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Home , Viral meningitis

IAR Journal of Medical Case Reports ISSN Print : 2709-3220 | ISSN Online : 2709-3239 Frequency : Bi-Monthly Language : English Origin : Kenya Website : https://www.iarconsortium.org/journal-info/iarjmcr Case Report

HSV6 as a Cause of Severe Complicated Meningo- in a Lebanese Immunocompotent Patient Article History Abstract: HHV-6 constitutes a widely spread viral among young Received: 25.10.2020 children population with a seroprevalence of > 80% in children > 2 years of age Accepted: 12.11.2020 (Ansari, A. et al., 2002). HHV-6 is an enveloped DNA belongs to the β- herpes virus family and, together with its closest homologue HHV-7, forms the Revision: 18. 11.2020 roseoloviruses subfamily (2). A wide range of clinical manifestation of HHV-6 Published: 20.11.2020 has been described which may vary with age and immune status of a child including acute febrile illness with or without rash, Roseola Infantum, febrile Author Details convulsion, meningo-encephalitis, hepatitis and mononucleosis-like illness, etc. Imad Chokr, MD1. Khadije El Sabeh, MD. Lea Here we report the case of a 2 years old boy previously healthy who presented Chokr1. Ounssi Hammoud. Oussama Skafi, with , lethargy, decreased level of consciousness and with neck stiffness, MD2. Ranad Gerges, MD1. Rouwayda Dana, diagnosed clinically with severe meningo-encephalitis and confirmed on MD. Bassem Abou Merhi, MD1. Rayane MRI. Human Herpes Virus 6 was the etiology of his encephalitis, verified by his Mahfouz, MD1 blood neuro-9 PCR. Authors Affiliations Keywords: Meningo-Encephalitis; Human herpes virus 6, 7; HSV. 1Lebanese University, Faculty of Medical Sciences, Pediatrics Department, Lebanon INTRODUCTION: 2Zahraa University Hospital, Neuro-Surgery Meningo-Encephalitis defined as an inflammatory condition of Department, Lebanon the brain parenchyma and the membranes surrounding the brain and Corresponding Author* , has been associated with serious side effects and constitutes a Bassem Abou Merhi, MD life threatening condition if untreated in the right way. Despite the How to Cite the Article: introduction of vaccines against , rubella, , and Imad Chokr, Chawki Hammoud, Lea Chokr, which had decreased the rate of encephalitis, remain Khadije El Sabeh, Oussama Skafi, Anthony the main causative agent of meningo-encephalitis throughout childhood. Chalfoun, Maarouf Hammoud, Bassem Abou Viruses can invade the CNS via viremia by crossing the blood-brain Merhi, and Rayane Mahfouz (2020); An barrier (e.g. Arboviruses) or by a retrograde axonal transport (e.g. Atypical Presentation of a Huge Brain virus) and it may infect neurons leading to cytotoxicity (e.g. herpes without Neurologic Sequalae in a 28 Days Old simplex virus; HSV) (Whitley, R. J. 1990). Reported HSV encephalitis Infant; .IAR J Med Cse Rep. 1(2)32-35. cases with subsequent or concurrent antibodies against brain antigens like Copyright @ 2020: This is an open-access article anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibodies have been distributed under the terms of the Creative Commons Attribution license which permits cited (Whitley, R. J. 1990). Meningo-encephalitis can rarely occur as a unrestricted use, distribution, and reproduction complication of HHV-6 or as the primary manifestation of HHV-6 in any medium for non commercial use infection in otherwise immunocompetent hosts. The high tropism of (NonCommercial, or CC-BY-NC) provided the HHV-6 towards the T cells may explain its ability to be the cause of original author and source are credited. persistent infection in different tissues including the salivary glands, in addition to its ability to the complement-regulatory trans membrane protein CD46 constitutes the only identified cellular receptor, this protein is ubiquitously expressed in humans, allowing the viruses to infect a wide range of cells and tissues, including cells from the (CNS) (Reynaud, J. M., & Horvat, B. 2013). In this article we report a case of HHV-6 meningo-encephalitis in a 2 year old previously healthy boy presented with clinical acute meningo-encephalitis confirmed by brain MRI, complicated by right hemiplegia, treated with full course of 21 days antiviral and antibacterial therapy and showed complete neurologic improvement without any sequalae.

