Herpesviruses and biomarkers in disseminated encephalomyelitis and multiple sclerosis in children (part II)

Skripchenko E.Yu.; Zheleznikova G.F.; Alekseeva L.A.; Skripchenko N.V.; Astapova A.V.; Gorelik Е.Yu.; Vilnits A.A.

doi:https://doi.org/10.17116/jnevro202112140293

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Abstract:

Recently, the problem of demyelinating diseases in children is still very acute. This occurs, on the one hand, by high access and specificity of diagnostic methods and, on the other hand — by high morbidity of children different neuroinfectious diseases which can lead to demyelinating diseases. This literature review presents the currently available information on the autoantibodies and neurospecific protein role in the development of multiple sclerosis and acute disseminative encephalitis in children. The authors also describe their experience of complex etiopatogenic therapy and cytoflavin use that helps to reduce frequency and expression of demyelinating process and endothelium dysfunction in case of active herpesvirus infection.

Keywords:

herpes viruses

children

multiple sclerosis

disseminated encephalomyelitis

demyelination

cytoflavin

prognosis

Authors:

Skripchenko E.Yu.

Pediatric Research and Clinical Center for Infectious Diseases;
Saint-Petersburg State Pediatric Medical University

Zheleznikova G.F.

Pediatric Research and Clinical Center for Infectious Diseases

Alekseeva L.A.

Pediatric Research and Clinical Center for Infectious Diseases

Skripchenko N.V.

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

Astapova A.V.

Pediatric Research and Clinical Center for Infectious Diseases

Gorelik Е.Yu.

Pediatric Research and Clinical Center for Infectious Diseases

Vilnits A.A.

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

Received:

08.02.2021

Accepted:

11.02.2021

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References:

