Acute Central Nervous System Infections Research Articles

Cytokine profile in patients with acute bacterial meningitis

BackgroundBacterial meningitis is a life-threatening disease with high mortality and common long-term sequelae. The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections. We aimed to examine correlations of interleukin (IL)-6, IL-8, IL-10, IL-12(p40), and tumor necrosis factor (TNF)-α levels with disease severity, complications, and outcome in patients with acute bacterial meningitis. MethodsThe study involved 30 patients with bacterial meningitis/meningoencephalitis admitted to the University Hospital St. George, Plovdiv over a period of 4 years. Patients were selected based on clinical presentation and laboratory abnormalities, consistent with a neuroinfection. Enzyme-linked immunosorbent assay was used to measure the studied cytokines in both cerebrospinal fluid (CSF) and serum in parallel. For microbiological diagnosis multiplex, polymerase chain reaction, and CSF culture were used. ResultsIn patients with acute bacterial meningitis CSF levels of IL-6, IL-8, IL-10, and TNF-α are significantly increased than in serum. CSF TNF-α, CSF IL-8, and CSF IL-10 had a moderate negative correlation to CSF glucose. It was found that serum IL-8 is significantly elevated in patients who experienced neurological complications, have severe clinical course, and in deceased patients. CSF IL-10 is increased only in patients with severe acute bacterial meningitis. ConclusionAmong patients with acute bacterial meningitis serum IL-8 could delineate these with increased risk of neurological complications, severe clinical course, and fatal outcome. Serum IL-8 and CSF IL-10 could be used as indicators of disease severity.

The usefulness of hematological parameters and cerebrospinal fluid indexes in the differential diagnosis of acute bacterial from viral meningitis

Central nervous system (CNS) infection is a medical emergency with an important cause of mortality worldwide. The 79 patients with confirmed acute CNS infection (48 bacterial and 31 viral meningitis) were evaluated. Bacterial meningitis score, cerebrospinal fluid (CSF)/serum glucose ratio, and CSF/serum albumin ratio had the highest area under the curves (0.873, 0.843, 0.810, respectively) for discriminating bacterial meningitis. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte ratio (PLR) and CSF lactate dehydrogenase have a good ability for the differential diagnosis of bacterial meningitis. CSF/serum glucose ratio, NLR (with a cut-off value> 8.87), large unstained cell, total protein, albumin, and procalcitonin levels were found to be predictors for mortality. NLR can be used as a biomarker to differentiate bacterial meningitis from viral meningitis and to predict the prognosis of CNS infection. CSF/serum albumin ratio and CSF lactate dehydrogenase can be used to predict bacterial meningitis as well as CSF/serum glucose ratio.

A prospective cohort study on glucose variability and clinical outcomes in comatose children due to acute central nervous system infections admitted in the pediatric intensive care unit

A prospective cohort study on glucose variability and clinical outcomes in comatose children due to acute central nervous system infections admitted in the pediatric intensive care unit

Hypertonic Saline Solution Compared to Mannitol for the Management of Elevated Intracranial Pressure in Children: A Systematic Review

Objective: To explore the effectiveness of commonly used dosing for mannitol (MN) compared with hypertonic saline solution (HSS) in children with elevated intracranial pressure (ICP) due to diabetic ketoacidosis (DKA), head trauma, or acute central nervous system (CNS) infections. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A structured literature review was carried out using the component of the PICO framework. The literature search was conducted in Medline, Ovid, Embase, Google Scholar, and PubMed. A combination of relevant search terms was used. Electronic searches were supplemented by manual searches of references of included studies and review articles. The duplicate citations were identified and removed. Results: A total of 169 articles were identified through the searches, while 8 articles met the inclusion criteria. The characteristics and results of included studies were discussed, regarding the study design, sample size, and outcome. Conclusions: Osmotic agents, such as HSS and MN are commonly used in the management of high ICP. HSS (3% or 7.5%) has superior therapeutic effects over MN (20%) in lowering increased ICP in children with cerebral edema. Key Words: Cerebral edema, Increased intracranial pressure, Children, Osmotic agents, Mannitol, hypertonic saline solution, systematic review, PRISMA.

