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BK virus (BKV) encephalitis is a rare complication after hematopoietic stem cell transplantation (HSCT). A 43-year-old woman with recurrent follicular lymphoma after autologous HSCT received allogeneic bone marrow transplantation from a human leukocyte antigen-matched related donor. Neutrophil engraftment was achieved on post-transplant day 13. Memory loss and noncooperative attitude toward the medical staff were observed on day 16, and her mental status worsened progressively. Magnetic resonance imaging (MRI) showed nonspecific findings on day 19; however, cerebrospinal fluid (CSF) analysis including real-time polymerase chain reaction on day 20 revealed elevated levels of BKV 4.67 × 10 4 copy/mL. BKV encephalitis was diagnosed based on CSF findings, intravenous administration of immunoglobulin and cidofovir was started, and the immunosuppressive agent dose was reduced. Diffusion-weighted MRI on day 28 showed signal abnormalities in the bilateral periventricular white matter. Although the follow-up CSF analysis on day 35 was negative for BKV, her mental status and MRI findings did not improve, and she died on day 55 because of respiratory failure. This case emphasizes the importance of considering BKV encephalitis as a differential diagnosis of post-transplant encephalitis, considering the central nervous system-associated immune reconstitution inflammatory syndrome in patients with worsening central nervous system findings after eradication of BKV in the CSF., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

ABSTRACT Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies. ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1 act : general activation of microglial cells; Iba1 nod : formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; pat early : patients treated with early high dose steroid shot; pat late : patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum.

Human herpesviruses (HHVs) cause a wide variety of central nervous system (CNS) infections including meningitis and encephalitis. While HHV-8 is not typically associated with neurological diseases, several studies have indicated a relationship, such as secondary central nervous system (CNS) metastases and a few isolated cases of HHV-8 encephalitis in acquired immunodeficiency syndrome (HIV). However, it has not been previously linked to encephalitis in solid organ transplantation (SOT). This case presents the first-ever instance of HHV-8 encephalitis in a SOT recipient. Our case highlights the association of HHV-8-related diseases, such as post-transplant Kaposi's Sarcoma (KS), with encephalitis. The patient was diagnosed with KS before developing neurological symptoms and received a prompt clinical response through intravenous foscarnet and ganciclovir treatment for 14 days. It is important to note that HHV-8 is a rare cause of encephalitis, and diagnosis requires a high index of suspicion in the appropriate clinical context, allowing for the use of antiviral therapy. This case also underscores the importance of considering the possibility of HHV-8-related diseases in SOT recipients, as they are at risk of developing such infections., (© 2024 Wiley Periodicals LLC.)

Human herpesvirus 6 (HHV-6) is a widely spread DNA virus that is ubiquitous and persistent with primary infection occurring in early childhood, with reactivation of the infection a common phenomenon in severely immunocompromised hosts, including hematopoietic stem cell transplant (HSCT) patients, influencing morbidity and mortality. A wide spectrum of clinical presentations is reported in the literature with HHV-6 reactivation including post-transplant limbic encephalitis (PALE). We report the unusual case of a 6-year-old female 107 days postallogenic HSCT due to transfusion dependent beta thalassemia major who developed acute cerebellitis with secondary supratentorial hydrocephalus that required invasive surgical intervention. In addition to accompanying imaging findings, the patient tested positive for HHV-6 by PCR from both serum and CSF samples and demonstrated dramatic improvement with the institution of steroid therapy in addition to ganciclovir treatment. The availability of rapid diagnostic measures in addition to a multidisciplinary approach is crucial to manage HHV-6 encephalitis and associated complications in HSCT patients., Competing Interests: The authors declare no conflict of interest.​, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Posterior leukoencephalopathy syndrome (PRES) is a rare neurological disease possibly associated with the use of calcineurin inhibitors like cyclosporine A (CSA). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the outbreak of coronavirus disease 19 (COVID-19) can cause neurological manifestations. We described a case of CSA-related PRES whose diagnosis was difficult due to a concurrent infection with SARS-CoV-2., Observation: The 16-year-old patient was known to have corticosteroid-resistant nephrotic syndrome secondary to minimal change disease. CSA was introduced, and on the fifth day of treatment, the patient presented with seizures followed by fever. Biological and magnetic resonance imaging data were in favor of SARS-CoV-2 encephalitis. Relief of immunosuppression by discontinuation of CSA was decided and the patient was put on anticonvulsants. After being declared cured of COVID-19, which was without other clinical signs, the CSA was reintroduced but the patient presented with seizures the next day. This allowed the physicians to rectify the diagnosis and relate the seizures to a CSA-related PRES., Conclusion: Infection with SARS-CoV-2 could be a differential diagnosis of a PRES related to calcineurin inhibitors.

Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Griesman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts., Case: Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction., Management and Outcome: She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The extracellular space (ECS) is an important barrier against viral attack on brain cells, and dynamic changes in ECS microstructure characteristics are closely related to the progression of viral encephalitis in the brain and the efficacy of antiviral drugs. However, mapping the precise morphological and rheological features of the ECS in viral encephalitis is still challenging so far. Here, a robust approach is developed using single-particle diffusional fingerprinting of quantum dots combined with machine learning to map ECS features in the brain and predict the efficacy of antiviral encephalitis drugs. These results demonstrated that this approach can characterize the microrheology and geometry of the brain ECS at different stages of viral infection and identify subtle changes induced by different drug treatments. This approach provides a potential platform for drug proficiency assessment and is expected to offer a reliable basis for the clinical translation of drugs., (© 2024 Wiley‐VCH GmbH.)

