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PubMed1986

Cerebrospinal fluid C-reactive protein in meningitis: diagnostic value and pathophysiology.

We examined the diagnostic value of C-reactive protein (CRP) in cerebrospinal fluid (CSF) on initial lumbar puncture in a prospective study including 126 patients (30 neonates, 96 infants and children) suspected of having meningitis. Twenty patients were considered to have bacterial and 25 were considered to have viral meningitis. In infants and children, a retrospectively chosen cut-off CRP titre of 4 (i.e. approximately equal to 0.4 mg/l CRP) had a sensitivity of 100% and a specificity of 94% for differentiating bacterial meningitis from both viral meningitis and normal. It was a more sensitive and selective test for differentiating bacterial from viral meningitis on initial CSF examination than was the CSF leucocyte count, glucose concentration or protein concentration. In neonates, no such cut-off CRP titre could be found, presumably due to the immaturity of the blood-CSF-barrier (B1-CSF-B) during the first weeks of life. In a parallel study including a non-selected group of 13 infants and children (4 without, 9 with bacterial meningitis), the serum/CSF CRP concentration ratios were determined and inserted in the individual B1-CSF-B diagrams according to Felgenhauer. The results were fully consistent with the hypothesis that the CRP concentration in CSF reflects the normal permeability characteristics of the B1-CSF-B, or the degree of its impairment. Based on our results, we recommend the CSF CRP estimation in the routine evaluation of infants and children suspected of having meningitis.

Adolescent↗
PubMed1996

Interleukin-8 in cerebrospinal fluid from patients with septic and aseptic meningitis.

Using a monoclonal antibody enzyme immunoassay, the concentration of interleukin-8 (IL-8) in cerebrospinal fluid (CSF) from 52 patients suspected of having meningitis was studied. The CSF IL-8 concentration was significantly higher in septic meningitis of known and unknown etiology than in aseptic meningitis and significantly higher in aseptic meningitis than in patients without meningitis. The CSF levels of IL-8 correlated with the levels of tumor necrosis factor-alpha, leukocyte count, neutrophil count, protein level, CSF/blood glucose ratio, and the number of days patients were hospitalized. The IL-8 values used to distinguish septic from aseptic meningitis, at a cut-off point of 3.00 micrograms/l, showed a sensitivity of 81%, a specificity of 92%, and a positive predictive value of 96%. The results suggest that determining IL-8 levels may be useful in the differential diagnosis of meningitis.

Adolescent↗
PubMed2003

The diagnostic difficulties of meningeal and intracerebral plasma cell granulomas--presentation of three cases.

Meningeal and intracerebral plasma cell granulomas are uncommon inflammatory lesions of unknown etiology. In this paper the diagnostic difficulties in two patients with meningeal plasma cell granuloma and one patient with intracerebral plasma cell granuloma are described. The first patient had an intracranial extra-axial lesion, which was first diagnosed as a meningioma. One and a half years later she underwent a second resection for recurrent tumor growth and the diagnosis of a meningeal plasma cell granuloma was made. The second patient was treated for a central nervous system B-cell lymphoma but proved to have an intracerebral plasma cell granuloma in retrospect 11 years later. In the third patient tuberculous meningitis was considered to be the most likely diagnosis because infratentorial contrast-enhanced thickened meninges (pachymeningitis) were found together with a high protein level in the cerebrospinal fluid and a positive Mantoux test. However, pathological examination of an extra-axial, cervical lesion that was operated upon revealed a meningeal plasma cell granuloma. These cases show the importance of diagnosing a meningeal or intracerebral plasma cell granuloma correctly, since it has both therapeutical and prognostic implications.

Adult↗
PubMed1996

Pharmacological characterization of nitric oxide production in a rat model of meningitis.

