Diagnostic Utility of Cerebrospinal Fluid Procalcitonin in Neonatal Meningitis.

We aimed to study the diagnostic utility of cerebrospinal fluid (CSF) procalcitonin (PCT) in neonates with meningitis. All the neonates with sepsis who qualified for lumbar puncture were prospectively evaluated. The neonates were classified into Meningitis and No meningitis group based on predefined criteria. CSF PCT was estimated in these neonates along with cytological and biochemical parameters. A total of 113 neonates were included in the study with 29 in the meningitis group and 84 in the no meningitis group. The median PCT levels were higher in babies with meningitis as compared to those without meningitis [0.194 (0.034-0.534) in meningitis group vs. 0.012 (0.012-0.012) ng/ml in no meningitis group, p < 0.001]. The area under curve for CSF PCT was 0.867 (0.77-0.95) and at a cut-off level of 0.120 ng/ml CSF PCT had a sensitivity of 83%, specificity of 84% and positive and negative predictive likelihood ratios of 5.35 and 0.20, respectively for the diagnosis of meningitis. CSF PCT has a good diagnostic accuracy similar to other parameters in the diagnosis of neonatal meningitis and can be considered as an additional diagnostic marker particularly when CSF culture is negative and cytochemical analysis is inconclusive.

Cerebrospinal Fluid Procalcitonin-A Potential Biomarker for Post-Craniotomy Bacterial Meningitis.

Background: The literature regarding the utility of cerebrospinal fluid (CSF) procalcitonin (PCT) in the diagnosis of post-craniotomy bacterial meningitis and differentiating it from aseptic meningitis is sparse. Materials and Methods: CSF total WBC count, sugar, protein, and PCT were measured in febrile patients with suspected post-craniotomy meningitis during the first 30 days following an intradural cranial procedure for non-trauma indications. Patients were diagnosed as postoperative bacterial meningitis if CSF culture was positive (PBM, n = 28) or postoperative aseptic meningitis if CSF culture was sterile and there was no evidence of systemic infection (PAM, n = 31). CSF cytochemical parameters and PCT values were compared between the groups. Normal values of CSF PCT were obtained from 14 patients with noninfectious indications with hydrocephalus. Results: There was no significant difference in CSF total WBC count, sugar, and protein levels between PAM and PBM groups. The median PCT level in CSF in the normal group was 0.03 ng/mL (interquartile range [IQR] 0.02-0.07 ng/mL). CSF PCT in the PBM group (median 0.37 ng/mL, IQR 0.2-1.4 ng/mL) was significantly higher than normal values as well as PAM group (median 0.12 ng/mL, IQR 0.07-0.26 ng/mL (P = 0.0004). The area under the receiver operating characteristic (ROC) curve for CSF PCT was 0.767. A cutoff value of 0.12 ng/mL yielded a sensitivity of 85.7% (95% CI: 67.3% to 96%), specificity of 51.6% (95% CI: 33% to 69.9%), positive predictive value of 61.5% (95% CI: 51.9% to 70.3%), and negative predictive value of 80% (95% CI: 60.3.8% to 91.3%). Conclusions: CSF PCT assay in patients who are febrile during the first 30 days post-non-trauma neurosurgical procedures has a role in the early diagnosis of bacterial meningitis.

Accuracy of Cerebrospinal Fluid C-Reactive Protein and Multiplex Polymerase Chain Reaction and Serum Procalcitonin in Diagnosis of Bacterial and Viral Meningitis in Children.

