INTRODUCTION — Childhood absence epilepsy (CAE) is a common generalized epilepsy syndrome with a presumed genetic cause, characterized by typical absence seizures (TAS) appearing in otherwise healthy school-aged children. CAE is one of the most common forms of pediatric epilepsy.
TAS manifest as episodes of sudden, profound impairment of consciousness without loss of body tone. They are characteristically provoked by hyperventilation and correspond with generalized 2.5 to 5 Herz spike wave activity on electroencephalogram (EEG). Seizures may be subtle and often go unnoticed for prolonged periods, even with multiple seizures per day.
In most cases, TAS are the only seizure type observed in CAE, and they respond well to ethosuximide as well as other broad spectrum antiseizure medications. CAE remits by early puberty in most patients without major sequelae, although persistent cognitive or psychiatric comorbidities may be present in some children.
The clinical features, diagnosis, treatment, and prognosis of CAE are discussed here. Other epilepsy syndromes with an onset in childhood are discussed separately. (See "Seizures and epilepsy in children: Classification, etiology, and clinical features" and "Epilepsy syndromes in children" and "Juvenile myoclonic epilepsy".)
EPIDEMIOLOGY — CAE is one of the most common forms of pediatric epilepsy, accounting for 12 percent of epilepsy diagnoses in one prospective community-based study that included 613 children with epilepsy aged 0 to 16 years [1,2]. Of note, estimates of the annual incidence of CAE are derived from studies performed in primarily White populations. In a retrospective analysis of EEG findings of Swedish children aged 0 to 15 years, the annual incidence of "absence epilepsy" was 6.3 per 100,000 [3]. In another report based on a questionnaire sent to patients with seizures in southwest France, the annual incidence of CAE was estimated at 8 per 100,000 [4].
CAE is one of the rare epilepsy syndromes in which prevalence is higher in girls than boys [5,6].
ETIOLOGY AND GENETICS — CAE is classified as an epilepsy syndrome with presumed genetic cause according to the current International League Against Epilepsy (ILAE) classification system [7,8]. In previous versions of the classification system, CAE was referred to as an idiopathic syndrome [9]. (See "ILAE classification of seizures and epilepsy".)
A genetic cause has been suggested by family and twin studies, although clear single-gene defects that reliably result in a typical CAE phenotype have not yet been identified. Family studies indicate a 17 percent risk of having typical absence seizures (TAS) in first-degree relatives of patients with CAE [10], and there is a higher concordance rate for CAE in monozygotic than dizygotic pairs [11].
Several candidate regions and genes have been identified as possible susceptibility loci in CAE. Copy number variations and microdeletions in regions such as 8q and 15q have been reported in a minority of patients with generalized epilepsy syndromes, including some with CAE [12,13]. One group performed sequencing of the 15q candidate region in 380 patients with CAE and identified heterozygous point mutations in NIPA2, a gene that encodes for a selective magnesium transporter, in 3 of 380 patients with CAE and in none of the 400 controls [14].
Most of the genes otherwise reported code for various subunits of gamma-aminobutyric acid A (GABA-A) receptors [15-22], GABA-B receptors [20,23], calcium channels [20,23-28], or chloride channels [29,30], although validation has generally been lacking and ethnic variation may contribute to the heterogeneity in findings [21,31-34].
Another gene of interest in CAE is SLC2A1, which encodes the type 1 glucose transporter (GLUT1). Mutations in SLC2A1 were found in up to 10 to 12 percent of children presenting with absence epilepsy starting before four years or refractory absences [35-39]. In contrast, no SLC2A1 mutations were found in 84 subjects with CAE as defined by the onset of absences after four years, documented electroclinical TAS with generalized 3 to 4 Hz spike wave and normal background EEG activity, normal neurodevelopmental examination, and normal brain imaging [40].
PATHOPHYSIOLOGY — Studies in humans and rodent models have implicated a variety of cortical and thalamocortical circuits in the genesis of typical absence seizures (TAS) [41].