Depending on its concentration and target site, nitric oxide (NO) is an intracellular messenger or inflammatory mediator. Recent research supports an expanded role for NO in the pathophysiology of neuroinflammatory diseases. Using analytical and pharmacological techniques, the present study identifies NO as a potential inflammatory mediator in experimental meningitis in the rat. Intracisternal administration of lipopolysaccharide (LPS) induced NO synthesis from the lateral and third ventricle choroid plexi and surface meninges but not from systemic white blood cells, suggesting that meningeal inflammation was restricted to the central nervous system. The time course of NO production revealed at 3 hr lag after intracisternal LPS, followed by a peak of 8 hr and subsequent decrease to baseline 24 hr after LPS dosing. The pharmacological rank order of NO synthase inhibitors in meningeal preparations (NG-aminoarginine > NG-methylarginine approximately aminoguanidine) was slightly different than the rank order for the LPS-stimulated monocyte-macrophage cell line, J774A.1 (NG-aminoarginine approximately NG-methylarginine > aminoguanidine). A prolonged inhibition of NO production was observed in cultured meningeal preparations or J774A.1 cells briefly exposed to and washed free from NO synthase inhibitors. These findings implicate NO as an inflammatory mediator during experimental meningitis, and suggest that NO synthase inhibitors might be potentially useful agents for meningeal inflammation.

Animals↗
PubMedDate not supplied

Carcinomatous meningitis arising from primary nasopharyngeal carcinoma.

Carcinomatous meningitis, also known as leptomeningeal metastasis and meningeal carcinomatosis, is the invasion of neoplastic cells into the leptomeninges. Head and neck cancers, especially nasopharyngeal carcinoma, give rise to carcinomatous meningitis very infrequently. In this case report, we present a rare case of carcinomatous meningitis with nasopharyngeal carcinoma as the primary source. In 1987, a 45-year-old white female presented with a few year history of chronic bilateral serous otitis media. She also complained of intermittent diplopia, right facial pain, right-sided headache, and, finally, right facial palsy. The patient was subsequently diagnosed with nasopharyngeal carcinoma by biopsy and treated with radiation as well as chemotherapy. Her neurological symptoms improved, and she did fairly well for several years. However, various neurologic symptoms started to recur, including right facial weakness, right facial numbness in the distribution of all 3 divisions of cranial nerve (CN) V, loss of taste as well as smell, and diplopia. In 1993, magnetic resonance imaging scan of the head revealed recurrence of nasopharyngeal carcinoma with involvement of the ethmoid sinuses as well as extension of the tumor into the frontotemporal leptomeninges. Over the course of the next 3 years, the patient experienced a very gradual decline with involvement of almost all of the CNs (CN I, II, III, V, VI, VII, VIII, IX, X, XII). This case report of carcinomatous meningitis from primary nasopharyngeal carcinoma is one of the few reported in the literature. Although very rare, nasopharyngeal carcinoma can give rise to carcinomatous meningitis, probably by direct invasion of malignant cells. We also review the literature with respect to the diagnosis and treatment of carcinomatosis meningitis.

Adult↗
PubMed2005

Marked elevation of cerebrospinal fluid white blood cell count: an unusual case of Streptococcus pneumoniae meningitis, differential diagnosis, and a brief review of current epidemiology and treatment recommendations.

The diagnosis of bacterial meningitis is rarely a difficult diagnostic dilemma when a patient presents with fever, headache, neck stiffness, and altered mental status. Unfortunately for the practicing clinician, patients are rarely that straightforward. Patients who are elderly, very young, or immuno-compromised often present with subtle findings, making the correct diagnosis a challenge. In addition, patients being treated with antibiotics may be misleading in their clinical presentation, leading to a missed diagnosis of meningitis. Only when one considers the diagnosis or obtains a sample of cerebrospinal fluid is the correct diagnosis made. Although the clinical scenario may suggest meningitis, it is the cerebrospinal fluid white blood cell count that establishes the definitive diagnosis. Despite the advent of systemic antibiotics over 50 years ago, bacterial meningitis continues to cause considerable morbidity and mortality worldwide. The following case report details a woman diagnosed with Streptococcus pneumoniae meningitis with an extremely high cerebrospinal white blood cell count. Although this is typically thought to be caused by abscesses or malignancy, meningitis alone may cause such an elevation. In addition, a brief review of the current epidemiology and treatment regimens for meningitis is discussed.

Abscess↗
PubMed2004

Persistent increase of matrix metalloproteinases in cerebrospinal fluid of tuberculous meningitis.

Matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by gelatin zymography and an enzyme-linked immunosorbent assay (ELISA) in a cerebrospinal fluid (CSF) from patients with tuberculous meningitis (n=24), acute aseptic meningitis (n=23) and the control (n=10). The MMP-2 and MMP-9 levels were significantly higher in the samples from the tuberculous meningitis patients than those from either the aseptic meningitis patients or the controls. In tuberculous meningitis, the patients with late neurologic complications had higher MMP-2 and MMP-9 levels than those without. The persistent increase in the MMP-2 and MMP-9 levels was associated with the development of complications following tuberculous meningitis. Inhibiting the MMPs may be an effective strategy for preventing or reducing the complications in tuberculous meningitis.

Electrophoresis, Polyacrylamide Gel↗
PubMed1998

The neurochemical markers in cerebrospinal fluid to differentiate between aseptic and tuberculous meningitis.

In this study, the use of neurochemical markers in patients with aseptic and tuberculous meningitis has been investigated. The cerebrospinal fluid levels of amino acids, nitrite (a metabolite of nitric oxide), vitamin B12 and homocysteine were quantitated in both groups of patients. Among the amino acids, aspartic acid and glutamic acid both excitatory amino acid, GABA, glycine and tryptophan were all significantly increased in both patient groups whereas decreased level of taurine and increased level of phenylalanine were only found in patients with tuberculous meningitis. The levels of nitrite and its precursor arginine were significantly higher in patients with tuberculous meningitis whereas unchanged levels were found in patients with aseptic meningitis. A significantly increased homocysteine level and a decreased level of vitamin B12 were found only in patients with tuberculous meningitis whereas unchanged levels were found in patients with aseptic meningitis. This indicates that patients with tuberculous meningitis are particularly prone to vitamin B12 deficiency resulting into increased level of HC, and involvement of free radical showing the importance of these biological markers for promoting the possibility for the design of therapeutic approach.

Adult↗
PubMed1998

Chemokine profiles in the cerebrospinal fluid (CSF) during the course of pyogenic and tuberculous meningitis.

The concentrations of the chemokines IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) were measured in 120 CSF samples from 23 patients with pyogenic meningitis and from 11 patients with tuberculous meningitis (TBM) and in 10 CSF from subjects with non-infectious neurological diseases. The chemokine concentrations in patients with meningitis were significantly higher than in control subjects (P<0.0001). The highest CSF levels were found for IL-8 (median 2917 pg/ml) and MCP-1 (median 2557 pg/ml), whereas those of MIP-1alpha were less significantly elevated (median 24 pg/ml) (P<0.0001). Patients with pyogenic meningitis had higher levels of IL-8 and MCP-1 than those with TBM (P<0.0001). In serial samples from patients with pyogenic meningitis IL-8 levels declined before MCP-1 and MIP-alpha. In the case of TBM, IL-8, MCP-1 and MIP-1alpha decreased more gradually during treatment and were detectable in the CSF for several weeks, without any characteristic time course of elimination. These data indicate that patients with pyogenic meningitis and TBM show different chemokine profiles in CSF. The distinct chemokine pattern could be responsible for a differential attraction and activation of leucocytes in the CSF which is reflected in differences in the inflammatory response and clinical course of pyogenic meningitis and TBM.

Adult↗
PubMed1999

Pneumococcal and Haemophilus influenzae meningitis in a children's hospital in Ethiopia: serotypes and susceptibility patterns.

Streptococcus pneumoniae and Haemophilus influenzae are responsible for most pyogenic meningitis cases in children in Ethiopia. Resistance of S. pneumoniae and H. influenzae to penicillin and chloramphenicol respectively has been reported globally. Resistance has been related to specific serotypes of S. pneumoniae or to beta-lactamase-producing H. influenzae strains. This study describes the serotypes/ serogroups and susceptibility pattern of the two organisms causing meningitis in Ethiopian children. There were 120 cases of meningitis caused by S. pneumoniae (46) and H. influenzae (74) over a period of 3 years (1993-95). Nineteen children died from pneumococcal and 28 from haemophilus meningitis. Penicillin-resistant pneumococcal meningitis (4/8 = 50%) caused a greater mortality rate than penicillin-susceptible pneumococcal meningitis (15/38 = 39%). Common serotypes accounting for 76% of S. pneumoniae were type 14, 19F, 20, 1, 18 and 5; and serotypes 14, 19F and 7 (accounting for 17% of strains) showed intermediate resistance to penicillin G. 97% of the H. influenzae isolates were type b, and in only two cases beta-lactamase-producing. 72% of isolates of the S. pneumoniae we identified belong to serotypes preventable by a 9-valent vaccine. Our study highlights the possibility of resistant pyogenic meningitis in children in Ethiopia due to emerging resistant strains of S. pneumoniae and H. influenzae isolates.

