A Meta-analysis of effectiveness and safety of steroids combined with antiepileptic drugs in the treatment of children with epileptic electrical status during sleep_Journal of Epilepsy

Authors：

TANG Lanfang ,  HU Yue

Department of Neurology, Children’s Hospital Affiliated to Chongqing Medical University; National Clinical Medical Research Center for Child Health and Disease; Key Laboratory of Child Developmental Disease Research of Ministry of Education; National International Science and Technology Cooperation Base for Major Childhood Developmental Diseases ; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China;

Corresponding author：

HU Yue, Email: huyue915@163.com

Keywords：

Epileptic electrical status during sleep; Steroids; Antiepileptic drugs; Combination therapy; Meta analysis

DOI：

10.7507/2096-0247.20210032

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Objective To systematically evaluate the efficacy of steroids combined with antiepileptic drugs compared with alone antiepileptic drugs in the treatment of children with epileptic electrical status during sleep to provide evidence-based medical basis for its treatment.Methods Electronic searches were maded in PubMed, Embase database, Cochrane Library, CNKI, Wanfang and the Chinese biomedical literature database for the literature about steroids combined with antiepileptic drugs compared with alone antiepileptic drugs in the treatment, and retrieval time is from January 1990 to October 2020. Two evaluators independently screened literature, extracted data, evaluated literature quality and risk of bias and checked each other. Meta analysis was performed by stata16.0 software.Results A total of 679 children with ESES were included in 10 studies, including 9 randomized controlled trials and 1 retrospective cohort study. Meta analysis results showed that there were statistically significant differences in clinical improvement rate [RR=1.31, 95%CI (1.21, 1.42), P<0.01], electroencephalogram discharge improvement rate [RR=1.35, 95%CI (1.25, 1.46), P<0.01] and cognitive intelligence score [SMD=1.19, 95%CI (0.80, 1.57), P<0.01] between steroids combined with antiepileptic drugs group and alone antiepileptic drugs group after 6 months follow-up. The incidence of adverse reactions in steroids combined with antiepileptic drugs group was higher than that in alone antiepileptic drugs group, and the difference was statistically significant [RR=4.13, 95%CI (1.06, 16.13), P<0.01]. All adverse reactions improved or disappeared after drug withdrawal.Conclusion Compared with alone antiepileptic drugs, steroids combined with antiepileptic drugs group has advantages in controlling epileptic seizures, improving electroencephalogram abnormalities and improving cognitive ability, and it is relatively safe.

Citation： TANG Lanfang, HU Yue. A Meta-analysis of effectiveness and safety of steroids combined with antiepileptic drugs in the treatment of children with epileptic electrical status during sleep. Journal of Epilepsy, 2021, 7(3): 197-207. doi: 10.7507/2096-0247.20210032 Copy

