Absence Epilepsy

Absence Epilepsy

An absence seizure is a generalized epileptic event with impairment of consciousness and generalized spike-and-slow-wave discharges, typically at 2.5- to 4-Hz without overt convulsive (tonic or clonic) activity

- a number of epileptic syndromes have absences as a component including some as a prominent or even required part

First described clinically in 1700's and term 'petit mal' introduced in 1815

- term pyknolepsy implies dense clustering of seizures (ie frequent events)

The Typical Absence Spell:

* Epileptic seizure

* Impairment of consciousness (sudden onset and offset)

- may be mild (even requiring special testing) or severe

- may see other manifestations, esp eyelid myoclonia, automatisms, and autonomic disturbances (termed "complex" absence if see these features) but typically no aura

- brief, lasting usually 5-10 seconds (almost always < 30 sec)

- none to little post-ictal disturbance

* Characteristic EEG change:

- 2.5- to 4-Hz generalized spike and slow wave discharges

(if < 2.5Hz then characterized as "atypical")

Typically inducible with hyperventilation

Atypical absences if:

- onset and offset less distinct / abrupt

- long duration, can last up to few minutes

- more pronounced changes in tone but less automatisms

- most with atypical absences have other seizure types and are cognitively impaired

- often seen as part of Lennox-Gastaux syndrome

- EEG shows slow spike and wave discharges (0.5 to 2.5 Hz) and interictal EEG more often abnormal (slowing, multiple spikes)

Absence status epilepticus:

- prolonged alteration (> 30 mins) in level of consciousness often with fluctuating course

- "twilight" state where often able to continue functioning but usually amnestic and not interact normally

- may see subtle automatisms or mild clonic / myoclonic movements

- primarily seen in children but can rarely occur in adults with absence epilepsies or elderly people on withdrawal of benzodiazepines

Syndromes with Typical Absences:

1. Childhood absence epilepsy (CAE) aka pyknolepsy

2. Juvenile absence epilepsy (JAE)

- these two differentiated mainly by age of onset

3. Juvenile myoclonic epilepsy (JME)

4. Myoclonic absence epilepsy (MAE)

- first three are considered idiopathic generalized epilepsies while the latter is thought to be cryptogenic / symptomatic (generalized)

Other proposed syndromes features absences include:

- Eyelid myoclonia with absences (EMA)

- Perioral myoclonia with absences (PMA)

- Stimulus-sensitive absence epilepsies

- Idiopathic generalized tonic clonic seizures on awakening

Some of these syndromes include a component of generalized tonic clonic (GTCS, grand mal) seizures and patient may come to attention only after having one of these

- retrospectively, had number of "staring" episodes prior to this

Detection and Differential Diagnosis of Absences:

- may be missed in babies if not associated with motor (eg myoclonic) components

- may be missed or misdiagnosed in adults as complex partial seizures as usually mild (with age) and can see elements of fear or derealization with them

- also ddx "daydreaming"

Ways to differentiate absence seizure from complex partial seizure:

- absences are shorter-lasting (< 30 seconds) while CPS usually 30 sec or more and more gradual offset (not so abrupt as absence)

- stereotyped automatisms common in CPS (eg grabbing, head turning) while automatisms can occur but not so stereotyped or prominent in absence

- no post-ictal confusion in absence vs post-ictal fatigue, confusion or even aphasia in CPS

- aura typically characteristic of CPS with limbic / psychic phenomena commonly, which typically do not occur in absences (although some "sensations" can occur)

- frequency of absence attacks much higher (many per day often) than CPS which are usually infrequent (once or twice a day to once or less per month)

- hyperventilation can induce absences but not CPS (as with photic stimulation in some absence epilepsies)

- EEG in absence attacks confirms generalized spike and slow wave discharges not seen in CPS (with focal onset of rhythmic activity / spikes)

Clues to differentiating specific syndromes listed below:

- the difference in prognosis of these various syndromes makes classification useful and important

- the pure syndromes with absences as predominant seizure type and no significant associated features (jerking, myoclonus, early GTCS) are CAE and JAE

- JME is a common syndrome with myoclonic jerks on awakening as hallmark of disease but up to 1/3 have absences that herald onset of disease

- may be hard to distinguish from simple absence epilepsies such as CAE / JAE

- absences in JME usually lack automatisms ("simple") and have less severe impairment of consciousness with fragmented multiple spike discharges on EEG

- absences are more of a problem in adolescents with JAE than JME but it may take time to see evolution of simple absences in early teen years into myoclonic jerks and GTCS of JME

- if see characteristic eyelid myoclonia, make diagnosis of EMA (see below);

- don’t confuse eye closing seen in other forms of absence with rhythmic jerking seen in eyelid myoclonia

- shorter duration, photosensitivity, and precipitation by eye closure enable recognition of this syndromic diagnosis

- myoclonic absence epilepsy also distinct with rhythmic myoclonic jerks of primarily upper body seen during absence spells