Current methods for microbiological diagnosis of acute central nervous system infections.

The incidence of infections affecting the central nervous system has increased in recent years, making neuroinfections a current global health problem. The central nervous system is quite well protected from the external and internal environments, although it is susceptible to infection by a wide variety of pathogens. The etiological diversity further complicates the management of such infections because it is important to identify correctly the specific cause in order to choose the most appropriate antimicrobial therapy. Diagnosis is made not only based on clinical and epidemiological data but also on the results of clinical laboratory and microbiological examination of cerebrospinal fluid. This article aims to review current microbiological methods in the diagnosis of acute central nervous system infections and help healthcare providers to recognize their advantages and limitations in order to manage their patients appropriately.

Viral aetiology of acute central nervous system infections in children, Iran.

Introduction. Viral infections are increasingly an important cause of central nervous system (CNS) complications.Hypothesis/Gap Statement. There is no comprehensive insight about CNS infections due to viral agents among Iranian children.Aim. This study aimed to investigate the viral aetiology, clinical and epidemiological profile of children with acute infections of the CNS.Methodology. A prospective study was conducted on children at the referral hospital in Isfahan, Iran, from June 2019 to June 2020. A multiplex PCR assay was used to detect the viral causative agent in cerebrospinal fluid and throat/rectal swab samples.Results. Among 103 patients with eligible criteria, a confirmed or probable viral aetiology was detected in 41 (39.8 %) patients, including enteroviruses - 56.1 %, herpes simplex virus 1/2 (HSV-1/2) - 31.7 %, Epstein-Barr virus - 17.1 %, varicella-zoster virus (VZV) - 9.7 %, influenza A virus (H1N1) -4.9 % and mumps - 2.4 %. There was a higher proportion of PCR-positive samples in infants than in other age groups. Encephalitis and meningoencephalitis were diagnosed in 68.3 % (28/41) and 22 % (9/41) PCR-positive cases, respectively.Conclusion. The findings of this research provide insights into the clinical and viral aetiological patterns of acute CNS infections in Iran, and the importance of molecular methods to identify CNS viruses. HSV and VZV were identified as important causes of encephalitis in young children.

Current Epidemiologic Status and Public Health Importance of Listeriosis: A Review

Listeriosis is a bacterial disease caused by different listeria species, among which Listeria monocytogenes are the most pathogenic species of ruminant animals and humans. This paper aimed to review current updates on the epidemiology and public health significance of listeriosis. The disease is an acute central nervous system infection, with associated abortions occurring in pregnant cattle. Reservoirs of infection are the soil and the intestinal tracts of asymptomatic animals, including wild and feral mammals, birds, and fish. Listeria, like other infections, occurs through ingestion as well as inhalation or direct contact and venereal transmission. In animals, listeriosis typically occurs after the consumption of contaminated silage or other feed sources. Consequently, contaminated food sources, such as raw meat and fish, unpasteurized dairy products, and uncooked vegetables, are good sources of infection in humans. The major clinical forms of listeriosis in cattle are encephalitis, abortion, Mastitis, iritis, The major clinical forms of listeriosis in cattle are encephalitis, abortion, mastitis, ophthalmitis, and keratoconjunctivitis ophthalmitis, iritis and keratoconjunctivitis. The disease can be tentatively diagnosed based on clinical symptoms, and its confirmation is achieved through serological tests and blood culture. Listeriosis shares similar clinical signs with other diseases, such as rabies, Coenurosis, and Scrapie. Response to antibiotic therapy may be poor in neural listeriosis. Prolonged high doses of ampicillin or amoxicillin combined with aminoglycosides may effectively prevent listeriosis in animals. Generally, disease prevention heavily depends on the protection of animal feed and vaccination. Moreover, humans are recommended to avoid eating and drinking uncooked meat and unpasteurized milk products.

