今日の臨床サポート

小児のてんかん(小児科)

著者: 阿部裕一 国立成育医療研究センター 小児内科系専門診療部 神経内科

監修: 五十嵐隆 国立成育医療研究センター

著者校正/監修レビュー済:2022/08/17
参考ガイドライン:
  1. 日本神経学会:てんかん診療ガイドライン2018
  1. 日本てんかん学会:てんかん学用語集 第6版
患者向け説明資料

概要・推奨   

  1. 断薬することの利益・不利益、抗てんかん薬を継続することの利益・不利益、後述の再発のリスクを家族・本人とよく話し合い、断薬の有無を決める。断薬しないという選択肢もある(推奨度1)
  1. なるべく再発を少なくするためには、断薬前の発作抑制期間は3 年とするのがよいと思われる。小児の良性てんかんでは2 年でもよい(推奨度1)
  1. 原則として単剤から使用することが推奨される(推奨度1)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
阿部裕一 : 未申告[2022年]
監修:五十嵐隆 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 定期レビューを行った。
  1. てんかんの診療の概要については『てんかん診療ガイドライン2018』を参考にしているが、てんかん発作型分類、てんかん分類については2017年に国際抗てんかん連盟(ILAE)によって作成された分類、用語を使用している(日本てんかん学会発刊の『てんかん学用語集 第6版』に日本語版が記載されている)。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. てんかんは、全年齢層で起こる中枢神経疾患である。世界的に有病率は人口1,000人あたり4~9人、日本におけるてんかんの有病率は1,000人あたり8.8人というデータがある[1][2]
  1. てんかんは種々の病因による慢性の脳疾患で、大脳神経細胞の過剰な放電による発作の反復(てんかん発作)を主徴とする。発作間欠期に種々の発達上の問題を伴うことがある。
  1. 発作が1回のみでも、再発リスクが60%以上と考えられる場合には、てんかんとみなして患者ケアを開始しうる。発作と器質的または間接的な成因およびてんかん性脳波異常所見が認められた小児などが該当する。
  1. てんかん発作は症状の氷山の一角であることも多く、小児の場合、発達全体に配慮した包括的治療が望まれる。
  1. 小児期に発症するてんかん症候群は多彩であり、臨床像や予後は一様ではなく、単一のプロトコールではカバーできない。
  1. 年齢依存性に発症するてんかん症候群があることは小児の特徴である。
  1. 発作予後に関して中心・側頭部棘波を示す小児てんかん(ローランドてんかん)等のように良好な経過をたどる群とレノックス・ガストー症候群のようにきわめて難治な群が存在する。
問診・診察のポイント  
  1. 周産期歴、てんかんや神経疾患などの家族歴、既往歴の聴取を行う。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

Abstract/Text Epidemiological surveys on epilepsy have been carried out repeatedly in Japan. However, at present, a population-based survey according to the International Classification for Epileptic Syndromes is considered to be especially important. We therefore carried out a population-based survey on children with epilepsy under thirteen years of age, who resided in Okayama Prefecture on December 31, 1999 as the prevalence day. The population of children in Okayama Prefecture under thirteen years of age on the prevalence day was 250,997. The lists of children with epilepsy were collected from the medical records of 45 hospitals, 36 clinics and 3 institutions in and around Okayama Prefecture. 1) 2,222 cases with active epilepsy were identified. The prevalence rate was 8.9 per 1,000. 2) This prevalence rate was almost equal to the previous result (8.2 per 1,000) given by another survey undertaken in 1975 for children under ten years of age in Okayama Prefecture. 3) If the cases with single seizure and/or the cases with seizures induced by fever are excluded, the prevalence rate decreased to 5.5 per 1,000. 4) 2,026 (91.2%) of the 2,222 cases were classified into three major categories of the International Classification of Epileptic Syndromes. They consisted of 1,557 cases (76.8%) with localization-related epilepsy, 449 cases (22.2%) with generalized epilepsy and 20 cases (1.0%) with undetermined epilepsy. 5) 303 (15.0%) of the 2,026 cases were classified into the epileptic syndromes. However, the majority of other cases consisted of nonspecific types of epilepsy, and could not be classified in detail. 6) The guideline for informed consent in epidemiological study published in 2000 by the Committee of the Japanese Ministry of Public Welfare will be useful for neuroepidemiological studies in the future.

PMID 11905016
Eiji Oka, Yoko Ohtsuka, Harumi Yoshinaga, Nagako Murakami, Katsuhiro Kobayashi, Tatsuya Ogino
Prevalence of childhood epilepsy and distribution of epileptic syndromes: a population-based survey in Okayama, Japan.
Epilepsia. 2006 Mar;47(3):626-30. doi: 10.1111/j.1528-1167.2006.00477.x.
Abstract/Text PURPOSE: A population-based survey childhood epilepsy was undertaken in Okayama Prefecture, Japan, to determine the prevalence rate and the distribution of epilepsies and epileptic syndromes according to the International Classification (ILAE, 1989).
METHODS: Information on patients younger than 13 years with active epilepsy was collected from medical records. Patients diagnosed with epilepsy according to clinical and EEG findings were put on the list even if those patients had had a single seizure or seizures occurring during febrile episodes.
RESULTS: In total, 2,220 cases were identified from a background population of 250,997. The prevalence rate was 8.8 per 1,000. If we exclude patients who had experienced a single seizure or seizures occurring during febrile episodes to compare our results with previous reports, the prevalence rate was 5.3 per 1,000. Of the 2,220 cases, 2,030 (91.4%) were classified into three major categories by ILAE classification. They consisted of 1,556 (76.7%) with localization-related epilepsy, 453 (22.3%) with generalized epilepsy, and 21 (1.0%) with undetermined epilepsy. Of the 2,030 cases, 309 (15.2%) were classified into epileptic syndrome categories, and 84.8% of the total were nonspecific types of epilepsy.
CONCLUSIONS: The prevalence rate of childhood epilepsy was distributed from 5.3 to 8.8 per 1,000. The appearance rate of various types of epileptic syndromes was low. Most cases could not be classified into the detailed categories of the International Classification (ILAE, 1989).

