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YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis.

YKL-40, a member of the family 18 glycosyl hydrolases, is secreted by activated neutrophils and macrophages. It is a growth factor for connective tissue cells and a potent migration factor for endothelial cells and may function in inflammation and tissue remodeling. YKL-40 was determined in 134 cerebrospinal fluid (CSF) samples taken on admission from patients suspected of having meningitis (48 with purulent meningitis, 49 with lymphocytic meningitis, 5 with encephalitis, and 32 without evidence of meningitis). YKL-40 levels in CSF were significantly higher in patients with purulent meningitis (median, 663 microg/liter [range, 20 to 8,960]) and encephalitis (5,430 microg/liter [620 to 11,600]) than in patients with lymphocytic meningitis (137 microg/liter [41 to 1,865]) or patients without meningitis (167 microg/liter [24 to 630]) (Kruskal-Wallis and Dunn multiple comparison tests, P < 0.001). CSF YKL-40 levels were also determined for 26 patients with purulent meningitis having a repuncture, and patients who died (n = 5) had significantly higher YKL-40 levels than patients who survived (n = 21) (2,100 microg/liter [1,160 to 7,050] versus 885 microg/liter [192 to 15,400], respectively; Mann-Whitney test, P = 0.018). YKL-40 was most likely locally produced, since patients with infections of the central nervous system had CSF YKL-40 levels that were at least 10-fold higher than the corresponding levels in serum (2,033 microg/liter [470 to 11,600] versus 80 microg/liter [19 to 195]). The CSF neopterin level was the biochemical parameter in CSF and blood that correlated best with CSF YKL-40 levels, indicating that YKL-40 may be produced by activated macrophages within the central nervous system. In conclusion, high levels of YKL-40 in CSF are found in patients with purulent meningitis.

Adult↗

Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis.

OBJECTIVE: To evaluate incidence and risk factors of postoperative meningitis, with special emphasis on antibiotic prophylaxis, in a series of 6243 consecutive craniotomies. METHODS: Meningitis was individualized from a prospective surveillance database of surgical site infections after craniotomy. Ventriculitis related to external ventricular drainage or cerebrospinal fluid shunt were excluded. From May 1997 until March 1999, no antibiotic prophylaxis was prescribed for scheduled, clean, lasting less than 4 hours craniotomies, whereas emergency, clean-contaminated, or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. From April 1999 until December 2003, prophylaxis was given to every craniotomy. Independent risk factors for meningitis were studied by a multivariate analysis. Efficacy of antibiotic prophylaxis in preventing meningitis was studied as well as consequences on bacterial flora. RESULTS: The overall meningitis rate was 1.52%. Independent risk factors were cerebrospinal fluid leakage, concomitant incision infection, male sex, and surgical duration. Antibiotic prophylaxis reduced incision infections from 8.8% down to 4.6% (P < 0.0001) but did not prevent meningitis: 1.63% in patients without antibiotic prophylaxis and 1.50% in those who received prophylaxis. Bacteria responsible for meningitis were mainly noncutaneous in patients receiving antibiotics and cutaneous in patients without prophylaxis. In the former, microorganisms tended to be less susceptible to the prophylactic antibiotics administered. Mortality rate was higher in meningitis caused by noncutaneous bacteria as compared with those caused by cutaneous microorganisms. CONCLUSION: Perioperative antibiotic prophylaxis, although clearly effective for the prevention of incision infections, does not prevent meningitis and tends to select prophylaxis resistant microorganisms.

Adult↗

Cephalosporins in the treatment of meningitis.

