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[CNS tumors with the clinical picture of meningitis].

Incidentally CNS tumours may simulate acute bacterial or viral meningitis, cerebral abscess, and tuberculous or luetic basal meningitis. 64 cases from the literature are analysed together with 2 personal observations. This form of presentation is found most frequently in high-grade malignancy, i.e. in glioblastoma, medulloblastoma and ependymoma. In the group of benign CNS neoplasms dermoid and epidermoid cysts are most often associated with the meningeal syndrome. The only criterion facilitating a differentiation between acute bacterial meningitis and CNS malignancy is CSF culture. In individual cases an afebrile course, a normal sedimentation rate, and a normal WBC count may help to differentiate. In the presence of basal meningitic or diencephalic symptoms related to a prolonged course discrimination between brain tumour an tuberculous or luetic meningitis may become extremely difficult. In these cases the determination of creatine kinase BB isoenzyme and carcinoembryonic antigen in CSF may overcome the difficulty.

Astrocytoma↗

Bacterial meningitis in Washington state.

During 1977 the state of Washington maintained a surveillance system for reporting cases of bacterial meningitis. Hemophilus influenzae meningitis was the most common etiologic agent causing bacterial meningitis. A high incidence rate for H. influenzae meningitis was found among American Indians less than five years ago. A focus of ampicillin-resistant H. influenzae meningitis was found in Pierce County among military dependents or persons who had family members or relatives working or attending school with Fort Lewis Army Base personnel. Although relationships between the individual cases were not detected, the surveillance system continues to seek some association.

Child, Preschool↗

Epidemiology of pediatric meningitis caused by Haemophilus influenzae B, Streptococcus pneumoniae and Neisseria meningitidis in Israel.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood. We report 3 year data on meningitis caused by Haemophilus influenzae b, Streptococcus pneumoniae and Neisseria meningitidis in Israeli children younger than 13 years of age. The data were obtained prospectively through an active surveillance system involving all 25 centers in which children are hospitalized. A case was defined by: a) culture positive cerebrospinal fluid; or b) positive blood culture with > 10 cells. During the study period, 482 cases of meningitis due to the three organisms were identified. Of these, 58%, 20% and 22% were caused by H. influenzae b, S. pneumoniae and N. meningitidis, respectively. The male/female ratio was 1.5:1. An over-representation of the non-Jewish population was seen only in cases caused by S. pneumoniae. The median age was 11 months and 59% of all cases occurred by the age of 12 months. The median age was 10, 12 and 36 months and the age-specific incidence for children aged 0-4 years was 18.5, 5.3 and 5.2 per 100,000, respectively, for H. influenzae b, S. pneumoniae and N. meningitidis. The chance of being hospitalized with meningitis during the first 5 years of life was estimated at 146.2 per 100,000. Meningitis was seasonal: 59% al all cases occurred during fall and winter and only 18% during summer. A total of 2,097 hospitalization days were required when extrapolated to a population in which 100,000 live births occur yearly. The case fatality rate was 2.2%, 5.9% and 6.3% for H. influenzae b, S. pneumoniae and N. meningitidis, respectively, with a higher fatality in females and non-Jews.

Adolescent↗

[Notes on cases of meningitis admitted to the Ospedale Cotugno of Naples in the period 1987-91].

The notification of the cases of meningitis admitted to the Hospital Cotugno of Naples in the period 1987-91 were analyzed by a retrospective study: aim of the study was to outline the epidemiological trend of meningitis and to evaluate the quality of the data around the change of the reporting system, which took place in 1991. We examined 566 clinical charts, selecting only the cases whose agents were identified. Our data agree with the national and international literature, with the exception that the majority of cases were produced by S. pneumoniae. Moreover, the data about tuberculous meningitis still show that the highest incidence occur in youth, while other Authors noticed a trend toward older ages. Further studies are in progress to improve the knowledge of tuberculous meningitis in our Country.

Adolescent↗

Timing of Administration of Antimicrobial Therapy in Bacterial Meningitis.

