The efficacy of haemoperfusion combined with continuous venovenous haemodiafiltration in the treatment of severe viral encephalitis in children.

BACKGROUND: This study investigated the efficacy of the integrated blood purification mode of early haemoperfusion (HP) combined with continuous venovenous haemodiafiltration (CVVHDF) in children with severe viral encephalitis, and evaluated the correlation of cerebrospinal fluid (CSF) neopterin (NPT) levels with prognosis. METHODS: The records of children with viral encephalitis who received blood purification treatment in the authors' hospital from September 2019 to February 2022 were retrospectively analysed. According to the blood purification treatment mode, they were divided into the experimental group (HP + CVVHDF, 18 cases), control group A (CVVHDF only, 14 cases), and control group B (16 children with mild viral encephalitis who did not receive blood purification treatment). The correlation between the clinical features, severity of the disease and the extent of lesions on brain magnetic resonance imaging (MRI) and the CSF NPT levels was analysed. RESULTS: The experimental group and control group A were comparable with respect to age, gender and hospital course (P > 0.05). There was no significant difference in speech and swallowing functions between the two groups after treatment (P > 0.05) and no significant difference in 7 and 14-day mortality (P > 0.05). The CSF NPT levels in the experimental group before treatment were significantly higher compared with control group B (P < 0.05). The extent of brain MRI lesions correlated positively with CSF NPT levels (P < 0.05). In the experimental group (14 cases), the serum NPT levels decreased after treatment, whereas the CSF NPT levels increased after treatment, and the differences were statistically significant (P < 0.05). Dysphagia and motor dysfunction correlated positively with CSF NPT levels (P < 0.05). CONCLUSION: Early HP combined with CVVHDF in the treatment of severe viral encephalitis in children may be a better approach than CVVHDF only for improving prognosis. Higher CSF NPT levels indicated the likelihood of a more severe brain injury and a greater possibility of residual neurological dysfunction.

Viral Encephalitis in Adults: A Narrative Review.

Viral infections of the central nervous system cause frequent hospitalization. The pathogenesis of viral encephalitis involves both the direct action of invading pathogens and the damage generated by the inflammatory reaction they trigger. The type of signs and symptoms presented by the patient depends on the severity and location of the ongoing inflammatory process. Most of the viral encephalitides are characterized by an acute development, fever, variable alterations in consciousness (confusion, lethargy, even coma), seizures (focal and generalized) and focal neurologic signs. The specific diagnosis of encephalitis is usually based on lumbar puncture. Cerebrospinal fluid examination should be performed in all patients unless absolutely contraindicated. Also, electroencephalogram and neuroimaging play a prominent role in diagnosis. Airway protection, ventilatory support, the management of raised intracranial pressure and correction of electrolyte disorders must be immediately considered in a patient with altered mental status. The only therapy strictly recommended is acyclovir in HSV encephalitis. The use of adjunctive glucocorticoids has poor-quality evidence in HSV, EBV, or VZV encephalitis. The role of antiviral therapy in other types of viral encephalitis is not well defined.

A Nanobody-Mediated Virus-Targeting Drug Delivery Platform for the Central Nervous System Viral Disease Therapy.

Viral diseases of the central nervous system (CNS) represent a major global health concern. Difficulties in treating these diseases are caused mainly by the biological tissues and barriers, which hinder the transport of drugs into the CNS. To counter this, a nanobody-mediated virus-targeting drug delivery platform (SWCNTs-P-A-Nb) is constructed for CNS viral disease therapy. Viral encephalopathy and retinopathy (VER), caused by nervous necrosis virus (NNV), is employed as a disease model. SWCNTs-P-A-Nb is successfully constructed by employing single-walled carbon nanotubes, amantadine, and NNV-specific nanobody (NNV-Nb) as the nanocarrier, anti-NNV drug, and targeting ligand, respectively. Results showed that SWCNTs-P-A-Nb has a good NNV-targeting ability in vitro and in vivo, improving the specific distribution of amantadine in NNV-infected sites under the guidance of NNV-Nb. SWCNTs-P-F-A-Nb can pass through the muscle and gill and be excreted by the kidney. SWCNTs-P-A-Nb can transport amantadine in a fast manner and prolong the action time, improving the anti-NNV activity of amantadine. Results so far have indicated that the nanobody-mediated NNV-targeting drug delivery platform is an effective method for VER therapy, providing new ideas and technologies for control of the CNS viral diseases. IMPORTANCE CNS viral diseases have resulted in many deadly epidemics throughout history and continue to pose one of the greatest threats to public health. Drug therapy remains challenging due to the complex structure and relative impermeability of the biological tissues and barriers. Therefore, development in the intelligent drug delivery platform is highly desired for CNS viral disease therapy. In the study, a nanobody-mediated virus-targeting drug delivery platform is constructed to explore the potential application of targeted therapy in CNS viral diseases. Our findings hold great promise for the application of targeted drug delivery in CNS viral disease therapy.

