Encephalitis Syndrome Research Articles

New treatments in neuroinflammatory disorders

The understanding of how to treat neuroinflammatory disorders is dependent upon a clear understanding of the mechanisms of disease, which are only recently becoming clear. One of the most significant advances has been discovery of autoantibody biomarkers which define treatable autoimmune encephalitis and autoimmune demyelination syndromes such as autoantibodies against NMDA-receptor, myelin oligodendrocyte glycoprotein and aquaporin-4. Although corticosteroids remain an essential part of early treatment as they reduce inflammation quickly, the therapeutic options are increasing due to our improved understanding of disease. Intravenous immunoglobulin is a useful anti-inflammatory therapy, although its mechanisms is broad, and its effects may vary from disease to disease. Plasma exchange is more stratght forward, as it removes pathogenic autoantibodies and other inflammatory proteins. Therapies which target B cell linage such as rituximab are increasingly used in autoimmune neurology, and there is recent scientific data showing that targeting CD20 B cells can be therapeutically effective in autoantibody syndromes. Recent understanding that complement plays a major role in aquaporin-4 NMOSD has resulted in the use of complement targting drugs such as eculizumab. Likewise, tocilizumab which targets interleukin 6 is an increasingly interesting option in autoimmune encephalitis patients who fail rituximab, and other neuroinflammatory disodrers which are not ‘autoantibody mediated’. Neuroinflammation can take other forms, and there is increasing interest in epigenetic immune dysfunction, and therefore the use of epigenetic therapeutics, which opens up the potential opportunity of repurposong drugs which are epigenetic modulators such as ketogenic diet, cannabidiol, and valproate, amongst many.

Japanese encephalitis in children from an endemic district of West Bengal, India: A hospital based observational study

Background: Japanese encephalitis (JE) is an important cause of viral encephalitis in children in South East Asian countries including India. Aims and Objective: We have done this study in an JE endemic district of India to know the demographic profile, clinical presentation, seasonal variation, outcome and about the vaccination status of the JE cases. Materials and Methods: This observational, cross sectional study was done for a period of one year in the Pediatric department of Burdwan Medical College, West Bengal in children up to the age of 12 year, presented with acute encephalitis syndrome (AES). Demographic data, clinical presentation and JE vaccination status were recorded and confirmed JE cases were detected by either serum or CSF JE IgM antibody. Outcome of the JE cases were noted as discharge, death or leave against medical advice (LAMA). Results: We have found confirmed JE in 18 children out of total 125 AES cases (14.4%). 61.1% of them were within 6 to 12 year age, mostly from low socioeconomic status and 100% case occurred during monsoon and post monsoon period. History, was of JE vaccination were present in only 11.1% case of JE. Most common presenting symptoms were high fever (100%), convulsion (94.4%) and altered sensorium (72.2%). 77.8% JE case were discharged and 11.1% expired. Conclusion: We must consider JE whenever a child from any endemic district comes with AES and we should try to bring every child under the JE vaccination coverage in the endemic regions globally to reduce the burden of this preventable encephalitis.

ACUTE ENCEPHALITIS SYNDROME IN CHILDREN: A DESCRIPTIVE CROSSSECTIONAL STUDY IN A RURAL BASED TERTIARY CARE HOSPITAL IN INDIA

Background: Acute Encephalitis Syndrome (AES) is a group of clinically similar neurologic manifestations due to encephalitis. AES is an important cause of mortality and morbidity in children in various parts of India. Most of the study has been done in adult population. So, I have done this study to evaluate clinical prole, short-term outcome and changing trends of etiologies of acute encephalitis in children. Methods: This is an institution-based descriptive cross-sectional study including sixty children aged one month to twelve years conducted over a period of one and half years in the pediatric department of a rural based medical college in India. Data collected in predesigned case record proforma and analysed with SPSS software version 25. Results: Incidence rate 4 per 1000 patients per year with 2 to 6 years age group with males predominating. Important presenting complaints were fever, convulsion, abnormal behavior, rash, vomiting, headache, lethargy, aphasia and quadriparesis. Poor Glasgow coma score (GCS), meningeal sign and raised intra cranial pressure were important examination ndings. Dengue and scrub typhus were important emerging etiologies replacing Japanese encephalitis. Overall mortality is around 13%. Conclusions:All febrile children with altered sensorium should be investigated for central nervous system (CNS) infection, unless clear evidence of another diagnosis. Viruses are the main culprit with Dengue and Scrub typhus being the important emerging etiology. Timely diagnosis and treatment can reduce morbidity and mortality signicantly.