Skripchenko NV, Ivanova GP, Skripchenko EY, Surovceva AV. Demyelinating diseases of the nervous system in children. Etiology, clinic, pathogenesis, diagnosis, treatment. M.: Kommentarij; 2016. (In Russ.).
Bykova OV, Platonova AN, Gol’tsova NV, Kuznetsova GV, Kuzenkova LM, Boyko AN. Early differential diagnostics and prolonged immunomodulatory therapy of chronic inflammatory demyelinating diseases of central nervous system in children and adolescents. Voprosy Sovremennoi Pediatrii. 2009;8:6:139-145. (In Russ.).
Brenton J, Banwell B. Therapeutic approach to the management of pediatric demyelinating disease: multiple sclerosis and acute disseminated encephalomyelitis. Neurotherapeutics. 2016;13:1:84-95. https://doi.org/10.1007/s13311-015-0396-0
Skripchenko NV, Ivanova GP, Skripchenko EYu, Egorova ES, Surovtseva AV. The efficacy of cytoflavin in disseminated encephalomyelitis in children. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova «Detskaya nevrologiya». 2017;11(2):67-74. (In Russ.). https://doi.org/10.17116/jnevro201711711267-74
Krupp L, Tardieu M, Amato M, Banwell B, Chitnis T, Dale R, Ghezzi A, Hintzen R, Kornberg A, Pohl D, Rostasy K, Tenembaum S, Wassmer E. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013;19:10:1261-1267. https://doi.org/10.1177/1352458513484547
Matricardi S, Farello G, Savasta S, Verrotti A. Understanding childhood neuroimmune diseases of the central nervous system. Front Pediatr. 2019;7:511. https://doi.org/10.3389/fped.2019.00511
Gray M, Gorelick M. Acute disseminated encephalomyelitis. Pediatric Emergency Care. 2016;32:6:395-400. https://doi.org/10.1097/PEC.0000000000000825
Thompson A, Banwell B, Barkhof F, Carroll W, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman M, Fujihara K, Galetta S, Hartung H, Kappos L, Lublin F, Marrie R, Miller A, Miller D, Montalban X, Mowry E, Sorensen P, Tintoré M, Traboulsee A, Trojano M, Uitdehaag B, Vukusic S, Waubant E, Weinshenker B, Reingold S, Cohen J. Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria. Lancet Neurol. 2018;17:2:162-173. https://doi.org/10.1016/S1474-4422(17)30470-2
Pohl D, Alper G, Van Haren K, Kornberg A, Lucchinetti C, Tenembaum S, Belman A. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome. Neurology. 2016;87:9(suppl 2):38-45. https://doi.org/10.1212/WNL.0000000000002825
Melnikov MV, Boiko OV, Lashch NYu, Popova EV, Martynov MYu, Boiko AN. Acute disseminated encephalomyelitis and multiple sclerosis: open questions of differential diagnosis demonstrated by the example of a clinical case. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova S.S. Korsakov Journal of Neurology and Psychiatry. 2012;112:9:52-58. (In Russ.).
Young N, Weinshenker B, Parisi J, Scheithauer B, Giannini C, Roemer S, Thomsen K, Mandrekar J, Erickson B, Lucchinetti C. Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis. Brain. 2010;133(Pt 2):333-348. https://doi.org/10.1093/brain/awp321
Skripchenko EYu, Ivanova GP, Skripchenko NV, Karev VE, Egorova ES, Zheleznikova GF, Surovtseva AV, Murina EA. Infectious vasculitis in the pathogenesis of demyelinating diseases of the central nervous system in children Rossijskij Vestnik Perinatologii i Pediatrii. 2018;3:63:76-82. (In Russ.). https://doi.org/10.21508/1027-4065-2018-63-3-76-83
Rumyantseva SA, Fedin AI, Bolevich SB, Silina EV, Vasil’ev YuD, Men’shova NI, Ilyukhina OA, Goluzova YuN. Influence of early correction of energy and free radical homeostasis on the clinical and morphological picture of cerebral infarction. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2010;110(8):16-21. (In Russ.).
Mazin PV, Sheshunov IV, Mazina NK. Meta-analytical evaluation of the clinical efficacy of cytoflavin in neurological diseases. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2017;3:28-39. (In Russ.). https://doi.org/10.17116/jnevro20171173128-39
Maevskij EI, Grishina EV, Rozenfel’d AS, Zyakun AM, Vereshhagina VM, Kondrashova MN. Anaerobic formation of succinate and ensuring its oxidation are possible mechanisms of cell adaptation to oxygen starvation. Biofizika. 2000;45(3):509-513. (In Russ.).
Esposito S, Di Pietro G, Madini B, Mastrolia M, Rigante D. A spectrum of inflammation and demyelination in acute disseminated encephalomyelitis (ADEM) of children. Autoimmun Rev. 2015;14:10:923-929. https://doi.org/10.1016/j.autrev.2015.06.002
Zheleznikova GF, Scripchenko NV, Alekseeva LA, Scripchenko EYu. Chemokines in the pathogenesis of multiple sclerosis. Ross Immunol Zhurn. 2017;11(20):4:15-29. (In Russ.).
Lehmann-Horn K, Kinzel S, Weber M. Deciphering the role of B cells in multiple sclerosis — towards specific targeting of pathogenic function. Int J Mol Sci. 2017;18:10:2048. https://doi.org/10.3390/ijms18102048
