Encephalitis Syndrome Research Articles

Utility of Film Array Meningoencephalitis Panel in Children With Acute Encephalitis Syndrome: A Single Centre Experience from South India

Utility of Film Array Meningoencephalitis Panel in Children With Acute Encephalitis Syndrome: A Single Centre Experience from South India

Epidemiology of Japanese Encephalitis in Central India after Implementing Immunization

Abstract Objective We report the epidemiology of Japanese encephalitis (JE) disease after the implementation of routine immunization in medium-endemic districts in the states of Maharashtra and Telangana in Central India. Methods We investigated acute encephalitis syndrome (AES) patients hospitalized from October 2018 to September 2020. Field visits were also made to the residences of 262 AES cases, including 54 JE cases. Results The overall case fatality ratio was 31%. Maharashtra state contributed 72% of JE and 67% of AES cases. The rural localities had a significantly higher number of JE cases than the urban areas. The occurrence of JE was reported year round, with most JE cases reported during the rainy season. Both AES and JE cases were reported mostly among children, with JE in 66% and non-JE AES in 70% of children. Conclusion The JE disease continues to affect the population after routine immunization. Surveillance, prevention, and control need to be enhanced to achieve accelerated control.

Efficacy and safety of phenytoin and levetiracetam for acute symptomatic seizures in children with acute encephalitis syndrome: an open label, randomised controlled trial

IntroductionSeizures represent a significant comorbidity in children with acute encephalitis syndrome (AES). Despite this, there is a notable absence of randomized controlled trials (RCTs) directly comparing antiseizure medications (ASMs) in children with AES. Materials and MethodsThis RCT aimed to assess the efficacy and safety of phenytoin and levetiracetam in controlling seizures among children with AES. Both ASMs were administered with a loading followed by maintenance dose. After a 12-week period, children exhibiting a normal electroencephalogram and no seizure recurrence underwent tapering and discontinuation of ASM. Clinical follow-up occurred daily for the first week, and subsequently at 4, 12, and 24 weeks, evaluating seizure recurrence, incidence of status epilepticus, cognition, behavior, functional status, ASM acquisition cost, and adverse effects. ResultsA total of 100 children (50 in each group) were enrolled. Within the first week, 5 and 3 children in the phenytoin and levetiracetam groups expired. Up to 1 week or death (whichever occurred earliest), 46 (92 %) and 44 (88 %) children remained seizure-free. Intention-to-treat analysis for both best and worst-case scenarios showed insignificant differences (p=0.52 and 1.0). No children experienced seizure recurrence after 1 week in either group. The number of patients with breakthrough status epilepticus, need for mechanical ventilation, duration of hospital stay, presence of epileptiform abnormalities in repeat electroencephalogram at 12 weeks, functional outcomes at 1, 12, and 24 weeks, as well as cognition and behavioral profiles at 24 weeks, were comparable in both groups (p>0.05 for all). However, the incidence of treatment-emergent adverse events (TEAEs) causally related to study medications was significantly higher in the phenytoin group (p=0.04). ConclusionLevetiracetam and phenytoin are comparable in efficacy in terms of achieving clinical seizure control in children with acute encephalitis syndrome, although levetiracetam group demonstrated fewer adverse effects.

Prospective Analysis of Acute Encephalitis Syndrome: Clinical Characteristics and Patient Outcomes in a Tertiary Care Pediatric Setting