Basal Ganglia Disease Mimicking Acute Encephalitis Syndrome Among Infants of Bodo Tribe, Assam

We conducted a review of hospital records of infants with acute encephalitis syndrome with bilateral symmetrical basal ganglia infarcts, between 2011-2015, at a single center in Assam. Thiamine (as part of multivitamin injection) was used in the treatment of 23 infants and not used in 27; Only 1 (3.7%) infant died in the former group and 20 infants (86.9%) died in the latter [RR (95% CI) 0.04 (0.006,0.29); P<0.001). Two infants on follow-up had normal development, both in the thiamine group. The study suggests the possibility of subclinical thiamine deficiency, mitochondrial diseases, or SLC19A3 gene mutation in this population.

Comparison of 4 weeks versus 12 weeks antiseizure medication for acute symptomatic seizures in children with Acute Encephalitis Syndrome: An open-label, randomized controlled trial

ObjectiveTo compare the proportion of children with seizure recurrence/s during 6-18 months of follow-up among children with acute symptomatic seizures underlying acute encephalitis syndrome (AES) treated with either 4 weeks or 12 weeks of antiseizure medication (ASM). MethodsEligible children aged 3 months to 12 years with acute symptomatic seizures underlying AES, receiving a single ASM at 4 weeks of illness, and without seizure recurrence from day 7–28 of illness were included in this comparative, parallel-group assignment, open-label, randomized control study (either 4 weeks or 12 weeks duration). The primary outcome was to compare proportions of children developing seizure recurrence over six months of follow-up. The secondary outcomes were to study seizure recurrence over 12–18 months follow-up and factor(s) associated with seizure recurrence. ResultsOf 232 children with AES screened, 60 eligible children were randomized in two groups. Baseline demographics were comparable (except the duration of illness) between the groups. Seizure recurrences at 6, 12 and 18 months were none, two (one in each group, relative risk 1.0, 95% CI 0.06–16.76; p-value >0.99), and six (one and five children in 4 and 12 weeks groups respectively, relative risk 0.17, 95% CI 0.01–1.62; p-value 0.19) respectively. There was no association of seizure recurrences with seizure characteristics, abnormal electroencephalography and neuroradiology. Children with disabilities at randomization had a higher risk of seizure recurrence at 18 months of follow-up (relative risk 7.16, 95% CI 1.1–43.9; p-value 0.049). SignificanceWith limitations of the study design, this study provides Class I evidence that a shorter duration (4 weeks) of ASM is comparable with 12 weeks therapy for preventing seizure recurrences in children with AES. Trial registrationClinical Trials.gov identifier: NCT03181945; Clinical Trial Registry of India identifier: CTRI/2017/06/008783.

Vaccination in acute immune-mediated/inflammatory disorders of the central nervous system.

This review article covers the vaccination related issues in autoimmune disorders of central nervous system (CNS) including narcolepsy, anti-NMDAR encephalitis, Rasmussen encephalitis and febrile infection related epilepsy syndrome (FIRES). Beyond these conditions the immune mediated epilepsies related with autoimmune CNS disorders are discussed and indications and contraindications of vaccinations in these cases are also considered.

Pseudotumor Cerebri Syndrome as a Neurologic Involvement of Multisystem Inflammatory Syndrome in Children: A Case Report

BackgroundCoronavirus disease 2019 may have neurological manifestations including meningitis, encephalitis, post-infectious brainstem encephalitis and Guillain-Barre syndrome. Neuroinflammation has been claimed as a possible cause. Here, we present a child with multisystem inflammatory syndrome in children (MIS-C) who developed pseudotumor cerebri syndrome (PTCS) during the disease course.CaseA 11-year-old girl presented with 5 days of fever, headache and developed disturbance of consciousness, respiratory distress, conjunctivitis and diffuse rash on her trunk. Immunoglobulin M and G antibodies against severe acute respiratory syndrome coronavirus 2 were positive in her serum. She was diagnosed with MIS-C. On day 10, she developed headache and diplopia. Left abducens paralysis and bilateral grade 3 papilledema were observed. Brain magnetic resonance imaging revealed optic nerve head protrusion, globe flattening. She was diagnosed with secondary PTCS. Papilledema and abducens paralysis improved under acetazolamide and topiramate. Neurological examination became normal after 2 months.ConclusionPTCS may emerge related to MIS-C.

Levels of Circulating NS1 Impact West Nile Virus Spread to the Brain.

