Cerebrospinal Fluid White Blood Cell Research Articles

Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology

ObjectivesThe aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. MethodsChildren aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. ResultsThe cohort included 3,002 children (median age 2·4 months); 1,101/3,002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <six months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age six months–nine years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. ConclusionsBacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FundingThis study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

Accuracy of automated analyzers for the estimation of CSF cell counts: A systematic review and meta-analysis.

This systematic review evaluates the evidence for accuracy of automated analyzers that estimate cerebrospinal fluid (CSF) white blood cell counts (WBC) compared to manual microscopy. Inclusion criteria of original research articles included human subjects, English language, and manual microscopy comparator. PUBMED, EMBASE and Cochrane Review databases were searched through 2019 and QUADAS-2 Tool was used for assessment of bias. Data were pooled and analyzed by comparison method, using random effects estimation. Among 652 titles, 554 abstracts screened, 104 full-text review, 111 comparisons from 41 studies were included. Pooled estimates of sensitivity and specificity (n = 7) were 95% (95%-CI 93%-97%) and 84% (95%-CI: 64%-96%), respectively. Pooled R2 estimates (n = 29) were 0.95 (95%-CI: 0.95-0.96); Pooled spearman rho correlation (n = 27) estimates were 0.95 (95% CI 0.95-0.96). Among those comparisons using Bland-Altman analysis (n = 11) pooled mean difference was estimated at 0.98 (95% CI-0.54-2.5). Among comparisons using Passing-Bablok regressions (n = 14) the pooled slope was estimated to be 1.05 (95% CI 1.03-1.07). Q tests of homogeneity were all significant with the exception of the Bland-Altman comparisons (I2 10%, p value 0.35). There is good overall accuracy for CSF WBC by automated hematologic analyzers. These findings are limited by the small sample sizes and inconsistent validation methodology in the reviewed studies.

Etiology, Clinical Presentation, and Outcomes of Bacterial Meningitis in Adult Patients: A Retrospective Study in Lithuania (2018-2021).

BACKGROUND Bacterial meningitis is a serious and life-threatening condition that requires prompt diagnosis and treatment. This retrospective study aimed to identify causes, presentation, and predictive factors for outcomes of community-acquired bacterial meningitis in 86 adults in Vilnius, Lithuania between 2018 and 2021. MATERIAL AND METHODS We performed a retrospective study of demographic, clinical, and laboratory records of 86 adult patients admitted to Vilnius University Hospital Santaros Clinics with a diagnosis of acute bacterial meningitis during the period of 2018-2021. RESULTS Of 86 patients, 54 (62.79%) were men. The median (Md) age of patients was 58 (range, 18-83) years and the median duration of hospitalization was 20 (range, 3-92) days. Patients were first hospitalized in the Intensive Care Unit (ICU) in 59.3% of cases. The most prevalent concerns were headache (66.28%), febrile temperature (56.98%), general fatigue (53.49%), and confusion/sleepiness (52.33%). Of 57 (66.28%) etiologically confirmed cases, the most prevalent agent was Listeria monocytogenes (29.82%), followed by Streptococcus pneumoniae (28.07%) and Neisseria meningitidis (28.07%). Patients with meningitis caused by L. monocytogenes were the oldest (P=0.003) and had the longest hospitalization (P<0.001). Fatigue was the prominent symptom in patients with meningococcal meningitis (81.2%, P=0.010). Twelve patients (13.95%) have died. Advanced age and low (<100 cells per μL) white blood cell (WBC) count in cerebrospinal fluid (CSF) were associated with lethal outcome, whereas headache was associated with favorable outcome. CONCLUSIONS Clinical characteristics of community-acquired acute bacterial meningitis differ based on etiological factors. Patient age, CSF WBC count, and headache may be significant predictive factors for outcomes of bacterial meningitis.

Clinical Characteristics, Treatment, and Outcomes of Veterans with Cerebrospinal Fluid Culture Positive for Gram-Negative Rod Bacteria: A Retrospective Analysis over 18 Years in 125 Veterans Health Administration Hospitals.

Optimal management for patients with bacterial ventriculitis/meningitis due to Gram-negative rods (GNRs) has yet to be well investigated. We assessed the clinical characteristics, treatment, and outcomes of patients with a positive cerebrospinal fluid (CSF) culture for GNRs. We conducted a retrospective cohort study of all patients with a positive CSF culture within the Veterans Health Administration (VHA) system during 2003-2020. Clinical and microbiological characteristics between the true meningitis and contamination groups were compared. Of the 5919 patients with positive CSF cultures among 125 nationwide VHA acute-care hospitals, 297 (5.0%) were positive for GNRs. Among 262 patients analyzed, 156 (59.5%) were assessed as patients with true meningitis, and 106 (40.5%) were assessed as patients with contaminated CSF cultures. Patients with true meningitis had a significantly higher CSF protein (median 168 vs 57mg/dL, p < 0.001), CSF white blood cell count (median 525 vs 3/µL, p = 0.008) and percentage of neutrophils in CSF (median 88 vs 4%, p < 0.001). Enterobacterales were more common in the true meningitis group, while unidentified GNR or polymicrobial CSF cultures were more common in the contamination group. The all-cause 90-day mortality was 25.0% (39/156) in patients with true meningitis and 10.4% (11/106) in those with contaminated CSF cultures. None of the 11 patients with contaminated CSF cultures who died were considered due to missed meningitis. More than 40% of patients with a positive CSF culture with GNR did not receive treatment without negative consequences. Careful clinical judgment is required to decide whether to treat such patients.

Levels of cytokines in the cerebrospinal fluid of patients with psychotic disorders compared to individually matched healthy controls

BackgroundIncreased peripheral cytokine levels have been observed in patients with psychotic disorders; however, large high-quality studies with individually matched healthy controls have been lacking regarding cytokines in cerebrospinal fluid (CSF) of individuals with psychotic disorders. MethodsPatients diagnosed with a non-organic, non-affective psychotic disorder (ICD-10: F20/22–29) within a year prior to inclusion and individually age- and sex-matched healthy controls were included by identical in- and exclusion criteria’s except for the psychiatric diagnoses. All participants were aged 18–50 years and individuals with neurological or immunological disorders were excluded. CSF cytokines were analyzed with MesoScale V-PLEX neuroinflammation panel. Co-primary outcomes were CSF interleukin-6 (IL-6) and IL-8. ResultsWe included 104 patients and 104 healthy controls, matching on age, sex and BMI. No significant differences were found for the primary outcomes IL-6 (relative mean difference (MD): 0.97, 95 %CI: 0.84–1.11, p = 0.637) or IL-8 (MD: 1.01, 95 %CI: 0.93–1.09, p = 0.895). Secondary analyses found patients to have higher IL-4 (MD: 1.30, 95 %CI: 1.04–1.61, p = 0.018), a trend towards higher IFN-γ (MD: 1.26, 95 %CI: 0.99–1.59, p = 0.056), and lower IL-16 (MD: 0.83, 95 %CI: 0.74–0.94, p = 0.004) than healthy controls, though not significant after correction for multiple testing. IL-8 and IL-16 were found positively associated with CSF white blood cells and CSF/serum albumin ratio. The study was limited by 77.9 % of the patients being on antipsychotic treatment at time of intervention, and that levels of nine of the 26 cytokines were below lower limit of detection (LLOD) in >50 % of samples; however, for the primary outcomes IL-6 and IL-8 more than 99.5 % of the samples were above LLOD and for IL-8 all samples exceeded the lower limit of quantification (LLOQ). ConclusionsWe found no evidence of increased IL-6 and IL-8 in patients with recent-onset psychotic disorders in contrary to previous findings in meta-analyses of CSF cytokines. Secondary analyses found indication of higher IL-4, decreased IL-16, and borderline increased IFN-γ in patients, neither of which have previously been reported on in CSF analyses of individuals with psychotic disorders.

Diagnostic Utility of Cerebrospinal Fluid White Blood Cell Components for the Identification of Bacterial Meningitis in Infants.

To evaluate the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU). We identified a cohort of infants discharged from a Pediatrix NICU between 1997 and 2020 who did not have an immunodeficiency, had at least 1 CSF culture collected within the first 120 days of life, and at least 1 CSF laboratory specimen obtained on the day of culture collection. We only included an infant's first CSF culture and excluded cultures from CSF reservoirs and those growing contaminants or nonbacterial organisms. We examined the utility of CSF WBC components to diagnose or predict bacterial meningitis by calculating sensitivity, specificity, positive and negative predictive values, likelihood ratios, and area under the receiver operating curve (AUC) at different cutoff values for each parameter. We performed subgroup analysis excluding infants treated with antibiotics the day before CSF culture collection. Of the 20 756 infants that met the study inclusion criteria, 320 (2%) were diagnosed with bacterial meningitis. We found (AUC [95% CI]) CSF WBC count (0.76 [0.73-0.79]), CSF neutrophil count (0.74 [0.70-0.78]), and CSF neutrophil percent (0.71 [0.67-0.75]) had the highest predictive values for bacterial meningitis, even when excluding infants with early antibiotic administration. No single clinical prediction rule had the optimal discriminatory power for predicting culture-proven bacterial meningitis, and clinicians should be cautious when interpreting CSF WBC parameters in infants with suspected meningitis.

Brain magnetic resonance imaging as predictors in pediatric anti-N-methyl-D-aspartate receptor encephalitis

ObjectiveTo investigate the associations between brain magnetic resonance imaging (MRI) changes and clinical profiles in children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. MethodsClinical data and brain MRI results of children diagnosed with anti-NMDAR encephalitis in Guangzhou Women and Children's Medical Center from October 2014 to June 2022 were retrospectively studied. ResultsA total of 143 children (Male: female 54:89) were enrolled, with a mean onset age of 6.8 years (6.8 ± 3.1). 40.6 % (58/143) of patients had abnormal initial brain MRI. Lesions in temporal lobe (34.5 %, 20/58) and frontal lobe (25.9 %, 15/58) were relatively common. Children with abnormal initial brain MRI were prone to have fever (P = 0.023), dystonia (P = 0.037), positive MOG antibodies (P = 0.015), higher cerebrospinal fluid (CSF) white blood cell count (WBC) (P = 0.019) and to receive rituximab treatment (P = 0.037). There were no significant differences in modified Rankin Scale (mRS) scores before immunotherapy, after immunotherapy and at last follow-up between the normal initial brain MRI group and abnormal group. No initial brain MRI changes were found to be associated with relapses. Brain MRI was reviewed in 72 patients at last follow-up with a median follow-up time of 25.5 months and 48.6 % (35/72) of patients had abnormal brain MRI. The mRS score of the group with normal brain MRI at last follow-up was significantly lower than that of the abnormal group. ConclusionsAbout 40.0 % of children with anti-NMDAR encephalitis had abnormal initial brain MRI. Initial brain MRI was associated with certain clinical profiles, but not with relapse and prognosis. Around half of patients had abnormal brain MRI at last follow-up and were prone to have higher mRS score.

Enterovirus Meningitis without Pleocytosis: a Retrospective Observational Study in Adults.

Reverse-transcription polymerase chain reaction (RT-PCR)-confirmed enterovirus (EV) meningitis without pleocytosis has only been previously reported in children. In this study, we examined the frequency of EV meningitis without pleocytosis in adults and compared its clinical features. We retrospectively analyzed the data of adult patients with EV meningitis confirmed using cerebrospinal fluid (CSF) RT-PCR. Among the 17 patients included in this study, 58.8% showed no pleocytosis. The median age and clinical symptoms did not differ between the pleocytosis and non-pleocytosis groups. There were no statistically significant differences in seasonal variation or time from the onset of meningitis symptoms to lumbar puncture. The peripheral white blood cell (WBC) count in patients with pleocytosis was significantly higher than that in patients without pleocytosis. The median CSF pressure showed a higher trend in the non-pleocytosis group. Patients with CSF pressures higher than normal were more common in the non-pleocytosis group. The median CSF protein values were higher than the normal values in both groups. We confirmed the high frequency of EV meningitis without pleocytosis in adults. Accurate diagnosis using RT-PCR is necessary when meningitis symptoms are prominent during an EV epidemic, and CSF protein levels and pressure are high, even if the CSF WBC count is normal.

Clinical characteristics, treatment, and outcome of low-risk non-HIV-associated cryptococcal meningitis: A retrospective cohort study.

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P=.012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP<250-mm H2O, 60.0% vs. 32.4%, P=.001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P<.001), higher baseline CSF white blood cell (median, 130 vs. 90, P=.029) and CSF protein (median, 0.87 vs. 0.73, P=.011). Multivariate analysis showed that baseline CSF OP<250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P=.019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P<.001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P<.001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP< 250-mm H2O were prone to the low-risk status.

Cerebrospinal fluid pleocytosis is associated with HIV-1 neuroinvasion during acute infection.

HIV-1 invades the brain within days post-transmission. This study quantitated cerebrospinal fluid (CSF) white blood cell count (WBC) and investigated whether it associated with plasma and CSF HIV-1 RNA during untreated acute HIV infection (AHI). Seventy participants underwent lumbar puncture during Fiebig stages I-V AHI. WBC and HIV-1 RNA with a lower limit of quantification (LLQ) of 80 copies/ml were measured in CSF. Sixty-nine (99%) participants were men, with a median age of 26. Their blood CD4 + and CD8 + T-cell counts were 335 [interquartile range (IQR) 247-553) and 540 (IQR 357-802) cells/μl, respectively. Forty-five (64%) were in Fiebig stages III-V whereas 25 (36%) were in Feibig stages I-II. Fifty-two (74%) experienced acute retroviral syndrome. Median plasma and CSF HIV-1 RNA were 6.10 (IQR 5.15-6.78) and 3.15 (IQR 1.90-4.11) log 10 copies/ml, respectively. Sixteen (23%) CSF samples had HIV-1 RNA below LLQ. Median CSF WBC was 2.5 (IQR 1-8) cells/μl. CSF pleocytosis (WBC >5) was observed in 33% and was only present in CSF samples with detectable HIV-1 RNA. The frequencies of CSF pleocytosis during Fiebig stages III-V and among CSF samples of higher viral load (>1000 copies/ml) were 42 and 45%, respectively. Pleocytosis independently associated with CSF HIV-1 RNA in multivariate analysis [adjusted coefficient: 0.79, 95% confidence interval (CI) 0.41-1.14), P  < 0.001] and a lower plasma to CSF HIV-1 RNA ratio ( P  < 0.001). CSF pleocytosis was present in one-third of participants with AHI. It associated with higher CSF HIV-1 RNA and a lower plasma to CSF HIV-1 RNA ratio, suggesting a potential association with HIV-1 neuroinvasion.

Cerebrospinal fluid indices as predictors of treatment response in autoimmune encephalitis.

Cerebrospinal fluid (CSF) indices reflecting intrathecal antibody production and blood-brain barrier impairment are not routinely assessed in patients with autoimmune encephalitis (AE). We aimed to study CSF indices and their association with the prognosis of AE. This retrospective cohort study conducted at Amrita Institute of Medical Sciences (AIMS), Kochi, India, included 60 patients aged more than 18 years with definite/probable/possible AE admitted to the Department of Neurology from August 2016 to November 2021. We introduced a classification of treatment response based on modified Rankin Scale change over time and treatment modalities. In our cohort of 60 patients (six [10%] seropositive cases), a good rapid treatment response was associated with CSF white blood cell count of more than 4 cells/mm3 (OR, 4.57; 95% CI 1.31-15.96; P=.02) and positive immunoglobulin G (IgG) Local Synthesis (OR, 7.27; 95% CI 1.56-33.86; P=.01). Albumin Index had association with a poor Glasgow Coma Scale score at the nadir of the disease (OR, 1.17; 95% CI 1.01-1.34; P=.04). Similar results were yielded in the seronegative cohort. IgG Local Synthesis appeared to be a strong predictor for good rapid treatment response in both univariate and multivariate (adjusted OR, 28.71; 95% CI 2.12-389.22; P= .01) analysis. Time to immunotherapy was reversely correlated with good response overall (in the cohort with outliers removed [N=49]: unadjusted OR 0.97, 95% CI 0.95-0.99; P= .01; adjusted OR 0.97; 95% CI 0.95-0.99; P= .008). CSF indices reflecting intrathecal antibody production and blood-brain barrier impairment appear to be promising predictors of disease severity and therapeutic response in patients with autoimmune encephalitis.

Clinical characteristics of patient with GFAP-IgG: A Review of 31 Patients from Two Tertiary Referral Centers in China

ABSTRACT Objective This study presents a comprehensive analysis of the clinical characteristics of 31 patients exhibiting cerebrospinal fluid (CSF) and/or serum positivity for GFAP-IgG, with a specific emphasis on 24 cases demonstrating only GFAP-IgG positivity. The investigation thoroughly evaluates their clinical, radiological, and laboratory features, as well as treatment responses, with the objective of offering clinicians potential diagnostic and therapeutic approaches. Methods A total of 31 patients with GFAP-IgG in the CSF and/or serum were registered between August 2016 and August 2021 at the General Hospital of Ningxia Medical University and Huashan Hospital of Fudan University. We retrospectively reviewed their clinical records. Results Overall, the patients were positive with GFAP-IgG in their CSF (15/31), in serum (6/31), and both CSF and serum (10/31). Among them, two were eventually diagnosed with astroglioma and primary central nervous system lymphoma, respectively; one patient had typical multiple sclerosis; three exhibited overlapping GFAP-IgG and aquaporin-4-IgG (AQP4-IgG); and one patient was coexisting N-Methyl-D-aspartate receptor IgG. The remaining 24 patients were only GFAP-IgG positive. In total, 22 out of the 24 patients had abnormal MRI outcomes, involving the brain, meninges, and spinal cord. Besides, seven of the 24 patients developed optic neuritis. The CSF protein levels positively correlated with the Expanded Disability Status Scale score (EDSSs). Significantly decreased EDSSs, modified Rankin Scale score, GFAP-IgG titer, CSF protein level, and CSF white blood cell counts were observed after immunomodulatory therapy. Conclusion The clinical manifestations of GFAP-IgG exhibit a wide range of phenotypes that lack specificity. These findings emphasize the significance of not exclusively relying on the presence of antibodies to diagnose GFAP-A, but rather integrating them with the clinical phenotypes. GFAP-IgG testing enables the diagnosis of autoimmune GFAP astrocytopathy, a treatable autoimmune disease affecting the central nervous system. This condition provides opportunities for investigating innovative mechanisms of CNS autoimmunity and inflammation.

Clinical Features of Cryptococcal Meningoencephalitis in HIV-Positive and -Negative Patients in a Resource-Limited Setting.

Cryptococcal meningoencephalitis is a systemic fungal infection in immunocompromised and immunocompetent individuals. This study investigated the clinical characteristics and factors associated with mortality in HIV-associated and non-HIV-associated cryptococcal meningoencephalitis in a resource-limited setting. This was a retrospective cohort study of patients with cryptococcal meningoencephalitis between January 2009 and December 2019 at a tertiary teaching hospital in Thailand. Overall, 1019 patients with cryptococcal meningoencephalitis were enrolled, and 923 (90.6%) were HIV-positive. The patients with HIV-associated cryptococcal meningoencephalitis were younger than the HIV-negative patients (37 versus 56 years, p < 0.01). The HIV-negative patients were more likely to have underlying conditions (52.1% versus 7.5%; p < 0.01), had a longer median duration of headaches prior to admission (14 days versus 6 days, p < 0.01), and were more likely to have an altered mental status at presentation (36.5% versus 18.6%, p < 0.01) and pulmonary involvement (15.6% versus 0.8%, p < 0.01). The HIV-positive patients had lower cerebrospinal fluid (CSF) white blood cell counts (4 versus 94 cells/mm3; p < 0.01), lower CSF protein (69 versus 157 mg/dL; p < 0.01), higher CSF glucose (38.8 versus 21 mg/dL; p < 0.01), and more frequent cryptococcemia (44.1% versus 20.5%; p < 0.01). The mortality rate was high but not significantly different between the two groups (30.2% versus 33.2%; p = 0.53). The HIV-positive patients with comorbidities, fever, an altered mental status at presentation, a CSF white blood cell count below 20 cell/mm3, fungemia, and positive CSF India ink were independently associated with 30-day mortality. In comparison, an altered mental status at presentation and fungemia were associated with 30-day mortality in HIV-negative patients. In conclusion, HIV-negative patients with cryptococcal meningoencephalitis had more extensive central nervous system inflammation, although the two groups' mortality rates were similar. Unfavorable prognostic factors included comorbidities, fever, an altered mental status at presentation, a low CSF white blood cell count, fungemia, and positive CSF India ink.

Development and validation of a machine learning model to predict prognosis in HIV-negative cryptococcal meningitis patients: a multicenter study.

To predict prognosis in HIV-negative cryptococcal meningitis (CM)patients by developing and validating a machine learning (ML)model. This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10weeks after the initiation of antifungal therapy. The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid(CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence(AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.

Enterovirus Central Nervous System Infection in Infancy, the Value of Routine Testing.

Human nonpolio enterovirus (EV) is a major cause of infection in neonates and infants; however, the clinical presentation and cerebrospinal fluid findings vary significantly. Infection caused by EV in patients under 1 year of age can present with a broad clinical spectrum, from fever to severe systemic and/or neurological disease. Retrospective cohort analysis of infants with EV central nervous system (CNS) infection presenting to a tertiary center between January 2017 and December 2022. We recorded patient demographics, parent-reported symptoms at presentation, and blood and cerebrospinal fluid (CSF) testing at presentation. Seventy-eight patients were included in the final study. Forty-one percent of infants with an EV CNS infection had a normal CSF white blood cell count. Clinical presentation was similar in infants with and without CSF pleocytosis. Median C-reactive protein was higher in cases of EV CNS infection without pleocytosis. EV CNS infection commonly presents without CSF pleocytosis. Testing for EV should be considered in febrile infants with no source regardless of CSF parameters.

Diagnosis of neurosyphilis in HIV-negative patients with syphilis: development, validation, and clinical utility of a suite of machine learning models

The ability to accurately identify the absolute risk of neurosyphilis diagnosis for patients with syphilis would allow preventative and therapeutic interventions to be delivered to patients at high-risk, sparing patients at low-risk from unnecessary care. We aimed to develop, validate, and evaluate the clinical utility of simplified clinical diagnostic models for neurosyphilis diagnosis in HIV-negative patients with syphilis. We searched PubMed, China National Knowledge Infrastructure and UpToDate for publications about neurosyphilis diagnostic guidelines in English or Chinese from database inception until March 15, 2023. We developed and validated machine learning models with a uniform set of predictors based on six authoritative diagnostic guidelines across four continents to predict neurosyphilis using routinely collected data from real-world clinical practice in China and the United States (through the Dermatology Hospital of Southern Medical University in Guangzhou [659 recruited between August 2012 and March 2022, treated as Development cohort], the Beijing Youan Hospital of Capital Medical University in Beijng [480 recruited between December 2013 and April 2021, treated as External cohort 1], the Zhongshan Hospital of Xiamen University in Xiamen [493 recruited between November 2005 and November 2021, treated as External cohort 2] from China, and University of Washington School of Medicine in Seattle [16 recruited between September 2002 and April 2014, treated as External cohort 3] from United States). We included all these patients with syphilis into our analysis, and no patients were further excluded. We trained eXtreme gradient boosting (XGBoost) models to predict the diagnostic outcome of neurosyphilis according to each diagnostic guideline in two scenarios, respectively. Model performance was measured through both internal and external validation in terms of discrimination and calibration, and clinical utility was evaluated using decision curve analysis. The final simplified clinical diagnostic models included neurological symptoms, cerebrospinal fluid (CSF) protein, CSF white blood cell, and CSF venereal disease research laboratory test/rapid plasma reagin. The models showed good calibration with rescaled Brier score of 0.99 (95% CI 0.98-1.00) and excellent discrimination (the minimum value of area under the receiver operating characteristic curve, 0.84; 95% CI 0.81-0.88) when externally validated. Decision curve analysis demonstrated that the models were useful across a range of neurosyphilis probability thresholds between 0.33 and 0.66 compared to the alternatives of managing all patients with syphilis as if they do or do not have neurosyphilis. The simplified clinical diagnostic models comprised of readily available data show good performance, are generalisable across clinical settings, and have clinical utility over a broad range of probability thresholds. The models with a uniform set of predictors can simplify the sophisticated clinical diagnosis of neurosyphilis, and guide decisions on delivery of neurosyphilis health-care, ultimately, support accurate diagnosis and necessary treatment. The Natural Science Foundation of China General Program, Health Appropriate Technology Promotion Project of Guangdong Medical Research Foundation, Department of Science and technology of Guangdong Province Xinjiang Rural Science and Technology（Special Commissioner）Project, Southern Medical University Clinical Research Nursery Garden Project, Beijing Municipal Administration of Hospitals Incubating Program.

Fulminant Anti-Myelin Oligodendrocyte Glycoprotein-Associated Cerebral Cortical Encephalitis: Case Series of a Severe Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Phenotype

BackgroundWe describe a cohort of children with severe myelin oligodendrocyte glycoprotein (MOG)-IgG-associated cerebral cortical encephalitis (CCE), manifesting with bilateral cortical cytotoxic edema and critical neurological illness. MethodsWe retrospectively reviewed our pediatric MOG antibody-associated disease (MOGAD) database and identified patients with specific radiographic pattern of bilateral, multifocal cortical cytotoxic lesions. We collected demographic, clinical, and outcomes data from these patients and compared select variables with radiographically distinct cerebral MOGAD syndromes (case-control analysis). We assessed the correlation of quantitative clinical variables with severity/outcomes measures using simple linear regression. ResultsSixty-five of 88 total MOGAD cases had cerebral disease, and six of 88 met inclusion criteria for fulminant CCE (f-CCE). Age range was 2 to 7 years; five of six were male. Six of six were critically ill with severe encephalopathy and seizures, two of six required barbiturate coma, and two of six required invasive intracranial pressure monitoring. Six of six required treatment escalation beyond steroids. Four of six had favorable outcome; two of six had moderate-severe disability. Compared with other cerebral MOGAD cases (n = 59), children with f-CCE were more likely to have critical illness and poor neurological outcomes scores. Neurofilament light chain and treatment latency positively correlated with intensive care unit length of stay and outcomes scores; cerebrospinal fluid (CSF) white blood cell count and neutrophil-to-lymphocyte ratio did not. ConclusionsPediatric CCE with bilateral cytotoxicity is associated with more fulminant disease and worse outcomes than other cerebral MOGAD syndromes.

Clinical Characteristics and Treatment Outcome of Eosinophilic Meningoencephalitis in South Indian Children: Experience From a Prospective Registry

BackgroundTo describe the clinical features and therapeutic outcomes of a prospective cohort of children with eosinophilic meningoencephalitis. MethodsChildren admitted with clinical features suggestive of meningitis along with cerebrospinal fluid (CSF) eosinophilia during the period of 14 years (2008 to 2021) were included. Their baseline characteristics, epidemiologic associations, and treatment outcomes were analyzed and compared with the previous studies. ResultsWe identified 25 children (13 males) satisfying the inclusion criteria. The median age at presentation was 3.9 years (range 0.8 to 17 years); 68% were aged less than two years. Fourteen (56%) children had a history of exposure to snails. Most of them presented with fever, headache, irritability, lateral rectus palsy, and early papilledema. Symptoms started three to 42 days (median duration: 14 days) before admission to our center. All children had peripheral eosinophilia, which ranged from 9% to 41%. The mean CSF white blood cell count was 416/mm3 (range 50 to 1245 cells/mm3) with CSF eosinophilia ranging from 11% to 80%. Brain magnetic resonance imaging was done in 24 children and was normal in 15 (62.5%). Leptomeningeal enhancement was seen in two (8.3%) children, and other nonspecific changes were noted in seven (29.1%) children. All children recovered without any neurological deficits with a standard treatment regimen of albendazole and oral steroids. All were asymptomatic at the last follow-up. None of them had any recurrence during the follow-up period. ConclusionWe report one of the largest clinical series of children with eosinophilic meningoencephalitis from an endemic area of South India.

Establishment of HIV-negative neurosyphilis risk score model based on logistic regression

ObjectiveTo establish the risk scoring model for HIV-negative neurosyphilis (NS) patients and to optimize the lumbar puncture strategy.MethodsFrom 2016 to 2021, clinical information on 319 syphilis patients was gathered. Multivariate logistic regression was used to examine the independent risk factors in NS patients who tested negative for human immunodeficiency virus (HIV). Receiver operating characteristic curves (ROC) were used to assess the risk scoring model’s capacity for identification. According to scoring model, the timing of lumbar puncture was suggested.ResultsThere were statistically significant differences between HIV-negative NS and non-neurosyphilis (NNS) patients in the following factors. These included age, gender, neuropsychiatric symptoms (including visual abnormalities, hearing abnormalities, memory abnormalities, mental abnormalities, paresthesia, seizures, headache, dizziness), serum toluidine red unheated serum test (TRUST), cerebrospinal fluid Treponema pallidum particle agglutination test (CSF-TPPA), cerebrospinal fluid white blood cell count (CSF-WBC), and cerebrospinal fluid protein quantification (CSF-Pro) (P < 0.05). Logistic regression analysis of HIV-negative NS patients risk factors showed that age, gender, and serum TRUST were independent risk factors for HIV-negative NS (P = 0.000). The total risk score (− 1 ~ 11 points) was obtained by adding the weight scores of each risk factor. And the predicted probability of NS in HIV-negative syphilis patients (1.6 ~ 86.6%) was calculated under the corresponding rating. ROC calculation results showed that the score had good discrimination value for HIV-negative NS and NNS: area under the curve (AUC) was 0.80, the standard error was 0.026 and 95% CI was 74.9–85.1% (P = 0.000).ConclusionThe risk scoring model in this study can classify the risk of neurosyphilis in syphilis patients, optimize the lumbar puncture strategy to a certain extent, and provide ideas for the clinical diagnosis and treatment of HIV-negative neurosyphilis.

Meta-analysis of Cerebrospinal Fluid Cell Count and Biochemistry to Diagnose Meningitis in Infants Aged 

Cerebrospinal fluid (CSF) white blood cell (WBC) count, protein, and glucose (cytochemistry) are performed to aid in the diagnosis of meningitis in young infants. However, studies have reported varying diagnostic accuracies. We assessed the diagnostic accuracy of CSF cytochemistry in infants below 90 days and determined the certainty of evidence. We searched PubMed, Embase, Cochrane Library, Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases in August 2021. We included studies that evaluated the diagnostic accuracy of CSF cytochemistry compared with CSF culture, Gram stain, or polymerase chain reaction in neonates and young infants <90 days with suspected meningitis. We pooled data using the hierarchical summary receiver operator characteristic (ROC) model. Of the 10,720 unique records, 16 studies were eligible for meta-analysis, with a cumulative sample size of 31,695 (15 studies) for WBC, 12,936 (11 studies) for protein, and 1,120 (4 studies) for glucose. The median (Q1, Q3) specificities of WBC, protein, and glucose were 87 (82, 91), 89 (81, 94), and 91% (76, 99), respectively. The pooled sensitivities (95% confidence interval [CI]) at median specificity of WBC count, protein, and glucose were 90 (88, 92), 92 (89, 94), and 71% (54, 85), respectively. The area (95% CI) under ROC curves were 0.89 (0.87, 0.90), 0.87 (0.85, 0.88), and 0.81 (0.74, 0.88) for WBC, protein, and glucose, respectively. There was an unclear/high risk of bias and applicability concern in most studies. Overall certainty of the evidence was moderate. A bivariate model-based analysis to estimate the diagnostic accuracy at specific thresholds could not be conducted due to a paucity of data. CSF WBC and protein have good diagnostic accuracy for the diagnosis of meningitis in infants below 90 days of age. CSF glucose has good specificity but poor sensitivity. However, we could not identify enough studies to define an optimal threshold for the positivity of these tests. · Median specificity of CSF leucocyte count, protein and glucose are similar in young infants.. · At median specificity, CSF leukocyte count and protein are more sensitive than glucose.. · Owing to inadequate data, bivariate modelling to suggest optimal diagnostic thresholds is not possible..