Abstract
Introduction
About 10% of seizures in children with epilepsy are typical absence seizures. Absence seizures have a significant impact on quality of life.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for typical absence seizures in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2007 (Clinical evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: clonazepam; ethosuximide; gabapentin; lamotrigine; and valproate.
Key Points
Absence seizures are characterised by sudden, brief, frequent periods of unconsciousness, which may be accompanied by automatic movements. They may occur alone, or may coexist with other types of seizures in a child with other epileptic syndromes.
Absence seizures have a typical spike and wave pattern on the EEG. Atypical absence seizures have different EEG changes and clinical manifestations, and have a different natural history and response to treatment.
Absence seizures can be differentiated from complex partial seizures by their abrupt ending and lack of a postictal phase.
About 10% of seizures in children with epilepsy are typical absence seizures, with genetic factors considered to be the main cause. Where they are the only manifestation of epilepsy, they generally resolve spontaneously by the age of 12 years.
Lamotrigine increases the likelihood of being seizure free compared with placebo, but it can cause serious skin reactions.
There is consensus that ethosuximide and sodium valproate are beneficial in childhood absence seizures, although we don't know this for sure.
Ethosuximide is associated with aplastic anaemia, skin reactions, and renal and hepatic impairment.
Valproate is associated with behavioural and cognitive abnormalities, liver necrosis, and pancreatitis.
We don't know whether clonazepam or gabapentin reduce the frequency of absence seizures.
About this condition
Definition
Absence seizures are sudden, frequent episodes of unconsciousness lasting a few seconds, and are often accompanied by simple automatisms or clonic, atonic, or autonomic components. Typical absence seizures display a characteristic EEG showing regular symmetrical generalised spike and wave complexes with a frequency of 3 Hz, and usually occur in children with normal development and intelligence. Typical absence seizures are often confused with complex partial seizures — especially in cases of prolonged seizure with automatisms. However, the abrupt ending of typical absence seizures, without a postictcal phase, is the most useful clinical feature in distinguishing the two types. Typical absence seizures should not be confused with atypical absence seizures — which differ markedly in EEG findings and ictal behaviour, and usually present with other seizure types in a child with a background of learning disability and severe epilepsy. Typical absence seizures may be the sole seizure type experienced by a child. If this is the case, and the child is of normal development and has no structural lesions, the child is said to have childhood absence epilepsy. Alternatively, typical absence seizures may coexist in children with other epileptic syndromes — such as juvenile myoclonic epilepsy or juvenile absence epilepsy, in which other seizure types are also present. This differentiation into typical versus atypical seizures is important, as the natural history and response to treatment vary between the two groups. Interventions for atypical absence seizures or for absence seizures secondary to structural lesions are not included in this review.
Incidence/ Prevalence
About 10% of seizures in children with epilepsy are typical absence seizures. Annual incidence has been estimated at 0.7 to 4.6/100,000 people in the general population, and 6 to 8/100,000 in children aged 0 to 15 years. Prevalence is 5 to 50/100,000 people in the general population. Similar figures were found in the USA (Connecticut) and in Europe-based (Scandinavia, France) population studies. Age of onset ranges from 3 to 13 years, with a peak at 6 to 7 years.
Aetiology/ Risk factors
The cause of childhood absence epilepsy is presumed to be genetic. Seizures can be triggered by hyperventilation in susceptible children. Some anticonvulsants, such as phenytoin, carbamazepine, and vigabatrin are associated with an increased risk of absence seizures.
Prognosis
In childhood absence epilepsy, in which typical absence seizures are the only type of seizures suffered by the child, seizures generally cease spontaneously by 12 years of age or sooner. Less than 10% of children develop infrequent generalised tonic clonic seizures, and it is rare for them to continue having absence seizures. In other epileptic syndromes (in which absence seizures may coexist with other types of seizure) prognosis is varied, depending on the syndrome. Absence seizures have a significant impact on quality of life. The episode of unconsciousness may occur at any time, and usually without warning. Affected children need to take precautions to prevent injury during absences, and should refrain from activities that would put them at risk if seizures occurred (e.g., climbing heights, swimming unsupervised, or cycling on busy roads). Often, school staff members are the first to notice the recurrent episodes of absence seizures, and treatment is generally initiated because of the adverse impact on learning.
Aims of intervention
Cessation or decrease in the frequency of seizures, with minimum adverse effects of treatment.
Outcomes
Seizure frequency often measured as normalisation of the EEG; adverse effects of treatment. We found no RCTs assessing quality of life.
Methods
Clinical Evidence search October 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to October 2007, Embase 1980 to October 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 3. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. We also searched for retractions of studies included in the Review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, open or blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was a minimum follow-up length of 6 weeks. We also did a cohort harms search for Gabapentin. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Absence seizures in children.
| Important outcomes | Seizure frequency | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for typical absence seizures in children? | |||||||||
| 1 (29) | Seizure frequency | Lamotrigine versus placebo | 4 | –3 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data, no blinding, and short follow-up. Directness point deducted for inclusion of treatment responders only |
| 1 (38) | Seizure frequency | Lamotrigine versus valproate | 4 | -1 | -1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for conflicting results |
| 3 (93) | Seizure frequency | Valproate versus ethosuximide | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for wide inclusion criteria |
| 1 (33) | Seizure frequency | Gabapentin versus placebo | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and short follow-up. Directness point deducted for use of extremely low dose |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Epileptic syndrome
The term used in the classification of childhood seizure disorders. It relates to a recognisable clinical and EEG pattern.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
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