PMID 16529631
S Shinnar, H Kang, A T Berg, E S Goldensohn, W A Hauser, S L Moshé
EEG abnormalities in children with a first unprovoked seizure.
Epilepsia. 1994 May-Jun;35(3):471-6.
Abstract/Text We examined EEG findings from an ongoing study of 347 children with a first unprovoked seizure. EEGs were available in 321 (93%), and 135 (42%) had an abnormal EEG. EEG abnormalities included focal spikes (n = 77), generalized spike and wave discharges (n = 28), slowing (n = 43), and nonspecific abnormalities (n = 7). Abnormal EEGs were more common in children with remote symptomatic seizures (60%) than in those with idiopathic seizures (38%) (p < 0.003), more common in partial seizures (56%) than in generalized seizures (35%) (p < 0.001), and more common in children age > 3 years (52%) than in younger children (12%) (p < 0.001). Records including both awake and sleep tracings were available in 148 (46%) cases. For 122 (38%) only awake tracings and for 51 (16%) only sleep tracings were available. Fifty-nine (40%) of the 148 patients with both an awake and asleep tracing had abnormal EEGs. Of 50 such EEGs with epileptiform abnormalities, 15 (30%) demonstrated the abnormality either only while awake (n = 8) or only while asleep (n = 7). Of 17 patients with EEG slowing, 8 showed slowing only in the awake tracing and 9 showed slowing in both the awake and asleep tracing. Children with even a single unprovoked seizure have a high incidence of EEG abnormalities. Obtaining a combined awake and sleep EEG significantly increases the yield of EEG abnormalities. In children with an idiopathic first seizure, EEG abnormalities are associated with an increased risk of seizure recurrence.

PMID 8026390
D Hirtz, S Ashwal, A Berg, D Bettis, C Camfield, P Camfield, P Crumrine, R Elterman, S Schneider, S Shinnar
Practice parameter: evaluating a first nonfebrile seizure in children: report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society.
Neurology. 2000 Sep 12;55(5):616-23.
Abstract/Text OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient management based on analysis of evidence. For this practice parameter, the authors reviewed available evidence on evaluation of the first nonfebrile seizure in children in order to make practice recommendations based on this available evidence.
METHODS: Multiple searches revealed relevant literature and each article was reviewed, abstracted, and classified. Recommendations were based on a three-tiered scheme of classification of the evidence.
RESULTS: Routine EEG as part of the diagnostic evaluation was recommended; other studies such as laboratory evaluations and neuroimaging studies were recommended as based on specific clinical circumstances.
CONCLUSIONS: Further studies are needed using large, well-characterized samples and standardized data collection instruments. Collection of data regarding appropriate timing of evaluations would be important.

PMID 10980722
Abstract/Text PURPOSE: The International League Against Epilepsy (ILAE) classification of the epilepsies is in increasingly widespread use. The following analysis was done to assess the interrater agreement in classifying epilepsy syndromes in children with newly diagnosed epilepsy.
METHODS: In a prospective, community-based study, 613 children with newly diagnosed epilepsy were recruited. Based on information available at diagnosis or generated as part of the initial diagnostic assessment, three pediatric neurologists independently classified epilepsy syndromes. Interrater agreement was assessed with kappa.
RESULTS: Interrater agreement was extremely good, with kappa scores > or = 0.80 for almost all comparisons. Relatively limited quality of the EEG and seizure information in some cases, as well as discrepancies between the two, were associated with a tendency for more disagreement.
CONCLUSIONS: A high degree of interrater agreement was obtained in this study, indicating that the system for classifying syndromes can be meaningfully used in a community-based sample. Quality of the information, which is often, by necessity, less than optimal in newly diagnosed epilepsy, is a potential barrier to identification of syndromes. A substantial proportion of children were classified into relatively nonspecific syndromes. Over time, additional information may come to light to allow more precise identification of their forms of epilepsy. In an epidemiologic setting, the ILAE classification of the epilepsies can be successfully used with a high degree of reliability to classify newly diagnosed epilepsy in children.

