Encephalitis In Children Research Articles

A Cost of Illness Analysis of Children with Encephalitis Presenting to a Major Hospital in Vietnam.

Encephalitis is a significant global health problem, especially in children. Knowledge of its economic burden is essential for policymakers in prioritizing the development and implementation of interventions but remains limited. An observational study was prospectively conducted at a major children's hospital in Ho Chi Minh City, Vietnam from 2020 to 2022. Data on direct medical costs, direct nonmedical costs, and productivity costs were collected alongside demographic information, clinical features, diagnosis, severity, and outcomes of study participants. This was used to undertake a cost of illness analysis from a societal perspective. Data were collected from a total of 164 pediatric patients. The median cost of illness was estimated at US $1,859 (interquartile range [IQR]: US $1,273-$3,128). The direct costs were the main cost driver, accounting for 83.9% of the total cost of illness (US $1,560; IQR: US $975-$2,460). The productivity costs accounted for a median of US $275 (IQR: US $154-$474). The cost of illness was higher in more severe patients, patients with sequelae, patients with morbidities, and ventilated patients. Most direct medical costs were attributed to hospitalization and resulted in out-of-pocket payments from the patient's family (30.2%; US $316). The results showed that the cost of illness of encephalitis in children is considerable and will be useful for policymakers in prioritizing resources for the development and implementation of intervention strategies to reduce the burden of pediatric encephalitis.

Epidemiology of pediatric meningitis and encephalitis in Japan: a cross-sectional study.

Information on the epidemiology and cause-specific clinical features of pediatric meningitis and encephalitis is limited, owing to conventional laboratory methods' limitations in identifying causative pathogens. The FilmArray Meningitis/Encephalitis (FA-M/E) panel, a molecular diagnostic tool, can detect 14 pathogens within 1 hour. We investigated meningitis and encephalitis epidemiology among children in Japan and FA-M/E panels' utility in their clinical management. This cross-sectional study was conducted among children aged 0-18 years admitted to seven regional hospitals in western Japan between October 2022 and September 2023. Cerebrospinal fluid (CSF) samples were collected from 221 children and tested using the FA-M/E panel. Clinical and microbiological data were reviewed retrospectively. Fifty-eight patients tested positive using the FA-M/E panel. Viral and bacterial pathogens were detected in 49 and nine cases, respectively. Human parechovirus and enterovirus occurred mainly in epidemic clusters during the summer and were primarily detected in young infants. Patients who tested positive for human parechovirus had a significantly higher frequency of sepsis-like manifestations and a lower frequency of CSF pleocytosis than did those who tested positive for enterovirus. CSF pleocytosis was absent in 30 patients who tested positive using the FA-M/E panel. Among the patients who tested positive for bacteria, three of the nine were not diagnosed using conventional culture methods, owing to prior antimicrobial therapy. The FA-M/E panel can identify bacterial and viral pathogens causing pediatric meningitis and characterize the epidemiology in local communities.IMPORTANCECulture and polymerase chain reactions have traditionally been used to identify microorganisms causing pediatric meningitis and encephalitis. However, the methods currently used to identify the causative microorganisms are limited, particularly in general hospitals. The FilmArray Meningitis/Encephalitis (FA-M/E) panel, a fully automated genetic testing system, can detect 14 pathogens using the multiplex polymerase chain reaction method. This study described the epidemiology of pediatric meningitis and encephalitis in Japan. The microorganisms causing acute meningitis and encephalitis in children in Japan were identified using the FilmArray Meningitis/Encephalitis panel. Testing cerebrospinal fluid using the FA-M/E panel is useful for the identification of the pathogen in children with community-acquired acute meningitis and encephalitis. This increases knowledge on the epidemiology and clinical manifestations of acute meningitis and encephalitis caused by specific pathogens and can be used to facilitate optimal patient management.

Prevalence & clinical outcome of autoimmune encephalitis versus viral encephalitis in children with acute encephalitis syndrome: A prospective observational study.