Background: One of the most frequent neurological emergencies in pediatrics, central nervous system infections cause a considerable amount of death and morbidity. Especially in newborns, the symptoms are frequently modest, therefore a strong index of suspicion is needed to make the diagnosis. Inadequate or delayed treatment may result in fatalities or other severe consequences.  Objective: To ascertain the frequency, clinical characteristics, and etiological makeup of kids hospitalized in tertiary PICU due to acute encephalitis syndrome. Results of kids referred to tertiary PICUs with acute encephalitis symptoms.  Study Design: Hospital based prospective study.  Participants: Children with AES from one month up to 18 years of age admitted in PICU of hospitals.  Intervention: Thorough clinical assessments were completed, and blood samples will be sent for various baseline biochemical analyses. In every instance, samples of blood and urine were sent for sensitivity and culture while adhering to strict aseptic protocol. In every incidence of fever with altered sensorium, neuroimaging and CSF analysis will be carried out.The history, clinical examination, and pertinent laboratory investigations are used to determine the etiology of AES.  Results: Out of the one hundred cases that were examined, five had J.E., thirty had rickettsia, twenty had dengue, one had varicella, twelve had COVID-19, five had measles, four were pyogenic, one had tuberculosis, twelve had ADEM, and nine were undiagnosed. A total of 45 patients were lost to follow-up throughout the follow-up period. Of the patients, 16 had hearing loss, 10 had speech loss, 15 had extra pyramidal abnormality, 21 had behavioral abnormality, and 21 had cranial nerve impairments.  Conclusion: AES is a persistent public health issue that requires immediate attention, as well as cooperation and support from other sectors. Strengthening primary health care is urgently needed to provide access to both routine and emergency care, both of which are essential for better results.

An Observational Study on Clinical Profile and Outcome of Japanese Encephalitis Patients Admitted in the Department of Medicine of a Tertiary Care Hospital of North Bank of Assam, India

Background: A significant public health issue in India is Japanese encephalitis (JE), which has a high fatality rate and causes residual neurological damage in survivors. The goal of the current study was to examine JE positive among patients who had been admitted with acute encephalitis syndrome (AES) and to analyse the differences in clinical profile, disease severity, neurological consequences, and mortality rate in Tezpur Medical College and Hospital. Methods: This study is a retrospective observational study in a patients who were diagnosed as Japanese encephalitis on the basis of JEV-specific IgM antibodies in blood and cerebrospinal fluid (CSF) samples. The study included 32 Japanese Encephalitis positive patients admitted in Tezpur Medical College and Hospital (who met the clinical case definition of AES) and thus, their clinical profile and outcome were analysed. Result: A total 32 JE cases were enrolled in the study diagnosed with CSF and Serum IgM ELISA antibody test. All of them were Serum IgM ELISA antibody positive, 9(28%) cases were both Serum and CSF IgM antibody positive. Most common age group affected was 12-20 years(31%). 59.37% cases recovered completely, 21.87% had neurological sequelae at the time of discharge and 18.75% died at ward. Conclusion: Japanese Encephalitis is one of the leading cause of AES in India. In our study it has been seen that GCS score on presentation and CSF cell counts has positive association with mortality and disease sequale. Adequate care and treatment should be provided in order to avoid subsequent complications/sequale. Proper vaccination and vector control can prevent or mitigate this disease.

Acute Encephalitis Syndrome in Children and Adolescents: A Five-Year Descriptive Study From South India

Acute Encephalitis Syndrome in Children and Adolescents: A Five-Year Descriptive Study From South India

Molecular and serological evidence of chikungunya virus infection with high case fatality among pediatric population with acute encephalitis syndrome: first report from Eastern Uttar Pradesh, India.

Acute encephalitis syndrome (AES) outbreaks in children of Eastern Uttar Pradesh (E-UP) region of India have been a longstanding public health issue, with a significant case fatality rate of 20-25%. Since past decade, a rise in chikungunya (CHIK) cases has been occurring, which is a reported etiology of AES. However, the burden of chikungunya virus (CHIKV) among pediatric AES (pAES) is unknown from E-UP. We included 238 hospitalized pAES cases. The presence of IgM antibodies for CHIKV, and Dengue virus (DENV) was tested, and RT-PCR was performed for CHIKV and DENV in serologically confirmed CHIKV and DENV pAES cases. Positive samples were sequenced using Sangers sequencing. Further, to check for co-infection, IgM antibodies for other AES etiologies including Japanese encephalitis virus (JEV), Leptospira and Orientia tsutsugamushi (OT) in serum were also investigated. IgM ELISA demonstrated 5.04% (12) positivity for CHIKV. Among CHIKV IgM positive, 3 (25%, 3/12) pAES patients died. CHIKV genome was detected in 3 pAES specimens. Among which, 2 CHIKV cases were also positive for OT DNA. Partially sequenced CHIKV were genotyped as ECSA. The overall finding indicates evidence of CHIKV infection with high case fatality among pAES patients from E-UP. This study advocates constant serological and molecular surveillance of CHIKV in AES endemic regions of India.