PMID 10219269
Chrysostomos P Panayiotopoulos, Michael Michael, Sue Sanders, Thalia Valeta, Michael Koutroumanidis
Benign childhood focal epilepsies: assessment of established and newly recognized syndromes.
Brain. 2008 Sep;131(Pt 9):2264-86. doi: 10.1093/brain/awn162. Epub 2008 Aug 21.
Abstract/Text A big advance in epileptology has been the recognition of syndromes with distinct aetiology, clinical and EEG features, treatment and prognosis. A prime and common example of this is rolandic epilepsy that is well known by the general paediatricians for over 50 years, thus allowing a precise diagnosis that predicts an excellent prognosis. However, rolandic is not the only benign childhood epileptic syndrome. Converging evidence from multiple and independent clinical, EEG and magnetoencephalographic studies has documented Panayiotopoulos syndrome (PS) as a model of childhood autonomic epilepsy, which is also common and benign. Despite high prevalence, lengthy and dramatic features, PS as well as autonomic status epilepticus had eluded recognition because emetic and other ictal autonomic manifestations were dismissed as non-epileptic events of other diseases. Furthermore, PS because of frequent EEG occipital spikes has been erroneously considered as occipital epilepsy and thus confused with the idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), which is another age-related but rarer and of unpredictable prognosis syndrome. Encephalitis is a common misdiagnosis for PS and migraine with visual aura for ICOE-G. Pathophysiologically, the symptomatogenic zone appears to correspond to the epileptogenic zone in rolandic epilepsy (sensory-motor symptomatology of the rolandic cortex) and the ICOE-G (occipital lobe symptomatology), while the autonomic clinical manifestations of PS are likely to be generated by variable and widely spread epileptogenic foci acting upon a temporarily hyperexcitable central autonomic network. Rolandic epilepsy, PS, ICOE-G and other possible clinical phenotypes of benign childhood focal seizures are likely to be linked together by a genetically determined, functional derangement of the systemic brain maturation that is age related (benign childhood seizure susceptibility syndrome). This is usually mild but exceptionally it may diverge to serious epileptic disorders such as epileptic encephalopathy with continuous spike and wave during sleep. Links with other benign and age-related seizures in early life such as febrile seizures, benign focal neonatal and infantile seizures is possible. Overlap with idiopathic generalized epilepsies is limited and of uncertain genetic significance. Taking all these into account, benign childhood focal seizures and related epileptic syndromes would need proper multi-disciplinary re-assessment in an evidence-based manner.

PMID 18718967
A Okumura, F Hayakawa, K Kuno, K Watanabe
Benign partial epilepsy in infancy.
Arch Dis Child. 1996 Jan;74(1):19-21.
Abstract/Text The aim was to examine the occurrence of benign partial epilepsy in infancy (BPEI). BPEI was defined as epilepsies with complex partial seizures (CPS) or secondary generalised seizures (SGS), or both, compatible with the following characteristics: normal development before and after onset, no underlying disorders, normal interictal electroencephalograms (EEGs), and good response to treatment. All 75 patients who developed epilepsy within the first 2 years of age between 1987 and 1993 were evaluated: 22 patients fulfilled the definition completely; eight had CPS only, four SGS only, and 10 had both CPS and SGS; 17 had clusters of seizures. Eight patients had a positive family history. The average age of onset of seizures was 5.9 months. Interictal EEGs were all normal. Response to treatment was excellent and the average period of seizure persistence was 3.0 months. All had normal psychomotor development. Patients with BPEI were more common in this study than previously reported.

PMID 8660038
D Hirtz, A Berg, D Bettis, C Camfield, P Camfield, P Crumrine, W D Gaillard, S Schneider, S Shinnar, Quality Standards Subcommittee of the American Academy of Neurology, Practice Committee of the Child Neurology Society
Practice parameter: treatment of the child with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
Neurology. 2003 Jan 28;60(2):166-75.
Abstract/Text The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence regarding risks and benefits. This parameter reviews published literature relevant to the decision to begin treatment after a child or adolescent experiences a first unprovoked seizure and presents evidence-based practice recommendations. Reasons why treatment may be considered are discussed. Evidence is reviewed concerning risk of recurrence as well as effect of treatment on prevention of recurrence and development of chronic epilepsy. Studies of side effects of anticonvulsants commonly used to treat seizures in children are also reviewed. Relevant articles are classified according to the Quality Standards Subcommittee classification scheme. Treatment after a first unprovoked seizure appears to decrease the risk of a second seizure, but there are few data from studies involving only children. There appears to be no benefit of treatment with regard to the prognosis for long-term seizure remission. Antiepileptic drugs (AED) carry risks of side effects that are particularly important in children. The decision as to whether or not to treat children and adolescents who have experienced a first unprovoked seizure must be based on a risk-benefit assessment that weighs the risk of having another seizure against the risk of chronic AED therapy. The decision should be individualized and take into account both medical issues and patient and family preference.

PMID 12552027
A Marson, A Jacoby, A Johnson, L Kim, C Gamble, D Chadwick, Medical Research Council MESS Study Group
Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial.
Lancet. 2005 Jun 11-17;365(9476):2007-13. doi: 10.1016/S0140-6736(05)66694-9.
Abstract/Text BACKGROUND: The relative risks and benefits of starting or withholding antiepileptic drug treatment in patients with few or infrequent seizures are unclear. We sought to compare policies of immediate versus deferred treatment in such patients and to assess the effects of these policies on short-term recurrence and long-term outcomes.
METHODS: We undertook an unmasked, multicentre, randomised study of immediate and deferred antiepileptic drug treatment in 1847 patients with single seizures and early epilepsy. Outcomes comprised time to first, second, and fifth seizures; time to 2-year remission; no seizures between years 1 and 3 and between years 3 and 5 after randomisation; and quality of life. Analysis was by intention to treat.
FINDINGS: 404 patients invited to join the trial did not consent to randomisation; 722 were subsequently assigned immediate treatment with antiepileptic drugs and 721 were assigned deferred treatment. Immediate treatment increased time to first seizure (hazard ratio 1.4 [95% CI 1.2 to 1.7]), second seizure (1.3 [1.1 to 1.6]), and first tonic-clonic seizure (1.5 [1.2 to 1.8]). It also reduced the time to achieve 2-year remission of seizures (p=0.023). At 5-years follow-up, 76% of patients in the immediate treatment group and 77% of those in the deferred treatment group were seizure free between 3 and 5 years after randomisation (difference -0.2% [95% CI -5.8% to 5.5%]). The two policies did not differ with respect to quality of life outcomes or serious complications.
INTERPRETATION: Immediate antiepileptic drug treatment reduces the occurrence of seizures in the next 1-2 years, but does not affect long-term remission in individuals with single or infrequent seizures.