Background & objectives Acute encephalitic syndrome (AES), encompasses a wide spectrum of potential causes, clinical presentations, and outcomes. While infectious encephalitis is generally considered more prevalent, autoimmune encephalitis is emerging as a significant aetiology. Neuronal autoantibodies have been identified independently or in association with acute viral encephalitis. The primary objective of this study was to ascertain the prevalence and clinical manifestation of autoimmune encephalitis as well as of coexisting viral markers in children with AES. Methods This study was a prospective observational investigation conducted in a hospital setting. It involved enrolling children with AES who were admitted to specific tertiary hospitals. Children were subjected to examinations to detect the presence of viral markers and neuronal autoantibodies in both their blood and cerebrospinal fluid (CSF). All the participants received treatment based on established guidelines and was followed for six months for outcome assessment. Results During the study period, 867 children with AES were examined. Among these cases, 37 children (4.2%) were diagnosed with autoimmune encephalitis, and all of them tested positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibodies. Evidence of viral infection was seen in 409 (47.1%) of cases, out of which nearly 254 (29.2%) children had detectable HSV IgM antibodies. Among the 37 children with autoimmune encephalitis, 25 (67.5%) had evidence of a viral trigger, with eight of them tested positive for HSV IgM antibodies. The clinical presentation of autoimmune-associated AES was similar to those with viral aetiology. Interpretation & conclusions Autoimmune encephalitis triggered by neurotropic (HSV) viral infection was more prevalent in this study than in the earlier reports. Typically, these children show positive responses to immunosuppressive treatments if administered promptly. It is hence advisable to assess children who exhibit behavioural issues and movement disorders for possible autoimmune encephalitis.

Relationship of cerebrospinal fluid and serum levels of SIL-2R, eNOS, and CD93 with the progression and prognosis of viral encephalitis in children

To investigate the relationship of cerebrospinal fluid and serum levels of soluble interleukin-2 receptor (SIL-2R), endothelial nitric oxide synthase (eNOS), and cluster of differentiation 93 (CD93) with the progression and prognosis of viral encephalitis (VE) in children. Prospectively, 102 children with VE admitted from January 2021 to January 2024 were selected as the VE group. The patients were divided into a mild subgroup (64 patients) and a severe subgroup (38 patients) according to disease progression. The patients were also divided into a good prognosis subgroup (29 patients) and a poor prognosis subgroup (73 patients) according to prognosis. A control group of 102 children with central nervous system diseases who were examined and found not to have VE during the same period was selected. The factors contributing to the poor prognosis of children with VE and the predictive value of SIL-2R, eNOS, and CD93 in cerebrospinal fluid and serum for the poor prognosis of children with VE were evaluated. Cerebrospinal fluid and serum SIL-2R, eNOS, and CD93 levels were significantly increased in the VE group, severe subgroup, and poor prognosis subgroup (P<0.05). Multivariate logistic regression analysis showed that high SIL-2R, eNOS, and CD93 levels in cerebrospinal fluid and serum were risk factors for poor prognosis in children with VE (P<0.05). Receiver operating characteristic curve analysis showed that the combination of cerebrospinal fluid SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE (P<0.05). Similarly, the combination of serum SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE (P<0.05). The cerebrospinal fluid and serum levels of SIL-2R, eNOS, and CD93 are significantly elevated in children with VE, and they are associated with VE progression and prognosis.

Analysis of risk factors and prediction model construction for varicella encephalitis in children: A retrospective cohort study.

This study aimed to analyze the risk factors for varicella encephalitis in children and establish a predictive model. This retrospective cohort study included a varicella encephalitis group (n = 75) and a varicella-non-encephalitis group (n = 135). Logistic regression analysis was employed to find risk factors for varicella encephalitis and create a predictive model. Older age, vomiting, poor mental status, and prolonged rash duration were independent risk factors for varicella encephalitis (p < .05). The predictive model for varicella encephalitis combined above four factors. The ROC curve of the predictive model showed an area under the curve of 0.955 (95% CI 0.925-0.986) for varicella encephalitis in children with a sensitivity of 94.7%, and a specificity of 86.0%. Children with varicella who are older, experience vomiting, exhibit poor mental status, or have a prolonged rash duration should be closely monitored clinically. The predictive model combining these four factors demonstrates good predictive efficiency.