Interest of rare autoantibodies in autoimmune encephalitis and paraneoplastic neurological syndromes: the utility (or futility) of rare antibody discovery.

The increasing recognition and diagnosis of autoimmune encephalitis (AE) and paraneoplastic neurological syndromes (PNS) is partly due to neural autoantibody testing and discovery. The past two decades witnessed an exponential growth in the number of identified neural antibodies. This review aims to summarize recent rare antibody discoveries in the context of central nervous system (CNS) autoimmunity and evaluate the ongoing debate about their utility. In the last 5 years alone 15 novel neural autoantibody specificities were identified. These include rare neural antibody biomarkers of autoimmune encephalitis, cerebellar ataxia or other movement disorders, including multifocal presentations. Although the clinical applications of these rare antibody discoveries may be limited by the low number of positive cases, they still provide important diagnostic, prognostic, and therapeutic insights.

Demographic Profile, Respiratory Presentation and Outcome Analysis of Acute Encephalitis Syndrome in a Tertiary Hospital in Bangladesh

Acute encephalitis syndrome has been a major health problem worldwide due to its high morbidity and mortality. The aim of this study was to find out the demographic profile of acute encephalitis syndrome and to determine the association of the outcome of the disease with the demographic factors and respiratory symptoms at presentation. This observational analytic cross-sectional study was conducted in the departments of Medicine, Paediatrics, and Neurology in Bangabandhu Sheikh Mujib Medical College Hospital in Bangladesh from September 2013 to August 2014. People of all ages who fulfilled the inclusion criteria of acute encephalitis syndrome were included in the study. In this study, 270 cases were diagnosed with acute encephalitis syndrome. Most cases were clustered around the age groups of 0-5 year (24.1%), 6-17 year (24.8%), and 18 -45 year (28.5%). Death was higher among the 18-45 age groups (33.3%) as well as in males (59.3%). Apart from neurological symptoms, respiratory symptoms on presentation were present in 66.9% cases with 89.6% death and this association was found statistically significant (p value < 0.001, AOR 6.96, COR 5.3 with 95% CI). Influence of socio-demographic factors and delay in seeking hospital admission on adverse outcome was not statistically significant. Most cases occurred in January-February (12.6% and 11.1%) and in July (14.4%). Overall mortality was 17.8%. Encephalitis presenting with respiratory symptoms in association carries higher mortality. Bangabandhu Sheikh Mujib Med. Coll. J. 2024;3(1):22-26

Predictors of mortality in acute encephalitis syndrome in children

Encephalitis is an important cause of morbidity, mortality and neurological sequelae in children globally. Causes are diverse and include viral and non-viral etiology as well as autoimmune processes. In the west autoimmune encephalitis are now most common than any single infectious cause, but in India infectious causes are still most common. It is critical to evaluate the immediately to reduce mortality and sequalae in Acute Encephalitis Syndrome (AES) patients. This study has been done to find out different predictors of mortality in outcome of AES at the end of hospital stay. To find out the predictors of mortality in children with acute encephalitis syndrome between age group of 1 month to 14 years. This was a cross sectional analytical study conducted over a period of two years. A total of 310 subjects were included in the study. Different clinical and laboratory parameters were taken to know the different significant predictors of mortality. A total of 310 cases were taken for the study from the age group of 1 month to 14 years. Out of these AES cases 22.5% cases died and 77.5% patients were discharged. Higher mortality was seen in 11-14 years of age group and females had higher mortality as compared to males. Only 5 variables that is refractory seizure, GCS<8, features of raised ICT, shock and requirement of ventilatory support were found to be significant (p<0.05) in predictors of mortality. Other variables like age, sex, socioeconomic status, fever altered sensorium, seizure, meningeal sign, laboratory investigations like serum sodium, total leucocyte count, serum creatinine, duration of hospitalisation were not found to be significant(p>0.05). AES is a disorder of multiple and varying etiology with significant mortality and morbidity. Early diagnosis, appropriate investigation, prompt management go a long way in reducing mortality and sequalae in AES. Refractory seizure, Glasgow Coma Score<8, features of raised Intracranial Tension, Shock and requirement of ventilatory support prognosticate the outcome of Acute Encephalitis Syndrome.

