Cytokines and neuron-specific proteins in pediatric viral encephalitis and convulsive syndrome. I. Viral encephalitis

Cover Page


Cite item

Full Text

Abstract

Convulsive syndrome in children is manifested in the three forms: febrile convulsions in acute infections, symptomatic convulsions during acute neuroinfection, as well as onset of epilepsy requiring careful differentiation to prescribe adequate therapy. A threat of convulsive syndrome spreads beyond complications related to ongoing infection, because its development is associated with the risk of emerging symptomatic epilepsy in the future. Postencephalitic epilepsy developing in children within the first years after viral encephalitis has been specifically highlighted. A necessity to identify groups at risk of developing epilepsy gave a momentum to seek out for biomarkers of epileptogenesis reflecting the features of systemic and local inflammatory process in the central nervous system during the immune response to infection. Cytokines mainly mediating inflammation are currently examined being studied as candidate biomarkers of the risk of epilepsy. On the other hand, neuron-specific proteins known as inflammation biomarkers identified in various diseases of the central nervous system are being investigated to reveal brain cell injury in neuroinfections and epilepsy. Here we review publications assessing a potential to use inflammation biomarkers (cytokines and neuron-specific proteins) to diagnose and monitor pediatric neurological diseases associated with convulsive syndrome. The first part of the review describes the results of determining the inflammation biomarkers in the blood and cerebrospinal fluid during acute viral encephalitis/encephalopathy associated with various neurotropic viruses (herpes viruses, flaviviruses, enteroviruses). A significance of diverse biomarkers in predicting an outcome and long-term disease consequences are discussed.

About the authors

L. A. Alekseeva

Pediatric Research and Clinical Center for Infectious Diseases

Email: kldidi@mail.ru
St. Petersburg Россия

G. F. Zheleznikova

Pediatric Research and Clinical Center for Infectious Diseases

Author for correspondence.
Email: zheleznikova.galina@gmail.com
St. Petersburg Россия

E. Y. Gorelik

Pediatric Research and Clinical Center for Infectious Diseases

Email: e.gorelik@mail.ru
ORCID iD: 0000-0002-3130-1717
St. Petersburg Россия

N. V. Skripchenko

Pediatric Research and Clinical Center for Infectious Diseases; St. Petersburg State Pediatric Medical University

