Cerebrospinal Fluid Leukocyte Count Research Articles

Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by an acute onset of severe headache and multi-focal segmental vasoconstriction of cerebral arteries resolving within 12weeks. Diagnostic criteria include normal or near-normal findings in cerebrospinal fluid (CSF) analysis, especially leucocyte levels<10/mm³. Distinguishing RCVS from primary angiitis of the central nervous system (PACNS) is essential to avoid unnecessary and sometimes unfavourable immunosuppressive treatment. We reviewed retrospectively the clinical and diagnostic data of 10 RCVS patients who presented in our neurological department from 1January 2013 to February 2017. The main purpose was to verify whether CSF leucocyte counts<10/mm³ serve to discriminate RCVS from PACNS. Five of six patients who underwent lumbar puncture presented with CSF leucocyte levels ≥10/mm³. Two patients had a history of misinterpretation of CSF pleocytosis as cerebral vasculitis and of immunosuppressive treatment. A complete restitution of cerebral vasoconstriction was evident in all. No patient had further cerebral strokes or bleedings without immunosuppressive treatment over more than 12weeks. Despite the established diagnostic criteria, RCVS can manifest with CSF leucocyte levels >10/mm³. Careful anamnesis and the response of 'vasculitis-like angiography' to nimodipine given as a test during angiography and as oral medication are key to differentiate RCVS from cerebral vasculitis.

Elevated leukocyte count in cerebrospinal fluid of patients with chronic inflammatory demyelinating polyneuropathy.

Cerebrospinal fluid (CSF) examination is often part of the diagnostic work-up of a patient suspected of having chronic inflammatory demyelinating polyneuropathy (CIDP). According to the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) criteria, an elevated protein level without pleocytosis (leukocytes <10cells/µl) is supportive of the diagnosis CIDP. It is unclear how many CSF leukocytes are compatible with the diagnosis CIDP and how extensive the diagnostic work-up should be in patients with a demyelinating neuropathy and pleocytosis. We performed a retrospective study at two tertiary neuromuscular referral clinics and identified 14 out of 273 (6%) patients with CIDP with elevated CSF leukocytes (≥10cells/µl). All these patients met the EFNS/PNS criteria for definite or probable CIDP. Eight patients (57%) presented with a subacute onset and four patients with an antecedent infection. Most patients responded well to therapy, and eight patients are currently in remission. In four patients, lumbar puncture was repeated. A spontaneous decrease in leukocytes before start of treatment was found in three patients. Our data indicate that a mild to moderate pleocytosis in CSF does not exclude the diagnosis of CIDP, especially in patients with a subacute onset of disease.

Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation

BackgroundVaricella zoster virus (VZV) reactivation spans the spectrum from uncomplicated segmental herpes zoster to life-threatening disseminated CNS infection. Moreover, in the absence of a small animal model for this human pathogen, studies of pathogenesis at the organismal level depend on analysis of human biosamples. Changes in cerebrospinal fluid (CSF) metabolites may reflect critical aspects of host responses and end-organ damage in neuroinfection and neuroinflammation. We therefore applied a targeted metabolomics screen of CSF to three clinically distinct forms of VZV reactivation and infectious and non-infectious disease controls in order to identify biomarkers for CNS involvement in VZV reactivation.MethodsMetabolite profiles were determined by targeted liquid chromatography-mass spectrometry in CSF from patients with segmental zoster (shingles, n = 14), facial nerve zoster (n = 16), VZV meningitis/encephalitis (n = 15), enteroviral meningitis (n = 10), idiopathic Bell’s palsy (n = 11), and normal pressure hydrocephalus (n = 15).ResultsConcentrations of 88 metabolites passing quality assessment clearly separated the three VZV reactivation forms from each other and from the non-infected samples. Internal cross-validation identified four metabolites (SM C16:1, glycine, lysoPC a C26:1, PC ae C34:0) that were particularly associated with VZV meningoencephalitis. SM(OH) C14:1 accurately distinguished facial nerve zoster from Bell’s palsy. Random forest construction revealed even more accurate classifiers (signatures comprising 2–4 metabolites) for most comparisons. Some of the most accurate biomarkers correlated only weakly with CSF leukocyte count, indicating that they do not merely reflect recruitment of inflammatory cells but, rather, specific pathophysiological mechanisms. Across all samples, only the sum of hexoses and the amino acids arginine, serine, and tryptophan correlated negatively with leukocyte count. Increased expression of the metabolites associated with VZV meningoencephalitis could be linked to processes relating to neuroinflammation/immune activation, neuronal signaling, and cell stress, turnover, and death (e.g., autophagy and apoptosis), suggesting that these metabolites might sense processes relating to end-organ damage.ConclusionsThe results provide proof-of-concept for the value of CSF metabolites as (1) disease-associated signatures suggesting pathophysiological mechanisms, (2) degree and nature of neuroinflammation, and (3) biomarkers for diagnosis and risk stratification of VZV reactivation and, likely, neuroinfections due to other pathogens.Trial registrationNot applicable (non-interventional study).

Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts >20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

Demographic, Clinical, and Immunologic Features of 389 Children with Opsoclonus-Myoclonus Syndrome: A Cross-sectional Study.

Pediatric-onset opsoclonus-myoclonus syndrome (OMS) is a devastating neuroinflammatory, often paraneoplastic, disorder. The objective was to characterize demographic, clinical, and immunologic aspects in the largest cohort reported to date. Cross-sectional data were collected on 389 children in an IRB-approved, observational study at the National Pediatric Myoclonus Center. Non-parametric statistical analysis was used. OMS manifested in major racial/ethnic groups, paralleling US population densities. Median onset age was 1.5 years (1.2–2 interquartile range), inclusive of infants (14%), toddlers (61%), and youngsters (25%). The higher female sex ratio of 1.2 was already evident in toddlers. Time to diagnosis was 1.2 months (0.7–3); to treatment, 1.4 months (0.4–4). Irritability/crying dominated prodromal symptomatology (60%); overt infections in <35%. Acute cerebellar ataxia was the most common misdiagnosis; staggering appeared earliest among 10 ranked neurological signs (P < 0.0001). Some untreated youngsters had no words (33%) or sentences (73%). Remote neuroblastic tumors were detected in 50%; resection was insufficient OMS treatment (58%). Age at tumor diagnosis related to tumor type (P = 0.004) and stage (P = 0.002). A novel observation was that paraneoplastic frequency varied with patient age—not a mere function of the frequency of neuroblastoma, which was lowest in the first 6 months of life, when that of neuroblastoma without OMS was highest. The cerebrospinal fluid (CSF) leukocyte count was minimally elevated in 14% (≤11/mm3) with normal differential, and commercially screened serum autoantibodies were negative, but CSF oligoclonal bands (OCB) and B cells frequency were positive (58 and 93%). Analysis of patients presenting on immunotherapy revealed a shift in physician treatment practice patterns from monotherapy toward multi-agent immunotherapy (P < 0.001); the number of agents/sequences varied. In sum, a major clinical challenge is to increase OMS recognition, prevent initial misdiagnosis, and shorten time to diagnosis/treatment. The index of suspicion for an underlying tumor must remain high despite symptoms of infection. The disparity in onset age of neuroblastoma frequency with that of neuroblastoma with OMS warrants further studies of potential host/tumor factors. OMS neuroinflammation is best diagnosed by CSF OCB and B cells, not by routine CSF or commercial antibody studies.

