|
儿童急性坏死性脑病免疫学治疗进展
|
Abstract:
儿童急性坏死性脑病(ANEC)是一种十分少见的暴发性急性脑病。通常以病毒感染相关的高热症状起病,随后迅速恶化,出现嗜睡、昏迷等进行性意识障碍表现,并伴有抽搐及局灶性神经功能缺损表现。该病起病急、病情重、发展迅速,本病预后极差,死亡率高,目前尚无针对ANEC的特异性治疗方法,通常以免疫治疗和对症支持治疗为主。早期诊断和干预对挽救患儿生命,减少病后后遗症状,提高患儿病后生活质量具有重要价值。本文回顾了近年来ANEC的相关研究进展,并重点对ANEC免疫学治疗主要研究进展进行综述,以期对ANEC的诊疗提供新的思路与方法。
Acute necrotizing encephalopathy of childhood (ANEC) is a rare form of fulminant acute encephalopathy. It usually starts with high fever symptoms related to viral infection, and then rapidly worsens, showing progressive consciousness disorders such as drowsiness and coma, accompanied by seizures and focal neurological deficits. The disease has acute onset, severe disease and rapid development, extremely poor prognosis and high mortality. At present, there is no specific treatment for ANEC, usually immunotherapy and symptomatic supportive therapy. Early diagnosis and intervention are of great value in saving the lives of the sick children, reducing the sequelae after the disease and improving the quality of life. This paper reviews the relevant research progress of ANEC in recent years, and focuses on the progress of ANEC immunology, in order to provide new ideas and methods for the diagnosis and treatment of ANEC.
[1] | Mizuguchi, M., Tomonaga, M., Fukusato, T. and Asano, M. (1989) Acute Necrotizing Encephalopathy with Widespread Edematous Lesions of Symmetrical Distribution. Acta Neuropathologica, 78, 108-111. https://doi.org/10.1007/bf00687411 |
[2] | Mizuguchi, M. (1997) Acute Necrotizing Encephalopathy of Childhood: A Novel Form of Acute Encephalopathy Prevalent in Japan and Taiwan. Brain and Development, 19, 81-92. https://doi.org/10.1016/s0387-7604(96)00063-0 |
[3] | Mizuguchi, M., Abe, J., Mikkaichi, K., Noma, S., Yoshida, K., Yamanaka, T., et al. (1995) Acute Necrotising Encephalopathy of Childhood: A New Syndrome Presenting with Multifocal, Symmetric Brain Lesions. Journal of Neurology, Neurosurgery & Psychiatry, 58, 555-561. https://doi.org/10.1136/jnnp.58.5.555 |
[4] | 王叶青, 李科纯, 杨颖, 等. 儿童急性坏死性脑病预后及影响因素分析[J]. 中华实用儿科临床杂志, 2022, 37(7): 530-533. |
[5] | 张涛, 王丽杰, 许巍, 等. 儿童急性坏死性脑病13例临床特点及预后随访[J]. 中华实用儿科临床杂志, 2022, 37(9): 665-670. |
[6] | Marco, E.J., Anderson, J.E., Neilson, D.E. and Strober, J.B. (2010) Acute Necrotizing Encephalopathy in 3 Brothers. Pediatrics, 125, e693-e698. https://doi.org/10.1542/peds.2009-1984 |
[7] | Kim, J.H., Kim, I., Lim, M.K., Park, M.S., Choi, C.G., Kim, H.W., et al. (2004) Acute Necrotizing Encephalopathy in Korean Infants and Children: Imaging Findings and Diverse Clinical Outcome. Korean Journal of Radiology, 5, 171-177. https://doi.org/10.3348/kjr.2004.5.3.171 |
[8] | Song, Y., Li, S., Xiao, W., Shen, J., Ma, W., Wang, Q., et al. (2020) Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy in Children: A Retrospective Single-Center Study. Medical Science Monitor, 26, e928374. https://doi.org/10.12659/msm.928374 |