This meta-analysis aims to evaluate the efficacy of Angong Niuhuang Pill (ANP) as an adjuvant therapy in the treatment of viral encephalitis. Seven databases (PubMed, Cochrane Library, Embase, SinoMed, CNKI, VIP and WanFang) were included for literature retrieval from inception to July 2023. Randomized controlled trials comparing ANP plus conventional therapy with conventional therapy alone were eligible. Pooled effect sizes and 95% confidence intervals (CIs) were calculated for evaluating efficacy and safety. Sensitivity analysis and publication bias assessments were performed for analyzing the inconclusiveness of findings. 13 studies involving 1045 cases were included for meta-analysis. Adjuvant treatment with ANP increased the probability of the total effective rate by 17% compared with conventional treatment (Risk ratios (RR) = 1.17, 95%CI [1.08, 1.27]). The disappearance time of clinical syndromes and signs was significantly decreased after adjuvant treatment with ANP, including the time of defervescence (weighted mean difference (WMD) = -1.59, 95%CI [-2.09, -1.09]), the time of consciousness recovery (WMD = -1.79, 95%CI [-2.06, -1.51]), the time of headache disappearance (WMD = -1.51, 95%CI [-1.93, -1.08]), the time of tic disappearance (WMD = -1.88, 95%CI [-2.39, -1.36]). The adjuvant efficacy of ANP for treating viral encephalitis (VE) appears to improve the total effective rate and shorten the disappearance time of clinical syndromes. More high-quality randomized controlled trials (RCTs) are needed to support our findings.

Objective: To determine the frequency of parenteral Acyclovir-induced Acute Kidney Injury (AKI) in patients with viral encephalitis., Study Design: Descriptive study. Place and Duration of the Study: Department of Neurology, Liaquat National Hospital, Karachi, from January to December 2021., Methodology: A total of 89 suspected and proven cases of encephalitis receiving IV Acyclovir were collated. All had extensive medical histories and underwent CSF studies with +/- brain imaging. CSF routine and viral PCR were done. Acyclovir-induced AKI was defined as a rise in serum creatinine of >0.3 mg/dl in 48 h or by ≥1.5 times the baseline value, and its severity was staged into 1 (risk), 2 (injury), and 3 (failure) according to the KDIGO guidelines (Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group, 2012). Patients' variables, including age, gender, presenting features, comorbid conditions, and CSF findings, were divided into two groups, i.e. with and without AKI., Results: This research included 89 patients with a mean age of 48 years. AKI occurred in 34 patients (38.2%). The frequency of AKI with Stage 1 was 24%, Stage 2 was 44%, and Stage 3 was 32%; approximately two-thirds of cases were in Stage 2 and 3 (p >0.05). Five patients (5.6%) from Stage 3, required dialysis., Conclusion: AKI is an important adverse effect of parenteral acyclovir, which necessitates its early identification and timely management. Renal function monitoring is essential for patients on Acyclovir treatment as they are at risk for AKI., Key Words: Acyclovir, Acute kidney injury, Viral encephalitis, Creatinine, Kidney Disease Improving Global Outcomes.

Background: Some patients with viral encephalitis in China seek treatment with Chinese patent medicine (CPM) to improve their symptoms, but few studies have focused on the impact of CPM on the prognosis of viral encephalitis (VE). The aim of this multicenter retrospective study was to assess the benefit of adjunctive CPM therapy on the outcome of children with VE in China., Methods: This study retrospectively included 834 children with viral encephalitis who were hospitalized at five medical institutions from 2018 to 2021. Univariate and multivariate logistic regression was used to assess the effect of CPM on sequelae in patients with VE. 1:1 propensity score matching was used to exclude the effect of confounding factors. Forest plots were used to observe the effect of CPM on the prognosis of VE in different subgroups., Results: There were fewer patients with sequelae in the group of patients using CPM regardless of whether they were matched or not. The results of multivariate logistic regression analysis showed that the use of CPM was an independent protective factor for the development of sequelae in VE patients (OR = 0.063, 95 % CI: 0.011-0.350, p = 0.002). Subgroup analyses showed that CPM was a protective factor for the development of sequelae regardless of the presence or absence of coma and comorbidities. In addition, we evaluated other outcome indicators and found shorter duration of illness, fever and headache in children with EV in the CPM group., Conclusion: Adjunctive CPM therapy may significantly reduce sequelae in children with VE, as well as effectively alleviate patients' clinical symptoms. However, more prospective studies and clinical trials are needed to further evaluate its efficacy and safety., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2023. Published by Elsevier GmbH.)

Introduction: Human herpesvirus 6B (HHV-6B) encephalitis is common in immunosuppressed patients and presents a diagnostic challenge for physicians. Metagenomic next-generation sequencing (mNGS) may facilitate early diagnosis of HHV-6B encephalitis. Herein, we described a case of HHV-6B encephalitis following transplantation for severe aplastic anemia (SAA) diagnosed by mNGS., Case Summary: A 31-year-old male underwent myeloablative haploid hematopoietic stem cell transplantation for the treatment of SAA. On day + 21 after transplantation, the patient developed symptoms such as sudden epilepsy, drowsiness, memory dislocation, and memory loss. HHV-6B encephalitis was confirmed based on cranial MRI and mNGS of cerebrospinal fluid. Following antiviral therapy with sodium foscarnet, the symptoms improved and HHV-6B was negative by mNGS. There were no serious sequelae. Currently, the patient is in good health and is still under follow-up., Conclusions: A case of HHV-6B encephalitis after SAA transplantation was diagnosed by mNGS of cerebrospinal fluid in time and was effectively treated with sodium foscarnet., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Kaile Zhang, Jianli Xu, Gang Chen, Ruixue Yang, Ming Jiang, Hailong Yuan.)