High-throughput sequencing unravels the cell heterogeneity of cerebrospinal fluid in the bacterial meningitis of children

Bacterial meningitis (BM) is a common life-threatening infection in children that occurs in the central nervous system (CNS). The cytologic examination of cerebrospinal fluid (CSF) is a key parameter in the diagnosis of BM, but the heterogeneity of cells in the CSF has not been elucidated, which limits the current understanding of BM neuroinflammation. In this study, CSF samples were collected from a number of BM patients who were in different stages of disease progression. Single-cell RNA-sequencing (scRNA-seq), with additional bulk transcriptome sequencing, was conducted to decipher the characteristics of CSF cells in BM progression. A total of 18 immune cell clusters in CSF were identified, including two neutrophils, two monocytes, one macrophage, four myeloid dendritic cells, five T cells, one natural killer cell, one B cell, one plasmacytoid dendritic cell, and one plasma cell subtype. Their population profiles and dynamics in the initial onset, remission, and recovery stages during BM progression were also characterized, which showed decreased proportions of myeloid cells and increased proportions of lymphoid cells with disease progression. One novel neutrophil subtype, FFAR2+TNFAIP6+ neutrophils, and one novel monocyte subtype, THBS1+IL1B+ monocytes, were discovered, and their quantity changes positively correlated with the intensity of the inflammatory response in the CSF during BM. In addition, the CSF of BM patients with unsatisfactory therapeutic responses presented with different cell heterogeneity compared to the CSF of BM patients with satisfactory therapeutic responses, and their CSF featured altered intercellular communications and increased proportions of type II myeloid dendritic cells and plasmacytoid dendritic cells. Moreover, the bulk transcriptome profiles of autologous CSF cells and peripheral blood leukocytes of BM patients showed that the immune cells in these two physiological compartments exhibited distinct immune responses under different onset conditions. In particular, the CSF cells showed a high expression of macrophage characteristic genes and a low expression of platelet characteristic genes compared with peripheral blood leukocytes. Our study conducted an in-depth exploration of the characteristics of CSF cells in BM progression, which provided novel insights into immune cell engagement in acute CNS infection.

Acute symptomatic seizures in adults: a study on etiological profile

Background: Acute symptomatic seizures are clinical seizures occurring in close temporal relationship with an acute central nervous system (CNS) insult, which may be metabolic, toxic, structural, infectious or inflammatory. Currently there is dearth of information on the epidemiology of acute symptomatic seizures among adult medical admissions in Bangladesh. This study was designed to determine the frequency of presentation and etiology of acute symptomatic seizures among adults.
 Methods: This was a cross-sectional study of adult patients admitted with new onset seizure under Neurology Department of BIRDEM General Hospital during the period of January 2019 to December 2020. Clinical assessment and relevant investigations were done and data were collected regarding their etiological diagnosis. Data were analyzed using statistical package for the social sciences (SPSS) version 23.
 Results: Total admission during the study period was 2920 and among them, 100 patients (male 62, female 38) were having their first symptomatic seizures giving a prevalence of 3.4%. They were between 18 to 82 years of age. The main etiology of acute symptomatic seizure was metabolic encephalopathy (42.0%) .It was followed by acute cerebrovascular disease (31.0%) and acute CNS infection (16%) . Acute cerebrovascular disease and metabolic encephalopathy were predominant causes of symptomatic seizure among the elderly and CNS infections among the middle aged adults. The majority (70.0%) of patients had generalized onset seizures. Focal seizures and focal to bilateral tonic clonic seazure were present in 22% and 8% of the patients respectively.
 Conclusion: This study showed that metabolic encephalopathy, acute cerebrovascular disease and CNS infections were the prominent causes of acute symptomatic seizures. Treatment strategies should aim for promt identification and management of these conditions as seizures may not recur when the underlying cause has been removed or the acute phase has elapsed.
 BIRDEM Med J 2022; 12(2): 99-105

Study of clinicodemographic profile of acute central nervous system infection in children and its correlation with neuroimaging

