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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (5): 948-953. doi: 10.19723/j.issn.1671-167X.2022.05.023

• 论著 • 上一篇    下一篇

儿童急性淋巴细胞白血病合并癫痫发作75例临床特征和预后分析

刘京1,陆爱东1,左英熹1,吴珺1,2,黄志卓1,贾月萍1,丁明明1,张乐萍1,秦炯1,*()   

  1. 1. 北京大学人民医院儿科, 北京 100044
    2. 北京大学首钢医院儿科, 北京 100144
  • 收稿日期:2022-07-11 出版日期:2022-10-18 发布日期:2022-10-14
  • 通讯作者: 秦炯 E-mail:qinjiong@pku.edu.cn
  • 作者简介:秦炯，医学博士，主任医师，教授，博士生导师，北京大学人民医院儿科主任，一直在北京大学从事儿科学、儿科神经病学、癫痫病学及发育行为儿科学的临床诊疗、教学及研究工作，曾任北京大学第一医院儿科主任。系统开展了小儿惊厥性脑损伤和癫痫的发生机制与干预研究，主持完成科技部支撑计划课题、卫生部临床学科重点项目、国家自然科学基金、北京市自然科学基金、北京市卫生健康委员会临床重点专科项目等。近5年来以责任作者或第一作者在国内外杂志发表论文60余篇，其中SCI论文20余篇。以第一完成人获省部级科技进步奖3项。历任中华医学会儿科学分会副主任委员、神经学组组长及名誉组长、全科医学学组副组长，中国抗癫痫协会常务理事、副会长兼秘书长及结节性硬化专业委员会主任委员，中国医师协会神经调控专业委员会副主任委员及儿科医师分会常务委员、委员，北京医师协会儿内科专科医师分会副会长，北京抗癫痫协会会长及名誉会长，北京医学会儿科学分会常务委员及发育行为儿科学组组长，亚洲大洋洲儿童神经病学协会中国代表等，任多家专业杂志编委、副主编。从事儿童神经病学及癫痫病学临床与研究30余年，在遗传学神经系统疾病、癫痫病及相关发育行为障碍的临床诊疗方面积累了丰富经验，先后主持制定完成相关疾病诊疗指南或专家共识10项
  • 基金资助:
    北京市临床重点专科项目(京卫医(2018)204号)

Clinical characteristics and prognosis of seizures in 75 children with acute lymphoblastic leukemia

Jing LIU1,Ai-dong LU1,Ying-xi ZUO1,Jun WU1,2,Zhi-zhuo HUANG1,Yue-ping JIA1,Ming-ming DING1,Le-ping ZHANG1,Jiong QIN1,*()   

  1. 1. Department of Pediatrics, Peking University People's Hospital, Beijing 100044, China
    2. Department of Pediatrics, Peking University Shougang Hospital, Beijing 100144, China
  • Received:2022-07-11 Online:2022-10-18 Published:2022-10-14
  • Contact: Jiong QIN E-mail:qinjiong@pku.edu.cn
  • Supported by:
    the Beijing Key Clinical Specialty Construction Project-Pediatrics(京卫医(2018)204号)

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摘要：

目的: 探讨急性淋巴细胞白血病患儿化疗过程中出现癫痫发作的临床特点、治疗和预后。方法: 回顾性分析2010年1月至2022年3月北京大学人民医院儿科收治的化疗过程中合并癫痫发作的急性淋巴细胞白血病患儿, 总结癫痫发作的发病率、发病时间、病因、治疗和预后。结果: 研究期间共收治急性淋巴细胞白血病患儿932例, 其中75例(8%)在化疗过程中合并癫痫发作症状, 男40例, 女35例, 中位年龄7.5岁(1~17岁)。43例(57.3%)患儿的癫痫发作发生在开始化疗的前2个月内, 直接原因分别为可逆性后部脑病综合征(15例)、脑出血(10例, 其中1例合并静脉窦血栓形成)、鞘内注射或全身应用氨甲蝶呤(11例)、脑脓肿(真菌性3例, 细菌性4例)、病毒性脑炎(2例)、热性惊厥(7例)、低钠血症(7例)、低钙血症(2例); 14例患儿的癫痫发作病因不明。64例患儿在癫痫发作后行头颅影像学检查, 其中37例(57.8%)异常; 44例行脑电图检查, 其中24例(54.4%)异常。55例患儿经规律化疗后骨髓持续缓解, 8例行造血干细胞移植, 9例死亡, 3例失访。18例(24%)患儿诊断为症状性癫痫, 多数予抗癫痫发作药物控制良好, 2例为药物难治性癫痫。结论: 癫痫发作在急性淋巴细胞白血病患儿中不少见, 最常见的病因为可逆性后部脑病综合征、氨甲蝶呤相关性神经毒性、脑出血。癫痫发作大多发生在化疗开始的2个月内; 在首次癫痫发作后, 应尽快完善神经影像学和脑电图检查以协助明确病因及指导治疗; 部分病例可发展为症状性癫痫, 大多数预后良好, 个别为药物难治性癫痫。