Bacterial meningitis is an important cause of morbidity and mortality in the United States and throughout the world. The diagnosis of bacterial meningitis is often delayed in patients as a result of numerous factors such as length of illness, use of radiologic imaging studies, and/or prior use of antimicrobial agents. Many textbooks emphasize the need for prompt initiation of antimicrobial therapy in a patient with suspected acute bacterial meningitis to prevent many of the long-term sequelae associated with this disorder. We have reviewed the literature to determine if there is a standard of care for timing of administration of antimicrobial therapy in patients with a diagnosis of acute bacterial meningitis. Although the clinical data are inconclusive, it makes intuitive sense to initiate antimicrobial therapy as soon as possible in any patient with suspected or proven bacterial meningitis before the patient's illness advances to a high level of clinical severity, beyond which antimicrobial therapy is less likely to be of benefit. However, clinical experiences suggest that patient outcome in bacterial meningitis is a result of multiple factors, since some patients treated within a few hours of symptoms develop an adverse outcome whereas others who are symptomatic for days prior to presentation suffer no adverse sequelae.

Journal Article↗

Treatment of Bacterial Meningitis.

The therapeutic approach to acute bacterial meningitis has changed in recent years as a result of changes in in vitro susceptibility of many meningeal pathogens to previously standard antimicrobial therapy. Given the emergence of strains of Streptococcus pneumoniae that are resistant to penicillin and the cephalosporins, the combination of vancomycin plus a third-generation cephalosporin is recommended as empiric therapy for suspected or proven pneumococcal meningitis, pending results of in vitro susceptibility testing. Strains of Neisseria meningitidis with reduced susceptibility to penicillin have also been described, although most patients with these resistant strains have recovered with standard penicillin therapy. Although the third-generation cephalosporins have greatly improved outcome in patients with meningitis caused by aerobic gram-negative bacilli, many organisms in this group are now resistant to these drugs; the carbapenems and fluoroquinolones may be effective alternative agents and have been successfully used in small case series. Further surveillance of the in vitro antimicrobial susceptibility patterns of meningeal pathogens is critical for future recommendations in the treatment of bacterial meningitis.

Journal Article↗

Fluoroquinolones in the Treatment of Meningitis.

The continuous increase of resistant pathogens causing meningitis has limited the efficacy of standard therapeutic regimens. Due to their excellent activity in vitro and their good penetration into the cerebrospinal fluid (CSF), fluoroquinolones appear promising for the treatment of meningitis caused by gram-negative microorganisms, ie, Neisseria meningitidis and nosocomial gram-negative bacilli. The newer fluoroquinolones (moxifloxacin, gemifloxacin, gatifloxacin, and garenoxacin) have excellent activity against gram-positive microorganisms. Studies in animal models and limited clinical data indicate that they may play a future role in the treatment of pneumococcal meningitis. Analysis of pharmacodynamic parameters suggests that CSF concentrations that produce a C(peak)/minimal bactericidal concentration (MBC) ratio of at least 5 and concentrations above the MBC during the entire dosing interval are a prerequisite for maximal bactericidal activity in meningitis. Of interest, newer fluoroquinolones act synergistically with vancomycin and beta-lactam antibiotics (ceftriaxone, cefotaxime, meropenem) against penicillin-resistant pneumococci in experimental rabbit meningitis, potentially providing a new therapeutic strategy. Clinical trials are needed to further explore the usefulness of quinolones as single agents or in combination with other drugs in the therapy of pneumococcal meningitis.

Journal Article↗

Experimental rabbit model of meningitis produced by Haemophilus influenzae serotype c.

