C-reactive protein as a predictor of meningitis in early onset neonatal sepsis: a single unit experience.

Objectives To determine whether there is a cut off value of serum C-reactive protein (CRP) associated with a higher risk of meningitis in suspected early onset sepsis (EOS) (onset birth to 7 days of life). Methods A retrospective cohort study on neonates admitted in neonatal intensive care unit at McMaster Children's Hospital from January 2010 to 2017 and had lumbar puncture (LP) and CRP for workup of EOS. Included subjects had either (a) non-traumatic LP or (b) traumatic LP with cerebral spinal fluid (CSF) polymerase chain reaction or gram stain or culture-positive or had received antimicrobials for 21 days. Excluded were CSF done for metabolic errors, before cytomegalovirus (CMV) treatment; from ventriculo-peritoneal (VP) shunts; missing data and contamination. Neonates were classified into definite and probable meningitis and on the range of CRP. We calculated sensitivity, specificity, and likelihood ratios for CRP values; and area under the receiver operating characteristic (AUROC) curve. Results Out of 609 CSF samples, 184 were eligible (28 cases of definite or probable meningitis and 156 controls). Sensitivity, specificity, predictive values, likelihood ratios, and AUROC were too low to be of clinical significance to predict meningitis in EOS. Conclusions Serum CRP values have poor discriminatory power to distinguish between subjects with and without meningitis, in symptomatic EOS.

Elevated Systemic IL-10 Levels Indicate Immunodepression Leading to Nosocomial Infections after Aneurysmal Subarachnoid Hemorrhage (SAH) in Patients.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a highly complex disease with very high mortality and morbidity. About one-third of SAH patients suffer from systemic infections, predominantly pneumonia, that can contribute to excess mortality after SAH. Immunodepression is probably the most important mechanism leading to infections. Interleukin-10 (IL-10) is a master regulator of immunodepression, but it is still not clear if systemic IL-10 levels contribute to immunodepression, occurrence of infections and clinical outcome after SAH. METHODS: This explorative study included 76 patients with SAH admitted to our neurointensive care unit within 24 h after ictus. A group of 24 patients without any known intracranial pathology were included as controls. Peripheral venous blood was withdrawn on day 1 and day 7 after SAH. Serum was isolated by centrifugation and stored at -80 °C until analysis. Serum IL-10 levels were determined by enzyme-linked immunoassay (ELISA). Patient characteristics, post-SAH complications and clinical outcome at discharge were retrieved from patients' record files. RESULTS: Serum IL-10 levels were significantly higher on day 1 and day 7 in SAH patients compared to controls. Serum IL-10 levels were significantly higher on day 7 in patients who developed any kind of infection, cerebral vasospasm (CVS) or chronic hydrocephalus. Serum IL-10 levels were significantly higher in SAH patients discharged with poor clinical outcome (modified Rankin Scale (mRS) 3-6 or Glasgow Outcome Scale (GOS) 1-3). CONCLUSION: Serum IL-10 might be an additional useful parameter along with other biomarkers to predict post-SAH infections.

A systematic review of cases of meningitis in the absence of cerebrospinal fluid pleocytosis on lumbar puncture.

BACKGROUND: Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF. Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject. METHODS: Ovid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values. RESULTS: A total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases. CONCLUSIONS: Meningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture.

Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis.

BACKGROUND: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. RESULTS: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. CONCLUSIONS: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.

Bilateral Peripheral Facial Paralysis Combined with HIV Meningitis During Acute HIV-1 Infection: A Case Report.

Here we reported a Chinese case of bilateral peripheral facial paralysis (PFP) in human immunodeficiency virusc (HIV) infected population. A 38-year-old homosexual male patient was referred to our hospital for bilateral facial paralysis. 21 days prior to admission he had developed high fever, chills, headache, fatigue, general malaise, nausea and vomiting. Neurological examination revealed bilateral ptosis of lower lip and cheeks, as well as failure of bilateral eyes closure. Analysis of cerebrospinal fluid (CSF) revealed pleocytosis, a marked rise of micro total protein and a marked rise of intrathecal lgG synthesis. The result of HIV-1 serology was positive by ELISA and that was confirmed by western blot. His CD4 + cell count was 180 cells/mm 3. HIV-1 viral load in CSF was almost 10 times higher than that in plasma. The patient's condition improved steadily and experienced complete resolution of bilateral PFP after 2 months.

