Childhood Absence Epilepsy

Childhood absence epilepsy (CAE), formerly known as pyknolepsy, is an idiopathic generalized epilepsy syndrome that begins in childhood, typically between the ages of 4 and 10, with a peak onset between 5 and 7 years. It is characterized by frequent absence seizures — brief episodes of impaired awareness that start and end suddenly, often accompanied by subtle automatisms such as eyelid fluttering or lip smacking. Seizures usually last less than 30 seconds and may occur dozens or even hundreds of times per day. Children with CAE are otherwise developmentally normal, and the electroencephalogram (EEG) shows characteristic generalized 3 Hz spike-and-wave discharges. The syndrome is genetically complex, with seizures believed to arise from thalamocortical network dysfunction. Prognosis is generally favorable, with many children achieving seizure remission during adolescence. Ethosuximide is the preferred first-line treatment.

Signs and symptoms

Childhood absence epilepsy is characterized by typical absence seizures — brief, generalized seizures with sudden onset and offset. During a seizure, the child may abruptly stop ongoing activity and appear to stare blankly, with impaired awareness. These episodes usually last between 10 and 30 seconds, after which the child resumes activity without confusion.

Subtle motor automatisms are common, including eyelid fluttering, lip smacking, or minor hand movements, though more pronounced motor features are unusual. Seizures often occur in clusters and may happen dozens of times per day. Typically, there are no aura or postictal symptoms.

Causes

CAE is considered a complex polygenic disorder. It is classified as an idiopathic generalized epilepsy (IGE), meaning that it arises without identifiable structural brain abnormalities and is presumed to have a strong genetic basis. Most cases are polygenic, involving the combined effect of common genetic variants that affect thalamocortical excitability, synaptic transmission, and ion channel regulation. Although CAE does not have a single defining mutation, several genes have been implicated in susceptibility. These include CACNA1H, which encodes a T-type calcium channel subunit (Cav3.2) involved in thalamic pacemaker activity, and GABRG2 and GABRA1, which encode subunits of the GABAA receptor. These findings support the role of impaired inhibitory neurotransmission and altered calcium signaling in the pathogenesis of absence seizures. However, these variants are neither specific nor necessary for the diagnosis, and no genetic test is currently diagnostic for CAE in the general population.

Pathophysiology

CAE is characterized by associated with generalized 2.5–4 Hz spike-and-wave discharges on electroencephalography (EEG), which are thought to result from abnormal oscillations within thalamocortical circuits. These involve interactions between the thalamic reticular nucleus, thalamocortical relay neurons, and cortical pyramidal cells, and reflect an imbalance between excitatory and inhibitory processes.

A key mechanism involves low-threshold T-type calcium channels, which are highly expressed in thalamic neurons and contribute to rhythmic burst firing. Overactivation of these channels is believed to support the generation and maintenance of spike-and-wave discharges. The effectiveness of ethosuximide, a first-line treatment for absence seizures, is thought to relate to its ability to block T-type calcium currents. Inhibitory signaling through GABAergic mechanisms also plays an important role. Abnormal GABA_A and GABA_B receptor activity within the thalamus and cortex has been observed in animal models of absence epilepsy, contributing to hypersynchronous network dynamics.

Diagnosis

The diagnosis of CAE diagnosed based on clinical history, EEG findings, and specific syndrome criteria. The syndrome requires the presence of typical absence seizures — brief generalized seizures with abrupt onset and offset, characterized by impaired awareness and, often, subtle automatisms. These episodes typically occur multiple times per day and begin and end abruptly. It typically occurs in otherwise typically developing children between 4 and 10 years of age.

EEG is essential for confirmation. The hallmark finding is a generalized, symmetric 3 Hz (range: 2.5–4 Hz) spike-and-wave discharge that coincides with the clinical absence. Hyperventilation is a reliable activation method, with typical discharges induced in up to 87% of cases. If no generalized spike-wave activity is observed after 3 minutes of hyperventilation in an untreated child, the diagnosis of CAE is unlikely. The background rhythm is typically normal.

Because staring is common in childhood, clinical distinction between absence seizures and behavioral staring spells is essential. Features suggestive of seizures include abrupt onset and offset, loss of facial expression, repetitive movements, unresponsiveness to external stimuli, and occurrence during active tasks.

The new classification of the epilepsy syndrome provides mandatory and exclusionary criteria, as well as some points that signs that should be considered as alerts. Alert features are uncommon in CAE but may occasionally occur. These include seizure onset between ages 2–3 or 11–13 years, absence seizures that are prolonged or infrequent, generalized tonic–clonic seizures before or during the period of frequent absences, and EEG abnormalities such as consistently unilateral discharges or a lack of response to hyperventilation. While the presence of an alert feature does not exclude the diagnosis, it reduces diagnostic confidence and should prompt careful reevaluation. The more alert features that are present, the greater the need to consider alternative epilepsy syndromes.

Exclusionary features are findings that are incompatible with a diagnosis of CAE. These include the presence of other seizure types (such as myoclonic, atonic, tonic, atypical absence, or focal seizures), seizure onset before age 2 or after age 13, moderate to profound intellectual disability, and diffuse EEG background slowing. When these features are present, a different diagnosis should be pursued.

Management

Ethosuximide is considered the first-line treatment for childhood absence epilepsy, based on comparative evidence from randomized and observational studies. A multicenter randomized controlled trial involving 453 children found that ethosuximide and valproate had similar efficacy in achieving seizure freedom after 16 weeks of treatment. However, ethosuximide was associated with a lower incidence of attentional side effects, whereas valproate increased the risk of attention deficit symptoms.

A prospective cohort study also found that ethosuximide was associated with a higher rate of complete remission compared to valproate, with a hazard ratio of 2.5 (95% CI: 1.1–6.0) in multivariate analysis. Based on these findings, ethosuximide is generally recommended as the preferred initial therapy. Valproate may be considered if ethosuximide is ineffective or not tolerated.

Epidemiology

CAE accounts for 10-17% of all cases of epilepsy in school-aged children. The incidence is approximately 6.3–8.0 children per 100 000 per year.

See also

* Generalized epilepsy with febrile seizures plus
* Calcium channel
* Spike and wave

References

{{DEFAULTSORT:Childhood Absence Epilepsy
Channelopathies
Epilepsy types
Seizure types