Anti-Bacterial Agents↗
PubMed2001

D- and L-lactate in rabbit and human bacterial meningitis.

Increased total CSF lactate is an important indicator differentiating bacterial from aseptic meningitis. Bacteria can produce D- and L-lactate; mammalian cells produce only L-lactate. We measured D- and L-lactate production of Streptococcus pneumoniae, Staphylococcus aureus, Neisseria meningitidis and Escherichia coli in vitro, of S. pneumoniae and E. coli in rabbit experimental meningitis and of various common pathogens in CSF from patients with bacterial meningitis. Despite marked in vitro production of D-lactate by S. aureus (maximum: 4.59 mmol/l; i.e. 34.9% of total lactate), N. meningitidis (4.62 mmol/l; i.e. 98.1%) and E. coli (3.14 mmol/l; i.e. 97.2%), minimal amounts were measured in human S. aureus (0.38 mmol/l; i.e. 1.3% of total lactate) or N. meningitidis (0.28 mmol/l; i.e. 3.9%) and experimental E. coli meningitis (0.75 mmol/l; i.e. 4.4%). In only 9 of 54 human CSF samples did D-lactate exceed 0.15 mmol/l. S. pneumoniae did not produce significant amounts of D-lactate in vitro (maximum: 0.55 mmol/l; i.e. 2.7% of total lactate), in experimental meningitis (0.18 mmol/l; i.e. 3%) or in human cases of meningitis (0.28 mmol/l; i.e. 1.9%). In conclusion, increased total CSF lactate in meningitis consists mainly of L-lactate and originates predominantly from host cells. CSF D-lactate is of limited diagnostic value.

Animals↗
PubMed2002

The changing epidemiology of bacterial meningitis and invasive non-meningitic bacterial disease in scotland during the period 1983-99.

We reviewed population-based laboratory reports of invasive meningococcal, pneumococcal, Haemophilus influenzae, Group B Streptococcus (GBS) and Listeria monocytogenes isolates in order to examine the changing epidemiology of meningitis and invasive non-meningitic disease (INMD) caused by these 5 pathogens in the 2 periods before (1983-91) and after (1992-99) routine use of H. influenzae type B conjugate vaccine (Hib) in Scotland. Neissieria meningitidis was the most common cause of meningitis, accounting for 39.2% of cases of meningitis in 1983-91 and 47% of cases in 1992-99, followed by H. influenzae (31%), Streptococcus pneumoniae (22.4%), GBS (3.9%) and L. monocytogenes (3.5%) in 1983-91 and S. pneumoniae (36.3%), H. influenzae (7.8%), GBS (6.1%) and L. monocytogenes (2.8%) in 1992-99. The important epidemiological features of meningitis and INMD caused by these 5 pathogens between 1983-91 and 1992-99 include: 1. The incidence of bacterial meningitis due to S. pneumoniae and GBS was stable; 2. S. pneumoniae was the predominant cause of INMD in both periods; 3. The incidences of INMD caused by N. meningitidis, GBS and S. pneumoniae increased, by 27%, 55% and 56%, respectively; 4. Decreases in the incidences of bacterial meningitis (by 50%) and INMD (by 50%) due to L. monocytogenes were detected; and 5. There were dramatic reductions in the proportions of bacterial meningitis (by 92%) and INMD (by 56%) due to H. influenzae in vaccinated and non-vaccinated individuals. Continued surveillance is necessary to monitor the disease trend, population at risk, serotype distribution and antimicrobial susceptibility in order to implement appropriate public health interventions against invasive bacterial disease.

Adolescent↗
PubMed2004

Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis.