Background: From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis., Objectives: The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis., Methods: A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included metaanalyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis., Results: Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both viruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may only have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID- 19 infections (long COVID-19) have been described but not with influenza infections. Mortality associated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease., Conclusion: Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both carry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treatment are available for both viruses., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rationale: Refractory hypotension is a life-threatening condition that can result from various causes. We report a rare case of refractory hypotension following herpes simplex virus type 1 encephalitis that was successfully treated with hormone therapy., Patient Concerns: The patient was a 66-year-old male who was admitted to the hospital because of fever, chills, convulsions, and impaired consciousness. He developed respiratory failure and was intubated. Cerebrospinal fluid metagenomic sequencing confirmed herpes simplex virus type 1 infection. He received piperacillin-tazobactam for anti-infection, acyclovir for antiviral therapy, and dexamethasone for anti-inflammatory therapy. He had repeated episodes of hypotension despite fluid resuscitation and vasopressor therapy., Diagnosis: The diagnosis of herpes simplex virus type 1 encephalitis complicated by refractory hypotension was based on the patient's epidemiological history, clinical manifestations, laboratory tests, and imaging studies. Cerebrospinal fluid examination was the most important diagnostic method, which could detect viral nucleic acids. Head magnetic resonance imaging showed a large recent lesion in the right temporal-parietal and insular lobes., Interventions: The treatment of refractory hypotension mainly included anti-infection, antiviral, anti-inflammatory, and hormone therapy. Hormone therapy used methylprednisolone shock treatment until tapering withdrawal. Other treatments included fluid resuscitation, vasopressors, anticonvulsants, etc., Outcomes: The patient's blood pressure stabilized after receiving methylprednisolone shock treatment, and his mean arterial pressure increased from 73 mm Hg to 92 mm Hg within 24 hours. Three months later, the patient's blood pressure was normal without medication, and he had a good social and physical recovery., Lessons: This case illustrates the possible role of hormone therapy in restoring blood pressure in patients with refractory hypotension following viral encephalitis. It suggests that adrenal insufficiency or autonomic dysfunction may be involved in the pathophysiology of this condition. Further studies are needed to confirm the efficacy and safety of hormone therapy in this setting., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE., Methods: We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1., Results: We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown., Conclusions: Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit., (© 2023. The Author(s).)

Herpes simplex encephalitis is a life-threatening disease of the central nervous system caused by herpes simplex viruses (HSVs). Following standard of care with antiviral acyclovir treatment, most patients still experience various neurological sequelae. Here we characterize HSV-1 infection of human brain organoids by combining single-cell RNA sequencing, electrophysiology and immunostaining. We observed strong perturbations of tissue integrity, neuronal function and cellular transcriptomes. Under acyclovir treatment viral replication was stopped, but did not prevent HSV-1-driven defects such as damage of neuronal processes and neuroepithelium. Unbiased analysis of pathways deregulated upon infection revealed tumour necrosis factor activation as a potential causal factor. Combination of anti-inflammatory drugs such as necrostatin-1 or bardoxolone methyl with antiviral treatment prevented the damages caused by infection, indicating that tuning the inflammatory response in acute infection may improve current therapeutic strategies., (© 2023. The Author(s).)

Background: Pseudorabies virus (PRV) was thought to only infect animals. Recent studies have shown that it can also infect human., Case Presentation: We report a case of pseudorabies virus encephalitis and endophthalmitis, diagnosed 89 days after onset, confirmed with intraocular fluid metagenomic next generation sequencing (mNGS) after the result of two cerebrospinal fluid (CSF) mNGS tests were negative. Although treatment with intravenous acyclovir, foscarnet sodium, and methylprednisolone improved the symptoms of encephalitis, significant diagnostic delay resulted in permanent visual loss., Conclusions: This case suggests that pseudorabies virus (PRV) DNA in the intraocular fluid may have a higher positivity than that in the CSF. PRV may persist in the intraocular fluid for an extended period and may thus require extended antiviral therapy. Patients with severe encephalitis and PRV should be examined with the focus on pupil reactivity and light reflex. A fundus examination should be performed in patients with a central nervous system infection, specifically, those in a comatose state, to help reduce eye disability., (© 2023. The Author(s).)

