Human Herpes Virus 7-related encephalopathy in children

Human Herpes Virus 7-related encephalopathy in children

Authors

  • Thomas Foiadelli Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • Virginia Rossi Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • Stefania Paolucci Molecular Virology Unit, Department of Diagnostic Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • Francesca Rovida Molecular Virology Unit, Department of Diagnostic Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • Federica Novazzi Molecular Virology Unit, Department of Diagnostic Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • Alessandro Orsini Pediatric Neurology, Pediatric University Department, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Italy
  • Ilaria Brambilla Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • Gian Luigi Marseglia Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • Fausto Baldanti Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Salvatore Savasta Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

Keywords:

ADEM, Encephalitis, HHV7, Meningoencephalitis, PANS, Pediatric.

Abstract

Background: Primary HHV7 infection is almost ubiquitous, and it can present as exanthema subitem. Little is known on the clinical relevance of HHV7 neuroinvasion in immunocompetent children.

Methods: We describe 12 patients (median age 9.45 years, 50% males) with acute encephalopathy and active HHV7 infection. In all patients, HHV7-DNA was detected on cerebrospinal fluid (CSF) by RT-PCR.

Results: 7/12 patients had meningoencephalitis (two with ADEM and one with MOG antibody-associated CIS); 5/12 showed acute neuropsychiatric symptoms. EEG showed anomalies exclusively in patients with meningoencephalitis. Six patients had RMN anomalies. CSF HHV7 copies ranged between 20 and 3,500 copies/mL (median 66 copies/mL) and mean HHV7 CSF/blood ratio was 0.75. Outcome was favorable in all children, although 3/12 had minor neurobehavioral sequelae. Mean follow-up period of 5.2 months.

Conclusions: HHV7 can determine neuroinvasion in immunocompetent children, leading to acute encephalopathy. Blood-brain barrier damage and high CSF/blood viral copies ratio correlated with a more severe presentation. We speculate on the importance of immune-mediated mechanisms in provoking clinical features.

References

Frenkel N, Schirmer EC, Wyatt LS, Katsafanas G, Roffman E, Danovich RM, et al. Isolation of a new herpesvirus from human CD4+ T cells. Proc Natl Acad Sci U S A. 1990;87(2):748-52.

Berneman ZN, Ablashi DV, Li G, Eger-Fletcher M, Reitz MS, Jr., Hung CL, et al. Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus. Proc Natl Acad Sci U S A. 1992;89(21):10552-6.

Kenneth J. Ryan e. Sherris medical microbiology : an introduction to infectious diseases: Third edition. Norwalk, Conn. : Appleton & Lange, [1994] ©1994; 1994.

Ward KN. The natural history and laboratory diagnosis of human herpesviruses-6 and -7 infections in the immunocompetent. J Clin Virol. 2005;32(3):183-93.

Huang LM, Lee CY, Liu MY, Lee PI. Primary infections of human herpesvirus-7 and herpesvirus-6: a comparative, longitudinal study up to 6 years of age. Acta Paediatr. 1997;86(6):604-8.

Tanaka K, Kondo T, Torigoe S, Okada S, Mukai T, Yamanishi K. Human herpesvirus 7: another causal agent for roseola (exanthem subitum). J Pediatr. 1994;125(1):1-5.

Torigoe S, Koide W, Yamada M, Miyashiro E, Tanaka-Taya K, Yamanishi K. Human herpesvirus 7 infection associated with central nervous system manifestations. J Pediatr. 1996;129(2):301-5.

Epstein LG, Shinnar S, Hesdorffer DC, Nordli DR, Hamidullah A, Benn EK, et al. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study. Epilepsia. 2012;53(9):1481-8.

Chapenko S, Roga S, Skuja S, Rasa S, Cistjakovs M, Svirskis S, et al. Detection frequency of human herpesviruses-6A, -6B, and -7 genomic sequences in central nervous system DNA samples from post-mortem individuals with unspecified encephalopathy. J Neurovirol. 2016;22(4):488-97.

Ongrádi J, Ablashi DV, Yoshikawa T, Stercz B, Ogata M. Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals. J Neurovirol. 2017;23(1):1-19.