[9] | Fernández-Blázquez, A., Castañón-Apilánez, M., Álvarez-Argüelles, M.E., Sabater-Cabrera, C., Rojo-Alba, S., Boga, J.A., et al. (2018) Neuroinvasion of influenza A/H3N2: a fatal case in an immunocompetent adult. Journal of NeuroVirology, 25, 275-279. https://doi.org/10.1007/s13365-018-0690-9 |
[10] | Holla, V.V., Gohel, A.B., Kartik, N. and Netravathi, M. (2021) Acute Necrotizing Encephalopathy as a Complication of Chikungunya Infection. Neurology India, 69, 490-492. https://doi.org/10.4103/0028-3886.314525 |
[11] | Huang, S., Chen, C., Chiu, P., Cheng, M., Lai, P. and Hsieh, K. (2004) Acute Necrotizing Encephalopathy of Childhood Associated with Influenza Type B Virus Infection in a 3-Year-Old Girl. Journal of Child Neurology, 19, 64-67. https://doi.org/10.1177/08830738040190010709 |
[12] | Tabarki, B., Thabet, F., Al Shafi, S., Al Adwani, N., Chehab, M. and Al Shahwan, S. (2013) Acute Necrotizing Encephalopathy Associated with Enterovirus Infection. Brain and Development, 35, 454-457. https://doi.org/10.1016/j.braindev.2012.07.001 |
[13] | Tran, T.D., Kubota, M., Takeshita, K., Yanagisawa, M. and Sakakihara, Y. (2001) Varicella-Associated Acute Necrotizing Encephalopathy with a Good Prognosis. Brain and Development, 23, 54-57. https://doi.org/10.1016/s0387-7604(00)00199-6 |
[14] | Ohsaka, M., Houkin, K., Takigami, M. and Koyanagi, I. (2006) Acute Necrotizing Encephalopathy Associated with Human Herpesvirus-6 Infection. Pediatric Neurology, 34, 160-163. https://doi.org/10.1016/j.pediatrneurol.2005.07.007 |
[15] | Mariotti, P., Iorio, R., Frisullo, G., Plantone, D., Colantonio, R., Tartaglione, T., et al. (2010) Acute Necrotizing Encephalopathy during Novel Influenza a (H1N1) Virus Infection. Annals of Neurology, 68, 111-114. https://doi.org/10.1002/ana.21996 |
[16] | Stevanović, V., Barušić, Z., Višković, K., Rode, O.Đ. and Tešović, G. (2018) Acute Necrotizing Encephalopathy of Childhood Associated with Human Herpes Virus 6 in Croatia. Neurological Sciences, 40, 639-641. https://doi.org/10.1007/s10072-018-3623-8 |
[17] | Virhammar, J., Kumlien, E., Fällmar, D., Frithiof, R., Jackmann, S., Sköld, M.K., et al. (2020) Acute Necrotizing Encephalopathy with SARS-CoV-2 RNA Confirmed in Cerebrospinal Fluid. Neurology, 95, 445-449. https://doi.org/10.1212/wnl.0000000000010250 |
[18] | Wu, X., Wu, W., Pan, W., Wu, L., Liu, K. and Zhang, H. (2015) Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder. Mediators of Inflammation, 2015, Article ID: 792578. https://doi.org/10.1155/2015/792578 |
[19] | Appavu, B., Foldes, S., Fox, J., Shetty, S., Oh, A., Bassal, F., et al. (2021) Treatment Timing, EEG, Neuroimaging, and Outcomes after Acute Necrotizing Encephalopathy in Children. Journal of Child Neurology, 36, 517-524. https://doi.org/10.1177/0883073820984063 |
[20] | Kubo, T., Sato, K., Kobayashi, D., Motegi, A., Kobayashi, O., Takeshita, S., et al. (2006) A Case of HHV-6 Associated Acute Necrotizing Encephalopathy with Increase of Cd56bright NKcells. Scandinavian Journal of Infectious Diseases, 38, 1122-1125. https://doi.org/10.1080/00365540600740520 |
