Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 435
Filter
1.
Tunis Med ; 102(7): 429-432, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38982969

ABSTRACT

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.


Subject(s)
COVID-19 , Cyclosporine , Posterior Leukoencephalopathy Syndrome , Humans , Posterior Leukoencephalopathy Syndrome/chemically induced , Posterior Leukoencephalopathy Syndrome/diagnosis , COVID-19/complications , COVID-19/diagnosis , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Diagnosis, Differential , Adolescent , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Seizures/etiology , Seizures/diagnosis , Calcineurin Inhibitors/adverse effects , Encephalitis, Viral/diagnosis , Encephalitis, Viral/drug therapy , Magnetic Resonance Imaging
2.
PLoS Pathog ; 20(6): e1012343, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38935789

ABSTRACT

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.


Subject(s)
Lipopeptides , Neurons , Rift Valley Fever , Rift Valley fever virus , Animals , Rift Valley fever virus/drug effects , Mice , Lipopeptides/pharmacology , Rift Valley Fever/virology , Rift Valley Fever/prevention & control , Neurons/metabolism , Neurons/virology , Mice, Inbred C57BL , Humans , Immunity, Innate/drug effects , Encephalitis, Viral/virology , Encephalitis, Viral/immunology , Encephalitis, Viral/prevention & control , Encephalitis, Viral/drug therapy , Antiviral Agents/pharmacology
3.
J Pediatr Hematol Oncol ; 46(6): e426-e429, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38832402

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Herpesvirus 6, Human , Hydrocephalus , Roseolovirus Infections , Humans , Herpesvirus 6, Human/isolation & purification , Hematopoietic Stem Cell Transplantation/adverse effects , Female , Hydrocephalus/etiology , Hydrocephalus/surgery , Child , Roseolovirus Infections/virology , Roseolovirus Infections/diagnosis , Roseolovirus Infections/complications , Roseolovirus Infections/drug therapy , Antiviral Agents/therapeutic use , Encephalitis, Viral/etiology , Encephalitis, Viral/virology , Encephalitis, Viral/diagnosis , Encephalitis, Viral/drug therapy , beta-Thalassemia/complications , beta-Thalassemia/therapy , Immunocompromised Host
4.
J Vis Exp ; (206)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38709054

ABSTRACT

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.


Subject(s)
Drugs, Chinese Herbal , Encephalitis, Viral , Randomized Controlled Trials as Topic , Humans , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Encephalitis, Viral/drug therapy
5.
Emerg Microbes Infect ; 13(1): 2350168, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38687703

ABSTRACT

ABSTRACTBorna 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; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum.


Subject(s)
Brain , Humans , Male , Female , Brain/virology , Brain/immunology , Borna Disease/drug therapy , Borna Disease/virology , Lymphocytes/immunology , Microfilament Proteins/metabolism , Leukocyte Common Antigens/metabolism , Glial Fibrillary Acidic Protein/metabolism , Calcium-Binding Proteins/metabolism , Immunosuppression Therapy , Borna disease virus/physiology , Encephalitis, Viral/drug therapy , Encephalitis, Viral/virology , Encephalitis, Viral/immunology , Neuroglia/virology , Neuroglia/metabolism
6.
Pediatr Infect Dis J ; 43(6): 582-586, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38380931

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Measles , Humans , Measles/complications , Female , Infant , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Measles virus/genetics , Immunocompromised Host , Antiviral Agents/therapeutic use , Measles-Mumps-Rubella Vaccine/adverse effects , Ribavirin/therapeutic use , Encephalitis, Viral/etiology , Encephalitis, Viral/drug therapy , Inclusion Bodies, Viral , Inosine Pranobex/therapeutic use , Measles Vaccine/adverse effects , Measles Vaccine/administration & dosage
7.
J Infect Dev Ctries ; 18(1): 152-157, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38377081

ABSTRACT

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.


Subject(s)
Anemia, Aplastic , Encephalitis, Viral , Encephalitis , Hematopoietic Stem Cell Transplantation , Herpesvirus 6, Human , Roseolovirus Infections , Male , Humans , Adult , Foscarnet/therapeutic use , Herpesvirus 6, Human/genetics , Anemia, Aplastic/therapy , Anemia, Aplastic/complications , Encephalitis, Viral/diagnosis , Encephalitis, Viral/drug therapy , Encephalitis, Viral/cerebrospinal fluid , Roseolovirus Infections/diagnosis , Roseolovirus Infections/drug therapy , Roseolovirus Infections/complications , Hematopoietic Stem Cell Transplantation/adverse effects , High-Throughput Nucleotide Sequencing , Sodium
8.
J Coll Physicians Surg Pak ; 34(2): 151-155, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38342863

ABSTRACT

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.


