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Syphilitic meningitis in HIV-patients with meningeal syndrome: report of two cases and review.

Few patients with symptomatic neurosyphilis present with signs and symptoms of acute meningitis. Here we report two cases of syphilitic meningitis diagnosed in HIV patients with meningeal syndrome. The first case, a 30-year-old black bisexual male, had concurrent meningeal and ocular syphilis with persistent unusually low CSF glucose levels. He responded well to 21 days of intravenous penicillin therapy. The second case was a 55-year-old female with epilepsy, depression, behavioral disorder and confusion. The diagnosis of HIV infection was made after onset of the syphilitic meningitis. She was treated with 21 days i.v. penicillin with improvement in her clinical condition. The clinical aspects of combined neurosyphilis and HIV infection, plus special features of diagnosis and treatment are discussed.

AIDS-Related Opportunistic Infections↗

[Does the estimation of acute phase protein concentrations in cerebrospinal fluid and/or in serum in patients with viral meningitis carry diagnostic importance? Part I. Lymphocytic meningitis caused by epidemic parotitis].

OBJECTIVE: We examined whether an acute phase reaction could occur in children with lymphocytic meningitis of homogeneous etiology (parotitis epidemic from the Paramyxoviridae family), a sign of which would be an increase in concentrations of acute phase proteins (APP's) in cerebrospinal fluid (CSF) and/or in blood serum. We also tested the usefulness of the determination of selected APP's concentrations in CSF and serum in diagnosis and monitoring of the course of the disease, provided that an increase in concentrations of selected APP's were discernible. METHODS: Cases were 78 children with lymphocytic meningitis as a complication of parotitis epidemic. Controls were 30 healthy children (control group K1) and 19 children hospitalized with suspected meningitis (control group K2). The following APP's presence in CSF and serum were tested: C-reactive protein (CRP), alpha-2-haptoglobin (HPT), alpha-1-antitripsin (AAT) and alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER) and alpha-2-macroglobulin (AMG). The results were compared and analyzed. RESULTS: The results of the research show a significant increase in all APP's determined, except for CRP and AAG, in children with parotidal meningitis. CONCLUSIONS: Determination of CRP concentration either in CSF or in serum is not useful in diagnosis of parotidal meningitis and in differentiation of lymphocytic and bacterial forms of the disease.

Acute-Phase Proteins↗

[Does the assay of acute phase protein concentrations in cerebrospinal fluid and/or in serum in patient with viral meningitis have a diagnostic value? Part II. Lymphocytic meningitis caused by echo 30 virus].

The aim of the study was to evaluate dynamics of selected acute phase proteins in serum and cerebrospinal fluid (CSF) in children with viral meningitis and to assess diagnostic power of protein determination for detection and treatment monitoring. 51 children with viral meningitis caused by ECHO 30 virus were included in the study group. Concentration of C-reactive protein (CRP), alpha 1-antitrypsin (AAT), alpha1-acid glycoprotein (AAG), alpha2-haptoglobin (HPT) and C3 complement fragment were determined in serum and CSF at entry and at day 14 after admittance to hospital. Control group for serum determination consisted in 30 healthy children (Group K1) and control group for CSF determination consisted in 19 hospitalized children in whom the diagnosis of meningitis was not confirmed (group K2). The greatest rise of acute phase proteins concentration was observed in children in case of HPT, AAG and C3 complement when determined in serum. Meningitis in children that was caused by ECHO 30 virus produces slight acute phase reaction that is more evident in serum than in CSF. It is confirmed by remarkable increase of AAG, HPT, C3 complement in serum and HPT in CSF either at entry or at the day 14. The determination of AAG, HPT and C3 complement in serum have diagnostic power that is strong enough to meningitis diagnostics and monitoring of treatment.

Acute-Phase Proteins↗

Pharmacokinetic and bacteriological correlations between antimicrobial therapy of experimental meningitis in rabbits and meningitis in humans: a review.