The virulence of Haemophilus influenzae type c when inoculated intracisternally (i.c.) into rabbits was evaluated. Rabbits are relatively resistant to infection with H. influenzae type b, such that inocula of the order of 10(6-9) cfu are required to produce meningitis in this model. In contrast, fatal meningitis was produced in this study when 10(3) cfu of a type-c strain were injected i.c. into rabbits. Numbers of bacteria in cerebrospinal fluid (CSF) of control (untreated) animals generally increased to 10(7) cfu/ml. Increases in white blood cells, protein and lactate in the CSF were similar to those which had been observed during meningitis due to Streptococcus pneumoniae in rabbits. The infection was amenable to therapy with ampicillin 50 mg/kg given intravenously 12 h after infection. Numbers of bacteria in CSF were reduced to 2.2 x 10(3) cfu/ml (SEM 0.2 x 10(3)) at 8 h after treatment with a single dose of ampicillin. Two doses of ampicillin, given 12 and 20 h after infection, significantly increased the mean survival time. In contrast to previous experimental studies with rabbits, the penetration of ampicillin into the CSF was high--46 (SEM 10) % of the blood level. Since considerable replication of H. influenzae type c occurred within the CSF in this model, the nature of the meningeal damage produced was likely to be similar to that which takes place in man. Hence, H. influenzae type c meningitis in rabbits may provide a useful model in which therapeutic and other experimental studies of H. influenzae meningitis can be performed.

Ampicillin↗

Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis and is independent of Toll-like receptor (TLR)4 and TLR2 signalling.

The interactions of Neisseria meningitidis with cells of the meninges are critical to progression of the acute, compartmentalized intracranial inflammatory response that is characteristic of meningococcal meningitis. An important virulence mechanism of the bacteria is the ability to shed outer membrane (OM) blebs containing lipopolysaccharide (LPS), which has been assumed to be the major pro-inflammatory molecule produced during meningitis. Comparison of cytokine induction by human meningeal cells following infection with wild-type meningococci, LPS-deficient meningococci or after treatment with OM isolated from both organisms, demonstrated the involvement of non-LPS bacterial components in cell activation. Significantly, recognition of LPS-replete OM did not depend on host cell expression of Toll-like receptor (TLR)4, the accessory protein MD-2 or CD14, or the recruitment of LPS-accessory surface proteins heat shock protein (HSP)70, HSP90alpha, chemokine receptor CXCR4 and growth differentiation factor (GDF)5. In addition, recognition of LPS-deficient OM was not associated with the expression of TLR2 or any of these other molecules. These data suggest that during meningococcal meningitis innate recognition of both LPS and non-LPS modulins is dependent on the expression of as yet uncharacterized pattern recognition receptors on cells of the meninges. Moreover, the biological consequences of cellular activation by non-LPS modulins suggest that clinical intervention strategies based solely on abrogating the effects of LPS are likely to be only partially effective.

Antigens, Surface↗

Mortality of Rocky Mountain elk in Michigan due to meningeal worm.

Mortality from cerebrospinal parelaphostrongylosis caused by the meningeal worm (Parelaphostrongylus tenuis) has been hypothesized to limit elk (Cervus elaphus nelsoni) populations in areas where elk are conspecific with white-tailed deer (Odocoileus virginianus). Elk were reintroduced into Michigan (USA) in the early 1900s and subsequently greatly increased population size and distribution despite sympatric high-density (>or=12/km2) white-tailed deer populations. We monitored 100 radio-collared elk of all age and sex classes from 1981-94, during which time we documented 76 mortalities. Meningeal worm was a minor mortality factor for elk in Michigan and accounted for only 3% of mortalities, fewer than legal harvest (58%), illegal kills (22%), other diseases (7%), and malnutrition (4%). Across years, annual cause-specific mortality rates due to cerebrospinal parelaphostrongylosis were 0.033 (SE=0.006), 0.029 (SE=0.005), 0.000 (SE=0.000), and 0.000 (SE=0.000) for calves, 1-yr-old, 2-yr-old, and >or=3-yr-old, respectively. The overall population-level mortality rate due to cerebrospinal parelaphostrongylosis was 0.009 (SE=0.001). Thus, meningeal worm had little impact on elk in Michigan during our study despite greater than normal precipitation (favoring gastropods) and record (>or=14 km2) deer densities. Further, elk in Michigan have shown sustained population rates-of-increase of >or=18%/yr and among the highest levels of juvenile production and survival recorded for elk in North America, indicating that elk can persist in areas with meningeal worm at high levels of population productivity. It is likely that local ecologic characteristics among elk, white-tailed deer, and gastropods, and degree of exposure, age of elk, individual and population experience with meningeal worm, overall population vigor, and moisture determine the effects of meningeal worm on elk populations.