Rate of Autoimmune Encephalitis in Children With First-Episode Psychosis

BackgroundAutoimmune encephalitis (AE) can present as first-episode psychosis (FEP) in children. An FEP diagnostic algorithm has been proposed, but how this algorithm applies to children is unknown. We assess the FEP diagnostic algorithm in children with FEP. MethodsThe FEP algorithm was applied to a retrospective cohort of children with FEP without other neurological symptoms. ResultsTwenty-four patients were included, with five AE (anti-N-methyl-d-aspartate receptor encephalitis) and 19 non-AE patients (12 primary psychiatric, two headaches, mycoplasma-related encephalitis, post–coronavirus disease 2019 encephalitis, drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome, cobalamin C deficiency, and two unknown). Some non-AE patients (five of 19 = 26%) received immunotherapies, with symptom resolution in one of five (20%) with immunotherapy and in four of 14 (29%) without immunotherapy. The FEP algorithm recommended cerebrospinal fluid (CSF) testing in all (five of five = 100%) patients with AE and in six of 19 (32%) non-AE patients, resulting in 100% sensitivity (95% confidence interval [CI]: 100% to 100%) and 45.5% specificity (95% CI: 16% to 75%), with a negative predictive value of 100% (95% CI: 100% to 100%). ConclusionsFEP can occur in children from different causes, including AE and metabolic conditions. Evaluation of FEP should be broad, especially without CSF evidence of inflammation. The FEP algorithm is useful to assess patients who would benefit from CSF testing and should be assessed in larger cohorts.

POST HERPETIC BASAL GANGLIA STROKE IN AN ADOLESCENT GIRL: BRIEF REVIEW OF LITERATURE AND A CASE REPORT

Herpes simplex encephalitis (HSE) is a leading cause of sporadic, non-epidemic viral encephalitis in children and adults. We report a very rare case of HSE complicated by multiple ischaemic infarcts involving both basal ganglia in a 15-year-old female adolescent admitted with complaints of headache and fever, irrational behavior and seizures. On clinical examination patient was unconscious with signs of raised intracranial pressure, right hemiparesis and meningeal irritation. She had elevated temperature (38.7°C), and anaemia (packed cell volume of 25.0%). Magnetic resonance imaging showed features of Multiple non-enhancing hypodensities in both basal ganglia with mild dilation of the 3rd and lateral ventricles. She was managed as a case of Post-encephalitis Basal ganglia stroke. The patient subsequently developed a repeat vascular event, with suspected haemorrhagic transformation after 4 weeks and succumbed to the illness.

Clinical characteristics and long-term outcome of CASPR2 antibody-associated autoimmune encephalitis in children

BackgroundContactin-associated protein-2(CASPR2) antibody-associated autoimmune encephalitis(AE) is rare in children. This study aimed to report the clinical characteristics and long-term outcome of CASPR2 autoimmunity in children to expand the disease spectrum.MethodsChildren who were hospitalized in our hospital with clinically suspected AE from May 2015 to April 2022 and underwent neuronal surface antibodies detections were retrospectively analyzed. Clinical data of patients with CASPR2 autoimmunity were collected.ResultsPatients who were positive for NMDAR-IgG, CASPR2-IgG, LGI1-IgG and IgLON5-IgG occupied 95.2%(119/125),3.2%(4/125),0.8%(1/125) and 0.8%(1/125), respectively.The median onset age of the 4 patients with CASPR2-IgG was 5.6 years. The most common symptoms were psychiatric symptoms/abnormal behavior(3/4) and sleep dysfunction(3/4). One patient developed a phenotype of Rasmussen encephalitis(RE). Tumor was absent in our patients. Two patients showed abnormal findings on initial brain magnetic resonance imaging(MRI) scans. All the patients showed favorable response to immunotherapy except the patient with RE experienced recurrent symptoms who finally achieved remission after surgery. All the patients had a favorable long-term outcome at the last follow-up(33-58months).ConclusionsCASPR2 autoimmunity may be the second most common anti-neuronal surface antibodies associated neurological disease in children. Psychiatric symptoms/abnormal behavior and sleep disorder were common in children with CASPR2-associated AE. Tumor was rare in those patients. Most pediatric patients had a favorable long-term outcome.

Changing Epidemiology of Hand, Foot, and Mouth Disease Causative Agents and Contributing Factors.