BACKGROUND: Meningitis is one of the most dangerous infection affecting children. The need for rapid and accurate diagnosis is mandatory for improving the outcome. AIM OF THE WORK: to evaluate the role of multiplex polymerase chain reaction (PCR), cerebrospinal fluid (CSF)-C-reactive protein (CRP) and serum procalcitonin (PCT) in diagnosis of meningitis and to detect its accuracy. PATIENTS AND METHODS: A cross-sectional study was carried out in University Children hospital, Faculty of Medicine, between November 2019 and September 2020. The study was approved by the Ethics Review Board of Faculty of Medicine, Assiut University, and informed written consent was obtained. The committee's reference number is 17200161. CLINICALTRIALS: gov ID: NCT03387969. 48 Children aged 2 to 18 years with meningitis were included. Detailed history and examination. Blood glucose level at time of admission prior to lumbar puncture, serum CRP level, serum PCT, CSF-CRP level and Multiplex PCR were evaluated. FUNDING: The study was supported by Grant Office of Faculty of Medicine, Assiut University with grant NO. 2018-01-04-006-R2. RESULTS: The mean age of children was 3.27 plus or minus 1.27 years. 35 (72.9%) cases were bacterial meningitis, while 13 (27.1%) cases were viral meningitis. Patients with bacterial meningitis had significantly higher serum CRP, serum PCT and higher CSF-CRP and significantly lower CSF/blood glucose compared to viral meningitis. Multiplex PCR had 94% sensitivity and 100% specificity for diagnosis of bacterial and viral meningitis. CONCLUSION: CSF-CRP, CSF/blood glucose, PCT and Multiplex-PCR may help in diagnosis and differentiation of bacterial and viral meningitis.

Comparison of C Reactive Protein and Procalcitonin Levels in Cerebrospinal Fluid and Serum to Differentiate Bacterial from Viral Meningitis.

GOALS: It is unclear whether C reactive protein (CRP) and procalcitonin (PCT) levels in cerebrospinal fluid (CSF) improve the accuracy compared to their serum levels for the differential diagnosis of infectious meningitis. The aim of this study was to compare the accuracy of CRP and PCT levels in CSF and serum in order to differentiate between bacterial and viral meningitis. PROCEDURES: CRP and PCT levels were measured in CSF and serum from patients with bacterial or viral meningitis. The diagnostic accuracy was determined using receiver operating characteristic curves (ROC), calculating the area under the ROC curve (AUC). RESULTS: Thirty patients were included in this study, 18 of whom had bacterial meningitis and 12 viral meningitis. The AUCs to differentiate bacterial from viral meningitis using serum CRP, CSF CRP, serum PCT and CSF PCT were 0.926; 0.898; 0.963; and 0.694 respectively. Serum CRP and PCT exhibited 100% and 88.9% sensitivity, 83.3% and 100% specificity with a cut-off =14.0 mg/L and 0.18 µg/L respectively. CONCLUSIONS: Levels of CRP and PCT in CSF did not present greater accuracy in differentiating bacterial from viral meningitis compared to serum levels. Serum CRP and PCT showed a high diagnostic accuracy, therefore its quantification is recommended in all patients with suspected infectious meningitis.

Diagnostic Value of CRP, Procalcitonin, and Ferritin Levels in Cerebrospinal Fluid of Children with Meningitis.

BACKGROUND AND OBJECTIVE: Bacterial meningitis is a serious disease with high rate of mortality and morbidity in children. Invasion of pathogens causes brain and meningeal inflammation, which leads to the release of biomarkers into cerebrospinal fluid (CSF). Identification of these biomarkers can help the physicians to differentiate between bacterial and aseptic meningitis. In the current study, some of these biomarkers such as Procalcitonin, C reactive protein (CRP), and Ferritin, were compared in cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis. METHODS: In a prospective cross sectional study in a referral children hospital in Tehran during 2011- 2013, the CSF levels of Procalcitonin, Ferritin, and CRP were measured in 57 children with clinically suspected meningitis. The Mann-Whitney u test and the chi-square test were used to compare two groups, children with bacterial and aseptic meningitis. The cut-offs of biomarker levels for differentiation between the 2 groups were constructed by receiver-operating - characteristic curve (ROC). RESULTS: 57 subjects (30 bacterial and 27 aseptic meningitis), were enrolled in this survey. In comparing the two groups, the CSF levels of Ferritin, CRP, and procalcitonin in bacterial meningitis were significantly higher than in aseptic meningitis (P values=˂0.001, 0.001, ˂0.001respectively), with sensitivity/ specificity being 92.9% / 68%, 92.9% / 84%, and 96.4% / 80%, respectively. Positive Predictive Values (PPV) were, correspondingly, 96.4%, 92.8%, and 92.8% for procalcitonin, Ferritin, and CRP. Corresponding Negative Predictive Values (NPV) were, respectively equal to 95.4%, 70%, and 88%. CONCLUSION: CSF of children with bacterial meningitis contains higher levels of inflammatory mediators including Procalcitonin, Ferritin, and CRP, compared to aseptic meningitis The biomarkers provided high sensitivity (especially PCT) and specificity (especially CRP). Using these complementary biomarkers would be useful for early diagnosis of bacterial meningitis and selection of appropriate treatment.

