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Childhood Absence Epilepsy
- Childhood absence epilepsy (CAE) is an age-dependent, idiopathic form of generalised epilepsy (IGE) characterised by multiple absence seizures per day, as well as bilateral, symmetrical, and synchronous discharges of 3-Hz generalised spike and waves (GSW) in the electroencephalogram.
- The 2017 International League Against Epilepsy (ILAE)classification suggested that the term IGE could be reserved for the four syndromes including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic–clonic seizures alone (GTCA)[1].
- CAE makes for 2% to 10% of all paediatric epilepsies and 8-15% of school-aged childhood epilepsies. Seizures occur many times daily and consist of brief staring spells, sometimes with rhythmic eye blinking or motor automatisms, lasting seconds, with immediate return to the baseline level of awareness and activity. Children with CAE develop normally, although attentional deficiencies or other subtle behavioural or cognitive abnormalities may be present at onset.
Investigations
- On electroencephalography (EEG), seizures are characterized by a highly recognizable pattern of generalized (bilateral, symmetric and synchronous) 3 Hz spike and wave discharges. See figure 1
- Consider the possibility of Glucose transporter 1 deficiency syndrome in a child who has absence seizures that started before the age of 4 years or who has absence seizures along with an abnormal neurologic exam or significant developmental delays.
Treatment
Three antiepileptic medications, namely ethosuximide (ETX), valproic acid (VPA), and Lamotrigine (LTG), have traditionally been the primary choices for treating childhood absence epilepsy (CAE). The 2010 Childhood Absence Epilepsy research presented conclusive evidence, classified as class I, supporting the use of ETX as the most effective initial treatment for CAE[2]. See algorithm figure 2.
- Because VPA slows down the metabolism of LTG by blocking liver enzymes, titration of LTG starts at an even lower dose, moves more slowly, and hits a lower target in a person who is also taking VPA than in a person who is not taking any other medication.
- There are important cognitive, behavioural, and psychological problems associated with CAE that need to be identified early and dealt with. Anxiety and attention deficit hyperactivity disorder (ADHD) are significantly associated with CAE[3].
Differentiating between CAE and JAE
- Age at onset of CAE is considered to be 2 to 13 years of age and for Juvenile Absence Epilepsy (JAE) to be 8 to 20 years of age; there is five years of overlap[4].
- Patients with JAE more often have GTCS and more frequently experience seizure-related injuries compared with patients with CAE
- Valproate can be considered as the drug of choice in men and lamotrigine as the first drug of choice in women with JAE. See table 1
Pathophysiology
- Absence seizures result from disruptions in thalamocortical rhythms via T-type calcium channel dysfunction.
see also Absence Seizures
Genetics
- There are few genes that confer monogenic risk for CAE, found through family studies or large cohort studies (e.g., GABRG2, GABRA1, SLC2A1[7]).
- Several recurring Copy Number Variations (CNVs), such as 15q11.2, 15q13.3, and 16p13.11 microdeletion[9], contribute to a complicated inheritance pattern seen in CAE.A chromosomal microarray should be requested for children with substantial learning difficulties due to the higher probability of pathogenic CNVs
Treatment resistant CAE
- If first- and second-line drugs don't work, clobazam might be worth a try. However, there isn't much literature on its use in treatment-resistant CAE
- The ketogenic diet has also been used successfully in children with treatment-resistant CAE[10]
References
1.
a
ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):512-521. doi: 10.1111/epi.13709. Epub 2017 Mar 8.
[PMID: 28276062] [PMCID: 5386840] [DOI: 10.1111/epi.13709] .
[PMID: 28276062] [PMCID: 5386840] [DOI: 10.1111/epi.13709] .
2.
a
A Practical Guide to Treatment of Childhood Absence Epilepsy. Paediatr Drugs. 2019 Feb;21(1):15-24. doi: 10.1007/s40272-019-00325-x.
[PMID: 30734897] [PMCID: 6394437] [DOI: 10.1007/s40272-019-00325-x] .
[PMID: 30734897] [PMCID: 6394437] [DOI: 10.1007/s40272-019-00325-x] .
3.
a
Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities. Epilepsia. 2008 Nov;49(11):1838-46. doi: 10.1111/j.1528-1167.2008.01680.x. Epub 2008 Jun 13.