Chan PK, Chik KW, To KF, Li CK, Shing MM, Ng KC, et al. Case report: human herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell transplant recipient. J Med Virol. 2002;66(4):493-6.

Ward KN, Andrews NJ, Verity CM, Miller E, Ross EM. Human herpesviruses-6 and -7 each cause significant neurological morbidity in Britain and Ireland. Arch Dis Child. 2005;90(6):619-23.

Pohl-Koppe A, Blay M, Jäger G, Weiss M. Human herpes virus type 7 DNA in the cerebrospinal fluid of children with central nervous system diseases. Eur J Pediatr. 2001;160(6):351-8.

Venâncio P, Brito MJ, Pereira G, Vieira JP. Anti-N-methyl-D-aspartate receptor encephalitis with positive serum antithyroid antibodies, IgM antibodies against mycoplasma pneumoniae and human herpesvirus 7 PCR in the CSF. Pediatr Infect Dis J. 2014;33(8):882-3.

Luzzi S, Del Maestro M, Elbabaa SK, Galzio R. Letter to the Editor Regarding "One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event". World Neurosurg. 2020;134:660.

Bellantoni G, Guerrini F, Del Maestro M, Galzio R, Luzzi S. Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case. eNeurologicalSci. 2019;14:31-3.

Ciappetta P, D'Urso P I, Luzzi S, Ingravallo G, Cimmino A, Resta L. Cystic dilation of the ventriculus terminalis in adults. J Neurosurg Spine. 2008;8(1):92-9.

Luzzi S, Giotta Lucifero A, Brambilla I, Semeria Mantelli S, Mosconi M, Foiadelli T, et al. Targeting the medulloblastoma: a molecular-based approach. Acta Biomed. 2020;91(7-s):79-100.

Watzinger F, Ebner K, Lion T. Detection and monitoring of virus infections by real-time PCR. Mol Aspects Med. 2006;27(2-3):254-98.

Baldanti F, Gatti M, Furione M, Paolucci S, Tinelli C, Comoli P, et al. Kinetics of Epstein-Barr virus DNA load in different blood compartments of pediatric recipients of T-cell-depleted HLA-haploidentical stem cell transplantation. J Clin Microbiol. 2008;46(11):3672-7.

Furione M, Rognoni V, Cabano E, Baldanti F. Kinetics of human cytomegalovirus (HCMV) DNAemia in transplanted patients expressed in international units as determined with the Abbott RealTime CMV assay and an in-house assay. J Clin Virol. 2012;55(4):317-22.

van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604-7.

Bigi S, Fischer U, Wehrli E, Mattle HP, Boltshauser E, Bürki S, et al. Acute ischemic stroke in children versus young adults. Ann Neurol. 2011;70(2):245-54.

Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al. 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):1261-7.

Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018;378(9):840-51.

Gastaldi M, Scaranzin S, Jarius S, Wildeman B, Zardini E, Mallucci G, et al. Cell-based assays for the detection of MOG antibodies: a comparative study. J Neurol. 2020;267(12):3555-64.

Chang K, Frankovich J, Cooperstock M, Cunningham MW, Latimer ME, Murphy TK, et al. Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. J Child Adolesc Psychopharmacol. 2015;25(1):3-13.

Yoshikawa T, Ihira M, Suzuki K, Suga S, Matsubara T, Furukawa S, et al. Invasion by human herpesvirus 6 and human herpesvirus 7 of the central nervous system in patients with neurological signs and symptoms. Arch Dis Child. 2000;83(2):170-1.

Corral Í, Sainz de la Maza S, Rodríguez M, Kawiorski MM, López-Martínez MJ, Galán JC. Molecular detection of human herpesvirus 7 DNA in cerebrospinal fluid from adult patients with neurological disorders. J Neurovirol. 2018;24(3):333-8.

Schwartz KL, Richardson SE, Ward KN, Donaldson C, MacGregor D, Banwell B, et al. Delayed primary HHV-7 infection and neurologic disease. Pediatrics. 2014;133(6):e1541-7.

Foiadelli T, Savasta S, Battistone A, Kota M, Passera C, Fiore S, et al. Nucleotide variation in Sabin type 3 poliovirus from an Albanian infant with agammaglobulinemia and vaccine associated poliomyelitis. BMC Infect Dis. 2016;16:277.

