Journal of Clinical Pediatrics >
Tocilizumab treatment for febrile infection-related epilepsy syndrome in children: 2 cases report and literature review
Received date: 2024-04-30
Accepted date: 2024-08-12
Online published: 2025-06-27
Objective To report the use of tocilizumab in 2 cases of children with febrile infection-ralated epilepsy syndrome (FIRES), and provide a reference for its therapeutic application. Methods A retrospective analysis was conducted on the clinical manifestations, diagnostic and treatment processes, and therapeutic responses to tocilizumab in two FIRES patients admitted to the pediatric intensive care unit of our hospital in 2023, and the relevant literatures were reviewed. Results Neither patient responded to multiple antiepileptic drugs, anesthetics, ketogenic diet therapy, or first-line immunotherapy (high-dose methylprednisolone and high-dose intravenous immunoglobulin). Following second-line immunotherapy with tocilizumab, epileptic seizures were effectively controlled without adverse reactions. After 4-6 months of follow-up, one patient experienced recurrence of epileptic seizures. Conclusions Tocilizumab demonstrates efficacy as a second-line immunotherapy for FIRES, with good tolerability, and represents a promising treatment option.
Key words： febrile infection-ralated epilepsy syndrome; tocilizumab; cytokine; child
LI Fan , HUANG Xianjie , FAN Yazhen , ZHAO Jianchuang , CUI Chenhang , GUO Qiliang , QIAO Junying . Tocilizumab treatment for febrile infection-related epilepsy syndrome in children: 2 cases report and literature review[J]. Journal of Clinical Pediatrics, 2025 , 43(7) : 532 -538 . DOI: 10.12372/jcp.2025.24e0426
| [1] | Payne ET, Koh S, Wirrell EC. Extinguishing febrile infection-related epilepsy syndrome: pipe dream or reality?[J]. Semin Neurol, 2020, 40(2): 263-272. |
| [2] | Van Baalen A, Vezzani A, H?usler M, et al. Febrile infection-related epilepsy syndrome: clinical review and hypotheses of epileptogenesis[J]. Neuropediatrics, 2017, 48(1): 5-18. |
| [3] | Wickstr?m R, Taraschenko O, Dilena R, et al. International consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection‐related epilepsy syndrome (FIRES): summary and clinical tools[J]. Epilepsia, 2022, 63(11):2827-2839. |
| [4] | Wickstrom R, Taraschenko O, Dilena R, et al. International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) incl. Febrile Infection-Related Epilepsy Syndrome (FIRES): statements and supporting evidence[J]. Epilepsia, 2022, 63(11): 2840-2864. |
| [5] | Lee GH, Kim J, Kim HW, et al. Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients[J]. Clin Neurol Neurosurg, 2021, 202: 106507. |
| [6] | 中华医学会神经病学分会感染性疾病与脑脊液细胞学学组. 中枢神经系统感染性疾病的脑脊液宏基因组学第二代测序应用专家共识[J]. 中华神经科杂志, 2021, 54(12): 1234-1240. |
| Chinese Society of Infectious Diseases and Cerebrospinal Fluid Cytology. Expert consensus on clinical application of metagenomic nextgeneration sequencing of cerebrospinal fluid in the diagnosis of infectious diseases of the central nervous system[J]. Zhonghua Shenjingke Zazhi, 2021, 54(12): 1234-1240. | |
| [7] | 王营, 马燕丽, 王媛, 等. 托珠单抗成功治疗儿童发热感染相关癫痫综合征1例及文献复习[J]. 中华神经科杂志, 2022, 55(11): 1277-1285. |
| Wang Y, Ma YL, Wang Y, et al. A case of febrile infectionrelated epilepsy syndrome in children successfully treated with tocilizumab and literature review[J]. Zhonghua Shenjingke Zazhi, 2022, 55(11): 1277-1285. | |
| [8] | Hirsch LJ, Gaspard N, Van Baalen A, et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions[J]. Epilepsia, 2018, 59(4): 739-744. |
| [9] | Mantoan Ritter L, Nashef L. New-onset refractory status epilepticus (NORSE)[J]. Pract Neurol, 2021: practneurol-2020-002534. |
| [10] | Van Baalen A. Febrile infection-related epilepsy syndrome in childhood: A clinical review and practical approach[J]. Seizure, 2023, 111: 215-222. |
| [11] | Hanin A, Cespedes J, Dorgham K, et al. Cytokines in new-onset refractory status epilepticus predict outcomes[J]. Ann Neurol, 2023, 94(1): 75-90. |
| [12] | Sakuma H, Horino A, Kuki I. Neurocritical care and target immunotherapy for febrile infection-related epilepsy syndrome[J]. Biomed J, 2020, 43(3): 205-210. |
| [13] | Sheppard M, Laskou F, Stapleton PP, et al. Tocilizumab (Actemra)[J]. Hum Vaccin Immunother, 2017, 13(9): 1972-1988. |
| [14] | Cantarín-Extremera V, Jiménez-Legido M, Duat-Rodríguez A, et al. Tocilizumab in pediatric refractory status epilepticus and acute epilepsy: Experience in two patients[J]. J Neuroimmunol, 2020, 340: 577142. |
| [15] | Nishimoto N, Terao K, Mima T, et al. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease[J]. Blood, 2008, 112(10): 3959-3964. |
| [16] | Aledo-Serrano A, Hariramani R, Gonzalez-Martinez A, et al. Anakinra and tocilizumab in the chronic phase of febrile infection-related epilepsy syndrome (FIRES): effectiveness and safety from a case-series[J]. Seizure, 2022, 100: 51-55. |
| [17] | Chee YC, Lim CH, Abdul Halim S, et al. Extinguishing FIRES using tocilizumab[J]. Neurology and Clinical Neuroscience, 2020, 8(4): 192-195. |
| [18] | Stredny CM, Case S, Sansevere AJ, et al. Interleukin-6 blockade with tocilizumab in anakinra-refractory febrile infection-related epilepsy syndrome (FIRES)[J]. Child Neurol Open, 2020, 7: 2329048x20979253. |
| [19] | Kurimoto T, Matsuoka T, Ami Y, et al. Anti-inflammatory and immune-mediated therapy for a case of febrile infection-related epilepsy syndrome with rapid recurrence[J]. Clin Case Rep, 2022, 10(6): e5952. |
| [20] | Goh Y, Tay SH, Yeo LLL, et al. Bridging the gap: tailoring an approach to treatment in febrile infection-related epilepsy syndrome[J]. Neurology, 2023, 100(24): 1151-1155. |
| [21] | Girardin ML, Flamand T, Roignot O, et al. Treatment of new onset refractory status epilepticus/febrile infection-related epilepsy syndrome with tocilizumab in a child and a young adult[J]. Epilepsia, 2023, 64(6): e87-e92. |
/
| 〈 |
|
〉 |