The synthesis of new cephalosporin antibiotics has provided agents which can effectively be used to treat most of the different forms of meningitis. None of the first generation cephalosporins can be considered acceptable as agents to treat meningitis. Cefuroxime can be used to treat meningitis due to Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis in children. Agents such as cefotaxime and ceftriaxone are appropriate for neonatal meningitis due to Escherichia coli and group B streptococci, but not Listeria monocytogenes. Cefotaxime, ceftriaxone, ceftizoxime and ceftazidime have all proved effective as therapy of meningitis in children and adults when the pathogens are pneumococci, H. influenzae or N. meningitidis, but they have not been shown to yield an improved mortality or lower morbidity in spite of much greater cerebrospinal fluid (CSF) bactericidal titres. Cefotaxime, ceftizoxime, ceftriaxone and ceftazidime have been effective as therapy of meningitis due to E. coli, K. pneumoniae and Proteus species, but failures have occurred with all of the cephalosporins when used to treat meningitis due to Enterobacter spp. and Serratia marcescens. Only ceftazidime yields adequate CSF concentrations to treat meningitis due to Pseudomonas aeruginosa. Overall, the cephalosporins can now be considered a major component of the therapy of acute bacterial meningitis irrespective of the age group to be treated.

Animals↗

Treatment options for the pharmacological therapy of neonatal meningitis.

Neonatal bacterial meningitis has a relatively low incidence in developed countries, but continues to cause morbidity and mortality despite advances in antimicrobial therapy. Bacterial pathogens commonly associated with neonatal meningitis include Group B streptococci, Escherichia coli K1 and other coliforms, Listeria monocytogenes and staphylococci. As it can be difficult to differentiate meningitis from septicaemia in neonates, empirical antibiotic therapy should be effective for both. Selection of an empirical antibiotic regimen should be based on: (a) bacterial prevalence and susceptibility; (b) drug characteristics; (c) postnatal age at the onset of disease; and (d) patient-specific factors. A penicillin in combination with an aminoglycoside or cefotaxime is commonly used in empirical therapies. The increased risk of staphylococcal infection in older neonates requires consideration of an antistaphylococcal antibiotic in the empirical therapy regimen. Once a causative organism has been identified, antimicrobial therapy should be directed towards that pathogen. Duration of therapy remains empirical, but should be at least 7 days for documented bacterial meningitis. Viral meningitis continues to have a high mortality despite the availability of antiviral agents. Adjunctive therapies may further reduce the morbidity and mortality of meningitis. While most of these therapeutic options have not been investigated in neonates, they may prove to be of benefit in the future. Anti-inflammatory agents, such as glucocorticoids, nonsteroidal anti-inflammatory agents and immunoglobulin, may modulate the inflammatory response of a meningeal infection. Other possible therapies in neonatal meningitis include cerebral blood flow modulators and disease prevention with maternal vaccines and perinatal antibiotics. Practical aspects of drug therapy such as route of administration and serum drug concentration monitoring can improve both drug therapy and patient outcome. While antibiotics have greatly improved the treatment outcome of neonatal meningitis, it is clear that additional intervention will be required to increase cure rates and reduce sequelae.

Humans↗

Bacterial meningitis in children: critical review of current concepts.

Acute bacterial meningitis is still an important cause of morbidity and mortality in children worldwide. Recently, Haemophilus influenzae type b (Hib), once a common cause of meningitis, has virtually disappeared in developed nations, reflecting the overwhelming success of Hib vaccination. Unfortunately, Hib remains a significant pathogen in resource-poor countries. The introduction of the conjugated pneumococcal vaccine in 2000 may lead to similar future trends as witnessed with Hib. As the resistance of Streptococcus pneumoniae to penicillin and cephalosporins continues to evolve, vancomycin has become an important antibacterial in the treatment of bacterial meningitis. The unreliable penetration of this agent into cerebrospinal fluid is of concern, which is compounded by the controversial use of corticosteroids in paediatric meningitis. Some data suggest that in certain situations the addition of rifampicin (rifampin) to ceftriaxone may be a better choice. While dexamethasone is now considered the standard adjunctive therapy in the treatment of pneumococcal meningitis in adult patients, the benefit in children is not so clear and remains controversial; thus, there is no definitive paediatric recommendation. Several anti-inflammatory agents currently under investigation may be used in the future as adjunctive therapy for bacterial meningitis. It is clear that the current concepts in the treatment of childhood bacterial meningitis are evolving, and other antibacterial options and possible alternatives such as carbapenems and fluoroquinolones should be considered. Fluid restriction because of the Syndrome of Inappropriate Antidiuretic Hormone Secretion is widely advocated and used. Yet, this practice was recently challenged. It seems that most patients with meningitis do not need fluid restriction. The overwhelming success of the conjugated Hib vaccine and the encouraging results of the new conjugated pneumococcal and meningococcal vaccines suggest that the ideal management of bacterial meningitis is prevention and vaccines development against the most common bacterial agents are the best solution.