Schwenkenbecher P, Wurster U, Konen F, Gingele S, Sühs K, Wattjes M, Stangel M, Skripuletz T. Impact of the McDonald criteria 2017 on early diagnosis of relapsing-remitting multiple sclerosis. Front Neurol. 2019;10:188. https://doi.org/10.3389/fneur.2019.00188.
Magliozzi R, Cross A. Can CSF biomarkers predict future multiple sclerosis disease activity and severity? Mult Scler. 2020;1352458519871818. https://doi.org/10.1177/1352458519871818
Reiber H, Teut M, Pohl D, Rostasy K, Hanefeld F. Paediatric and adult multiple sclerosis: age-related differences and time course of the neuroimmunological response in cerebrospinal fluid. Mult Scler. 2009;15:12:1466-1480. https://doi.org/10.1177/1352458509348418
Makhani N, Lebrun C, Siva A, Narula S, Wassmer E, Brassat D, Brenton J, Cabre P, Dallière C, de Seze J, Dubief F, Inglese M, Langille M, Mathey G, Neuteboom R, Pelletier J, Pohl D, Reich D, Rojas J, Shabanova V, Shapiro E, Stone R, Tenembaum S, Tintoré M, Uygunoglu U, Vargas W, Venkateswaren S, Vermersch P, Kantarci O, Okuda D, Pelletier D. Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome. Mult Scler J Exp Transl Clin. 2019;5:1:1-9. https://doi.org/10.1177/2055217319836664
Sinclair A, Wienholt L, Tantsis E, Brilot F, Dale R. Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology. Dev Med Child Neurol. 2013;55:1:71-75. https://doi.org/10.1111/j.1469-8749.2012.04443.x
Alper G, Heyman R, Wang L. Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features. Dev Med Child Neurol. 2009;51:6:480-486. https://doi.org/10.1111/j.1469-8749.2008.03136.x
Dale R, Morovat A. Interleukin-6 and oligoclonal IgG synthesis in children with acute disseminated encephalomyelitis. Neuropediatrics. 2003;34:3:141-145. https://doi.org/10.1055/s-2003-41281
Skripchenko NV, Ivanova GP, Skripchenko EY, Surovtseva AV, Murina EA, Zheleznikova GF, Alekseeva LA. Clinical laboratory differential diagnosis of encephalitis, disseminated encephalomyelitis and multiple sclerosis in children. Pediatria. 2017;96:4:34-42. (In Russ.).
Skripchenko EY, Alekseeva LA, Skripchenko NV, Bessonova TV. Comparative characteristic of laboratory indicators for encephalitis, disseminated encephalomyelitis and multiple sclerosis in children. Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology. 2018;13:3:25-35. https://doi.org/10.17650/2073-8803-2018-13-3-25-35
Presslauer S, Milosavljevic D, Huebl W, Aboulenein-Djamshidian F, Krugluger W, Deisenhammer F, Senel M, Tumani H, Hegen H. Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome. A multicenter study. Mult Scler. 2016;22:502-510. https://doi.org/10.1177/1352458515594044
Totolyan NA, Gotovchikov AA, Lapin SV, Maksimov IV, Kodzaeva AYu, Prakhova LN, Ilves AG, Skoromets AP, Totolyan AA, Skoromets AA. Intrathecal immunoglobulin production in the diagnosis and differential diagnosis of multiple sclerosis. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2012;112:9(2):73-86. (In Russ.).
Nazarov VD, Makshakov GS, Mazing AV, Surkova EA, Krasnov VS, Shumilina MV, Totolyan NA, Evdoshenko EP, Lapin SV, Emanuel VL, Skoromets AA. Diagnostic value of immunoglobulin free light chains at the debut of multiple sclerosis. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2017;117:2(2):60-65. (In Russ.). https://doi.org/10.17116/jnevro20171172260-65
Zheleznikova GF, Scripchenko NV, Ivanova GP, Surovzeva AV, Scripchenko EY. Immunopathogenesis factors of multiple sclerosis. Rus Journal of Immunology. 2015;9:3:261-282. (In Russ.).
Tolpeeva OZ, Zakharova MN. The diagnostic significance of antibodies to myelin proteins in demyelinating diseases of the central nervous system. Neirochimiya. 2017;34:2:108-117. (In Russ.). https://doi.org/10.7868/S1027813317010137
O’Connor K, Lopez-Amaya C, Gagne D, Lovato L, Moore-Odom N. Anti-mielin antibodies modulate clinical expression of childhood multiple sclerosis. J Neuroimmunol. 2010;223:1-2:92-99. https://doi.org/10.1016/j.jneuroim.2010.02.019
Van Haren K, Tomooka B, Kidd B, Banwell B, Bar-Or A, Chitnis T, Tenembaum S, Pohl D, Rostasy K, Dale R, O’Connor K, Hafler D, Steinman L, Robinson W. Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing-remitting multiple sclerosis. Mult Scler. 2013;19:13:1726-1733. https://doi.org/10.1177/1352458513485653
Reindl M, Waters P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol. 2019;15:2:89-102. https://doi.org/10.1038/s41582-018-0112-x