Email: snv@niidi.ru
ORCID iD: 0000-0001-8927-3176
St. Petersburg Россия

A. A. Zhirkov

Pediatric Research and Clinical Center for Infectious Diseases

Email: ant-zhirkov@yandex.ru
ORCID iD: 0000-0002-7720-2175
St. Petersburg Россия

References

  1. Алексеева Л.А., Скрипченко Н.В., Бессонова Т.В., Монахова Н.Е., Григорьев С.Г. Маркеры повреждения нейронов и глии в цереброспинальной жидкости при менингитах у детей // Клиническая лабораторная диагностика. 2017. Т. 62, № 4. С. 204—210. doi: 10.18821/0869-2084-2017-62-4-204-210(In Russ.)
  2. Белялетдинова И.Х., Голосная Г.С., Митрофанова И.В., Прыткова М.И. Клинико-лабораторная характеристика энцефалитов, вызванных вирусом простого герпеса у детей // Лечение и профилактика. 2016. Т. 20, № 4. С. 64—68.
  3. Вашура Л.В., Савенкова М.С., Заваденко Н.Н. Роль герпесвирусов в генезе судорожных состояний у детей: современный взгляд на проблему // Педиатрия. Журнал им. Г.Н. Сперанского. 2016. Т. 95, № 4. С. 203—208.
  4. Горелик Е.Ю., Войтенков В.Б., Скрипченко Н.В., Вильниц А.А., Иванова М.В., Климкин А.В. Острые нейроинфекции и симптоматическая эпилепсия у детей: причинно-следственные связи (обзор литературы) // Журнал инфектологии. 2017. Т. 9, № 3. С. 5-13. doi: 10.22625/2072-6732-2017-9-3-5-13(In Russ.)
  5. Железникова Г.Ф., Скрипченко Н.В., Моргацкий Н.В., Монахова Н.Е., Керимова Л.В. Иммунопатогенетические особенности клещевого энцефалита у детей и эффект терапии // Нейроиммунология. 2008. Т. 6, № 1-2. С. 13-22.
  6. Ильинских Н.Н., Замятина Е.В., Ильинских Е.Н., Полежаев В.С. Иммуноцитологические прогностические критерии острого клещевого энцефалита // Современные проблемы науки и образования. 2018. № 2. С. 31.
  7. Крылова Н.В., Леонова Г.Н., Павленко Е.В., Запорожец Т.С., Смолина Т.П., Гажа А.К., Новиков Д.В., Ченцова И.В. Комплексная оценка состояния иммунной системы при различных формах клещевого энцефалита в остром периоде // Медицинская иммунология. 2012. Т. 14, № 4-5. C. 313-320. doi: 10.15789/1563-0625-2012-4-5-313-320 (In Russ.)
  8. Попонникова Т.В., Галиева Г.Ю., Новиков В.Э., Галаганова Л.Г. Клещевой энцефалит у детей: особенности клиники и дифференциальной диагностики в современных условиях // Русский журнал детской неврологии. 2011. Т. 6, № 2. С. 11-24.
  9. Попонникова Т.В., Бедарева Т.Ю., Вахрамеева Т.Н., Галиева Г.Ю. Цитокиновый профиль в остром периоде клещевых нейроинфекций у детей // Журнал неврологии и психиатрии им. С.С. Корсакова. 2010. Т. 110, № 5. С. 9-12.
  10. Симонова Е.В., Харламова Ф.С., Учайкин В.Ф., Дроздова И.М., Егорова Н.Ю. Поражение центральной нервной системы при герпесвирусной моно- и микст-инфекции 6-го типа у детей // Педиатрия. Журнал им. Г.Н. Сперанского. 2016. Т. 95, № 2. С. 22-29.
  11. Скрипченко Н.В., Кривошеенко Е.М., Команцев В.Н., Горелик Е.Ю., Минченко С.И. Гетерогенность судорожного синдрома при инфекционных заболеваниях у детей. В кн.: Нейроинфекции у детей. СПб., 2015. С. 691-707.
  12. Студеникин В.М., Турсунхужаева С.Ш., Шелковский В.И., Пак Л.А. Фебрильные судороги у детей: теоретические и практические аспекты // Вопросы практической педиатрии. 2010. Т. 5, № 2. С. 66-74.
  13. Agut H., Bonnafous P., Gautheret-Dejean A. Laboratory and clinical aspects of human herpesvirus 6 infections. Clin. Microbiol. Rev., 2015, vol. 28, no. 2,pp. 313-335. doi: 10.1128/CMR.00122-14
  14. Bardina S., Lim J. The role of chemokines in the pathogenesis of neurotropic flaviviruses. Immunol. Res., 2012, vol. 54, no. 1-3, pp. 121-132. doi: 10.1007/s12026-012-8333-3