Genetic predisposition to autoimmune encephalitis and paraneoplastic neurological syndromes.

We summarize the recent discoveries on genetic predisposition to autoimmune encephalitis and paraneoplastic neurological syndromes (PNS), emphasizing clinical and pathophysiological implications. The human leukocyte antigen (HLA) is the most studied genetic factor in autoimmune encephalitis and PNS. The HLA haplotype 8.1, which is widely known to be related to systemic autoimmunity, has been only weakly associated with a few types of autoimmune encephalitis and PNS. However, the strongest and most specific associations have been reported in a subgroup of autoimmune encephalitis that comprises antileucine-rich glioma-inactivated 1 (LGI1) limbic encephalitis, associated with DRB1∗07 : 01 , anticontactin-associated protein-like 2 (CASPR2) limbic encephalitis, associated with DRB1∗11 : 01 , and anti-IgLON5 disease, associated with DRB1∗10 : 01∼DQA1∗01∼DQB1∗05 . Non-HLA genes have been poorly investigated so far in autoimmune encephalitis, mainly in those lacking HLA associations such as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, with only a few genome-wide association studies (GWAS) reporting equivocal results principally limited by small sample size. Genetic predisposition seems to be driven mostly by HLA in a group of autoimmune encephalitis characterized by being nonparaneoplastic and having predominantly IgG4 autoantibodies. The contribution of non-HLA genes, especially in those diseases lacking known or strong HLA associations, will require large cohorts enabling GWAS to be powerful enough to render meaningful results.

Japanese Encephalitis Outbreak in Young Adults of Bastar District in Chhattisgarh: A Short Observational Study.

Background Instant infections in children due to acute encephalitis syndrome (AES) were reported in a tribal district of Bastar in Chattisgarh, India, between August 2018 and August 2019. Objective The study was conducted to explore the possibility of a viral cause indicating an outbreak. Methods Clinical surveys and serological investigation tests were conducted to identify the viral etiology. The Bastar area in Chhattisgarh reported factors such as paddy fields near homes, a high pig-to-cattle ratio, a significant presence of Culex vishnui mosquitoes, low socioeconomic status, and a lack of health awareness among the tribal people. Result This study, conducted at the Late Baliram Kashyap Memorial Government Medical College in Jagdalpur, Bastar, Chhattisgarh, India, analyzed 128 samples from fever cases out of 213 patients visiting the Japanese encephalitis virus (JEV) testing center. Among these samples, 71 cases exhibited AES, and subsequent JEV IgM ELISA testing identified 18 cases as JEV-positive, signifying recent JEV infections. Notably, the overwhelming majority (94.44%) of JEV-positive patients were under 16 years old, highlighting the heightened vulnerability of children to JEV illness in the Bastar region. Although male patients accounted for 61.11% of the JEV-positive cases compared to 38.88% of female patients, statistical analysis revealed that this gender disparity was not statistically significant (p-value = 0.18). Conclusion The study emphasizes the significance of identifying the etiology and delivering evidence-based care to patients with AES. Improved diagnosis and management of AES may result from a greater comprehension of the advantages and disadvantages associated with the application and administration of common laboratory and diagnostic algorithms.

Efficacy and safety of ketamine for pediatric and adolescent super-refractory status epilepticus and the effect of cerebral inflammatory conditions

ObjectiveTo investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology. MethodsThis retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups. ResultsThe median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8–15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration. ConclusionsKetamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.