Animal models of bacterial meningitis have been developed to study antimicrobial pharmacokinetics and efficacy for eliminating bacteria from cerebrospinal fluid (CSF) and to study pathophysiology. The correlation between observations in the rabbit model and in paediatric patients with meningitis was evaluated. When dosages of the beta-lactam or aminoglycosidic antibiotics which will produce serum concentrations approximating those in the human were given to rabbits, the degree of penetration of antibiotics into CSF and the bactericidal activity in CSF were comparable in rabbits and humans. Differing rates of elimination of Gram-negative enteric bacteria from rabbit CSF correlated directly with the bactericidal titres. However, in children with meningitis, this correlation was not found. Instead, it appeared that there was a critical level of bactericidal activity of 1:8 at which optimal killing of bacteria occurred. Increasing the bactericidal activity beyond that point did not accelerate elimination of bacteria from CSF. It is concluded that the rabbit model of bacterial meningitis is useful for predicting pharmacokinetics and activity of new antibiotics in CSF, but not for predicting differing degrees of effectiveness among antibiotics.

Animals↗

Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges.

The interactions of bacterial pathogens with cells of the human leptomeninges are critical events in the progression of meningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the interactions of the meningeal pathogens Escherichia coli K1, Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. A rank order of association with meningioma cells was observed, with N. meningitidis showing the highest levels of adherence, followed by E. coli, S. pneumoniae and H. influenzae. Neisseria meningitidis and H. influenzae did not invade meningioma cells or induce cell death, but induced a concentration-dependent secretion of inflammatory mediators. Neisseria meningitidis induced higher levels of IL-6, MCP-1, RANTES and GM-CSF than H. influenzae, but there was no significant difference in the levels of IL-8 induced by both pathogens. Streptococcus pneumoniae was also unable to invade meningioma cells, but low concentrations of bacteria failed to stimulate cytokine secretion. However, higher concentrations of pneumococci led to cell death. By contrast, only E. coli K1 invaded meningioma cells directly and induced rapid cell death before an inflammatory response could be induced. These data demonstrate that the interactions of different bacterial pathogens with human meningeal cells are distinct, and suggest that different intervention strategies may be needed in order to prevent the morbidity and mortality associated with bacterial meningitis.

Bacterial Adhesion↗

Liquor:serum quotients of IgG and albumin in patients with meningism, meningitis and multiple sclerosis.

Liquor:serum quotients of IgG and albumin in patients with meningism, meningitis and multiple sclerosis have been studied. Abnormal quotients indicative of disturbed blood-brain barrier function and/or intrathecal IgG synthesis were found in various proportions of all 3 groups of patients. In some patients with aseptic meningitis and meningism, the abnormal quotients were comparable with those found in patients with multiple sclerosis. The reason for this is unknown. An unspecific reaction to febrile illness may be involved. As a consequence, the findings of abnormal liquor:serum quotients of IgG and albumin should be evaluated with great caution in patients with recent or present febrile illness.

Adolescent↗

Possibility of diagnosing meningitis by gas chromatography: cryptococcal meningitis.

Cerebrospinal fluid (CSF) from eight patients with cryptococcal meningitis, from ten patients with viral meningitis, and from four control patients without meningitis were analyzed by electron-capture gas-liquid chromatography (EC-GLC). All cryptococcal specimens had similar EC-GLC profiles, and these differed from those of the controls. Viral EC-GLC patterns were different from those obtained with specimens from the patients with cryptococcal infection and from the controls. In addition, specimens from patients with various types of viral infections gave profiles that differed from each other. Two normal CSFs were inoculated with Cryptococcus neoformans; aliquots of these cultures showed an EC-GLC pattern very similar to that seen in CSF of patients with cryptococcal meningitis. The EC-GLC procedure is rapid, reproducible, and easy to perform and may hold promise as an additional aid in the diagnosis of cryptococcal infection.

Cerebrospinal Fluid↗

Morphological indications for considerable diffuse reabsorption of cerebrospinal fluid in spinal meninges particularly in the areas of meningeal funnels. An electronmicroscopical study including tracing experiments in rats.