  15. Bartolini L., Theodore W., Jacobson S., Gaillard W. Infection with HHV-6 and its role in epilepsy. Epilepsy Res., 2019, vol. 153, pp. 34-39. doi: 10.1016/j.eplepsyres.2019.03.016
  16. Czupryna P., Grygorczuk S., Pancewicz S., Swierzbinska R., Zajkowska J., Krawczuk K., Dunaj J., Filipiuk J., Kruszewska E., Borawski K., Moniuszko-Malinowska A. Evaluation of NSE and S100B in patients with tick-borne encephalitis. Brain Behav., 2018, vol. 8, no. 12: e01160. doi: 10.1002/brb3.1160
  17. Dittrich S., Sunyakumthorn P., Rattanavong S., Phetsouvanh R., Panyanivong P., Sengduangphachanh A., Phouminh P., Anantatat T., Chanthongthip A., Lee S., Dubot-Peres A., Day N., Paris D., Newton P., Turner G. Blood-brain barrier function and biomarkers of central nervous system injury in rickettsial versus other neurological infections in Laos. Am. J. Trop. Med. Hyg, 2015, vol. 93, no. 2,pp. 232-237. doi: 10.4269/ajtmh.15-0119
  18. Epstein L., Shinnar S., Hesdorffer D., Nordli D., Hamidullah A., Benn E., Pellock J., Frank L., Lewis D., Moshe S., Shinnar R., Sun S. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study. Epilepsia, 2012, vol. 53, no. 9, pp. 1481-1488. doi: 10.1111/j.1528-1167.2012.03542.x
  19. Fowler A., Ygberg S., Bogdanovic G., Wickstrom R. Biomarkers in cerebrospinal fluid of children with tick-borne encephalitis: association with long-term outcome. Pediatr. Infect. Dis. J., 2016, vol. 35, no. 9, pp. 961-966. doi: 10.1097/INF.0000000000001210
  20. Grygorczuk S., Swierzbinska R., Kondrusik M., Dunaj J., Czupryna P., Moniuszko A., Siemieniako A., Pancewicz S. The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis. J. Neuroinflammation., 2018, vol. 15, no. 1,pp. 115-135. doi: 10.1186/s12974-018-1138-0
  21. Hoshino A., Saitoh M., Oka A., Okumura A., Kubota M., Saito Y., Takanashi J., Hirose S., Yamagata T., Yamanouchi H., Mizuguchi M. Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes. Brain Dev., 2012, vol. 34, no. 5, pp. 337-343. doi: 10.1016/j.braindev.2011.07.012
  22. Ichiyama T., Ito Y., Kubota M., Yamazaki T., Nakamura K., Furukawa S. Serum and cerebrospinal fluid levels of cytokines in acute encephalopathy associated with human herpesvirus-6 infection. Brain Dev., 2009, vol. 31, no. 10,pp. 731-738. doi: 10.1016/j.braindev.2008.11.005
  23. Ichiyama T., Shoji H., Takahashi Y., Matsushige T., Kajimoto M., Inuzuka T., Furukawa S. Cerebrospinal fluid levels of cytokines in non-herpetic acute limbic encephalitis: comparison with herpes simplex encephalitis. Cytokine, 2008, vol. 44, no. 1, pp. 149-153. doi: 10.1016/j.cyto.2008.07.002
  24. Kalita J., Misra U., Mani V., Bhoi S. Can we differentiate between herpes simplex encephalitis and Japanese encephalitis? J. Neurol. Sci., 2016, vol. 366,pp. 110-115. doi: 10.1016/j.jns.2016.05.017
  25. Kalita J., Srivastava R., Mishra M., Basu A., Misra U. Cytokines and chemokines in viral encephalitis: a clinicoradiological correlation. Neurosci. Lett, 2010, vol. 473, no. 1, pp. 48-51. doi: 10.1016/j.neulet.2010.02.017
  26. Kamei S., Taira N., Ishihara M., Sekizawa T., Morita A., Miki K., Shiota H., Kanno A., Suzuki Y., Mizutani T., Itoyama Y., Morishima T., Hirayanagi K. Prognostic value of cerebrospinal fluid cytokine changes in herpes simplex virus encephalitis. Cytokine, 2009, vol. 46, no. 2, pp. 187-193. doi: 10.1016/j.cyto.2009.01.004
  27. Kawabe S., Ito Y., Ohta R., Sofue A., Gotoh K., Morishima T., Kimura H. Comparison of the levels of human herpesvirus 6 (HHV6) DNA and cytokines in the cerebrospinal fluid and serum of children with HHV-6 encephalopathy. J. Med. Virol., 2010, vol. 82, no. 8, pp. 1410-1415. doi: 10.1002/jmv.21808
