收稿日期: 2022-07-11
网络出版日期: 2022-10-14
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
Received date: 2022-07-11
Online published: 2022-10-14
Supported by
the Beijing Key Clinical Specialty Construction Project-Pediatrics(京卫医(2018)204号)
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。
刘京 , 陆爱东 , 左英熹 , 吴珺 , 黄志卓 , 贾月萍 , 丁明明 , 张乐萍 , 秦炯 . 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[J]. 北京大学学报(医学版), 2022 , 54(5) : 948 -953 . DOI: 10.19723/j.issn.1671-167X.2022.05.023
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.
| 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. |
| 2 | Fasano RE , Bergen DC . Intractable epilepsy in patients treated for childhood acute lymphocytic leukemia[J]. Seizure, 2009, 18 (4): 298- 230. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 17 | Antunes NL . Seizures in children with systemic cancer[J]. Pe-diatr Neurol, 2003, 28 (3): 190- 193. |
| 18 | Banerjee JS , Heyman M , Palom?ki 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 23 | Ranta S , Tuckuviene R , M?kipernaa 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. |
| 24 | Nowak-G?ttl 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. |
| 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. |
| 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 , Niinim?ki R , L?hteenm?ki 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. |
| 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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