Rationale: Excessive daytime sleepiness (EDS) is a clinical manifestation of various disorders. Here, we report 2 cases of EDS related to Epstein-Barr virus (EBV) encephalitis., Patient Concerns: Both the patients were elderly men. Case 1 presented with EDS with headache and fever. Case 2 was presented with EDS only. The 2 patients slept normally at night without taking sleeping pill. They were able to get up and go to the toilet and eat by themselves during the day, but they almost slept at other times., Diagnosis: After admission, a lumbar puncture was performed to collect the cerebrospinal fluid, and next-generation sequencing showed that EBV infection was detected. Combined with the patient's head magnetic resonance imaging and clinical features, a diagnosis of EBV encephalitis was made., Interventions: Both patients received antiviral therapy., Outcomes: Case 1 had a rapid improvement in headache and fever and was discharged from the hospital after the symptoms of EDS gradually improved. In case 2, EDS symptoms gradually improved. Two patients were followed up for 3 months after discharge, and the outcome was good., Lessons: EDS can also be the main clinical manifestation of viral encephalitis, and we should diagnose and identify it early and treat it promptly., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Human herpesvirus-6 (HHV-6), in particularly HHV-6B, can reactivate in immunocompromised patients. Especially after stem cell transplantation, reactivation of HHV-6 can cause complications, such as limbic encephalitis. We present a case of a 61-year-old man with B-cell non-Hodgkin lymphoma. He presented with subacute lethargy, confusion and hyperhidrosis. Following this, we will give a short review of the literature considering clinical and technical features as well as treatment options., (© 2022. The Author(s) under exclusive licence to Belgian Neurological Society.)

Although acute encephalopathy is quite commonly seen in patients of SARS-CoV-2 infection, encephalitis characterised by brain inflammation is relatively rare. Encephalitis caused by Herpes simplex type 1 is the most common cause of identified sporadic encephalitis, and early diagnosis and prompt treatment can prevent the devastating outcome. In this brief communication, we report a case of SARS-CoV-2 associated haemorrhagic encephalitis mimicking herpes encephalitis. In today's pandemic era, it is especially important to distinguish herpes encephalitis from SARS-CoV-2-associated encephalitis as treatment and prognosis of both the conditions differ greatly. This case highlights the importance of suspecting SARS-CoV-2 infection in a patient presenting with clinical symptoms and brain imaging suggestive of Herpes encephalitis., (© 2022. Crown.)

Background: The aim of this study was to systematically evaluate the efficacy and prognosis of acyclovir combined with naloxone in the treatment of patients with viral encephalitis (VE)., Methods: PubMed, Web of Science, Embase, CNKI, and WanFang Data were searched for relevant literature published between 2000 and 2021. Meta-analysis was performed using Stata16.0 software. The treatment group was treated with acyclovir combined with naloxone, and the control group was treated with acyclovir alone., Results: A total of 12 studies with 986 participants were included. Compared with the control group, the treatment group could not only significantly improve the treatment response rate (OR = 5.53, 95% CI: 3.50, 8.74; P  ≤ 0.001), but also reduce the incidence of adverse reactions (OR = 0.25, 95% CI: 0.17, 0.38; P  ≤ 0.001). In addition, the combined treatment significantly inhibited the levels of inflammatory factors and neuron-specific enolase (NSE) in VE patients. The time for cerebrospinal fluid to return to normal (SMD = -2.73, 95% CI: -2.96, -2.51; P  ≤ 0.001), as well as the disappearance time of meningeal irritation (SMD = -3.58, 95% CI: -4.96, -2.20; P  ≤ 0.001), headache (SMD = -3.87, 95% CI: -5.84, -1.91; P  ≤ 0.001), convulsion (SMD = -3.65, 95% CI: -4.56, -2.75; P  < 0.001), tic (SMD = -4.083, 95% CI: -5.18, -2.98; P  ≤ 0.001) and disturbance of consciousness (SMD = -4.96, 95% CI: -6.28, -3.63; P  ≤ 0.001) in the treatment group were significantly shorter than those in the control group., Conclusion: A combination of acyclovir and naloxone can reduce the inflammatory response and shorter the time to symptom relief and disappearance, which is worthy of clinical promotion., Competing Interests: The authors claim that there is no conflict of interest between them., (Copyright © 2022 Wei Wang et al.)

Background: For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis., Methods: We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used., Results: We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033-0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events., Conclusion: Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed., (© 2021. The Author(s).)

Viral encephalitis is a severe syndrome that can lead to encephalopathy, seizures, focal deficits, and neurological sequelae and death. It is mainly caused by neurotropic herpes viruses (i.e., HSV and VZV), although other pathogens may be observed in specific geographic regions or conditions. Recent advances in neuroimaging and molecular biology (PCR, metagenomics) allow for faster and more accurate etiological diagnoses, although their benefits need to be confirmed to provide guidelines for their use and interpretation. Despite intravenous acyclovir therapy and supportive care, outcomes remain poor in about two-thirds of herpes encephalitis patients requiring ICU admission. Randomized clinical trials focusing on symptomatic measures (i.e. early ICU admission, fever control, and treatment of seizures/status epilepticus) or adjunctive immunomodulatory therapies (i.e. steroids, intravenous immunoglobulins) to improve neurologic outcomes have not been conducted in the ICU setting. Large prospective multicenter studies combining clinical, electrophysiological, and neuroimaging data are needed to improve current knowledge on care pathways, long-term outcomes, and prognostication., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, a single negative study should not exclude future development, especially if CNS symptoms are present. Acute graft-versus-host disease and cord blood transplantation are both significant risk factors for HHV-6 encephalitis. Human leukocyte antigen (HLA) mismatch, engraftment complications, or certain HLA alleles have also been associated with HHV-6 encephalitis. Chromosomally integrated HHV-6 must also be ruled out to prevent inappropriate and potentially harmful administration of antivirals. Due to the severe short- and long-term sequelae of HHV-6 encephalitis, appropriate treatment should be administered as soon as possible.