Most data point to prominent involvement of deep layers of the frontal and somatosensory cortex in the generation of slow wave discharges, with rapid spread to other regions of the cortex and secondary invasion of the thalamus [42-44]. The orbital-medial frontal and medial-lateral parietal cortices have been implicated in studies utilizing simultaneous EEG and functional MRI during typical slow wave discharges [45,46]. In another study, the posterior cortical regions were active at the onset of the slow wave discharge, followed by spread to other areas later in the seizure, including the thalamic medial dorsal nuclei and the thalamostriate network [47].
Animal data indicate that particular cortical and thalamic excitability and coupling conditions must occur to produce the slow wave discharges of TAS [42]. Enhanced tonic gamma-aminobutyric acid A (GABA-A) receptor inhibition in thalamocortical neurons has been demonstrated to be necessary and sufficient for the expression of TAS in various pharmacologic and genetic mouse models [48]. Such inhibition is due to increased extracellular GABA concentrations related to dysfunction of GAT-1, an astrocytic transporter involved in GABA synaptic uptake [48].
CLINICAL FEATURES
Clinical presentation — The median age of onset of CAE is six years [49,50]. The majority of patients present between four and ten years of age [5]. Up to 20 percent of children have a history of febrile seizures and nearly half have a first- or second-degree relative with seizures [49].
Seizure semiology — The hallmark seizure type of CAE is the typical absence seizure. Other seizure types are rare in CAE.
●Typical absence seizures (TAS) present as short and frequent episodes of profound impairment of consciousness without loss of body tone, lasting about 10 seconds. They are abrupt in onset and termination and easily provoked by hyperventilation. These typically come to the attention of parents, caregivers, or teachers after a prolonged period of observation, despite their high frequency. TAS may occur tens of times daily, but their subtle clinical symptoms allow them to go unnoticed or misdiagnosed as inattention.
The electroclinical spectrum of TAS in CAE is illustrated by two studies that reviewed a combined total of over 2000 absence seizures in more than 450 drug-naïve children with a new diagnosis of CAE [49,51]:
•Earliest clinical sign – Approximately half of all recorded seizures begin with an arrest in activity, which is typically complete. Less common first signs include eyelid movements, eye opening, and oral automatisms.
•Ictal signs and symptoms – The majority of electrographic seizures (approximately 80 percent) are associated with at least one clinical sign. The three most common seizure features are pause/stare (80 to 95 percent), motor automatisms (40 to 60 percent), and eye involvement (55 percent). About one-third of seizures involve three hertz (Hz) regular eyelid movements. Motor automatisms are predominantly oral.
•Seizure duration – The average seizure duration is 9 to 10 seconds. Approximately 25 percent of seizures last less than four seconds and approximately 10 percent are longer than 20 seconds.
Hyperventilation is an effective trigger of TAS, provoking seizures in 90 percent of children old enough to perform the maneuver [49]. TAS are not provoked by sensory or visual stimuli.
The presence of violent limb myoclonias, head nods, hypotonia, or focal signs are not consistent with TAS and should raise suspicion for other types of seizures, such as atypical absences or focal seizures. In addition, atypical absences should be suspected if the duration of the events exceeds the classic 10 to 20 seconds of TAS, especially if onset and termination are progressive rather than abrupt. (See 'Differential diagnosis' below.)
●Generalized tonic clonic seizures (GTCS) have been reported in up to 60 percent of children in some series [5,50], the true proportion is likely much lower when stringent diagnostic criteria for CAE are used. In two contemporary long-term follow studies of children with CAE, only 12 to 13 percent of children with CAE developed GTCS [52,53]. In the larger series, the median time to development of GTCS was 4.7 years, and the median age at first GTCS was 13 years [53]. GTCS rarely occur before puberty in CAE, and their presence during the active TAS stage of CAE is sometimes considered exclusionary for the diagnosis. (See 'Diagnosis' below.)
Cognition and behavior — Children with CAE typically have intact cognition and intellect at the time of diagnosis, although formal neurocognitive testing may detect mild deficits in a variety of domains, particularly executive function. This is illustrated by the following reports:
●In a study that compared neuropsychological and academic function in 94 children aged 8 to 18 years with new-onset epilepsy to 72 healthy subjects, specific difficulties in fine motor skills and executive functions were noted in children with both childhood and juvenile absence epilepsy [54].