Background: Infection of central nervous system (CNS) is most common cause of fever associated with signs and symptoms of CNS disease in children. Viral infections of CNS are more common than other infections. Radiology and pathology go together in understanding etiology causing CNS infections which have similar clinical manifestations making specific diagnosis difficult. The present study aims to study the utility of different neuroimaging patterns in diagnosis of acute CNS infection. Aims include: to study utility and pattern of neuroimaging in CNS infection in paediatric age group, and to study socio-demographic and clinical profile of CNS infection in children.Methods: Prospective observational study in children 1 month-12 years who presented with CNS infection.Results: Total 58 cases were suspected to have CNS infection, which was more prevalent in 1 month-1 year (27.58%), followed by 5-8 year (24.13%), 1-3 year (22.41), >8 year (20.68%) and 3-5 year (5.17%). Neuroimaging was done in all suspected case (58) of CNS infection in which 30 (51.7%) had abnormal neuroimaging where 3(10%) showed pyogenic meningitis, 7 (23.23%) tubercular meningitis (TBM), 4 (13.13%) tuberculoma, 3 (10%) TBM and tuberculoma, 4 (13.3%) viral meningitis, 1 (3.3%) herpes simplex encephalitis (HSE), 1 (3.3%) COVID encephalitis, 4 (13.3%) acute disseminated encephalomyelitis (ADEM) while 2 (6.66%) brain abscess. Correlation between final diagnosis and neuroimaging was 100% in ADEM, brain abscess, tuberculoma, TB spine, HSV followed by TBM (77.77%), pyogenic meningitis (27.27%) and viral encephalitis (26.66%). Clinically diagnosed acute CNS infection was confirmed in 51.72% and wrong in 48.27%.Conclusions: CNS infections were more common in less than 5 years age. Approximately 50% patients had abnormal neuroimaging finding. It was found that neuroimaging was more accurate in early diagnosis, categorization of CNS infection and detection of complications with high sensitivity.

Clinical Profile and Outcome of Children with Acute Central Nervous System (CNS) Infection from a Tertiary Care Centre in the Present Vaccination Era

Introduction: Meningitis is a common tropical infection which causes significant morbidity and mortality in children. Vaccination is available now-a-days for Haemophilus influenza and pneumococcus which are the common infection causing meningitis. Profile of acute Central Nervous System (CNS) infection in children varies with time to time as it depends on the organism, age, seasonal period, outbreaks, immunisation and place. Aim: To study the clinical, microbiological, radiological profile and outcome of children with acute CNS infection in a tertiary care centre in the present vaccination era. Materials and Methods: This prospective observational study was done in the Department of Paediatrics, Government Dharmapuri Medical College Hospital, Tamil Nadu, India, from December 2018 to June 2020. Total 50 children from one month to 12 years with features of acute CNS infection were included in the study. Clinical features, Cerebrospinal Fluid (CSF) and serology findings, Computed Tomography (CT) scan findings and outcome were taken for analysis. The data were entered in Microsoft Excel software and analysed using Statistical Package for the Social Sciences (SPSS) version 23.0. Results: During the study period, 50 children were diagnosed with acute CNS infection. A total of 37 (74%) children were less than 3 years and 31 (62%) male children were commonly affected. Fever 42 (84%), seizures 46 (92%) and altered sensorium 31 (62%) were the common symptoms. Status epilepticus 40 (87%), shock 18 (36%), respiratory distress 16 (32%) were common findings. In CSF, elevated cell count, reduced sugar, elevated protein were seen in 21 (42%), 14 (28%) and 27 (54%), respectively. Pneumococcus 3 (6%), Japanese Encephalitis (JE) 8 (16%), dengue 5 (10%), herpes 4 (8%), scrub typhus (aetiological agent Orientia tsutsugamushi) 2 (4%) were the common aetiological agents for CNS infection. CT brain was abnormal in 8 (16%) children. Nine children died (18%) and rest 41 (82%) recovered. Conclusion: In the present vaccination era, viruses and tropical fevers- JE, dengue, herpes and scrub typhus were common causes for acute CNS infection in children. Common clinical features were status epilepticus, fever, altered sensorium, respiratory distress and shock. Initial stabilisation of physiological status, specific management and JE vaccination are mandatory to improve the outcome in CNS infection.