Hand, foot, and mouth disease (HFMD) is a common viral infection primarily affecting children. It causes vesicles on the skin and inside the mouth. Although most cases get better on their own, severe cases can lead to complications such as brain stem encephalitis, meningoencephalitis, acute flaccid paralysis, and pulmonary edema. Hand, foot, and mouth disease is caused by various enteroviruses, with enterovirus A71 (EV-A71) and coxsackievirus A16 being the most common. However, recent studies have shown a shift in the molecular epidemiology of HFMD-causing pathogens, with coxsackievirus A6 and coxsackievirus A10 causing more infections. In addition, extensive recombination events have been identified among enterovirus strains, which may have a role in faster evolution and extinction of dominant enterovirus serotypes. Other strains of enterovirus can also cause severe complications, and there has been an increase in mortality associated with brain stem encephalitis in children under 3 years of age and teenagers. Currently, there are no effective antiviral therapies available to treat enterovirus infections. Vaccines against EV-A71 have been approved and are now used in mainland China. Studying the changing epidemiology of HFMD pathogens and the evolution patterns of its causative agents is crucial in developing effective prevention and control strategies. Increased interest in the molecular epidemiology of HFMD causative agents has led to a better understanding of the critical drivers of HFMD outbreaks, which can inform efforts to prevent and control the disease.

Clinical and Etiological Profile of Children With Acute Viral Encephalitis in a Tertiary Care Hospital: A Cross-Sectional Study.

Acute encephalitis refers to the clinical diagnosis of children who have a sudden onset of symptoms and show evidence of inflammatory lesions in the brain. Timely diagnosis is crucial for both lifesaving measures and the preservation of brain functions. The objective of the study was to determine the clinical and etiological profile of acute viral encephalitis in children within a tertiary care hospital. This hospital-based cross-sectional study was conducted in the Pediatric Intensive Care Unit (PICU) at Dr. D. Y. Patil Medical College, Hospital, and Research Centre in Pune. The study included children aged one month to 12 years diagnosed with suspected viral encephalitis. Over 22 months, from August 2022 to June 2024, 35 children who met the inclusion criteria were enrolled. Data collection involved clinical examinations, laboratory investigations, and imaging studies, following informed consent from the parents or guardians. The study examined 35 patients with suspected acute encephalitis syndrome (AES) and found a male-to-female ratio of 3.4:1. Among the patients, 22 (62.85%) had a confirmed viral etiology, while 13 (37.17%) had an unknown etiology. The most common virus isolated was mumps, with school-age children most affected. The cases were concentrated in the Chikhali, Bhosari, Nigdi, and Chinchwad regions. Symptoms included fever, seizures, vomiting, and altered mental status. Low vaccination rates were observed, and the Glasgow Coma Scale (GCS) scores, shock incidence, and ventilation showed an association with mortality. Most patients required intensive care, antiedema measures, antibiotics, and antivirals. The mortality rate was 11.4%, with 17% of patients discharged with neurological sequelae. Causative agents such as mumps, herpes simplex virus (HSV), dengue, and many other viruses are now more prevalent than the Japanese encephalitis (JE) virus. Bad clinical course and fatal outcomes are observed in patients affected with rabies, HSV, and H1N1 influenza virus. Factors such as GCS scores, shock, and need for ventilation play a significant role in determining patient prognosis. Early detection and prompt treatment may aid in betteroutcomes for patients.

La Crosse virus encephalitis in children.

La Crosse virus encephalitis (LACV-E) is among the most common neuroinvasive arthropod-borne viral infections of childhood in North America. Children are uniquely predisposed to symptomatic disease, whereas symptomatic adult infections remain uncommon. Infection results frequently in neurologic symptomatology including headaches, seizures, and altered mentation, often necessitating hospitalization and significant diagnostic evaluation. The purpose of this review is to provide a contemporary assessment of clinical, laboratory, and neurobehavioral outcomes of children with LACV-E. Common clinical manifestations at presentation, specifically seizure activity and altered mental status, are independent predictors of disease severity. Epileptiform discharges on electroencephalogram (EEG) during hospitalization may predict long-term epilepsy diagnosis. Lastly, long-term neurologic sequelae from acute infection is persistent and likely under-recognized among children with LACV-E. As climate change alters the geographic distribution of mosquito borne illnesses, a possibility of regional expansion of La Crosse virus (LACV) endemicity exists. The above data highlight readily identifiable features and testing modalities for clinicians who may encounter this viral infection. Importantly, an emphasis on long term neurobehavioral follow up is necessary to better identify and provide support of affected individuals. Future research in identifying host immune responses to LACV infection, as well as therapeutic options, are needed.