Transmission and scanning electron microscopical observations in the rat indicate a considerable capacity of the spinal meninges to reabsorb cerebrospinal fluid. The density of blood vessels and lymphatics in the duramater is extremely high, particularly in the areas of meningeal funnels and spinal nerve root sleeves. Arterioles with closely related unmyelinated nerve fibres, many fenestrated capillaries and venules predetermine these areas as sites where absorption processes could take place. At certain sites of the meningeal angle region, the arachnoid membrane, mostly multilayered, is reduced to only three or four layers. Intercellular discontinuities and cytoplasmic fenestrations occurring in the arachnoid lining cell layer result in direct communications between the subarachnoid space and cisterns of the arachnoid "reticular layer". These cisterns are partly fluid-filled, partly occupied by a net of collagen fibre bundles. Some cisterns harbour macrophages that often project filiform processes through the lining cell layer into the subarachnoid space, contacting cerebrospinal fluid. Desmosomes and gap junctions are present in all layers of the arachnoid. However, tight junctions and the continuous electrondense intercellular gap, known to occur normally within the "arachnoid barrier layer", were not seen in many sites of the meningeal angle region. Numerous arachnoid cells display a high degree of vesiculation. Cationized ferritin, introduced in vivo into the rat subarachnoid space, passes inter- and intracellularly from the cerebrospinal fluid compartment through the arachnoid membrane, reaching dural blood vessels and lymphatics. Tracer could be visualized both in the cytoplasm of the endothelium and on the luminal surface of the cells. Tracer also passed through pial cell layers into pial vessels, through leptomeningeal sheaths into vessels crossing the subarachnoid space, into the connective tissue compartment and into vessels of spinal dorsal root ganglia. In the angle region, a particularly large number of macrophages can be found on the surface of leptomeninges, within the arachnoid reticular layers, and in close relation to dural and epidural capillaries, venules and lymphatics. Their possible role in the process of cerebrospinal fluid reabsorption is discussed.

Absorption↗

Past and current roles for cephalosporin antibiotics in treatment of meningitis. Emphasis on use in gram-negative bacillary meningitis.

The therapy of gram-negative bacillary meningitis is less than adequate to date; the agents recommended do not achieve bactericidal levels in purulent cerebrospinal fluid. Because optimal antibiotic therapy of meningitis occurs when the cerebrospinal fluid level of an antibiotic is above the concentration needed to kill the offending pathogen, another group of agents needs to be considered. The newer cephalosporins or cehalosporin-type antibiotics (cefotaxime, moxalactam), by virtue of their marked activity against gram-negative bacilli and their ability to achieve significant CSF levels, merit serious consideration as therapy for gram-negative bacillary meningitis. Investigators in Europe and the United States have developed preliminary data demonstrating the efficacy of these agents in a growing number of cases. In the group presented herein, of the 35 cases in which gram-negative bacillary meningitis was treated with the newer cephalosporins, there were only four failures.

Adolescent↗

Herpes simplex virus type 2 recurrent meningitis (Mollaret's meningitis): a consideration for the recurrent pathogenesis.

We report a 44-year-old Japanese woman with herpes simplex virus (HSV) type 2 recurrent meningitis (Mollaret's meningitis). The diagnosis was confirmed by nested polymerase chain reaction in her cerebrospinal fluid, but the patient's conventional HSV antibodies by complement fixation, neutralizing test or enzyme immunoassay showed low titres with low lymphoproliferative response. Several similar cases are discussed. Although the reason for the recurrent pathogenesis is uncertain, our report suggests that the low immune response including immune evasion may be involved in the pathogenesis of HSV type 2 recurrent meningitis. For this patient, long-term suppressive and patient-initiated therapies were conducted to prevent the recurrence of meningitis.

Acyclovir↗

Where is the meningitis belt? Defining an area at risk of epidemic meningitis in Africa.

Mapping an area at risk of epidemics of meningococcal meningitis in Africa has significant implications for their prevention and case treatment, through the targeted development of improved surveillance systems and control policies. Such an area was described using information obtained from published and unpublished reports of meningitis epidemics between 1980 and 1999 and cases of meningococcal disease reported by surveillance systems to WHO. The Sahel bore the greatest epidemic burden, with over two-thirds of documented outbreaks and high attack rates. In addition to those already in the Meningitis Belt, countries affected included Guinea-Bissau, Guinea, Côte d'Ivoire, Togo, the Central African Republic and Eritrea. Elsewhere epidemics were reported from a band of countries around the Rift Valley and Great Lakes regions extending as far south as Mozambique and from here west to Angola and Namibia in southern Africa. The cumulative pan-continental analysis provided evidence of an epidemic-susceptible area which extends beyond the region accepted as the Meningitis Belt and which, moreover, may be partially determined by the physical environment, as shown by a striking correspondence to the 300-1100-mm mean annual rainfall isohyets.