Application value of procalcitonin in patients with central nervous system infection.

OBJECTIVE: To study the application value of procalcitonin (PCT) in patients with central nervous system (CNS) infection. PATIENTS AND METHODS: A total of 66 patients, including 24 patients with suppurative meningitis, 20 patients with viral meningitis and 22 patients with tuberculous meningitis, were enrolled. 20 patients admitted to the hospital due to epilepsy or headache without infection in the same period were enrolled as the control group. PCT, high-sensitivity C-reactive protein (Hs-CRP), high-sensitivity C-reactive protein (Hs-CRP), protein quantification, chloride and glucose in serum and cerebrospinal fluid, were collected. RESULTS: The serum PCT level in suppurative meningitis group was significantly higher than that in other three groups. The dynamic monitoring of suppurative meningitis group on admission, at 72 h and 1 week after treatment showed that the serum PCT level was significantly decreased. PCT levels in cerebrospinal fluid in suppurative meningitis group, viral meningitis group and tuberculous meningitis group were decreased successively, and the differences were statistically significant. The detection of PCT in cerebrospinal fluid was more valuable than serum PCT detection in distinguishing tuberculous meningitis from viral meningitis. Continuous monitoring of changes in PCT in cerebrospinal fluid showed that there was no statistically significant difference before and after treatment. PCT level in cerebrospinal fluid was positively correlated with the serum PCT, cerebrospinal fluid white blood cell (WBC), and protein content in cerebrospinal fluid. CONCLUSIONS: The dynamic changes of serum PCT in patients with suppurative meningitis can be used to evaluate the disease, guide the clinical medication, and monitor the prognosis.

Cerebrospinal fluid procalcitonin as a biomarker of bacterial meningitis in neonates.

OBJECTIVE: The objective of the study was to study the performance of cerebrospinal fluid (CSF) procalcitonin as a marker for bacterial meningitis in neonates, and to determine its optimal 'cutoff' in CSF that can be called significant for the diagnosis. STUDY DESIGN: Neonates qualifying for lumbar puncture were prospectively studied. Procalcitonin and established CSF parameters were recorded. RESULTS: At a cut-off value of 0.33 ng ml-1, CSF procalcitonin had a sensitivity of 0.92, specificity of 0.87, with positive and negative likelihood ratios of 7.13 and 0.092, respectively. The area under the curve for different CSF parameters was: 0.926 (0.887 to 0.964) (P<0.001) for procalcitonin, 0.965 (0.956 to 0.974) for total leukocyte count, 0.961 (0.94 to 0.983) for neutrophil count, 0.874 (0.825 to 0.923) for protein, 0.946 (0.914 to 0.978) for sugar and 0.92 (0.955 to 0.992) for CSF:serum sugar ratio. The lumbar puncture was traumatic in 36 (21.4%) patients; out of these 15 (41.7%) had bacterial meningitis and 21 (58.3%) had no meningitis. In traumatic lumbar tap group, the median (IQR) CSF procalcitonin in patients with and without meningitis was 1.41 (0.32-3.42) ng/ml and 0.21(0.20-0.31) ng/ml respectively (p<0.05). CONCLUSIONS: Procalcitonin measurement has diagnostic efficiency similar to the established CSF markers. Routine assessment of procalcitonin in clean non-contaminated CSF may not yield additional information, but it may have clinical utility in situations where diagnosis of meningitis is in dilemma, as in the case of blood contamination of CSF in traumatic lumbar punctures.

