Juvenile absence epilepsy

C P Panayiotopoulos MD PhD (Dr. Panayiotopoulos of St. Thomas' Hospital has no relevant financial relationships to disclose.)
Jerome Engel Jr MD PhD, editor. (Dr. Engel of the David Geffen School of Medicine at the University of California, Los Angeles, has no relevant financial relationships to disclose.)
Originally released October 18, 1993; last updated September 4, 2016; expires September 4, 2019

This article includes discussion of juvenile absence epilepsy, epilepsy with spanioleptic absences, JAE, and nonpyknoleptic absence epilepsy. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Juvenile absence epilepsy is a genetically determined idiopathic generalized epilepsy syndrome with a peak onset at 9 to 13 years of age. It manifests with severe and frequent absence seizures. The majority of patients also have generalized tonic-clonic seizures, and a few also have sporadic myoclonic jerks. EEG shows classical generalized 3 Hz spike-and-slow-wave discharges. Response to appropriate pharmacological treatment is usually excellent, but relapses are probably unavoidable on drug withdrawal. Appropriate antiepileptic treatments include sodium valproate, ethosuximide, lamotrigine, and possibly levetiracetam. Most of the other antiepileptic drugs, such as carbamazepine, gabapentin, eslicarbazepine, lacosamide, oxcarbazepine, phenytoin, pregabalin, tiagabine, and vigabatrin, are contraindicated. In this article, the author details clinical, electroencephalographic, genetic, and management aspects of juvenile absence epilepsy and emphasizes how its differential diagnosis compares with other focal and generalized epileptic syndromes.

Key points

 

• Juvenile absence epilepsy is a genetically determined idiopathic generalized epilepsy characterized by (a) typical absence seizures of high daily frequency and severe impairment of consciousness and (b) generalized tonic-clonic seizures. Myoclonic jerks also occur, but these are mild and with no particular circadian distribution.

 

• The differential diagnosis includes other types of syndromes manifesting with typical absence seizures, such as childhood absence epilepsy, juvenile myoclonic epilepsy, idiopathic generalized epilepsy with phantom absences, and absence seizures associated with glucose transporter 1 deficiency syndrome.

 

• Most of the available evidence is inconclusive regarding the evolution and prognosis of juvenile absence epilepsy. This is because classification criteria are markedly different in the relevant reports or of insufficiently short follow-up periods. The prevailing view is that most patients with juvenile absence epilepsy usually respond well to appropriate pharmacological treatment, but this should probably be life-long.

 

• Sodium valproate, lamotrigine, and possibly levetiracetam are the most effective antiepileptic drugs. Ethosuximide is highly efficacious for absence seizures. Most of the other antiepileptic drugs are contraindicated.

Historical note and terminology

The first description of juvenile absence epilepsy was probably by Janz and Christian in 1957, when they categorized patients with non-pyknoleptic absences (Janz and Christian 1994). Doose and associates found that peak age at onset in children with absence seizures congregated into 3 groups: children 4 to 8 years of age with childhood absence epilepsy (female preponderance); children younger than 4 years of age; and children 10 to 12 years of age (no sex differences) and with cycloleptic (in cycling clusters) or spanioleptic (spanios=rare) absences and frequently generalized tonic-clonic seizures (Doose et al 1965).

The Commission on Classification and Terminology of the International League Against Epilepsy (ILAE) made important progress by accurately defining and differentiating typical absences of idiopathic generalized epilepsies versus atypical absences of symptomatic generalized epilepsies (Commission of Classification and Terminology of the International League Against Epilepsy 1981). However, all epilepsies with typical absence seizures remained for a long time clustered in the group of "petit mal" and were considered a form of "centrencephalic epilepsy." In 1989, the ILAE Commission recognized the heterogeneity of epilepsies with absence seizures and proposed to distinguish 3 syndromes of idiopathic generalized epilepsy (childhood absence epilepsy, juvenile absence epilepsy, and juvenile myoclonic epilepsy) (Commission on Classification and Terminology of the International League Against Epilepsy 1989). Furthermore, it also recognized typical absence seizures in "other idiopathic generalized epilepsies," in "idiopathic generalized epilepsies with specific provocation," and also in a syndrome of cryptogenic generalized epilepsy (epilepsy with myoclonic absences). Panayiotopoulos and colleagues described syndrome-related characterization of absence seizures with video-EEG analysis (Panayiotopoulos et al 1989a; Panayiotopoulos et al 1989b; Panayiotopoulos 1995; Panayiotopoulos 2010; Giannakodimos and Panayiotopoulos 1996).