关键词: 癫痫发作, 急性淋巴细胞白血病, 儿童, 抗肿瘤联合化疗方案

Abstract:

Objective: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. Methods: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. Results: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. Conclusion: Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.

Key words: Seizures, Acute lymphoblastic leukemia, Child, Antineoplastic combined chemotherapy protocols

中图分类号: 

  • R733.71

图1

脑电图显示睡眠期左侧枕区频繁中-高波幅棘波、棘慢波发放(9岁男性患儿，诊断为急性淋巴细胞白血病，可逆性后部脑病综合征)"

1 Millan NC , Pastrana A , Guitter MR , et al. Acute and sub-acute neurological toxicity in children treated for acute lymphoblastic leukemia[J]. Leuk Res, 2018, 65, 86- 93.
doi: 10.1016/j.leukres.2017.12.010
2 Fasano RE , Bergen DC . Intractable epilepsy in patients treated for childhood acute lymphocytic leukemia[J]. Seizure, 2009, 18 (4): 298- 230.
doi: 10.1016/j.seizure.2008.10.008
3 Nassar SL , Conklin HM , Zhou Y , et al. Neurocognitive outcomes among children who experienced seizures during treatment for acute lymphoblastic leukemia[J]. Pediatr Blood Cancer, 2017, 64 (8): e26436.
doi: 10.1002/pbc.26436
4 Ghanem KM , Dhayni RM , Al-Aridi C , et al. Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management[J]. Pediatr Blood Cancer, 2017, 64 (12): e26694.
doi: 10.1002/pbc.26694
5 Khan RB , Sadighi ZS , Zabrowski J , et al. Imaging patterns and outcome of posterior reversible encephalopathy syndrome during childhood cancer treatment[J]. Pediatr Blood Cancer, 2016, 63 (3): 523- 526.
doi: 10.1002/pbc.25790
6 Baytan B , Evim MS , Güler S , et al. Acute central nervous system complications in pediatric acute lymphoblastic leukemia[J]. Pediatr Neurol, 2015, 53 (4): 312- 318.
doi: 10.1016/j.pediatrneurol.2015.03.006
7 Seetharam S , Thankamony P , Gopakumar KG , et al. Higher incidence of syndrome of inappropriate antidiuretic hormone secretion during induction chemotherapy of acute lymphoblastic leukemia in Indian children[J]. Indian J Cancer, 2019, 56 (4): 320- 324.
doi: 10.4103/ijc.IJC_737_18
8 张之南, 沈悌. 血液病诊断及疗效标准[M]. 3版 北京: 科学出版社, 2008: 119- 120.
9 薛玉娟, 吴珺, 左英熹, 等. 儿童Ph染色体阳性急性淋巴细胞白血病的预后因素分析[J]. 中华血液学杂志, 2018, 39 (3): 219- 224.
10 Fisher RS , van Emde Boas W , Blume W , et al. Epileptic seizures and epilepsy: Definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)[J]. Epilepsia, 2005, 46 (4): 470- 472.
doi: 10.1111/j.0013-9580.2005.66104.x
11 Fisher RS , Acevedo C , Arzimanoglou A , et al. ILAE official report: A practical clinical definition of epilepsy[J]. Epilepsia, 2014, 55 (4): 475- 482.
doi: 10.1111/epi.12550
12 Phillips NS , Khan RB , Li C , et al. Seizures' impact on cognition and quality of life in childhood cancer survivors[J]. Cancer, 2022, 128 (1): 180- 191.
doi: 10.1002/cncr.33879
13 Anastasopoulou S , Heyman M , Eriksson M , et al. Seizures during treatment of childhood acute lymphoblastic leukemia: A population-based cohort study[J]. Eur J Paediatr Neuro, 2020, 27, 72- 77.
doi: 10.1016/j.ejpn.2020.04.004
14 徐敏, 周文杰, 汤继宏, 等. 儿童急性淋巴细胞白血病伴癫痫发作51例临床分析[J]. 临床儿科杂志, 2022, 40 (2): 118- 122.
15 González-Otárula KA , álvarez BM , Dubeau F . Drug-resistant epilepsy after treatment for childhood acute lymphocytic leukaemia: From focal epilepsy to Lennox-Gastaut syndrome[J]. Epileptic Disord, 2016, 18 (4): 447- 453.