Tea F, Lopez J, Ramanathan S, Merheb V, Lee F, Zou A, Pilli D, Patrick E, van der Walt A, Monif M, Tantsis E, Yiu E, Vucic S, Henderson A, Fok A, Fraser C, Lechner-Scott J, Reddel S, Broadley S, Barnett M, Brown D, Lunemann J, Dale R, Brilot F. Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination. Acta Neuropathol Commun. 2019;7:1:145. https://doi.org/10.1186/s40478-019-0786-3
McLaughlin K, Chitnis T, Newcombe J, Franz B, Kennedy J, McArdel S, Kuhle J, Kappos L, Rostasy K, Pohl D, Gagne D, Ness J, Tenembaum S, O’Connor K, Viglietta V, Wong S, Tavakoli N, de Seze J, Idrissova Z, Khoury S, Bar-Or A, Hafler D, Banwell B, Wucherpfennig K. Age-dependent B cell autoimmunity to a myelin surface antigen in pediatric multiple sclerosis. J Immunol. 2009;183:6:4067-4076. https://doi.org/10.4049/jimmunol.0801888
Di Pauli F, Mader S, Rostasy K, Schanda K, Bajer-Kornek B, Ehling R, Deisenhammer F, Reindl M, Berger T. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases. Clin Immunol. 2011;138:3:247-254. https://doi.org/10.1016/j.clim.2010.11.013
Hacohen Y, Absoud M, Deiva K, Hemingway C, Nytrova P, Woodhall M, Palace J, Wassmer E, Tardieu M, Vincent A, Lim M, Waters P. Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children. Neurol Neuroimmunol Neuroinflamm. 2015;2:2:e81. https://doi.org/10.1212/NXI.0000000000000081
Oka M, Hasegawa S, Matsushige T, Inoue H, Kajimoto M, Ishikawa N, Isumi H, Ichiyama T. Tau protein concentrations in the cerebrospinal fluid of children with acute disseminated encephalomyelitis. Brain Dev. 2014;36:1:16-20. https://doi.org/10.1016/j.braindev.2012.11.013
Kothur K, Wienholt L, Tantsis E, Earl J, Bandodkar S, Prelog K, Tea F, Ramanathan S, Brilot F, Dale R. B Cell, Th17, and neutrophil related cerebrospinal fluid cytokine/chemokines are elevated in MOG antibody associated demyelination. PLoS One. 2016;11:2:e0149411. https://doi.org/10.1371/journal.pone.0149411
Waters P, Fadda G, Woodhall M, O’Mahony J, Brown R, Castro D, Longoni G, Irani S, Sun B, Yeh E, Marrie R, Arnold D, Banwell B, Bar-Or A. Serial anti-myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes. JAMA Neurol. 2020;77:1:82-93. https://doi.org/10.1001/jamaneurol.2019.2940
Horellou P, Wang M, Keo V, Chrétien P, Serguera C, Waters P, Deiva K. Increased interleukin-6 correlates with myelin oligodendrocyte glycoprotein antibodies in pediatric monophasic demyelinating diseases and multiple sclerosis. J Neuroimmunol. 2015;289:1-7. https://doi.org/10.1016/j.jneuroim.2015.10.002
Mane-Martinez M, Olsson B, Bau L, Matas E, Cobo-Calvo A, Andreasson U, Blennow K, Romero-Pinel L, Martínez-Yélamos S, Zetterberg H. Glial and neuronal markers in cerebrospinal fluid in different types of multiple sclerosis. J Neuroimmunol. 2016;299:112-117. https://doi.org/10.1016/j.jneuroim.2016.08.004
Siller N, Kuhle J, Muthuraman M, Barro C, Uphaus T, Groppa S, Kappos L, Zipp F, Bittner S. Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis. Mult Scler. 2019;25:5:678-686. https://doi.org/10.1177/1352458518765666
Vorob’eva AA, Fominykh VV, Onufrieva MV, Zakharova MN, Gulyaeva NV. Phosphorylated neurofilament heavy subunits as a marker of neurodegeneration in demyelinating diseases of the CNS. Neirochimiya. 2014;31:3:254-259. (In Russ.). https://doi.org/10.7868/S1027813314030145
Rostasy K, Withut E, Pohl D, Lange P, Ciesielcyk B, Diem R, Gärtner J, Otto M. Tau, phospho-tau, and S-100B in the cerebrospinal fluid of children with multiple sclerosis. J Child Neurol. 2005;20:10:822-825. https://doi.org/10.1177/08830738050200100801
Ichiyama T, Shoji H, Kato M, Sawaishi Y, Ozawa H, Matsubara T, Furukawa S. Cerebrospinal fluid levels of cytokines and soluble tumour necrosis factor receptor in acute disseminated encephalomyelitis. Eur J Pediatr. 2002;161:3:133-137. https://doi.org/10.1007/s00431-001-0888-2
Bukhalko MA, Skripchenko EYu, Alekseeva LA, Skripchenko NV, Monakhova NE, Grigoriev SG. Vitamin D and neurospecific proteins in children with inflammatory demyelinating diseases of central nervous system. Pediatrician (St. Petersburg). 2019;10:3:17-24. (In Russ.). https://doi.org/10.17816/PED10317-24
Skripchenko EY, Lobzin VY, Astapova AV, Lobzin YV, Skripchenko NV, Vilnitz AA, Gorelik EY, Pulman NF, Alekseeva LA, Klimkin AV, Murina EV, Voitenkov BV, Goleva OV. The method of prognosis chronical disseminated encephalomyelitis transformation in multiple sclerosis in children. https://findpatent.ru/patent/274/2740243.html
Baumann M, Sahin K, Lechner C, Hennes E, Schanda K, Mader S, Karenfort M, Selch C, Häusler M, Eisenkölbl A, Salandin M, Gruber-Sedlmayr U, Blaschek A, Kraus V, Leiz S, Finsterwalder J, Gotwald T, Kuchukhidze G, Berger T, Reindl M, Rostásy K. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry. 2015;86:3:265-272. https://doi.org/10.1136/jnnp-2014-308346