PMID 15950714
E H Reynolds, S D Shorvon
Monotherapy or polytherapy for epilepsy?
Epilepsia. 1981 Feb;22(1):1-10.
Abstract/Text Although anticonvulsant polytherapy has been widely and traditionally used in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. It does, however, lead to problems of chronic toxicity, drug interactions, failure to evaluate individual drugs, and sometimes exacerbation of seizures. There are many causes of polytherapy which could be avoided by more careful monitoring and supervision of therapy. Studies in new, previously untreated referrals suggest there is considerable potential for monotherapy. In the event of failure of optimum monotherapy, the value of polytherapy is not yet clear. In chronic patients on polytherapy there may be scope for careful rationalization to two or sometimes one drug, with reduction in chronic toxicity and sometimes improved seizure control. Reduction of therapy, however, may be impossible or hazardous due to withdrawal seizures. Even after successful reduction, seizure control is much less satisfactory than in new referrals. It is easier to avoid polytherapy than to reduce it. There is a need to define more carefully the limits of effective anticonvulsant therapy.

PMID 6781884
E Hancock, J Osborne, P Milner
Treatment of infantile spasms.
Cochrane Database Syst Rev. 2003;(3):CD001770. doi: 10.1002/14651858.CD001770.
Abstract/Text BACKGROUND: Infantile spasms (West's Syndrome) is a syndrome which includes a peculiar type of epileptic seizure, usually hypsarrhythmia and in the majority of people, psychomotor retardation. It remains poorly understood and despite modern imaging techniques an underlying cause is often not found. Little is known about their pathophysiological basis and treatment remains problematic.
OBJECTIVES: To compare the effects of single drugs used to treat infantile spasms in terms of long-term psychomotor development, subsequent epilepsy, control of the spasms and adverse effects.
SEARCH STRATEGY: Our search included the Cochrane Epilepsy Group trials register, MEDLINE (1966 to 2003) and EMBASE (1981 to 2003), contacting pharmaceutical companies and appeals at international conferences.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of the administration of drugs to people with infantile spasms.
DATA COLLECTION AND ANALYSIS: Three reviewers independently selected trials for inclusion and extracted data. Outcomes included cessation of spasms, time to cessation of spasms, participants with cessation of spasms remaining spasm free, reduction in spasms, resolution of hypsarrhythmia, subsequent epilepsy rates and adverse effects.
MAIN RESULTS: Eleven RCTs were included, who in total recruited just 514 participants and tested eight different drugs. Overall, methodology of the studies was poor. No study assessed long-term psychomotor development or onset of other seizure types. One small study found vigabatrin to be more efficacious than hydrocortisone in stopping infantile spasms in a group of people with tuberous sclerosis. One underpowered study showed a trend for vigabatrin to be more efficacious than placebo in stopping infantile spasms. Two small studies when combined showed ACTH to be more efficacious than low-dose prednisone (2 mg/kg). One study also suggested that control of spasms occurred more frequently with high dose vigabatrin as compared to low dose vigabatrin. It was not possible to compare reduction in the number of spasms between the different treatments because of differences in methods of analysis. Overall, only 18 individuals were reported to have been withdrawn from the trial treatments due to adverse effects and 4 deaths were reported.
REVIEWER'S CONCLUSIONS: We found no single treatment to be proven to be more efficacious in treating infantile spasms than any of the others (other than vigabatrin in the treatment of infantile spasms in tuberous sclerosis in one underpowered study). Few studies considered psychomotor development or subsequent seizure rates as outcomes and none had long-term follow-up. Further trials with larger numbers of participants, and longer follow-up are required.

PMID 12917912
S Yanagaki, H Oguni, K Hayashi, K Imai, M Funatuka, T Tanaka, M Yanagaki, M Osawa
A comparative study of high-dose and low-dose ACTH therapy for West syndrome.
Brain Dev. 1999 Oct;21(7):461-7.
Abstract/Text PURPOSE: A prospective randomized controlled study was conducted for the purpose of identifying the lowest effective ACTH dose, with the fewest adverse effects, for the treatment of West syndrome (WS).
SUBJECTS AND METHODS: Twenty-five subjects with cryptogenic (CWS, n = 9) or symptomatic (SWS, n = 16) WS were enrolled in this study. They were randomly assigned to receive either low-dose (0.005 mg/kg per day = 0.2 IU/kg per day) or high-dose (0.025 mg/kg per day = 1 IU/kg per day) synthetic ACTH therapy. ACTH was administered every morning for 2 weeks and tapered to zero over the subsequent 2 weeks. Both effectiveness and adverse effects were compared between the two treatment regimens in each type of WS.
RESULT: After completion of the treatment protocol in the CWS group, spasms and hypsarrhythmia were completely suppressed in 3/4 (75%) given the low-dose and 5/5 (100%) given the high-dose treatment. In the SWS group, the spasms and hypsarrhythmia disappeared in 6/8 (75%) in each dose group. There were no significant differences in initial responses between the low-dose and high-dose treatments for either type of WS (P > 0.05). Long-term seizure and developmental outcomes, assessed in the 17 responders who were followed up for longer than 1 year after the completion of ACTH therapy, were also essentially the same. We did not recognize differences in side effect profiles between the two treatment regimens with the exceptions of sleepiness and brain shrinkage estimated by CT scan, both of which were significantly milder in the low-dose than in the high-dose group (P < 0.05).
CONCLUSION: Unexpectedly, this prospective randomized controlled study demonstrated the dose of ACTH required for spasm cessation and disappearance of the hypsarrhythmic EEG pattern to be lower than previously believed. A low-dose regimen should thus be considered for CWS, and for SWS associated with significant cerebral atrophy.