- perioral myoclonia (PMA) often misdiagnosed as focal motor epilepsy (jerking of facial muscles) or as pyknolepsy in some children

- best confirmed with video-EEG showing jerks coinciding with polyspikes on EEG

- onset of GTCS at same age or before absences, brief duration, and absence status delineate this syndrome vs other epilepsies

Childhood Absence Epilepsy (CAE):

Pyknolepsy involves school-age children (peaks at age 6-7) who are otherwise normal but may have a familial predisposition to developing frequent (daily or more) brief absence seizures

- classified as an idiopathic generalized epilepsy (benign with good prognosis)

- EEG shows characteristic bilateral, synchronous, symmetrical spike-waves (usually 3 Hz) with normal background

- may develop GTCS in adolescence or absences may simply remit (but should NOT have GTCS before onset of absences in CAE)

Accounts for 2-10% of childhood epilepsies, with annual incidence of 2-8 per 100,000

- age of onset 4-8 years (peak at 6 years)

- more frequent in girls (up to 2:1)

- up to 44% have family history of epilepsy including GTCS and febrile convulsions (and MZ twins have 75% concordance)

- mode of transmission unclear

- not clearly correlated with perinatal events but higher incidence of febrile seizures (10-30%)

Thalamus felt to have central role in pathogenesis

- no consistent discrete structural abnormality found (possibly microdysgenesis)

- abnormal oscillatory rhythms in thalamocortical loops

- T-type calcium channels of GABAergic neurons in reticular nuclei of thalamus play role in spike-wave discharge generation (and potentiation of GABA-B receptor-mediated inhibition can worsen absences; avoid certain AEDs e.g. vigabatrin, tiagabine)

Clinical picture:

- "transient loss of consciousness without conspicuous convulsions" (Gowers)

- patient stops whatever they are doing, may turn pale, quivering of eyelids (unsustained)

- does not speak and amnestic for that period

- automatisms may occur (in 2/3) but not stereotyped

- lasts seconds to < 1 minute usually (mean 12 sec) but occur many times per day

- abrupt return to normal LOC without post-ictal deficits

- spells precipitated by hyperventilation (useful in clinical exam and EEG) = will suddenly stop overbreathing when enter absence spell

- normal intelligence and development otherwise usually

EEG:

- normal interictal patterns or rhythmic posterior delta activity

- ictal EEG shows generalized spike or double-spike and slow wave complexes at 3 Hz (no slower than 2.7 Hz, no more than 4 Hz) in initial phase, frequency declines with time

- discharges last 4-20 seconds

Long-Term Outcome:

- in pure CAE, good prognosis with most remitting within 2-6 years with few developing GTCS later in life

- better prognosis for recovery / remission with early onset (< 6 years) than later in childhood

- 1/3 continue to have absences in adulthood but usually less frequent and less severe, but GTCS almost inevitable in this population (also infrequent and treatment responsive usually)

- GTCS esp if early in course indicate a worse prognosis (usually indicates not pure CAE but JME, JAE or other syndrome)

Exclusion Criteria for CAE:

- absences with marked eyelid or perioral myoclonus (syndromes of EMA, PMA)

- absences with marked limb and trunk rhythmic myoclonic jerks (MAE)

- absences with single ictal myoclonic jerks of limbs, trunk, head

- absences with mild or clinically undetectable impairment of consciousness (often seen in JME or other forms or idiopathic generalized epilepsy)

- other seizures not usually seen in CAE including GTCS early in course, myoclonic jerks

- stimulus-sensitive absences incl. photosensitive

- EEG should not show fragmented discharges, multiple spikes (more than 3 spikes per slow wave complex) as seen often in JME, EMA, PMA; marked variations in intradischarge frequency not seen, brief discharges < 4 sec or abnormal background (but may see centrotemporal or occipital spikes coexisting with CAE)

- mental retardation

Treatment:

- some may not require treatment if rare spells, but most have frequent attacks that impair school performance and can lead to accidental injury

- valproic acid & ethosuximide considered first-line and equally effective as monotherapy for absences in CAE (work in over 80%)

- valproate also controls GTCS so preferred if not pure form of CAE and risk of GTCS

- if resistant to monotherapy, may try combination of two AEDs (works in 50% of these)

- lamotrigine may also be tried, alone, or better in combination with valproate

- other medications that may be effective include acetazolamide, benzodiazepines (eg clobazam, clonazepam)

- avoid carbamazepine, phenytoin and especially vigabatrin and tiagabine which can exacerbate absences

- may try to withdraw AED therapy after 2 years free of seizures

Juvenile Absence Epilepsy:

- same type of episodes as CAE but manifests around puberty with less frequent spells and more frequent association with GTCS (often near onset, on awakening)

Epidemiology:

- comprises roughly 10% of idiopathic generalized epilepsies

- 20% of all absence epilepsies and half as common as JME

- equally distributed between sexes

- may account for equal number of adults with continuing absences vs pyknoleptic

- often have family history of seizures, incl. GTCS

Clinical Features:

- typical absences with onset between 7 and 16 years of age (peak 10-12 yrs)

- less severe impairment in LOC (may continue activity during spell)

- less frequent absences than CAE, occurring < 1-10 per day but slightly longer duration (16 sec)

- may present with GTCS and risk of status (both absence and convulsive)

- myoclonic jerks in 15-25%

- GTCS infrequent but after awakening, precipitated by sleep deprivation, alcohol, fatigue

Prognosis:

- probably a lifelong disorder although can be controlled in 70-80%

- absences can become less with age, and myoclonic jerks not troublesome

Treatment:

- drug of choice given frequent association with GTCS is valproate (VPA)

- can add lamotrigine or ethosuximide if uncontrolled only on VPA

- avoid AEDs that worsen absences including carbamazepine, phenytoin, vigabatrin

- higher incidence of photosensitivity and polyspikes; higher discharge frequency

Myoclonic Absence Epilepsy (MAE):

- Absences accompanied by severe bilateral rhythmical clonic jerks often with tonic contraction (awareness of jerks may be preserved)

- onset around 7 years, more in males

- rare accounting for 1% of childhood epilepsies

- EEG shows typical bilaterally synchronous symmetrical 3 Hz spike wave discharges

- seizures many times a day, esp on awakening and can be precipitated by hyperventilation

- more resistant to therapy and associated with mental deterioration (before onset in 45% and developing during course in 25%)

- half remit over 5-6 years while remainder (often with other associated seizure types) persisted over years (few evolve into Lennox-Gastaux syndrome)

- management similar to CAE and JAE above

Eyelid Myoclonia with Absences (EMA):

- rare syndrome of idiopathic generalized epilepsy (accounts for 10% of IGE with absences)

- predominant feature being myoclonus localized to eyelids, which may be alone or associated with absence spell (mild impairment in consciousness)

- eyelid myoclonia consists of rhythmic fast jerks of eyelids, often with upward jerking of eyeballs and head (may have tonic component of these muscles as well)

- seizures are brief (3-6 seconds) and occur mainly after eye closure

- do NOT see absences without myoclonia but with treatment or aging may see myoclonia not progressing to any absence spells

- onset usually in early childhood (mean 6 yrs) with frequent spells (hundreds per day);

- all are photosensitive (less sensitive with age); esp common in women

- EEG shows brief generalized polyspikes (or slow waves at 3- to 6-Hz) with eye closure

- may develop GTCS esp with flickering lights, sleep deprivation, fatigue or alcohol

- infrequent random myoclonic jerks of limbs occur in 1/2

- resistant to treatment (even with valproate) and can be lifelong problem

- may require combination therapy with valproate and ethosuximide / benzodiazepines

Perioral Myoclonia with Absences (PMA):

- syndrome of IGE with frequent absence spells and ictal localized rhythmic myoclonus of perioral facial muscles (contractions of orbicularis oris with protrusion of lips, twitching of corners of mouth from depressor anguli oris; rarely jaw jerking from muscles of mastication)

- jerks last for duration of epileptic discharge / absence attack with frequency of jerking corresponding to frequency of polyspike discharges

- onset anywhere from 2 to 13 years (median 10 yrs); normal intelligence

- seizure frequency can be high or occasional but brief lasting only few seconds

- frequent occurrence of absence status and GTCS (in half these precede onset of absences)

- GTCS usually infrequent (once a month or less) and often heralded by clusters of absences

- family history often positive for seizure disorders

- ictal EEG shows high-amplitude generalized discharges of rhythmic spike and slow waves at 3-4 Hz (may be irregular) without photosensitivity

- often persists into adult life and is resistant to therapy

- recommend that when cluster of absences occur or absence status, take 2000 mg of valproate orally or 10 mg diazepam rectally to terminate event and prevent GTCS

Phantom Absences:

- group of patients with absences that are so subtle that they are imperceptible to observers and not realized by patients

- only documented on video-EEG recordings and breath counting during hyperventilation

- usually brief (few seconds) with 3- to 4-Hz spike or polyspike and slow wave discharges

- simple absences with eyelid blinking

- may also have GTCS but not photosensitive and no myoclonic jerks

Symptomatic / Cryptogenic Absences:

- absences usually seen in idiopathic generalized epilepsies

- can occasionally be symptomatic, due to known disorder of the CNS (including traumatic, metabolic, inflammatory) as well as malformations / heterotopias

- mesial surfaces of frontal lobes may generate absences

- EMA and MAE more often linked to secondary epilepsies

References:

Browne and Holmes. Handbook of Epilepsy. 2004.

Segan. Absence seizures. eMedicine.

Panayiotopolous CP. Absence epilepsies. In Engel J, Pedley TA. Epilepsy: the comprehensive CD-ROM. 1999.

Last update: May 2004

Reviewed by: pending

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