The incidence of infectious diseases and viruses other than SARS-CoV-2 amongst hospitalised children in Oslo, Norway during the Covid-19 pandemic 2020–2021

BackgroundMeasures to reduce spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the Covid-19 pandemic 2020–2021 may impact other microbiological agents. We aimed to investigate the incidence of infectious diseases and the incidence of viruses other than SARS-CoV-2 amongst children at The Department of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway during 2020–2021 compared to previous years. MethodsData from April 1st 2020 – March 31st 2021 were compared to data from corresponding 12-months periods 2017–2020. ICD-10 infectious disease diagnoses were collected from the Hospital Diagnosis and Procedure Registry and results of virus PCR analyses of different specimens (mainly nasopharyngeal (NF) and faecal samples) were collected from the Laboratory System at the Department of Microbiology. ResultsThe number of hospital contacts with acute bronchiolitis, viral pneumonia, gastroenteritis and viral central nervous system infections were reduced by 90% (p<0.0001), 89% (p<0.0001), 74% (p<0.0001) and 78% (p<0.01), respectively. Respiratory syncytial virus (RSV), influenza virus A and B and Human metapneumovirus (HMPV) were almost completely absent during the pandemic period. The proportions of rhinovirus positive NF samples were 31.7% vs. 34.9% (p<0.05), but not significantly different for adenovirus. The proportions of positive faecal samples were 1% vs. 10% for adenovirus (p<0.00001) and 3.3% vs. 12% for norovirus (p<0.00001), but not significantly different for rotavirus. The proportions of enterovirus positive samples were 3.5% vs. 21.6% (p<0.00001). ConclusionThe incidence of several paediatric infectious diseases mainly of viral aetiology declined significantly during the Covid-19 pandemic. Some common respiratory viruses were almost completely absent.

Human viral encephalitis associated with suid herpesvirus 1.

BackgroundSuid herpesvirus type 1 (SHV1) is a type of neurotropic virus able to infect various species. However, the clinical cases of human SHV1 encephalitis are still rarely reported, and the clinical characteristics, treatment, and prognosis of human SHV1 encephalitis are still unclear.MethodsIn this study, we reported 2 cases of human encephalitis associated with SHV1 infection and reviewed the other 18 cases from the literatures. A total of 20 cases with human SHV1 encephalitis were summarized and re-analyzed.ResultsNineteen of 20 patients had a history of swine-related occupational exposure before illness onset. All patients initially presented with influenza-like symptoms and then developed seizures, disturbed consciousness, and endophthalmitis. All patients with clinical outcome of modified Rankin Scale of 5 or 6 suffered from rapid progressive respiratory failure. The results of cerebrospinal fluid (CSF) indicated aseptic or viral infection. MRI findings of SHV1 encephalitis were prone to distribute in temporal-frontal and insular cortex, which was similar to the pattern of herpes simplex virus encephalitis, while some cases with involvements of gray matter nuclei had a high rate of mortality. Metagenomic next-generation sequencing (mNGS) revealed that all patients had unique SHV1 sequences with variable reads in the CSF.ConclusionsThe variant SHV1 can cause a new type of human viral encephalitis, characterized by acute, fulminating, and catastrophic central nervous system infection. Rapid progressive respiratory failure and extensive lesions of deep gray matter nuclei might be indicators to poor prognosis. No approved treatments for the encephalitis are available, but it is possible to diagnose encephalitis quickly by mNGS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10072-021-05633-0.