Objectives: Enterovirus (EV) is a frequent cause of encephalitis. The optimal therapeutic approach remains a matter of debate. We present the case of an immunosuppressed patient with EV encephalitis treated successfully with intravenous immunoglobulin (IVIG) and report the results of a systematic review on the characteristics of EV encephalitis, as well as the safety and efficacy of IVIG therapy., Methods: A systematic review was conducted using the PubMed, Cochrane Database, BIOSIS Previews, and ClinicalTrials.gov databases to identify all reports on patients with EV encephalitis as of December 31, 2020. The main outcomes assessed were the efficacy and safety of the respective therapeutic approach., Results: A total of 73 articles were included: one prospective trial, one retrospective and prospective case series, one purely retrospective case series, and 70 case reports. The case reports included a total of 101 patients. Immunosuppressed patients were at higher risk of contracting EV encephalitis and experiencing a fatal course. Hypogammaglobulinaemia particularly predisposes to EV disease, even with a moderate reduction in serum IgG levels. IVIG therapy in the immunosuppressed may confer a survival advantage., Conclusions: IVIG therapy is rarely associated with severe adverse events and may be considered in immunosuppressed patients with EV encephalitis. Future trials should investigate the optimal IVIG dosing and route of application, the benefit of antibody-enriched IVIG preparations, and the serum immunoglobulin level that should trigger prophylactic replacement., Competing Interests: Declarations Conflict of interest JW reports personal fees from Boehringer Ingelheim and personal fees from UCB, outside the submitted work. AL reports grants from Roche GmbH, outside the submitted work. TvO reports grants, personal fees, and non-financial support from Novartis Pharma, personal fees from Roche Pharma, personal fees from Biogen Idec Austria, personal fees from Liva Nova, grants from Grossegger & Drbal GmbH, grants from Merck, personal fees from Indivior Austria GmbH, personal fees and non-financial support from gtec GmbH Austria, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Philips, personal fees and non-financial support from UCB Pharma, personal fees from Almirall, and personal fees from Eisai, outside the submitted work; he is also Web Editor-in-Chief of the European Academy of Neurology (EAN), co-chair of the EAN Scientific Panel for Epilepsy, and vice president of the Österreichische Gesellschaft für Epileptologie (Austrian ILAE chapter). JP and AT report no disclosures., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A number of viruses, including Herpes Simplex Virus (HSV), West Nile Virus (WNV), La Crosse Virus (LACV), Zika virus (ZIKV) and Tick-borne encephalitis virus (TBEV), have the ability to gain access to the central nervous system (CNS) and cause severe neurological disease or death. Although encephalitis cases caused by these viruses are generally rare, there are relatively few treatment options available for patients with viral encephalitis other than palliative care. Many of these viruses directly infect neurons and can cause neuronal death. Thus, there is the need for the identification of useful therapeutic compounds that can inhibit virus replication in neurons or inhibit virus-induced neuronal cell death. In this paper, we describe the methodology to test compounds for their ability to inhibit virus-induced neuronal cell death. These protocols include the isolation and culturing of primary neurons; the culturing of neuroblastoma and neuronal stem cell lines; infection of these cells with viruses; treatment of these cells with selected drugs; measuring virus-induced cell death using MTT or XTT reagents; analysis of virus production from these cells; as well as the basic understanding in mode of action. We further show direct evidence of the effectiveness of these protocols by utilizing them to test the effectiveness of the polyphenol drug, Rottlerin, at inhibiting Zika virus infection and death of neuronal cell lines.

Purpose: Encephalitis secondary to human herpesvirus 6 (HHV-6) infection is frequently encountered in immunocompromised patients; in contrast, HHV-6 encephalitis in immunocompetent patients is rare. There are only 3 reports of status epilepticus due to HHV-6 encephalitis in immunocompetent adults. In the present study, a case of refractory status epilepticus secondary to HHV-6 encephalitis was reported in an immunocompetent female., Case Report: We report a case of a previously healthy 46-year-old female who presented with a one-week history of back pain, fever and generalized tonic-clonic seizures that progressed to status epilepticus. The video electroencephalography showed epileptiform discharges on both frontotemporal regions. Neuroimaging showed hyperintensities on the bilateral insula and temporal lobes. The cerebrospinal fluid showed elevated pressure and was positive for HHV-6. She was given ganciclovir and a total of eleven antiepileptic drugs. Despite these medications, she developed refractory status epilepticus and eventually succumbed due to multiple medical complications., Conclusion: This case highlights HHV-6 encephalitis as an important diagnostic consideration in patients presenting with refractory status epilepticus, regardless of immune status.

A 25-year-old female veterinarian presented with 1-week of flu-like symptoms followed by progressive encephalopathy. She was originally from Nicaragua and had been in the USA for 4 months. In the emergency department, she was confused and non-verbal with meningismus and facial myoclonus, but with an otherwise non-focal neurological exam. MRI brain abnormalities were consistent with viral encephalitides. Influenza B was detected via nasopharyngeal swab PCR. Mental status improved rapidly with oseltamivir. In such presentations, especially during flu season, influenza encephalitis must be considered, to facilitate early recognition of this entity and allow for targeted treatment.