The ILAE Task Force classified juvenile absence epilepsy as a syndrome of adolescence (Engel 2001; Engel 2006; Berg et al 2010; Commission on Classification and Terminology of the International League Against Epilepsy 2014).

Definition and inclusion and exclusion criteria. Juvenile absence epilepsy is not precisely defined, and there are many areas of uncertainly regarding what this syndrome is and how it overlaps with other idiopathic generalized epilepsies (Hirsch et al 2008; Panayiotopoulos 2008; Panayiotopoulos 2010). Thus, epidemiology, genetics, age at onset, clinical manifestations, other types of seizures, long-term prognosis, and treatment may not accurately reflect the syndrome of juvenile absence epilepsy.

The 1989 ILAE Classification broadly defines juvenile absence epilepsy as follows:

 

The absences of juvenile absence epilepsy are the same as in pyknolepsy, but absences with retropulsive movements are less common. Manifestation occurs around puberty. Seizure frequency is lower than in pyknolepsy, with absences occurring less frequently than every day, mostly sporadically. Association with GTCS is frequent, and GTCS precedes the absence manifestations more often than in childhood absence epilepsy, often occurring on awakening. Not infrequently, the patients also have myoclonic seizures. Sex distribution is equal. The spike-waves are often greater than 3 Hz. Response to therapy is excellent (Commission on Classification and Terminology of the International League Against Epilepsy 1989).

However, age at onset (around puberty) and frequency of seizures (less frequent than of childhood absence epilepsy) are insufficient criteria for the categorization of any syndrome.

Video: Early onset juvenile absence epilepsy
For example, we have studied 71 adults with onset of typical absences after the age of 10 years (median 13 years). Typical absences were verified by EEG or video EEG. Two thirds were women (43 patients). Mean age at last follow-up was 36 years. In 65 patients (92%), absences continued during adulthood. All but 2 patients had generalized tonic-clonic seizures with a mean age at onset of 19 years. A total of 33 patients (47%) also had myoclonic jerks with a mean age at onset of 16 years. One third of the patients (26 patients) were clinically or EEG photosensitive. In terms of epileptic syndromes, 21 patients had juvenile myoclonic epilepsy, 13 had phantom absences with GTCS, 11 had juvenile absence epilepsy, 5 had eyelid myoclonia with absences, 3 had perioral myoclonia with absences, 2 had purely photosensitive idiopathic generalized epilepsy, 2 had GTCS on awakening, and 1 had absences with single myoclonic jerks; 13 patients could not be classified. Patients with briefer, milder, and later onset absence seizures had a worse prognosis (Panayiotopoulos 2010).

Table 1 shows inclusion and exclusion criteria for juvenile absence epilepsy (Panayiotopoulos 2010).

Table 1. Main Inclusion and Exclusion Criteria of Juvenile Absence Epilepsy

Inclusion criteria for juvenile absence epilepsy:

 

(1) Unequivocal clinical evidence of absence seizures with severe impairment of consciousness. All patients may have generalized tonic-clonic seizures. One fifth have myoclonic jerks, but these are mild and do not show the circadian distribution of juvenile myoclonic epilepsy.

 

(2) Documentation of ictal 3 to 4 Hz generalized discharges of spike-polyspike-slow waves longer than 4 seconds that are associated with severe impairment of consciousness and often with automatisms. Normal EEGs in treated patients are common.

Exclusion criteria for juvenile absence epilepsy (the following may be incompatible with juvenile absence epilepsy):

 

Clinical exclusion criteria:

   

(1) Absences with marked eyelid or perioral myoclonus or marked single or rhythmic limb and trunk myoclonic jerks.

   

(2) Absences with exclusively mild or clinically undetectable impairment of consciousness.

   

(3) Consistent visual, photosensitive, and other sensory precipitation of clinical absences is probably against the diagnosis of juvenile absence epilepsy. However, on EEG, intermittent photic stimulation often facilitates generalized discharges and absences.

