Editor(s): Edward
B Bromfield, MD, Chief, Division of Epilepsy and Sleep, Associate
Professor of Neurology, Department of Neurology, Brigham and Women's
Hospital; Harvard Medical School; Francisco Talavera, PharmD, PhD,
Senior Pharmacy Editor, eMedicine; Jose E Cavazos, MD, PhD,
Assistant Professor, Departments of Medicine (Neurology) and Pharmacology,
University of Texas Health Science Center at San Antonio; Selim R
Benbadis, MD, Professor, Director of Comprehensive Epilepsy
Program, Departments of Neurology and Neurosurgery, University of South
Florida College of Medicine; and Nicholas Lorenzo, MD,
Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists
and Consultants
Background: Absence seizures are a type of generalized
seizures. They were first described Poupart in 1705, and later by Tissot in
1770, who used the term petit access. In 1824, Calmeil used the term absence.
In 1935, Gibbs, Davis, and Lennox described the association of impaired
consciousness and 3-Hz spike-and-slow-wave complexes on electroencephalograms
(EEGs).
Absence seizures occur in both idiopathic and symptomatic generalized
epilepsies. Among the idiopathic, or primary, generalized epilepsies (ie,
with age-related onset), absence seizures are seen in childhood absence
epilepsy (CAE, or pyknolepsy), juvenile absence epilepsy (JAE), and juvenile
myoclonic epilepsy (JME, or impulsive petit mal seizures). The seizures in
these conditions are called typical absence seizures and usually associated
with 3-Hz spike-and-slow-wave complexes on EEG. In CAE, seizures are frequent
and brief, lasting just a few seconds (pyknoleptic). Some children can have
hundreds of 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 symptomatic generalized epilepsies, absence seizures are often
associated with slow spike-wave complexes of 1.5-2.5 Hz; these are also
called sharp-and-slow-wave complexes. These seizures are termed atypical
absence seizures.
Pathophysiology: 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; concordance in monozygotic
twins is 75%. Family members may have other forms of idiopathic or genetic
epilepsy (eg, febrile convulsions, generalized tonic-clonic [GTC] seizures).
Several animal models demonstrate the genetic basis for absence seizures.
A strain of Wistar rat, ie, genetic absence epilepsy rats from Strasbourg
(GAERS), is a polygenetic model 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 (ETX), but the underlying cellular mechanisms for the generation
of the discharges are not identical.
Several mutations of genes which encode protein subunits in various ion
channels have been found in patients and family members with idiopathic
epilepsies. Some forms of JME and absence epilepsy have been shown to result
from mutations in Ca++ channels.
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 of secondary generalized
epilepsies and the other seizure types that accompany them, and their
management, are not discussed in this article.
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. In 1953, bilaterally synchronous spike-and-wave discharges
were recorded by using depth electrodes placed in the thalamus of a child
with absence seizures.
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. 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. 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 GABAB receptor activation in the
thalamus, leading to generalized spike-wave activity.
Frequency:
In the US: 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, with some studies showing a 2:1
female-to-male ratio. Other studies have shown no difference between the
sexes.
Absence epilepsy with myoclonus has a male
predominance.
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.
CAE onset is at age 4-8 years, with peak onset
at age 6-7 years.
JAE onset is at age 7-14 years, with peak
onset at age 10-12 years. Onset of JAE with myoclonus averages about age
7 years.
JME has a more varied age of onset (8-26 y),
but 79% of patients have an onset at age 12-18 years. 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.
Children with idiopathic generalized epilepsies
may present with a history of staring spells, but infrequent absence
seizures may not be diagnosed until a GTC 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 following up what
is happening; 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.
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, may stop and
stand motionless or 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.
Table 1. Clinical and EEG Findings in Typical
and Atypical Absence Seizures*
Type of Clinical Seizure
EEG Findings
Typical absence
Impairment of consciousness only
Mild clonic components
Atonic components
Tonic component
Automatisms
Autonomic components
Usually regular and
symmetrical 3 Hz, possible 2- to 4-Hz spike-and-slow-wave complexes, and
possible multiple spike-and-slow-wave complexes
Atypical absence
Changes in tone more pronounced
than those of typical absence seizure
Nonabrupt onset and/or cessation abrupt
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
Source.—Adapted from Dreifuss, 1977. *May be seen alone or in combination.
Absence seizures may be confused with complex
partial seizures, especially in cases of prolonged seizures with
automatisms (see Table
2). The occurrence of automatisms is dependent on duration of the
seizure; the longer the seizure, the more likely automatisms are to
occur (see Image 1).
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.
Table 2. Differentiating Features of Complex
Partial and Absence Seizures
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
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.
In symptomatic generalized epilepsies,
physical and/or 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.
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 (BZP), and other sedatives is also a common cause.
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