PMID 10522523
M Ito
Extremely low-dose ACTH therapy for West syndrome in Japan.
Brain Dev. 2001 Nov;23(7):635-41.
Abstract/Text Adrenocorticotropic hormone (ACTH) therapy is a widely used and effective treatment for West syndrome. However, serious adverse effects can occur during or shortly after ACTH therapy. Synthetic ACTH has been reported to cause more adverse effects than natural ACTH. Currently, most Japanese pediatric neurologists try other non-hormonal treatments before using ACTH therapy, but even then, they use extremely low dosages of synthetic ACTH. The extremely low-dose synthetic ACTH therapy currently used in Japan is as effective for treatment of West syndrome as the higher doses reported in previous studies from Japan and Western countries. The dosage and duration of synthetic ACTH therapy should be as low as possible to avoid serious adverse effects. Close monitoring of the adverse effects, especially subdural hematoma, is necessary even when extremely low dosages of ACTH are administered.

PMID 11701268
M Ito, T Seki, Y Takuma
Current therapy for West syndrome in Japan.
J Child Neurol. 2000 Jun;15(6):424-8.
Abstract/Text We sent questionnaires concerning the current therapy for West syndrome to 208 institutions at which pediatric care members of the Japan Epilepsy Society were working. Of these, 129 (62%) institutions responded. Vitamin B6 was the preferred first-line drug, followed by the combination of vitamin B6 and valproate or monotherapy with valproate. Corticotropin was the third choice among the drugs. The dosage of corticotropin was lower than previously reported. The treatment of West syndrome is not well established at present and further research is needed to improve the therapeutic protocol.

PMID 10868790
Abstract/Text The long-term efficacy and adverse-event profiles of sodium valproate and carbamazepine in children with newly diagnosed primary generalised or partial epilepsy were compared at 63 outpatient clinics. Children with two or more generalised tonic-clonic or partial seizures in the previous six months were randomised to oral sodium valproate (N = 130) or oral carbamazepine (N = 130) and followed for three years as outpatients. Dosages were increased as needed until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine were equally effective in achieving high levels of seizure control in both primary generalised seizures and partial seizures with or without generalisation. Adverse events were mostly mild, few necessitating drug withdrawal. Those particularly associated with valproate were weight increase, alopecia and appetite increase, and with carbamazepine, rashes, somnolence, diplopia and abnormal gait/ataxia.

PMID 7851677
Abstract/Text In order to collect local data for children with Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS), we conducted a retrospective study of 50 Chinese children (32 males and 18 females) with BECTS diagnosed in two regional hospitals in Hong Kong from 1995 to 1998. Their peak age of onset was 7 years (range 3-13 years) and a male predominance was observed. Seven patients (14%) had a past history of febrile convulsions and five cases (10%) had a family history of epilepsy. The presentation was protean, but most of them had infrequent, short, nocturnal generalised seizures. The EEG spike foci were most frequently found in mid-temporal regions, followed by centrotemporal regions. Fourteen percent of children did not require anti-epileptic drug treatment. For those who were treated, they were easily controlled on a low dose of carbamazepine (median dosage of 12.75 mg/kg per day) or sodium valproate (median dosage of 20 mg/kg per day). Our study suggested a generally good prognosis for BECTS. No risk factors of frequent seizure recurrence could be identified.

PMID 12907271
M de Silva, B MacArdle, M McGowan, E Hughes, J Stewart, B G Neville, A L Johnson, E H Reynolds
Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.
Lancet. 1996 Mar 16;347(9003):709-13.
Abstract/Text BACKGROUND: The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.
METHODS: Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.
FINDINGS: The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.