Pediatric Autoimmune Encephalitis: A Nationwide Study in Latvia.

Autoimmune encephalitis (AE) is the third most common encephalitis in children. Diagnosis can be challenging due to overlapping and diverse clinical presentations as well as various investigation results. This study aims to characterize the clinical, diagnostic features, as well as treatment and outcomes of AE in children and determine the incidence of pediatric AE in Latvia. The study was conducted at the Children's Clinical University Hospital in Riga. The study participants were patients under the age of 18 years diagnosed with AE from 2014 to 2022. Data regarding clinical characteristics, investigation findings, treatment strategy, and outcomes were retrospectively collected from the medical history data system. We included 18 pediatric patients diagnosed with AE. The mean incidence of pediatric AE in Latvia was 0.56 per 100,000 children. Most patients (66.6%) had seronegative AE. In the seropositive group, the most common was anti-methyl-D-aspartate receptor AE, with two patients having other antibodies. The most prevalent clinical features were personality change, cognitive impairment, autonomic dysfunction, and movement disorders. The majority of patients (58.8%) received first-line treatment only. More than half (55.6%) of our AE patient group had long-term sequelae. Our study shows that the pediatric AE incidence in Latvia is similar to what has been previously reported in other studies. A relatively high proportion of seronegative AE was present in our cohort, indicating that awareness of possible misdiagnosis should be raised. Further research is needed to better understand the underlying mechanisms, characterize clinical features, and determine the treatment of choice in different situations to improve long-term outcomes.

Chandipura Virus Forms Cytoplasmic Inclusion Bodies through Phase Separation and Proviral Association of Cellular Protein Kinase R and Stress Granule Protein TIA-1.

Negative-strand RNA viruses form cytoplasmic inclusion bodies (IBs) representing virus replication foci through phase separation or biomolecular condensation of viral and cellular proteins, as a hallmark of their infection. Alternatively, mammalian cells form stalled mRNA containing antiviral stress granules (SGs), as a consequence of phosphorylation of eukaryotic initiation factor 2α (eIF2α) through condensation of several RNA-binding proteins including TIA-1. Whether and how Chandipura virus (CHPV), an emerging human pathogen causing influenza-like illness, coma and death, forms IBs and evades antiviral SGs remain unknown. By confocal imaging on CHPV-infected Vero-E6 cells, we found that CHPV infection does not induce formation of distinct canonical SGs. Instead, CHPV proteins condense and co-localize together with SG proteins to form heterogeneous IBs, which ensued independent of the activation of eIF2α and eIF2α kinase, protein kinase R (PKR). Interestingly, siRNA-mediated depletion of PKR or TIA-1 significantly decreased viral transcription and virion production. Moreover, CHPV infection also caused condensation and recruitment of PKR to IBs. Compared to SGs, IBs exhibited significant rapidity in disassembly dynamics. Altogether, our study demonstrating that CHPV replication co-optimizes with SG proteins and revealing an unprecedented proviral role of TIA-1/PKR may have implications in understanding the mechanisms regulating CHPV-IB formation and designing antiviral therapeutics. Importance: CHPV is an emerging tropical pathogen reported to cause acute influenza-like illness and encephalitis in children with a very high mortality rate of ~70%. Lack of vaccines and an effective therapy against CHPV makes it a potent pathogen for causing an epidemic in tropical parts of globe. Given these forewarnings, it is of paramount importance that CHPV biology must be understood comprehensively. Targeting of host factors offers several advantages over targeting the viral components due to the generally higher mutation rate in the viral genome. In this study, we aimed at understanding the role of SGs forming cellular RNA-binding proteins in CHPV replication. Our study helps understand participation of cellular factors in CHPV replication and could help develop effective therapeutics against the virus.

Integrating DNA/RNA microbe detection and host response for accurate diagnosis, treatment and prognosis of childhood infectious meningitis and encephalitis

BackgroundInfectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy.MethodsHere we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL).ResultsOur pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM.ConclusionsThis study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.

Epidemiological characteristic of viral encephalitis in children and adolescents in Henan Province, 2012-2023

Objective: To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023. Methods: The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases. Results: A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years (χ2=5.33,P=0.021; χ2=48.14,P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions: From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.

