Juvenile Absence Epilepsy criteria (Panayiotopoulos 2010)

Panayiotopoulos CP and Engel J
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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 (GLUT1) 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 nomenclature

  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; 1989b; Panayiotopoulos 1995; 2010; Giannakodimos and Panayiotopoulos 1996).

  The ILAE Task Force classified juvenile absence epilepsy as a syndrome of adolescence (Engel 2001; 2006; Berg et al 2010).

  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; 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. 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).

Clinical manifestations

  Frequent and severe typical absences are the characteristic and defining seizures of juvenile absence epilepsy.   The usual frequency of absences is approximately 1 to 10 per day, but this may be much higher for some patients (Wolf 1992; Obeid 1994; Panayiotopoulos 2010). Almost all patients also develop generalized tonic-clonic seizures, and one fifth of them also suffer from mild myoclonic jerks.

  Typical absences are severe and frequent, often daily, and very similar to those of childhood absence epilepsy, although they may be milder. The hallmark of the absence is abrupt, brief, and severe impairment of consciousness with total or partial unresponsiveness. Mild or inconspicuous impairment of consciousness, such as of phantom absences, is not compatible with juvenile absence epilepsy. The ongoing voluntary activity usually stops at onset but may be partly restored during the ictus. Automatisms are frequent, usually occurring 6 to 10 seconds after the onset of the EEG discharge.   In juvenile absence epilepsy, mild myoclonic elements of the eyelids are common during the absence. However, more severe and sustained myoclonic jerks of facial muscles may indicate other idiopathic generalized epilepsies with absences. Severe eyelid or perioral myoclonus, rhythmic limb-jerking, and single or arrhythmic myoclonic jerks of the head, trunk, or limbs during the absence ictus are probably incompatible with juvenile absence epilepsy.

  Duration of the absences varies from 4 to 30 seconds, but it is usually long (approximately 16 seconds) (Panayiotopoulos et al 1989b; Engel 2006).

  Generalized tonic-clonic seizures are probably unavoidable in untreated patients. They occur in 80% of patients, often after awakening, although nocturnal or diurnal generalized tonic-clonic seizures may also be experienced (Doose et al 1965; Wolf and Inoue 1984; Wolf 1992; Obeid 1994; Panayiotopoulos et al 1995; Oller 1996; Thomas 2010; Gelisse et al 2012). Generalized tonic-clonic seizures are usually infrequent, but they may also become severe and intractable.

  Myoclonic jerks occurring in 15% to 25% of patients are infrequent, mild, and of random distribution (Commission on Classification and Terminology of the International League Against Epilepsy 1989; Panayiotopoulos 2008; 2010; Hirsch et al 2008; Thomas 2010; Gelisse et al 2012). They usually occur in the afternoon hours when the patient is tired, rather than in the morning after awakening. The concept that myoclonic jerks do not occur in juvenile absence epilepsy (Sadleir et al 2008; Scheffer and Berg 2008) is inconsistent with worldwide evidence and the ILAE definition (Commission on Classification and Terminology of the International League Against Epilepsy 1989).

  Absence status epilepticus is truly generalized nonconvulsive (without any type of jerks or convulsions) and occurs in one fifth of patients (Agathonikou et al 1998).

  Rarely, patients with juvenile absence epilepsy may present with an uncommon evolution of generalized to focal seizures followed by secondary generalization (double generalization phenomenon) (San-Juan et al 2011).

  Seizure-precipitating and facilitating factors. Mental and psychological arousal is the main precipitating factor for typical absences. Conversely, sleep deprivation, fatigue, alcohol, excitement, and lights alone or usually in combination are the main facilitating factors for generalized tonic-clonic seizures. Some authors reported that 8% to 56% of juvenile absence epilepsy patients suffered from photosensitivity clinically or on EEG (Wolf 1992; Lu et al 2008). However, clinical photosensitivity that is a consistent provocation of seizures (absences, generalized tonic-clonic seizures, or jerks) may be incompatible with juvenile absence epilepsy. These patients may have other idiopathic generalized epilepsies (Panayiotopoulos 2010). EEG photosensitivity that is facilitation but not consistent provocation of absences by intermittent photic stimulation may not be uncommon in juvenile absence epilepsy.

  Age and sex at onset. Age at onset is primarily 9 to 13 years (70% of the patients), but the range is from 5 to 20 years (Wolf 1992; Obeid 1994; Hirsch et al 2008; Panayiotopoulos 2010; Thomas 2010; Gelisse et al 2012). Myoclonic jerks and generalized tonic-clonic seizures usually begin 1 to 10 years after the onset of absences. Rarely, generalized tonic-clonic seizures may precede the onset of absences (Wolf 1992). Both sexes are equally affected.

Juvenile Absence Epilepsy summary

http://www.chp.edu/CHP/juvenile+absence+epilepsy

Symptoms
Juvenile absence epilepsy (JAE) is a common type of epilepsy that typically begins on or after puberty, between the ages of 10 and 17. About one-third of patients with JAE have a family history of seizures. Children may experience a few absence seizures per day, which are characterized by a brief altered state of conscious and staring episodes. The child may also experience tonic-clonic seizures upon awakening.
Diagnosis
EEG testing shows a 3 Hz generalized spike and waves. CT and MRI scans of the brain are typically normal.

Treatment
Seizures are controlled with medication in 80 percent of cases. Ethosuximide, valproate and lamotrigine are typically prescribed for JAE. Some patients with JAE do not outgrow their seizures and will need take medication for the rest of their lives. Individuals are encouraged to get enough sleep and avoid alcohol to reduce the likelihood of seizures.