Age Distribution↗

[Etiology and evolution of bacterial meningitis in a pediatric center]

OBJECTIVE: To establish the prevalence of the etiological agents of bacterial meningitis in a reference center for the treatment of infectious diseases in the state of Minas Gerais. METHODS: Descriptive study including all children with probable diagnosis of meningitis between June/1999 and November/1999. RESULTS: There were 210 cases of meningitis, and 111 (52.9%) were caused by bacteria. Actually, 52 were probable bacterial meningitis (with liquor alterations) and 59 were confirmed (with culture and/or antigen tests). The main agents were: Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. The initial treatment for children aged between three months and five years consisted of ampicillin and chloramphenicol. Later, the antibiotic was changed to penicillin in cases of Neisseria meningitidis and Streptococcus pneumoniae. and to chloramphenicol in cases of Haemophilus influenzae. Extended spectrum antimicrobial agents were used on clinical or laboratory basis, but resistant microorganisms were not found in cultures. CONCLUSIONS: The epidemiology of meningitis should be continuous and should consider local data in order to guide antimicrobial therapy. The continuous monitoring of the prevalent agents in each institution and their resistance is fundamental to the selection of antimicrobial drugs, preserving the antimicrobial agents, and causing less interference with individual colonization, without contributing to the increasing resistance of the agents responsible for meningeal infections.

Journal Article↗

Cerebrospinal fluid alpha-1-antitrypsin alpha-1-antitrypsin-elastase complex levels in meningitis.

Alpha-1-antitrypsin (A-1-AT) and A-1-AT-elastase complex levels in cerebrospinal fluid have been evaluated in 11 children with viral meningitis (VM), 14 with bacterial meningitis (BM), 10 with tuberculous meningitis (TBM) and 10 investigated for, but found not to have meningitis (NM). A-1-AT concentrations in the NM group were lower than in the BM group (P = 0.0002) and the TBM group (P = 0.0005) but did not differ from the concentrations in VM; those in the VM group were lower than in the BM group (P = 0.0001) and the TBM group (P = 0.003) but no difference was found between the BM and TBM groups. A-1-AT-elastase complex concentrations in CSF were lower in the NM group than the BM group (P = 0.0001) or the TBM group (P = 0.0089), however those in the BM group were significantly higher than in the TBM group (P = 0.0001). A significant correlation existed in CSF between the protein concentrations and neutrophil counts as well as the A-1-AT and A-1-AT-elastase complex concentrations.

Adolescent↗

Meningitis and sensorineural hearing loss.

A 12 month retrospective study was conducted on 54 children discharged from the Children's Hospital, Birmingham, Alabama, with a diagnosis of generalized meningitis, a major cause of post-natal sensorineural hearing loss (SNHL). Of these high risk patients, 38 or 70% had Haemophilus influenza meningitis and fully 40% of those children tested audiometrically were determined to have SNHL. Because there would appear to be an increase in SNHL in the post meningeal population, all children with a diagnosis of Haemophilus influenza, pneumococcal, or meningococcal meningitis should have an audiological workup, preferably prior to discharge from the hospital.

Adolescent↗

Comparison of cryptococcal and tuberculous meningitis.

Twenty-six patients had cryptococcal meningitis and 16 patients had tuberculous meningitis. Underlying conditions were mostly immunosuppressive diseases in patients with cryptococcosis and chronic debilitating diseases in patients with tuberculosis. There were few distinguishing charact eristics between the two infections with regard to symptoms and signs. The presence of a miliary pattern on chest roentgenogram and inappropriate secretion of antidiuretic hormone were nonspecific but helpful signs supporting a diagnosis of tuberculous meningitis; the presence of cryptococcal antigen was both a specific and sensitive indicator of cryptococcal meningitis. Acid-fast smears of CSF and the tuberculin skin test were of little help diagnostically, being positive in only 18% and 31%, respectively, of patients with tuberculous meningitis. Substantial delays in diagnosis and treatment were associated with increased mortality.