Serological Response Predicts Normalization of Cerebrospinal Fluid Abnormalities at Six Months after Treatment in HIV-Negative Neurosyphilis Patients

This study aimed to determine whether a serological response could predict the normalization of cerebrospinal fluid (CSF) abnormalities at 6 months after treatment in human immunodeficiency virus (HIV)-negative neurosyphilis patients. A total of 123 neurosyphilis patients were recruited at baseline, 58 of these patients undergoing treatment, repeated CSF examinations and serological tests for syphilis at 6 months after treatment were included in the follow-up study. Before treatment, the CSF rapid plasma reagin (RPR) titer, CSF Treponema pallidum particle agglutination (TPPA) titer, CSF leukocyte count, and CSF protein concentration were correlated with both serum RPR and TPPA titers. At 6 months after treatment, 28 and nine patients achieved serological responses of RPR and TPPA tests, respectively. The sensitivities of the serological response of RPR and TPPA tests for identifying the normalization of CSF abnormalities were 60.0∼83.3% and 17.1~22.2%, respectively; and 75.0∼91.3% of patients showing serological response of RPR test also achieved CSF normalization, suggesting that the serological response could predict CSF normalization to some degree. Particularly, in patients with ≥8-fold decreases in the serum RPR titer, the CSF RPR, CSF leukocyte count, and CSF protein concentration had normalized, and follow-up lumbar puncture could be reduced considering the resolution of neurological symptoms.

Cerebrospinal fluid pleocytosis level as a diagnostic predictor? A cross-sectional study

BackgroundLumbar puncture with quantification of leukocytes and differential count of cellular subsets in the cerebrospinal fluid is a standard procedure in cases of suspected neuroinfectious conditions. However, a number of non-infectious causes may result in a low leukocyte number (0–1000 cells/ml). We wanted to assess the diagnostic diversity of unselected adult patients with pleocytosis in the cerebrospinal fluid.MethodsThe study is based on data from cerebrospinal fluid (CSF) analyses of all adult patients (15 years or older) admitted to a large university hospital in Denmark during a two-year period (2008–2009). Data from the local patient administrative system supplied with data from patient charts were combined with laboratory data.ResultsA total of 5390 cerebrospinal fluid samples from 3290 patients were included. Pleocytosis >5 leucocytes/μl was found in samples from 262 patients of which 106 (40.5%) were caused by infection of the central nervous system (CNS), 20 (7.6%) by infection outside CNS, 79 (30.2%) due to non-infectious neurological diseases, 23 (8.8%) by malignancy, and 34 (13.0%) caused by other conditions. Significantly higher mean CSF leukocytes was found in patients suffering from CNS infection (mean 1135 cells/μl, p-value <0.0001).ConclusionsCNS infection, non-infectious neurological disease, malignancy, and infection outside CNS can cause pleocytosis of the cerebrospinal fluid. Leukocyte counts above 100/μl is mainly caused by CNS infection, whereas the number of differential diagnoses is higher if the CSF leukocyte counts is below 50/μl. These conditions are most commonly caused by non-infectious neurological diseases including seizures.

Cerebrospinal fluid pleocytosis in infectious and noninfectious central nervous system disease: A retrospective cohort study.

Cerebrospinal fluid (CSF) analysis is the most important tool for assessing central nervous system (CNS) disease. An elevated CSF leukocyte count rarely provides the final diagnosis, but is almost always an indicator of inflammation within the CNS.The present study investigated the variety of diseases associated with CSF pleocytosis.CSF analyses were identified through the biochemical database used in the capital region of Denmark in the period from 2003 to 2010. In patients >15 years, clinical diagnoses associated with the finding of a CSF leukocyte count >10 × 106 cells/L were obtained from discharge records and patient files.A total of 1058 CSF samples from 1054 patients were included in the analysis. The median age was 50 (interquartile range: 36–67) and 53% were male. Eighty-one different diagnoses were identified in 1058 cases with an elevated CSF leukocyte count, besides unknown causes. Infections were the most common cause of CSF pleocytosis (61.4%) followed by miscellaneous causes (12.7%), vascular (9.7%), neurodegenerative (7%), neoplastic (5%), and inflammatory conditions (4.2%). Only infections presented with leukocyte counts >10,000 × 106/L. Infections represented 82.6% of all cases with a leukocyte count >100 × 106/L whereas 56.3% of cases with at leukocyte counts <100 × 106/L were dominated by disease not related to infection.The present study may serve as a reminder to clinicians of what diseases and disease categories to suspect when patients present with CSF biochemistry indicating CNS inflammation.