Africa↗

Recurring episodes of meningitis (Mollaret's meningitis) with one showing an association with herpes simplex virus type 2.

Benign recurrent aseptic (Mollaret's) meningitis is a rare disease of unknown aetiology. We report the case of a 27-year-old woman who experienced three episodes of lymphocytic meningitis. Human Simplex Virus (HSV) type 2 DNA was detected in the CSF by PCR amplification indicating the diagnosis of recurrent HSV type 2 meningitis. Our observation suggests that search of herpes virus DNA by PCR amplification on CSF may be useful in unexplained recurrent meningitis.

Adult↗

Epidemiology of childhood bacterial meningitis in Poland. Incidence of bacterial meningitis with special reference to Haemophilus influenzae type b among children 0-59 months old in the former Kielce and Bydgoszcz districts in Poland in 1998-1999.

Population based surveillance was undertaken to assess the incidence of meningitis caused by Haemophilus influenzae type b in children 0-59 months old in Kielce and Bydgoszcz districts in Poland in 1998 and 1999. The cases were prospectively identified in pediatric and neuroinfection wards of local hospitals where all cases of children with suspected meningitis are referred in both districts. The mean annual incidence of meningitis caused by Haemophilus influenzae type b in children 0-59 months old in Kielce district during the study period was estimated at 3.1 per 100,000 per year (10.3% of cases of bacterial meningitis with confirmed etiology). In Bydgoszcz district, the annual incidence was 9.7 per 100,000 (50% of confirmed cases). These estimations are lower than reported in most Western European countries before the immunization against Hib was introduced. Small numbers of Hib vaccinations reported from both districts do not seem likely to have influenced the data significantly.

Child, Preschool↗

[Recurrent aseptic meningitis (Mollaret meningitis)--spontaneous and drug-induced origin].

Since its initial description by Mollaret in 1944, the etiology of the chronic aseptic meningitis has remained unknown. This rare disease may cause diagnostic problems if bacterial or viral causes are suspected. A different form of aseptic meningitis may be seen following a variety of drug treatments, especially with non-steroidal anti-rheumatic drugs: In many reports since 1978, meningitic attacks following administration of ibuprofen have been reported. We describe two cases of Mollaret-Meningitis with certain specialities: one case shows clear encephalitic involvement with aphasia in all six attacks. In the other case, five meningitic attacks appeared spontaneously, while two were drug-induced: the first attack was seen after a lumbar myelography with lopamidol and one attack appeared two hours after oral administration of 400 mg ibuprofen. It is suggested that Mollaret-Meningitis is a special form of a drug-induced allergic reaction, the provoking agent of which remains unknown.

Aged↗

Primary meningeal sarcomas with leiomyoblastic differentiation: a proposal for a new subtype of primary meningeal sarcomas.

Two cases of primary meningeal sarcoma with leiomyoblastic differentiation are presented. In case no. 1, the tumor showed anaplastic spindle cell tumor components intermingled with anaplastic meningothelial components. Meningothelial tumor cells gradually became transformed into spindle tumor cells. Spindle tumor cells reacted with antisera to muscle actin (HHF-35) and alpha-smooth muscle actin. However, unchanged meningothelial tumor cells did not react with the antisera to HHF-35 and alpha-smooth muscle actin. Electron microscopy showed condensations of cytoplasmic fibers and pinocytotic vesicles in spindle tumor cells similar to those seen in smooth muscle cells. In case no. 2, the tumor cells consisted predominantly of sheets of round or polygonal cells as seen in an epithelioid leiomyosarcoma. The neoplastic cells had frequent nuclear inclusions, such as those seen in meningiomas. Immunohistochemically, the tumor cells reacted with antisera to desmin and to HHF-35. Electron microscopy showed a basal lamina around the cytoplasm of tumor cells. Intranuclear inclusions with various cytoplasmic organelles were frequently observed in the tumor cells, as in meningiomas. Interdigitating cytoplasmic processes and intercellular junctional complexes, however, were not found in the tumor cells. Two possible hypotheses explain the occurrence of leiomyoblastic characteristics of these cases. In case no. 1, leiomyoblastic cells originated from meningothelial cells with the advancement of meningothelial anaplasia. In case no. 2, pluripotential mesenchymal cells in the meninges differentiated into meningothelial and smooth-muscle cell lines at the time of tumor growth. With consideration of previous publications on primary meningeal sarcoma, these cases are the first reported primary meningeal sarcoma with leiomyoblastic and meningothelial differentiation.

