Introduction
Background
Absence seizures are a type of generalized seizures.1,2 They were first described by Poupart in 1705, and later by Tissot in 1770, who used the term petit access. In 1824, Calmeil used the term absence.3 In 1935, Gibbs, Davis, and Lennox described the association of impaired consciousness and 3-Hz spike-and-slow-wave complexes on electroencephalograms (EEGs).4
Absence seizures occur in both idiopathic and symptomatic generalized epilepsies.5 Among the idiopathic generalized epilepsies, absence seizures are seen in childhood absence epilepsy (pyknolepsy), juvenile absence epilepsy, and juvenile myoclonic epilepsy (impulsive petit mal).6 The seizures in these conditions are called typical absence seizures and are usually associated with generalized 3-4 Hz spike-and-slow-wave complexes on EEG.7
In childhood absence epilepsy, seizures are frequent and brief, lasting just a few seconds (pyknoleptic). Some children can have many such seizures per day. In other epilepsies, particularly those with an older age of onset, the seizures can last several seconds to minutes and may occur only a few times a day (called nonpyknoleptic or spanioleptic absence seizures). Myoclonic and tonic-clonic seizures may also be present, especially in syndromes with an older age of onset. In these syndromes, the discharge frequency may be faster than 3 Hz.
In the cryptogenic or symptomatic generalized epilepsies, absence seizures are often associated with slow spike-wave complexes of 1.5-2.5 Hz6 ; these are also called sharp-and-slow-wave complexes. These seizures may be associated with loss of axial tone and head nodding or a fall may occur. Increased tone, autonomic features, and automatisms may also be seen. Absence seizures associated with slow spike-wave complexes are called atypical absence seizures.8
Pathophysiology
The pathophysiology of absence seizures is not fully understood. In 1947, Jasper and Droogleever-Fortuyn electrically stimulated nuclei in the thalami of cats at 3 Hz and produced bilaterally synchronous spike-and-wave discharges on EEG.23 In 1953, bilaterally synchronous spike-and-wave discharges were recorded by using depth electrodes placed in the thalamus of a child with absence seizures.24
In 1977, Gloor demonstrated that the bilaterally synchronous 3-Hz spike-wave discharges in the feline penicillin model of absence seizures were generated in the cortex.25 This led to the corticoreticular theory of primarily generalized seizures.
Abnormal oscillatory rhythms are believed to develop in thalamocortical pathways. This involves GABA-B–mediated inhibition alternating with glutamate-mediated excitation. The cellular mechanism is believed to involve T-type calcium currents. T channels of the GABAergic reticular thalamic nucleus neurons appear to play a major role in the spike-wave discharges of the GABAergic thalamic neurons.26 GABA-B inhibition appears to be altered in absence seizures, and potentiation of GABA-B inhibition with tiagabine (Gabitril), vigabatrin (Sabril), and possibly gabapentin (Neurontin) results in exacerbation of absence seizures. Enhanced burst firing in selected corticothalamic networks may increase GABA-B receptor activation in the thalamus, leading to generalized spike-wave activity.
Frequency
United States
The incidence is 1.9-8 cases per 100,000 population.
Mortality/Morbidity
- No deaths result directly from absence seizures. Accidents from driving or operating dangerous machinery during absence may result in death.
- In children with absence seizures due to secondary generalized epilepsies, death is related to the underlying disease.
- The morbidity from typical absence seizures is related to the frequency and duration of the seizures, as well as to the patient's activities; effective treatment ameliorates these factors.
- Educational problems and behavioral problems are sequelae of unrecognized, frequent seizures.
Race
No racial predilection is known.
Sex
- Absence seizures are generally believed to be more common in females and in males. Up to two thirds of children with childhood absence epilepsy are girls.9,27
- Absence epilepsy with myoclonus has a male predominance.28
Age
The generalized idiopathic epilepsies have age-related onset. Onset of absence seizures in children with symptomatic generalized epilepsies depends on the underlying disorder. While many of these disorders may have their onset at an early (prenatal, perinatal, or postnatal) age, absence seizures do not appear until later in childhood. An example is the Lennox-Gastaut syndrome. The cause may be a genetic disorder or a perinatal insult, but the absence seizures do not present until age 1-8 years.29
- Childhood absence epilepsy onset is at age 4-8 years, with peak onset at age 6-7 years.27
- Juvenile absence epilepsy onset is generally around puberty. Actual age of onset may vary, depending on whether pyknoleptic (8.3 ± 4.5 years) or nonpyknoleptic seizures occur (14.8 ± 8.3 years).30
- Juvenile myoclonic epilepsy has a more varied age of onset (8-26 y), but 79% of patients have an onset at age 12-18 years.31 Because the absence and myoclonic seizures are brief, they often go unrecognized, and many patients do not present until they experience a tonic-clonic seizure.