The role of immunoglobulin in cerebrospinal fluid on the differential diagnosis of autoimmune encephalitis and viral encephalitis in children

BackgroundA case-control study was conducted to analyze the role of cerebrospinal fluid immunoglobulin in the differential diagnosis of autoimmune encephalitis and viral encephalitis in children.MethodsOne hundred and twenty patients with autoimmune encephalitis (AE) treated in our hospital from February 2021 to February 2022 were included as the observation group (AE group). 100 patients with viral encephalitis (VE group) were selected as the control group. The clinical data of all patients were collected and analyzed retrospectively. Immunoglobulin G (IgG) and immunoglobulin A (IgA)in cerebrospinal fluid of the two patients were measured by immune turbidimetry. Immunoglobulin M (IgM), and the diagnostic value of immunoglobulin in cerebrospinal fluid (CSF) in patients with AE was analyzed by receiver working curve (ROC).ResultsThe level of IgG in the cerebrospinal fluid of the AE group was higher than that of the VE group, and the level of IgM was lower than that of the VE group, and the difference was statistically significant (P < 0.05). There was no significant difference in IgA levels between the two groups (P > 0.05). In terms of Magnetic Resonance (MR) features, the paraventricular, hippocampal, occipital and parietal lobes were more involved in AE patients, frontal and temporal lobes were more involved in VE patients, and paraventricular and occipital lobes were involved in MS. The proportion of bilateral extensive lesions in both groups was significantly higher than 50%. The proportions of patients in the AE group involving the lateral ventricle, insula, and parietal lobes were significantly higher than those in the VE group, and the proportions involving the basal ganglia, temporal lobes, and frontal lobes were significantly lower than those in the VE group, and the differences were statistically significant (All P < 0.05). The Area Under Curve (AUC) of IgG, IgA and IgM alone in the diagnosis of AE were 0.795(0.587–0.762), 0.602(0.502–0.631) and 0.627(0.534–0.708), respectively with the sensitivity values of 81.24% and 65.608, respectively and the specificity values of 65.08%, 57.54% and 75.01% respectively. The AUC of IgA + IgM in the diagnosis of AE was 0.733(0.617–0.849), and the sensitivity and specificity are 62.58% and 75.07% respectively. The AUC of IgA + IgG in the diagnosis of AE was 0.823(0.730–0.917), and the sensitivity and specificity were 81.24% and 67.54% respectively. The AUC of IgG + IgM in the diagnosis of AE was 0.886(0.814 ~ 0.958), and the sensitivity and specificity were 84.48% and 77.59% respectively. The AUC of IgA + IgM + IgG in the diagnosis of AE was 0.924 (0.868–0.981) with the sensitivity of 93.82%, and the specificity of 77.56%.ConclusionThe level of immunoglobulin in cerebrospinal fluid can be used as an effective reference index for the diagnosis of AE. The combined detection of IgA, IgM and IgG can improve the accuracy, sensitivity and specificity of AE.

Endemic La Crosse Virus Neuroinvasive Disease in North Carolina Residents: 2000-2020.

La Crosse virus neuroinvasive disease (LACVND) is the most common cause of arboviral encephalitis in children within the United States; in North Carolina, it is the most prevalent endemic mosquito-borne disease in humans. Here we report a surveillance summary of confirmed and probable LACVND during 2000-2020 using North Carolina Electronic Disease Surveillance System data, and we describe associated demographic characteristics, spatiotemporal distribution, clinical features, and mortality rates. A total of 355 cases (74.9% confirmed) were reported from 41 North Carolina counties; most cases (92%) occurred in 19 Western North Carolina counties. An average of 17 cases were reported annually with the majority (94%) of cases occurring between mid-June and early October (epiweeks 25-41). The median case age was nine years (range: 1-95 years), 79% were aged ≤ 18 years, and 56.6% were male. Cases commonly presented with headache (95.4%), fever (95.1%), and altered mental status (80.8%); encephalitis (82.0%) and meningitis (45.9%) were frequently diagnosed. Encephalitis was more common in children (87%) than adults (62%) (P < .001). Similarly, seizures were more common in children (54%) than adults (27%) (P < .01). The case fatality rate was 1.4%; however, differences in age-specific rates were observed. Changes in case definitions and reporting requirements, missing data, different reporting sources, and the retrospective nature of this study are all important limitations of our study. Given the persistent endemicity of La Crosse virus in Western North Carolina, clinicians and public health providers should consider La Crosse virus disease in all individuals, especially children, with compatible symptoms and a travel history to endemic counties. Prevention measures and educational outreach/public health messaging should focus on caregivers and children in Western North Carolina counties and during times when transmission risk is higher (i.e., summer and early fall).