●In a small study that included 16 children with CAE, 14 children with type 1 diabetes, and 15 healthy controls, children with CAE performed similarly to other groups on measures of global intellectual function, memory, and academic achievement but had significantly more executive dysfunction, as measured by deficits in problem solving, letter fluency, complex motor control, attention/behavioral inhibition, and psychosocial function [55].
●In a larger study that examined behavioral, cognitive, and linguistic comorbidities in 69 children with CAE and 103 age-matched healthy subjects, children with CAE had significantly lower scores on global, verbal, and performance intellectual quotients and speech language quotients [56].
Similar findings have also been reported in children with other generalized epilepsy syndromes that are typically associated with a favorable prognosis. In these studies, cognitive, social, emotional, or psychiatric comorbidities frequently antedate the epilepsy onset and require special educational interventions [54-59].
Psychiatric comorbidity — Psychiatric comorbidities are common in children with CAE. In a study that included 69 children with CAE, 61 percent had a psychiatric diagnosis (mostly attention deficit and hyperactivity disorder [ADHD] or anxiety), and 33 percent had behavioral or social problems [56]. Other studies have also reported higher rates of ADHD, anxiety, depression, social isolation, and low self-esteem in patients with CAE compared with healthy subjects [60-62]. In a large randomized trial that included nearly 450 children with newly diagnosed CAE, 36 percent of children had baseline attention deficits despite intact cognitive functioning [63].
ADHD appears to be a core feature of CAE in many children and is not simply the result of frequent seizures. The pattern of deficits tends to be more inattentive than hyperactive, which can make recognition of the deficits difficult for teachers and parents or caregivers [63,64]. Seizure duration rather than overall seizure frequency is one predictor of attentional dysfunction, but additional risk factors are not well established. In the randomized study mentioned above, the rate of subtle attentional difficulties was higher in the 30 percent of children who had at least one seizure longer than 20 seconds on initial EEG [65]. In the same study, overall number of seizures was not associated with measures of attention or executive function.
ELECTROENCEPHALOGRAPHY — EEG in patients with suspected CAE should be a sleep-deprived video-EEG study that includes both intermittent photic stimulation (IPS) and hyperventilation (HV) in order to maximize the chance of recording an absence seizure.
Among 47 consecutive patients with newly diagnosed CAE, diagnostic 30-minute sleep-deprived video EEG recordings captured an average of 6 seizures per child; of these, 47 percent occurred with HV, 25 percent during drowsiness, 13 percent during the awake state, 9 percent during IPS, and 7 percent during sleep [49]. At least one seizure was provoked during HV in 83 percent of children.
Interictal EEG — The interictal EEG in CAE shows normal background activity, although it is common to see occasional generalized spike wave discharges or focal abnormalities. In a review 445 pre-treatment EEGs, occipital intermittent rhythmic delta activity (OIRDA) was noted in 21 percent, focal sharp waves in 2.5 percent, and focal slowing in 0.7 percent [65]. In another study, focal intermittent paroxysmal activity was noted in 38 percent of 29 children with CAE, consisting in most cases of frontal spike wave or polyspike and wave discharges [66].
Ictal EEG — The EEG appearance of a typical absence seizure (TAS) consists of generalized 2.5 to 5 Herz (Hz) spike wave discharges (classically, 3 Hz) with abrupt onset and termination (waveform 1) [49]. Spike wave discharges are frequently disorganized, and pre- and post-ictal slowing is often present [49].
The morphologic characteristics of the spike wave discharges vary across recordings. In one study, 87 percent of spike wave discharges contained only one or two spikes per wave during the seizure; four or more spikes per wave were present in 8 percent of the 47 children when analyzed individually [49]. In another study, single spike wave discharges were noted in 604 of 721 discharges (84 percent), whereas polyspike wave discharges were present in only 3 percent [65].