Background: biomarkers can be helpful in identifying patients who may profit by explicit treatments or evaluating the reaction to the treatment of specific disease. Finding unique biomarkers in the process of disease could help clinicians in identifying serious disease in the early stage, so as to improve prognosis., Objective: these investigations, nonetheless, have made constrained progress. Numerous infections are known to cause intense viral encephalitis (VE) in people which can cause a variable level of meningeal just as parenchymal aggravation. Initial clinical manifestations in most encephalitis are nonspecific, resembling a viral-like illness. However, with disease progression, symptoms can become quite severe and fatal, including prominent cranial hypertension, cognitive problems, cerebral hernia and respiratory failure. Forwards: the clinical and research center discoveries in huge numbers of those viral issues are to a great extent comparable and in this way increasingly explicit biomarkers for indicative and prognostic intentions are justified. These biomarkers are progressively significant in the acknowledgment and treatment of the viral central nervous system (CNS) issue., Conclusion: Clinical manifestations have been the indicative approaches for analysis of viral encephalitis. Lots of studies have been endeavored to distinguish progressively objective laboratory-based quantitative CSF biomarkers for VE., (© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.)

The complexity of the central nervous system (CNS) is not recapitulated in cell culture models. Thin slicing and subsequent culture of CNS tissue has become a valued means to study neuronal and glial biology within the context of the physiologically relevant tissue milieu. Modern membrane-interface slice culturing methodology allows for straightforward access to both CNS tissue and feeding medium, enabling experimental manipulations and analyses that would otherwise be impossible in vivo. CNS slices can be successfully maintained in culture for up to several weeks for investigation of evolving pathology and long-term intervention in models of chronic neurologic disease.Herein, membrane-interface slice culture models for studying viral encephalitis and myelitis are detailed, with emphasis on the use of these models for investigation of pathogenesis and evaluation of novel treatment strategies. We describe techniques to (1) generate brain and spinal cord slices from rodent donors, (2) virally infect slices, (3) monitor viral replication, (4) assess virally induced injury/apoptosis, (5) characterize "CNS-specific" cytokine production, and, (6) treat slices with cytokines/pharmaceuticals. Although our focus is on CNS viral infection, we anticipate that the described methods can be adapted to address a wide range of investigations within the fields of neuropathology, neuroimmunology, and neuropharmacology.

Introduction: Everolimus is a mammalian target of rapamycin inhibitor and is approved as second-line treatment or beyond for renal cell carcinoma. We report a case of a 75-year-old male treated with everolimus for metastatic renal cell carcinoma, after sunitinib treatment, who was diagnosed with human herpesvirus 6 encephalitis., Case Report: After 39 months of everolimus, 10 mg per day, our patient was admitted with fever, consciousness disorders and a partial epileptic crisis. Laboratory tests revealed lymphopenia (170 lymphocytes/mm 3 ), and polymerase chain reaction in cerebrospinal fluid was positive for human herpesvirus 6. Brain magnetic resonance imaging study demonstrated hippocampal abnormality and a pontine lesion., Management and Outcome: The patient stopped everolimus treatment indefinitely. He received ganciclovir initially intravenously, with a rapid clinical improvement, as well as polyvalent immunoglobulins were given to correct hypogammaglobulinemia. Two months later, antiviral therapy was switched to oral ganciclovir, which was never stopped. A new lumbar puncture was performed one month after the initiation of antiviral treatment, which did not reveal human herpesvirus 6 DNA anymore., Discussion: Human herpesvirus 6 encephalitis is more common in hematopoietic stem cell transplant recipients and HIV patients. This is the first case probably associated to everolimus treatment. In contrast to most patients diagnosed with this infection, who either die or develop neurologic sequelae, our patient almost fully recovered two months later.

Influenza encephalopathy, a rare manifestation of influenza infection in the adult population which is not widely recognised, can present with confusion and focal neurological symptoms, including aphasia. The aim of this report is to illustrate the unique presentation of influenza encephalopathy and discuss the need for close attention to and monitoring of this rare but highly fatal disease.A 28-year-old woman was admitted with acute-onset confusion and incoherent speech. CT of the head was unremarkable. Cerebrospinal fluid analysis showed elevation of protein, but was otherwise unremarkable. A detailed history revealed recent upper respiratory symptoms which prompted a rapid influenza test which was positive and oseltamivir was started. The patient's confusion and aphasia gradually improved and her speech was back to her baseline by the next day., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Enteroviruses are one of the most important causes of viral encephalitis in the neonatal period. However, the non-specificity of the symptoms presented renders its diagnosis challenging. Intracranial MRI has been reported to be a very useful imaging modality that can detect the characteristic white matter lesions around the periventricular regions. In this study, we report a case of a patient with neonatal encephalitis who presented with normal white blood cell counts in the initial cerebrospinal fluid analysis. A lumbar puncture retap identified pleocytosis, and polymerase chain reaction assays detected enterovirus 71 in the blood and stool samples. Furthermore, MRI revealed atypical disseminated cortical and subcortical white matter lesions on diffusion weighted images, and neuroradiological re-evaluation showed necrotic changes 2 weeks later. This unique case expands our knowledge of the spectrum of neurological disorders due to enterovirus 71 infection in neonatal period.