1.	Altunel A, Altunel EÖ, Sever A, et al. Response to adrenocorticotropic in attention deficit hyperactivity disorder-like symptoms in electrical status epilepticus in sleep syndrome is related to electroencephalographic improvement: A retrospective study. Epilepsy & Behavior, 2017, 74: 161-166.
2.	Van Den Munckhof B, Van Dee V, Sagi L, et al. Treatment of electrical status epilepticus in sleep: A pooled analysis of 575 cases. Epilepsia, 2015, 56(11): 38-46.
3.	Jeong A, Strahle J, Vellimana AK. Hemispherotomy in children with electrical status epilepticus of sleep. Journal of Neurosurgery, 2017, 19(1): 56-62.
4.	Kramer U, Sagi L, Goldberg-Stern H. Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES). Epilepsia, 2009, 50(6): 17-24.
5.	Scheltens-de Boer M. Guidelines for EEG in encephalopathy related to ESES/CSWS in children. Epilepsia, 2009, 50: 7-13.
6.	De Negri M. Electrical status epilepticus during sleep (ESES). Different clinical syndromes: Towards a unifying view? Brain and Development, 1997, 19(7): 47-51.
7.	冯启蒙, 邓星强. 甲泼尼龙冲击联合丙戊酸钠治疗儿童睡眠期癫痫性电持续状态的临床研究. 中西医结合心脑血管病杂志, 2019, 17(12): 1903-1905.
8.	刘忠良, 张晶卉, 孙聪玲. 甲泼尼龙冲击治疗儿童睡眠中癫痫性电持续状态的临床疗效研究. 中华妇幼临床医学杂志(电子版), 2014, 10(6): 745-747.
9.	陈会, 刘平, 陈嘉蕾, 等. 甲泼尼龙治疗睡眠期癫痫性电持续状态临床观察. 儿科药学杂志, 2017, 28(6): 6-9.
10.	蔡慧强, 张端秀. 甲泼尼龙冲击联合左乙拉西坦治疗儿童睡眠期癫痫性电持续状态的临床研究. 中国实用乡村医生杂志, 2020, 27(6): 28-31.
11.	林芳萍, 孙皎. 激素冲击疗法对癫痫儿童的影响. 现代实用医学, 2017, 29(10): 1373-1375.
12.	张军利, 郭爱萍, 谢冰, 等. 甲泼尼龙冲击治疗睡眠期癫痫性电持续状态患儿临床疗效及对智力水平的影响. 临床心身疾病杂志, 2020, 26(1): 31-33.
13.	浮纪玲. 甲泼尼龙冲击疗法辅助治疗儿童睡眠期癫痫性电持续状态的临床效果. 现代诊断与治疗, 2020, 31(9): 1376-1377.
14.	李彦卿, 王庆, 程成, 等. 甲泼尼龙对睡眠中癫痫性电持续状态患儿脑电图棘慢波指数、Gesell 评分、临床发作次数及 GAL、NPY 表达水平的影响. 临床和实验医学杂志, 2020, 19(5): 519-522.
15.	郭峰. 甲泼尼龙冲击对儿童睡眠中癫痫性电持续状态的治疗效果观察. 继续医学教育, 2016, 30(1): 144-145.
16.	王朋朋, 谢鹤, 吴淑庄, 等. 甲泼尼龙冲击对儿童睡眠中癫痫性电持续状态的治疗效果观察. 临床医学工程, 2015, 22(2): 172-173.
17.	Zhang W-N, Zou L-P, Ju J, et al. Therapeutic effects of Ievetiracetam on electrical status epilepticus during sleep in children. Chinese Journal of Contemporary, 2012, 14(5): 340-343.
18.	Vrielynck P, Ghariani S, Lienard F, et al. Topiramate in epileptic syndromes of childhood with continuous spike-and-wave during sleep: Retrospective study of 23 cases. Epilepsia, 2014, 55(suppl. 2): 244-246.
19.	Inutsuka M, Kobayashi K, Oka M, et al. Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders. Brain and Development, 2006, 28(5): 281-286.
20.	Gertsch EA, Chapman KE, Laoprasert P, et al. Safety and efficacy of high-dose diazepam for treatment of electrical status epilepticus during slow wave sleep. Epilepsy Currents, 2013, 13(suppl. 1): 387-388.
21.	Klehm J, FernÁndez IS, Peters J, et al. Response of seizures and epileptiform activity to high-dose clobazam treatment. Epilepsy Currents, 2014, 14(suppl. 1): 212.
22.	Değerliyurt A, Yalnizoğlu D, Bakar EE, et al. Electrical status epilepticus during sleep: A study of 22 patients. Brain and Development, 2015, 37(2): 250-264.
23.	陈静, 杨志仙, 刘晓燕, 等. 甲泼尼龙冲击治疗对儿童睡眠中癫痫性电持续状态的疗效. 中华儿科杂志, 2014, 52(9): 678-682.
24.	Pavlidis E, Møller RS, Nikanorova M, et al. Idiopathic encephalopathy related to status epilepticus during slow sleep (ESES) as a "pure" model of epileptic encephalopathy. An electroclinical, genetic, and follow-up study. Epilepsy and Behavior, 2019, 97: 244-252.
25.	Bobbili DR, Lal D, May P, et al. Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy. European journal of human genetics, 2018, 26(2): 258-264.
26.	Gencpinar P, Dundar NO, Tekgul H. Electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome in children: An electroclinical evaluation according to the EEG patterns. Epilepsy & Behavior, 2016, 61: 107-111.
27.	Meng L-P, Dai Y-Y. A clinical analysis of electrical status epilepticus during sleep in children and a follow-up study of methylprednisolone pulse therapy. Chinese Journal of Contemporary Pediatrics, 2019, 21(4): 348-353.
28.	Jovic N, Stevanovic G, Borkovic M, et al. Efficacy and safety of intravenous methylprednisolone pulse therapy in epileptic encephalopathy with electrical status epilepticus during sleep. Epilepsia, 2018, 59(suppl. 3): 111.
29.	张慧敏, 温晓红, 黄金华, 等. 韦氏儿童智力量表第四版在癫痫儿童认知评估中的应用. 中国儿童保健杂志, 2018, 26(10): 1120-1123.
30.	Buzatu M, Bulteau C, Altuzarra C, et al. Corticosteroids as treatment of epileptic syndromes with continuous spike-waves during slow-wave sleep. Epilepsia, 2009, 50(suppl. 7): 68-72.
31.	Sinclair DB, Snyder TJ. Corticosteroids for the treatment of Landau-Kleffner syndrome and continuous spike-wave discharge during sleep. Pediatric Neurology, 2005, 32(5): 300-306.
32.	van den Munckhof B, Alderweireld C, Davelaar S, et al. Treatment of electrical status epilepticus in sleep: Clinical and EEG characteristics and response to 147 treatments in 47 patients. European Journal of Paediatric Neurology, 2018, 22(1): 64-71.
33.	Hempel A, Frost M, Agarwal N. Language and behavioral outcomes of treatment with pulse-dose prednisone for electrical status epilepticus in sleep (ESES). Epilepsy & Behavior, 2019, 94: 93-99.
34.	Chen J, Yang Z, Liu X, et al. Efficacy of methylprednisolone therapy for electrical status epilepticus during sleep in children. Chinese Journal of Pediatrics, 2014, 52(9): 678-682.
35.	Pera MC, Randazzo G, Masnada S, et al. Intravenous methylprednisolone pulse therapy for children with epileptic encephalopathy. Functional Neurology, 2015, 30(3): 173-179.

