Cerebrospinal fluid leukocyte aggregation in meningitis

OBJECTIVE: To evaluate whether the difference in aggregation of cerebrospinal fluid cells from patients with bacterial, viral, aseptic and partially treated meningitis can be used for diagnostic purposes. METHODS: Cerebrospinal fluid samples of 100 patients with meningitis (15 bacterial, 13 partially treated, 10 viral and 62 aseptic) were compared on the basis of the predefined leukocyte aggregation score (LAS). RESULTS: Mean LAS was 56% in the bacterial meningitis group (range, 15 to 90%), 5.8% in the partially treated meningitis group (range, 0 to 27%), 2% in the proven viral meningitis group (range, 0 to 5%) and 2% in the aseptic meningitis group (range, 0 to 15%). All patients with bacterial meningitis had a LAS of > 15%, whereas all those with viral or aseptic meningitis had a score of < 15%. Although most patients with partially treated meningitis had a low LAS, several had higher scores, which may indicate bacterial infection. There was no statistical correlation between number of cells, type of cells (mononuclear or polymorphonuclear) or cerebrospinal fluid protein and glucose concentration and degree of leukocyte aggregation for the different groups. CONCLUSION: Measurement of the LAS may contribute to the immediate differential diagnosis of bacterial or viral meningitis, especially in patients with very high pleocytosis, as sometimes seen in enteroviral meningitis. It may also serve as a guide for the likelihood of bacterial infection in cases of partially treated meningitis. Additional studies are needed to confirm these observations.     

Lysozyme activity in cerebrospinal fluid. Studies in inflammatory and non-inflammatory CNS disorders

Lysozyme activity was measured in cerebrospinal fluid (CSF) from 114 patients with inflammatory (bacterial and serous meningitis, polyradiculitis, encephalitis) and non-inflammatory (multiple sclerosis, CNS tumors, cerebral vascular diseases) CNS diseases. Highly elevated values were found consistently in patients with bacterial meningitis. Elevated values were found also in patients with encephalitis, polyradiculitis, multiple sclerosis and CNS tumors, but a considerable overlapping between these groups and normal controls precludes the use of CSF lysozyme measurements as a diagnostic aid in the latter disease groups. Simultaneous measurements of lysozyme, albumin and IgG in CSF and serum suggested that the mechanism for increased CSF lysozyme values in bacterial meningitis is mainly a breakdown of the blood/brain barrier, whereas the increased CSF lysozyme values in the remaining groups of patients are more likely caused by production of lysozyme by cells within the meninges (neutrophilic granulocytes, monocytes?).     

Impact of deltamethrin impregnated mosquito nets on the transmission of malaria in the coastal lagoon area, Benin]

Neopterin has been determined in blood as a marker of cellular immune system activation. We studied cerebrospinal fluid (CSF) neopterin levels in children with neurologic diseases, and the following results were obtained: (1) CSF neopterin levels markedly increased at the acute phase of bacterial meningitis, aseptic meningitis, and encephalitis as compared with those in patients without neurologic diseased. (2) In the CSF of patients with bacterial meningitis and aseptic meningitis, neopterin levels decreased more rapidly than the total cell count and 2'5' oligoadenylate synthetase (2-5 AS) did. (3) CSF neopterin in patients with non-infectious neurologic diseases was almost equal to that in patients without neurologic diseases. (4) There was no correlation between CSF neopterin and other CSF values, such as total cell count, mononuclear cell count, protein, and 2-5 AS. These results suggest that CSF neopterin is a useful marker of inflammatory central nervous diseases.     

