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An increase in the number of herpes zoster patients has been reported since universal varicella immunization was introduced, perhaps because of reduced opportunities for varicella patients to experience the natural booster effect caused by reexposure. We investigated recent trends of varicella zoster virus (VZV)-related central nervous system (CNS) infections at a university hospital in Japan. We enrolled patients with suspected CNS infection during 2013-2022 and tested cerebrospinal fluid samples by real-time PCR for DNA from 7 human herpesviruses. VZV DNA was the most commonly detected in 62 (10.2%) of 615 patients. Kulldorff's circular spatial scan statistics demonstrated a significant temporal cluster of patients with VZV-related CNS infections during 2019-2022 (p = 0.008). Among persons with such infections, the percentage with aseptic meningitis was significantly higher during 2019-2022 (86.8%), when the temporal cluster of cases occurred, than during 2013-2018 (50.0%) (p = 0.0029).

Objectives: Acute central nervous system (CNS) infections in children can lead to neurological complications and mortality. This study aimed to identify the clinical manifestations, laboratory parameters, and cerebrospinal fluid characteristics indicative of CNS infections and define the risk factors that lead to pediatric intensive care unit (PICU) admission in the pediatric population of Şanlıurfa, a city in southeastern Turkey., Methods: This retrospective analysis included patients aged 1 month to 18 years who were treated for acute CNS infections in the Şanlıurfa Training and Research Hospital between January 2020 and May 2023. Clinical data were obtained from the hospital electronic medical records., Results: A total of 68 patients with acute CNS infections were included in this study. The median patient age was 3 (0.94-8.75) years. Fever was the most prevalent symptom in 92.6% of the patients. Of the total, 25% (n = 17) of the patients had an identified causative agent and 35.3% (n = 24) were admitted to the PICU. Serum C-reactive protein (CRP) levels were significantly higher in patients with bacterial meningitis than in those with viral meningitis (p = 0.007). Patients with impaired consciousness and seizure were significantly more likely to require admission to the PICU than patients without these conditions (both p < 0.001). Patients requiring PICU admission had significantly higher platelet counts (p = 0.01)., Conclusions: Impaired consciousness, seizure, and thrombocytosis on admission were important risk factors for PICU admission. Serum CRP levels can serve as an indicator of bacterial meningitis. A combination of physical findings from clinical evaluations and laboratory data is necessary to accurately diagnose bacterial CNS infections., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of the Harran University Faculty of Medicine (No. HRÜ/24.04.35), and the requirement for informed consent was waived by the Ethics Committee of the Harran University Faculty of Medicine because of the retrospective nature of the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Human parechoviruses (HPeVs) are known to cause meningo-encephalitis among neonates and infants. We aimed to describe the epidemiology of HPeVs causing central nervous system infections in Alberta from 2014 to 2019 with comparison of known HPeV-3 and emerging HPeV-5. Genomic analysis was completed on a subset of HPeV-5 strains to understand genetic relatedness to other known strains. All cerebrospinal fluid (CSF) samples in Alberta with detection of HPeVs were identified and a case review of medical records was conducted, retrospectively, to gather demographic and clinical details. Descriptive and analytic statistics were used to describe and compare the characteristics of cases affected by HPeV-3 with HPeV-5. Genome amplification was completed on six HPeV-5 samples. During the study period, 18,882 CSF samples were tested; 56 were positive for HPeV-3 or HPeV-5, and 52 patients were included in this study (40 HPeV-3 cases and 12 HPeV-5). A total of 40% of cases occurred in 2016, and 64% of infections occurred in the months of August to October. The mean age of cases was 18 days for HPeV-5 compared with 26 days for HPeV-3 ( p = 0.045). Phylogenetic comparison showed similarity to a recombinant strain reported in Australia. HPeV meningo-encephalitis affected neonates/infants, mostly in late summer/early fall, and genomic sequencing of new strains can contribute to understanding the epidemiology of HPeV infections globally.

To analyze the risk factors of secondary Central nervous system infections (CNSIs) after craniotomy, and to establish an individualized predictive model for CNSIs risk. The independent risk factors were screened by univariate and multivariate logistic regression analysis. Logistic regression, naive bayes, random forest, light GBM and adaboost algorithms were used to establish predictive models for secondary CNSIs after craniotomy. The predictive model based on the Adaboost algorithm demonstrated superior prediction performance compared to the other four models. Under 5-fold cross validation, the accuracy was 0.80, the precision was 0.69, the recall was 0.85, the F1-score was 0.76, the area under the ROC curve was 0.897,and the average precision was 0.880. The top 5 variables of importance in Adaboost model were operation time, indwelling time of lumbar drainage tube, indwelling lumbar drainage tube during operation, indwelling epidural drainage tube during operation, and GCS score. In addition, Adaboost model with the best prediction performance was used for clinical verification, and the prediction results were compared with the actual occurrence of CNSIs after surgery. The results showed that the accuracy of Adaboost model in predicting CNSIs was 60%, the accuracy of Adaboost model in predicting non-CNSIS was 92%, and the overall prediction accuracy was 76%., (© 2024. The Author(s).)

Human Herpesviruses (HHVs) play a significant role in neurological diseases such as encephalitis and meningitis, adding significant morbidity. This study aims to retrospectively analyze the effect of HHVs on patients with neurological symptoms, focusing on the Herpesviridae family's contributions to central nervous system (CNS) infections., Methods: This retrospective cohort study included 895 patients suspected of viral CNS infections, utilizing molecular diagnosis via qPCR to identify HHVs in cerebrospinal fluid (CSF) samples. This was conducted at a reference tertiary care hospital for infectious diseases in the western Brazilian Amazon from January 2015 to December 2022, focusing on the Herpesviridae family's clinical repercussions and of Cytomegalovirus in CNS infections., Results: The findings revealed that 7.5% of the analyzed samples tested positive for HHVs, with Human Cytomegalovirus (HCMV) and Epstein-Barr Virus (EBV) being the most prevalent. A significant association was found between HHVs and neurological diseases such as encephalitis and meningitis, especially among people living with HIV/AIDS (PLWHA), highlighting the opportunistic nature of these viruses. The study underscores the critical role of CSF analysis in diagnosing CNS infections and the complexity of managing these infections in HIV patients due to their immunocompromised status., Conclusions: The results emphasize the need for comprehensive diagnostic approaches and tailored treatment strategies for CNS infections in immunocompromised individuals. The study calls for ongoing research and advancements in clinical practice to improve patient outcomes facing CNS infections, particularly those caused by HHVs.