Dengue virus (DENV) and West Nile virus (WNV) are arthropod-transmitted flaviviruses that cause systemic vascular leakage and encephalitis syndromes, respectively, in humans. However, the viral factors contributing to these specific clinical disorders are not completely understood. Flavivirus nonstructural protein 1 (NS1) is required for replication, expressed on the cell surface, and secreted as a soluble glycoprotein, reaching high levels in the blood of infected individuals. Extracellular DENV NS1 and WNV NS1 interact with host proteins and cells, have immune evasion functions, and promote endothelial dysfunction in a tissue-specific manner. To characterize how differences in DENV NS1 and WNV NS1 might function in pathogenesis, we generated WNV NS1 variants with substitutions corresponding to residues found in DENV NS1. We discovered that the substitution NS1-P101K led to reduced WNV infectivity in the brain and attenuated lethality in infected mice, although the virus replicated efficiently in cell culture and peripheral organs and bound at wild-type levels to brain endothelial cells and complement components. The P101K substitution resulted in reduced NS1 antigenemia in mice, and this was associated with reduced WNV spread to the brain. Because exogenous administration of NS1 protein rescued WNV brain infectivity in mice, we conclude that circulating WNV NS1 facilitates viral dissemination into the central nervous system and impacts disease outcomes. IMPORTANCE Flavivirus NS1 serves as an essential scaffolding molecule during virus replication but also is expressed on the cell surface and is secreted as a soluble glycoprotein that circulates in the blood of infected individuals. Although extracellular forms of NS1 are implicated in immune modulation and in promoting endothelial dysfunction at blood-tissue barriers, it has been challenging to study specific effects of NS1 on pathogenesis without disrupting its key role in virus replication. Here, we assessed WNV NS1 variants that do not affect virus replication and evaluated their effects on pathogenesis in mice. Our characterization of WNV NS1-P101K suggests that the levels of NS1 in the circulation facilitate WNV dissemination to the brain and affect disease outcomes. Our findings facilitate understanding of the role of NS1 during flavivirus infection and support antiviral strategies for targeting circulating forms of NS1.

Seasonal abundance of Leptotrombidium deliense, the vector of scrub typhus, in areas reporting acute encephalitis syndrome in Gorakhpur district, Uttar Pradesh, India.

The rickettsial pathogen Orientia tsutsugamushi, causing scrub typhus, has been implicated as a major cause of acute encephalitis syndrome (AES) in many places in India including Gorakhpur district of Uttar Pradesh. Seasonal abundance of the principal vector mite of the pathogen, Leptotrombidium deliense, its animal hosts, and prevalence of infection on them are important attributes in the assessment of outbreaks of the disease. Hence, these aspects were investigated, seasonally, in rural villages of Gorakhpur district, where peak incidence of AES cases were reported. A total of 903 animals (rodents/shrews) was collected using 6484 Sherman traps in eight study villages (14% overall trap rate). A sum of 5526 trombiculid mites comprising 12 species was collected from 676 live rodents/shrews screened. Suncus murinus, the Asian house shrew was the predominant species (67%). Among trombiculids, the principal vector mite, L. deliense, was predominant (64.7%) and its infestation index (i.e., average number of chiggers per host animal) was 5.3. The L. deliense infestation index was higher during July to November with a peak in October. Out of 401 animal sera samples screened, 68% were positive for antibodies against O. tsutsugamushi. Of 465 blood samples tested by nested PCR, seven were positive for the 56kDa gene of O. tsutsugamushi. In conventional PCR, 41 out of 265 samples were positive for the 60kDa groEL gene of O. tsutsugamushi. Among the 5526 mite samples, tested as 352 pools through nested PCR, four pools were positive for 56kDa gene. Phylogenetic analysis of 56 and 60kDa genes confirmed circulation of Karp and TA678 (rodents) and TA678 (mite) serotypes of O. tsutsugamushi in Gorakhpur. Peak incidence of AES in Gorakhpur district occurs during the rainy season (July-October), coinciding with the peak abundance of L. deliense. These results indicate involvement of L. deliense as the vector mite transmitting the scrub typhus pathogen O. tsutsugamushi to humans in the rural areas of Gorakhpur district, India.

P 24. Dysphagia in NMOSD and MOGAD: Swallowing endoscopy as a surrogate of brain involvement?