[21] | Mizuguchi, M., Yamanouchi, H., Ichiyama, T. and Shiomi, M. (2007) Acute Encephalopathy Associated with Influenza and Other Viral Infections. Acta Neurologica Scandinavica, 115, 45-56. https://doi.org/10.1111/j.1600-0404.2007.00809.x |
[22] | Aydin, H., Ozgul, E. and Agildere, A.M. (2010) Acute Necrotizing Encephalopathy Secondary to Diphtheria, Tetanus Toxoid and Whole-Cell Pertussis Vaccination: Diffusion-Weighted Imaging and Proton MR Spectroscopy Findings. Pediatric Radiology, 40, 1281-1284. https://doi.org/10.1007/s00247-009-1498-9 |
[23] | Huber, J.N., Berg, A.D. and Bula-Rudas, F. (2020) Acute Necrotizing Encephalopathy due to Streptococcus Pneumoniae: An Uncommon Pathogen in a Devastating Disease. Pediatric Neurology, 108, 126-127. https://doi.org/10.1016/j.pediatrneurol.2020.03.002 |
[24] | Qin, N., Wang, J., Peng, X. and Wang, L. (2023) Pathogenesis and Management of Acute Necrotizing Encephalopathy. Expert Review of Neurotherapeutics, 23, 641-650. https://doi.org/10.1080/14737175.2023.2224503 |
[25] | Pongpitakmetha, T., Hemachudha, P., Rattanawong, W., Thanapornsangsuth, P., Viswanathan, A. and Hemachudha, T. (2022) COVID-19 Related Acute Necrotizing Encephalopathy with Extremely High Interleukin-6 and RANBP2 Mutation in a Patient with Recently Immunized Inactivated Virus Vaccine and No Pulmonary Involvement. BMC Infectious Diseases, 22, Article No. 640. https://doi.org/10.1186/s12879-022-07610-0 |
[26] | Fan, X., Huang, L., Li, S., Yang, S., Song, Y., Chen, Q., et al. (2022) Clinical Evaluation of Acute Necrotizing Encephalopathy in Children. Frontiers in Pediatrics, 10, Article 947693. https://doi.org/10.3389/fped.2022.947693 |
[27] | Neilson, D.E., Adams, M.D., Orr, C.M., et al. (2009) Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2. American Journal of Human Genetics, 84, 44-51. |
[28] | Chen, Y., Mizuguchi, H., Yao, D., Ide, M., Kuroda, Y., Shigematsu, Y., et al. (2005) Thermolabile Phenotype of Carnitine Palmitoyltransferase II Variations as a Predisposing Factor for Influenza‐Associated Encephalopathy. FEBS Letters, 579, 2040-2044. https://doi.org/10.1016/j.febslet.2005.02.050 |
[29] | Hashizume, C., Kobayashi, A. and Wong, R.W. (2013) Down-Modulation of Nucleoporin RanBP2/Nup358 Impaired Chromosomal Alignment and Induced Mitotic Catastrophe. Cell Death & Disease, 4, e854-e854. https://doi.org/10.1038/cddis.2013.370 |
[30] | Neilson, D.E., Eiben, R.M., Waniewski, S., Hoppel, C.L., Varnes, M.E., Bangert, B.A., et al. (2003) Autosomal Dominant Acute Necrotizing Encephalopathy. Neurology, 61, 226-230. https://doi.org/10.1212/01.wnl.0000073544.28775.1a |
[31] | Neilson, D.E., Feiler, H.S., Wilhelmsen, K.C., Lynn, A., Eiben, R.M., Kerr, D.S., et al. (2004) Autosomal Dominant Acute Necrotizing Encephalopathy Maps to 2q12.1‐2q13. Annals of Neurology, 55, 291-294. https://doi.org/10.1002/ana.10849 |
[32] | 吴连洪, 胡越. RANBP2基因相关家族性急性坏死性脑病一家系报道及文献复习[J]. 重庆医科大学学报, 2021, 46(9): 1116-1120. |
[33] | Lee, Y., Hwang, S. and Kwon, S. (2019) Acute Necrotizing Encephalopathy in Children: A Long Way to Go. Journal of Korean Medical Science, 34, e143. https://doi.org/10.3346/jkms.2019.34.e143 |