 

EEG exclusion criteria:

   

(1) Irregular, arrhythmic generalized discharges of spike-polyspike-slow waves with marked variations of the intradischarge frequency.

   

(2) Significant variations between the spike/multispike-slow-wave relationships in generalized discharges of spike-polyspike-slow waves.

   

(3) Predominantly brief discharges (shorter than 4 seconds).

Used with permission from (Panayiotopoulos 2010).

In the new online diagnostic manual of the epilepsies by the ILAE Commission on Classification and Terminology, the following description is given of juvenile absence epilepsy (Commission on Classification and Terminology of the International League Against Epilepsy 2014): “This genetic generalized epilepsy is characterized by absence seizures that are not very frequent in an otherwise normal adolescent or adult. Generalized convulsive seizures typically also occur. With absence seizures in a child aged between 8 and 12 years, a diagnosis of juvenile absence epilepsy or childhood absence epilepsy depends on the frequency of the absence seizures.

Juvenile absence epilepsy. This genetic generalized epilepsy is characterized by absence seizures that are not very frequent in an otherwise normal adolescent or adult. Also, generalized convulsive seizures typically occur. With absence seizures in a child between 8 and 12 years of age, a diagnosis of juvenile absence epilepsy or childhood absence epilepsy depends on the frequency of the absence seizures.

 

Note. A genetic generalized epilepsy is an epilepsy with generalized seizures associated with generalized epileptiform EEG patterns, such as generalized spike wave activity.

Clinical context. This epilepsy syndrome is characterized by absence seizures that have onset from 8 to 20 years of age (peak 9 to 13 years). Less commonly, adolescents may present with generalized convulsive seizures prior to onset of absences. Treatment is usually required for life. Both males and females are affected. Antecedent, birth, and neonatal history are normal. Neurologic examination and head size are normal. Development and cognition prior to presentation are typically normal. Attention deficit hyperactivity disorder and learning difficulties may also occur. A previous history of febrile seizures is seen occasionally.

Mandatory seizures. Absence seizures are mandatory; these are not as frequent as seen in childhood absence epilepsy. During absence seizures with incomplete loss of awareness an adolescent can respond to commands but has difficulty doing complex tasks. Absence status epilepticus can occur. Generalized convulsive seizures are common (in 80% of cases) and seen within 30 minutes of waking, but frequency is variable. Myoclonic seizures or any other type of seizures are excluded.

Exclusionary.

 

• If myoclonic seizures with absences, consider juvenile myoclonic epilepsy
• Any other seizure types

EEG background. The background is normal. Occipital intermittent rhythmic delta activity (OIRDA) may be seen.

 

Caution. Generalized slowing is not seen.
Caution. If focal slowing consistently is seen over 1 area, then consider structural brain abnormality.

Interictal EEG. There may be generalized spike-and-wave, fragments of generalized spike-and-wave, or polyspike-and-wave.

 

Caution. Although focal spikes can occur, if they consistently arise in 1 area, consider structural brain abnormality.
Caution. If slow spike-and-wave (<2.5Hz) is not seen, consider other epilepsy syndromes.

Imaging. Neuroimaging is normal. If the clinical presentation and EEG are typical for juvenile absence epilepsy and there are no atypical features, imaging is not required.

Genetics. It has a complex inheritance. Genes linked to this syndrome include GABRG2, CACNA1A, and others.

Family history of seizures/epilepsy. A family history is occasionally present, typically with family members having a related genetic generalized epilepsy.

Differential diagnoses.

 

• Juvenile myoclonic epilepsy : The presence of myoclonic seizures distinguishes juvenile absence epilepsy from this syndrome.

 

• Childhood absence epilepsy: Consider if there are frequent (multiple daily) absence seizures in a child younger than 12 years of age.

 

• Epilepsy with eyelid myoclonias: Consider if there are repetitive, rhythmic, fast greater than 4 Hz) jerks of the eyelids, with upward deviation of the eyeballs and with head extension; seizures are very frequent.

 

• Epilepsy with myoclonic absences: Consider if there are 3 Hz myoclonic jerks of upper limbs with tonic abduction.

 

• Structural brain abnormality : Consider if absence or generalized convulsive seizures with focal features are seen consistently from seizure to seizure.

Adapted from (Commission on Classification and Terminology of the International League Against Epilepsy 2016).

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.