Seroprevalence of neuronal antibodies in diseases mimicking autoimmune encephalitis

Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays and lineblots. However, lineblots may reveal the presence of neuronal antibodies in patients with various non-autoimmune etiologies. Herein we describe patients with non-autoimmune etiologies (cohort B) and detectable neuronal antibodies and compare them to definite cases of autoimmune encephalitis (cohort A) for differences in clinical data. All patients positive for at least one neuronal antibody were retrospectively evaluated for autoimmune encephalitis and/or paraneoplastic neurological syndrome between 2016 and 2022. 39 cases in cohort B and 23 in cohort A were identified. In cohort B, most common diagnoses were neurodegenerative disorders in 9/39 (23.1%), brain tumors in 6/39 (15.4%) while most common detected antibodies were anti–titin (N10), anti-recoverin (N11), anti-Yo (N8) and all were detected in serum only. Differential aspects between cohort A and B were CSF pleocytosis (14/23 (60.8%) vs 11/35 (31.4%), p = 0.042, respectively), MRI features suggestive of encephalitis (6/23 (26.1%) vs 0 (0%), p = 0.002, respectively) and epilepsy restricted to temporal lobes (14/23 (60.9%) vs 2/30 (6.7%), p = 0.0003, respectively). A large proportion of lineblot results were non-specific when only serum was tested and were frequently found in non-autoimmune neurological conditions.

Clinico-epidemiological presentations and management of Nipah virus infection during the outbreak in Kozhikode district, Kerala state, India 2023.

India experienced its sixth Nipah virus (NiV) outbreak in September 2023 in the Kozhikode district of Kerala state. The NiV is primarily transmitted by spillover events from infected bats followed by human-to-human transmission. The clinical specimens were screened using real-time RT-PCR, and positive specimens were further characterized using next-generation sequencing. We describe here an in-depth clinical presentation and management of NiV-confirmed cases and outbreak containment activities. The current outbreak reported a total of six cases with two deaths, with a case fatality ratio of 33.33%. The cases had a mixed presentation of acute respiratory distress syndrome and encephalitis syndrome. Fever was a persistent presentation in all the cases. The Nipah viral RNA was detected in clinical specimens until the post-onset day of illness (POD) 14, with viral load in the range of 1.7-3.3 × 104 viral RNA copies/mL. The genomic analysis showed that the sequences from the current outbreak clustered into the Indian clade similar to the 2018 and 2019 outbreaks. This study highlights the vigilance of the health system to detect and effectively manage the clustering of cases with clinical presentations similar to NiV, which led to early detection and containment activities.

Correlation between clinical-laboratory profile and outcome of AES cases in children: A hospital-based study

Objective: This study aims to determine the correlation between clinical as well as laboratory profile changes with the outcome of acute encephalitis syndrome (AES) cases. Materials and Methods: This prospective observational study was conducted in the Department of Pediatrics at Jorhat Medical College and Hospital, Assam over a period of 1 year where 49 diagnosed cases of AES in children aged between 1 month and 12 years were enrolled. Results: The study found that fever (100%) and altered sensorium (100%) were the most common clinical presentations in AES cases, followed by seizure (63%), headache (34.7%), vomiting (26.5%), diarrhea (22.4%), etc. Japanese encephalitis (JE) was the most common cause of AES (28.6%), followed by herpes simplex virus (4.1%), pyogenic meningitis (4.1%), and tubercular meningitis (2%), etc. However, the majority of cases (61.2%) were found to have an unknown etiology. Among the 49 cases, 27 (55.1%) recovered without neurological sequelae, 8 (16.8%) had neurological sequelae, and 14 (28.6%) died during the course of treatment. The most common neurological sequelae observed were motor deficit (37.5%), behavioral disorders, aphasia (25% each), and cranial nerve palsy. Glasgow coma scale (GCS) at the time of admission and during the time of hospital stay was found to have a significant (p&lt;0.05) correlation with outcome in AES patients. Conclusion: The study concludes that AES cases commonly present with fever, altered sensorium, seizure, headache, vomiting, and signs of meningeal irritation. JE remains a major known cause of AES in children in this region of India. GCS at the time of admission and during the time of hospital stay were found to have a significant correlation with outcome. The neurological sequelae highlight the need for global attention to combat them save the lives of children.

