Childhood and juvenile absence epilepsy are forms of idiopathic (genetic) generalized epilepsy that are characterized by seizures that involve sudden arrest in activity, awareness, and responsiveness, and may include some mild motor features. Typical absence seizures usually last less than 20 s and end as abruptly as they start. Patients have no recollection of the event and often return immediately to their previous activity with little or no postictal alterations in functioning. Generalized 3 Hz spike-and-wave discharges on EEG are required for the diagnosis and are strongly correlated with the clinical events.
Childhood absence epilepsy (CAE)
Juvenile absence epilepsy (JAE)
The incidence of CAE is estimated at 6–8% per 100,000 in children younger than 15 years, and the estimated prevalence is 10–12% in children younger than 16 years with epilepsy. The incidence of JAE is less clear, but it is accepted as being less common than CAE. Some estimates suggest that JAE occurs in 10–15% of individuals with epilepsy, though there is likely a pattern of under diagnosis in this condition due to less frequent seizure and the higher rate of other seizure types. CAE is typically considered to be more common in females, but gender differences in JAE have not been reported.
CAE is strongly associated with a family history of seizures, and there is robust concordance among identical twins. Siblings of patients with CAE have about a 10% chance of having seizures, and about one third of patients with CAE have a family member with epilepsy. Heritability of the spike-and-wave trait has been found to peak at the age of 10 years and goes away almost completely by the age of 40. Only about 20% of family members with the spike-and-wave trait develop epilepsy. Multiple genes likely account for transmission, but the causal influences are believed to be multifactorial, depending on both genetic and nongenetic factors. Causal factors in JAE have not been well-studied but may be similar to what is found in CAE.
Natural History, Prognostic Factors, and Outcomes
Typical age of onset in CAE is between 3 and 10 years, with average age of onset of 6 years. Rare cases of onset prior to 3 years of age have been reported. Most cases of JAE are believed to manifest between 10 and 17 years, and average age of onset is 12 or 13 years. Because of variability in onset, there is diagnostic overlap between CAE and JAE, potentially amounting to about 22% of cases with absence seizures. EEG and clinical findings are often useful in differentiating CAE from JAE in older children and younger adolescents, and it is highly unusual for a child with CAE to experience onset of seizures after 11 years of age.
CAE and JAE are both associated with favorable outcomes. Most patients with CAE experience remission of seizures by mid-adolescence, with only a small proportion experiencing absence seizures into adulthood. About 40% of patients with CAE also exhibit generalized tonic-clonic seizures that emerge around the time of puberty, are relatively easy to control, and more commonly persist into adulthood than absence seizures. Generalized tonic-clonic seizures are significantly more common in JAE and occur in about 80% of cases. Some patients with JAE also exhibit myoclonic seizures, but they are typically mild and infrequent. While most patients with CAE become seizure-free by adolescence, seizure outcome in JAE is not well known.
CAE is considered a benign childhood epilepsy because of relatively good seizure and functional outcomes. Seizure control is less common in JAE, but functional outcomes may be similar. Further research is needed to examine this. Tonic-clonic seizures are believed to be a marker for poorer seizure outcome in both CAE and JAE. Functional outcomes in CAE are thought to be most heavily influenced by psychosocial factors, such as family adjustment, support systems, educational attitudes, and stigma toward the condition. Cognitive and/or behavioral side effects from antiepileptic drug (AED) therapy may also limit outcomes.
Neuropsychology and Psychology of Absence Epilepsy
Cognitive functioning in CAE is traditionally considered “benign” because children typically present with normal intelligence and exhibit no significant impairments in functional outcomes. However, more recent research has found evidence that patients with CAE are more prone to having cognitive deficits and psychosocial problems, and they are more likely to receive special education services and display low academic achievement. While patients with poor seizure control exhibit the greatest difficulties, cognitive and behavioral problems are also experienced by patients with good seizure control. While limited information is known about cognitive and psychological functioning in JAE, some reports suggest that about one-third of patients have attention, concentration, or memory problems before their diagnosis of JAE. These cognitive concerns may improve with treatment.