Clinical Parameters, Routine Inflammatory Markers, and LTA4H Genotype as Predictors of Mortality Among 608 Patients With Tuberculous Meningitis in Indonesia.

Damaging inflammation is thought to contribute to the high morbidity and mortality of tuberculous meningitis (TBM), but the link between inflammation and outcome remains unclear. We performed prospective clinical and routine laboratory analyses of a cohort of adult patients with TBM in Indonesia. We also examined the LTA4H promoter polymorphism, which predicted cerebrospinal fluid (CSF) leukocyte count and survival of Vietnamese patients with TBM. Patients were followed for >1 year. We included 608 patients with TBM, of whom 67.1% had bacteriological confirmation of disease and 88.2% had severe (ie, grade II or III) disease. One-year mortality was 43.7% and strongly associated with decreased consciousness, fever, and focal neurological signs. Human immunodeficiency virus (HIV) infection, present in 15.3% of patients, was associated with higher mortality and different CSF characteristics, compared with absence of HIV infection. Among HIV-uninfected patients, mortality was associated with higher CSF neutrophil counts (hazard ratio [HR], 1.10 per 10% increase; 95% confidence interval [CI], 1.04-1.16), low CSF to blood glucose ratio (HR, 1.16 per 0.10 decrease; 95% CI, 1.04-1.30), CSF culture positivity (HR, 1.37; 95% CI, 1.02-1.84), and blood neutrophilia (HR, 1.06 per 109 neutrophils/L increase; 95% CI, 1.03-1.10). The LTA4H promoter polymorphism correlated with CSF mononuclear cell count but not with mortality (P = .915). A strong neutrophil response and fever may contribute to or be a result of (immuno)pathology in TBM. Aggressive fever control might improve outcome, and more-precise characterization of CSF leukocytes could guide possible host-directed therapeutic strategies in TBM.

Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment

BackgroundMitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.MethodsWe quantified cell-free mtDNA in CSF by droplet digital PCR in 332 CHARTER participants who underwent comprehensive neuropsychiatric evaluation. NC performance was assessed using the global deficit score (GDS) as either a continuous or a binary measure (GDS ≥ 0.5, impaired vs. GDS < 0.5, unimpaired). CSF, clinical, and biomarker data from the earliest available time point were analyzed. Cell-free mtDNA associations with CSF inflammation and iron-related biomarkers [CXCL10, IL-6, IL-8, TNF-a, transferrin (TF), ceruloplasmin (CP), and vascular endothelial growth factor (VEGF)], VL, and GDS were evaluated by multivariable regression.ResultsCSF cell-free mtDNA levels were significantly lower in participants with undetectable (vs. detectable) VL in either plasma (p < 0.001) or CSF (p < 0.001) and in those on antiretroviral therapy (ART; p < 0.001). Participants on ART with undetectable VL in both CSF and plasma had lower mtDNA levels than those with detectable VL in both compartments (p = 0.001). Higher mtDNA levels were observed in participants in the highest vs. lowest tertile (T3 vs. T1) of CSF CXCL10 (T3 vs. T1, p < 0.001) and TNF-a (T3 vs. T1, p < 0.05) in unadjusted analyses. MtDNA levels also correlated with CSF leukocyte count. After adjusting for CSF leukocyte count and VL, mtDNA levels were also associated with other inflammation- and iron-related biomarkers in CSF, including TF (T3 vs. T1, p < 0.05) and CP (T3 vs. T1, p < 0.05). With additional correction for ART use, mtDNA was also negatively associated with CSF VEGF (p < 0.05) and IL-6 (p = 0.05). We observed no associations of CSF mtDNA levels with age or GDS-defined NC impairment.ConclusionsCSF cell-free mtDNA levels were associated with HIV RNA and ART status, as well as with biomarkers of iron transport and VEGF, a growth factor with known effects on mitochondrial integrity and autophagy. CSF mtDNA may be a biomarker of iron dysregulation and/or neuroinflammation during HIV infection.

BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset

BackgroundB lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS.MethodsPaired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh).ResultsCompared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes (p < 0.01), lower values of BAFF Index (11.9 ± 6.1 vs 17.5 ± 5.2, p < 0.01), and higher CSF CXCL13 levels (27.7 ± 33.5 vs 0.9 ± 1.5, p < 0.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis (r > 0.5 and p < 0.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB− (p < 0.05) and HC (p < 0.01), and correlated to CSF CXCL13 concentrations (r 0.77, p < 0.001).The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41 ± 0.1 vs 2.49 ± 0.1 mm, p < 0.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB−.ConclusionsThe intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by higher leukocyte counts in the CSF and early evidence of cortical thinning, further suggesting a role for this chemokine as a possible marker of disease severity.

The Importance of Haematological and Biochemical Findings in Patients with West Nile Virus Neuroinvasive Disease.

SummaryBackgroundWest Nile virus neuroinvasive disease (WNND) occurs in less than 1% of infected people. Leukocytosis with lymphocytopenia, mild anaemia, thrombocytopenia, elevated liver and muscle enzymes and hyponatremia are occasionally present in patients with WNND. Cerebrospinal fluid (CSF) findings resemble other viral neuroinfections. The purpose of this study is to pre sent some of the most important laboratory findings of our patients with WNND and to evaluate their correlation with fatal outcome.MethodsThe study included 161 patients with WNND. Their blood and CSF samples were cytobiochemically analysed and the obtained variables were then tested for predictive significance of the disease outcome, or used for differentiation between two clinical syndromes (encephalitis vs meningitis).ResultsWest Nile encephalitis was present in 127 (78.9%) patients and West Nile meningitis was diagnosed in 34 (21.1%) cases. Leukocytosis was found in 45.9% patients. CRP level higher than 100 mg/L was registered only in those with encephalitis (p=0.020). CSF leukocyte count was 146±171 per microlitre, with slight lymphocytic predominance (mean 52%). Hypoglycorrhachia was registered in 9.3% of our patients with WNND. Twenty-eight (17.4%) patients died and all of them had encephalitis. Independent predictors of fatal outcome in WNND were serum CRP > 100 mg/L (p=0.011) and CSF proteins > 1 g/L (p=0.002).ConclusionsWNND usually affects older males. Prolonged neutrophilic predominance in CSF can occasionally be present, as well as hypoglycorrhachia. Patients with encephalitis, high serum CRP and high CSF protein level have a higher risk of fatal outcome.

Repeat lumbar puncture in adults with bacterial meningitis

In a prospective nationwide cohort study performed in the Netherlands from 2006 to 2014 we analysed clinical and laboratory characteristics of adults with community-acquired bacterial meningitis who underwent repeat lumbar puncture. Repeat lumbar puncture was performed in 124 of 1490 included episodes (8%), most commonly because of clinical deterioration (42%). Median cerebrospinal fluid (CSF) leucocyte count on admission was 1473 cells/mm3. Median CSF cell count showed a decrease of 19% when repeated within 2 days; of 84% within 3–7 days, of 93% within 8–14 days and of 98% within 15–21 days. Repeat lumbar puncture confirmed the diagnosis of meningitis in eight patients with normal initial CSF examination. Repeat CSF cultures yielded bacteria in nine patients, which led to identification of an underlying source of infection in two. We conclude that repeat lumbar puncture is performed in a small proportion of adults. Although it should not be seen as routine it can be useful in selected cases to confirm diagnosis, to exclude relapsing or persistent infection, or for therapeutic purpose in communicating hydrocephalus.