Integration of IgM ELISA and 56 kDa gene PCR in management of pediatric acute encephalitis syndrome associated with scrub typhus

ObjectivesTo identify the potential target genes for detection of Orientia tsutsugamushi (OT) in pediatric acute encephalitis syndrome (pAES). MethodsDNA was extracted from whole blood of 100 pAES cases having tested positive (n = 41) and negative (n = 59) for scrub typhus (ST) by IgM ELISA. These samples were subjected to standard PCR for 56 kDa, 47 kDa, 16 s rRNA, groEL, traD genes and the newly identified 27 kDa gene. ResultsAmong the selected gene targets, 56 kDa demonstrated its superiority for OT detection over the other tested genes. The presence of OT was confirmed via PCR targeting 56 kDa gene in 17 out of the 41 (41.4 %) IgM-positive ST AES cases and 38 out of the 59 (64.4 %) ST IgM negative cases. None of the other gene targets were amplified. ConclusionIntegration of serological diagnosis with molecular diagnostics targeting the 56 kDa gene for routine testing of AES patients would facilitate detection of OT in AES endemic regions.

Acute encephalitis syndrome

Abstract Acute encephalitis syndrome (AES) is a serious disorder characterized by the sudden onset of inflammation in the brain, which may lead to life-threatening clinical situations. This syndrome encompasses a range of neurological disorders, including, but not limited to, viral and bacterial infections, toxins, and metabolic causes. It includes a wide array of spectrum of diseases, and diagnosis is based on clinical symptoms and a wide range of investigations. Treatment is usually symptomatic, and in some instances, definitive treatment is available. Long-term sequelae of AES can include cognitive deficits, behavioral changes, motor impairments, and epilepsy. Rehabilitation and supportive care are often necessary.

Nipah Virus: Understanding the new emerging global threat

Nipah virus, newly emerged zoonosis, is caused by the flying foxes. It has reported occasional outbreaks of encephalitis and respiratory syndrome and a significant mortality rate. Since 1998, when it was first identified in the Malaysia outbreak, this rare brain-damaging virus infection continues to emerge in different parts of the world. Although the risk of infection is imposed on almost a quarter of the world, due to widely distributed natural host, no approved specific treatment and vaccine available till now, but research continues. Therefore, a detailed discussion on this forthcoming infection need to be done. This review article aims on the current scenario of the infection caused by the Nipah virus as well as emphasize on the potential of Nipah virus infection to become global threat in future. Further, this article provides comprehensive review of the infection transmission, its sign and symptoms, diagnosis, and treatment methods with emphasis on prevention and control measures.

Autoantibody-mediated central nervous system channelopathies.

The autoimmune channelopathies represent a rapidly evolving scientific and clinical domain. The description of channels, expressed on neurons and glia, as targets of autoantibodies in neuromyelitis optica, autoimmune encephalitis, and related syndromes have revolutionized many areas of neurologic practice. To date, tens of surface antibody specificities have been described, a number that is likely to continue to increase. A central paradigm for all these disorders is that of pathogenic autoantibodies which target extracellular epitopes accessible for binding in vivo. Hence, in these disorders, the autoantibodies are causative diagnostic tools, and provide valuable reagents to model the diseases. Their production by B-lineage cells provides opportunities to study and modulate their production. Across these syndromes, early recognition and treatment are critical since most respond to immunotherapies. Yet, several unmet medical needs persist within treated patient populations, and widespread clinical under-recognition remains a challenge. In this review, we summarize the neuroscience and immunologic basis of autoantibody-mediated central nervous system channelopathies, the molecular effects of the autoantibodies, clinical phenotypes, and treatment approaches. We describe progress since the inauguration of the field through to open questions and potential future directions.