In up to 50 percent of cases, the earliest ictal abnormalities are focal [49]. This is often predominant in the frontal leads bilaterally, a phenomenon referred to as "frontal lead-in" or "frontal absences" by some authors [67,68]. Similar features have also been reported arising from the occipital lobes [49].
The ictal EEG of atypical absences usually shows discharges of irregular generalized spike waves of lower frequency (< 2.5 Hz) than those observed in typical absence seizures (TAS).
NEUROIMAGING — Brain magnetic resonance imaging (MRI) is by definition normal in patients with CAE, and structural imaging is not necessary for the diagnosis if patients have typical clinical and EEG findings. Imaging is indicated only if there are focal findings on clinical or EEG evaluation.
High-resolution structural imaging has been used to demonstrate subtle anatomical variation in various brain regions in patients with CAE, although the functional and clinical significance of these findings is uncertain. Reported abnormalities include decreased thalamic grey matter volume and subcallosal gyrus atrophy [69], grey matter loss in the left orbital-frontal gyrus and bilateral temporal lobes [70], and amygdala volume loss in CAE patients with symptoms of attention deficit hyperactivity disorder [71]. Volumetric analyses of 3Tesla MRI scans in 18 patients with CAE and 18 age-matched control subjects showed that patients with CAE had reduced bilateral frontotemporal cortical grey matter volume and increased posterior medial cortical thickness [72].
DIAGNOSIS — CAE is diagnosed based on history, physical examination, and video-EEG findings. The most widely accepted diagnostic criteria were proposed by Panayiotopoulos in 1997 and accepted by the International League Against Epilepsy (ILAE) in 2005 [5,73].
According to these criteria, a diagnosis of CAE requires all of the following:
●Age at onset of 4 to 10 years
●Normal neurological and developmental state
●Brief (4 to 20 seconds) and frequent (tens per day) absence seizures, with abrupt and severe loss of consciousness
●Generalized rhythmic spikes or double spike wave discharges at around 3 Hz
In addition, the following criteria are exclusionary for the diagnosis of CAE:
●Other seizure types preceding or observed during the active stage of typical absence seizures
●Massive and sustained eyelid, perioral, head or limb myoclonias
●Mild or no impairment of consciousness during the spike wave discharge
●Spike wave discharges of less than 4 seconds
●More than 3 spikes or spike wave fragmentation
●Visual or other sensory seizure precipitants
Of note, some authors in the field consider these criteria as too strict, given the significant demographic, clinical and electroencephalographic heterogeneity demonstrated in at least one large series [49]. In addition, children with TAS beginning before the age of three who otherwise fulfill the above criteria may show a similarly favorable clinical course as those with CAE [74].
DIFFERENTIAL DIAGNOSIS — The first step in the differential diagnosis of CAE is to identify the nature of the paroxysmal events and determine whether they are electroclinical typical absence seizures (TAS) or nonepileptic staring spells. This is usually easy to do, and often only requires a short video-EEG recording [65]. Non-epileptic staring spells can occur in normal children as well as in association with attention deficit hyperactivity disorder, autism, and intellectual disability. Unlike TAS, staring spells can be interrupted by tactile or vocal stimulation, rarely occur during physical activity, and are never associated with automatisms or other motor signs. (See "Nonepileptic paroxysmal disorders in children", section on 'Nonepileptic staring spells'.)
In addition to CAE, TAS may be seen in other generalized epilepsy syndromes, including juvenile absence epilepsy (JAE) and juvenile myoclonic epilepsy (JME), as well as rare cases of type 1 glucose transporter (GLUT1) deficiency syndrome:
●Juvenile absence epilepsy – JAE is a generalized epilepsy also characterized by TAS but with a later peak age of onset of 10 to 12 years. In addition to later age of onset, distinguishing features of JAE include myoclonic seizures in approximately one fifth of patients and a higher incidence of generalized tonic clonic seizures (GTCS), which are uncommon in CAE.