Direct comparison of the diagnostic accuracy between blood and cerebrospinal fluid procalcitonin levels in patients with meningitis

ObjectiveTo compare the clinical utility of serum and cerebrospinal fluid (CSF) procalcitonin (PCT) for the diagnosis of bacterial meningitis (BM) among patients with suspected meningitis. MethodsPatients with meningitis-like symptoms (n=120), admitted to the Second People's Hospital of Wuxi or the Changhai Hospital of Shanghai between January 2011 and December 2013, were prospectively and consecutively enrolled in this study. BM was finally diagnosed by CSF culture, Gram staining, quantitative polymerase chain reaction (qPCR), and treatment response. The diagnostic accuracy of the serum and CSF PCT was assessed by receiver operator characteristic (ROC) curve analysis. The relationship between CSF and serum PCT levels as well as the CSF leukocyte count and protein level was analyzed by Spearman's correlation analysis. ResultsPCT level in both the serum and CSF was significantly increased in the BM patients. The area under ROC curve of serum PCT for the diagnosis of BM was 0.96 (95% confidence interval (CI): 0.93–1.00), significantly higher than that of CSF PCT (0.90, 95% CI: 0.83–0.96). Using 0.88ng/mL as the threshold, the diagnostic sensitivity, specificity, and accuracy of serum PCT for the diagnosis of BM were 0.87 (95% CI, 0.73–0.95), 1.00 (95% CI, 0.95–1.00), and 95%, respectively. The serum PCT level was positively correlated with the CSF PCT level, leukocyte count, and protein level. ConclusionBoth the serum and CSF PCT had a high diagnostic value for BM among suspected meningitis patients, and serum PCT demonstrated a superior diagnostic value compared to CSF PCT.

How frequently external ventricular drainage device should be changed in children with ventriculoperitonel shunt infection?

Objective:The purpose of the presenting study was to determine how frequently external ventricular drainage (EVD) device should be changed in children with ventriculopertienal shunt (VPS) infection during prolonged intravenous antimicrobial therapy.Methods:In this retrospective study, 25 children with VPS infection were evaluated between January 2012 and December 2013. In these children VPS was surgically removed and appropriate antimicrobial therapy was administered according to cerebrospinal culture results. Data noted about how frequently EVD device had been changed, the number of cells on direct observation of cerebrospinal fluid (CSF), glucose and protein levels of CSF, and CSF culture results were obtained from patients’ records.Results:Total 25 children were included in the study. The median age was three months (1 and 65 months). In 44% of children, Staphylococcus epidermidis was isolated. During treatment period, EVD catheter has changed one to six times. A total of 68 EVD catheters were changed in these patients. When the duration of ventriculostomy catheter and leukocyte count in CSF were evaluated on daily basis, leukocyte count was decreased 5 units per day in children whose catheter remained less than 10 days. However, in children whose catheter remained more than 10 days leukocyte count was decreased 2.21 units per day.Conclusions:In children with VPS infection, EVD device should be changed at every 10 days for the rapid resolution of the infection.

Flow Cytometric Leukemic Blasts Detection in Cerebrospinal Fluid of Children with Acute Lymphoblastic Leukemia