Гастроінтестинальні симптоми при гострих нейроінфекціях у дітей

Актуальність. При тяжких формах інфекційних захворювань окрім локального запалення можуть відбуватися вторинні ураження органів шлунково-кишкового тракту (ШКТ). Мета дослідження. Вивчити семіотику та епідеміологію гастроінтестинальних симптомів у дітей з гострими нейроінфекціями. Матеріали та методи. Дослідження обсерваційне ретроспективне, типу «випадок — контроль». Був проведений аналіз історій хвороби дітей віком від 1 місяця до 18 років, які проходили стаціонарне лікування з приводу гострих нейроінфекцій (менінгіт, енцефаліт та енцефаломієлополінейропатія). Результати. Дослідження включало 117 дітей з гострими інфекційними ураженнями нервової системи. Клінічні симптоми ураження ШКТ спостерігались у 83 (70,9 %) дітей. У симптоматиці переважали порушення моторики кишечника (запор і діарея). Прояви ураження гепатобіліарної системи у вигляді підвищення трансаміназ (аланінамінотрансферази (АЛТ), лужної фосфатази (ЛФ), гамма-глутамілтранспептидази (ГГТП)) та/або змін при ультразвуковому дослідженні (збільшення розмірів, дифузні структурні зміни) спостерігались у 39,1 % хворих. Серед лабораторних показників підвищені рівні АЛТ у 8,3 % пацієнтів, білірубін підвищений тільки в однієї дитини, ЛФ вище вікової норми у 11,8 %, підвищення ГГТП від вікової норми — у 31,3 % хворих. Рівень біомаркеру I-FABP був підвищений у 86,4 % хворих, L-FABP — у всіх (100 %) пацієнтів. Клінічні прояви гастроінтестинальної дисфункції (наявність принаймні одного з гастроінтестинальних симптомів) мали обернений зв’язок з віком дитини (точково-бісеріальний коефіцієнт кореляції (rpb) = –0,19; p = 0,033), корелювали з перебуванням у відділенні анестезіології та інтенсивної терапії (відношення шансів (ВШ) = +5,25; 95% довірчий інтервал (ДІ) 1,62–16,97), проведенням штучної вентиляції (ВШ = +4,5; 95% ДІ 1,00–21,69), рівнем I-FABP (rpb = 0,34; p = 0,019). Висновки. Серед гастроінтестинальних симптомів при гострих нейроінфекціях у дітей найчастіше зустрічаються порушення моторики кишечника у вигляді запору та діареї. Ураження гепатобіліарної системи переважно проявляються помірними змінами лабораторних показників. Біомаркери I-FABP та L-FABP є високочутливими тестами для діагностики ураження ШКТ і гепатобіліарної системи.

Epidemiology Profile of Viral Meningitis Infections Among Patients in Qatar (2015–2018)

Background: Little is known about the etiology of meningitis in the MENA region, including Qatar. Viral agents are considered the major cause for meningitis worldwide. Here, we present primary data about the etiology and clinical and demographic characteristics of viral meningitis (VM) in Qatar between 2015 and 2018.Methods: We retrospectively collected data from Hamad Medical Corporation (HMC), which provides about 80% of healthcare services in Qatar. Data were collected for the period between 2015 and 2018. During this time period, 6,705 specimens were collected from patients with suspected meningitis attending HMC and primary healthcare centers. These specimens were tested for a panel of viruses using the “FTD Viral meningitis” multiplex real-time PCR kit that detects Adenovirus (ADV), Human herpesvirus 1&2 (HSV1 and HSV2), Epstein–Barr virus (EBV), Enteroviruses (EV), Cytomegalovirus (CMV), Varicella zoster virus (VZV), and Parechovirus (PV).Results: Only 10.9% (732/6,705) of all suspected meningitis cases were caused by viral agents. 60.9% of the reported cases were males, compared to 39.1% in females. Most of the infections (73.9%) were reported in children younger than 10 years of age. EV were identified as the main causative agent (68.7%), followed by EBV (7.5%) and ADV (6.8%). Other viral agents including VZV, PV, HSV-1, and HSV-2 were also detected with a lower frequency. Confirmed VM were more prevalent among Qatari subjects compared to other nationalities. We observed no specific seasonality of viral agents, but a slight rise was recorded during the spring seasons (March to June). Fever (59.4%, 435/732) and acute central nervous system (CNS) infection (15.6%, 114/732) were initial symptoms of most cases.Conclusion: This is the first report about the molecular epidemiology of VM in Qatar. In line with the international records, our data showed that EV is responsible for 68.7% of Qatar's VM cases. Further studies are needed to genotype and serotype the identified viruses.