Child↗

IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis.

The fatality rate associated with Streptococcus pneumoniae meningitis remains high despite adequate antibiotic treatment. IL-1 is an important proinflammatory cytokine, which is up-regulated in brain tissue after the induction of meningitis. To determine the role of IL-1 in pneumococcal meningitis we induced meningitis by intranasal inoculation with 8 x 10(4) CFU of S. pneumoniae and 180 U of hyaluronidase in IL-1R type I gene-deficient (IL-1R(-/-)) mice and wild-type mice. Meningitis resulted in elevated IL-1alpha and IL-1beta mRNA and protein levels in the brain. The absence of an intact IL-1 signal was associated with a higher susceptibility to develop meningitis. Furthermore, the lack of IL-1 impaired bacterial clearance, as reflected by an increased number of CFU in cerebrospinal fluid of IL-1R(-/-) mice. The characteristic pleocytosis of meningitis was not significantly altered in IL-1R(-/-) mice, but meningitis was associated with lower brain levels of cytokines. The mortality was significantly higher and earlier in the course of the disease in IL-1R(-/-) mice. These results demonstrate that endogenous IL-1 is required for an adequate host defense in pneumococcal meningitis.

Animals↗

[Pneumococcal meningitis: epidemiological, clinical and bacteriological characteristics].

OBJECTIVE: To analyze the epidemiological and clinical features of pneumococcal meningitis. PATIENTS AND METHODS: We performed a retrospective study of 53 cases of pneumococcal meningitis that occurred in 47 pediatric patients in our hospital between 1977 and 2000. Four children had recurrent meningitis. In all patients Streptococcus pneumoniae was isolated from cerebrospinal fluid culture. The epidemiological, bacteriological and clinical characteristics were studied. RESULTS: Pneumococcal meningitis represented 6 % of bacterial meningitis in our environment with 2-3 cases registered per year. Seventy-two percent of cases occurred in winter and spring. The age of affected children was between 1 month and 13 years. Sixty-five percent of children older than 2 years had a predisposing disease. Penicillin-resistant strains were detected in 1990 and cefotaxime-resistant strains were isolated in 1994. Seven children (13 %) had severe neurological sequels and two (4 %) died. CONCLUSIONS: Pneumococcal meningitis produces higher morbidity and mortality than other types of bacterial meningitis. The disease usually affects children younger than 2 years and older children with a predisposing disease. In the last few years, the importance of pneumococcal meningitis has increased due to the lower incidence of other types of bacterial meningitis. Because of beta-lactam resistant strains, initial empirical treatment should include vancomycin. The above data suggest the advisability of the generalized use of heptavalent pneumococcal conjugate vaccine in the pediatric population in our environment.

Adolescent↗

Meningococcal meningitis outbreak control strategies.