Background. Neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD) are demyelinating disorders that typically affect the optic nerves and the spinal cord. However, recent studies have demonstrated various forms of brain involvement indicating encephalitic syndromes, which consequently are included in the diagnostic criteria for both. Swallowing is processed in a distributed brain-network and is therefore disturbed in many neurological diseases. Objective. The aim of this study was to investigate the occurrence of oropharyngeal dysphagia in NMOSD and MOGAD and to further assess the value of flexible endoscopic evaluation of swallowing (FEES) as a surrogate parameter of brain involvement. Methods. 13 Patients with NMOSD and MOGAD (mean age 54.2 ± 18.6 years, men: 13) who received FEES during clinical routine were retrospectively reviewed: Their extent of oropharyngeal dysphagia was rated using an ordinal dysphagia severity scale. FEES-results were compared to a control group of healthy individuals. Dysphagia severity was correlated with the presence of clinical and radiological signs of brain involvement, the Expanded Disability Status Scale (EDSS) and the occurrence of pneumonia. Results. Oropharyngeal dysphagia was present in 8/13 patients, including 6 patients without other clinical indication of brain involvement. Clinical or subclinical swallowing impairment was significantly more severe in patients with NMOSD and MOGAD compared to the healthy individuals ( p = 0.009) and correlated with clinical signs of brain involvement ( p = 0.019), higher EDSS ( p = 0.006) and pneumonia ( p = 0.019). Conclusion. Oropharyngeal dysphagia can occur in NMOSD and MOGAD and might be associated with pneumonia and disability. FEES may help to detect subclinical brain involvement.

Inducing sterile pyramidal neuronal death in mice to model distinct aspects of gray matter encephalitis

Up to one person in a population of 10,000 is diagnosed once in lifetime with an encephalitis, in 50–70% of unknown origin. Recognized causes amount to 20–50% viral infections. Approximately one third of affected subjects develops moderate and severe subsequent damage. Several neurotropic viruses can directly infect pyramidal neurons and induce neuronal death in cortex and hippocampus. The resulting encephalitic syndromes are frequently associated with cognitive deterioration and dementia, but involve numerous parallel and downstream cellular and molecular events that make the interpretation of direct consequences of sudden pyramidal neuronal loss difficult. This, however, would be pivotal for understanding how neuroinflammatory processes initiate the development of neurodegeneration, and thus for targeted prophylactic and therapeutic interventions. Here we utilized adult male NexCreERT2xRosa26-eGFP-DTA (= ‘DTA’) mice for the induction of a sterile encephalitis by diphtheria toxin-mediated ablation of cortical and hippocampal pyramidal neurons which also recruits immune cells into gray matter. We report multifaceted aftereffects of this defined process, including the expected pathology of classical hippocampal behaviors, evaluated in Morris water maze, but also of (pre)frontal circuit function, assessed by prepulse inhibition. Importantly, we modelled in encephalitis mice novel translationally relevant sequelae, namely altered social interaction/cognition, accompanied by compromised thermoreaction to social stimuli as convenient readout of parallel autonomic nervous system (dys)function. High resolution magnetic resonance imaging disclosed distinct abnormalities in brain dimensions, including cortical and hippocampal layering, as well as of cerebral blood flow and volume. Fluorescent tracer injection, immunohistochemistry and brain flow cytometry revealed persistent blood–brain-barrier perturbance and chronic brain inflammation. Surprisingly, blood flow cytometry showed no abnormalities in circulating major immune cell subsets and plasma high-mobility group box 1 (HMGB1) as proinflammatory marker remained unchanged. The present experimental work, analyzing multidimensional outcomes of direct pyramidal neuronal loss, will open new avenues for urgently needed encephalitis research.

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam.

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children's hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Molecular Detection and Genetic Characterization of Orientia tsutsugamushi from Hospitalized Acute Encephalitis Syndrome Cases During Two Consecutive Outbreaks in Eastern Uttar Pradesh, India.

Background: Seasonal outbreaks of acute encephalitis syndrome (AES) have been reported especially in the pediatric population with a high case fatality rate in Eastern Uttar Pradesh, India. Orientia tsutsugamushi (OT) is a causative agent of scrub typhus that has been recently identified as a major cause of AES. However, the specific genotypes of OT responsible for AES cases of this region are not known. Therefore, the present study was undertaken to understand the molecular epidemiology of OT prevailing in the AES endemic Eastern Uttar Pradesh region of India. Methods: The study was conducted on 2529 hospitalized AES cases from August 2016 to December 2017. The presence of antibodies against OT from cerebrospinal fluid (CSF) and serum samples were tested using OT IgM enzyme-linked immunosorbent assay (ELISA), whereas OT DNA was tested from whole blood and CSF specimens targeting the partial gene of 56 kDa using nested PCR. Phylogenetic analysis was conducted with sequences (n = 241) generated in this study. Findings: Among the studied AES cases, 50% were found positive for antibodies against OT, whereas 37% of cases were positive for OT DNA. The genetic analysis study revealed that Gilliam (93.8%) is the prevailing genotype of OT followed by Karp (6.16%) genotype in AES cases. Furthermore, the Gilliam strains of this study showed they were >99% identical to earlier reported Gilliam strains from AES cases. Conclusion: We observed the presence of two main OT genotypes in AES cases, among which the majority of OT genotypes fall under the Gilliam clade. The understanding of predominant genotype will be beneficial for its future implications in vaccine development strategies and the development of rapid diagnostic tests.