A Prospective Cohort Study on Serum Sodium and Clinical Outcome in Pediatric Nontraumatic Coma.

To study the serum sodium level and clinical outcome in pediatric nontraumatic coma. A prospective cohort study was conducted in a tertiary care pediatric intensive care unit (PICU) from September 2015 to June 2016. Children aged < 13 y with nontraumatic coma [modified-Glasgow Coma Scale (m-GCS) score ≤ 8 or fall of ≥ 3 from baseline within 24h of admission] were included. Children who received intravenous fluids for > 24h, those with developmental delay, or died within 24h of admission were excluded. The serum sodium profile (mEq/L) in the first 72h and clinical outcome [mortality, length of stay in mechanical ventilation, PICU, and hospital] were studied. Eighty patients [Died n = 26 and Survived n = 54] were enrolled. Median [interquartile range (IQR)] age and m-GCS were 21 (4-78) mo and 9 (7-11), respectively. The mean [standard deviation (SD)] Pediatric Risk of Mortality-III (PRISM-III) was 17.7 (4). The most common etiology was acute central nervous system (CNS) infections (30%, n = 24) followed by an intracranial bleed (11.3%, n = 9). Mean (Standard error, SE) sodium levels and fluctuation of serum sodium from baseline up to 72h were similar between nonsurvivors and survivors [140.8 (1.3) vs. 139.6 (0.8), p = 0.421] and [1.2 (0.3) vs. 0.8 (0.2), p = 0.307], respectively. On multivariate analysis, the need for vasoactive therapy was an independent predictor of mortality [adjusted odds ratio = 20.78, 95% CI 4.24-101.85, p = < 0.001, R2 = 0.62]. Mean serum sodium within normal range and fluctuation of serum sodium of 0.8 to 1.2mEq/L over 72h was not associated with poor outcomes in pediatric nontraumatic coma. Vasoactive therapy was an independent predictor of mortality.

Viral Metagenomic Analysis of Cerebrospinal Fluid from Patients with Acute Central Nervous System Infections of Unknown Origin, Vietnam.

Central nervous system (CNS) infection is a serious neurologic condition, although the etiology remains unknown in >50% of patients. We used metagenomic next-generation sequencing to detect viruses in 204 cerebrospinal fluid (CSF) samples from patients with acute CNS infection who were enrolled from Vietnam hospitals during 2012–2016. We detected 8 viral species in 107/204 (52.4%) of CSF samples. After virus-specific PCR confirmation, the detection rate was lowered to 30/204 (14.7%). Enteroviruses were the most common viruses detected (n = 23), followed by hepatitis B virus (3), HIV (2), molluscum contagiosum virus (1), and gemycircularvirus (1). Analysis of enterovirus sequences revealed the predominance of echovirus 30 (9). Phylogenetically, the echovirus 30 strains belonged to genogroup V and VIIb. Our results expanded knowledge about the clinical burden of enterovirus in Vietnam and underscore the challenges of identifying a plausible viral pathogen in CSF of patients with CNS infections.

Clinical Profile and Outcome of Children with Acute Central Nervous System Infection in Kerala, India

Background and aims: Infection of the central nervous system is a significant cause of morbidity and mortality in children. The aim of this study was to evaluate clinical profile and outcome of children aged 1 month to 15 years admitted with acute central nervous system infection between 2008 and 2020 in the Department of Pediatrics, Ananthapuri Hospitals and Research Institute, Thiruvananthapuram, India. Materials and methods: This was a case record based retrospective study. Results: Of 62 children, 44 had meningitis and 18 had encephalitis. Most patients were in the age group 1-5 years old and males were the predominant sex (70.96%). Eighteen patients with meningitis had a clinical triad of fever, headache, and vomiting, while only three with encephalitis experienced this. Seizures and altered sensorium were seen significantly more in children with encephalitis. Cerebrospinal fluid pleocytosis was seen in significantly more patients with meningitis compared with patients with encephalitis. Aetiology for meningitis included pneumococcus, Orientia tsutsugamushi (scrub typhus), meningococcus, and Angiostrongylus cantonensis infection. Causes of encephalitis included enterovirus, mumps virus, herpes simplex virus, dengue virus, and H1N1 influenza virus infection. Paediatric intensive care unit admission was more common for patients with encephalitis. One child with pneumococcal meningitis and another with dengue encephalitis died. Seizures were the most common sequelae. Conclusion: Typical clinical features were not present in most patients with meningitis; therefore, a high index of suspicion is needed for early diagnosis. Exact aetiologies could not be identified in most of the patients. Pneumococcus, scrub typhus, and meningococcus were the aetiological agents identified for meningitis. Encephalitis was attributed to dengue virus, herpes simplex virus, enterovirus, mumps virus, and H1N1 influenza virus infection.