[PMID: 18557780] [DOI: 10.1111/j.1528-1167.2008.01680.x] .
[PMID: 18557780] [DOI: 10.1111/j.1528-1167.2008.01680.x] .
4.
a
ILAE definition of the Idiopathic Generalized Epilepsy Syndromes: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022 Jun;63(6):1475-1499. doi: 10.1111/epi.17236. Epub 2022 May 3.
[PMID: 35503716] [DOI: 10.1111/epi.17236] .
[PMID: 35503716] [DOI: 10.1111/epi.17236] .
5.
a
Historical trend toward improved long-term outcome in childhood absence epilepsy. Epilepsy Res. 2019 May;152:7-10. doi: 10.1016/j.eplepsyres.2019.02.013. Epub 2019 Feb 25.
[PMID: 30856420] [PMCID: 6573015] [DOI: 10.1016/j.eplepsyres.2019.02.013] .
[PMID: 30856420] [PMCID: 6573015] [DOI: 10.1016/j.eplepsyres.2019.02.013] .
6.
a
Long-term seizure outcome in patients with juvenile absence epilepsy; a retrospective study in a tertiary referral center. Seizure. 2014 Jun;23(6):443-7. doi: 10.1016/j.seizure.2014.03.002. Epub 2014 Mar 12.
[PMID: 24684814] [DOI: 10.1016/j.seizure.2014.03.002] .
[PMID: 24684814] [DOI: 10.1016/j.seizure.2014.03.002] .
7.
a
Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1. Ann Neurol. 2009 Sep;66(3):415-9. doi: 10.1002/ana.21724.
[PMID: 19798636] [DOI: 10.1002/ana.21724] .
[PMID: 19798636] [DOI: 10.1002/ana.21724] .
8.
a
Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy. Ann Neurol. 2017 Mar;81(3):444-453. doi: 10.1002/ana.24886.
[PMID: 28165634] [PMCID: 6171340] [DOI: 10.1002/ana.24886] .
[PMID: 28165634] [PMCID: 6171340] [DOI: 10.1002/ana.24886] .
9.
a
Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain. 2010 Jan;133(Pt 1):23-32. doi: 10.1093/brain/awp262. Epub 2009 Oct 20.
[PMID: 19843651] [PMCID: 2801323] [DOI: 10.1093/brain/awp262] .
[PMID: 19843651] [PMCID: 2801323] [DOI: 10.1093/brain/awp262] .
10.
a
Do patients with absence epilepsy respond to ketogenic diets?. J Child Neurol. 2011 Feb;26(2):160-5. doi: 10.1177/0883073810376443. Epub 2010 Jul 20.
[PMID: 20647578] [DOI: 10.1177/0883073810376443] .
[PMID: 20647578] [DOI: 10.1177/0883073810376443] .
11.
a
A multicenter, randomized, placebo-controlled trial of levetiracetam in children and adolescents with newly diagnosed absence epilepsy. Epilepsia. 2011 Apr;52(4):802-9. doi: 10.1111/j.1528-1167.2010.02976.x. Epub 2011 Feb 14.
[PMID: 21320119] [DOI: 10.1111/j.1528-1167.2010.02976.x] .
[PMID: 21320119] [DOI: 10.1111/j.1528-1167.2010.02976.x] .
12.
a
Levetiracetam in absence epilepsy. Dev Med Child Neurol. 2008 Nov;50(11):850-3. doi: 10.1111/j.1469-8749.2008.03099.x. Epub 2008 Sep 19.
[PMID: 18808424] [DOI: 10.1111/j.1469-8749.2008.03099.x] .
[PMID: 18808424] [DOI: 10.1111/j.1469-8749.2008.03099.x] .
13.
a
Aggravation of absence seizure related to levetiracetam. Eur J Paediatr Neurol. 2011 Nov;15(6):508-11. doi: 10.1016/j.ejpn.2011.05.007. Epub 2011 Jun 15.
[PMID: 21680209] [DOI: 10.1016/j.ejpn.2011.05.007] .
[PMID: 21680209] [DOI: 10.1016/j.ejpn.2011.05.007] .
Discussion