DYNAMICS OF THE VEGETATIVE NERVOUS SYSTEM FUNCTIONAL STATE IN INTERACTION WITH THE CHANGES IN ADRENOCORTICOTROPIC AND SOMATOTROPIC HORMONES IN PATIENTS WITH SEROUS MENINGITIS.

The study included 64 patients with serous meningitis, in which the heart rate variability (HRV) spectrum, the content of ACTH and STH in serum was studied in the course of the commonly accepted treatment. The purpose of the study was to analyze the dynamics of indicators of functional state of the autonomic nervous system in correlation with changes of adrenocorticotropic and somatotropic hormones in patients with serous meningitis. According to the results, serous meningitis were predominantly moderate in severity, with generalization in the clinical picture dominated through general toxicosis, general cerebral and meningeal syndromes, but changes in the spectral parameters of HRV showed a marked imbalance with a shift in the functional activity of the autonomic nervous system towards vagotonia in combination with an ACTH level increase and STH decrease in serum (p<0.01). The purpose of the study was to analyze the dynamics of indicators of functional state of the autonomic nervous system in correlation with changes of adrenocorticotropic and somatotropic hormones in patients with serous meningitis. According to the results, serous meningitis were predominantly moderate in severity, with generalization in the clinical picture dominated by general toxicosis, general cerebral and meningeal syndromes, but changes in the spectral parameters of HRV showed a marked imbalance with a shift in the functional activity of the autonomic nervous system towards vagotonia in combination with an ACTH level increase and STH decrease in serum (p<0.01).

C-Reactive Protein (CRP) levels in neonatal meningitis in England: an analysis of national variations in CRP cut-offs for lumbar puncture.

BACKGROUND: Recent National Institute for Health and Care Excellence (NICE) CG149 guidelines suggest considering performing a lumbar puncture (LP) to investigate for meningitis in early-onset sepsis in a neonate when a C-reactive protein (CRP) level >10mg/L, but the evidence for this recommendation is poorly defined. METHODS: Data on trust-wide LP protocols, neonatal meningitis incidence, lumbar punctures, and CRP levels seen in cases of neonatal meningitis were asked of all 137 trusts in England that recorded a birth in 2017. Our local Kingston Hospital data on every LP performed was obtained to estimate the specificity of CRP rises. RESULTS: 73/123 (59.3%) of trusts follow the NICE CG149 recommendation of considering an LP if the CRP >10mg/L. The national incidence of neonatal meningitis was 0.467/1,000 births, and an LP was performed in 1.37% of all babies, which was significantly higher in trusts considering the CRP > 10mg/L cut-off. A CRP > 10mg/L cut-off sensitivity was 88.9% based on the highest CRP level 4 days around the LP from national data of 199 cases; specificity was 78.8% based on our single-unit analysis. CONCLUSIONS: Proposing a universal CRP > 10mg/L cut-off for a lumbar puncture has been counter-productive in England. Following it generates significantly more LPs, to the point that 40.7% of trusts have chosen not to follow it. It also has poor sensitivity missing over 11% of meningitis. We therefore do not recommend a universal cut-off, rather considering the whole clinical picture (including prematurity) when considering whether to do an LP.

Serum procalcitonin in bacterial & non-bacterial meningitis in children.

BACKGROUND: Bacterial meningitis is a paediatric emergency with high mortality and morbidity requiring prompt diagnosis and treatment. Clinically, it is often difficult to differentiate between bacterial and non-bacterial meningitis. Several studies have demonstrated the raised values of serum procalcitonin (PCT) in bacterial infections including meningitis but without definite cut-off guidelines. Hence, this study was done to evaluate serum PCT as a marker to differentiate bacterial and non-bacterial meningitis in children and assess its efficacy. METHODS: It was a cross-sectional study done over a period of 5 months (Aug 2016-Dec 2016) in the department of Paediatrics, B P Koirala Institute of Health Sciences (BPKIHS). Fifty children aged 3 months to 15 years with suspected meningitis were enrolled and investigated with relevant investigations like complete blood counts, and cerebrospinal fluid (CSF) analysis along with serum PCT. Patients were classified into bacterial (22) and non-bacterial meningitis (28) according to clinical & CSF findings and data analysed using SPSS software. RESULTS: Serum PCT levels were significantly higher in bacterial meningitis group (median = 2.04 (1.2-3.18) ng/ml) compared with non-bacterial meningitis (median = 0.35 (0.18-0.35) ng/ml); p < 0.001. The sensitivity and specificity of serum PCT in diagnosis of bacterial meningitis at cut-off level of 0.5 ng/ml were 95.45% and 84.61% respectively. Procalcitonin showed maximum area under receiver operating characteristics (ROC) curve 0.991 (0.974-1.00) (p < 0.001) compared to total leukocyte count and CSF cytochemistry. CONCLUSION: Serum PCT has high sensitivity and specificity for early diagnosis of bacterial meningitis in children. Hence it can be a useful adjunct in differentiating bacterial and non-bacterial meningitis for prompt and better management of the children.