PMID 8601999
Ingo Borggraefe, Michaela Bonfert, Thomas Bast, Bernd Axel Neubauer, Klaus Juergen Schotten, Kai Maßmann, Soheyl Noachtar, Ingrid Tuxhorn, Theodor W May, Florian Heinen, German HEAD Study Group
Levetiracetam vs. sulthiame in benign epilepsy with centrotemporal spikes in childhood: a double-blinded, randomized, controlled trial (German HEAD Study).
Eur J Paediatr Neurol. 2013 Sep;17(5):507-14. doi: 10.1016/j.ejpn.2013.03.014. Epub 2013 Apr 30.
Abstract/Text OBJECTIVE: To show non-inferiority of levetiracetam to sulthiame with respect to efficacy, tolerability and safety in benign epilepsy with centrotemporal spikes in a prospective, double-blinded randomized controlled trial.
METHODS: A sample size of 60 subjects (treatment group) was calculated to show reliable statistical results for non-inferiority. A total of 44 patients could be randomly allocated to either (LEV or STM) treatment group. Explorative data analysis was performed to investigate differences in the number of treatment failure events (occurrence of a seizure during the observation period of 6 months) and total dropouts. In addition, information of the occurrence of adverse events was collected.
RESULTS: 43 patients were analyzed. One patient had to be excluded due to protocol violation. Treatment failure events occurred in four patients (19.0%) in the LEV treatment group and in two patients (9.1%) in the STM treatment group, respectively, (p = 0.412). The number of dropouts due to adverse reactions was five in the LEV treatment group and one in STM treatment group (23.8% vs. 4.5%, respectively, p = 0.095). Severe adverse events occurred in patients treated with LEV (n = 2, 9.5%). The total number of dropouts due to either seizure recurrence or adverse events was significantly higher in the LEV group (n = 9, 42.9%) compared to the STM group (n = 3, 13.6%, p = 0.03).
INTERPRETATION: The study results concerning non-inferiority were not conclusive, as the calculated sample size was not reached to support sufficient statistical power due to limited recruitment in a 26 months period. The rates of seizure free patients were [relatively] high in both groups. However, the results indicate that termination of drug treatment due to seizure recurrence or adverse events occurred more frequently in the LEV group compared to STM. Behavioral disturbances were the most common adverse event causing study termination.

Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
PMID 23642492
Giangennaro Coppola, Emilio Franzoni, Alberto Verrotti, Caterina Garone, Jasenka Sarajlija, Francesca Felicia Operto, Antonio Pascotto
Levetiracetam or oxcarbazepine as monotherapy in newly diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS): an open-label, parallel group trial.
Brain Dev. 2007 Jun;29(5):281-4. doi: 10.1016/j.braindev.2006.09.008. Epub 2006 Oct 20.
Abstract/Text To evaluate the efficacy and tolerability of levetiracetam or oxcarbazepine as monotherapy in children with newly diagnosed benign epilepsy with centrotemporal spikes (BECTS). Twenty-one children (11 males, 10 females), aged between 5 and 13 years (mean 10.5 years), and 18 (10 M, 8 F), aged between 3.3 and 14 years (mean 8.4 years), were randomised to receive monotherapy with levetiracetam or oxcarbazepine, respectively. LEV was titrated up to 20-30 mg/kg/once or twice a day, and OXC up to 20-35 mg/kg once or twice a day. Thirty-nine consecutive children (21 males, 18 females), aged between 3.3 and 14 years (mean 10.7 years), were recruited into the study. Twenty-one were randomised on LEV (11 male, 10 female; mean age 10.5 years), and 18 on OXC (10 male, 8 female; mean age 8.4 years). After a mean follow-up period of 18.5 months (range 12-24 months), 19 out of 21 patients (90.5%) on levetiracetam, and 13 out of 18 (72,22%) on oxcarbazepine did not have further seizures. Mean serum level of LEV was 4.1 microg/ml (range 1.3-9.0), and of OXC was 15.2 microg/ml (range 4.2-27.5). Adverse side effects on LEV were reported in 3 children (14.3%), represented by mild and transient decreased appetite (2) and cephalalgia (1). They were reported on OXC in 2/18 (11.1%), including headache (1), and sedation (1). These preliminary data from an open, parallel group study suggest that levetiracetam and oxcarbazepine may be potentially effective and well tolerated drugs for children with BECTS who require treatment.

PMID 17055681
E B Posner, K Mohamed, A G Marson
Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents.
Cochrane Database Syst Rev. 2003;(3):CD003032. doi: 10.1002/14651858.CD003032.
Abstract/Text BACKGROUND: Absence seizures are brief epileptic seizures which present in childhood and adolescence. They are characterised by sudden loss of awareness and an electroencephalogram (EEG) typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of anticonvulsant for a child with typical absence seizures.
OBJECTIVES: To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures, when compared with placebo or each other.
SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1, 2003), MEDLINE (January 1966 to March 2003) and EMBASE (1988 to March 2003). We also contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively.
SELECTION CRITERIA: Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with absence seizures: ethosuximide; sodium valproate; lamotrigine or placebo.
DATA COLLECTION AND ANALYSIS: Outcome measures were: (i) proportion of individuals seizure free at 1, 6 and 18 months post randomisation; (ii) people with a 50% or greater reduction in seizure frequency; (iii) normalisation of EEG and/or negative hyperventilation test and (iv) adverse effects. Data were independently extracted by two reviewers. Results are presented as relative risks (RR) with 95% confidence intervals (95% CI).
MAIN RESULTS: Four small trials were found, which were of poor methodological quality. One trial (29 participants) compared lamotrigine with placebo using a response conditional design. Individuals taking lamotrigine were significantly more likely to be seizure free than participants taking placebo during this short trial. Three studies compared ethosuximide, but because of diverse study designs and populations studied, we decided not to pool results in a meta-analysis. None of these studies found a difference between valproate and ethosuximide with respect to seizure control, but confidence intervals were wide and the existence of important differences could not be excluded.
REVIEWER'S CONCLUSIONS: Although ethosuximide, lamotrigine and valproate are commonly used to treat people with absence seizures we have insufficient evidence to inform clinical practice, and the few trials included in this review were of poor methodological quality. More trials of better quality are needed.