CASE DESCRIPTION: We present the case of an almost two years old boy previously healthy, born by cesarean section with no ICN admission, his past medical and surgical histories are negative, no previous hospitalization or recurrent . The child had normal neurodevelopmental history (no delay in milestones), vaccination history was up to date (according to his age). He presented with a history of somnolence, change in level of consciousness and high grade fever that developed progressively over the last three days. In the ED he was febrile, tachycardic, normotensive, and lethargic with hyperextended neck. His physical exam was significant for neck stiffness, normally reactive pupils, poorly responsive

Available: https://iarconsortium.org/journal-info/iarjmcr 32

Imad Chokr et al., IAR J Med Cse Rep; Vol-1, Iss- 2 (Nov-Dec, 2020): 32-35 baby; his was 11-12. Urgently first dose of Ceftriaxone, Vancomycin and Amikacin were given and CT brain done showing total enfacement of the brain tissue with no evidence of the sulcal pattern Figure 1, CRP was elevated associated with left shift leukocytosis. The patient was admitted to PICU, infectious disease specialist and neurologist were consulted, IV antibiotics meningeal dose continued, acyclovir added, was contraindicated because of brain , methylprednisolone added to treatment. 48 hours after admission, clinical improvement started to show with reduced neck stiffness and slowly recovering mental status (he started to follow command by eye movements according to the corresponding direction with slight neck deviation, good muscle strength and slight improvement in swallowing). Repeated CT brain revealed a large area of focal hypo density involving the left fronto-parietal lobe and Sylvian fissure, focal densities were also noted involving the left thalamus and retro thalamic area with persistence of the effacement of the brain tissue and compression of the ventricular system, Mannitol was started and MRI brain was scheduled.

Figure 1: CT scan of brain showing total enfacement of the brain tissue with no evidence of the sulcal pattern.

However patient suddenly deteriorated on the same day with acute onset of right hemiparesis, abnormal movements of upper and lower extremities, so an urgent MRI showed findings compatible with including ischemic components associated with thrombophlebitis (partial vein thrombosis) involving the superior dural sagittal venous sinus and internal cerebral vein near the great vein of Galen Figure 2.

Figure 2 MRI brain showing findings compatible with meningoencephalitis including ischemic components associated with thrombophlebitis (partial vein thrombosis) involving the superior dural sagittal venous sinus and internal cerebral vein near the great vein of Galen.

Neurosurgeon was consulted and phenytoin started. EEG was abnormal revealing Theta waves alternating with polymorphic Alpha waves and consistent with brain injury. MRV was significant for endoluminal filling defect involving the superior sagittal venous sinus consistent with partial vein thrombosis and also mild narrowing at the union of great vein of Galen and internal cerebral vein, coagulation studies came back normal. The patient was kept under close observation and monitoring in PICU, he was on room air with no respiratory distress, stable hemodynamically with persistent fever, echocardiography, abdominal CT scan were normal. Neurologically, the patient improved gradually over the following 2 weeks and regained his normal level of consciousness and most of his sensory and motor power on the right side. MRI repeated after 12 days showed partial regression of the previous findings. Although clinical improvement was obvious, fever persisted, viral panel (whole blood multiplex real time PCR) was positive for Human Herpes Virus 6. Table 1 33

Imad Chokr et al., IAR J Med Cse Rep; Vol-1, Iss- 2 (Nov-Dec, 2020): 32-35 Table 1: Viral meningitis panel (Neuro 9) positive for HHV6

Patient received 20 days of IV antibiotics and Acyclovir and was discharged home after resorption of fever and almost total recovery of neurological functions.