[34] | Shukla, P., Mandalla, A., Elrick, M.J. and Venkatesan, A. (2022) Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface between Systemic Infection and Neurologic Injury. Frontiers in Neurology, 12, Article 628811. https://doi.org/10.3389/fneur.2021.628811 |
[35] | Aiba, H., Mochizuki, M., Kimura, M. and Hojo, H. (2001) Predictive Value of Serum Interleukin-6 Level in Influenza Virus-Associated Encephalopathy. Neurology, 57, 295-299. https://doi.org/10.1212/wnl.57.2.295 |
[36] | Kansagra, S.M. and Gallentine, W.B. (2011) Cytokine Storm of Acute Necrotizing Encephalopathy. Pediatric Neurology, 45, 400-402. https://doi.org/10.1016/j.pediatrneurol.2011.09.007 |
[37] | Lin, Y., Lee, K., Ro, L., Lo, Y., Huang, C. and Chang, K. (2019) Clinical and Cytokine Profile of Adult Acute Necrotizing Encephalopathy. Biomedical Journal, 42, 178-186. https://doi.org/10.1016/j.bj.2019.01.008 |
[38] | Ma, T. and Zhu, X. (2011) Neurotoxic Effects of Lnterleukin-6 and Sodium Nitroprusside on Cultured Rat Hippocampal Neurons. Arzneimittelforschung, 50, 512-514. https://doi.org/10.1055/s-0031-1300239 |
[39] | Yoshida, T., Tamura, T., Nagai, Y., Ueda, H., Awaya, T., Shibata, M., et al. (2013) MRI Gadolinium Enhancement Precedes Neuroradiological Findings in Acute Necrotizing Encephalopathy. Brain and Development, 35, 921-924. https://doi.org/10.1016/j.braindev.2012.11.011 |
[40] | Gika, A.D., Rich, P., Gupta, S., Neilson, D.E. and Clarke, A. (2009) Recurrent Acute Necrotizing Encephalopathy Following Influenza a in a Genetically Predisposed Family. Developmental Medicine & Child Neurology, 52, 99-102. https://doi.org/10.1111/j.1469-8749.2009.03405.x |
[41] | Okumura, A., Abe, S., Kidokoro, H. and Mizuguchi, M. (2009) Acute Necrotizing Encephalopathy: A Comparison between Influenza and Non‐influenza Cases. Microbiology and Immunology, 53, 277-280. https://doi.org/10.1111/j.1348-0421.2009.00124.x |
[42] | Shirai, T., Fujii, H., Ono, M., Watanabe, R., Shirota, Y., Saito, S., et al. (2013) A Novel Autoantibody against Ephrin Type B Receptor 2 in Acute Necrotizing Encephalopathy. Journal of Neuroinflammation, 10, Article No. 893. https://doi.org/10.1186/1742-2094-10-128 |
[43] | Okumura, A., Mizuguchi, M., Kidokoro, H., Tanaka, M., Abe, S., Hosoya, M., et al. (2009) Outcome of Acute Necrotizing Encephalopathy in Relation to Treatment with Corticosteroids and Gammaglobulin. Brain and Development, 31, 221-227. https://doi.org/10.1016/j.braindev.2008.03.005 |
[44] | Jiang, J., Wang, Y.E., Palazzo, A.F. and Shen, Q. (2022) Roles of Nucleoporin RanBP2/Nup358 in Acute Necrotizing Encephalopathy Type 1 (ANE1) and Viral Infection. International Journal of Molecular Sciences, 23, Article 3548. https://doi.org/10.3390/ijms23073548 |
[45] | Sazgar, M., Robinson, J.L., Chan, A.K.J. and Sinclair, D.B. (2003) Influenza B Acute Necrotizing Encephalopathy: A Case Report and Literature Review. Pediatric Neurology, 28, 396-399. https://doi.org/10.1016/s0887-8994(03)00008-0 |