Reduced impact of viral load of HHV-6 in liquor on severity of AESD due to exanthema subitum: A case report and literature review.

BACKGROUND: The most common causative pathogen of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was reported as HHV-6. Although excitotoxic injury with delayed neuronal death is considered to be a possible pathogenesis of AESD, the detailed pathophysiology remains unclear. CASE PRESENTATION: We present a twelve-month-old girl with AESD due to HHV-6 primary infection. She was successfully treated for AESD including targeted temperature management and the administration of vitamin B1, B6, and L-carnitine. Although the viral load of HHV-6 in her liquor was high (12,000 copies/mL), she fully recovered without antiviral agent use. DISCUSSION: There has been no study focusing on the HHV-6 viral load in patients with AESD, and only a few case reports have been published. We reviewed the clinical features and viral load in the liquor of our case and four reported infants with AESD due to HHV-6 primary infection who had real-time PCR tests results. Viral loads in the three patients with a poor prognosis were 31.5, negative, and 3,390 copies/mL, respectively. On the other hand, the copy numbers of HHV-6 DNA in the two patients with no sequelae were 12,000 and 106 copies/mL, respectively, and our case had the highest viral load among the five summarized patients.

The roles of microglia in viral encephalitis: from sensome to therapeutic targeting.

Viral encephalitis is a devastating disease with high mortality, and survivors often suffer from severe neurological complications. Microglia are innate immune cells of the central nervous system (CNS) parenchyma whose turnover is reliant on local proliferation. Microglia express a diverse range of proteins, which allows them to continuously sense the environment and quickly react to changes. Under inflammatory conditions such as CNS viral infection, microglia promote innate and adaptive immune responses to protect the host. However, during viral infection, a dysregulated microglia-T-cell interplay may result in altered phagocytosis of neuronal synapses by microglia that causes neurocognitive impairment. In this review, we summarize the current knowledge on the role of microglia in viral encephalitis, propose questions to be answered in the future and suggest possible therapeutic targets.

Treatment of Viral Encephalitis.

Viral encephalitis is difficult to treat. Herpes simplex encephalitis has been successfully treated with acyclovir, but is still a cause for significant morbidity even with that treatment. A rare form of autoimmune encephalitis related to NMDA receptor antibody after infection by herpes simplex can be treated with corticosteroid therapy. Arthropod-borne encephalitides, such as West Nile virus encephalitis and Eastern equine encephalitis, are primarily treated with supportive measures. Attempts have been made to use immunoglobulin therapy with limited effects. Progressive multifocal leukoencephalopathy has been treated with an emerging immune activation therapy in a limited number of patients with incomplete success.

Bilateral Necrotizing Retinitis following Encephalitis Caused by the Pseudorabies Virus Confirmed by Next-Generation Sequencing.

Purpose: The objective of this study was to report a case of bilateral necrotizing retinitis following viral encephalitis caused by the pseudorabies virus.Case report: A 49-year-old male had decreased bilateral visual acuity after the recovery of consciousness for one month. He had been in an unconsciousness status due to encephalitis for two months before the ocular symptoms developed. He was a pig slaughterer. Ocular ultrasound showed bilateral vitreous haze and retinal detachment. A vitrectomy and silicone oil tamponade were performed on the left eye. During surgery, massive periphery retinal necrosis appearing as a tattered fish net, and multiple retinal holes were observed. The pseudorabies virus was detected by next-generation sequencing in the vitreous specimen.Conclusion: The pseudorabies virus may cause bilateral necrotizing retinitis following viral encephalitis among those with close contact to pigs. Intraocular fluid provides a greater selection of samples and a longer time window for pathogenic detection.

SARS-CoV-2 Encephalitis in a 20-year old Healthy Female.

We report a 20-year-old female with SARS-CoV-2 encephalitis who presented with 4 days of upper respiratory symptoms, fevers and sudden acute altered mental status. An extensive work up led to the most likely cause for the neurologic decompensation to be viewed as SARS-CoV-2 symptomology.

A case of human herpesvirus 6 encephalitis following pediatric hematopoietic stem cell transplantation: early diagnosis and treatment matters.