Clinical
History
- Children with idiopathic generalized epilepsies may present with a history of staring spells, but infrequent absence seizures may not be diagnosed until a generalized tonic-clonic seizure has occurred.
- Other symptoms, such as behavioral problems, may be the presenting complaint. Although the brief attacks are unrecognized, the lapses of awareness interfere with attention; as a result, the child becomes frustrated.
- Decline in school performance may be an indication of the onset or breakthrough of absence seizures.
- In symptomatic generalized epilepsies, atypical absence seizures often occur in the setting of developmental delay or mental retardation. (See Table 1 for features of typical and atypical absence seizures.) Other seizure types can be present, such as myoclonic, tonic, atonic, tonic-clonic, and even partial seizures.
Physical
- Physical and neurologic findings are normal in children with idiopathic generalized epilepsies. Having the child hyperventilate for 3-5 minutes can often provoke absence seizures. This procedure can easily be performed in the clinic or office, and the result is diagnostic.
- Ictal features
- On clinical examination, typical absence seizures appear as brief staring spells.
- Patients have no warning or postictal phase, and if engaged in gross motor activity, such as walking, they may stop and stand motionless or they may continue to walk.
- Children are not responsive during the seizure and have no memory of what happened during the attack; they are generally unaware that a seizure has occurred.
- See Table 1 below.
- Absence seizures may be confused with complex partial seizures, especially in cases of prolonged seizures with automatisms (see Table 2 below). The occurrence of automatisms is dependent on duration of the seizure; the longer the seizure, the more likely automatisms are to occur (see image below).33
Percentage of absence seizures with automatisms as a function of duration in seconds. (Data gathered from Penry et al, 1975 33.)
- Atypical absence seizures, which occur in patients with symptomatic generalized epilepsies, are usually longer than typical absences and often have more gradual onset and resolution.
- Although absence seizures may share many clinical features with complex partial seizures, the abrupt ending of typical absence seizures, without a postictal phase, is the most useful clinical feature in distinguishing the 2 conditions.
- On clinical examination, typical absence seizures appear as brief staring spells.
- In symptomatic generalized epilepsies, physical and neurologic findings may be abnormal, reflecting the underlying disorder.
- Physical examination may reveal stigmata of a genetic disease, such as a neurocutaneous disorder (eg, tuberous sclerosis) or an inborn error of metabolism.
- Neurologic examination may show signs of developmental delay or more specific signs, such as spastic paresis in cerebral palsy.
Open table in new window
Table
| Type of Clinical Seizure | EEG Findings | |
| Typical absence | Impairment of consciousness only | Usually regular and symmetrical 3 Hz, possible 2- to 4-Hz spike-and-slow-wave complexes, and possible multiple spike-and-slow-wave complexes |
| Mild clonic components | ||
| Atonic components | ||
| Tonic component | ||
| Automatisms | ||
| Autonomic components | ||
| Atypical absence | Changes in tone more pronounced than those of typical absence seizure | EEG more heterogeneous than in typical absence; may include irregular spike-and-slow-wave complexes, fast activity, or other paroxysmal activity; abnormalities bilateral but often irregular and asymmetric |
| Nonabrupt onset or cessation abrupt | ||
| Type of Clinical Seizure | EEG Findings | |
| Typical absence | Impairment of consciousness only | Usually regular and symmetrical 3 Hz, possible 2- to 4-Hz spike-and-slow-wave complexes, and possible multiple spike-and-slow-wave complexes |
| Mild clonic components | ||
| Atonic components | ||
| Tonic component | ||
| Automatisms | ||
| Autonomic components | ||
| Atypical absence | Changes in tone more pronounced than those of typical absence seizure | EEG more heterogeneous than in typical absence; may include irregular spike-and-slow-wave complexes, fast activity, or other paroxysmal activity; abnormalities bilateral but often irregular and asymmetric |
| Nonabrupt onset or cessation abrupt | ||
*May be seen alone or in combination.