Manti S, Licari A, Montagna L, Votto M, Leonardi S, Brambilla I, et al. SARS-CoV-2 infection in pediatric population. Acta Biomed. 2020;91(11-s):e2020003.

Savasta S, Rovida F, Foiadelli T, Campana AM, Percivalle E, Marseglia GL, et al. West-Nile virus encephalitis in an immunocompetent pediatric patient: successful recovery. Ital J Pediatr. 2018;44(1):140.

Orsini A, Corsi M, Santangelo A, Riva A, Peroni D, Foiadelli T, et al. Challenges and management of neurological and psychiatric manifestations in SARS-CoV-2 (COVID-19) patients. Neurol Sci. 2020;41(9):2353-66.

Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10(12):835-44.

Foà-Tomasi L, Avitabile E, Ke L, Campadelli-Fiume G. Polyvalent and monoclonal antibodies identify major immunogenic proteins specific for human herpesvirus 7-infected cells and have weak cross-reactivity with human herpesvirus 6. J Gen Virol. 1994;75 ( Pt 10):2719-27.

Sutherland S, Christofinis G, O'Grady J, Williams R. A serological investigation of human herpesvirus 6 infections in liver transplant recipients and the detection of cross-reacting antibodies to cytomegalovirus. J Med Virol. 1991;33(3):172-6.

Morris NA, Kaplan TB, Linnoila J, Cho T. HSV encephalitis-induced anti-NMDAR encephalitis in a 67-year-old woman: report of a case and review of the literature. J Neurovirol. 2016;22(1):33-7.

Nosadini M, Granata T, Matricardi S, Freri E, Ragona F, Papetti L, et al. Relapse risk factors in anti-N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol. 2019;61(9):1101-7.

Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, et al. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med. 1994;331(7):432-8.

Fay AJ, Noetzel MJ, Mar SS. Pediatric Hemorrhagic Brainstem Encephalitis Associated With HHV-7 Infection. Pediatr Neurol. 2015;53(6):523-6.

Luzzi S, Crovace AM, Del Maestro M, Giotta Lucifero A, Elbabaa SK, Cinque B, et al. The cell-based approach in neurosurgery: ongoing trends and future perspectives. Heliyon. 2019;5(11):e02818.

Giotta Lucifero A, Luzzi S, Brambilla I, Trabatti C, Mosconi M, Savasta S, et al. Innovative therapies for malignant brain tumors: the road to a tailored cure. Acta Biomed. 2020;91(7-s):5-17.

Luzzi S, Giotta Lucifero A, Brambilla I, Magistrali M, Mosconi M, Savasta S, et al. Adoptive immunotherapies in neuro-oncology: classification, recent advances, and translational challenges. Acta Biomed. 2020;91(7-s):18-31.

Foiadelli T, Naso M, Licari A, Orsini A, Magistrali M, Trabatti C, et al. Advanced pharmacological therapies for neurofibromatosis type 1-related tumors. Acta Biomed. 2020;91(7-s):101-14.

Giotta Lucifero A, Luzzi S, Brambilla I, Schena L, Mosconi M, Foiadelli T, et al. Potential roads for reaching the summit: an overview on target therapies for high-grade gliomas. Acta Biomed. 2020;91(7-s):61-78.

Wilbur C, Bitnun A, Kronenberg S, Laxer RM, Levy DM, Logan WJ, et al. PANDAS/PANS in childhood: Controversies and evidence. Paediatr Child Health. 2019;24(2):85-91.

Kirvan CA, Swedo SE, Snider LA, Cunningham MW. Antibody-mediated neuronal cell signaling in behavior and movement disorders. J Neuroimmunol. 2006;179(1-2):173-9.

Berzero G, Campanini G, Vegezzi E, Paoletti M, Pichiecchio A, Simoncelli AM, et al. Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts. Neurol Neuroimmunol Neuroinflamm. 2021;8(2).

Downloads

Published

21-03-2022

How to Cite

1.
Human Herpes Virus 7-related encephalopathy in children. Acta Biomed [Internet]. 2022 Mar. 21 [cited 2024 Jun. 30];92(S4):e2021415. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/12664