often incomplete with continued purposeful activity
  • Postictal confusion sometimes occur.
  • Associated clinical features more pronounced and frequent than in typical absence; atonia is most common.
  • Associated with syndromic epilepsies, such as Lennox-Gastaut and nonsyndromic epilepsies in patients with developmental delay
• Absence with special features
  • Myoclonic absence:
    • Rhythmic clonic jerking at 2 to 4 Hz which lasts 5 to 10 seconds
    • Unlike myoclonic seizures with no impairment of consciousness, brief lapses of awareness are characteristic of myoclonic absence.
  • Eyelid myoclonia:
    • Rhythmic clonic jerking of the eyelids at 5 to 6 Hz which lasts 3 to 5 seconds
    • Eyelid myoclonia with absence associated with an impairment of consciousness

Specific diagnoses according to ILAE (2010):

• CAE
  • Also known as pyknolepsy
  • Typical absence seizures are the only seizure type in 90% of children.
  • 10% develop additional generalized tonic–clonic seizures.
  • Seizures last ~10 seconds and often occur hundreds of times per day.
  • Normal neurologic state and development
  • Spontaneous remission occurs in 65–70% of patients during adolescence.
• JAE
  • Typical absence seizures are the main seizure type.
  • Seizures last longer than in CAE and occur usually less than once a day.
  • Generalized tonic–clonic seizures occur in most patients, often in the first 1 to 2 hours after awakening.
  • Seizures often persist into adulthood.

Epidemiology

• Predominant age
  • CAE: onset ages 4 to 10 years, with peak at ages 5 to 8 years
  • JAE: onset ages 9 to 16 years, with peak at ages 10 to 12 years
• Predominant gender
  • Female > male (3:2 to 2:1)
  • Epilepsy with myoclonus has male predominance.

Incidence
6 to 8/100,000 per year

Prevalence
5 to 50/100,000

Etiology and Pathophysiology

• Corticoreticular theory implicates abnormal activity in thalamocortical circuits.
• Thalamic reticular nucleus is responsible for both normal sleep spindles and pathologic slow-wave discharges; contains inhibitory γ-aminobutyric acid-ergic (GABAergic) neurons
• These neurons affect low-threshold calcium currents.
• These circuits can fire in oscillatory/rhythmic fashion:
  • Normally, activation of GABA_A receptors causes 10-Hz oscillations in sleep spindle frequency.
  • If GABA_B receptors are strongly activated, oscillation frequency will be 3 to 4 Hz, similar to spike-and-wave typical absence seizure frequency.

• 70–85% concordance occurs in monozygotic twins; 82% share EEG features.
• 33% concordance among first-degree relatives
• 15–45% have a family history of epilepsy.
• Complex multifactorial inheritance
• For childhood absence, genes/loci implicated include 6q, 8q24, and 5q14.
• Mutations of GABA_A receptor and voltage-gated Ca²⁺ channel are implicated.

Commonly Associated Conditions

• 3–8% of CAE cases evolve into juvenile myoclonic epilepsy.
• Associated with difficulties in visual attention and visuospatial skills, verbal learning and memory, and reduced language abilities
• Children with CAE have elevated rates of behavioral and psychiatric comorbidities including attentional deficits, anxiety, depression, isolation, and low self-esteem.
• A large study in 2010 detected overall normal cognition, but 35% of subjects had pretreatment attentional deficits that did not resolve with seizure control.