Objective: To analyze the clinical efficacy of naloxone combined with acyclovir in the treatment of children viral encephalitis and the impacts on inflammatory factors IL-1 and IL-6., Patients and Methods: 96 children with viral encephalitis were retrospectively analyzed. They were treated from July 2013 to January 2014 in our hospital. They were divided into control group (45 cases treated with acyclovir) and observation group (51 cases treated with acyclovir combined with naloxone). Both groups were treated with comprehensive measures. Changes of the content of serum IL-1 and IL-6 in the two groups before and after treatment were monitored by enzyme-linked immunosorbent assay (ELISA). Signs, recovery time of clinical symptoms, total effective rate, occurrence of adverse reactions and adverse reactions after treatment of children in the two groups were compared., Results: Levels of serum IL-1 and IL-6 of children in the control group and the observation group decreased after treatment, and the decrease was greater in the observation group (p<0.05). Signs and recovery time of clinical symptoms of the observation group were significantly shorter than that of the control group (p<0.05). Indexes of serum in the observation group were significantly lower than those of the control group after treatment (p<0.05). The total effective rate of the observation group was significantly higher than that of the control group (p<0.05). The prevalence of adverse reactions and sequelae in the observation group were lower than those in the control group (p<0.05)., Conclusions: In the treatment of children, viral encephalitis has naloxone combined with ganciclovir had a more significant effect on the decrease of levels of serum IL-1 and IL-6; naloxone combined with acyclovir in the treatment of children viral encephalitis had better effects, lower adverse reactions and lower prevalence of sequelae compared with sole medication, which is worth clinical promotion.

The COVID-19 pandemic that attracted global attention in December 2019 is well known for its clinical picture that is consistent with respiratory symptoms. Currently, the available medical literature describing the neurological complications of COVID-19 is gradually emerging. We hereby describe a case of a 31-year-old COVID-19-positive patient who was admitted on emergency basis. His clinical presentation was primarily neurological, rather than the COVID-19's classical respiratory manifestations. He presented with acute behavioural changes, severe confusion and drowsiness. The cerebrospinal fluid analysis was consistent with COVID-19 encephalitis, as well as the brain imaging. This experience confirms that neurological manifestations might be expected in COVID-19 infections, despite the absence of significant respiratory symptoms. Whenever certain red flags are raised, physicians who are involved in the management of COVID-19 should promptly consider the possibility of encephalitis. Early recognition of COVID-19 encephalitis and timely management may lead to a better outcome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of our study was to compare the course of TBE in children and adults. A retrospective analysis of the medical records of 669 patients was performed. The patients were categorized into 2 groups: Group I with 68 children and group II with 601 adults. TBE symptoms in children were milder compared with adults, with meningitis in 97% of cases. In adults, meningoencephalitis and meningoencephalomyelitis made up 49.26% of cases. Nausea and vomiting are more frequent in children, while neurological manifestations are more frequent in adults. There were no differences in CSF pleocytosis at the onset of disease in both groups, while CSF protein concentration was higher in adults. Children treated with corticosteroids over 7 days had higher checkup pleocytosis than pleocytosis at the onset of disease compared with adults. Corticosteroid use prolongs the disease duration but does not influence the development of TBE sequelae. Children had more favourable outcomes than adult patients.

HIV-associated neuroinflammation is primarily driven by CNS macrophages including microglia. Regulation of these immune responses, however, remains to be characterized in detail. Using the SIV/macaque model of HIV, we evaluated CNS expression of triggering receptor expressed on myeloid cells 2 (TREM2) which is constitutively expressed by microglia and contributes to cell survival, proliferation, and differentiation. Loss-of-function mutations in TREM2 are recognized risk factors for neurodegenerative diseases including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Nasu-Hakola disease (NHD); recent reports have also indicated a role for TREM2 in HIV-associated neuroinflammation. Using in situ hybridization (ISH) and qRT-PCR, TREM2 mRNA levels were found to be significantly elevated in frontal cortex of macaques with SIV encephalitis compared with uninfected controls (P = 0.02). TREM2 protein levels were also elevated as measured by ELISA of frontal cortex tissue homogenates in these animals. Previously, we characterized the expression of CSF1R (colony-stimulating factor 1 receptor) in this model; the TREM2 and CSF1R promoters both contain a PU.1 binding site. While TREM2 and CSF1R mRNA levels in the frontal cortex were highly correlated (Spearman R = 0.79, P < 0.001), protein levels were not well correlated. In SIV-infected macaques released from ART to study viral rebound, neither TREM2 nor CSF1R mRNA increased with rebound viremia. However, CSF1R protein levels remained significantly elevated unlike TREM2 (P = 0.02). This differential expression suggests that TREM2 and CSF1R play unique, distinct roles in the pathogenesis of HIV CNS disease.

Although infectious mononucleosis due to Epstein-Barr virus (EBV) is a common disease among young individuals, central nervous system (CNS) complications are rare. In this report, we describe a case of CNS complications caused by EBV in a previously healthy young woman. She presented to our hospital with a 9-day history of headache and sore throat, followed by the development of fever and facial edema 6 days prior to admission. On Day 2 of admission, she was confused (Glasgow Coma Scale score: 10 points) and had fever, muscle weakness in her right arm and leg, stiff neck, and roving eye movement. We detected EBV in a cerebrospinal fluid (CSF) sample using a polymerase chain reaction (PCR) test. The magnetic resonance imaging of her brain revealed dural enhancement and right parietal and temporal lobe lesions. She was treated with acyclovir and high-dose steroid therapy. She responded well to treatment, recovered without neurologic sequelae, and was discharged home on Day 12. Our experience suggests that PCR detection of EBV DNA in CSF may be useful in diagnosing EBV encephalitis and that prognosis may be associated with an area of the brain that is affected and the time from symptom onset to starting treatment., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Pseudorabies virus (PRV) primarily infects swine but can infect cattle, dogs, and cats. Several studies have reported that PRV can cross the specie barrier and induce human encephalitis, but a definitive diagnosis of human PRV encephalitis is debatable due to the lack of PRV DNA detection. Here, we report a case of human PRV encephalitis diagnosed by the next-generation sequencing (NGS) of PRV sequences in the cerebrospinal fluid (CSF) of a patient. A male pork vendor developed fever and seizures for 6 days. NGS results showed PRV sequences in his CSF and blood. Sanger sequencing showed that PRV DNA in the CSF and PRV antibodies in both the CSF and blood were positive. MRI results revealed multiple inflammatory lesions in the bilateral hemisphere. Based on the clinical and laboratory data, we diagnosed the patient with PRV encephalitis. This case suggests that PRV can infect humans, causing severe viral encephalitis. People at risk of PRV infection should improve their self-protection awareness.