doi: 10.1684/epd.2016.0879
16 Khan RB , Morris EB , Pui CH , et al. Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies[J]. J Child Neurol, 2014, 29 (6): 774- 781.
doi: 10.1177/0883073813488675
17 Antunes NL . Seizures in children with systemic cancer[J]. Pe-diatr Neurol, 2003, 28 (3): 190- 193.
doi: 10.1016/S0887-8994(02)00508-8
18 Banerjee JS , Heyman M , Palomäki M , et al. Posterior reversible encephalopathy syndrome: Risk factors and impact on the outcome in children with acute lymphoblastic leukemia treated with Nordic protocols[J]. J Pediatr Hematol Oncol, 2018, 40 (1): e13- e18.
doi: 10.1097/MPH.0000000000001009
19 Grioni D , Pavan F , Prunotto G , et al. Should posterior reversible encephalopathy syndrome be mainly considered an epileptic disorder? Results of a sequential neurophysiological study in a pediatric cohort[J]. Neuropediatrics, 2017, 48 (2): 72- 78.
doi: 10.1055/s-0037-1598251
20 Fugate JE , Rabinstein AA . Posterior reversible encephalopathy syndrome: Clinical and radiological manifestations, pathophysiology, and outstanding questions[J]. Lancet Neurol, 2015, 14 (9): 914- 925.
doi: 10.1016/S1474-4422(15)00111-8
21 Watanabe K , Arakawa Y , Oguma E , et al. Characteristics of methotrexate-induced stroke-like neurotoxicity[J]. Int J Hematol, 2018, 108 (6): 630- 636.
doi: 10.1007/s12185-018-2525-0
22 Bhojwani D , Sabin ND , Pei D , et al. Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia[J]. J Clin Oncol, 2014, 32 (9): 949- 959.
doi: 10.1200/JCO.2013.53.0808
23 Ranta S , Tuckuviene R , Mäkipernaa A , et al. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia: A multicentre study from the Nordic Society of Paediatric Haematology and Oncology[J]. Br J Haematol, 2015, 168 (4): 547- 552.
doi: 10.1111/bjh.13162
24 Nowak-Göttl U , Kenet G , Mitchell LG , et al. Thrombosis in childhood acute lymphoblastic leukaemia: Epidemiology, aetiology, diagnosis, prevention and treatment[J]. Best Pract Res Clin Haematol, 2009, 22 (1): 103- 114.
doi: 10.1016/j.beha.2009.01.003
25 林舒鹏, 宋华, 沈和萍, 等. 急性淋巴细胞白血病患儿中可逆性脑病临床总结[J]. 临床儿科杂志, 2019, 37 (5): 326- 330.
doi: 10.3969/j.issn.1000-3606.2019.05.002
26 Beghi E , de Maria G , Gobbi G , et al. Diagnosis and treatment of the first epileptic seizure: Guidelines of the Italian League Against Epilepsy[J]. Epilepsia, 2006, 47 (Suppl 5): 2- 8.
27 Rahiman EA , Rajendran A , Sankhyan N , et al. Acute neurological complications during acute lymphoblastic leukemia therapy: A single-center experience over 10 years[J]. Indian J Cancer, 2021, 58 (4): 545- 552.
28 Banerjee J , Niinimäki R , Lähteenmäki P , et al. The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia[J]. Pediatr Blood Cancer, 2020, 67 (2): e27999.
29 Maytal J , Grossman R , Yusuf FH , et al. Prognosis and treatment of seizures in children with acute lymphoblastic leukemia[J]. Epilepsia, 1995, 36 (8): 831- 836.
doi: 10.1111/j.1528-1157.1995.tb01622.x
30 中国抗癫痫协会. 临床诊疗指南: 癫痫病分册(2015修订版)[M]. 北京: 人民卫生出版社, 2015.
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ISSN 1671-167X
CN 11-4691/R
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