Diagnostic and prognostic value of procalcitonin for early intracranial infection after craniotomy.

Intracranial infection is a common clinical complication after craniotomy. We aimed to explore the diagnostic and prognostic value of dynamic changing procalcitonin (PCT) in early intracranial infection after craniotomy. A prospective study was performed on 93 patients suspected of intracranial infection after craniotomy. Routine peripheral venous blood was collected on the day of admission, and C reactive protein (CRP) and PCT levels were measured. Cerebrospinal fluid (CSF) was collected for routine biochemical, PCT and culture assessment. Serum and CSF analysis continued on days 1, 2, 3, 5, 7, 9, and 11. The patients were divided into intracranial infection group and non-intracranial infection group; intracranial infection group was further divided into infection controlled group and infection uncontrolled group. Thirty-five patients were confirmed with intracranial infection after craniotomy according to the diagnostic criteria. The serum and cerebrospinal fluid PCT levels in the infected group were significantly higher than the non-infected group on day 1 (P<0.05, P<0.01). The area under curve of receiver operating characteristics was 0.803 for CSF PCT in diagnosing intracranial infection. The diagnostic sensitivity and specificity of CSF PCT was superior to other indicators. The serum and CSF PCT levels have potential value in the early diagnosis of intracranial infection after craniotomy. Since CSF PCT levels have higher sensitivity and specificity, dynamic changes in this parameter could be used for early detection of intracranial infection after craniotomy, combined with other biochemical indicators.

Diagnostic Accuracy of Cerebrospinal Fluid Procalcitonin in Bacterial Meningitis Patients with Empiric Antibiotic Pretreatment.

Accurate diagnosis of bacterial meningitis (BM) relies on cerebrospinal fluid (CSF) Gram staining and bacterial culture, which often present high false-negative rates because of antibiotic abuse. Thus, a novel and reliable diagnostic biomarker is required. Procalcitonin (PCT) has been well demonstrated to be specifically produced from peripheral tissues by bacterial infection, which makes it a potential diagnostic biomarker candidate. Here, we performed a prospective clinical study comprising a total of 143 patients to investigate the diagnostic value of CSF PCT, serum PCT, and other conventional biomarkers for BM. Patients were assigned to the BM (n = 49), tuberculous meningitis (TBM) (n = 25), viral meningitis/encephalitis (VM/E) (n = 34), autoimmune encephalitis (AIE) (n = 15), or noninflammatory nervous system diseases (NINSD) group (n = 20). Empirical antibiotic pretreatment was not an exclusion criterion. Our results show that the CSF PCT level was significantly (P < 0.01) higher in patients with BM (median, 0.22 ng/ml; range, 0.13 to 0.54 ng/ml) than in those with TBM (median, 0.12 ng/ml; range, 0.07 to 0.16 ng/ml), VM/E (median, 0.09 ng/ml; range, 0.07 to 0.11 ng/ml), AIE (median, 0.06 ng/ml; range, 0.05 to 0.10 ng/ml), or NINSD (median, 0.07 ng/ml; range, 0.06 to 0.08 ng/ml). Among the assessed biomarkers, CSF PCT exhibited the largest area under the receiver operating characteristic curve (0.881; 95% confidence interval, 0.810 to 0.932; cutoff value, 0.15 ng/ml; sensitivity, 69.39%; specificity, 91.49%). Our study sheds light upon the diagnostic dilemma of BM due to antibiotic abuse. (This study has been registered at ClinicalTrials.gov under registration no. NCT02278016.).