Human herpesvirus 6 (HHV-6) is one of the life-threatening infectious complications with significant morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Clinically, the diagnosis of HHV-6 encephalitis can be challenging due to a lack of specific symptoms and definitive diagnostic tests. We report a pediatric HSCT recipient who developed late-onset HHV-6 encephalitis without typical radiographic findings. The routine viral infection monitoring protocol contributed to the prompt diagnosis of HHV-6 encephalitis and early therapeutic intervention. The patient was treated successfully without any neurological complications attributable to HHV-6 encephalitis. HHV-6 encephalitis should remain in the differential diagnosis as an important but treatable disease, even for several months after HSCT and even without radiographic findings. Whenever HHV-6 encephalitis is suspected, antivirals should be initiated promptly to prevent its complications.

Viral encephalitis: a practical review on diagnostic approach and treatment / Encefalite viral: uma revisão prática sobre abordagem diagnóstica e tratamento

Abstract Objectives To review the diagnostic criteria for encephalitis and encephalopathy of presumed infectious etiology, as well as the diagnostic workup for viral encephalitis and its treatment approaches. The authors also intended to summarize relevant information on specific viruses frequently found in Brazil. Source of data Literature search on Pubmed/MEDLINE using the following keywords: "viral", "encephalitis", "child", or "adolescents", filtering for articles on humans and in English. Summary of data Viral encephalitis is the most common cause of encephalitis and is responsible for high rates of morbidity, permanent neurologic sequelae, and according to the virus, may have high mortality rates. The most common etiologies are herpesviruses 1 and 2 (HSV-1 and HSV-2), non-polio enterovirus, and arboviruses (in Brazil, dengue, Zika, and chikungunya). Other relevant etiologies are seasonal influenza, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and the re-emergent measles. Conclusion Clinical data, laboratory results, and neuroimaging findings support the diagnosis of encephalitis and the specific viral etiology. To increase the likelihood of etiologic confirmation, it is important to know the best approach to collecting samples and to choose the best identification technique for each virus. The differential diagnosis of viral encephalitis includes other infections and immune-mediated inflammatory central nervous system disorders.

Resumo Objetivos Revisar os critérios diagnósticos para encefalite e encefalopatia de etiologia infecciosa presumida, assim como a investigação diagnóstica para encefalite viral e suas abordagens terapêuticas. Além disso, pretendemos resumir tópicos relevantes sobre os vírus específicos frequentemente encontrados no Brasil. Fonte de dados Pesquisa bibliográfica feita nos bancos de dados Pubmed/Medline utilizando as seguintes palavras-chave: "viral", "encephalitis", "child" ou "adolescents", limitando os artigos a estudos em humanos e escritos em inglês. Resumo dos dados A encefalite viral é a causa mais comum de encefalite e é responsável por altas taxas de morbidade, sequelas neurológicas permanentes e, de acordo com o vírus, altas taxas de mortalidade. As etiologias mais comuns são herpes vírus 1 e 2 (HSV-1 e HSV-2), enterovírus não pólio e arbovírus (no Brasil, Dengue, Zika e Chikungunya). Outras etiologias relevantes são a influenza sazonal, o citomegalovírus (CMV), o vírus Epstein-Barr (EBV), o herpes vírus humano 6 (HHV-6) e o sarampo reemergente. Conclusão Dados clínicos, resultados laboratoriais e de neuroimagem apoiam o diagnóstico de encefalite e a etiologia viral específica. Para aumentar a probabilidade de confirmação etiológica, é importante conhecer a melhor abordagem para coletar amostras e escolher a melhor técnica de identificação para cada vírus. O diagnóstico diferencial de encefalite viral inclui outras infecções e distúrbios inflamatórios do sistema nervoso central imunomediados.

Viral encephalitis: a practical review on diagnostic approach and treatment.

OBJECTIVES: To review the diagnostic criteria for encephalitis and encephalopathy of presumed infectious etiology, as well as the diagnostic workup for viral encephalitis and its treatment approaches. The authors also intended to summarize relevant information on specific viruses frequently found in Brazil. SOURCE OF DATA: Literature search on Pubmed/MEDLINE using the following keywords: "viral", "encephalitis", "child", or "adolescents", filtering for articles on humans and in English. SUMMARY OF DATA: Viral encephalitis is the most common cause of encephalitis and is responsible for high rates of morbidity, permanent neurologic sequelae, and according to the virus, may have high mortality rates. The most common etiologies are herpesviruses 1 and 2 (HSV-1 and HSV-2), non-polio enterovirus, and arboviruses (in Brazil, dengue, Zika, and chikungunya). Other relevant etiologies are seasonal influenza, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and the re-emergent measles. CONCLUSION: Clinical data, laboratory results, and neuroimaging findings support the diagnosis of encephalitis and the specific viral etiology. To increase the likelihood of etiologic confirmation, it is important to know the best approach to collecting samples and to choose the best identification technique for each virus. The differential diagnosis of viral encephalitis includes other infections and immune-mediated inflammatory central nervous system disorders.

