Primary Human herpesvirus 7 (HHV7) infection is almost ubiquitous, and mostly asymptomatic in children, in whom it can present as exanthema subitum. Little is known on the clinical relevance of HHV7 neuroinvasion in immunocompetent children. This series describes 10 patients (median age 10 years, M:F=4:6), with acute encephalopathy in whom HHV7-DNA was detected on cerebrospinal fluid (CSF) by RT-PCR. All patients were healthy before the acute event. 6/10 patients had meningoencephalitis, two of which with acute disseminated encephalomyelitis; 4/10 showed acute neuropsychiatric symptoms. None of them presented the classical skin rash, but five had fever. Electroencephalogram (EEG) showed abnormalities (focal and generalized slowing) exclusively in patients with meningoencephalitis. 5/10 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 0.88. 4/10 patients had pleocytosis and 1/10 hyperproteinorrachia on CSF. Polyclonal bands on CSF and sera were found in 5/7 patients, one patient had intratecal IgG synthesis. Total Ig, IgG-subclasses, and lymphocyte populations were within normal ranges in all patients. CSF/sera IL-17 dosages were performed in two patients, resulting in the upper range-limits. Outcome was favourable in all children, although 3/10 had minor neurological and cognitive sequelae. Mean follow-up period of 5.2 months. 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. Little is known about the role of cytokine pattern alterations during HHV7 encephalitis. We speculate on the importance of immune-mediated mechanisms in provoking clinical features. Future perspectives will investigate cytokine profiles and the role of the immune system in the pathogenesis of HHV7-related encephalopathy. Short-term outcome was favourable in all children, even without any specific antiviral therapy. Further studies are needed to better understand both clinical phenotype and long-term outcome associated with HHV-7 encephalopathy.
L’infezione primaria da Herpesvirus 7 (HHV7) è ubiquitaria durante la prima infanzia, con prevalenza >90% nei primi cinque anni di vita; decorre in modo asintomatico o associato a sesta malattia. Scopo dello studio è stato approfondire la rilevanza clinica della capacità neuroinvasiva di HHV7 in bambini immunocompetenti. Si tratta di uno studio retrospettivo di 10 casi (età mediana: 10 anni, M:F=4:6) ricoverati per encefalopatia acuta/subacuta presso la Clinica Pediatrica del Policlinico S. Matteo (Pavia) dal 2012 al 2018, il cui liquor cefalorachidiano (LCR) è risultato positivo per HHV7-DNA tramite RT-PCR. Tutti i pazienti erano immunocompetenti e precedentemente sani. 6/10 mostravano un quadro meningoencefalitico (e.g. alterato stato di coscienza, agitazione, crisi epilettiche e deficit neurologici focali di nuova insorgenza, segni meningei), di cui due encefalomieliti acute disseminate (ADEM); 4/10 presentavano un quadro neuropsichiatrico acuto (PANS). L’elettroencefalogramma (EEG) presentava anomalie lente (diffuse o focali) in tutti i casi di meningoencefalite, assenti nei quadri psicotici. Alterazioni della RMN erano evidenti in 5/10. Le copie di HHV7 su LCR erano comprese tra 20 e 3,500/mL (mediana 66 copie/mL), con un rapporto medio LCR/sangue di 0.88. 4/10 mostravano pleiocitosi, 1/10 iperproteinorrachia. In 7/10 è stato realizzato l’isoelettrofocusing e valutata la presenza di danno di barriera ematoencefalica (BEE): bande oligoclonali sono state evidenziate in un paziente con sintomi menignoencefalitici; 5/10 avevano bande policlonali su liquor e siero; un solo caso di ADEM aveva danno di BEE. L’outcome è stato favorevole per tutti i pazienti, con sintomi neuropsichiatrici persistenti all’ultimo follow-up in due casi. Follow-up medio: 5.2 mesi. In conclusione, è evidente come HHV7 possa invadere il SNC in bambini immunocompetenti, generando quadri encefalopatici acuti di tipo meningoencefalitico o neuropsichiatrico. La presenza di danno di BBE e un elevato rapporto LCR/siero di copie virali si associano a maggior severità clinica. L’outcome a breve termine è generalmente favorevole, anche in assenza di specifiche terapie antivirali. Ulteriori studi sono necessari per caratterizzare il fenotipo clinico e l’outcome a lungo termine dell’encefalopatia da HHV7.
Encefalopatia acuta da Herpes virus umano 7 (HHV-7): studio retrospettivo su una coorte di pazienti pediatrici
ROSSI, VIRGINIA
2018/2019
Abstract
Primary Human herpesvirus 7 (HHV7) infection is almost ubiquitous, and mostly asymptomatic in children, in whom it can present as exanthema subitum. Little is known on the clinical relevance of HHV7 neuroinvasion in immunocompetent children. This series describes 10 patients (median age 10 years, M:F=4:6), with acute encephalopathy in whom HHV7-DNA was detected on cerebrospinal fluid (CSF) by RT-PCR. All patients were healthy before the acute event. 6/10 patients had meningoencephalitis, two of which with acute disseminated encephalomyelitis; 4/10 showed acute neuropsychiatric symptoms. None of them presented the classical skin rash, but five had fever. Electroencephalogram (EEG) showed abnormalities (focal and generalized slowing) exclusively in patients with meningoencephalitis. 5/10 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 0.88. 4/10 patients had pleocytosis and 1/10 hyperproteinorrachia on CSF. Polyclonal bands on CSF and sera were found in 5/7 patients, one patient had intratecal IgG synthesis. Total Ig, IgG-subclasses, and lymphocyte populations were within normal ranges in all patients. CSF/sera IL-17 dosages were performed in two patients, resulting in the upper range-limits. Outcome was favourable in all children, although 3/10 had minor neurological and cognitive sequelae. Mean follow-up period of 5.2 months. 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. Little is known about the role of cytokine pattern alterations during HHV7 encephalitis. We speculate on the importance of immune-mediated mechanisms in provoking clinical features. Future perspectives will investigate cytokine profiles and the role of the immune system in the pathogenesis of HHV7-related encephalopathy. Short-term outcome was favourable in all children, even without any specific antiviral therapy. Further studies are needed to better understand both clinical phenotype and long-term outcome associated with HHV-7 encephalopathy.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
Per maggiori informazioni e per verifiche sull'eventuale disponibilità del file scrivere a: unitesi@unipv.it.
https://hdl.handle.net/20.500.14239/25125