C-reactive protein and immature-to-total neutrophil ratio have no utility in guiding lumbar puncture in suspected neonatal sepsis.

AIM: Meningitis may complicate neonatal sepsis, but there is scant evidence to inform the decision to perform a lumbar puncture (LP) and considerable variation in practice. We investigated whether inflammatory markers - C-reactive protein (CRP) and immature-to-total neutrophil ratio (ITR) - were predictive of meningitis or significant cerebrospinal fluid (CSF) pleocytosis and useful in guiding the decision to perform a LP. METHODS: We studied all inpatients in a single tertiary neonatal unit who were <6 months of age who had a LP performed between March 2011 and October 2014. We categorised CSF results as follows: (i) culture-positive meningitis; (ii) probable culture-negative meningitis but meeting a priori criteria for significant CSF leucocytosis; or (iii) no evidence of meningitis. CRP and ITR obtained within 48 h of LP were analysed. We assessed the test performance of CRP and ITR by area under receiver operating characteristic curves. RESULTS: A total of 757 (male 471, 62.2%) infants were included. The median (interquartile range) gestational age was 38.4 weeks (30-40.3), and birthweight was 2940 g (1330-3560). Ten (1.3%) infants had culture-positive meningitis; 71 (9.4%) were classified as probable culture-negative meningitis and 676 (89.3%) as non-meningitis. The area under receiver operating characteristic curve for culture-positive and probable culture-negative meningitis was 0.43 for CRP (95% confidence interval 0.36-0.51) and 0.58 for ITR (0.51-0.65). At a CRP threshold of 30 mg/L, there was a positive likelihood ratio (LR) of 0.77 and a negative LR of 1.44. CONCLUSIONS: CRP and ITR perform poorly in identifying infants with confirmed or probable meningitis. The decision to perform an LP should be more focused on clinical grounds and/or a positive blood culture and less on inflammatory or haematological markers in isolation.

Autochthonous Case of Eosinophilic Meningitis Caused by Angiostrongylus cantonensis, France, 2016.

We report a case of a 54-year-old Moroccan woman living in France diagnosed with eosinophilic meningitis caused by Angiostrongylus cantonensis. Diagnosis was based on clinical symptoms and confirmed by testing of serum and cerebrospinal fluid samples. Physicians should consider the risk for A. cantonensis infection outside of endemic areas.

Increased BAFF and APRIL levels in the cerebrospinal fluid of patients with anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis.

Hypertrophic pachymeningitis (HP) is an inflammatory disorder involving intracranial or spinal thickened dura mater. It has been recognized that anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis may lead to HP; however, the immune-mediated pathogenesis of ANCA-related HP (ANCA-HP) remains elusive. In the present study, we analyzed B-cell activation factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) expression in the cerebrospinal fluid (CSF) and serum of patients with ANCA-HP, multiple sclerosis (MS), and non-inflammatory neurological disorders (NIND). BAFF and APRIL levels in the CSF were significantly higher in patients with ANCA-HP than in those with MS and NIND. In addition, a positive correlation between BAFF levels in the CSF and IgG-index was found in patients with ANCA-HP. On the other hand, no correlation was detected between CSF and serum levels of BAFF or APRIL. The results suggest that increased levels of BAFF and APRIL produced in the central nervous system may influence the development of ANCA-HP.

Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection.

Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis of a complete reference genome and 81 draft sequences from clonal complex 180, the predominant serotype 3 clone in much of the world, found most sampled isolates belonged to a clade affected by few diversifying recombinations. However, other isolates indicate significant genetic variation has accumulated over the clonal complex's entire history. Two closely related genomes, one from the blood and another from the cerebrospinal fluid, were obtained from a patient with meningitis. The pair differed in their behaviour in a mouse model of disease and in their susceptibility to antimicrobials, with at least some of these changes attributable to a mutation that up-regulated the patAB efflux pump. This indicates clinically important phenotypic variation can accumulate rapidly through small alterations to the genotype.

Increased concentration of interferon lambda-3, interferon beta and interleukin-10 in the cerebrospinal fluid of patients with tick-borne encephalitis.

Tick-borne encephalitis (TBE) has a wide clinical spectrum, from asymptomatic to severe encephalitis, and host-dependent factors determining the outcome remain elusive. We have measured concentrations of pro-inflammatory/Th1 interferon-γ (IFNγ), immunomodulatory/Th2 interleukin-10 (IL-10), anti-viral type I (IFNß) and type III (IFNλ3) interferons in cerebrospinal fluid (csf) and serum of 18 TBE patients, simultaneously genotyped for polymorphisms associated with the expression of genes IFNL3 (coding IFNλ3), IL10, CD209 and CCR5. IL-10, IFNß and IFNλ3 were up-regulated in csf, with IFNλ3 level higher in patients with the milder clinical presentation (meningitis) than in meningoencephalitis. There was an increased serum IFNß and a tendency for increased serum IL-10 in meningitis patients. Genotype in rs12979860 locus upstream of IFNL3 was associated with IFNλ3 expression and in rs287886 (CD209) - IL-10 expression. IL-10, IFNß and IFNλ3 are expressed and play a protective role in TBE and their expression in TBE patients is associated with genetic polymorphisms.

Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody.

The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting TH1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.

Fibronectin changes in eosinophilic meningitis with blood-CSF barrier disruption.

Fibronectin, which is present at relatively low levels in healthy central nervous systems (CNS), shows increased levels in meningitis. In this study, fibronectin processing was correlated with the increased permeability of the blood-cerebrospinal fluid (CSF) barrier as well as with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. The immunohistochemistry results show matrix metalloproteinase-9 (MMP-9) is localized in the choroid plexus epithelium. Coimmunoprecipitation demonstrated fibronectin strongly binds MMP-9. Furthermore, treatment with the MMP-9 inhibitor GM6001 significantly inhibited fibronectin processing, reduced the blood-CSF barrier permeability, and decreased the eosinophil counts. The decreased fibronectin processing in CSF implies decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. Therefore, increased fibronectin processing may be associated with barrier disruption and participate in the extravasation and migration of eosinophils into the CNS during experimental parasitic infection.

Serological and molecular detection of Toscana and other Phleboviruses in patients and sandflies in Tunisia.

BACKGROUND: Our aim is to detect the infection by Toscana virus (TOSV) and other Phleboviruses in the sera and cerebro-spinal fluid (CSF) of patients with meningitis in Tunisia. We examined various species of phlebotomus present in Tunisia to determine whether or not a direct relationship exists between cases of meningitis and the viruses circulating in the insect vectors. METHODS: Patients with the meningeal syndrome were tested for anti-TOSV IgM and IgG using an indirect Enzyme-Linked Immunosorbent Assay (ELISA) and for the presence of TOSV and other Phleboviruses using a RT-PCR test. RESULTS: Of 263 patients were tested using ELISA of which 12.16% (n = 32/263) were IgM positive for anti TOSV. Of these 32 patients, 78% (n = 25/32) were IgG positive. 12.86% (n = 18/140) of the CSF samples tested by RT-PCR were positive for the Toscana virus. CONCLUSIONS: This study confirms, for the first time, that TOSV is involved in a neurological disorder in North Africa. The incidence of this involvement in Tunisia conforms with observations made in other Mediterranean countries. Moreover, for the first time, a molecular approach was used to detect SFSV in a Tunisian patient displaying neurological symptoms.

A mysterious back pain.

IgG4-related disease is a fibroinflammatory condition that affects many different organs. The common pathological findings of this disease include storiform fibrosis and dense infiltration of lymphocytes rich in IgG4-positive plasma cells. We herein presents the diagnosis and treatment of a case with a newly recognized condition - IgG4-related pachymeningitis.

Three-year follow-up of rheumatoid meningitis with matrix metalloprotease-9 levels in the serum and cerebrospinal fluid as indicators of disease activity: A case report.