1. Altunel A, Altunel EÖ, Sever A, et al. Response to adrenocorticotropic in attention deficit hyperactivity disorder-like symptoms in electrical status epilepticus in sleep syndrome is related to electroencephalographic improvement: A retrospective study. Epilepsy & Behavior, 2017, 74: 161-166.
2. Van Den Munckhof B, Van Dee V, Sagi L, et al. Treatment of electrical status epilepticus in sleep: A pooled analysis of 575 cases. Epilepsia, 2015, 56(11): 38-46.
3. Jeong A, Strahle J, Vellimana AK. Hemispherotomy in children with electrical status epilepticus of sleep. Journal of Neurosurgery, 2017, 19(1): 56-62.
4. Kramer U, Sagi L, Goldberg-Stern H. Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES). Epilepsia, 2009, 50(6): 17-24.
5. Scheltens-de Boer M. Guidelines for EEG in encephalopathy related to ESES/CSWS in children. Epilepsia, 2009, 50: 7-13.
6. De Negri M. Electrical status epilepticus during sleep (ESES). Different clinical syndromes: Towards a unifying view? Brain and Development, 1997, 19(7): 47-51.
7. 冯启蒙, 邓星强. 甲泼尼龙冲击联合丙戊酸钠治疗儿童睡眠期癫痫性电持续状态的临床研究. 中西医结合心脑血管病杂志, 2019, 17(12): 1903-1905.
8. 刘忠良, 张晶卉, 孙聪玲. 甲泼尼龙冲击治疗儿童睡眠中癫痫性电持续状态的临床疗效研究. 中华妇幼临床医学杂志(电子版), 2014, 10(6): 745-747.
9. 陈会, 刘平, 陈嘉蕾, 等. 甲泼尼龙治疗睡眠期癫痫性电持续状态临床观察. 儿科药学杂志, 2017, 28(6): 6-9.
10. 蔡慧强, 张端秀. 甲泼尼龙冲击联合左乙拉西坦治疗儿童睡眠期癫痫性电持续状态的临床研究. 中国实用乡村医生杂志, 2020, 27(6): 28-31.
11. 林芳萍, 孙皎. 激素冲击疗法对癫痫儿童的影响. 现代实用医学, 2017, 29(10): 1373-1375.
12. 张军利, 郭爱萍, 谢冰, 等. 甲泼尼龙冲击治疗睡眠期癫痫性电持续状态患儿临床疗效及对智力水平的影响. 临床心身疾病杂志, 2020, 26(1): 31-33.
13. 浮纪玲. 甲泼尼龙冲击疗法辅助治疗儿童睡眠期癫痫性电持续状态的临床效果. 现代诊断与治疗, 2020, 31(9): 1376-1377.
14. 李彦卿, 王庆, 程成, 等. 甲泼尼龙对睡眠中癫痫性电持续状态患儿脑电图棘慢波指数、Gesell 评分、临床发作次数及 GAL、NPY 表达水平的影响. 临床和实验医学杂志, 2020, 19(5): 519-522.
15. 郭峰. 甲泼尼龙冲击对儿童睡眠中癫痫性电持续状态的治疗效果观察. 继续医学教育, 2016, 30(1): 144-145.
16. 王朋朋, 谢鹤, 吴淑庄, 等. 甲泼尼龙冲击对儿童睡眠中癫痫性电持续状态的治疗效果观察. 临床医学工程, 2015, 22(2): 172-173.
17. Zhang W-N, Zou L-P, Ju J, et al. Therapeutic effects of Ievetiracetam on electrical status epilepticus during sleep in children. Chinese Journal of Contemporary, 2012, 14(5): 340-343.
18. Vrielynck P, Ghariani S, Lienard F, et al. Topiramate in epileptic syndromes of childhood with continuous spike-and-wave during sleep: Retrospective study of 23 cases. Epilepsia, 2014, 55(suppl. 2): 244-246.
19. Inutsuka M, Kobayashi K, Oka M, et al. Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders. Brain and Development, 2006, 28(5): 281-286.
20. Gertsch EA, Chapman KE, Laoprasert P, et al. Safety and efficacy of high-dose diazepam for treatment of electrical status epilepticus during slow wave sleep. Epilepsy Currents, 2013, 13(suppl. 1): 387-388.
21. Klehm J, FernÁndez IS, Peters J, et al. Response of seizures and epileptiform activity to high-dose clobazam treatment. Epilepsy Currents, 2014, 14(suppl. 1): 212.