AIMS: To determine the level of serum procalcitonin and cerebrospinal fluid cytokines in children with bacterial or viral meningitis and to document the use of these parameters in differential diagnosis. RESULTS: Before the start of antibiotic treatment, serum procalcitonin and tumor necrosis factor alpha levels were found to be higher in acute bacterial meningitis compared with viral meningitis and with the control group. Similarly, cerebrospinal fluid interleukin-6 levels were found to be significantly higher in children with acute bacterial meningitis compared with viral meningitis. However, no significant difference was determined between groups in respect to the cerebrospinal fluid interleukin-8 level. CONCLUSION: Serum procalcitonin and cerebrospinal fluid tumor necrosis factor alpha levels can be used in the early diagnosis of bacterial meningitis. Similarly, they may be useful adjuncts in differential diagnosis of bacterial and viral meningitis.

Calcitonin↗
PubMed2001

Characterization of chemical meningitis after neurological surgery.

We reviewed the records of 70 consecutive adult patients with meningitis after a neurosurgical procedure, to determine the characteristics that might help to distinguish a sterile postoperative chemical meningitis from bacterial infection. The spinal fluid profiles in bacterial and chemical meningitis are similar. The exceptions are that a spinal fluid white blood cell count > 7500/microL (7500 x 10(6)/L) and a glucose level of < 10 mg/dL were not found in any case of chemical meningitis. The clinical setting and clinical manifestations were distinct enough that no antibiotic was administered after lumbar puncture to 30 (43%) of the 70 patients with postoperative meningitis. Chemical meningitis was infrequent after surgery involving the spine and sinuses. Patients with chemical meningitis did not have purulent wound drainage or significant wound erythema or tenderness, coma, new focal neurological findings, or onset of a new seizure disorder. They rarely had temperatures > 39.4 degrees C or cerebrospinal fluid rhinorrhea or otorrhea.

Adult↗
PubMed2004

Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) blocks activation of caspase-3, reduces translocation of apoptosis-inducing factor (AIF), attenuates excitotoxicity of glutamate, and increases antioxidant enzyme activities. The mechanisms of neuroprotection suggest that BDNF may be beneficial in bacterial meningitis. METHODS: To assess a potentially beneficial effect of adjuvant treatment with BDNF in bacterial meningitis, 11-day-old infant rats with experimental meningitis due to Streptococcus pneumoniae or group B streptococci (GBS) were randomly assigned to receive intracisternal injections with either BDNF (3 mg/kg) or equal volumes (10 mu L) of saline. Twenty-two hours after infection, brains were analyzed, by histomorphometrical examination, for the extent of cortical and hippocampal neuronal injury. RESULTS: Compared with treatment with saline, treatment with BDNF significantly reduced the extent of 3 distinct forms of brain cell injury in this disease model: cortical necrosis in meningitis due to GBS (median, 0.0% [range, 0.0%-33.7%] vs. 21.3% [range, 0.0%-55.3%]; P<.03), caspase-3-dependent cell death in meningitis due to S. pneumoniae (median score, 0.33 [range, 0.0-1.0] vs. 1.10 [0.10-1.56]; P<.05), and caspase-3-independent hippocampal cell death in meningitis due to GBS (median score, 0 [range, 0-2] vs. 0.88 [range, 0-3.25]; P<.02). The last form of injury was associated with nuclear translocation of AIF. CONCLUSION: BDNF efficiently reduces multiple forms of neuronal injury in bacterial meningitis and may hold promise as adjunctive therapy for this disease.

Animals↗
PubMedDate not supplied

Role of fluid-attenuated inversion recovery in the diagnosis of meningitis: comparison with contrast-enhanced magnetic resonance imaging.