●Juvenile myoclonic epilepsy – Approximately 20 to 40 percent of patients with JME have TAS, which typically begin several years before the onset of myoclonic seizures and GTCS. Compared with CAE, the TAS that occur in JME are typically milder and shorter, and the spike wave discharges on EEG are often of slightly higher frequency (ie, 4 to 6 Hz). (See "Juvenile myoclonic epilepsy".)
●GLUT1 deficiency syndrome – In patients with early-onset absences (ie, <4 years of age), GLUT1 deficiency syndrome should also be considered [36,75]. GLUT1 deficiency is a genetic disorder characterized by impaired glucose transport across the blood brain barrier. The diagnosis is suggested by a low cerebrospinal fluid glucose level and can be confirmed in most cases by genetic testing for SLC2A1. The phenotypic spectrum includes not only early-onset absence seizures but also other forms of generalized epilepsies, developmental delay and paroxysmal exertional dyskinesias that usually emerge during childhood or adolescence [39,76-78].
Treatment with the ketogenic diet can result in marked clinical improvement. Other dietary interventions are also under investigation. In small pilot studies, consumption of triheptanoin, a medium-chain triglyceride, has been associated with significant reduction in spike-wave burden, improvement in neuropsychological performance, and fewer paroxysmal motor events in children with GLUT1 deficiency who were not receiving the ketogenic diet [79,80]. (See "Seizures and epilepsy in children: Clinical and laboratory diagnosis", section on 'Laboratory and genetic testing in undiagnosed epilepsy' and "Ketogenic dietary therapies for the treatment of epilepsy", section on 'Particularly responsive conditions'.)
Atypical absences or absences with special features are usually observed in more severe forms of epilepsy, such as Lennox-Gastaut syndrome, epilepsy with myoclonic absences, or epilepsy with eyelid myoclonias [7]. (See "Lennox-Gastaut syndrome".)
TREATMENT
Goals of therapy — Typical absence seizures are characteristically extremely frequent, occurring multiple times each day. Once they are recognized, they should be treated to improve quality of life, school performance, and social acceptance, and possibly to reduce the risk of (rarely) associated convulsive seizures. Complete seizure freedom can often be attained by pharmacologic treatment.
First-line therapy — Ethosuximide is recommended as first-line therapy in most children with CAE [81].
This recommendation is supported by results of a randomized, double-blind trial that compared the efficacy and tolerability of ethosuximide, valproate, and lamotrigine in 453 children with CAE. After 16 weeks of treatment, ethosuximide and valproate were significantly more effective than lamotrigine (16-week freedom from seizure rates of 53, 58, and 29 percent, respectively), and the rate of drug discontinuation for adverse effects was similar among the three groups [82]. However, valproate was associated with more frequent attentional dysfunction than ethosuximide (49 versus 33 percent) [63,82]. A follow-up study that assessed the same parameters after 12 months of treatment also confirmed that ethosuximide had better efficacy than lamotrigine and fewer side effects than valproate [83].
The typical starting dose of ethosuximide is 5 to 10 mg/kg/day in two divided doses for children younger than six years, and 250 mg twice daily for children age six years and older. The usual maintenance dose is 15 to 40 mg/kg/day in divided doses. Blood levels should be checked initially after one to three weeks, with a goal therapeutic concentration of 40 to 100 mcg/mL. The most common side effects include nausea, vomiting, sleep disturbance, drowsiness, and hyperactivity. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Ethosuximide'.)
Initial monotherapy should not be abandoned before ensuring that the maximum tolerated dose has been achieved. In most cases, response can be assessed clinically, as TAS are usually easy to follow once they are recognized. In some cases, EEG can be used to aid in determining the response to therapy if the clinical improvement is unclear after two to four weeks of therapy.
Patients who fail or do not tolerate first-line therapy — In patients who have inadequate control of TAS or intolerable side effects on ethosuximide, we suggest switching to valproate monotherapy, although lamotrigine may be a better alternative in females of childbearing age based on the increasingly well characterized fetal risks of valproate. (See "Risks associated with epilepsy during pregnancy and postpartum period", section on 'Valproate' and "Risks associated with epilepsy during pregnancy and postpartum period", section on 'Neurodevelopmental risks of ASMs'.)