Patients with CAE do not have a characteristic cognitive profile. Cognitive difficulties have been reported in multiple domains, including attention, executive functioning, memory, and visual-spatial processing. A study by Caplan et al. (2008) revealed the presence of subtle cognitive impairments in children with CAE. When compared with controls, they found that children with CAE (ages 6.7–11.2 years) had significantly lower intelligence, as measured by the Wechsler Intelligence Scale for Children – Revised/Third Edition. While, as a group, children with CAE performed in the average range, they were below the performance of a control group. Similar differences were noted on verbally based and visually based intellectual tasks. The difference in performance IQ was less robust, but still significant, between children with CAE and controls. Among their sample of 69 children with CAE, 27% demonstrated overall intelligence at least one standard deviation below the mean. Similar rates were found for VIQ and PIQ. Their spoken language quotient (SLQ), as measured by various versions of the Test of Language Development, was average, but it was also lower than controls. A high percentage of children with CAE performed at least one standard deviation below the mean on language measures.
In the double-blind, randomized controlled clinical trial conducted by the Childhood Absence Epilepsy Study Group, 36% of children with CAE had pretreatment attention problems at a rate estimated to be fourfold that of the general population (Masur et al. 2013). This was despite average intelligence and otherwise normal neurocognitive functioning. Attention problems were disproportionately higher for children being treated with valproic acid. Preferential cognitive deficits in executive functioning have been found in multiple studies affecting problem solving, planning, and fluency.
Caplan et al. (2008) confirmed that children with CAE are at higher risk for emotional and behavioral problems. Among the 69 children with CAE in their sample, 30% had a diagnosis of attention-deficit/hyperactivity disorder (ADHD), with 52% of those children diagnosed as ADHD-inattentive type. Moreover, about 29% of their sample were diagnosed with a form of internalizing psychopathology. Among those children, 75% had a diagnosis of anxiety, 20% had a diagnosis of depression, and 5% had both anxiety and depression. After controlling for IQ and demographic variables, children with CAE were found to have significantly higher ratings on scales of the Child Behavior Checklist (CBCL) that assess attention problems, somatic problems, social problems, withdrawal, and thought problems. The authors discovered that children with lower intelligence had greater social problems, and females in the CAE sample were almost six times more likely to be diagnosed with an anxiety disorder. In addition, children with CAE were more likely to be diagnosed with ADHD or anxiety if they had more frequent seizures or a longer duration of illness. Verrotti et al. (2015) proposed that it is unclear whether psychological concerns in CAE are a consequence of disease related factors or are part of the epileptic syndrome; however, a recent report by Schwartz and Titus (2015) with the BASC-2 suggested that children with CAE may be more predisposed to depression than other epilepsy syndromes.
Children and adolescents with CAE and JAE typically present with no focal neurological abnormalities on examination. The presence of absence seizures is a defining feature of absence epilepsy, and hyperventilation or light stimulation can be highly effective at eliciting an event. In CAE, absence seizures occur multiple times per day, but, in JAE, seizures are less frequent.
Absence seizures can be either typical or atypical, and discrimination between the two types is typically accomplished through EEG and clinical presentation. While typical absence seizures are characterized by clearly delineated episodes of activity arrest and impaired consciousness for less than 20 s, atypical absence seizures are associated with less abrupt onset and termination, and they may more commonly involve various semiological phenomena. Atypical absence seizures are also frequently observed in epilepsy syndromes that are characterized by more severely impaired neurocognitive functioning, such as Lennox-Gastaut syndrome. Tonic seizures are also frequently present in children with atypical absence seizures.