Meningococcal meningitis has been occurring worldwide in both endemic and epidemic forms. Serogroup A accounts for majority of cases of epidemic as well as endemic Meningococcal meningitis in developing nations, whereas group C and group B causes epidemic and endemic meningococcal meningitis in developed countries. Person to person spread of N. meningitides generally occurs through inhalation of droplets of infected nasopharyngeal secretions by direct or indirect oral contact. Incubation period varies from 2 to 10 days. N. meningitides typically causes acute infective illness characterized by sequential development of upper respiratory tract infection, meningococcemia, meningitis and focal neurological deficit. Over 90 per cent cases of adult meningococcal infections have cerebrospinal meningitis, whereas in children prevalence of meningitis is much lower (50 per cent). Acute meningitis manifests with fever, severe headache, vomiting and neck stiffness. Presentations may be non-specific in infants, elderly and in patients with fulminant meningococcemia. Diagnosis is confirmed with cerebrospinal fluid analysis. Overall mortality due to meningitis is usually around 10 per cent. In meningococcal septicemia, the case fatality rate may exceed 50 per cent. Preventive strategies include vaccination, chemoprophylaxis and early detection and treatment. Mass vaccination campaign, if appropriately carried out, has been documented to halt an epidemic of meningococcal disease due to serogroup A or C. In the present review we have discussed the available evidence with regards to prevention at primary, secondary and tertiary level. Public health approach to an outbreak of meningococcal meningitis in a community or an organization is also outlined.

Disease Outbreaks↗

Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective, population-based surveillance study.

OBJECTIVE: To assess the incidence of meningitis caused by Haemophilus influenzae type b (Hib) among children in Bulgaria and to provide evidence for an informed decision on the use of Hib vaccines in Bulgaria. METHODS: From 1 July 1997 to 31 December 1999, active surveillance for meningitis was conducted in six regions. For children with suspected meningitis, a cerebrospinal fluid (CSF) specimen was sent for cytology, chemistry, latex agglutination testing, culture and sensitivity. FINDINGS: During the 2.5-year study period, surveillance was conducted among 138 249 children aged <5 years - a sample representing 40% of all Bulgarian children in this age group. Overall, 285 children with suspected meningitis were identified. In eight children, clinical symptoms of meningitis resolved rapidly before a CSF specimen could be obtained. Of the remaining 277 children, 121 (44%) were classified as having probable bacterial meningitis on the basis of a CSF examination. An organism was identified for 88 (73%) of the 121 cases with probable bacterial meningitis. There were 21 cases of Hib, giving a mean annual incidence of 6.1 Hib meningitis cases per 100 000 children <5 years; the case-fatality rate was 10%. Nearly 60% of Hib isolates were resistant to one or more antibiotics, but they were not resistant to third-generation cephalosporins. CONCLUSION: On the basis of these findings, Hib conjugate vaccines have been included in the list of vaccines recommended for children by the Bulgarian Ministry of Health. The recommended initial treatment for paediatric bacterial meningitis has been changed to third-generation cephalosporins.

Anti-Bacterial Agents↗

Cost-utility analysis of patient care in children with meningeal signs.

OBJECTIVES: We designed a model of diagnostic and therapeutic interventions applied in children with meningeal signs. Using this model, we determined in a cost-utility analysis the consequences for society of different diagnostic strategies in terms of quality-adjusted life-years (QALYs) and costs. METHODS: Data were used from 360 children (0.1-15 years) visiting the pediatric emergency department of the Sophia Children's Hospital Rotterdam, The Netherlands (1988-98) with meningeal signs. Model inputs included probabilities of meningitis and adverse outcome, QALYs for years lived with long-term sequelae, and costs of tests and treatments. Mean outcome measures were costs and effects of diagnostic and therapeutic interventions in children suspected of bacterial meningitis, key determinants of the model outcomes, and evaluation of alternative diagnostic strategies and two vaccination programs in an analysis. RESULTS: The population comprised 99 children with bacterial meningitis (adverse outcome in 10), 36 with serious other bacterial infections, and 225 with self-limiting diseases. Key determinants were the risk of bacterial meningitis or sequelae, costs of treatment, and long-term morbidity. Minimizing lumbar punctures and empirical treatments using a diagnostic decision rule, without missing a single case of meningitis, was a dominant strategy to actual practice. Vaccination strategies of Streptococcus pneumoniae and Neisseria meningitidis resulted in our model in incremental cost-utility ratios of 401,965 Euro dollar ([symbol: see text])/QALY and [symbol: see text]22,635/QALY, respectively. CONCLUSIONS: Costs of long-term morbidity of bacterial meningitis largely outweigh diagnostic and treatment costs. Modeling interventions in children at risk of bacterial meningitis should include long-term consequences in terms of costs and QALYs.

Child, Preschool↗

Epidemiology of Haemophilus influenzae type b meningitis in Taiwan, 1997 and 2000.

In order to determine the incidence of Haemophilus influenzae type b (Hib) meningitis in Taiwan, we analyzed the National Health Insurance Research Database (NHIRD). We identified cases that were younger than 5 years old and diagnosed with Hib meningitis from the NHIRD in both 1997 and 2000. Sixteen and 8 children with Hib meningitis were identified in the NHIRD for 1997 and 2000, respectively. The majority of cases were 2 years old and under. The overall fatality rate was 8.33%. Assuming similar proportions of Hib meningitis in cases of meningitis with identified causes and meningitis without identified causes, the annual incidence of Hib meningitis in children younger than 5 years old was estimated to be 5.57 and 3.22 per 100,000 in years 1997 and 2000, respectively. The incidence of Hib meningitis in Taiwan is lower than in western countries and other Asian countries. This is consistent with the notion that Hib meningitis incidence is low in Chinese populations. The decline in incidence from 1997 to 2000 is likely a result of the introduction of a self-paid Hib vaccine in Taiwan, starting in 1993. The availability of the NHIRD provides an extra tool for the epidemiological study of infectious diseases in Taiwan and can be valuable for similar studies.

Age Distribution↗

[Epidemiology of bacterial meningitis in France in 2002].

In France, two sources of data, the mandatory notification and the hospital laboratory network EPIBAC, allow the health authorities to monitor the incidence of bacterial meningitis. In 2002 around 1,500 cases were estimated in France. The more common microorganisms were: Streptococcus pneumoniae 49% (incidence 1.19/100,000), Neisseria meningitidis 33% (incidence 0.83) and Streptococcus agalactiae (Streptococcus B) 11% (incidence 0.27). Listeria monocytogenes accounted for 4% of the cases (incidence 0.11) and Haemophilus influenzae accounted for 3% (incidence 0.08). Trends in incidence showed an increase of meningococci meningitis since 1996, a steady decrease of H. influenzae and Listeria meningitis since 1992, and a quasi stable number of pneumococci meningitis, streptococci B meningitis and tuberculosis meningitis in the last 10 years. The impact of preventive measures on the incidence of Listeria meningitis and H. influenzae b meningitis has been clearly demonstrated through the dramatic decrease of meningitis due to these microorganisms.

Adolescent↗

[Recurrent aseptic meningitis secondary to taking ibuprofen and ketorolac].

INTRODUCTION: Aseptic meningitis is a process that is characterised by an inflammatory reaction of the meninges that is not due to any infectious agent. Its aetiology is varied and is most frequently caused by rheumatologic and/or autoimmune processes, chemical or medication-induced meningitis, the most notable drugs involved being antibiotics and non-steroidal anti-inflammatory drugs (NSAI). CASE REPORT: We report the case of a 70-year-old male, with no relevant history, who was admitted to hospital five times over a period of 16 months because of acute meningitis with polymorphonuclear pleocytosis, high protein levels in cerebrospinal fluid and normal glucose in cerebrospinal fluid. No evidence of an infectious causation, chemical meningitis, carcinomatosis or autoimmune disease was found and the patient was diagnosed with recurrent aseptic meningitis. It was found that the patient had taken ibuprofen or ketorolac on several occasions, a few hours before the appearance of symptoms. These episodes were quickly resolved after withdrawal of this medication. CONCLUSIONS: A number of NSAI have been reported as inducers of aseptic meningitis, one of the most notable being ibuprofen. We report the case of a patient who, as a consequence of taking ibuprofen and ketorolac, presented episodes of recurrent aseptic meningitis. To our knowledge this side effect of ketorolac has not been reported before. Its clinical features are impossible to differentiate from those of infectious meningitis. Diagnosis is reached by exclusion and a careful pharmacological study, including over-the-counter drugs like some of the NSAI, must be performed in patients with this condition, since it is a problem that can easily be solved by withdrawing the drug that causes it.

Aged↗

The use of the bromine partition test in the diagnosis and prognosis of tuberculous meningitis.

The bromine partition test was successfully used to differentiate cases of proven tuberculous meningitis from patients with aseptic and non-tuberculous meningitis. Forty patients, 22 males and 18 females aged 5 to 30 years (mean 13.5 +/- 6.2), were included in the study. Nineteen patients were confirmed to have tuberculous meningitis, 12 had aseptic meningitis, and 9 bacterial meningitis. All patients received 0.6 mci/kg of bromine 82 administered through a nasogastric tube as ammonium bromide dissolved in 5 ml of isotonic sodium chloride. The serum to CSF bromine ratio was then calculated 48 hours after the dose. The test was then repeated 8 days later in patients with bacterial meningitis and 8, 90, and 180 day later in patients with tuberculous meningitis. The test was very useful in quickly differentiating cases of aseptic from bacterial and tuberculous meningitis and was also a useful prognosticator in patients with severe tuberculous meningitis.

Adolescent↗

Prevention and treatment of meningeal leukemia in children.

The prevention of meningeal leukemia has long been a keystone in its cure. The need was recognized when it became apparent in the 1950s and 1960s that meningeal relapse heralded hematologic relapse and a fatal course and that its incidence increased as systemic chemotherapy became more effective in controlling hematologic and visceral leukemia. Evasion of a biologic safety net, the blood-CSF barrier, is required to prevent meningeal leukemia. Three methods are used: meningeal radiotherapy, intrathecal administration of antileukemia drugs, and high-dosage intravenous antileukemia drugs. Recent and current clinical studies reflect a continuing dialogue about which methods are preferable and under what circumstances. For prevention of meningeal leukemia, extended intrathecal therapy and intensive systemic chemotherapy appear to be as effective as radiotherapy for most patients. For treatment of overt meningeal leukemia, meningeal radiotherapy may be necessary. However, its administration compromises subsequent systemic chemotherapy so that delay may be advisable to allow intensive systemic chemotherapy for control of concurrent hematologic and visceral leukemia, whether clinically evident or not. For patients with meningeal leukemia at diagnosis, cranial irradiation may be delayed or possibly omitted if evidence of disease is minimal and intrathecal and systemic chemotherapy are intensive. For those who develop meningeal leukemia while on therapy or after its completion, cranial or craniospinal irradiation is probably required as well as intensive intrathecal and systemic chemotherapy. Hopefully, current and future studies will dispel the uncertainties and better quantitate risks and benefits of alternative methods. Whatever method is used, careful attention to technical details is required to assure optimal efficacy at the least possible expense in immediate toxicity and late sequelae.

Child↗

Can seizures be the sole manifestation of meningitis in febrile children?

OBJECTIVE: It is frequently taught that lumbar puncture is a mandatory procedure in many or all children who have fever and a seizure, because the convulsion may represent the sole manifestation of bacterial meningitis. We attempted to determine the incidence of this occult manifestation of meningitis. DESIGN: Retrospective case series. SETTING AND PATIENTS: 503 consecutive cases of meningitis in children aged 2 months to 15 years seen at two referral hospitals during a 20-year period. MAIN OUTCOME MEASURES: Signs and symptoms of meningitis in patients having associated seizures. RESULTS: Meningitis was associated with seizures in 115 cases (23%), and 105 of these children were either obtunded or comatose at their first visit with a physician after the seizure. The remaining 10 had relatively normal levels of consciousness and either were believed to have viral meningitis (2) or possessed straightforward indications for lumbar puncture: nuchal rigidity (6), prolonged focal seizure (1), or multiple seizures and a petechial rash (1). No cases of occult bacterial meningitis were found. CONCLUSION: In our review of 503 consecutive children with meningitis, none were noted to have bacterial meningitis manifesting solely as a simple seizure. We suspect that this previously described entity is either extremely rare or nonexistent. Commonly taught decision rules requiring lumbar puncture in children with fever and a seizure appear to be unnecessarily restrictive.