Background: Central nervous system (CNS)-directed treatment has reduced risk of CNS relapse for childhood acute lymphoblastic leukemia (ALL), which accounts for 30-40% of initial relapses. Compared with CNS-negative patients, patients with CNS leukemia (>5 leukocytes/µL cerebrospinal fluid (CSF) and lymphoblasts) suffer from more CNS+ relapses. Conventional cytology (CC) is specific (>95%), but nonsensitive (<50%), since leukocytes in CSF decay within few hours after lumbar puncture.Method: We prospectively assessed centralised multi-parameter flow cytometry (FCM) of fixated CSF versus local CC in Nordic/Baltic childhood ALL. Diagnostic samples from 172 children aged 0-18 years with de novo and eight children with relapsed ALL were investigated in 297 CSF samples from 180 patients. Kinetics of disappearance of leukemic cells in the CSF was evaluated until day 15. Antibody-combinations reflected the immunophenotype of leukemic blasts in bone marrow.Result: Of 172 newly diagnosed patients, 51 (30%) had CSF involvement by FCM, while CC was positive in 16 patients (9%) (p<0.001). CSF involvement was detected by both FCM and CC in four of eight patients with relapse (50%). Among newly diagnosed patients, samples positive by FCM and CC had higher leukemic blast count compared to samples positive by FCM only (medians: 0.545 (range: 0.005-4.801) versus 0.016 (range: 0.003-1.38) leukemic blasts/µL; p<0.001). Among newly diagnosed patients with samples positive by FCM and CC, the CSF blast count was related to the CSF leukocyte count (rs=0.82; p=0.001). Compared to newly diagnosed patients who were FCM-negative, those with FCM-positivity had higher WBC (median: 37 versus 9 x 109/L; p<0.001), were younger (medians: 3 versus 5 years, p=0.04), and more often had T-cell ALL (12/51 (24%) versus (6/121 (5%), p<0.001). Five (16%) of 31 newly diagnosed patients with FCM detected blasts at diagnosis and available data at day 15 still had CSF leukemic blasts on day 15. So far the two patients who later developed CNS and/or bone marrow relapse were positive by flow (1.38 and 0.178 blasts/µL), but CNS negative by CC or had CSF leukocyte count <5/µL and lymphoblasts on CC, respectively.Conclusion: Leukemic blasts are present in spinal fluid of one third of newly diagnosed ALL. CSF involvement is associated with other higher risk characteristics. The prognostic value of these findings awaits prospective evaluation. DisclosuresNo relevant conflicts of interest to declare.

Risk Factors for Acute Symptomatic Seizure in Bacterial Meningitis in Children.

The aim of this study was to investigate the association between clinical and laboratory parameters at admission and the occurrence of in-hospital symptomatic seizures in children with acute bacterial meningitis in Brazil. A retrospective case-control study in 270 children with confirmed bacterial meningitis, aged from 1 month to 14 years, was conducted between January 2004 and December 2008. Associations with the occurrence of in-hospital epileptic seizures were adjusted using stepwise multiple logistic regression analysis. Sixty-seven children suffered at least one in-hospital epileptic seizure. After multivariate analysis, the independent predictors considered for in-hospital epileptic seizures were as follows: age less than 2 years (odds ratio = 0.97; 95% confidence interval 0.97-0.98), pneumococcal etiology (odds ratio = 4.55; 95% confidence interval 1.88-11.0); altered mental status (odds ratio = 3.47; 95% confidence interval 1.66-7.26) and cerebrospinal fluid leukocyte count below 1000 cells (odds ratio = 2.14; 95% confidence interval 0.99-4.60). Mortality was higher in patients with intrahospital epileptic seizures compared to those without (25/67 [37.3%] vs 9/203 [4.43%], P < .001].

Predictive value of decoy receptor 3 in postoperative nosocomial bacterial meningitis.