Objective: The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific to Brazil., Methods: A retrospective cross-sectional study was performed from January 2017 to December 2021., Results: A total of 469 children with seizure and fever were analyzed. The identified event was the first in 65.9% (n = 309). A total of 54.2% (n = 254) of patients had a simple febrile seizure. Infectious focus, excluding previous central nervous system (CNS) infection, was identified in 35.6% (n = 167) patients. Meningitis was identified in 7.7% (n = 36) patients, all of them were viral. Patients with CNS infection had a higher frequency of symptoms such as nausea and vomiting, drowsiness, headache, and higher level of leukocytosis. A longer duration of fever was found to be more strongly associated with CNS infection., Conclusions: When considering the use of lumbar puncture in febrile seizure, it is important to conduct a comprehensive evaluation that considers multiple factors, including clinical signs, symptoms, and the overall clinical context. Meningeal signs may be less prominent, and other symptoms such as lethargy, irritability, and vomiting may serve as more reliable indicators. Although clinical examination suggestive of meningitis remains an important factor, the recurrence of febrile seizures and a longer length of fever can provide additional insights and aid in decision-making regarding lumbar puncture., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Parechovirus (HpEV) and Enterovirus (EV) infections in children mostly have a mild course but are particularly fearsome in newborns in whom they may cause aseptic meningitis, encephalitis, and myocarditis. Our study aimed to describe the clinical presentations and peculiarities of CNS infection by HpEV and EV in neonates. This is a single-center retrospective study at Istituto Gaslini, Genoa, Italy. Infants aged ≤ 30 days with a CSF RTq-PCR positive for EV or HpEV from January 1, 2022, to December 1, 2023, were enrolled. Each patient's record included demographic data, blood and CSF tests, brain MRI, therapies, length of stay, ICU admission, complications, and mortality. The two groups were compared to identify any differences and similarities. Twenty-five patients (15 EV and 10 HpEV) with a median age of 15 days were included. EV patients had a more frequent history of prematurity/neonatal respiratory distress syndrome (p = 0.021), more respiratory symptoms on admission (p = 0.012), and higher C-reactive protein (CRP) levels (p = 0.027), whereas ferritin values were significantly increased in HpEV patients (p = 0.001). Eight patients had a pathological brain MRI, equally distributed between the two groups. Three EV patients developed myocarditis and one HpEV necrotizing enterocolitis with HLH-like. No deaths occurred.  Conclusion: EV and HpEV CNS infections are not easily distinguishable by clinical features. In both cases, brain MRI abnormalities are not uncommon, and a severe course of the disease is possible. Hyper-ferritinemia may represent an additional diagnostic clue for HpEV infection, and its monitoring is recommended to intercept HLH early and initiate immunomodulatory treatment. Larger studies are needed to confirm our findings. What is Known: • Parechovirus and Enteroviruses are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants. • The clinical course and distinguishing features of Parechovirus and Enterovirus central nervous system infections are not well described. What is New: • Severe disease course, brain MRI abnormalities, and complications are not uncommon in newborns with Parechovirus and Enteroviruses central nervous system infections. • Hyper-ferritinemia may represent an additional diagnostic clue for Parechovirus infection and its monitoring is recommended., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Central nervous system (CNS) infections in solid organ transplant (SOT) recipients may present atypical or nonspecific symptoms. Due to a wider range of infectious agents compared with immunocompetent hosts, diagnosis is challenging. This review categorizes CNS infections in SOT recipients by cause., Recent Findings: New studies have reported new data on the epidemiology and the risk factors associated with each specific pathogen described in this review. Additionally, we included the treatment recommendations., Summary: The latest findings give us an insight into the different pathogens causing infectious neurologic complications in SOT recipients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality., Recent Findings: In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics., Summary: A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV., Methods: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up., Results: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7-30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation., Conclusion: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services., (© 2024. The Author(s).)

Purpose: The goal of this study was to investigate severe central nervous system infections (CNSI) in adults admitted to the intensive care unit (ICU). We analyzed the clinical presentation, causes, and outcomes of these infections, while also identifying factors linked to higher in-hospital mortality rates., Materials and Methods: We conducted a retrospective multicenter study in Rio de Janeiro, Brazil, from 2012 to 2019. Using a prediction tool, we selected ICU patients suspected of having CNSI and reviewed their medical records. Multivariate analyses identified variables associated with in-hospital mortality., Results: In a cohort of 451 CNSI patients, 69 (15.3%) died after a median 11-day hospitalization (5-25 IQR). The distribution of cases was as follows: 29 (6.4%) had brain abscess, 161 (35.7%) had encephalitis, and 261 (57.8%) had meningitis. Characteristics: median age 41 years (27-53 IQR), 260 (58%) male, and 77 (17%) HIV positive. The independent mortality predictors for encephalitis were AIDS (OR = 4.3, p = 0.01), ECOG functional capacity limitation (OR = 4.0, p < 0.01), ICU admission from ward (OR = 4.0, p < 0.01), mechanical ventilation ≥10 days (OR = 6.1, p = 0.04), SAPS 3 ≥ 55 points (OR = 3.2, p = 0.02). Meningitis: Age > 60 years (OR = 234.2, p = 0.04), delay >3 days for treatment (OR = 2.9, p = 0.04), mechanical ventilation ≥10 days (OR = 254.3, p = 0.04), SOFA >3 points (OR = 2.7, p = 0.03). Brain abscess: No associated factors found in multivariate regression., Conclusions: Patients' overall health, prompt treatment, infection severity, and prolonged respiratory support in the ICU all significantly affect in-hospital mortality rates. Additionally, the implementation of CNSI surveillance with the used prediction tool could enhance public health policies., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest in writing this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Central nervous system (CNS) infections are important causes of mortality and morbidity in children, and they are related to severe problems such as hearing loss, neurological sequelae, and death. The objective was to describe clinical and laboratory exam profiles of children who were diagnosed with CNS infections., Methods: We conducted a cross-sectional study based on medical records, which included pediatric patients aged from 3 months to 15 years, with a clinical suspicion of CNS infection between January 2014 to December 2019. The pathogens were confirmed in cerebrospinal fluid (CSF) samples using Gram staining, cell culture, molecular diagnostics (PCR and qPCR), and serology., Results: Out of the 689 enrolled patients, 108 (15.6%) had laboratory-confirmed infections in CSF. The most common bacterial pathogens isolated from the culture were Neisseria meningitidis serogroup C in 19, Streptococcus pneumoniae in 11, and Haemophilus influenzae in seven samples. The viruses identified were Enterovirus , Cytomegalovirus , Var icella-zoster virus , Epstein-Barr virus , and arbovirus. No patient was found to be positive for Herpes simplex virus 1 and 2 . Patients with viral infections showed altered levels of consciousness ( p  = 0.001) when compared to bacterial infections., Conclusion: This study shows the presence of important vaccine-preventable pathogens, and different families of viruses causing CNS infections in the pediatric patients of Manaus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Marinho, Ferreira, Barrionuevo, Melo, Cordeiro, Pinto, Monte, da Silva, Martins, Reis, Tufic-Garutti, Sampaio, de Castro, Feitoza, da Rocha, de Lima Ferreira and Bastos.)

In 2022, a surge in cases of pediatric human parechovirus (HPeV) central nervous system infections in young infants was seen at our institution. Despite the dramatic increase in the number of cases seen that year, the clinical features of the illness were similar to prior years. The recent pediatric HPeV surge highlights the need to evaluate treatment options and standardize follow-up to better understand the long-term prognosis of infants with HPeV infection., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Central nervous system (CNS) viral infections are critical causes of morbidity and mortality in children; however, comprehensive data on etiology is lacking in developing countries such as Indonesia. To study the etiology of CNS infections in a pediatric population, 50 children admitted to two hospitals in Bandung, West Java, during 2017-2018 were enrolled in a CNS infection study. Cerebrospinal fluid and serum specimens were tested using molecular, serological, and virus isolation platforms for a number of viral and bacteriological agents. Causal pathogens were identified in 10 out of 50 (20%) and included cytomegalovirus (n = 4), Streptococcus pneumoniae (n = 2), tuberculosis (n = 2), Salmonella serotype Typhi (n = 1) and dengue virus (n = 1). Our study highlights the importance of using a wide range of molecular and serological detection methods to identify CNS pathogens, as well as the challenges of establishing the etiology of CNS infections in pediatric populations of countries with limited laboratory capacity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt., (© 2023. The Author(s).)

Background: Consensus guidelines for antibiotic prophylaxis in endoscopic endonasal surgery (EES) have not been developed. The study objective was to define the microbiologic and clinical characteristics of post-EES central nervous system (CNS) infections., Methods: This was a single-center retrospective study of patients >18 years of age who underwent EES between January 2010 and July 2021 at a high-volume skull base center. Patients with confirmed CNS infection within 30 days of EES were included. During the study period, the standard prophylaxis regimen was ceftriaxone 2 g every 12 hours for 48 hours. For patients with a documented penicillin allergy, vancomycin plus aztreonam was recommended., Results: In total, 2440 EES procedures were performed on 2005 patients; the CNS infection rate was 1.8% (37/2005). CNS infections were more common among patients with a history of previous EES (6.5%; 20/307) compared with those who did not (1%; 17/1698; P < 0.001). The median time from EES to CNS infection was 12 (6-19) days. Thirty-two percent (12/37) of CNS infections were polymicrobic, which was more common among patients without previous EES (52.9%; 9/17) compared with those with previous EES (15%; 3/20; P = 0.03). Across all cases, Staphylococcus aureus (n = 10) and Pseudomonas aeruginosa (n = 8) were commonly isolated pathogens. Among those with confirmed methicillin-resistant Staphylococcus aureus (MRSA) nares colonization before EES, 75% (3/4) developed MRSA CNS infections compared with 6.1% (2/33) of noncolonized patients (P = 0.005)., Conclusions: CNS infection after EES is rare and causative pathogens vary. Further studies are needed to identify the impact of MRSA nares screening on antimicrobial prophylaxis before EES., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: At present, central nervous system (CNS) infection in patients with traumatic brain injury is usually diagnosed according to the clinical manifestations and results of cerebrospinal fluid (CSF) bacterial culture. However, there are difficulties in obtaining specimens in the early stage., Aim: To develop and evaluate a nomogram to predict CNS infections in patients with severe traumatic brain injury (sTBI) after craniotomy., Methods: This retrospective study was conducted in consecutive adult patients with sTBI who were admitted to the neurointensive care unit (NCU) between January 2014 and September 2020. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were applied to construct the nomogram, and k-fold cross-validation (k = 10) to validate it., Findings: A total of 471 patients with sTBI who underwent surgical treatment were included, of whom 75 patients (15.7%) were diagnosed with CNS infections. The serum level of albumin, cerebrospinal fluid (CSF) otorrhoea at admission, CSF leakage, CSF sampling, and postoperative re-bleeding were associated with CNS infections and incorporated into the nomogram. Our model yielded satisfactory prediction performance with an area under the curve value of 0.962 in the training set and 0.942 in the internal validation. The calibration curve exhibited satisfactory concordance between the predicted and actual outcomes. The model had good clinical use since the DCA covered a large threshold probability., Conclusion: Individualized nomograms for CNS infections in sTBI patients could help physicians screen for high-risk patients to perform early interventions, reducing the incidence of CNS infections., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the risk factor associated with central nervous system infection, a rare and dire complication after spinal surgery., Methods: Univariate and multivariate logistic regression analyses were performed to screen for the independent risk factors. According to the different administration methods of antibiotics, patients were divided into intravenous and intrathecal groups. The differences in time needed for body temperature, white blood cells (WBC), and C-reactive protein (CRP) to return to normal and the time of antibiotic application were compared between the 2 groups. In addition, the differences in WBC, neutrophil ratio, CRP, procalcitonin in blood, and WBC in cerebrospinal fluid were compared before intrathecal injection, after the first one, and the last one. The incidence of complications in the 2 groups was observed., Results: Dural tears, laminectomy, and operation time >3 hours were identified as independent risk factors. The time needed for body temperature, WBC, and CRP to return to normal and the antibiotic application time were significantly different between the 2 groups (all P < 0.05). Before and after the first intrathecal injection and after the last intrathecal injection, the differences in WBCs, neutrophil ratios, CRP, procalcitonin in blood, and cerebrospinal fluid-WBC were statistically significant in overall and pairwise comparisons (P < 0.05). Complications occurred in 2 and 14 cases, respectively., Conclusions: The independent risk factors for central nervous system infection after spinal surgery were a dural tear, laminectomy, and operation time > 3 hours. Combined intravenous and intrathecal injections of antibiotics led to a better effect than intravenous injection alone; however, this approach was associated with more complications., (Copyright © 2022. Published by Elsevier Inc.)

Diagnostic radiologists can increase their clinical value by supplementing image pattern recognition with knowledge of epidemiology and geographic distribution of central nervous system (CNS) infections and their causative organisms. This article reviews the changing global disease patterns, as well as zoonotic outbreaks of henipaviruses, coronaviruses, and other emerging, reemerging, and vector-borne organisms; case examples highlight typical imaging features of CNS infections and their mimics. Technical advances in neuroimaging help to enhance the value of radiologists to the multidisciplinary team and the responses to future pandemic preparation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Viral central nervous system (CNS) infections seriously threaten the life and health of children, with a high mortality and severe sequelae in China and globally. Surveillance of viral CNS infections in children is important, especially in hospitalized children, to facilitate disease evaluation., Methods: In this study, we collected the data on the discharged Face Sheet of Medical Records from database from 2016 to 2020 and analyzed the epidemiologic characteristics and disease burden of hospitalized children (≤18 years old) with viral CNS infections in China. We classified the discharge diagnosis of viral CNS infection as viral encephalitis (VE), viral meningitis (VM), viral meningoencephalitis (VME), viral encephalomyelitis (VEM), and viral meningomyelitis (VMM)., Results: A total of 42,641 cases of viral CNS infections were included in the database, consisting of 39,279 cases with VE (92.47%), 2011 cases with VM (4.73%), 1189 cases with VME (2.80%), 118 cases with VEM (0.28%), and 44 cases with VMM (0.10%). The number of hospitalized patients with viral CNS infections accounted for 0.74% (42,641 of 5,790,910) of all hospitalized cases. The onset of viral CNS infections presented seasonal characteristic, with peaks in June to July and December to January. Seizures are the most frequent complication of this disorder. Median length of stay and inpatient expenditures for patients with viral CNS infections were 9 days and 1144.36 USD. Causative viruses were identified in 4.33% (1848 of 42,641) of patients., Conclusions: This study will help understand the clinical epidemiology and disease burden of hospitalized children with viral CNS infections in China., (Copyright © 2022 Elsevier Inc. All rights reserved.)

From July to October 2020, 99 cases of central nervous system (CNS) infections were identified in Thai Binh Pediatric Hospital, Viet Nam, representing a five-fold increase compared to the baseline incidence during the previous five years. Clinical data were retrospectively collected. Cerebrospinal fluid specimens (CSF) were secondarily tested for pathogens using viral culture and PCR assays. Patient median age was 5 years (0-12 years); 58.6% were male. Of these children, 83.8% had CSF white blood culture (WBC) counts of ≥ 10 cells/µL, including 58 of 99 (58.6%) with a WBC count ≥ 100 cells/µL. Overall, 72 (72.7%) patients had confirmed infections with a pathogen identified in the CSF, the majority of which (66) were enterovirus. Sequencing results suggested that the rise of incidence observed in 2020 was due to Echovirus 4 ( n  =  45), Echovirus 30 ( n  =  8), and Echovirus 6 ( n  =  1) circulation. A confirmed CNS infection was significantly associated with older age (≥5 years, OR = 3.64, p  = 0.03) and with an increased WBC count in the CSF (OR = 6.38, p -value = 0.01 for WBCs from 10 to <100 and OR = 7.90, p -value = 0.002 for WBCs ≥100). Ninety-seven (97) of 99 (98.0%) children received empiric antimicrobial treatment, and 35 (35.3%) were treated with multiple antibiotics. Eighty-four (84) patients (84.9%) were discharged home, and 11 (11.1%) were transferred to the National Hospital because their condition had worsened. No deaths were recorded. Point-of-care tests, including real-time PCR assays to identify common pathogens, should be implemented for more accurate diagnosis and more appropriate antibiotic use.

Knowledge of the clinical presentation of central nervous system (CNS) infections and the causative pathogens is crucial for appropriate diagnosis and rapid initiation of appropriate treatment to prevent severe neurological sequelae. The aim of this study is to understand the aetiology of CNS infections based on the clinical presentation of Vietnamese patients. A prospective hospital-based cohort study was conducted between May 2014 and May 2017. We screened 137 patients with clinically suspected CNS infection for fungal, bacterial and viral pathogens using their cerebrospinal fluid (CSF) and blood cultures. In addition, DNA or RNA extracted from CSF samples were subjected to nucleic acid testing (NAT) with a selective panel of bacterial, viral and fungal pathogens. At least one pathogen could be detected in 41% (n = 56) of the patients. The main pathogens causing CNS infections were Streptococcus suis (n = 16; 12%) and Neisseria meningitidis (n = 9; 7%), followed by Herpes simplex virus 1/2 (n = 4; 3%) and Klebsiella pneumoniae (n = 4; 3%). Other pathogens were only identified in a few cases. Patients with bacterial CNS infections were significantly older, had a worse outcome, a lower Glasgow Coma Scale (GCS), a higher rate of speech impairment and neck stiffness than patients with viral or tuberculous CNS infections. In northern Vietnam, adults are mostly affected by bacterial CNS infections, which have a severe clinical course and worse outcomes compared to viral or tuberculous CNS infections. Clinicians should be aware of the regional occurrence of pathogens to initiate rapid and appropriate diagnosis and treatment., (© 2022. The Author(s).)

Background: Few studies have explored the Central Nervous System (CNS) infection illness trajectory among older persons with dementia in sub-Saharan African (SSA) settings. This study explored the Caregiver's perspectives on the Central Nervous System infection illness trajectory among the older persons with dementia in Northern Uganda., Methods: This was a qualitative study conducted in Lira District northern Uganda in March 2022 amongst purposively selected 20 caregivers of the older persons aged 50 + years with a positive history of CNS infection and later life dementia. Data were collected using an in-depth interview guide. Audio recordings and field notes of the interviews were undertaken. The interviews generated data on the CNS infection illness trajectory from onset to the current demented state of the older persons. The audio-recorded interviews were transcribed verbatim before manual reflective thematic analysis., Results: Older persons with a positive history of CNS infection illness and later life dementia in rural northern Uganda presented with symptoms of early life CNS infection illness ranging from neck pain, back pain, chronic headache, and fatigue. There were also manifestations of comorbidities particularly road traffic accidents involving traumatic injury to the head, neck, and spine, high blood pressure, chronic headache, and or their medications in the older person's trajectory to later life dementia. A plurality of healthcare which included both formal and informal healthcare medicines was sought and utilized for the treatment and care of the CNS infection illness and dementia by the older persons amidst improper diagnosis and mismanagement., Conclusions and Recommendations: Older persons with early-life CNS infections illness and later-life dementia were reported to present with symptoms including neck pain, back pain, chronic headache, high blood pressure, and fatigue. The reported symptoms of CNS infection illness may be intertwined with co-morbidities particularly traumatic injury involving the head, neck, and spine, high blood pressure, and chronic headache. Healthcare professionals should integrate routine screening of older persons for the history of CNS infections, chronic headache, high blood pressure, trauma to the head, neck, and spine, and dementia and early treatment., (© 2022. The Author(s).)

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.

Background: Community-acquired central nervous system infections (CA-CNS infections) have the characteristics of acute onset and rapid progression, and are associated with high levels of morbidity and mortality worldwide. However, there have been only limited studies on the etiology of this infections. Here, metagenomic next-generation sequencing (mNGS), a comprehensive diagnosis method, facilitated us to better understand the etiology of CA-CNS infections., Methods: We conducted a single-center retrospective study between September 2018 and July 2021 in which 606 cerebrospinal fluid (CSF) samples were collected from suspected CNS infectious patients for mNGS testing, and all positive samples were included in this analysis., Results: After the exclusion criteria, a total of 131 mNGS-positive samples were finally enrolled. Bacterial, viral, fungal, parasitic, specific pathogen and mixed infections were accounted for 32.82% (43/131), 13.74% (18/131), 0.76% (1/131), 2.29% (3/131) and 6.87% (9/131), respectively. A total of 41 different pathogens were identified, including 16 bacteria, 12 viruses, 10 fungi, and 1 parasite and 3 specific pathogens. The most frequent infecting pathogens are Epstein-Barr virus (n = 14), Herpes simplex virus 1 (n = 14), Mycobacterium tuberculosis (n = 13), Streptococcus pneumoniae (n = 13), and Cryptococcus neoformans (n = 8). Some difficult-to-diagnose pathogen infections were also detected by mNGS, such as Streptococcus suis , Pseudorabies virus , Bunyavirus , Orientia tsutsugamushi and Toxoplasma gondii ., Conclusion: In this study, mNGS identified a wide variety of pathogens of CA-CNS infections and many of which could not be detected by conventional methods. Our data provide a better understanding of the etiology of CA-CNS infections and show that mNGS represents a comparative screening of CSF in an unbiased manner for a broad range of human pathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wu, Shi, Liu, Xu, Dai, Chang and Ma.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Ritu Banjeree reports grant support from the National Institute for Allergy and Infectious Diseases, National Institutes of Health for an unrelated rapid diagnostics trial. Romney M. Humphries reports grant support from bioMerieux, Momentum BioSciences, Ltd, and Specific Diagnostics; contract and grant support from Qiagen; consulting fees from bioMerieux, Merck, Pattern Bioscience, Inc., Qiagen, QPex Biopharma, Inc., Specific Diagnostics, and Torus; vice chairmanship of the Infectious Diseases Society of America Diagnostics Committee, and membership on the American Society for Microbiology Professional Practices Committee, College of American Pathologists Microbiology Committee, and Clinical and Laboratory Standards Institute Antimicrobial Susceptibility Testing subcommittee; and stock options in Accelerate Diagnostics and Specific Diagnostics. Mary-Margaret A. Fill reports sponsored travel from the Council of State and Territorial Epidemiologists to attend the 2022 conference. No other potential conflicts of interest were disclosed.

Objectives: To describe the epidemiology and clinical presentation of central nervous system (CNS) infections in solid organ transplant (SOT) recipients in the current era of transplantation., Methods: Patients from the Swiss Transplant Cohort Study (STCS) transplanted between 2008 and 2018 were included with a median follow-up of 3.8 years. Epidemiological, microbiological, and clinical data were extracted from the STCS database and patients' medical records. We calculated incidence rates and 90-day survival of transplant recipients with CNS infection., Results: Among 4762 patients, 42 episodes of CNS infection in 41 (0.8%) SOT recipients were identified, with an overall incidence rate of 2.06 per 1000 patient-years. Incidence of CNS infections was similar across all types of transplantations. Time to CNS infection onset ranged from 0.6 to 97 months after transplant. There were 22/42 (52.4%) cases of viral infections, 11/42 (26.2%) of fungal infections, 5/42 (11.9%) of bacterial infections and 4/42 (9.5%) of probable viral/bacterial etiology. Clinical presentation was meningitis/encephalitis in 25 cases (59.5%) and brain-space occupying lesions in 17 cases (40.5%). Twenty-three cases (60.5%) were considered opportunistic infections. Diagnosis were achieved mainly by brain biopsy/necropsy (15/42, 36%) or by cerebrospinal fluid analysis (20/42, 48%). Up to 40% of cases (17/42) had concurrent extra-neurological disease localizations. Overall, 90-day mortality rate was 29.0% (73.0% for fungal, 14.0% for viral and 11.0% for bacterial and probable infections, p<0.0001)., Conclusions: CNS infections were rare in the STCS, with viral meningoencephalitis being the most common disease. Fungal infections were associated with a high mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The epidemiology of central nervous system (CNS) infections in tropical Australia is incompletely defined., Methods: A retrospective study of all individuals in Far North Queensland, tropical Australia, who were diagnosed with a CNS infection between January 1, 2000, and December 31, 2019. The microbiological aetiology of the infection was correlated with patients' demographic characteristics and their clinical course., Results: There were 725 cases of CNS infection during the study period, meningitis (77.4%) was the most common, followed by brain abscess (11.6%), encephalitis (9.9%) and spinal infection (1.1%). Infants (24.3%, p<0.0001) and Aboriginal and Torres Strait Islander Australians (175/666 local residents, 26.3%, p<0.0001) were over-represented in the cohort. A pathogen was identified in 513 cases (70.8%); this was viral in 299 (41.2%), bacterial in 175 (24.1%) and fungal in 35 (4.8%). Cryptococcal meningitis (24 cases) was diagnosed as frequently as pneumococcal meningitis (24 cases). There were only 2 CNS infections with a S. pneumoniae serotype in the 13-valent pneumococcal vaccine after its addition to the National Immunisation schedule in 2011. Tropical pathogens-including Cryptococcus species (9/84, 11%), Mycobacterium tuberculosis (7/84, 8%) and Burkholderia pseudomallei (5/84, 6%)-were among the most common causes of brain abscess. However, arboviral CNS infections were rare, with only one locally acquired case-a dengue infection in 2009-diagnosed in the entire study period. Intensive Care Unit admission was necessary in 14.3%; the overall case fatality rate was 4.4%., Conclusion: Tropical pathogens cause CNS infections as commonly as traditional bacterial pathogens in this region of tropical Australia. However, despite being highlighted in the national consensus guidelines, arboviruses were identified very rarely. Prompt access to sophisticated diagnostic and supportive care in Australia's well-resourced public health system is likely to have contributed to the cohort's low case-fatality rate., Competing Interests: The authors have declared that no competing interests exist.

Background: The Old world Alphavirus, Middelburg virus (MIDV), is not well known and although a few cases associated with animal illness have previously been described from Southern Africa, there has been no investigation into the association of the virus with human illness. The current study aimed to investigate possible association of MIDV infection with febrile or neurological manifestations in hospitalized or symptomatic patients fromGauteng, South Africa., Methods: This study is a descriptive retrospective and prospective laboratory based study. Archived cerebrospinal fluid (CSF) samples submitted to the National Health Laboratory Service (NHLS), Tshwane Academic division for viral investigation from public sector hospitals in Gauteng as well as EDTA (ethylenediaminetetraacetic acid) whole blood samples from ad hoc cases of veterinary students, presenting with neurological and febrile illness, were selected and screened for the presence of alphaviruses using real-time reverse transcription(rtRT) PCR.Virus isolations from rtRT-PCR positive samples were conducted in Vero cell culture and used to obtain full genome sequences. Basic descriptive statistical analysis was conducted using EpiInfo., Results: MIDV was detected by rtRT-PCR in 3/187 retrospective CSF specimens obtained from the NHLS from hospitalised patients in the Tshwane region of Gauteng and 1/2 EDTA samples submitted in the same year (2017) from ad hoc query arbovirus cases from veterinary students from the Faculty of Veterinary Science University of Pretoria.Full genome sequences were obtained for virus isolates from two cases; one from an EDTA whole blood sample (ad hoc case) and another from a CSF sample (NHLS sample).Two of the four Middelburg virus positive cases,for which clinical information was available, had other comorbidities or infections at the time of infection., Conclusion: Detection of MIDV in CSF of patients with neurological manifestations suggests that the virus should be investigated as a human pathogen with the potential of causing or contributing to neurological signs in children and adults., Competing Interests: The authors have declared that no competing interests exist. Author Anton Stoltz was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contribution to the best of their knowledge.

We aimed to conduct a systematic review and meta-analysis of studies on central nervous system (CNS) infections in patients with SLE, in order to describe their clinical and microbiological characteristics, and outcomes. A systematic search of PubMed/Medline and Embase electronic databases was performed (March 2021) to identify all published studies on CNS infections and their characteristics in patients with SLE. A random-effects model was adopted and findings were reported with 95% CI. Overall, 6 studies involving 17 751 patients with SLE and 209 SLE cases with CNS infection were included in our meta-analysis. The frequency rate of CNS infections in patients with SLE was 0.012 (95% CI: 0.008 to 0.018). Meningitis was the most common clinical syndrome (93.5%, n=109/114, 95% CI: 82.6% to 97.8%) and Cryptococcus neoformans (35.9%, n=55, 95% CI: 27.2% to 45.7%) and Mycobacterium tuberculosis (27.1%, n=43, 95% CI: 14.6% to 44.8%) were the most common causative pathogens. Our patient-pool showed a mean SLE Disease Activity Index (SLEDAI) score of 7.9 (95% CI: 6.1 to 9.6), while 92.4% (n=72/76, 95% CI: 83.0% to 96.8%) of cases were on oral systemic corticosteroids, with a prednisone equivalent mean daily dose of 30.9 mg/day (95% CI: 18.0 to 43.7). Our meta-analysis revealed a mortality rate of 29.0% (95% CI: 15.0% to 48.6%). Clinicians should maintain a high index of suspicion for cryptococcal and tuberculosis (TB) meningitis in patients with SLE with suspected CNS infection, particularly in those with higher SLEDAI and on higher doses of systemic corticosteroids. In conclusion, initiation of empiric antituberculous treatment for patients with SLE who are highly suspected to have CNS TB is warranted while awaiting the results of diagnostic tests. Antifungals might also be potentially useful empirically in patients with SLE who are suspected to have fungal CNS infections. However, with respect to side effects such as toxicity and high cost of antifungals, decision regarding early antifungal therapy should be guided by early and less time-consuming fungal diagnostic tests., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Varicella zoster virus (VZV) causes infections of the central nervous system (CNS) manifesting as meningitis or encephalitis. It is not commonly tested in CNS infections when compared with enterovirus (EV) and herpes simplex virus 1 (HSV-1) and 2 (HSV-2). Cerebrospinal fluid (CSF) findings of viral CNS infections are thought to be comparable., Aims: To describe the manifestations of VZV CNS infections and ascertain if there is a predominant syndrome. To compare CSF parameters of VZV with EV, HSV-1 and HSV-2., Methods: Retrospective study at two hospitals in Brisbane, reviewing medical notes and laboratory information system for results between January 2001 and 2019. The following parameters were recorded - disease classification, presence of rash, duration of symptoms prior to hospitalisation, length of admission, duration of antiviral treatment and 30-day mortality. CSF biochemistry, cell count (differential), PCR for VZV, EV, HSV-1 and HSV-2 were recorded. Statistical analysis of CSF parameters included Student's t-test and linear regression., Results: Incidence of meningitis was comparable to encephalitis (44 vs 39%) in 52 cases. CSF protein in VZV was significantly elevated compared with EV (median 1121 vs 569 mg/L; P < 0.001) as was CSF monocytosis (96% vs 61%; P < 0.001). CSF parameters between VZV, HSV-1 and HSV-2 were similar. VZV had a higher incidence than HSV-1 or 2, while it was tested one-third as often., Conclusions: VZV CNS infection cannot be predicted by syndrome. CSF findings are markedly different from EV but like HSV-1 and 2. VZV should be routinely tested with HSV-1 and 2 when viral CNS infection is suspected., (© 2020 Royal Australasian College of Physicians.)

Central nervous system (CNS) infections are important causes of morbidity and mortality worldwide. In Bolivia, aetiologies, case fatality, and determinants of outcome are poorly characterised. We attempted to investigate such parameters to guide diagnosis, treatment, prevention, and health policy. From Nov-2017 to Oct-2018, we prospectively enrolled 257 inpatients (20.2% HIV-positive patients) of all ages from healthcare centers of Cochabamba and Santa Cruz, Bolivia with a suspected CNS infection and a lumbar puncture performed. Biological diagnosis included classical microbiology, molecular, serological and immunohistochemical tests. An infectious aetiology was confirmed in 128/257 (49.8%) inpatients, including, notably among confirmed single and co-infections, Cryptococcus spp. (41.7%) and Mycobacterium tuberculosis (27.8%) in HIV-positive patients, and Mycobacterium tuberculosis (26.1%) and Streptococcus pneumoniae (18.5%) in HIV-negative patients. The total mortality rate was high (94/223, 42.1%), including six rabies cases. In multivariate logistic regression analysis, mortality was associated with thrombocytopenia (Odds ratio (OR) 5.40, 95%-CI 2.40-11.83) and hydrocephalus (OR 4.07, 95%-CI 1.35-12.23). The proportion of untreated HIV patients, late presentations of neurotuberculosis, the rate of pneumococcal cases, and rabies patients who did not benefit from a post-exposure prophylaxis, suggest that decreasing the burden of CNS infections requires reinforcing health policy regarding tuberculosis, rabies, S. pneumoniae vaccination, and HIV-infections., (© 2021. The Author(s).)

Abstract: Three α-herpesviruses are known to be associated with central nervous system (CNS) infection; however, there are limited data on the incidence and clinical characteristics of α-herpesviruses CNS infections. This study aimed to assess the clinical manifestations, laboratory findings, and outcomes in patients with human herpes simplex virus 1 (HSV-1), human herpes simplex virus 2 (HSV-2), and varicella-zoster virus (VZV) CNS infections.We identified cases of HSV-1, HSV-2, and VZV CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with HSV-1, HSV-2, and VZV polymerase chain reaction positivity in cerebrospinal fluid (CSF) who visited Pusan National University Hospital between 2010 and 2018.During the 9-year study period, a total of 727 CSF samples were examined, with 72.2% (525/727) patients identified as having a CNS infection. Of 471 patients with aseptic meningitis and encephalitis, the causative virus was identified in 145 patients, and no virus was detected in 337 patients. A total of 15.2% (80/525) were diagnosed with one of the 3 herpesviruses as causative agents, 59 patients had meningitis, and 21 patients had encephalitis. Eleven patients with HSV-1, 27 patients with HSV-2, and 42 patients with VZV CNS infections were included. The distribution of cases by age showed different patterns depending on the type of herpesvirus infection. Compared with the HSV-1 group, the median age in the HSV-2 group was younger (HSV-1: 58 years; HSV-2: 38 years; P = .004), and patients with VZV infections showed a bimodal age distribution. Encephalitis was more common in the HSV-1 group, and HSV-1 infection was associated with a poor prognosis at discharge. CSF white blood cell counts were significantly lower in patients infected with HSV-1 (117 × 106 cells/L) than in patients infected with VZV (301 × 106 cells/L) (P = .008).These 3 herpesviruses are important causes of CNS infections regardless of immunologic status. HSV-1 infection was commonly associated with encephalitis and poor prognosis; HSV-2 and VZV CNS infections were associated with a low risk of mortality and neurological sequelae., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cerebrospinal fluid (CSF) immune alterations have been associated with mental disorders, neurological disease, and CNS infections; however, comprehensive large-scale longitudinal CSF studies are lacking., Methods: By using the Clinical Laboratory Information System (LABKA) Research Database in the Central Denmark Region (1994-2012), we included 15,030 individuals tested for CSF WBC, CSF/serum albumin ratio, IgG index, total protein, albumin, or IgG with follow-up for the risk of mental disorders, psychotropic prescriptions, neurological diseases, or CNS infections, estimated by Cox regression., Results: Among individuals receiving a mental disorder diagnosis (N = 1,147) after a CSF test, 30·0% had an abnormal CSF test result, while for those with a neurological disease (N = 3,201), 39·9% had abnormal test results, and among individuals with CNS infections (N = 1,276), 73·0% had abnormal test results. Individuals with abnormal CSF test results had an increased risk of mental disorders (HR = 3·20; 95%CI = 2·86-3·59), neurological diseases (HR = 12·40; 95%CI = 11·65-13·20), and CNS infections (HR = 338·59; 95%CI = 299·06-383·35) compared to individuals not registered with a CSF test. However, the risk of mental disorders was higher (P < 0·001) after CSF test results within the normal range (HR = 4·45; 95%CI = 4·08-4·86), whereas for neurological diseases (HR = 9·72; 95%CI = 9·19-10·29) and CNS infections (HR = 55·17; 95%CI = 47·12-64·60), the risk was highest after abnormal CSF test results (all P < 0·001). The risk of organic mental disorders tended to be highest in individuals with abnormal CSF test results (HR = 19·30; 95%CI = 13·44-27·71) even though not significantly different from the risk in the group of individuals with CSF test results in the normal range (HR = 13·55; 95%CI = 9·36-19·60) (P ≥ 0·05). Abnormal CSF test results were associated with an elevated risk of psychotropic prescriptions (HR = 3·91; 95%CI = 3·66-4·18), as were CSF test results within the normal range (HR = 4·26; 95%CI = 4·03-4·51) (P < 0·05)., Conclusions: Immunological CSF abnormalities are associated with an increased risk of mental disorders, neurological disease, and particularly CNS infections; however, the included CSF parameters were not specific for mental disorders and the relevant CSF biomarkers in psychiatry are yet to be discovered., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The prognosis of central nervous system infections caused by enteroviruses partially depends on the viral genotype, which is not provided by current point-of-care diagnostic methods. In this study, next-generation sequencing identified an echovirus 9 directly from the cerebrospinal fluid of a patient presenting with meningitis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Neurological complications are some of the most important complications that can occur in a patient undergoing haematopoietic stem cell transplantation (HSCT), not only because of the high mortality rate, but also because of the sequelae that appear in survivors. The causes of such complications are manifold and very often coexist in the same patient: toxicity of the conditioning regimen, graft-versus-host disease and its treatment, infections and their treatment, platelets and coagulation disorders, liver failure or arterial hypertension with low platelet count., Aims: The aim of the present study is to provide a clinical description and to describe the risk factors for complications involving the central nervous system that may occur during the course of HSCT, in order to assist in the early detection of these disorders that may have a negative influence on the morbidity and mortality of these patients., Development: The following types of neurological complications are described: central nervous system infections, vascular complications, pharmacological toxicity, metabolic complications, immune-mediated disorders and post-HSCT carcinogenesis, and effects of graft-versus-host disease and thrombotic microangiopathy on the nervous system., Conclusions: The patient undergoing HSCT is at particular risk for the development of neurological complications. Early diagnosis and treatment are needed to try to reduce the high morbidity and mortality in these patients.

Background: Central nervous system (CNS) infections are relatively rare but are associated with high mortality worldwide. Empirical antimicrobial therapy is crucial for the survival of patients with CNS infections, and should be based on the knowledge of the pathogen distribution and antibiotic sensitivities. The aim of this study was to investigate the features of pathogens in patients with CNS infections in North China and evaluate the risk factors for mortality and multi-drug-resistant (MDR) bacterial infections., Methods: A retrospective study was conducted with patients with positive cerebrospinal fluid (CSF) cultures in a teaching hospital from January 2012 to December 2019. The following data were collected: demographic characteristics, laboratory data, causative organisms and antimicrobial sensitivity results. Data were analyzed with SPSS 16.0. Univariate analysis and binary logistic regression analyses were performed to identify the risk factors for mortality and MDR bacterial infections., Results: A total of 72 patients were diagnosed with CNS infections, and 86 isolates were identified. The proportions of Gram-positive bacteria, Gram-negative bacteria and fungi were 59.3, 30.2 and 10.5%, respectively. The predominant Gram-positive bacteria was Coagulase-negative Staphylococci. Acinetobacter baumannii, Escherichia coli and Klebsiella spp. were the predominant Gram-negative bacteria. Compared to 2012-2015 years, the proportion of Gram-negative bacteria increased markedly during 2016-2019 years. Coagulase-negative Staphylococci, Streptococcus pneumoniae and Enterococcus faecium had 100% sensitivity to vancomycin, teicoplanin and linezolid. Acinetobacter baumannii and Klebsiella pneumoniae were 100% sensitive to tigecycline. Escherichia coli had 100% sensitivity to amikacin, meropenem and imipenem. The overall mortality rate in the 72 patients was 30.6%. In multivariate analysis, age > 50 years, pulmonary infections and CSF glucose level < the normal value were associated with poor outcomes. CSF adenosine deaminase level > the normal value and the presence of external ventricular drainage/lumbar cistern drainage were associated with MDR bacterial infections., Conclusions: The mortality rate due to CNS infections reached 30.6% in our study. The proportion of Gram-negative bacteria has increased markedly in recent years. We should give particular attention to patients with risk factors for mortality and MDR bacterial infections mentioned above., (© 2021. The Author(s).)

Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.

Background: Viruses are a common cause of central nervous system (CNS) infections. However, studies of CNS viral pathogens in pediatric patients are poorly explored because viral infections are often erroneously diagnosed as bacterial infections., Methods: 299 CNS samples were collected from pediatric patients aged from one month to 14 years old. A total of 140 viral meningitis cases that met the inclusion criteria were included in this study. In 38 of the 140 cerebral spinal fluid (CSF) samples (27.1%), conventional and real-time PCR were used to identify viruses commonly associated with CNS infections., Results: Among them, 23 patients (16.5%) tested positive for flaviviruses such as dengue, Zika, and yellow fever virus, eight patients (5.7%) were positive for enterovirus (ENTV), and six patients (4.3%) were positive for human herpesvirus 1/2. We also identified one case of dengue virus and ENTV co-infection., Conclusions: A correlation between clinical symptoms and laboratory findings for the viruses was identified. Our study also reinforces the importance of including viruses in the laboratory diagnosis of CNS infections especially flaviviruses, which assists public health authorities in implementing early interventions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Problem: Celiac disease is an autoimmune disease, patients with celiac have increased risk for infections, and offspring of celiac mothers have increased morbidity. The aim of the study was to assess long-term infectious morbidity among offspring of pregnant women with celiac disease., Method of Study: A population-based cohort study was conducted, including all singleton deliveries between the years 1991-2014 at a tertiary medical center. The offsprings were subdivided into two groups: offsprings of mothers with and without celiac disease. Data on demographics, maternal, perinatal, and long-term hospitalizations for infectious morbidity were compared between the two groups., Results: During the study period there were 210 (0.09%) deliveries of mothers with celiac, and they were compared to 242170 (99.91%) deliveries of non-celiac mothers. Cumulative infectious morbidity was significantly higher in offspring of mothers with celiac compared to offspring of mothers without celiac (Kaplan-Meier, log-rank p = .004). Specifically, among the offspring of mothers with celiac significantly higher rates of bacteremia was noted (1.0% vs. 0.1%; p = .001), and infections of the central nervous system (1% vs. 0.2%; p = .028). In the Cox multivariable model which accounted for confounding variables, being born to mothers with celiac disease was associated with significantly increased risk for long-term infectious morbidity of the offspring (adjusted HR = 1.6, 95% CI 1.165-2.357, p = .005)., Conclusions: Maternal celiac disease is an independent risk factor for long-term infectious morbidity for the offspring., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Enterovirus (EV) is commonly associated with central nervous system (CNS) syndromes. Recently, gastroenteric viruses, including rotavirus (RVA), human astrovirus (HAstV), and norovirus (NoV), have also been associated with CNS neurological disorders. The aim of the present study was to investigate the presence of EV, RVA, HAst, and NoV associated to CNS infections with undiagnosed etiology in Northwest region of São Paulo State, Brazil, and to conduct the molecular characterization of the positive samples detected. A total of 288 cerebrospinal fluid samples collected from July to December 2017 were tested for EV and NoV by quantitative real-time polymerase chain reaction (RT-qPCR), HAstV by conventional RT-PCR, and RVA by enzyme-linked immunosorbent assay. Positive-EV samples were inoculated in cells lines, amplified by RT-PCR and sequenced. RVA, NoV, and HAstV were not detected. EV infection was detected in 5.5% (16/288), and five samples successful genotyped: echovirus 3 (E3) (1/5), coxsackie virus A6 (CVA6) (1/5), and coxsackie virus B4 (CVB4) (3/5). Meningitis was the main syndrome observed (12/16; 75%). CVA6, CVB4, and E3 were identified associated with aseptic meningitis. Reports of CVA6 associated with aseptic meningitis are rare, E3 had not been previously reported in Brazil, and epidemiological data on CVB4 in the country is virtually unknown. The present investigation illustrates the circulation of diverse EV types in a small regional sample set and in a short period of time, highlighting the importance of an active EV surveillance system in CNS infections. Enhanced understanding of undiagnosed CNS infections will assist in public health and health care planning., (© 2020 Wiley Periodicals LLC.)

Background: The pathogens involved in central nervous system (CNS) infections are various, such as viruses, bacteria, and fungi, so a syndromic approach can be required. In addition, since their rapid and accurate detection is very crucial, molecular diagnostics using cerebrospinal fluid is becoming the emerging standard method., Methods: The study was conducted retrospectively to identify the incidence and distribution patterns of the pathogens according to gender, age, season, and month and to analyze their codetection from August 2017 to July 2020. It was also conducted to investigate turn-around times (TATs) according to the detection method. The detection methods were FilmArray® Meningitis/Encephalitis (M/E) method (FilmArray), Cepheid® Xpert EV assay (Xpert), and Multiplex PCR method for five species of bacteria., Results: The overall incidence for at least one pathogen was 13.9% (346/2,496). The highest incidence was shown in age group 4 (3 - 6 years), with 27.4%. The detection rates by FilmArray, Xpert, and Multiplex PCR method were 39.8%, 41.7%, and 0.4%, respectively. Enterovirus (EV) showed the highest incidence rate, which accounted for 37.0%. The distribution of the pathogens according to the age groups were the highest in age group 4, with 47.5% (168/354), followed by 27.4% (97/354) in age group 5. Of the ten cases in which bacteria were detected, S. agalactiae accounted for 60.0% (6/10), most of which occurred in age group 1. E. coli K1, L. monocytogenes, and N. meningitidis were not detected. In the viral distribution, EV accounted for the highest proportion in all age groups. The overall proportion of EV accounted for 87.6% (310/354), followed by human parechovirus with 2.8% (10/354). The most commonly detected season was summer, comprising 75.1%. A total of eight cases of co-detection with two pathogens accounted for 1.6% (8/507) in FilmArray. In FilmArray, all TATs were found to be shorter than Xpert., Conclusions: The information on the incidence and distribution patterns of the pathogens causing CNS infections and their rapid detection are critically important to clinicians in the management of immunocompromised patients, elderly, and children. The expeditious molecular diagnostics for these pathogens would be valuable in medical decisions by clinicians.

Background: Central nervous system (CNS) infections can be caused by a variety of viruses, but in a significant number of patients no viral or other pathogen can be identified using routine diagnostic work-up. Interestingly, several case reports and series described Hepatitis E virus (HEV) as a potential pathogen. However, systematic studies have not been conducted so far., Methods: We identified 243 patients from Southwestern Germany with acute CNS infections of unknown cause treated in our clinic between 2008 and 2018, of which serum and/or cerebrospinal fluid (CSF) samples were available. These patients were retrospectively tested for anti-HEV IgM and IgG antibodies. In addition, HEV PCR was performed in the majority of cases including IgM-negative patients with symptom onset <8 days. 263 healthy individuals served as controls., Results: Evidence of an acute HEV infection was found in four patients (1.7%). Three had recent HEV infection defined as positive anti-HEV IgM and IgG antibodies, one had current HEV infection defined as (additional) detection of HEV RNA in serum. However, anti-HEV IgM and IgG seroprevalence did not differ significantly from controls, though these had considerably lower IgM levels. Interestingly, anti-HEV IgG seroprevalence was unexpectedly high (30.7%) and revealed an age-dependent increase to more than 50% in patients older than 60 years., Conclusion: This study supports previous findings that HEV could play a role in acute CNS infections. Therefore, we encourage testing for acute HEV infection if no other pathogen can be identified. However, further studies are necessary to prove a causal role., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Parechovirus A type 3 (PeV-A3) is associated with central nervous system infection in young infants. There are limited data regarding long-term outcomes, mostly reported from Australia and European populations. The objective of this study was to assess frequency of neurodevelopmental impairment (NDI) following PeV-A3 infection in our US cohort., Methods: Infants hospitalized during the 2014 outbreak with laboratory-confirmed PeV-A3 infection were evaluated with medical history, neurologic examination, parental completion of Ages and Stages Questionnaire and developmental assessment using Bayley Scales of Infant and Toddler Development, Third Edition cognitive, motor and language quotients. Determination of NDI was based on published criteria. Relationship of severity of PeV disease to outcome measures was determined using Fisher exact, χ2 and Mann-Whitney U test as appropriate., Results: Nineteen children, term gestation, were evaluated at ~3 years of age; PeV-A3 illness was uncomplicated for 6 (32%), complex, non-neurologic for 9 (47%) and encephalitis/seizures for 4 (21%). No differences were noted in mean Bayley Scales of Infant and Toddler Development, Third Edition quotients between infants by clinical presentation. Quotients for all were within 1 SD of population norms. Two (11%) children had mild NDI; 1 with mild cerebral palsy. Ages and Stages Questionnaire results included 11% at referral level and 37% suspect concern. Parents of 6 (32%) noted behavior concerns. These findings were unrelated to severity of the PeV-A3 illness., Conclusions: Parent concerns were identified frequently following infant PeV-A3 disease. Eleven percent had neurodevelopmental impairment at 3 years of age. Severity at presentation did not correlate with adverse childhood outcomes. Longitudinal developmental monitoring following infantile PeV-A3 disease is warranted., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To investigate the clinical use of multiplex polymerase chain reaction (mPCR) in Japan, epidemiological and clinical data for central nervous infections are needed. Here, we report on the epidemiology and economic burden of central nervous system infections and a simulation of the cost-benefit analysis of the Filmarray® Meningitis/Encephalitis (FAME) test for possible clinical use in Japan. We performed FAME tests on samples from 27 patients with pleocytosis aged between 0 and 20 years seen in six community hospitals in Nara and Osaka prefectures. All clinical management procedures were performed without knowledge of the mPCR test results. We analyzed the clinical data and calculated the required reduction in average length of stay for the FAME test to be cost-beneficial. Among the 27 cases, the FAME test revealed causal pathogens in 13 cases (48.1%). The average medical and social costs per case were ¥299,118 ($2,719.2) and ¥171,768 ($1,561.5), respectively. The minimal needed reduction in average length of stay for the FAME test to be cost-beneficial was 0.32- 0.86 days per meningitis case. The result can be informative for evaluating the cost-effectiveness of the clinical use of the FAME test in Japan.

Background/aim: The purpose of this study was to evaluate the etiology, clinical characteristics, and outcome of nontraumatic coma (NTC) among children admitted to a pediatric intensive care unit (PICU)., Materials and Methods: A total of 159 children with NTC were included in the study. The modified Glasgow coma scale (GCS) was used to assess consciousness. Patients were classified with regard to etiology. For each patient, demographic and clinical characteristics, survival and degree of disability at PICU discharge were recorded., Results: Median age was 55 months (IQR: 17.0 - 109.0). The most common cause of NTC was neuroinfection (31.4%) followed by toxic- metabolic conditions (25.8%) and epileptic disorder (15.1%). There was no significant relationship between the level of encephalopathy at admission and NTC etiology. A total of 13 patients died (8.2%). Among the survivors, 61.6% were discharged without any neurologic deficit, 2.8% had severe neurologic disability, and 3.4% were in a vegetative state. Complete neurological recovery was significantly more common in patients with toxic metabolic disease, whereas neurological deficits were more frequent in patients with tuberculous meningo-encephalitis (P = 0.01 and P = 0.04, respectively). Higher pediatric risk of mortality III (PRISM III) score at PICU admission (Odds ratio: 1.51, 95% CI: 1.19 - 1.92; P < 0.001) was the only variable that was independently associated with mortality. The length of stay (LOS) at hospital (Odds ratio: 0.73, 95% CI: 0.58-0.91; P = 0.006) was associated with improved odds of survival., Conclusions: Although results obtained from this single-center study cannot be generalized to the pediatric population, the contribution to the literature in terms of the relationships between NTC etiology, and outcome can be crucial for clinical decision-making. We report neuroinfection as the most common cause of NTC, and the only factor that was closely associated with mortality was PRISM III score. Length of hospital stay was inversely correlated to patient mortality., Competing Interests: The authors have no conflict of interest and also declare that no funding was received for the conduct of this study., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0-16 years) with suspected meningitis-encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray ® ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1-60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF ( n = 45/50), pharyngeal swabs ( n = 15/29) and stools ( n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates.

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.

Infections of the central nervous system (CNS) are a leading cause of mortality in low- and middle-income countries. We studied the spectrum, aetiology and outcome of CNS infections in 401 consecutive patients aged ≥12 years admitted at the medical emergency centre of PGIMER, Chandigarh, India. An aetiological diagnosis was made in 365 (91.0%) patients, with 149 (40.8%) microbiologically confirmed cases. CNS tuberculosis was the most prevalent cause (51.5%), followed by viral meningoencephalitis (13.9%), community-acquired bacterial meningitis (9.7%), cryptococcal meningitis (6.2%), scrub typhus meningoencephalitis (1.7%), neurocysticercosis (1.7%) and fungal brain abscess (1.7%). Human immunodeficiency virus (11.0%) and diabetes mellitus (6.2%) remained the usual predisposing conditions. We found a mortality rate of 27.9%, highest in cases without an aetiology (64.5%). Tuberculosis remained the most common cause; however, an increasing number of scrub typhus, dengue, fungal infections and non-classical bacterial pathogens may indicate a change in the epidemiology of community-acquired CNS infections in India.