Diagnostic and prognostic value of procalcitonin for early intracranial infection after craniotomy

Intracranial infection is a common clinical complication after craniotomy. We aimed to explore the diagnostic and prognostic value of dynamic changing procalcitonin (PCT) in early intracranial infection after craniotomy. A prospective study was performed on 93 patients suspected of intracranial infection after craniotomy. Routine peripheral venous blood was collected on the day of admission, and C reactive protein (CRP) and PCT levels were measured. Cerebrospinal fluid (CSF) was collected for routine biochemical, PCT and culture assessment. Serum and CSF analysis continued on days 1, 2, 3, 5, 7, 9, and 11. The patients were divided into intracranial infection group and non-intracranial infection group; intracranial infection group was further divided into infection controlled group and infection uncontrolled group. Thirty-five patients were confirmed with intracranial infection after craniotomy according to the diagnostic criteria. The serum and cerebrospinal fluid PCT levels in the infected group were significantly higher than the non-infected group on day 1 (P<0.05, P<0.01). The area under curve of receiver operating characteristics was 0.803 for CSF PCT in diagnosing intracranial infection. The diagnostic sensitivity and specificity of CSF PCT was superior to other indicators. The serum and CSF PCT levels have potential value in the early diagnosis of intracranial infection after craniotomy. Since CSF PCT levels have higher sensitivity and specificity, dynamic changes in this parameter could be used for early detection of intracranial infection after craniotomy, combined with other biochemical indicators.

Procalcitonin in cerebrospinal fluid in meningitis: a prospective diagnostic study.

OBJECTIVES: Bacterial meningitis is a severe but treatable condition. Clinical symptoms may be ambiguous and current diagnostics lack sensitivity and specificity, complicating diagnosis. Procalcitonin (PCT) is a protein that is elevated in serum in bacterial infection. We aimed to assess the value of PCT in cerebrospinal fluid (CSF) in the diagnosis of bacterial meningitis. METHODS: We included patients with bacterial meningitis, both community acquired and post neurosurgery. We included two comparison groups: patients with viral meningitis and patients who underwent lumbar punctures for noninfectious indications. We calculated mean differences and 95% confidence intervals of procalcitonin in CSF and plasma in patients with and without bacterial meningitis. RESULTS: Average PCT concentrations in CSF were 0.60 ng mL-1 (95% CI: 0.29-0.92) in the bacterial meningitis group (n = 26), 0.81 (95% CI: 0.33-1.28) in community-acquired meningitis (n = 16) and 0.28 (95% CI: 0.10-0.45) in postneurosurgical meningitis (n = 10), 0.10 ng mL-1 (95% CI: 0.08-0.12) in the viral meningitis group (n = 14) and 0.08 ng mL-1 (95% CI: 0.06-0.09) in the noninfectious group (n = 14). Mean difference of PCT-CSF between patients with community-acquired bacterial meningitis and with viral meningitis was 0.71 ng mL-1 (95% CI: 0.17-1.25) and 0.73 ng mL-1 (95% CI: 0.19-1.27) for community-acquired bacterial meningitis versus the noninfectious group. The median PCT CSF: plasma ratio was 5.18 in postneurosurgical and 0.18 in community-acquired meningitis (IQR 4.69 vs. 0.28). CONCLUSION: Procalcitonin in CSF was significantly higher in patients with bacterial meningitis when compared with patients with viral or no meningitis. PCT in CSF may be a valuable marker in diagnosing bacterial meningitis, and could become especially useful in patients after neurosurgery.

[Neurological presentations of bacterial meningitis in children: current possibilities of diagnosis and treatment]. / Nevrologicheskie proyavleniya bakterial'nykh meningitov u detei: sovremennye vozmozhnosti diagnostiki i lecheniya.

AIM: To improve clinical/laboratory diagnosis of bacterial meningitis (BM) in children. MATERIAL AND METHODS: Fifty-seven patients, aged from 4 months to 12 years, with BM were examined. Bacteriological study of the mucus from the nasopharynx, sterility tests of blood and cerebrospinal fluid (CNF), clinical and biochemical tests, serological study of paired samples of plasma - indirect hemagglutination test, latex agglutination assay, immunological study of plasma and CNF with the determination of interferon -α, -ß and -γ, interferon procalcitonin and neopterin with ELISA were performed at admission and after CNF remediation. Molecular-genetic study of the blood serum and CNF using PCR, neurosonography, computed tomography and MRI of the brain were done as well. RESULTS AND CONCLUSION: Most of the patients had generalized meningococcus infection (64,9%). Hib-meningitis, pneumococcus meningitis and other forms were less frequent. Characteristics of neurological presentations of BM depending on the etiology, somatic complications and time from the manifestation of symptoms were described. Clinical/biochemical criteria of BM and correlations between procalcitonin, neopterin and interleukin-8 in the CNF and blood of the patients and disease severity as well as between the level of inflammatory reactions in the CNF and the BM form were established. These results are important for the development of informative biomarkers for the prognosis of BM course and outcome.

Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis.

OBJECTIVE: The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients. DESIGN: Prospective, open-label, observational, cohort study. SETTING: Neurosurgical ICU, Chang Gung Memorial Hospital. PATIENTS: Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis. INTERVENTION: Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1ß, interleukin-6, interleukin-8, transforming growth factor-ß, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques. MEASUREMENT AND MAIN RESULTS: Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1ß, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1ß, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever. CONCLUSION: The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1ß, and interleukin-8 in a temporal manner may indicate early bacterial meningitis development in neurosurgical patients, enabling earlier diagnostic certainty and improved patient outcomes.

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

OBJECTIVE: To compare the clinical utility of serum and cerebrospinal fluid (CSF) procalcitonin (PCT) for the diagnosis of bacterial meningitis (BM) among patients with suspected meningitis. METHODS: Patients 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. RESULTS: PCT 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. CONCLUSION: Both 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.

Can Procalcitonin in Cerebrospinal Fluid be a Diagnostic Tool for Meningitis?

BACKGROUND: To study the levels of procalcitonin (PCT) in patients with meningitis and control group and compare them with established markers of infection--such as C-reactive protein (CRP), high-sensitivity CRP, and WBC--in cerebrospinal fluid (CSF) and assess the possible discriminative role of PCT in the differential diagnosis of meningitis from other noninfectious diseases. METHODS: We studied CSF samples of patients from Intensive Care Unit, Internal Medicine, Neurology, Hematology, and Pediatric departments. The total number of patients included in the study was 58. The samples were divided into three groups: group 1 with bacterial meningitis (BM) central nervous system (n = 19); group 2 with viral meningitis (VM, n = 11); and group 3, control group, with noninfectious diseases (n = 28). RESULTS: Values of PCT levels >0.5 ng/ml were considered as abnormal. In group 1, mean PCT levels were 4.714 ± 1.59 ng/ml. In group 2, all patients had PCT <0.5 ng/ml (0.1327 ± 0.03 ng/ml). In group 3, the mean PCT levels were <0.1 ng/ml. CONCLUSION: PCT values in CSF can be very helpful in distinguishing BM from VM and other noninfectious diseases.

The diagnostic value of cerebrospinal fluids procalcitonin and lactate for the differential diagnosis of post-neurosurgical bacterial meningitis and aseptic meningitis.

OBJECTIVES: Distinguishing between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. This study aims to evaluate the combined diagnostic value of CSF procalcitonin and lactate as novel PNBM markers in hospitalized post-neurosurgery patients. DESIGN AND METHODS: This study was performed using CSF samples, collected by lumbar puncture, from 178 PNBM-suspected patients enrolled in a retrospective clinical study. The levels of CSF procalcitonin and lactate were appropriately assayed and the combined diagnostic value of these markers was assessed using receiver operating characteristic (ROC) curves, a two by two table, and non-parametric tests. RESULTS: Fifty of the 178 patients were diagnosed with PNBM, based on the clinical symptoms and laboratory results. These PNBM patients showed significantly elevated levels of CSF procalcitonin and CSF lactate compared with the non-PNBM group (p<0.001 for both). It was revealed that the cut-off values for the diagnosis of PNBM were: 0.075ng/mL (sensitivity, 68%; specificity, 73%) for procalcitonin and 3.45mmol/L (sensitivity, 90%; specificity, 85%) for lactate. A serial test combining the levels of these two markers showed decreased sensitivity (64%) and increased specificity (91%), compared with either marker alone. In contrast, a parallel test combining the levels of these both markers showed increased sensitivity (96%) and decreased specificity (65%), compared with either marker alone. CONCLUSION: Our study shows that the combined use of CSF procalcitonin and lactate can reliably distinguish between PNBM and non-PNBM and can be included in the design of diagnostic approaches to circumvent the shortcomings of conventional methods.