In the randomized trial described above, 208 patients who experienced treatment failure during the double-blind phase were enrolled in an open-label extension study and randomly assigned to second monotherapy with one of the remaining two study drugs [84]. After 16 to 20 weeks of therapy, freedom from seizure rates were higher for ethosuximide and valproate (53 and 58 percent, respectively) than for lamotrigine (29 percent). For ethosuximide and valproate, these response rates are comparable with those observed in the first-line setting [82] and support the practice of using second monotherapy rather than add-on therapy in children who do not respond adequately to first-line therapy.
For patients who develop generalized tonic clonic seizures on ethosuximide, valproate is also an effective second-line therapy, either as an add-on agent or as monotherapy, since it may be effective for both seizure types [81].
Additional options for refractory CAE include topiramate [85], benzodiazepines [5], acetazolamide [5], ketogenic dietary therapy, and vagus nerve stimulation. For all of these options, trials that formally evaluate their effectiveness and side effect profile are lacking [86]; however, observational data suggest benefit.
CAE may respond to ketogenic dietary therapy when antiseizure medications are incompletely effective [87,88]. In a case series of 21 patients with childhood and juvenile absence epilepsy, use of the classic ketogenic diet or modified Atkins diet was associated with a >50 percent seizure reduction in 82 percent and compete seizure remission in 19 percent [87]. In the same report, a review of published studies that included 133 patients with absence epilepsy found similar results; 69 percent had a >50 percent seizure reduction and 34 percent became seizure-free. (See "Ketogenic dietary therapies for the treatment of epilepsy".)
Vagus nerve stimulation has been shown to reduce seizure frequency in six patients with CAE and refractory absences [89]. (See "Vagus nerve stimulation therapy for the treatment of epilepsy" and "Ketogenic dietary therapies for the treatment of epilepsy".)
There are mixed reports from small studies with regard to levetiracetam in CAE, with one study suggesting efficacy [90], another reporting aggravation of absences in certain patients [91], and a third study of 72 children showing apparent benefit in 25 percent but a high rate of discontinuation (74 percent) due to poor seizure control and/or side effects [92].
Drugs to avoid — Several antiseizure medications have the potential to aggravate absence seizures in patients with CAE and should be avoided. These include carbamazepine, vigabatrin, gabapentin, and tiagabine. Phenytoin and phenobarbital are known for their ineffectiveness in treating absences and should also be avoided [5].
Duration of therapy — In most cases, seizures respond well to first-line drug therapy and remit before puberty. Antiseizure medication therapy should be continued for a minimum of two years of seizure freedom. After this period, progressive tapering of antiseizure medications can be considered.
PROGNOSIS — Although CAE is often perceived as a benign form of epilepsy, observational studies with long-term follow up describe a fairly wide range of seizure outcomes in children with CAE. Much of the variability likely relates to differences in diagnostic classification over the years, however, and the inclusion of patients who ultimately go on to have juvenile myoclonic epilepsy (JME) or other syndromes associated with lower rates of seizure remission. Strict use of the 2005 International League Against Epilepsy (ILAE) criteria may identify a more homogeneous subgroup of patients with an excellent prognosis [93].
In one study that included 72 children initially diagnosed with CAE, approximately two-thirds of patients were seizure free at a minimum follow up of nine years after seizure onset [50]. Seventeen percent were still having seizures but did not take medications. Forty-four percent of patients not in remission had progressed to JME. Significant factors predicting no remission included cognitive difficulties at onset, absence status epilepticus before or during drug treatment, generalized tonic clonic or myoclonic seizures after treatment onset, abnormal background on initial EEG, and a history of generalized seizures in first-degree relatives.
In another study, over 90 percent of children with CAE diagnosed according to the 1989 ILAE classification were seizure free after a mean follow-up of 15 years [52]. Those who fulfilled the 2005 criteria had fewer generalized tonic clonic seizures, but their final overall outcome was not significantly different than those who did not. The total duration of epilepsy and the mean age at final remission were 3.9 and 9.5 years, respectively. Epilepsy duration was longer in those children who had become seizure-free more than six months after treatment initiation [52].