Meteorological association for prevalence dynamics of Acute Encephalitis Syndrome: a modeling study

Meteorological association for prevalence dynamics of Acute Encephalitis Syndrome: a modeling study

Economic and disease burden of Japanese encephalitis in Zhejiang Province, 2013-2018.

BackgroundJapanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013–2018, to increase disease awareness and provide evidence for effective health policy.Methodology/Principle findingsWe merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013–2018 in Zhejiang Province. Direct costs were extracted from hospitals’ billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013–2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73–36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%).Conclusions/SignificanceJE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.

A Study of Occurrence of Acute Encephalitis Syndrome Admitted in PICU and Their Outcome- A Hospital Based Study

A Study of Occurrence of Acute Encephalitis Syndrome Admitted in PICU and Their Outcome- A Hospital Based Study

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children’s hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children's hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review.

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis, was first reported by Lai et al. The AMPAR antibodies target against extracellular epitopes of the GluA1 or GluA2 subunits of the receptor. AMPARs are expressed throughout the central nervous system, especially in the hippocampus and other limbic regions. Anti-AMPAR encephalitis was more common in middle-aged women and most patients had an acute or subacute onset. Limbic encephalitis, a classic syndrome of anti-AMPAR encephalitis, was clinically characterized by a subacute disturbance of short-term memory loss, confusion, abnormal behavior and seizure. Magnetic resonance imaging often showed T2/fluid-attenuated inversion-recovery hyperintensities in the bilateral medial temporal lobe. For suspected patients, paired serum and cerebrospinal fluid (CSF) testing with cell-based assay were recommended. CSF specimen was preferred given its higher sensitivity. Most patients with anti-AMPAR encephalitis were complicated with tumors, such as thymoma, small cell lung cancer, breast cancer, and ovarian cancer. First-line treatments included high-dose steroids, intravenous immunoglobulin and plasma exchange. Second-line treatments, including rituximab and cyclophosphamide, can be initiated in patients who were non-reactive to first-line treatment. Most patients with anti-AMPAR encephalitis showed a partial neurologic response to immunotherapy.

Japanese Encephalitis and Other Acute Encephalitis Syndrome in the Khurda, Odisha, India

Background: Japanese Encephalitis (JE) is caused by Japanese encephalitis virus (JEV), a mosquito-borne flavivirus (family Flaviviridae, genus Flavivirus). In India a large number (10-15%) of cases of Acute Encephalitis Syndrome (AES) is due to Japanese encephalitis with a case fatality rate of 18%. In Odisha, sporadic cases of JE/AES cases have been reported since 2011. A case-control study was conducted in Khurda district of Odisha to assess the burden of Japanese encephalitis and the associated risk factors. Methods: A probable case of AES/JE is defined as any child of 0-15 year age with onset of illness between September 1-December 31, 2017, residing in the Khurda district of Odisha, presenting with an “acute onset of fever, change in mental status (such as confusion, disorientation, delirium or coma) and/ or new onset of seizures”.. A 1to 2 age matched case-control study was conducted. Data was analysed using SPSS version 15.0.Results: We enrolled 13 cases and 26 controls between September 1-December 31, 2017. People living in close proximity to the agricultural fields(OR:15.63) rearing livestock at their house and having animal shed at proximity (OR:3.02 and 6.57 respectively) are at higher risk of getting the disease. Presence of waterbodies within 200-meter distance of the household (OR: 9.05) and stagnant water in the surrounding of the houses (OR: 12.38) were at higher risk of getting AES/JE.People using peri-domestic space for toilet (OR: 3.6) and having Practice of open air defecation (OR: 12.38) were are at higher risk of getting the disease.Conclusion: Improvement of water and sanitation practices among the community by empowering the village water hygiene and sanitation committee and village gram panchayat. That will also involve building of toilets in the houses. Vector control activities like insecticide fogging, IRS spraying and distribution of long lasting insecticide treated nets are to be taken into consideration, especially in the rural parts of the district where it is not done regularly. Vaccination coverage of Japanese Encephalitis vaccine is to be increased.