PMID 12917940
Tracy A Glauser, Avital Cnaan, Shlomo Shinnar, Deborah G Hirtz, Dennis Dlugos, David Masur, Peggy O Clark, Edmund V Capparelli, Peter C Adamson, Childhood Absence Epilepsy Study Group
Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy.
N Engl J Med. 2010 Mar 4;362(9):790-9. doi: 10.1056/NEJMoa0902014.
Abstract/Text BACKGROUND: Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined.
METHODS: In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons.
RESULTS: The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03).
CONCLUSIONS: Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)

2010 Massachusetts Medical Society
PMID 20200383
E Hancock, H Cross
Treatment of Lennox-Gastaut syndrome.
Cochrane Database Syst Rev. 2003;(3):CD003277. doi: 10.1002/14651858.CD003277.
Abstract/Text BACKGROUND: The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and personality disorders. It occurs more frequently in males and onset is usually before the age of eight with a peak between three and five years. Late cases occurring in adolescence and early adulthood have rarely been reported. Language is frequently affected with both slowness in ideation and expression in addition to difficulties of motor dysfunction. Severe behavioural disorders (for example hyperactivity, aggressiveness and autistic tendencies)and personality disorders are nearly always present. There is also a tendency for psychosis to develop with time. The long-term prognosis is poor; although the epilepsy often improves, complete seizure freedom is rare and conversely the mental and psychiatric disorders tend to worsen with time.
OBJECTIVES: To compare the effects of pharmaceutical therapies used to treat Lennox-Gastaut syndrome in terms of control of seizures and adverse effects. Many people who suffer from this syndrome will already be receiving other antiepileptic medications at the time of their entry into a trial. However, for the purpose of this review we will only consider the effect of the single therapeutic agent being trialed (often as add-on therapy).
SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register (March 2003), MEDLINE (1966 to March 2003) and EMBASE (1980 to March 2003). In addition, we contacted pharmaceutical companies and colleagues in the field to ascertain any unpublished/ongoing studies.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of the administration of drug therapy to patients with Lennox-Gastaut syndrome.
DATA COLLECTION AND ANALYSIS: Data was independently extracted by two reviewers. Analysis included assessing study quality, as well as statistical analysis of the effects on overall seizure rates and effects on specific seizure types (eg drop attacks), adverse effects and mortality.
MAIN RESULTS: We found five RCTs, but were unable to perform any sort of meta-analysis, because each trial looked at different populations, different therapies and considered different outcomes.
REVIEWER'S CONCLUSIONS: The optimum treatment for Lennox-Gastaut syndrome remains uncertain and no study to date has shown any one drug to be highly efficacious; lamotrigine, topiramate and felbamate may be helpful as add-on therapy. Until further research has been undertaken clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.

PMID 12917958
Eleanor C Hancock, Helen H J Cross
Treatment of Lennox-Gastaut syndrome.
Cochrane Database Syst Rev. 2009 Jul 8;(3):CD003277. doi: 10.1002/14651858.CD003277.pub2. Epub 2009 Jul 8.
Abstract/Text BACKGROUND: The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behaviour disorders. It occurs more frequently in males and onset is usually before the age of eight, with a peak between three and five years. Late cases occurring in adolescence and early adulthood have rarely been reported. Language is frequently affected, with both slowness in ideation and expression in addition to difficulties of motor dysfunction. Severe behavioural disorders (for example hyperactivity, aggressiveness and autistic tendencies) and personality disorders are nearly always present. There is also a tendency for psychosis to develop with time. The long-term prognosis is poor; although the epilepsy often improves, complete seizure freedom is rare and conversely the mental and psychiatric disorders tend to worsen with time.
OBJECTIVES: To compare the effects of pharmaceutical therapies used to treat Lennox-Gastaut syndrome in terms of control of seizures and adverse effects. Many people who suffer from this syndrome will already be receiving other antiepileptic medications at the time of their entry into a trial. However, for the purpose of this review we will only consider the effect of the single therapeutic agent being trialed (often as add-on therapy).
SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (February 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009), and MEDLINE (1950 to January 2009). We also searched EMBASE (1980 to March 2003). We imposed no language restrictions. We searched the ISRCTN register for ongoing trials and in addition, we contacted pharmaceutical companies and colleagues in the field to seek any unpublished or ongoing studies.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of the administration of drug therapy to patients with Lennox-Gastaut syndrome.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. Analysis included assessing study quality, as well as statistical analysis of the effects on overall seizure rates and effects on specific seizure types (e.g. drop attacks), adverse effects and mortality.
MAIN RESULTS: We found seven RCTs, but were unable to perform any meta-analysis, because each trial looked at different populations, different therapies and considered different outcomes.
AUTHORS' CONCLUSIONS: The optimum treatment for Lennox-Gastaut syndrome remains uncertain and no study to date has shown any one drug to be highly efficacious; rufinamide, lamotrigine, topiramate and felbamate may be helpful as add-on therapy. Until further research has been undertaken, clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.