Subject(s)
Acute Kidney Injury , Drug-Related Side Effects and Adverse Reactions , Encephalitis, Viral , Adult , Humans , Middle Aged , Acyclovir/adverse effects , Retrospective Studies , Risk Factors , Acute Kidney Injury/chemically induced , Acute Kidney Injury/therapy , Encephalitis, Viral/drug therapy , Encephalitis, Viral/chemically induced , Creatinine
9.
Adv Mater ; 36(18): e2311457, 2024 May.
Article in English | MEDLINE | ID: mdl-38243660

ABSTRACT

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.


Subject(s)
Antiviral Agents , Encephalitis, Viral , Extracellular Space , Machine Learning , Quantum Dots , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Extracellular Space/metabolism , Animals , Quantum Dots/chemistry , Encephalitis, Viral/drug therapy , Mice , Brain/diagnostic imaging , Brain/pathology , Rheology , Humans
10.
Phytomedicine ; 124: 155303, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176272

ABSTRACT

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.


Subject(s)
Encephalitis, Viral , Nonprescription Drugs , Child , Humans , Retrospective Studies , Prospective Studies , Encephalitis, Viral/drug therapy , Disease Progression , China
11.
Front Immunol ; 14: 1240089, 2023.
Article in English | MEDLINE | ID: mdl-37809102

ABSTRACT

Autoimmune encephalitis is a rare but critical complication of COVID-19. The management of COVID-19-associated autoimmune encephalitis includes the use of steroids, intravenous immunoglobulin (IVIG), plasmapheresis, and monoclonal antibody therapy. This study presented a patient with critical COVID-19 autoimmune encephalitis who rapidly recovered after the initiation of corticosteroids and IVIG therapy. This study reviewed the current literature on the pathophysiological mechanisms, diagnosis, and management of COVID-19-associated autoimmune encephalitis.


Subject(s)
Autoimmune Diseases of the Nervous System , COVID-19 , Encephalitis, Viral , Humans , Immunoglobulins, Intravenous/therapeutic use , COVID-19/complications , Steroids/therapeutic use , Encephalitis, Viral/drug therapy , Autoimmune Diseases of the Nervous System/drug therapy
12.
Front Immunol ; 14: 1258048, 2023.
Article in English | MEDLINE | ID: mdl-37781407

ABSTRACT

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a treatable autoimmune disorder affecting the central nervous system. Despite extensive research, the exact etiology and pathogenesis of this condition remain unclear. In recent years, autoimmune encephalitis (AE) after viral encephalitis (VE) has gathered significant attention. Here, we present a case report of autoimmune GFAP astrocytopathy after VE in a 43-year-old Asian male with a history of oral and labial herpes. The patient presented with high-grade fever, headache, urinary retention, unresponsiveness, and apathy. Elevated levels of protein and GFAP-IgG were observed in the cerebrospinal fluid (CSF), and enhanced brain magnetic resonance imaging (MRI) revealed linear enhancement oriented radially to the ventricles. Treatment with intravenous immunoglobulin (IVIG) resulted in symptom relief, reduced lesion enhancement, and decreased protein levels. This case report highlights bimodal encephalitis with no discernible interval between VE and autoimmune GFAP astrocytopathy, which poses diagnostic challenges. Notably, autoimmune GFAP astrocytopathy is a novel form of autoimmune encephalitis, and its treatment lacks sufficient clinical experience. Intriguingly, our patient demonstrated sensitivity to IVIG, a treatment that differed from past reports. Therefore, further exploration of treatment strategies for this condition is warranted.


Subject(s)
Autoimmune Diseases of the Nervous System , Encephalitis, Viral , Encephalitis , Humans , Male , Adult , Immunoglobulins, Intravenous/therapeutic use , Glial Fibrillary Acidic Protein , Encephalitis/diagnosis , Encephalitis/drug therapy , Encephalitis/etiology , Encephalitis, Viral/drug therapy
13.
Medicine (Baltimore) ; 102(42): e34988, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37861560

ABSTRACT

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.


Subject(s)
Encephalitis, Herpes Simplex , Encephalitis, Viral , Hypotension , Male , Humans , Aged , Acyclovir/therapeutic use , Encephalitis, Herpes Simplex/drug therapy , Encephalitis, Viral/diagnosis , Encephalitis, Viral/drug therapy , Methylprednisolone/therapeutic use , Hypotension/etiology , Hypotension/complications , Anti-Inflammatory Agents/therapeutic use , Hormones/therapeutic use , Antiviral Agents/therapeutic use
14.
Nat Microbiol ; 8(7): 1252-1266, 2023 07.
Article in English | MEDLINE | ID: mdl-37349587

ABSTRACT

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.