  28. Kawamura Y., Nakayama A., Kato T., Miura H., Ishihara N., Ihira M., Takahashi Y., Matsuda K., Yoshikawa T. Pathogenic role of human herpesvirus 6B infection in mesial temporal lobe epilepsy. J. Infect. Dis., 2015, vol. 212, no. 7, pp. 1014-1021. doi: 10.1093/infdis/jiv160
  29. Koh S. Role of neuroinflammation in evolution of childhood epilepsy. J. Child. Neurol., 2018, vol. 33, no. 1, pp. 64-72. doi: 10.1177/0883073817739528
  30. Lee W., Yu T., Chang W., Shau W. Risk factors for postencephalitic epilepsy in children: a hospital-based study in Taiwan. Eur. J. Paediatr. Neurol., 2007, vol. 11, no. 5, pp. 302-309. doi: 10.1016/j.ejpn.2007.02.011
  31. Li Y., Li H., Fan R., Wen B., Zhang J., Cao X., Wang C., Song Z., Li S., Li X., Lv X., Qu X., Huang R., Liu W. Coronavirus infections in the central nervous system and respiratory tract show distinct features in hospitalized children. Intervirology, 2016, vol. 59, no. 3, pp. 163-169. doi: 10.1159/000453066
  32. Michael B., Griffiths M., Granerod J., Brown D., Davies N., Borrow R., Solomon T. Characteristic cytokine and chemokine profiles in encephalitis of infectious, immune-mediated, and unknown aetiology. PLoS One, 2016, vol. 11, no. 1: e0146288. doi: 10.1371/journal.pone.0146288
  33. Misra U., Kalita J. Seizures in encephalitis: predictors and outcome. Seizure, 2009, vol. 18, no. 8, pp. 583-587. doi: 10.1016/j.seizure.2009.06.003
  34. Mohammadpour T., Gafnza-Lein M., Jafarpour S., Brinegar K., Kapur K., Loddenkemper T. HHV-6 and seizure: A systematic review and meta-analysis. J. Med. Virol., 2017, vol. 89, no. 1, pp. 161-169. doi: 10.1002/jmv.24594
  35. Motojima Y., Nagura M., Asano Y., Arakawa H., Takada E., Sakurai Y., Moriwaki K., Tamura M. Diagnostic and prognostic factors for acute encephalopathy. Pediatr. Int., 2016, vol. 58, no. 11, pp. 1188-1192. doi: 10.1111/ped.12995
  36. Nagasaka M., Morioka I., Kawabata A., Yamagishi Y., Iwatani S., Taniguchi-Ikeda M., Ishida A., Iijima K., Mori Y. Comprehensive analysis of serum cytokines/chemokines in febrile children with primary human herpes virus-6B infection. J. Infect. Chemother., 2016, vol. 22, no. 9,pp. 593-598. doi: 10.1016/j.jiac.2016.05.010
  37. Park J., Suh G., Shin H. Association between cerebrospinal fluid S100B protein and neuronal damage in patients with central nervous system infections. Yonsei Med J., 2013, vol. 54, no. 3, pp. 567-571. doi: 10.3349/ymj.2013.54.3.567
  38. Peng Q., Tao S., Yu N., Zhou X., Peng Y., Fu N. Elevated levels of cerebrospinal fluid S100B are associated with brain injury and unfavorable outcomes in children with central nervous system infections. Int. J. Neurosci., 2017, vol. 127, no. 1, pp. 1-9. doi: 10.3109/00207454.2015.1135334
  39. Rana A., Musto A. The role of inflammation in the development of epilepsy. J. Neuroinflammation, 2018, vol. 15, no. 1, p. 144. doi: 10.1186/s12974-018-1192-7
  40. Rismanchi N., Gold J., Sattar S., Glaser C., Sheriff H., Proudfoot J., Mower A., Crawford J., Nespeca M., Wang S. Epilepsy after resolution of presumed childhood encephalitis. Pediatr. Neurol., 2015, vol. 53, no. 1,pp. 65-72. doi: 10.1016/j.pediatrneurol.2015.03.016
  41. Rohlwink U., Figaji A. Biomarkers ofbrain injury in cerebral infections. Clin. Chem, 2014, vol. 60, no. 6,pp. 823—834. doi: 10.1373/clinchem.2013.212472
  42. Shiihara T., Miyake T., Izumi S., Watanabe M., Kamayachi K., Kodama K., Nabetani M., Ikemiyagi M., Yamaguchi Y., Sawaura N. Serum and cerebrospinal fluid S100B, neuron-specific enolase, and total tau protein in acute encephalopathy with biphasic seizures and late reduced diffusion: a diagnostic validity. Pediatr. Int., 2012, vol. 54, no. 1, pp. 52—55. doi: 10.1111/j.1442-200X.2011.03454.x