Newborns are particularly susceptible to severe forms of herpes simplex virus 1 (HSV-1) infection, including encephalitis and multisystemic disseminated disease. The underlying age-dependent differences in the immune response that explain this increased susceptibility relative to the adult population remain largely understudied. Using a murine model of HSV-1 infection, we found that newborn mice are largely susceptible to intracranial and intraperitoneal challenge while adult mice are highly resistant. This age-dependent difference correlated with differential basal-level expression of components of innate immune signaling pathways, which resulted in dampened interferon (IFN) signaling in the newborn brain. To explore the possibility of modulating the IFN response in the newborn brain to recapitulate the adult phenotype, we administered exogenous IFN-β in the context of disseminated HSV-1 infection. IFN-β treatment resulted in significantly increased survival and delayed viral neuroinvasion in the newborn. These effects were associated with changes in the type I IFN response in the brain, reduced viral replication in the periphery, and the stabilization of the blood-brain barrier (BBB). Our study reveals important age-dependent differences in the innate immune response to HSV-1 infection and suggests a contribution of the BBB and the brain parenchyma in mediating the increased susceptibility to HSV-1 infection observed in the newborn. These results could provide the basis for potential new therapeutic strategies for life-threatening HSV-1 infection in newborns. IMPORTANCE Herpes simplex virus (HSV) is a ubiquitous human pathogen affecting 50 to 80% of the population in North America and Europe. HSV infection is commonly asymptomatic in the adult population but can result in fatal encephalitis in the newborn. Current treatment with acyclovir has improved mortality in the newborn; however, severe neurologic sequelae are still a major concern following HSV encephalitis. For this reason, there is a critical need to better understand the underlying differences in the immune response between the two age groups that could be used to develop more effective treatments. In this study, we investigated differences in the innate immune response to viral infection in the brains of newborn and adult mice. We found that, similar to humans, newborn mice are more susceptible to HSV infection than the adult. Increased susceptibility was associated with dampened innate immune responses in the newborn brain that could be rescued by administering interferon beta., (Copyright © 2020 Giraldo et al.)

Objective: To describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon., Methods: Retrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR., Results: Twenty patients were identified (13 males). The average age was 49.7±22.2 years. The most common complaint was headache (n=17/20). Common comorbidities included hypertension (n=7/20) and diabetes mellitus (n=5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5±6.6 vs. 12.2±5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae., Conclusion: VZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Human herpesvirus 6 (HHV-6) infection is the cause of roseola infantum in children. The reactivation of HHV-6 is associated with multiple clinical syndromes including encephalitis and myelitis, especially in haematopoietic stem cell transplant recipients. However, the virus can cause encephalitis in other immunosuppressed as well as immunocompetent individuals. We report a case of a 70-year-old woman who was immunocompromised secondary to treatment of rheumatoid arthritis with leflunomide and methotrexate. The patient presented with acute ataxia, diplopia and dysarthria. MRI brain showed an enhancing lesion in the midbrain. The diagnosis of HHV-6 encephalitis was made after HHV-6 A DNA was detected in both serum and cerebrospinal fluid. Treatment consisted of a 3-week course of intravenous ganciclovir along with physiotherapy. At a 3-month follow-up, repeat MRI brain showed a decrease in size and oedema of the lesion and the patient's neurological function was improved., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The standard for diagnosing meningoencephalitis includes cerebrospinal fluid (CSF) culture and viral polymerase chain reaction (PCR). Approval of the FilmArray® BioFire® Meningitis/Encephalitis (ME) panel has reduced time to detection of several pathogens and improved diagnostic sensitivity. The objective of this study was to determine the impact on intravenous (IV) acyclovir duration of the ME panel compared to previously utilized CSF studies within a large health system with a central laboratory. A multicenter quasi-experimental cohort study of adult and pediatric patients was conducted (n = 208). The primary endpoint was duration of IV acyclovir, which was decreased (41.6 v. 30.8 hours; P < 0.01) with the ME panel. Secondary outcomes including test-turnaround time (TAT) and the impact of utilizing a central laboratory were explored. Subgroup analyses demonstrated that number of daily couriers from hospital to the central laboratory (0 versus 7 versus 3 versus 2 couriers) and hospital distance from the central laboratory (0 versus 1-10 versus 11-20 versus 21-30 miles) significantly impacted TAT (P < 0.01). While duration of IV acyclovir for the entire healthcare system was reduced, the duration at individual sites was not impacted by number of couriers or distance from the central laboratory., (Copyright © 2019 Elsevier Inc. All rights reserved.)