Human encephalitis complicated with bilateral acute retinal necrosis associated with pseudorabies virus infection: A case report.

We report the case of a patient who presented with viral encephalitis and a pulmonary infection complicated with bilateral acute retinal necrosis after direct contact with diseased swine. Next-generation sequencing of the cerebrospinal fluid and vitreous humor detected pseudorabies virus (PRV) simultaneously. Intravenous acyclovir and dexamethasone treatment improved the symptoms of encephalitis, and vitrectomy surgery with silicone oil tamponade was used to treat the retinal detachment. This case implies that PRV can infect humans; thus, self-protection is imperative when there is contact with animals.

Akinetic mutism and status epilepticus due to Epstein Barr virus encephalitis.

Neurological complications of Epstein Barr virus (EBV) infection are infrequent and may include occasionally encephalitis, usually with a benign evolution. We here report on an aggressive case of EBV encephalitis in a 14-year-old boy with extensive basal ganglia involvement, and to a lesser degree of brain cortex who presented atypically with akinetic mutism and non-convulsive status epilepticus, requiring intensive care but showed a favorable outcome. EBV encephalitis is uncommon and its best management is unclear. Its pathophysiology is not well understood but could include autoimmunity. Onconeuronal and synaptic antibodies were negative in serum and cerebrospinal fluid, including the dopamine D2 receptor. To the best of our knowledge, this is the first report to evaluate antibodies to D2 receptors in EBV encephalitis. Corticosteroid therapy is usually recommended but the use of acyclovir is controversial. Intensive care is required in severe cases to assure a favorable outcome.

Long-term outcome in neuroZika: When biological diagnosis matters.

OBJECTIVE: To characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection. METHODS: We conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak. RESULTS: Eighty-seven patients, including 6 children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.0%) followed by encephalitis or encephalomyelitis (20.7%), isolated single or multiple cranial nerve palsies (9.2%), other peripheral manifestations (6.9%), and stroke (1.1%). Fourteen patients (16.1%), including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases, all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 13-17 months) was available for 76 patients. Residual disability (modified Rankin Scale score ≥2) was identified in 19 (25.0%) patients; in 6 cases (7.9%), disability was severe (modified Rankin Scale score ≥4). Among patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odds ratio 9.19; confidence interval 1.12-75.22; p = 0.039). CONCLUSIONS: NeuroZika spectrum represents a heterogeneous group of clinical neurologic manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurologic disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalized patients.

Encefalopatía en paciente anciano tras diagnóstico de gripe por el virus influenza B: a propósito de un caso / Encephalopathy in an elderly patient after an influenza B flu diagnosis: a case report

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[Сases of human convalescence from rabies and lifetime diagnostics of lyssavirus encephalitis.]

Notwithstanding the availability of effective vaccines, 40 - 60 thousand rabies cases in humans are reported every year. Almost always the disease is fatal because therapeutic treatment of lyssavirus encephalitis has not been developed. Since 1970 the number of reports on rare cases of convalescence including those using experimental treatment protocols has been gradually increasing 20 cases of convalescence, "partial" convalescence or long-term survival of humans (1970-2015) were selected as they were complaint with laboratory criteria of active lyssavirus infection. Children and teenagers were predominant in the analyzed group (85%). The cases were irregularly spread between the continents: Asia - 6 cases, North America - 6 cases, Africa - 2 cases and Europe - 1 case. India and the USA were on the top of the list of countries by the number of described cases. More than 60% humans were infected from dogs, three cases got infection from bats and 2 cases were allegedly associated with an unknown lyssavirus and an unidentified infection source. 70% cases were vaccinated and 10% cases were treated with gamma globulin before the disease onset. Serological tests for detection of antibodies to lyssaviruses in cerebrospinal fluid of infected humans were typically used for diagnostic laboratory verification. Less than 30% IFA and PCR positives were obtained. Lyssaviruses were never detected. Only 4 convalescent patients were treated using experimental protocols. 80% cases demonstrated severe neurological consequences, four (may be more) patients died afterwards within the period from two months to four years. Different perspectives on prospects of Milwaukee protocol use and other therapeutic techniques are given.

[Encephalitis by type B influenza: a pediatric clinical case and literature review.] / L'encefalopatia da influenza tipo B: descrizione di un caso clinico pediatrico e revisione della letteratura.

We report the case of a 6-year-old girl who presented with encephalitis during type B influenza. The clinical picture was characterized by an alteration of the state of consciousness associated with focal neurological signs with electroencephalographic changes and brain MRI. Clinical improvement was rapid and without neurological outcomes. The clinical characteristics, the pathogenic mechanisms, the prognosis and the therapy of neuroinfluenza cases are described.