22. Değerliyurt A, Yalnizoğlu D, Bakar EE, et al. Electrical status epilepticus during sleep: A study of 22 patients. Brain and Development, 2015, 37(2): 250-264.
23. 陈静, 杨志仙, 刘晓燕, 等. 甲泼尼龙冲击治疗对儿童睡眠中癫痫性电持续状态的疗效. 中华儿科杂志, 2014, 52(9): 678-682.
24. Pavlidis E, Møller RS, Nikanorova M, et al. Idiopathic encephalopathy related to status epilepticus during slow sleep (ESES) as a "pure" model of epileptic encephalopathy. An electroclinical, genetic, and follow-up study. Epilepsy and Behavior, 2019, 97: 244-252.
25. Bobbili DR, Lal D, May P, et al. Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy. European journal of human genetics, 2018, 26(2): 258-264.
26. Gencpinar P, Dundar NO, Tekgul H. Electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome in children: An electroclinical evaluation according to the EEG patterns. Epilepsy & Behavior, 2016, 61: 107-111.
27. Meng L-P, Dai Y-Y. A clinical analysis of electrical status epilepticus during sleep in children and a follow-up study of methylprednisolone pulse therapy. Chinese Journal of Contemporary Pediatrics, 2019, 21(4): 348-353.
28. Jovic N, Stevanovic G, Borkovic M, et al. Efficacy and safety of intravenous methylprednisolone pulse therapy in epileptic encephalopathy with electrical status epilepticus during sleep. Epilepsia, 2018, 59(suppl. 3): 111.
29. 张慧敏, 温晓红, 黄金华, 等. 韦氏儿童智力量表第四版在癫痫儿童认知评估中的应用. 中国儿童保健杂志, 2018, 26(10): 1120-1123.
30. Buzatu M, Bulteau C, Altuzarra C, et al. Corticosteroids as treatment of epileptic syndromes with continuous spike-waves during slow-wave sleep. Epilepsia, 2009, 50(suppl. 7): 68-72.
31. Sinclair DB, Snyder TJ. Corticosteroids for the treatment of Landau-Kleffner syndrome and continuous spike-wave discharge during sleep. Pediatric Neurology, 2005, 32(5): 300-306.
32. van den Munckhof B, Alderweireld C, Davelaar S, et al. Treatment of electrical status epilepticus in sleep: Clinical and EEG characteristics and response to 147 treatments in 47 patients. European Journal of Paediatric Neurology, 2018, 22(1): 64-71.
33. Hempel A, Frost M, Agarwal N. Language and behavioral outcomes of treatment with pulse-dose prednisone for electrical status epilepticus in sleep (ESES). Epilepsy & Behavior, 2019, 94: 93-99.
34. Chen J, Yang Z, Liu X, et al. Efficacy of methylprednisolone therapy for electrical status epilepticus during sleep in children. Chinese Journal of Pediatrics, 2014, 52(9): 678-682.
35. Pera MC, Randazzo G, Masnada S, et al. Intravenous methylprednisolone pulse therapy for children with epileptic encephalopathy. Functional Neurology, 2015, 30(3): 173-179.

Journal of Epilepsy

A Meta-analysis of effectiveness and safety of steroids combined with antiepileptic drugs in the treatment of children with epileptic electrical status during sleep

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