Table 2. Differentiating Features of Complex Partial and Absence SeizuresOpen table in new window
Table
| Feature | Complex Partial | Absence |
| Onset | May have simple partial onset | Abrupt |
| Duration | Usually >30 s | Usually <30 s |
| Automatisms | Present | Duration dependent |
| Awareness | No | No |
| Ending | Gradual postictal | Abrupt |
| Feature | Complex Partial | Absence |
| Onset | May have simple partial onset | Abrupt |
| Duration | Usually >30 s | Usually <30 s |
| Automatisms | Present | Duration dependent |
| Awareness | No | No |
| Ending | Gradual postictal | Abrupt |
Causes
After noncompliance with treatment, lack of sleep is the most frequent cause of seizure exacerbations. Drugs that lower the seizure threshold (eg, alcohol, cocaine, high-dose penicillin, isoniazid [INH] overdose, neuroleptics) are most likely to cause seizures in patients with epilepsy. Withdrawal of alcohol, benzodiazepines, and other sedatives are also common causes.
The etiology of idiopathic epilepsies with age-related onset is genetic. About 15-40% of patients with these epilepsies have a family history of epilepsy; overall concordance in monozygotic twins is 74% with a 100% concordance during the peak age of phenotypic expression.9 Family members may have other forms of idiopathic or genetic epilepsy (eg, febrile convulsions, generalized tonic-clonic seizures).
Several animal models demonstrate the genetic basis for absence seizures. A strain of Wistar rat, genetic absence epilepsy rats from Strasbourg (GAERS), is a polygenetic model10 in which all animals have clinical seizures consisting of a behavioral arrest with twitching of facial muscles. This is associated with bilateral synchronous spike-wave discharges. Several single-gene loci in mice, when mutated, result in generalized spike-wave epilepsy. The tottering (chromosome 8), lethargic (chromosome 2), stargazer (chromosome 15), mocha (chromosome 10), and ducky (chromosome 9) loci all have generalized 6-per-second spike-wave EEG paroxysms that are associated with clinical seizures consisting of behavioral arrest. All types respond to ethosuximide, but the underlying cellular mechanisms for the generation of the discharges are not identical.11
The idiopathic generalized epilepsies are a group of primary generalized epilepsies with absence, myoclonic, and tonic-clonic seizures. Based on age of onset and seizure types, some can be grouped into well-recognized syndromes such as childhood absence epilepsy, juvenile absence epilepsy, and juvenile myoclonic epilepsy, but other syndromes such as generalized epilepsy with febrile seizures plus (GEFS+), or patients who have childhood absence epilepsy that leads into juvenile myoclonic epilepsy illustrate that these syndromes represent a genetically determined lower threshold to have seizures. The idiopathic generalized epilepsies are best viewed as a spectrum of clinical syndromes12 with varied genetic causes that affecting the function of ion channels.Genetic studies have shown that these syndromes are channelopathies, but different gene mutations have been found in the same syndromes. Juvenile myoclonic epilepsy has been linked to chromosome 613,14 with linkage to chromosome 6p12 in Mexican families15 . More recently, mutations in the EFHC1 gene were found in Mexican16,17 and Italian families18 with juvenile myoclonic epilepsy, but not in a group of Dutch families19 .
Childhood absence epilepsy with generalized tonic-clonic seizure has been linked to chromosome 8q24 in a 5-generation family from Bombay, India.20 Childhood absence epilepsy with febrile seizures has been linked to the GABA(A) receptor γ2 subunit (GABRG2) on chromosome 5q3.1-33.121 . More recently, a mutation in the GABA(A) receptor gene GABRB3 was found in Mexican families with childhood absence epilepsy. Mutations showed hyperglycosylation in vitro with reduced GABA-evoked current density from whole cells. Expression of this gene in the developing brain may help explain an age-related onset and remission in childhood absence epilepsy.22
In symptomatic generalized epilepsies, absence seizures are due to a wide variety of causes that, at an early stage of neural development, result in diffuse or multifocal brain damage. The causes and management of secondary generalized epilepsies, and the other seizure types that accompany them, are not discussed in this article. See Epilepsy in Children with Mental Retardation and Lennox-Gastaut Syndrome for more information.
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Further Reading
Keywords
absence seizure, petit mal seizures, generalized seizures, idiopathic generalized epilepsy, symptomatic generalized epilepsy, seizure treatment, epilepsy treatment, idiopathic generalized epilepsies, childhood absence epilepsy, pyknolepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, impulsive petit mal seizures, typical absence seizures, symptomatic generalized epilepsies, nonpyknoleptic seizures, spanioleptic absence seizures