Analysis of synaptic proteins in the cerebrospinal fluid as a new tool in the study of inborn errors of neurotransmission.

In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiological and diagnostic purposes in investigation of inherited disorders of neurotransmission. Dopamine receptor type 2 (D2R), dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were analysed in CSF samples from 30 healthy controls (11 days to 17 years) by western blot analysis. Because VMAT2 was the only protein with intracellular localisation, and in order to compare results, GABA vesicular transporter, which is another intracellular protein, was also studied. Spearman's correlation and Student's t tests were applied to compare optical density signals between different proteins. All these synaptic proteins could be easily detected and quantified in the CSF. DAT, D2R and GABA VT expression decrease with age, particularly in the first months of life, reflecting the expected intense synaptic activity and neuronal circuitry formation. A statistically significant relationship was found between D2R and DAT expression, reinforcing the previous evidence of DAT regulation by D2R. To our knowledge, there are no previous studies on human CSF reporting a reliable analysis of these proteins. These kinds of studies could help elucidate new causes of disturbed dopaminergic and gabaergic transmission as well as understanding different responses to L-dopa in inherited disorders affecting dopamine metabolism. Moreover, this approach to synaptic activity in vivo can be extended to different groups of proteins and diseases.

Procalcitonin is elevated in the cerebrospinal fluid of patients with dementia and acute neuroinflammation.

Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis in blood. Here we measured PCT by immunoassay in CSF and matched serum/plasma samples of controls and patients with different primary dementia disorders and acute neuroinflammation. PCT in CSF was significantly increased in patients with probable Alzheimer's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and acute neuroinflammation (encephalitis, meningitis) compared to non-demented controls. In contrast, PCT levels in matched plasma samples were normal in dementia groups, but elevated in meningitis/encephalitis. Our results indicate a central production of PCT and suggest PCT as a valuable marker candidate for the monitoring of dementia and acute neuroinflammation.

Elevated procalcitonin as a diagnostic marker in meningococcal disease.

Patients with meningococcal disease who seek medical attention can create a diagnostic dilemma for clinicians due to the nonspecific nature of the disease's presentation. This study assesses the diagnostic accuracy of procalcitonin levels in the setting of meningococcal disease. Two emergency department cohorts (A and B) were studied between 2002 and 2005, during the current epidemic of serogroup B meningococcal disease in New Zealand. Cohort A consisted of 171 patients, all with confirmed meningococcal disease (84 children, 87 adults). Cohort B consisted of a large (n=1,524) consecutively recruited population of febrile patients who presented to the emergency department, 28 of whom had confirmed meningococcal disease. Within the meningococcal disease cohort (cohort A), the geometric mean procalcitonin level was 9.9 ng/ml, with levels being higher in children than in adults (21.6 vs. 4.6 ng/ml, p=0.01). The overall sensitivity of elevated procalcitonin, using a cutoff of 2.0 ng/ml in children and 0.5 ng/ml in adults, was 0.93 (95%CI: 0.88-0.96). Despite the higher cutoff level for paediatric patients, a trend towards greater sensitivity existed in children (0.96 vs. 0.90; p=0.08). Elevated procalcitonin was correlated with whole blood meningococcal load (r=0.50) and Glasgow Meningococcal Sepsis Prognostic Score (r=0.40). Within the cohort of patients who were febrile on presentation (cohort B), the specificity of elevated procalcitonin in meningococcal disease was 0.85 (95% CI: 0.83-0.87), the positive and negative likelihood ratios were 6.1 and 0.08, respectively, and the sensitivity of elevated procalcitonin (0.93; 95% CI: 0.76-0.99) was corroborated. Measurement of procalcitonin is a useful tool in patients with nonspecific febrile illnesses when the possibility of meningococcal disease is present. The diagnostic accuracy surpasses that of current early laboratory markers, allowing results to be used to guide decisions about patient management.