Nosocomial bacterial meningitis requires timely treatment, but what is difficult is the prompt and accurate diagnosis of this disease. The aim of this study was to assess the potential role of decoy receptor 3 (DcR3) levels in the differentiation of bacterial meningitis from non-bacterial meningitis. A total of 123 patients were recruited in this study, among them 80 patients being with bacterial meningitis and 43 patients with non-bacterial meningitis. Bacterial meningitis was confirmed by bacterial culture of cerebrospinal fluid (CSF) culture and enzyme-linked immunosorbent assay (ELISA) was used to detect the level of DcR3 in CSF. CSF levels of DcR3 were statistically significant between patients with bacterial meningitis and those with non-bacterial meningitis (p < 0.001). A total of 48.75% of patients with bacterial meningitis received antibiotic >24 h before CSF sampling, which was much higher than that of non-bacterial meningitis. CSF leucocyte count yielded the highest diagnostic value, with an area under the receiver operating characteristic curve (ROC) of 0.928, followed by DcR3. At a critical value of 0.201 ng/mL for DcR3, the sensitivity and specificity were 78.75% and 81.40% respectively. DcR3 in CSF may be a valuable predictor for differentiating patients with bacterial meningitis from those with non-bacterial meningitis. Further studies are needed for the validation of this study.

Analysis of clinical outcomes in pediatric bacterial meningitis focusing on patients without cerebrospinal fluid pleocytosis.

Cerebrospinal fluid (CSF) cell count and biochemical examinations and cultures form the basis for the diagnosis of bacterial meningitis. However, some patients do not have typical findings and are at a higher risk of being missed or having delayed treatment. To better understand the correlation between CSF results and outcomes, we evaluated CSF data focusing on the patients with atypical findings. This study enrolled CSF culture-proven bacterial meningitis patients aged from 1 month to 18 years in a medical center. The patients were divided into "normal" and "abnormal" groups for each laboratory result and in combination. The correlations between the laboratory results and the outcomes were analyzed. A total of 175 children with confirmed bacterial meningitis were enrolled. In CSF examinations, 16.2% of patients had normal white blood cell counts, 29.5% had normal glucose levels, 24.5% had normal protein levels, 10.2% had normal results in two items, and 8.6% had normal results in all three items. In logistic regression analysis, a normal CSF leukocyte count and increased CSF protein level were related to poor outcomes. Patients with meningitis caused by Streptococcus pneumoniae and hyponatremia were at a higher risk of mortality and the development of sequelae. In children with bacterial meningitis, nontypical CSF findings and, in particular, normal CSF leukocyte count and increased protein level may indicate a worse prognosis.

PO-0341 Neutrophil Cd64 Index (cd64in) In Cerebrospinal Fluid Is A Promising Marker Of Bacterial Ventriculitis In Children With External Ventricular Drainage

<h3>Background and aims</h3> Bacterial ventriculitis is common in children with temporary external ventricular drains and diagnosis is challenging due to frequent reoperations, blood contamination of cerebrospinal fluid (CSF), presence of chemical ventriculitis and elevation of blood laboratory markers by concomitant bacterial infection. <h3>Methods</h3> Prospective, observational study enrolling children with external ventricular drainage at surgical ward and paediatric intensive care unit. CD64in in CSF together with CSF leukocyte count, glucose, proteins and blood leukocyte and differential count, CRP, PCT were studied at the time of suspected ventriculitis. CD64in was measured by flow cytometry (Trillium Diagnostics, LLC, Brewer, ME). Wilcoxon-test was used for comparison between groups and diagnostic accuracy determined by the area under the ROC curves (AUC) was defined for each marker. <h3>Results</h3> Thirty-three episodes of clinically suspected ventriculitis in twenty-one children (male 14, female 7, median age: 9 months, range: 8 days-167 months) were observed during a 26-month period. Episodes were classified into those with microbiologically proven ventriculitis (13 episodes: 9 Gram-positive and 4 Gram-negative) and those with microbiologically negative CSF (20 episodes). CD64in was the only CSF marker that could differentiate between groups (p = 0.0003); its diagnostic accuracy was 0.875 (95% CI: 0.713–0.963). Among blood markers only CRP and band neutrophils differentiated between groups (p = 0.0032 and p = 0.0463) with their diagnostic accuracy of 0.808 (0.633–0.923) and 0.721 (0.524–0.870); respectively. <h3>Conclusions</h3> CD64in in CSF is a promising diagnostic marker of bacterial ventriculitis in children with external ventricular drainage before microbiological confirmation.