[46] | Akiyoshi, K., Hamada, Y., Yamada, H., Kojo, M. and Izumi, T. (2006) Acute Necrotizing Encephalopathy Associated with Hemophagocytic Syndrome. Pediatric Neurology, 34, 315-318. https://doi.org/10.1016/j.pediatrneurol.2005.08.030 |
[47] | Cain, D.W. and Cidlowski, J.A. (2017) Immune Regulation by Glucocorticoids. Nature Reviews Immunology, 17, 233-247. https://doi.org/10.1038/nri.2017.1 |
[48] | Kim, Y. and You, S.J. (2012) A Case of Acute Necrotizing Encephalopathy Associated with Parainfluenza Virus Infection. Korean Journal of Pediatrics, 55, 147-150. https://doi.org/10.3345/kjp.2012.55.4.147 |
[49] | Chang, H., Hsia, S., Lin, J., Chan, O., Chiu, C. and Lee, E. (2022) Early High-Dose Methylprednisolone Therapy Is Associated with Better Outcomes in Children with Acute Necrotizing Encephalopathy. Children, 9, Article 136. https://doi.org/10.3390/children9020136 |
[50] | Lee, V.W.M., Khoo, T.B., Teh, C.M., Heng, H.S., Li, L., Yusof, Y.L.M., et al. (2023) Factors Associated with Outcomes of Severe Acute Necrotizing Encephalopathy: A Multicentre Experience in Malaysia. Developmental Medicine & Child Neurology, 65, 1256-1263. https://doi.org/10.1111/dmcn.15536 |
[51] | Geng, C., Zhao, W., Wang, Z., Wu, J., Jiang, D., Jiang, N., et al. (2023) Acute Necrotizing Encephalopathy Associated with COVID-19: Case Series and Systematic Review. Journal of Neurology, 270, 5171-5181. https://doi.org/10.1007/s00415-023-11915-8 |
[52] | Bigi, S., Banwell, B. and Yeh, E.A. (2014) Outcomes after Early Administration of Plasma Exchange in Pediatric Central Nervous System Inflammatory Demyelination. Journal of Child Neurology, 30, 874-880. https://doi.org/10.1177/0883073814545883 |
[53] | 倪婧雯, 李树军, 方柯南. 儿童急性坏死性脑病研究进展[J]. 临床荟萃, 2020, 35(11): 1045-1048. |
[54] | Okajima, K., Hayakawa, I., Tsuboi, N., Shimura, K., Ishiguro, A. and Abe, Y. (2022) Early Therapeutic Plasma Exchange May Lead to Complete Neurological Recovery in Moderate to Severe Influenza-Associated Acute Necrotizing Encephalopathy. Brain and Development, 44, 492-497. https://doi.org/10.1016/j.braindev.2022.03.004 |
[55] | Li, K., Zhang, T., Liu, G., Jin, P., Wang, Y., Wang, L., et al. (2021) Plasma Exchange Therapy for Acute Necrotizing Encephalopathy of Childhood. Pediatric Investigation, 5, 99-105. https://doi.org/10.1002/ped4.12280 |
[56] | Huang, R.Z., Zhang Y.J., Wang, J.L., Su, Y.M. and Ren, Z.X. (2022) Favorable Outcome with Early and Repeated Continuous Renal Replacement Therapy in Acute Necrotizing Encephalopathy. Indian Journal of Pediatrics, 89, 412-412. https://doi.org/10.1007/s12098-021-04012-z |
[57] | Park, J.T., Lee, H., Kee, Y.K., et al. (2016) High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial. American Journal of Kidney Diseases, 68, 599-608. |
[58] | Zhang, R., Zhao, X., Li, W. and Gao, Y. (2024) Refractory Anti-N-Methyl-D-Aspartate Receptor Autoimmune Encephalitis Induced by Ovarian Teratoma: A Case Report. Clinical Neuropharmacology, 47, 62-64. https://doi.org/10.1097/wnf.0000000000000581 |