Serum Procalcitonin Levels in Patients with Acute Central Nervous System Infections

BACKGROUND: Bacterial infections of the brain are associated with high mortality and neurological sequelae, whereas viral diseases are usually self-limiting. A fast and easy-to-perform biomarker is needed to improve management in these patients.&#x0D; AIM: Procalcitonin (PCT) testing has already been implemented in many laboratories for evaluating septic patients and it is an easily accessible biomarker, so we aimed to examine its role specifically in discriminating acute bacterial from viral infections of the central nervous system (CNS).&#x0D; MATERIALS AND METHODS: This prospective study included 80 patients with both clinical symptoms and laboratory findings suggesting acute CNS infection. The microbiological analysis included direct microscopy, culturing, latex-agglutination test, and multiplex polymerase chain reaction. PCT levels were measured by enzyme-linked fluorescent assay technology.&#x0D; RESULTS: Following the results of the microbiological analysis, the cases were divided into three groups – bacterial 26.3% (n = 21), viral 17.5% (n = 14), and unidentified neuroinfections – 56.2% (n = 45). A statistically significant difference in the median serum PCT was observed between the bacterial and viral neuroinfections (p = 0.004) as well as between bacterial and unidentified infections of the brain (p = 0.000). No significant difference was found (p = 1.000) when comparing viral and unidentified neuroinfection. The area under the receiver operating characteristic curve for serum PCT was 0.823 but could be increased to 0.929 when combining serum PCT and C-reactive protein (CRP).&#x0D; CONCLUSION: Serum PCT levels are significantly higher in patients with acute bacterial infections of the brain. As a stand-alone biomarker, its discriminatory power is not superior to the classical laboratory parameters in the cerebrospinal fluid and serum CRP. However, when combined with serum CRP, excellent discriminatory power is observed.

Insight into the divergent role of TRAIL in non-neoplastic neurological diseases.

Tumour necrosis factor–related apoptosis‐inducing ligand (TRAIL) is a member of the tumour necrosis factor (TNF) superfamily which mainly induces apoptosis of tumour cells and transformed cell lines with no systemic toxicity, whereas they share high sequence homology with TNF and CD95L. These unique effects of TRAIL have made it an important molecule in oncology research. However, the research on TRAIL‐related antineoplastic agents has lagged behind and has been limited by the extensive drug resistance in cancer cells. Given the several findings showing that TRAIL is involved in immune regulation and other pleiotropic biological effects in non‐malignant cells, TRAIL and its receptors have attracted widespread attention from researchers. In the central nervous system (CNS), TRAIL is highly correlated with malignant tumours such as glioma and other non‐neoplastic disorders such as acute brain injury, CNS infection and neurodegenerative disease. Many clinical and animal studies have revealed the dual roles of TRAIL in which it causes damage by inducing cell apoptosis, and confers protection by enhancing both pro‐ and non‐apoptosis effects in different neurological disorders and at different sites or stages. Its pro‐apoptotic effect produces a pro‐survival effect that cannot be underestimated. This review extensively covers in vitro and in vivo experiments and clinical studies investigating TRAIL. It also provides a summary of the current knowledge on the TRAIL signalling pathway and its involvement in pathogenesis, diagnosis and therapeutics of CNS disorders as a basis for future research.