PMID 19588340
A T Berg, S Shinnar
Relapse following discontinuation of antiepileptic drugs: a meta-analysis.
Neurology. 1994 Apr;44(4):601-8.
Abstract/Text The estimates in the literature of the risk of seizure relapse after antiepileptic medications are withdrawn range from less than 10% to nearly 70%. There is also little coherence regarding predictors of successful medication withdrawal. We performed a meta-analysis of the published literature to date to determine the risk of relapse at 1 and 2 years after discontinuation of medications and to examine the strength of association between the risk of relapse and three commonly assessed clinical factors: age of onset of epilepsy, presence of an underlying neurologic condition, and an abnormal EEG. We established criteria for inclusion of a study in the analysis, and 25 studies met these criteria. Overall, the risk of relapse at 1 year was 0.25 (95% CI, 0.21 to 0.30) and at 2 years it was 0.29 (95% CI, 0.24 to 0.34). Relative to epilepsy of childhood onset, epilepsy of adolescent onset was associated with a relative risk of relapse of 1.79 (95% CI, 1.46 to 2.19). Compared with childhood-onset epilepsy, adult-onset epilepsy was associated with a relative risk of 1.34 (95% CI, 1.00 to 1.81). Patients with remote symptomatic seizures were more likely to relapse than patients with idiopathic seizures; the relative risk was 1.55 (95% CI, 1.21 to 1.98). An abnormal EEG was associated with a relative risk of 1.45 (95% CI, 1.18 to 1.79). Although these figures help provide an estimate of an individual's likelihood of relapse, they should not be used as the sole basis on which to make the decision on discontinuation of medications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 8164811
S Shinnar, A T Berg, S L Moshé, H Kang, C O'Dell, M Alemany, E S Goldensohn, W A Hauser
Discontinuing antiepileptic drugs in children with epilepsy: a prospective study.
Ann Neurol. 1994 May;35(5):534-45. doi: 10.1002/ana.410350506.
Abstract/Text In a prospective study, antiepileptic drugs were discontinued in 264 children with epilepsy after a mean seizure-free interval of 2.9 years. They were then followed for a mean of 58 months to ascertain whether seizures recurred. Seizures recurred in 95 (36%) of the children. Etiology was a significant predictor of outcome (relative risk [RR] = 1.81). On multivariable analysis, significant factors in the idiopathic group included age at onset above 12 years (RR = 5.4), a family history of seizures (RR = 3.1), the presence of slowing on the electroencephalogram prior to medication withdrawal (RR = 2.4), and a history of atypical febrile seizures (RR = 2.8). Specific epileptic syndromes such as juvenile myoclonic epilepsy and benign rolandic epilepsy were also significant predictors of outcome. In the remote symptomatic group, significant predictors of outcome included age at onset older than 12 years (RR = 3.6), moderate to severe mental retardation (IQ < 50) (RR = 2.8), a history of atypical febrile seizures (RR = 2.0), and a history of absence seizures (RR = 0.4). The majority of children with epilepsy in remission while on antiepileptic drug therapy will remain seizure free when medications are withdrawn. A few readily available parameters distinguish those with a good prognosis from those in whom seizures are likely to recur. These data provide the framework for the clinical decision making for withdrawal of medications in these children.

PMID 8179299
J I Sirven, M Sperling, D M Wingerchuk
Early versus late antiepileptic drug withdrawal for people with epilepsy in remission.
Cochrane Database Syst Rev. 2001;(3):CD001902. doi: 10.1002/14651858.CD001902.
Abstract/Text BACKGROUND: Antiepileptic drugs ( AEDs) are used to prevent seizures but are associated with both short and long term adverse effects. When epilepsy is in remission, it may be in the patient's best interest to discontinue medication. However, the optimal timing of AED discontinuation is not known.
OBJECTIVES: To quantify seizure relapse risk after early (less than two seizure free years) versus late (more than two seizure free years) AED withdrawal in adult and pediatric epilepsy patients. To assess which variables modify the risk of seizure recurrence.
SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled trials register (Cochrane Library Issue 4, 2000), MEDLINE (January 1996 to January 2001), EMBASE, Index Medicus, CINAHL, as well as hand-searching of journals.
SELECTION CRITERIA: Randomized controlled trials that evaluate withdrawal of AEDs after varying periods of seizure remission in adult and pediatric epilepsy patients with or without blinding were included. Included studies compared an early versus late AED discontinuation.
DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Relative risks with 95% confidence intervals were calculated for each trial. Summary relative risks and 95% confidence intervals for dichotomous data were calculated using a random effects model. A test of statistical heterogeneity was conducted for each pooled relative risk calculation.
MAIN RESULTS: Seven eligible controlled trials were included in the analysis representing 924 randomized pediatric patients. There were no eligible trials evaluating adult seizure free patients. The pooled relative risk for seizure relapse in early versus late AED withdrawal was 1.32 (95% confidence interval 1.02 to 1.70). On the basis of this estimate, the number needed to harm, that is expose an individual to a higher risk of seizure relapse because of early withdrawal of AED, is 10. Early discontinuation was associated with greater relapse rates in patients with partial seizures[pooled RR = 1.52; 95% confidence interval 0.95 to 2.41] or an abnormal EEG [pooled RR=1.67; 95% confidence interval 0.93 to 3.00].
REVIEWER'S CONCLUSIONS: There is evidence to support waiting for at least two or more seizure free years before discontinuing AEDs in children, particularly if individuals have an abnormal EEG and partial seizures. There is insufficient evidence to establish when to withdraw AEDs in pediatric patients with generalized seizures. There is no evidence to guide the timing of withdrawal of AEDs in adult seizure free patients. Further blinded randomized controlled trials are needed to identify the optimal timing of AED withdrawal and risk factors predictive of relapse.

PMID 11687000

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