Subject(s)
Encephalitis, Viral , Herpes Simplex , Herpesvirus 1, Human , Humans , Herpesvirus 1, Human/genetics , Herpes Simplex/complications , Herpes Simplex/drug therapy , Acyclovir/pharmacology , Acyclovir/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Encephalitis, Viral/drug therapy , Organoids
15.
BMC Neurol ; 23(1): 192, 2023 May 16.
Article in English | MEDLINE | ID: mdl-37194001

ABSTRACT

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.


Subject(s)
Aqueous Humor , Blindness , Encephalitis, Viral , Endophthalmitis , Herpesvirus 1, Suid , Pseudorabies , Pseudorabies/complications , Pseudorabies/diagnosis , Pseudorabies/drug therapy , Encephalitis, Viral/complications , Encephalitis, Viral/diagnosis , Encephalitis, Viral/drug therapy , Endophthalmitis/diagnosis , Endophthalmitis/drug therapy , Endophthalmitis/virology , Herpesvirus 1, Suid/genetics , Herpesvirus 1, Suid/isolation & purification , Metagenomics , High-Throughput Nucleotide Sequencing , Delayed Diagnosis , Humans , Male , Middle Aged , Aqueous Humor/virology , Acyclovir/therapeutic use , Foscarnet/therapeutic use , Methylprednisolone/therapeutic use , Antiviral Agents/therapeutic use , Blindness/virology , DNA, Viral/isolation & purification
16.
J Neurol ; 270(7): 3603-3615, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37060361

ABSTRACT

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.


Subject(s)
Encephalitis, Viral , Steroids , Humans , Steroids/therapeutic use , Anti-Inflammatory Agents , Encephalitis, Viral/drug therapy
18.
Front Immunol ; 13: 930031, 2022.
Article in English | MEDLINE | ID: mdl-36177038

ABSTRACT

Most non-polio enterovirus infections in immunocompetent individuals are acute and self-limiting in nature; however, infection can be severe, chronic and have devastating outcomes in immunocompromised hosts. Therapeutic strategies have predominantly involved supportive care, with the lack of approved antiviral treatments proving challenging for management. We report a case of an 8-month-old child who presented with severe enterovirus encephalitis following gene therapy for X-linked severe combined immunodeficiency (X-SCID) and who demonstrated clinical and microbiological improvement after a novel regimen of favipiravir, fluoxetine, and high-dose intravenous immunoglobulin (IVIg). The patient presented 6 weeks post-gene therapy with rapid neurological deterioration in the context of incomplete immune reconstitution, with microbiological and radiological evidence confirming enterovirus encephalitis. His neurologic examination stabilised 8 weeks after treatment, and he subsequently demonstrated excellent immune recovery. This is the first case report of combined therapy with favipiravir, fluoxetine, and high-dose IVIg in the context of severe enterovirus encephalitis in an immunocompromised host. This case highlights the importance of considering enterovirus encephalitis in immunocompromised patients presenting with both acute and chronic neurological signs, as well as developmental regression. The demonstrated treatment success and the associated low risk of toxicity warrant further investigation of this therapeutic regimen.


Subject(s)
Encephalitis, Viral , Enterovirus Infections , Enterovirus , Amides , Antiviral Agents/therapeutic use , Encephalitis, Viral/diagnosis , Encephalitis, Viral/drug therapy , Enterovirus Infections/diagnosis , Enterovirus Infections/drug therapy , Fluoxetine , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Male , Pyrazines
19.
Medicine (Baltimore) ; 101(34): e30327, 2022 Aug 26.
Article in English | MEDLINE | ID: mdl-36042651

ABSTRACT

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.


Subject(s)
Disorders of Excessive Somnolence , Encephalitis, Viral , Epstein-Barr Virus Infections , Aged , Disorders of Excessive Somnolence/diagnosis , Disorders of Excessive Somnolence/drug therapy , Disorders of Excessive Somnolence/etiology , Encephalitis, Viral/complications , Encephalitis, Viral/diagnosis , Encephalitis, Viral/drug therapy , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/drug therapy , Headache/etiology , Herpesvirus 4, Human , Humans , Male
20.
J Healthc Eng ; 2022: 8593251, 2022.
Article in English | MEDLINE | ID: mdl-35399846

ABSTRACT

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.


Subject(s)
Drugs, Chinese Herbal , Encephalitis, Viral , Acyclovir , Drugs, Chinese Herbal/therapeutic use , Encephalitis, Viral/drug therapy , Humans , Naloxone/therapeutic use , Prognosis
SELECTION OF CITATIONS
SEARCH DETAIL