Rheumatoid meningitis (RM) is an extra-articular complication of rheumatoid arthritis (RA). Although reports of RM sine arthritis exist, most patients with this presentation were diagnosed with RA within one year of RM onset. There are no established biomarkers reflecting the disease activity of RM. This case report highlights the elevation of matrix metalloprotease (MMP)-9 levels during the acute phase of RM and decline during remission. Additionally, this is the first case report of RA diagnosed three years after the onset of RM. It is important to further validate the utility of MMP-9 and conduct long-term follow-up of RM sine arthritis.

Interleukin-6, vascular endothelial growth factor and transforming growth factor beta 1 in canine steroid responsive meningitis-arteritis.

BACKGROUND: Steroid Responsive Meningitis-Arteritis (SRMA) is a common cause of inflammation of the canine central nervous system (CNS). To investigate if transforming growth factor beta 1 (TGF-ß1), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) are involved in the production of excessive immunoglobulin A (IgA), the induction of acute phase proteins and in the development of a systemic necrotizing vasculitis, characteristic of SRMA, these three signalling proteins were evaluated. RESULTS: Cerebrospinal fluid (CSF) and serum samples of dogs during the acute phase of SRMA (SRMA) were tested for IL-6, VEGF and TGF- ß1. Results were compared to those of dogs affected with SRMA during treatment (SRMA Th) and during relapse (SRMA R), to dogs with other meningoencephalomyelitides (ME), with miscellaneous non-inflammatory diseases of the CNS (CNS-Mix), with idiopathic epilepsy (IE), with systemic inflammatory diseases (Syst. Infl.) and with healthy dogs (Healthy). Concentrations of IL-6 and VEGF in CSF were significantly elevated in the SRMA group compared to the other disease categories (p<0.05). The CSF concentrations of TGF-ß1 were increased in SRMA group, but statistically significant differences were found only in comparison with Healthy and CNS-Mix groups. No differences were detected in the serum concentrations of TGF-ß1 between the different groups. In untreated SRMA patients, a positive correlation (rSpear = 0.3549; P=0.0337) between concentrations of TGF-ß1 and IgA concentration was found in CSF, while concentrations of IL-6 and VEGF in CSF positively correlated with the degree of pleocytosis (rSpear=0.8323; P<0.0001 and rSpear=0.5711; P=0.0166, respectively). CONCLUSIONS: Our results suggest that these three signalling proteins are biomarkers of disease activity in SRMA. VEGF might play an important role in the development of a systemic arteritis. TGF-ß1 is considered to be involved in the excessive IgA production, while IL-6 in the pleocytosis. The combined intrathecal increase of TGF-ß1 and IL-6 detected in SRMA could possibly force CD4 progenitors to differentiate towards the newly described Th17 lymphocyte subset and enhance the autoimmune response.

Expressions of brain-derived neurotrophic factor (BDNF) in cerebrospinal fluid and plasma of children with meningitis and encephalitis/encephalopathy.

Many reports in the field of childhood brain disorders have documented that brain-derived neurotrophic factor (BDNF) affects central nervous system (CNS) functions. In this clinical study, BDNF levels were evaluated in association with pediatric CNS infections. BDNF levels in the serum and cerebrospinal fluid (CSF) of 42 patients admitted during 5-year period, due to CNS infections, were measured by enzyme-linked immunosorbent assays (ELISAs). Control samples were collected from 108 patients with non-CNS infections (urinary tract infection, acute upper respiratory infection, acute gastroenteritis, etc.). Mean values of BDNF levels, at various ages, were determined and compared. BDNF levels were below the sensitivity of the ELISA in most CSF samples from the control group, but were significantly elevated in the patients with bacterial meningitis. The serum BDNF levels were elevated in all subgroups of patients with CNS infections, and the elevation was particularly notable in those with bacterial meningitis. BDNF expression in the CSF was correlated with CSF interleukin (IL)-6 levels as well as with blood platelet counts and neurological prognoses in those with bacterial meningitis. No correlation was found between BDNF levels and serum leukocyte numbers or C-reactive protein (CRP) levels. BDNF levels were found to be elevated in the serum and CSF of pediatric patients with CNS infections, particularly those with bacterial meningitis. Monitoring the changes in serum and CSF levels of BDNF may facilitate the diagnosis of acute meningitis and acute encephalopathy and allow the differential diagnosis of specific CNS infections.