[59] | 周益平, 陈伟明, 朱晓东, 等. 托珠单抗辅助治疗儿童危重型急性坏死性脑病的初步观察[J]. 中华儿科杂志, 2024, 62(8): 764-769. |
[60] | Hosie, P.H., Lim, C., Scott, T.R.D., Cardamone, M., Farrar, M.A., Frith, C., et al. (2023) Treatment of Severe Acute Necrotizing Encephalopathy of Childhood with Interleukin-6 Receptor Blockade in the First 24 H as Add-On Immunotherapy Shows Favorable Long-Term Outcome at 2 Years. Brain and Development, 45, 401-407. https://doi.org/10.1016/j.braindev.2023.03.002 |
[61] | Koh, J.C., Murugasu, A., Krishnappa, J. and Thomas, T. (2019) Favorable Outcomes with Early Interleukin 6 Receptor Blockade in Severe Acute Necrotizing Encephalopathy of Childhood. Pediatric Neurology, 98, 80-84. https://doi.org/10.1016/j.pediatrneurol.2019.04.009 |
[62] | Yokota,, S., Imagawa,, T., Miyamae,, T., Ito,, S., Nakajima,, S., Nezu, A., et al. (2000) Hypothetical Pathophysiology of Acute Encephalopathy and Encephalitis Related to Influenza Virus Infection and Hypothermia Therapy. Pediatrics International, 42, 197-203. https://doi.org/10.1046/j.1442-200x.2000.01204.x |
[63] | Kumakura, A., Iida, C., Saito, M., Mizuguchi, M. and Hata, D. (2011) Pandemic Influenza A-Associated Acute Necrotizing Encephalopathy without Neurologic Sequelae. Pediatric Neurology, 45, 344-346. https://doi.org/10.1016/j.pediatrneurol.2011.08.004 |
[64] | Kobayashi, Y., Kanazawa, H., Hoshino, A., Takamatsu, R., Watanabe, R., Hoshi, K., et al. (2019) Acute Necrotizing Encephalopathy and a Carnitine Palmitoyltransferase 2 Variant in an Adult. Journal of Clinical Neuroscience, 61, 264-266. https://doi.org/10.1016/j.jocn.2018.11.045 |
[65] | Sell, K., Storch, K., Hahn, G., Lee-Kirsch, M.A., Ramantani, G., Jackson, S., et al. (2016) Variable Clinical Course in Acute Necrotizing Encephalopathy and Identification of a Novel RANBP2 Mutation. Brain and Development, 38, 777-780. https://doi.org/10.1016/j.braindev.2016.02.007 |
[66] | Yao, M., Cai, M., Yao, D., Xu, X., Yang, R., Li, Y., et al. (2015) Abbreviated Half-Lives and Impaired Fuel Utilization in Carnitine Palmitoyltransferase II Variant Fibroblasts. PLOS ONE, 10, e0119936. https://doi.org/10.1371/journal.pone.0119936 |
[67] | 罗泽民, 李久伟, 刘星宇, 等. RANBP2基因突变致家族性急性坏死性脑病患儿的诊治并文献复习[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(4): 398-408. |
[68] | Osterholm, M.T., Kelley, N.S., Sommer, A. and Belongia, E.A. (2012) Efficacy and Effectiveness of Influenza Vaccines: A Systematic Review and Meta-analysis. The Lancet Infectious Diseases, 12, 36-44. https://doi.org/10.1016/s1473-3099(11)70295-x |
[69] | Hannoun, C., Megas, F. and Piercy, J. (2004) Immunogenicity and Protective Efficacy of Influenza Vaccination. Virus Research, 103, 133-138. https://doi.org/10.1016/j.virusres.2004.02.025 |
[70] | Muthuri, S.G., Venkatesan, S., Myles, P.R., et al. (2014) Effectiveness of Neuraminidase Inhibitors in Reducing Mortality in Patients Admitted to Hospital with Influenza A H1N1pdm09 virus Infection: A Meta-Analysis of Individual Participant Data. The Lancet Respiratory Medicine, 2, 395-404. |