Herpes simplex and lymphocytic choriomeningitis viruses in infections of the central nervous system--clinical and cerebrospinal fluid characteristics

INTRODUCTION: A great number of various viruses are stated as the cause of acute infections and damages of the central nervous system. In most cases these are minor damages which exhibit as meningeal syndrome and a specific finding in the cerebrospinal fluid. According to the dominant location, central nervous system infections can take a form of meningitis, encephalitis or myelitis. Since the inflammatory process of the meninges can not be separated from the inflammatory process of the brain, we usually speak of meningoencephalitis. The etiological diagnosis of meningitis and encephalitis is established by isolating the virus from the cerebrospinal fluid and by finding the presence of the specific antibodies in the blood and in the cerebrospinal fluid. The most common causes of the viral meningitis are Enteroviruses, the Mumps virus, Arthropode borne viruses, the Herpes viruses, Adeno viruses and the Lymphocytic choriomeningitis virus. The aim of our study was to establish the correlation between the clinical features and immunological and cerebrospinal fluid changes and the degree of the damage to the blood-brain barrier during the infections of the central nervous system, caused by the Herpes Simplex virus and the Lymphocytic choriomeningitis virus. MATERIAL AND METHODS: From a group of 103 patients, who had been treated for viral meningitis and meningoencephalitis, a group of 27 patients with established specific viral etiology--Herpes Simplex virus and Lymphocytic choriomeningitis virus, had been taken into the account. Herpes Simplex infection had been proven by the complement binding reaction and the neutralisation test of the even samples of serum. The diagnosis of Lymphocytic choriomeningitis was confirmed by the immunofluorescence test of the pharynx swabs and cerebrospinal fluid. The clinical features, such as body temperature, encephalitic signs, and electroencephalographic findings had been followed and compared. RESULTS: Herpes Simplex infection had been found in 20 patients, Lymphocytic choriomeningitis had been proven in 7 patients. All the patients had increased body temperature. Only four of the patients exhibited encephalitic signs, all infected by the Herpes Simplex virus. Patients from the Herpes Simplex group showed various degrees of consciousness disturbances, ranging from somnolence to coma, while the Lymphocytic choriomeningitis patients exhibited none. Higher pleocytosis and protein level had been found in the Lymphocytic choriomeningitis group. DISCUSSION: Viral diseases of the central nervous system are the result of the direct damage of the brain and meninges by the virus and immunological processes. Herpes Simplex meningitis usually has a good prognosis. Lymphocytic choriomeningitis has longer course of the disease and exhibits more severe clinical features. CONCLUSION: In cases of the central nervous system infections, caused by Herpes Simplex virus or Lymphocytic choriomeningitis virus, the correlation between the severeness of clinical features and the degree of damage of the blood-brain barrier, the level of pleocytosis and the increase of the cerebrospinal fluid proteins had been established.     

Heparin inhibits leukocyte rolling in pial vessels and attenuates inflammatory changes in a rat model of experimental bacterial meningitis

Heparin is a natural proteoglycan that was first described in 1916. In addition to its well characterized effect on blood coagulation, it is becoming clear that heparin also modulates inflammatory processes on several levels, including the interference with leukocyte-endothelium interaction. Anecdotal observations suggest a better clinical outcome of heparin-treated patients with bacterial meningitis. The authors demonstrate that heparin, a glycosaminoglycan, inhibits significantly in the early phase of experimental pneumococcal meningitis the increase of 1) regional cerebral blood flow (125 +/- 18 versus 247 +/- 42%), 2) intracranial pressure (4.5 +/- 2.0 versus 12.1 +/- 2.2 mm Hg), 3) brain edema (brain water content: 78.23 +/- 0.33 versus 79.49 +/- 0.46%), and 4) influx of leukocytes (571 +/- 397 versus 2400 +/- 875 cells/microL) to the cerebrospinal fluid compared with untreated rats. To elucidate the possible mechanism of this observation, the authors investigated for the first time leukocyte rolling in an inflammatory model in brain venules by confocal laser scanning microscopy in vivo. Heparin significantly attenuates leukocyte rolling at 2, 3, and 4 hours (2.8 +/- 1.3 versus 7.9 +/- 3.2/100 microm/min), as well as leukocyte sticking at 4 hours (2.1 +/- 0.4 versus 3.5 +/- 1.0/100 microm/min) after meningitis induction compared with untreated animals. The authors conclude that heparin can modulate acute central nervous system inflammation and, in particular, leukocyte-endothelium interaction, a key process in the cascade of injury in bacterial meningitis. They propose to evaluate further the potential of heparin in central nervous system inflammation in basic and clinical studies.     