Typical absence seizures can be subdivided into simple or complex. Simple typical absence seizures constitute about 90% of cases and may involve only minor motor mannerisms (e.g., mild eyelid fluttering) and usually last less than 10 s. Patients with complex typical absence seizures display more involvement of motor features, such as automatisms or decreased or increased muscle tone.
Complex partial seizures can often mimic absence seizures, particularly when their expression is limited. Typical absence seizures can be distinguished from complex partial seizures because they are briefer, more frequent, and have no postictal impairment. EEG characteristics and the presence of various seizure types often distinguish atypical absence seizures from complex partial epilepsy.
When evaluating for the presence of absence seizures, it is important to consider whether the episodes can be accounted for by variations in attention. This is especially important when considering the high rate of attention problems in children with epilepsy. Attempting to determine the degree of responsiveness during the episodes often helps with making the differential diagnosis; however, this can be difficult to determine when episodes are very brief. Moreover, it is not uncommon for patients to have both absence seizures and attention problems. Therefore, a child’s ability to respond during an episode cannot be used to rule-out the presence of absence seizures. Sometimes a neuropsychological assessment can be helpful in differentiating between absence seizures and episodes of inattention. If the examiner has experience with absence seizures, the neuropsychological assessment can provide multiple hours of one-on-one observation and interaction that might provide opportunities to observe the episodes and attempt to elicit responses. This can also be helpful if mental fatigue tends to elicit more events.
On EEG, absence seizures are characterized by paroxysmal bursts of high amplitude 2.5–4 Hz spike and slow waves that are superimposed on a normal background. The bursts vary in length (3–20 s), and the clinical absence is time-locked to the burst period. This activity (clinical and electrographic) can be provoked during a routine EEG recording using the hyperventilation activation procedure and, infrequently, from photic stimulation.
Response to AED therapy in CAE and JAE is good, and ethosuximide is considered the drug of first choice. Valproic acid or lamotrigine have also been recommended. In rare cases of more difficult to control seizures, polytherapy may be needed. In patients with CAE, a seizure-free period of 2 years is often recommended prior to discontinuation of therapy; however, this should be determined on a case-by-case basis. About 40% of children with CAE develop generalized tonic-clonic seizures. Patients with JAE will require longer treatment and may continue using AEDs indefinitely. In adolescent patients, it is important to educate about the increased risk of seizures with poor medication compliance, alcohol consumption, or sleep deprivation.
References and Readings
- Berkovic, S. F., & Benbadis, S. (2001). Childhood and juvenile absence epilepsy. In E. Wyllie (Ed.), The treatment of epilepsy: Principles and practice (3rd ed., pp. 485–490). Philadelphia: Lippincott Williams & Wilkins.Google Scholar
- Holtkamp, M. (2017). Genetic generalized epilepsies with adolescent onset. In J. M. Pellock, D. R. Nordli Jr., R. Sankar, & J. W. Wheless (Eds.), Pellock’s pediatric epilepsy: Diagnosis and therapy (4th ed., pp. 337–346).Google Scholar
- Masur, D., Shinnar, S., Cnaan, A., Shinnar, R. C., Clark, P., Wang, J., Weiss, E. F., Hirtz, D. G., Glauser, T. A., & Childhood Absence Epilepsy Study Group. (2013). Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy. Neurology, 81, 1572–1580.CrossRefPubMedPubMedCentralGoogle Scholar
- Pearl, P. L., & Holmes, G. L. (2017). Childhood absence epilepsy. In J. M. Pellock, D. R. Nordli Jr., R. Sankar, & J. W. Wheless (Eds.), Pellock’s pediatric epilepsy: Diagnosis and therapy, (4th ed) pp. 309–336).Google Scholar
- Schwartz, J. K., & Titus, J. B. (2015). Executive functioning and behavioral profiles in childhood absence epilepsy and juvenile myoclonic epilepsy [Abstract]. Journal of the International Neuropsychological Society, 21(s1), 87–88.Google Scholar