OBJECTIVE: Fluid-attenuated inversion recovery (FLAIR) has shown promise in the detection of subarachnoid space disease. The exact role of FLAIR in the diagnosis of meningitis has not been established. The purpose of this study was to evaluate FLAIR in the detection of meningitis in comparison with contrast-enhanced T1-weighted images (T1WI) in a blinded-reader study. We describe hyperintense sulci (HS) on FLAIR sequence in meningitis in relation to cerebrospinal fluid (CSF) protein and effective echo time (TE). METHODS: Two observers blinded to clinical information reviewed magnetic resonance (MR) images of patients with the diagnosis of meningitis and those of age-matched controls. The diagnosis was confirmed from chart review and CSF results. FLAIR images were obtained with 2 different TE values of 120 milliseconds and 150 milliseconds. FLAIR changes were correlated with CSF protein concentration and contrast-enhanced T1WI. RESULTS: Twenty-eight MR images of meningitis patients were reviewed. There were 23 abnormal MR images including 16 abnormal FLAIR scans with hyperintense sulci and 23 with leptomeningeal enhancement on contrast-enhanced T1WI. HS on FLAIR correlated with leptomeningeal enhancement on contrast-enhanced T1WI. Four viral and 1 bacterial meningitis had normal MR images (FLAIR and postcontrast TIWI). Two different TE values were used: 120 milliseconds (n = 15) and 150 milliseconds (n = 13). All patients with effective TE of 150 milliseconds. and CSF protein of more than 132 mg/dL had hyperintense sulci whereas patients with effective TE of 120 milliseconds and CSF protein of 257 mg/dL or more had HS. CONCLUSIONS: The sensitivity of contrast-enhanced T1WI was higher than FLAIR. HS on FLAIR correlated with contrast enhancement on T1WI. However, the sensitivity of FLAIR depends on CSF protein concentration threshold for (CSF hyperintensity) for a given effective TE. FLAIR cannot replace contrast-enhanced T1WI in diagnosing meningitis.

Adolescent↗
PubMed2001

Sinusitis complicated by meningitis: current management.

OBJECTIVES: Meningitis is the most common intracranial complication of sinusitis. We review the incidence, current management, outcomes, and complications of this serious infection. Our study also examines the evolving roles of endoscopic sinus surgery and other new therapeutic and diagnostic modalities in our armamentarium. STUDY DESIGN: A retrospective chart review was performed at a tertiary academic medical center of all patients diagnosed with sinusitis with complications between January 1985 and December 1999. METHODS: The patients were divided into two main groups: intracranial versus orbital complications. Meningitis was the most common intracranial complication. Data on patients with sinusitis and meningitis were collected and analyzed. RESULTS: Intracranial complications were present in 39 of 82 patients whereas orbital complications were noted in 43 patients. Twenty-one of the 39 intracranial complications were meningitis. The most common computed tomography finding in adults (54%) was sphenoid sinusitis. All patients with AIDS (6 of 21) had unique cryptococcus meningitis. In patients without AIDS, the most common organism was Streptococcus pneumoniae (10 of 21). The most common sequela was seizure disorder (4 of 21). Endoscopic sinus surgery was performed on 7 of 21 patients. One patient with AIDS who had sinusitis and meningitis died. CONCLUSIONS: Meningitis as a complication of sinusitis may still pose a serious threat. Although outcomes are encouraging, sequelae such as seizure disorders and hearing loss are common complications. The introduction of high-resolution computed tomography scans and magnetic resonance imaging and the availability of wide-spectrum antibiotics have improved our management significantly.

Adolescent↗
PubMed1991

A prefecture-wide survey of mumps meningitis associated with measles, mumps and rubella vaccine.

A survey of untoward reactions, especially central nervous system reactions, after the administration of a newly introduced measles, mumps and rubella (MMR) vaccine in Gunma Prefecture, Japan, was initiated soon after 4 patients were hospitalized for aseptic meningitis. Thirty-five, 6 and 2 children developed meningitis, convulsive disorders and parotitis, respectively, within 2 months after MMR vaccination during the 8-month period extending from April to November, 1989. The time lag between MMR vaccination and meningitis ranged from 14 to 28 days in the 35 cases of meningitis. Mumps virus, isolated from the cerebrospinal fluid in 13 patients with aseptic meningitis, was characterized by determination of the nucleotide sequences of the P gene as mumps vaccine strain. The incidence of aseptic meningitis with positive mumps vaccine virus was estimated to be 0.11% (0.3% as a whole) during the 8 months from April to November and increased to 0.3% (0.7% as a whole) in September and October. We conclude that the incidence of aseptic meningitis after MMR vaccination seems to be higher than that reported previously.

Adolescent↗