Increased creatine kinase brain isoenzyme concentration in cerebrospinal fluid with meningitis

CPK-BB (CK-BB) isoenzyme is an intracellular enzyme released in various neurologic conditions, including central nervous system (CNS) infections. Activity of CK-BB in cerebrospinal fluid (CSF) was determined in 80 children by electrophoresis and densitometry. The possible correlation between CNS infection and CK concentrations was assessed. Significantly elevated concentrations of CK activity (P < 0.01) in the CSF were found in children with bacterial meningitis as compared with children with either aseptic meningitis or normal CSF findings. The data suggest the possibility of utilizing CSF CK activity to differentiate between bacterial and viral meningitis in situations where a routine CSF examination is inconclusive.     

Experimental reproduction of a spiking mortality syndrome of turkeys

We measured the levels of interleukin-6 (IL-6), albumin, C-reactive protein (CRP) and alpha 2 macroglobulin (alpha 2M), all of which have different spectrums of molecular weight, in the cerebrospinal fluid (CSF) and serum in 121 patients to evaluate damage to the blood-cerebrospinal fluid barrier (BCB) in meningitis. There was an extraordinary high level of IL-6 in the CSF when patients had bacterial or viral meningitis, but the level returned to a normal range within a week in almost all of these cases. There were no significant differences in CSF albumin levels among the different disease groups. The CRP level in CSF is considered to correlate with the serum level, and CSF CRP was higher in bacterial meningitis than in viral meningitis, however, CRP in CSF was increased in some of the infectious diseases without meningitis. The alpha 2M in CSF, which tends to be at extraordinarily high levels when there is damage to the BCB, correlated highly with CSF cell counts. CSF IL-6 seemed to be a useful indicator to identify the acute active phase of meningitis. CRP and alpha 2M in CSF are considered to be useful to differentiate bacterial meningitis, bacterial infection without meningitis and viral meningitis. Extraordinarily high levels of alpha 2M, which has a high molecular weight, in CSF is indicative of BCB damage.     

Soluble adhesion molecules in CSF are increased in children with severe head injury

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.     

Basic fibroblast growth factor in experimental and clinical bacterial meningitis

Basic fibroblast growth factor (bFGF), a neurotrophic factor in the CNS, is expressed at high levels in response to seizures or strokes. We examined the expression of bFGF during experimental bacterial meningitis and the levels of bFGF in the cerebrospinal fluid (CSF) of children with bacterial meningitis. For the experimental study, a mouse model of meningitis was established by intracranial injection of Streptococcus pneumoniae. Twenty-four hours after induced meningitis, the brains were sectioned and stained immunohistochemically for bFGF. Neutrophils and macrophages infiltrating the leptomeninges and the ventricles exhibited strong bFGF immunoreactivity. The neurons in the areas adjacent to the inflamed ventricles also showed enhanced bFGF expression. For the clinical study, we used an enzyme immunoassay to measure bFGF in CSF in 18 children with bacterial meningitis, 12 with aseptic meningitis, and 18 controls. The CSF levels of bFGF were twice as high in children with bacterial meningitis (medians 6.75-7.21 pg/mL) compared with those who had aseptic meningitis (2.9 pg/mL) or in control subjects (2.65 pg/mL, p < 0.0001, respectively). In patients with bacterial meningitis who survived, CSF bFGF decreased significantly after 24-50 h of antibiotic therapy (p < 0.0005). Patients who developed major sequelae or died had much higher levels of CSF bFGF than those without (134.9 pg/mL versus 7.38 pg/mL, p < 0.05). These findings of enhanced immunoreactivity of bFGF in experimental bacterial meningitis and an association of CSF levels of bFGF with disease severity in childhood bacterial meningitis suggest a biologic role for this neurotrophic factor in the pathophysiology of bacterial meningitis.     