Clinical analysis of 9 children with refractory N-methyl-D-aspartate receptor antibody encephalitis children treated with tocilizumab

Objective: To analyze the clinical features of children with refractory N-methyl-D-aspartate (NMDA) receptor antibody encephalitis treated with tocilizumab. Methods: Demographic and clinical manifeatations, immunotherapy and prognosis data of 9 children with refractory NMDA receptor antibody encephalitis who received tocilizumab in the Department of Pediatrics Neurology, XiangYa Hospital of Central South University from August 2021 to September 2023 were collected retrospectively. Prognosis was evaluated using the modified Rankin scale at initial diagnosis, at the initiation of tocilizumab treatment, and at the last follow-up. Treatment related complications, neuroimaging, and electroencephalography data were analyzed. Results: Among the 9 children, 6 were male and 3 were female, with an onset age of 4.2 (2.8, 8.7) years. At the onset of the disease, 9 children had a modified Rankin scale score of 5. When tocilizumab treatment was initiated, 7 children had a score of 5, and 2 children had a score of 4. The interval between the onset and initiation of tocilizumab treatment was 12 (5, 27) months, and the treatment frequency was 8 (5, 13) times. The follow-up time was 2.8 (1.5, 3.7) years. At the last follow-up, the symptoms of 9 children, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction, were improved to varying degrees, and none of them had seizures. At the last follow-up, 4 cases with a modified Rankin scale score of 0, 1 case with a score of 1, 2 cases with a score of 3, 1 case with a score of 4 and 1 case with a score of 5. The modified Rankin scale at the last follow-up was significantly different from that at the start of tocilizumab (Z=-2.56, P=0.014). All children had no serious adverse reactions during the treatment. Conclusions: After treatment with tocilizumab, the symptoms in patievts with refractory NMDA receptor antibody encephalitis, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction were improved, and none of them had seizures. The modified Rankin scale were improved, and the safety was good.

A child with anti-N-methyl-D-aspartate autoimmune encephalitis presenting with frank psychosis: a case report

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common autoimmune encephalitis in children. The clinical manifestations and disease course of pediatric anti-NMDA receptor encephalitis have been comprehensively desibed in the literature and showed some differences compared with adult patients in tumor association, neurological presentation, and frequency of symptoms. In general, neurological symptoms were more common than psychiatric symptoms as the initial signs of presentation in children in most of the previous cohorts. They also tend to present with behavior changes, temper tantrums, hyperactivity, and irritability, instead of overt psychotic symptoms. In this article, we report a 12 years old boy with Anti NMDA encephalitis, showing a rare initial presentation of pure psychosis, after obtaining the consent of his parents.

Current Status of La Crosse Virus in North America and Potential for Future Spread.

La Crosse virus (LACV) is an arthropod-borne RNA virus with substantial potential for future spread in North America. La Crosse virus is responsible for La Crosse encephalitis, a leading cause of arboviral encephalitis in children in the United States. Primarily transmitted by Aedes triseriatus (Eastern treehole) mosquitos and amplified by small mammal hosts, LACV has caused infections throughout the upper Midwest and, more recently, the mid-Atlantic and southeastern United States. Notably, in recent years, infections have also been identified increasingly in the Appalachian region. Anthropogenic and environmental factors have likely contributed to recent LACV spread, including the introduction of invasive vector species (especially Ae. albopictus), biotic interactions between and among vector and host species, land-use change, habitat disturbance, increased human travel and transport, and rising global temperatures. Prevention and control strategies, such as increased surveillance of vector and host populations, increased awareness among populations at risk for infection, and increased awareness among physicians are needed to limit future spread. Continued climate change with increases in global temperatures and erratic weather patterns may result in the expansion of competent mosquito vector species and thus could facilitate the geographic spread of LACV.