A relatively small proportion of children with typical absence seizures are refractory to typical therapeutic approaches for a prolonged period. In one study of 92 such children with refractory typical absence seizures, approximately 50 percent eventually achieved prolonged seizure freedom with or without antiseizure medications [94].
Despite favorable rates of seizure freedom by adolescence, psychiatric and behavioral comorbidities are common in children with CAE and can persist even in the absence of ongoing seizures. Recognition of comorbid diagnoses such as attention deficit hyperactivity disorder (ADHD) is important, because effective treatments exist, and ADHD has been associated with decreased health-related quality of life in children with epilepsy. This is discussed in more detail separately. (See "Epilepsy in children: Comorbidities, complications, and outcomes", section on 'Psychiatric and behavioral health'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in children".)
SUMMARY AND RECOMMENDATIONS
●Childhood absence epilepsy (CAE) is a generalized epilepsy characterized by typical absence seizures (TAS) occurring in otherwise healthy children. It is one of the most common forms of pediatric epilepsy, accounting for approximately 12 percent of all cases of childhood-onset epilepsy. In contrast with most pediatric epilepsy syndromes, the prevalence of CAE is higher in girls than in boys. (See 'Epidemiology' above.)
●CAE is classified as an epilepsy syndrome with presumed genetic cause according to the current International League Against Epilepsy (ILAE) classification system. A genetic cause has been suggested by family and twin studies, although clear single-gene defects that reliably result in CAE have not yet been identified. (See 'Etiology and genetics' above.)
●The median age of onset of CAE is six years, with the majority of patients presenting between the ages of four and ten years of age. (See 'Clinical presentation' above.)
●The hallmark seizure type is the typical absence seizure (TAS), characterized by profound impairment of consciousness, abrupt in onset and termination, lasting an average of 10 seconds. TAS are frequently associated with early arrest in activity, staring, repetitive eyelid movements, and automatisms. (See 'Seizure semiology' above.)
●Although children with CAE typically have normal development and intellect, formal neurocognitive testing may detect mild deficits in a variety of domains, particularly executive function. Comorbid attention deficit hyperactivity disorder and anxiety are common. (See 'Cognition and behavior' above and 'Psychiatric comorbidity' above.)
●The classic EEG pattern of TAS consists of discrete periods of generalized 3 hertz spike wave discharges that are easily provoked by hyperventilation. (See 'Electroencephalography' above.)
●The diagnosis of CAE is made in a child with normal development who presents between the ages of 4 and 10 years with frequent spells of altered consciousness that are confirmed to be TAS by video EEG. Features that are considered exclusionary for the diagnosis of CAE include seizure types other than TAS at the time of diagnosis, atypical absence features such as massive and sustained myoclonias, and visual or sensory seizure precipitants. (See 'Diagnosis' above.)
●The differential diagnosis of TAS in a child includes nonepileptic staring spells, which can be seen in association with normal development, attention deficit hyperactivity disorder, autism, and intellectual disability. In addition to CAE, TAS may also be seen in other generalized epilepsy syndromes such as juvenile absence epilepsy and juvenile myoclonic epilepsy. (See 'Differential diagnosis' above.)
●In children with newly diagnosed CAE, we recommend ethosuximide rather than valproic acid or lamotrigine as first-line therapy (Grade 1B). Ethosuximide is well tolerated and associated with complete seizure freedom in over half of children after 16 weeks of therapy. (See 'Treatment' above.)
●For children who fail or do not tolerate first-line therapy with ethosuximide, we suggest switching to valproic acid monotherapy (Grade 2B). Lamotrigine is a reasonable alternative in females of childbearing age based on the increasingly well characterized fetal risks of valproate. (See 'Patients who fail or do not tolerate first-line therapy' above.)
●The overall prognosis of CAE is favorable. In most cases, seizures respond well to the first-line drug monotherapy and remit before puberty, without cognitive sequelae. (See 'Prognosis' above.)