Cerebrospinal fluid bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in children with meningitis treated with high-dosage cefotaxime

We determined cefotaxime and desacetyl-cefotaxime concentrations in children with bacterial meningitis receiving high-dose cefotaxime (300 mg/kg of body weight/day) and concomitant dexamethasone therapy. The median peak cerebrospinal fluid cefotaxime and desacetyl-cefotaxime concentrations were 4.7 and 8.1 microg/ml, respectively. In vitro bactericidal activity (>99.9% killing in 6 h) was found in 17 (94%), 13 (72%), and 8 (44%) of 18 cerebrospinal fluid specimens against cefotaxime-susceptible, -intermediate (MIC, 1 microg/ml), and -resistant (MIC, 4 microg/ml) strains, respectively. High-dose cefotaxime, while safe, is not reliably sufficient therapy for cephalosporin-nonsusceptible pneumococcal meningitis, and combination therapy is recommended.     

Role of neutrophil-endothelial cell adhesion in inflammatory disorders

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.     

Recurrent pyogenic granuloma or Warner and Wilson-Jones syndrome

Here we report a case of pneumococcal meningitis with bilateral sensorineural hearing loss at the onset. The patient was a 60-year-old man who a few days before visiting our hospital experienced common cold-like symptoms, and then he suddenly developed bilateral hearing loss. Examination of the cerebrospinal fluid (CSF) on the day of admission revealed pleocytosis and his CSF culture demonstrated pneumococci. Otorhinolaryngological examinations disclosed bilateral severe sensorineural hearing loss due to cochlear impairment. Many cases of bacterial meningitis concomitant with hearing loss have been reported, but a case of meningitis starting with sudden hearing loss is rare.     

The dilemma of partially treated bacterial meningitis

An analysis of 62 patients with pyogenic meningitis is presented, 23 (37%) of whom had received pre-diagnosis antibiotic therapy. Positive bacteriological identification could be achieved in 73% of the partially treated group as opposed to 97% in the previously untreated group but otherwise such pre-treatment made little impact on the diagnosis, characteristic cerebrospinal fluid changes sufficient for diagnostic purpose being present in all but one case. The study also fails to demonstrate any advantage of immunoelectroosmophoresis over conventional bacteriology in the problem cases of partially treated bacterial meningitis.     

Encephalitis and meningitis

Inflammation of the brain and meninges is a common cause of neurologic dysfunction in dogs and cats. A wide range of infectious agents has been demonstrated to cause encephalitis an meningitis, although there are many inflammatory conditions for which an etiology has not been found. Analysis of cerebrospinal fluid is the most useful diagnostic test to identify central nervous system inflammation. This article discusses the common causes of encephalitis and meningitis in dogs and cats, focusing on clinical presentation, diagnostic findings, treatment modalities, and prognosis.     

Effects of contrast on attraction of the housefly, Musca domestica, to visual targets

There is evidence that the treatment of bacterial meningitis with antibiotics liberates harmful bacterial products in the subarachnoid space (SAS). This enhances meningeal inflammation and in particular the recruitment of leukocytes into the cerebrospinal fluid (CSF), which has been shown to be more harmful than beneficial in this disease. In this study, we used a rabbit meningitis model based on intracisternal injection of live Streptococcus pneumoniae. Ampicillin (40 mg/kg of body weight given intravenously [i.v.] 16 h after induction of meningitis) caused a fivefold increase in CSF leukocytes over a 4-h period. Inhibition of leukocyte rolling by treatment with the polysaccharide fucoidin (10 mg/kg, i.v.) prevented the enhanced leukocyte extravasation into the SAS and attenuated the leakage of plasma proteins over the blood-brain barrier. These results suggest that certain polysaccharides that block leukocyte rolling have the potential to reduce leukocyte-dependent central nervous system damage in bacterial meningitis.     