Adolescent↗

Embryonic and fetal development of structures associated with the cerebro-spinal fluid in man and other species. Part I: The ventricular system, meninges and choroid plexuses.

Little is known about the development of the central nervous system (CNS) in humans. Ethical considerations preclude experimental studies in this field, and as a result most available data on human ontogenesis are descriptive. Comparative anatomic and embryologic studies have demonstrated that the main developmental milestones are conserved across species, and their results can be used to suggest a likely scenario for human development. The development of the ventricles, meninges, and choroid plexuses are discussed in this article. The central cavity of the neural tube is formed during neurulation, which occurs during the fourth gestational week. The first milestone is occlusion of the spinal neurocele (the central canal in the neural tube) shortly after neurulation. This prevents free communication between the ventricular system and the amniotic cavity. The second milestone is development of the meninges, which separate the central nervous system from the rest of the body. The embryonic origin of the meninges varies across species. In birds (and probably in mammals), the spinal meninges are derived from the somitic mesoderm, the brainstem meninges from the cephalic mesoderm, and the telencephalic meninges from the neural crest. Differentiation of the meninges, which involves formation of the subarachnoid space, occurs early, before the cerebrospinal fluid (CSF) begins to flow around the CNS. During ontogenesis, the meninges play a key role in regulating the growth of underlying nervous structures. They induce the formation of the superficial glial limiting layer and stimulate the growth of precursors located in the superficial blastemas of the cerebellum and hippocampus. The choroid plexuses are complex specialized structures that produce most of the CSF. Their epithelium derives from the neural tube epithelium and their mesenchyma from the meninges. Of the many enzymes produced in the choroid plexuses, some reflect the pivotal metabolic role of these structures (alkaline and acid phosphatases, magnesium-dependent ATPase, glucose-6-phosphatase, thiamine pyrophosphatase, adenylate cyclase, oxidoreductase, esterases, hydrolases, cathepsin D, and glutathion S-transferase). The two enzymes that are crucial to the production of CSF are Na+/K+ ATPase and carbonic anhydrase. Inactivation of catecholamines is mediated by catechol-O-methyltransferase and by the monoamine oxidases A and B. The morphology and synthesis profile of the choroid plexuses changes during development, although little is known about these changes in humans.

Animals↗

TNF-alpha and IL-6 in the diagnosis of bacterial and aseptic meningitis in children.

The objective of this study was to analyze the usefulness of tumor necrosis factor-alpha and interleukin-6 cerebrospinal fluid concentrations for the differential diagnosis between bacterial and aseptic meningitis in children and in the prognostic evaluation. A cross-sectional study was performed on 35 children between 1 month and 12 years of age with suspected meningitis. Cytokines determination was performed by enzyme-linked immunosorbent assay technique. The Mann-Whitney test and Spearman's correlation coefficients were used for statistical analysis. Six children presented bacterial meningitis, 13 aseptic, and 16 had no meningitis. The tumor necrosis factor-alpha concentrations were significantly higher in the bacterial meningitis group as compared with the aseptic group (P = 0.001) and among groups with and without meningitis (P = 0.000). There was correlation between tumor necrosis factor-alpha and cerebrospinal fluid leukocytes (P = 0.019), protein (P = 0.000), and glucose (P = 0.038). There was no association between cytokines and complications of the meningitis. The tumor necrosis factor-alpha concentrations in the cerebrospinal fluid were useful markers for distinguishing bacterial from aseptic meningitis and were demonstrated to be useful in evaluating the intensity of the inflammatory process in the central nervous system.

Case-Control Studies↗