  43. Shiihara T., Miyake T., Izumi S., Sugihara S., Watanabe M., Takanashi J., Kubota M., Kato M. Serum and CSF biomarkers in acute pediatric neurological disorders. Brain Dev., 2014, vol. 36, no. 6, pp. 489—495. doi: 10.1016/j.braindev.2013.06.011
  44. Studahl M., Rosengren L., Gunther G., Hagberg L. Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. J. Neurol., 2000, vol. 247, no. 8, pp. 636-642. doi: 10.1007/s004150070134
  45. Studahl M., Gunther G., Rosengren L. Serum S-100B protein levels in patients with herpes simplex encephalitis and tick-borne encephalitis — a marker of CNS damage during the initial stage of disease. J. Neurol., 2009, vol. 256, no. 4, pp. 586-590. doi: 10.1007/s00415-009-0124-y
  46. Tanuma N., Miyata R., Kumada S., Kubota M., Takanashi J., Okumura A., Hamano S., Hayashi M. The axonal damage marker tau protein in the cerebrospinal fluid is increased in patients with acute encephalopathy with biphasic seizures and late reduced diffusion. Brain Dev., 2010, vol. 32, no. 6, pp. 435-439. doi: 10.1016/j.braindev.2009.07.004
  47. Tanuma N., Miyata R., Nakajima K., Okumura A., Kubota M., Hamano S., Hayashi M. Changes in cerebrospinal fluid biomarkers in human herpesvirus-6-associated acute encephalopathy/febrile seizures. Mediators Inflamm., 2014, vol. 2014: 564091. doi: 10.1155/2014/564091
  48. Tsukahara H., Fujii Y., Matsubara K., Yamada M., Nagaoka Y., Saito Y., Yashiro M., Tsuge M., Goto S., Kitamura T., Hata A., Ichiyama T., Morishima T. Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy. Pediatr Int., 2013, vol. 55, no. 4, pp. 461-464. doi: 10.1111/ped.12094
  49. Wang S., Lei H., Liu C. Cytokine immunopathogenesis of enterovirus 71 brain stem encephalitis. Clin. Dev. Immunol., 2012, vol. 2012:876241. doi: 10.1155/2012/876241
  50. Ye N., Gong X., Pang L., Gao W., Zhang Y., Li X., Liu N., Li D., Jin Y., Duan Z. Cytokine responses and correlations there of with clinical profiles in children with enterovirus 71 infections. BMC Infect. Dis., 2015, vol. 15, pp. 225-234. doi: 10.1186/s12879-015-0965-1
  51. Yoshikawa T., Kato Y., Ihira M., Nishimura N., Ozaki T., Kumagai T., Asano Y. Kinetics of cytokine and chemokine responses in patients with primary human herpesvirus 6 infection. J. Clin. Virol., 2011, vol. 50, no. 1,pp. 65-68. doi: 10.1016/j.jcv.2010.09.017
  52. Youn Y., Sung I., Lee I. The role of cytokines in seizures: interleukin (IL)-1p, IL-1Ra, IL-8, and IL-10. Korean J. Pediatr., 2013, vol. 56, no. 7,pp. 271-274. doi: 10.3345/kjp.2013.56.7.271
  53. Zajkowska J., Moniuszko-Malinowska A., Pancewicz S., Muszynska-Mazur A., Kondrusik M., Grygorczuk S., Swierzbinska-Pijanowska R., Dunaj J., Czupryna P. Evaluation of CXCL10, CXCL11, CXCL12 and CXCL13 chemokines in serum and cerebrospinal fluid in patients with tick borne encephalitis (TBE). Adv. Med. Sci., 2011, vol. 56, no. 2, pp. 311-317. doi: 10.2478/v10039-011-0033-z
  54. Zhang S., Xu M., Xu H., Li X., Ding S., Wang X., Li T., Lu Q. Immunologic characterization of cytokine responses to enterovirus 71 and coxsackie virus A16 infection in children. Medicine (Baltimore), 2015, vol. 94, no. 27: e1137. doi: 10.1097/MD.0000000000001137

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2020 Alekseeva L.A., Zheleznikova G.F., Gorelik E.Y., Skripchenko N.V., Zhirkov A.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies