Cerebrospinal Fluid Leukocyte Research Articles

Glioma grade and post-neurosurgical meningitis risk.

Post-neurosurgical meningitis (PNM) constitutes a grave complication associated with substantial morbidity and mortality. This study aimed to determine the risk factors predisposing patients to PNM following surgery for low- and high-grade gliomas. We conducted a retrospective analysis encompassing all patients who underwent glioma surgery involving craniotomy at Turku University Hospital, Turku, Finland, between 2011 and 2018. Inclusion criteria for PNM were defined as follows: (1) Positive cerebrospinal fluid (CSF) culture, (2) CSF leukocyte count ≥ 250 × 106/L with granulocyte percentage ≥ 50%, or (3) CSF lactate concentration ≥ 4mmol/L, detected after glioma surgery. Glioma grades 3-4 were classified as high-grade (n = 261), while grades 1-2 were designated as low-grade (n = 84). Among the 345 patients included in this study, PNM developed in 7% (n = 25) of cases. The median time interval between glioma surgery and diagnosis of PNM was 12days. Positive CSF cultures were observed in 7 (28%) PNM cases, with identified pathogens encompassing Staphylococcus epidermidis (3), Staphylococcus aureus (2), Enterobacter cloacae (1), and Pseudomonas aeruginosa (1). The PNM group exhibited a higher incidence of reoperations (52% vs. 18%, p < 0.001) and revision surgery (40% vs. 6%, p < 0.001) in comparison to patients without PNM. Multivariable analysis revealed that reoperation (OR 2.63, 95% CI 1.04-6.67) and revision surgery (OR 7.08, 95% CI 2.55-19.70) were significantly associated with PNM, while glioma grade (high-grade vs. low-grade glioma, OR 0.81, 95% CI 0.30-2.22) showed no significant association. The PNM rate following glioma surgery was 7%. Patients requiring reoperation and revision surgery were at elevated risk for PNM. Glioma grade did not exhibit a direct link with PNM; however, the presence of low-grade gliomas may indirectly heighten the PNM risk through an increased likelihood of future reoperations. These findings underscore the importance of meticulous post-operative care and infection prevention measures in glioma surgeries.

Breaking Barriers: Unveiling Sex-Related Differences in Cerebrospinal Fluid Analysis-A Narrative Review.

(1) Background: The recent emphasis on sexual and gender diversity's impact on human health underscores the need for tailored diagnostic and therapeutic approaches in neurology. The aim of this article is to conduct a narrative review of the available scientific literature on sex differences in cerebrospinal fluid analysis. (2) Methods: The literature search encompassed PubMed databases, focusing on cerebrospinal fluid analysis and sex differences, considering parameters like cerebrospinal fluid protein content, cell count, albumin quotient (QAlb) and intrathecal IgG synthesis. (3) Results: Nine articles from the past two decades were identified, revealing limited research in this area. Males consistently exhibited higher cerebrospinal fluid protein content and albumin quotient values across various pathologies and age groups. Consequently, males more frequently manifested blood-cerebrospinal fluid barrier dysfunction than females. No significant sex differences were observed in cerebrospinal fluid leukocyte count or intrathecal IgG synthesis. (4) Conclusions: This review highlights the dearth of research on sex differences in cerebrospinal fluid analysis, despite consistent findings of higher protein content and albumin quotient values in males. Revisiting current diagnostic thresholds based on sex is crucial for accurate prognosis and personalised treatment strategies in neurological disorders. Moving towards sex-specific approaches in clinical practice is imperative for advancing personalised medicine.

Expansion of highly interferon-responsive T cells in early-onset Alzheimer's disease.

Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer's disease (EOAD). We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital polymerase chain reaction (ddPCR) data from CD4 T cells from participants with EOAD and clinically normal controls. We analyzed PBMCs from 16 individuals by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAGhi T cells in EOAD. Isolating CD4 T cells from 19 individuals, including four cases analyzed by scRNA-seq, we confirmed increased expression of ISAGhi marker genes. Publicly available cerebrospinal fluid leukocyte scRNA-seq data from late-onset mild cognitive impairment and AD also revealed increased expression of interferon-response genes. Antiviral-like ISAGhi T cells are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted. Interferon-responsive T cells expanded in early-onset Alzheimer's disease (AD). Increased interferon-associated gene expression present in early- and late-onset AD. Peripheral immune changes in T and NK cells driven by females with early-onset AD.

Protocol for the study of bedside CSF analysis by urinary reagent strips and comparison with traditional laboratory measurements in a tertiary care centre in rural India

Abstract* Background Meningitis is an infection of leptomeninges. It is an emergency life-threatening condition that requires prompt treatment initiation. Diagnosis is the rate-limiting step because cerebrospinal fluid (CSF) analysis requires experienced personnel. Therefore, this study was conducted to assess the utility of urinary reagent strips for the rapid bedside diagnosis of CSF glucose, proteins, and leukocytes. Objective To determine the efficacy of a urinary reagent strip for bedside analysis of cerebrospinal fluid (CSF) samples. Methods This prospective comparative study will be conducted in the Department of Neonatology and Pediatrics, Jawaharlal Nehru Medical College, Sawangi, Wardha. CSF samples from patients suspected of infection of the central nervous system (CNS) and awaiting diagnosis will be subjected to semi-quantitative analysis using a urinary reagent strip (for glucose, proteins, and leukocytes). The results were compared with the laboratory results of the individual samples. Result After completing the study, we determined the efficacy of the urinary reagent strips in bedside estimation of CSF glucose, protein, and leukocyte levels in terms of sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy. Conclusion This study provides insight into the utility of urinary reagent strips for rapid bedside diagnosis of CSF samples from patients suspected of having an infection.

Aseptic meningitis and Fabry disease.

Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features. We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases. Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis. Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro-inflammatory signaling pathways.

H-intensity scale score to estimate CSF GluN1 antibody titers with one-time immunostaining using a commercial assay.

Anti-NMDA receptor encephalitis is an autoimmune disorder caused by autoantibodies (abs) against the conformational epitope on GluN1 subunits. GluN1-abs have been determined with cell-based assay (CBA) co-expressing GluN1/GluN2 subunits. However, commercial fixed CBA expressing only GluN1 subunit has increasingly been used in clinical practice. The ab titers can be determined with serial dilutions, but its clinical significance remains unclear. We aimed to develop an H-intensity scale (HIS) score to estimate GluN1-ab titers in cerebrospinal fluid (CSF) with one-time immunostaining using both commercial CBA and immunohistochemistry and report its usefulness. "H" is the initial of a patient with high CSF GluN1-ab titers (1:2,048). We first determined the reliability of CBA in 370 patients with suspected autoimmune encephalitis by comparing the results between commercial CBA and established assay in Dalmau's Lab. Then, we made positive control panels using the patient H's CSF diluted in a fourfold serial dilution method (1:2, 1:8, 1:32, 1:128, 1:512, and 1:2,048). Based on the panels, we scored the intensity of ab reactivity of 79 GluN1-ab-positive patients' CSF (diluted at 1:2) on a scale from 0 to 6 (with ≥1 considered positive). To assess inter-assay reliability, we performed immunostaining twice in 21 patients' CSF. We investigated an association between the score of CSF obtained at diagnosis and the clinical/paraclinical features. The sensitivity and specificity of CBA were 93.7% (95% CI: 86.0-97.3) and 98.6% (95% CI: 96.5-99.5), respectively. Linear regression analysis showed a good agreement between the scores of the first and second assays. Patients with a typical spectrum, need for mechanical ventilation support, autonomic symptoms/central hypoventilation, dyskinesias, speech dysfunction, decreased level of consciousness, preceding headache, ovarian teratoma, and CSF leukocyte count >20 cells/µL had a higher median HIS score than those without, but HIS score was not associated with sex, age at onset, or seizure. HIS score at diagnosis had a significant effect on 1-year functional status. The severity of disease and four of the six core symptoms were associated with higher GluN1-ab titers in CSF at diagnosis, which may play a role in poor 1-year functional status. An incomplete phenotype can be attributed to low CSF GluN1-ab titers.

The application value of metagenomic next-generation sequencing technology in the diagnosis and treatment of neonatal infectious meningitis – a single center retrospective case-control study

ABSTRACT Objective This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis. Methods From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group (n = 27) and infectious meningitis with mNGS (-) group (n = 26), respectively. Results (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636–0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group (p < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072–10.737; adjusted OR = 15.580, 95%CI: 2.114–114.798]. Conclusion Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

Granulocytes in cerebrospinal fluid of adults suspected of a central nervous system infection: a prospective study of diagnostic accuracy.

Cerebrospinal fluid (CSF) granulocytes are associated with bacterial meningitis, but information on its diagnostic value is limited and primarily based on retrospective studies. Therefore, we assessed the diagnostic accuracy of CSF granulocytes. We analyzed CSF granulocytes (index test) from all consecutive patients in two prospective cohort studies in the Netherlands. Both studies included patients ≥ 16years, suspected of a central nervous system (CNS) infection, who underwent a diagnostic lumbar puncture. All episodes with elevated CSF leukocytes (≥ 5 cells per mm3) were selected and categorized by clinical diagnosis (reference standard). Of 1261 episodes, 625 (50%) had elevated CSF leukocytes and 541 (87%) were included. 117 of 541 (22%) were diagnosed with bacterial meningitis, 144 (27%) with viral meningoencephalitis, 49 (9%) with other CNS infections, 76 (14%) with CNS autoimmune disorders, 93 (17%) with other neurological diseases and 62 (11%) with systemic diseases. The area under the curve to discriminate bacterial meningitis from other diagnoses was 0.97 (95% confidence interval [CI] 0.95-0.98) for CSF granulocyte count and 0.93 (95% CI 0.91-0.96) for CSF granulocyte percentage. CSF granulocyte predominance occurred in all diagnostic categories. A cutoff at 50% CSF granulocytes gave a sensitivity of 94% (95% CI 90-98), specificity of 80% (95% CI 76-84), negative predictive value of 98% (95% CI 97-99) and positive predictive value of 57% (95% CI 52-62). CSF granulocytes have a high diagnostic accuracy for bacterial meningitis in patients suspected of a CNS infection. CSF granulocyte predominance occurred in all diagnostic categories, limiting its value in clinical practice.

Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIVRNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4+ T-cell count nadir (p < 0.001), lower serum globulins (p = 0.003), and lower CSF leukocytes (p < 0.001). Without ART, one in 13 PWH had persistently undetectable CSF HIV RNA, while persistent CSF/plasma discordance was extremely rare over years. Immune responses, inflammation, BBB permeability, and iron and lipid metabolism were all associated with HIV replication in CSF.

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy

ObjectivesWe evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. MethodsCases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1β, CRP and procalcitonin concentrations were measured with Luminex technology. ResultsIn 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1β (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). ConclusionCSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.

Temporal Changes in CSF Cell Parameters After SAH: Comparison of Ventricular and Spinal Drain Samples.

Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)-derived and lumbar spinal drain-derived samples. We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19days after aSAH separately for EVD-derived and spinal drain-derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling. We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4-5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64-618 × 106). The cell ratio and index peaked at 8-9days (0.90% [IQR 0.35-1.98%] and 2.71 [IQR 1.25-6.73], respectively). In spinal drain-derived samples, the leucocyte count peaked at days 6-7, reaching a median of 238 × 106 (IQR 60-396 × 106). The cell ratio and index peaked at 14-15days (4.12% [IQR 0.63-10.61%]) and 12-13days after aSAH (8.84 [IQR 3.73-18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain-derived samples at days 6-17, and the cell ratio as well as the cell index was significantly higher in spinal drain-derived samples compared to EVD samples at days 10-15. CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable.

Comparing clinical features, severity and prognosis of autoimmune encephalitis and with and without oligoclonal bands.

This study aimed to examine the clinical distinctions among patients diagnosed with autoimmune encephalitis (AE) based on the presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCBs). Additionally, it sought to explore the relationship between OCBs and the severity and prognosis of autoimmune encephalitis. A retrospective analysis was conducted on 94 patients diagnosed with AE at the People's Hospital of Zhengzhou University between October 2016 and June 2022. The patients were divided into OCB-positive and OCB-negative groups based on CSF-OCBs. Patient severity at admission was assessed utilizing the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) and the modified Rankin scale (mRS). Additionally, some oligoclonal-positive patients underwent dynamic longitudinal analysis of cerebrospinal fluid test indices. The mRS score was ultimately employed to evaluate patients' short-term prognosis (6 months) and long-term prognosis (at least 12 months) following immunotherapy. Of the 94 patients, 34 (36.2%) belonged to the OCB-positive group, while 60 (63.8%) belonged to the OCB-negative group. The group with anti-n-methyl-d-aspartate receptor (anti-NMDAR) encephalitis exhibited the highest rate of oligoclonal positivity at 27 (49.1%), followed by anti-aminobutyric acid B receptor (GABABR) encephalitis with 4 cases (30.8%), anti-contactin-associated protein-like 2 (CASPR2) encephalitis with 2 cases (20%), and anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis with 1 case (6.25%). No statistically significant differences were found between the two groups regarding gender, age, prodromal symptoms, psychiatric disorders, seizures, language disorders, motor dysfunction, cognitive dysfunction, tumor incidence, and magnetic resonance imaging (MRI) abnormalities (p > 0.05). The OCB-positive group exhibited higher rates of autonomic dysfunction, intensive care unit (ICU) admission, CSF leukocytes, and IgG index compared to the OCB-negative group (p < 0.05). Additionally, the OCB-positive group had significantly higher median CASE and mRS scores prior to immunotherapy than the OCB-negative group (p < 0.001 and p < 0.001). Furthermore, in both short-term follow-up and long-term follow-up, the OCB-positive group had a significantly lower proportion of patients with a favorable prognosis compared to the OCB-negative group (50% vs. 71.7, 61.8% vs. 83.3%; p = 0.036, p = 0.002). Autonomic dysfunction, ICU admission, leukocytes in the cerebrospinal fluid, and elevated IgG index are more commonly observed in OCB-positive patients. OCB-positivity has also been linked to the severity and prognosis of AE, making it a potential biomarker. Initial OCB testing aids clinicians in identifying potentially critically ill patients early and monitoring disease progression, thereby optimizing clinical treatment decisions.

The Prognostic Nutritional Index and Mortality in Patients With Ventriculoperitoneal Shunt Infection

The objective of this study was to investigate the relationship between mortality and the prognostic nutritional index (PNI) in the pediatric patient group with ventriculoperitoneal shunt (VPS) infection. A total of 63 pediatric patients with a VPS infection and positive cerebrospinal fluid (CSF) culture were retrospectively registered. The CSF specimens were analyzed to conduct culture and microscopic evaluation. A total of 44.4% of the cases were men and 55.6% of the cases were women. Patients were divided into 2 groups (survivor and non-survivor patients). When survivor and non-survivor patients were compared, it was found that CSF leukocytes, CSF glucose, CSF protein, CSF/blood glucose ratio, lymphocyte, albumin, and PNI levels were lower in the non-survivor patients’ group. Nevertheless, blood glucose and CRP (C-reactive protein) were significantly higher in the non-survivor patients’ group than in the survivor patients’ group. In our investigation, we suggested that low PNI was related to high mortality in cases of VPS infection.

Viral lumbosacral radiculitis (Elsberg syndrome) in Denmark

PurposeTo describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome).MethodsNationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020.ResultsTwenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27–43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31–514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%).ConclusionsUrinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up.

Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

Relationship between catheter related cerebrospinal fluid infections and systemic immune-inflammation index.

This study investigated the relationship between the systemic immune inflammation index (SII) and catheter-related infections and their effects on prognosis in pediatric patients. A total of 56 pediatric patients diagnosed with ventriculoperitoneal (V-P) shunt infection between January 2017 and October 2019 were included. V-P shunt infection diagnosis was made based on clinical findings. All cerebrospinal fluid (CSF) samples were subjected to direct microscopic examination and culture. Protein, glucose, and sodium levels in CSF, CSF leukocytes, and hematological and biochemical parameters were measured. Fifty-six patients with growth in CSF culture were included in this study. 55.4% of the cases were female and 44.6% male. V-P shunt was detected in 82.1% of the cases and external ventricular drainage (EVD) catheter-related infection in 17.9%. The CSF/blood glucose ratio was significantly lower (p=0.046), and SII was significantly increased (p=0.002) in non-coagulase-negative staphylococci. Early and appropriate antibiotic therapy reduces morbidity and mortality in catheter-related infections. However, it is important to start empirical antibiotherapy until culture results are expected. Therefore, further research on the estimation of possible factors is needed.

Characterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis

PurposeThere is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital.MethodsA retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis.ResultsThe most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p < 0.001). The CHANCE score was developed to differentiate BM from other causes of CSF pleocytosis: Multivariate regression revealed that CSF cell count > 100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956).ConclusionOverall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making.

Clinical risk factors for recurrence of myelin oligodendrocyte glycoprotein antibody-associated disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS demyelinating disease that targets myelin oligodendrocyte glycoprotein and recurs in approximately 50% of patients after the initial episode. Multiple relapses may have adverse consequences, but the factors influencing relapse are unclear. This study analyzed the clinical risk factors for relapse in patients with MOGAD. Twenty-four MOGAD patients diagnosed at the Department of Neurology, First Hospital of Shanxi Medical University from March 2018 to November 2020 were retrospectively analyzed in this study. The patients were divided into a monophasic course and a relapsing course according to their disease process. The patients' epidemiological characteristics, clinical symptoms, laboratory tests, imaging features, and regression were summarized. Comparisons were made between the monophasic and relapsing course to identify the possible factors associated with the clinical features and recurrence. At a mean follow-up of 15 months (range: 8 to 24 months), seventeen of the 24 patients (70.8%) had monophasic disease, and 7 (29.2%) had relapsing disease. Among the 24 patients, 17 patients (70.9%) had low Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) serum titers (<1:100), and 7 patients (29.1%) had high MOG-IgG serum titers (≥1:100). Compared to the monophasic course group, patients in the relapsing course group had higher serum antibody titers (71.4% vs. 11.7%, P=0.035). Onset phenotypes included encephalitis (50%), myelitis (45.8%), and optic neuritis (45.8%), with 66.7% of patients starting with a single phenotype and 33.3% starting with two or more phenotypes. Optic neuritis was more common in the relapsing course group (85.7%) than the monophasic course group (29.4%) (P=0.023). There was no significant difference between the two groups in the proportion of myelitis and encephalitis. A previous history or background of immunological disease was present in 33.3% of patients, with a significantly higher proportion in the relapsing course group than in the monophasic course group (71.4% vs. 17.6%, P=0.021). Regarding ancillary examinations, the relapsing course group was more likely to have CSF leukocytes higher than 50/mm3 than the monophasic course group (60% vs. 0, P=0.045), while there was no difference in the number and site distribution of the lesions on MRI. Our study suggests that the most common clinical manifestations of MOGAD are diminished visual acuity, limb/facial numbness, and ocular/orbital pain. The onset phenotype consisting of optic neuritis, a history of immune disease, high antibody titers (≥1:100), and high cerebrospinal fluid leukocytes (above 50/mm3) suggests a high likelihood of MOGAD recurrence.

Meta-analysis of Cerebrospinal Fluid Cell Count and Biochemistry to Diagnose Meningitis in Infants Aged < 90 Days.

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..

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis. We report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome. A total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150-380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1-1:32), while the median serum MOG antibody titer was 1:32 (1:10-1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike-slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses. FLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.