ISCUSSION: sequelae. (You, S. J. 2020) Two cases were reported in D 2018 and 2020 about pediatric patients who died Viral infection of the brain leads to meningitis, because of HHV-6 encephalitis due to associated brain meningo-encephalitis, or encephalitis, in descending edema (Miyahara, H. et al., 2018; & Sevilla-Acosta, F. order of frequency (Whitley, R. J. 1990). Encephalitis is et al., 2020). In 2000, Taferner et al., reported four the of the central nervous system cases of encephalitis with refractory brain edema parenchyma and is manifested by neurologic treated with craniectomy (Taferner, E. et al., 2001). To dysfunction with symptoms like altered mental status, the best of our knowledge, this is the first case of behavior, or personality; motor or sensory deficits; pediatric meningo-encephalitis caused by HHV6 speech or movement disorders; ; hemiparesis; infection, associated with brain ischemia due to and paresthesis (Cherry, J.D. et al., 2009). Human thrombophlebitis and with mild neurologic sequelae. herpesvirus 6 (HHV-6) is the common collective name Our patient presented with altered mental status and for Human betaherpesvirus 6A (HHV-6A) and Human fever and soon after deteriorated with new onset right betaherpesvirus 6B (HHV-6B), two of the nine hemiparesis, imaging showing signs of meningo- herpesviruses known to have humans as their primary encephalitis, brain edema and partial vein thrombosis (Adams, M. J., & Carstens, E. B. 2012). They are with normal coagulation studies. All the studies double stranded DNA viruses within the reported that early treatment with antiviral agents and Betaherpesvirinae subfamily and of the genus immunomodulatory agents (e.g., steroids, IVIg) (You, Roseolovirus (Jaworska, J. et al., 2010). HHV-6 was S. J. 2020) and immediate management of brain edema identified as the causative agent of the common are essential for the survival of the patient affected by childhood disease Roseola Infantum (Exanthem HHV6 meningo-encephalitis. The baby in this case Subitum, also called Roseola or sixth disease) improved with treatment consisting of acyclovir, (Yamanishi, K. et al., 1988). Encephalitis of variable corticosteroids and Mannitol and regained almost severity can occur as a complication of Roseola or as normal neurologic function. the primary manifestation of HHV-6 infection in otherwise immunocompetent hosts (Ahtiluoto, S. et al., 2000; McCullers, J. A. et al., 1995; Ohsaka, M. et al., CONCLUSION: 2006; Mannonen, L. et al., 2007; Crawford, J. R. et al., HHV6 infection is not always benign and 2007; & Provenzale, J. M. et al., 2010). In complicated courses of the disease should be considered immunosuppressed hosts, reactivation is associated with in children with neurologic symptoms, treatment should a worse outcome such as encephalitis, hepatitis, or graft be started in early stages to prevent poor outcome. rejection. In immunocompetent hosts, this persistent infection is generally of no consequence (Marseglia, L. REFERENCES: et al., 2016). However, HHV6 associated meningo- 1. Ansari, A., Li, S., Abzug, M. J., & Weinberg, A. encephalitis in immunocompetent patients has been (2002) Human Herpesviruses 6 and 7 and Central described in only few case reports with not well defined Nervous System Infection in Children. EID Journal incidence and clinical syndrome. A study conducted in Metrics University of Colorado School of 2020 on nine patients positive for HHV-6 showed the Medicine, Denver, Colorado, USA. The Children’s following results: three (33.3%) had encephalitis, three Hospital, Denver, Colorado, USA; May 2002. (33.3%) had meningitis, one (11.1%) had complex 2. Reynaud, J. M., & Horvat, B. (2013). Human febrile , and two (22.2%) had fever alone. All Herpesvirus 6 and Neuroinflammation .Hindawi patients with HHV-6 and encephalitis had neurologic 34

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