Chemotactic activity on mononuclear cells in the cerebrospinal fluid of patients with viral meningitis is mediated by interferon-gamma inducible protein-10 and monocyte chemotactic protein-1

In viral meningitis the inflammatory response involves activated T cells and monocytes which are recruited into the subarachnoid space. To identify the chemotactic signals attracting the cells to the site of infection in the meninges, we measured the levels of two CXC chemokines, interferon-gamma (IFN-gamma) inducible protein (IP)-10 and monokine induced by IFN-gamma, four CC chemokines, monocyte chemotactic protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, as well as the cytokines interleukin (IL)-15 and IL-16 in the cerebrospinal fluid (CSF) of patients suffering from viral meningitis. The results point to an involvement of two chemokines, MCP-1 and IP-10, since (1) unlike the other cytokines, MCP-1 and IP-10 were present in 97% and 79% of the CSF, respectively, at concentrations sufficient to induce chemotaxis of mononuclear cells; (2) more than 90% of the CSF of viral meningitis induced chemotaxis of peripheral blood mononuclear cells (PBMC) and all of them induced chemotaxis of activated T cells, and (3) the CSF-mediated chemotaxis of PBMC was inhibited by anti-MCP-1 antibodies and chemotaxis of activated T cells was abolished by the combination of anti-MCP-1 and anti-IP-10 antibodies. Our data provide evidence that MCP-1 and IP-10 lead to accumulation of activated T cells and monocytes in the CSF compartment in viral meningitis.     

Changes in cerebrospinal fluid biotinidase activity in Staphylococcus aureus meningitis

An early increase in activity of biotinidase in the cerebrospinal fluid (CSF) during the course of acute Staphylococcus aureus meningitis in a subject with subacute sclerosing panencephalitis (SSPE) is reported. A possible role of CSF biotinidase in the hydrolysis of specific opioid neuropeptides during acute inflammatory processes involving the CSF-central nervous system compartment is suggested.     

Effect of ethnic media on cervical cancer screening rates

We report the case of an immunocompetent patient who has been the subject of 39 episodes of recurrent pneumococcal meningitis over a 20 year period. The recurrences of bacterial meningitis due to cerebrospinal fluid leakage and the presence of chronic sinusitis were not influenced by the surgical repair of a fistula and the repeated surgical draining interventions on suppurating chronic sinusital foci. Phenoxymethylpenicillin treatment reduced the number of recurrences and the combination of pneumococcal vaccine and penicillin prophylaxis allowed a 5 year period free of any recurrences.     

Diagnosis of meningococcal meningitis by broad-range bacterial PCR with cerebrospinal fluid

We used broad-range bacterial PCR combined with DNA sequencing to examine prospectively cerebrospinal fluid (CSF) samples from patients with suspected meningitis. Fifty-six CSF samples from 46 patients were studied during the year 1995. Genes coding for bacterial 16S and/or 23S rRNA genes could be amplified from the CSF samples from five patients with a clinical picture consistent with acute bacterial meningitis. For these patients, the sequenced PCR product shared 98.3 to 100% homology with the Neisseria meningitidis sequence. For one patient, the diagnosis was initially made by PCR alone. Of the remaining 51 CSF samples, for 50 (98.0%) samples the negative PCR findings were in accordance with the negative findings by bacterial culture and Gram staining, as well as with the eventual clinical diagnosis for the patient. However, the PCR test failed to detect the bacterial rRNA gene in one CSF sample, the culture of which yielded Listeria monocytogenes. These results invite new research efforts to be focused on the application of PCR with broad-range bacterial primers to improve the etiologic diagnosis of bacterial meningitis. In a clinical setting, Gram staining and bacterial culture still remain the cornerstones of diagnosis.