Aged↗

Prospective, randomized, investigator-blinded study of the efficacy and safety of meropenem vs. cefotaxime therapy in bacterial meningitis in children. Meropenem Meningitis Study Group.

OBJECTIVES: To compare the efficacy and safety of meropenem with cefotaxime for the treatment of infants and children with bacterial meningitis. METHODS: Infants and children with strongly suspected or documented bacterial meningitis were randomly assigned in a prospective multicenter study to receive either meropenem or cefotaxime. Patients were assessed at the end of therapy and at 5 to 7 weeks and 5 to 7 months after the end of treatment for the presence of neurologic and sensory neural sequelae. RESULTS: A total of 258 children were randomized to either treatment group. A further 8 patients with suspected pneumococcal meningitis were treated with meropenem without randomization. Of the randomized patients 154 were fully evaluable, 79 in the meropenem group and 75 in the cefotaxime group. At the end of treatment there were no significant differences in clinical outcome between the two treatment groups. Clinical cure with or without sequelae was achieved in 97 and 96% of the meropenem- and cefotaxime-treated patients, respectively. At the end of treatment and at 5 to 7 weeks, 46 and 54% of meropenem patients were cured with no sequelae, respectively. Corresponding results for cefotaxime patients were 56 and 58%. All pathogens were eradicated. In total 37 patients had seizures during treatment, 15 (12%) in the meropenem and 22 (17%) in the cefotaxime group. None of the seizures was considered to be drug-related. CONCLUSIONS: This trial shows that meropenem is suitable therapy for bacterial meningitis in infants and children and that it offers an efficacy and safety profile similar to that of cefotaxime.

Cefotaxime↗

Evaluation of meningococcal meningitis vaccination strategies for the meningitis belt in Africa.

BACKGROUND: Although the meningococcal polysaccharide vaccine has contributed to the control of Group A meningitis in the "meningitis belt" of Africa, recurrent large outbreaks have led to questions regarding vaccination strategy. We evaluated current and hypothetical vaccination strategies for the region. METHODS: A model was formulated to analyze the effectiveness and costs of vaccine campaigns in response to outbreaks based on 7 years of weekly incidence data from Burkina Faso. Additional models analyzed the potential impact and costs of either a 1- or 4-dose routine scheduled delivery of meningococcal polysaccharide vaccine based on data reported to the World Health Organization from 16 countries during 1948 through 1996. Vaccine efficacy, vaccination coverage and economic data from literature reviews provided model assumptions. RESULTS: For Burkina Faso neither 1- nor 4-dose vaccination schedules would prevent >30% of meningitis cases compared with the 42% prevented through an outbreak response program of vaccinating districts, which reach an incidence of 15 per 100000 persons for 2 weeks. For the entire meningitis belt, routine coverage with the 1- or 4-dose schedule meningococcal vaccine would require 4.9 and 19.6 million doses annually, respectively, for an annual net cost of $4.4 to $12.3 million and prevent an average 10300 to 12600 cases (23 to 28%), assuming a long term vaccine efficacy of 50%. In addition an initial "catch-up" campaign costing up to $72 million to vaccinate the population from 1 to 30 years of age would be required before achieving that level of effectiveness. CONCLUSION: Given the relatively poor routine vaccination coverage in this region, current strategies of vaccination campaigns that achieve higher coverage would generally be more effective and less costly than the modeled routine scheduled programs, assuming that campaigns can be rapidly implemented. Until a better vaccine is available, countries in this region would be more efficient in improving the response times to outbreaks, perhaps through improved surveillance, and in bolstering existing vaccination infrastructures rather than embarking on strategies of questionable effectiveness.

Africa↗

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group.

Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: -0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: -3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.

Adolescent↗