Adolescent↗

Anaerobic meningitis and bacteremia caused by Fusobacterium species.

In the two cases of anaerobic meningitis and bacteremia caused by Fusobacterium species described, upper respiratory tract infection preceded the onset of meningitis. Isolation of the causative organism and appropriate antibiotic therapy resulted in cures in both patients. Although extremely rare, these organisms should be considered as possible causative agents in meningitis when routine cultures are negative, and appropriate anaerobic culture techniques should be employed, especially when sinus, otitic, or mastoid symptoms precede or accompany the onset of meningitis. Susceptibility testing of these organisms is necessary to ensure proper therapy because of the resistance of some anaerobes to antibiotics commonly employed in meningitis. In this regard, metronidazole, which provides excellent cerebrospinal fluid levels, may prove to be an effective agent in anaerobic infections of the central nervous system.

Adolescent↗

Value of cerebrospinal fluid analysis in the differential diagnosis of meningitis: a study in 710 patients with suspected central nervous system infection.

A prospective study to determine the value of cerebrospinal fluid analysis in the differential diagnosis of meningitis was performed in 710 consecutively observed patients, both children and adults, who underwent lumbar puncture due to suspected central nervous system infection. Diagnoses included acute or presumed bacterial meningitis (n = 79), acute or presumed viral meningoencephalitis (n = 218), acute unclassified meningitis (n = 6), other infections of the central nervous system (n = 37), non-infectious neurological diseases (n = 76) and control patients (n = 294). The sensitivity, specificity and predictive values were determined for cerebrospinal fluid white blood cell count, total protein, lactate, glucose and C-reactive protein levels as well as the blood/cerebrospinal fluid glucose ratio. Determination of cerebrospinal fluid levels of lactate (greater than or equal to 3.5 mmol/l) was found to be superior to the other tests. The C-reactive protein level gave no additional diagnostic information when the lactate level was determined. The white blood cell count, and total protein and glucose levels were often unreliable tools for differential diagnosis, largely due to low sensitivity at realistic discriminatory limits. The study confirms that no cerebrospinal fluid test is fully reliable in distinguishing bacterial meningitis from other forms of meningitis.

Adolescent↗

Childhood bacterial meningitis in Pondicherry, South India.

OBJECTIVE: To identify causative bacteria from cerebrospinal fluid (CSF) of children with meningitis and analyse various clinical and laboratory parameters. METHODS: Over a 20 month period, September 1994 to April 1996, one hundred episodes of acute bacterial meningitis in children aged 1 month-12 years were studied in a tertiary urban hospital in South India. Organisms were isolated from the cerebrospinal fluid (CSF) in 35% of cases. Among infants and children, the two major pathogens were H. influenzae (17%) and S. pneumoniae (12%). RESULTS: The illness at presentation was mild in 13% and severe in 36% of cases. The association of subdural effusion in children with Salmonella Gp B meningitis merits attention. The overall case fatality rate was 25%. S. pneumoniae had a higher case fatality rate than Salmonella Gp B and H. influenzae (50% vs 17% vs 12%). All the three infants below 3 months of age with S. pneumoniae meningitis died. On analysis of selected clinical and laboratory features by discriminant analysis, CSF culture was the significant (P = 0.02) variable in relation to outcome. In pneumococcal meningitis, CSF WBC count was a highly significant variable in relation to outcome (Wilk's Lambda 0.15, F = 24.64, P = 0.0002). CONCLUSION: Prevention of infections due to H. influenzae and S. pneumoniae should be given higher priority.

Analysis of Variance↗

Neoplastic meningitis: diagnosis and treatment considerations.

Neoplastic meningitis is an increasingly recognized complication of advanced metastatic cancer and, if left undiagnosed or untreated, is characterized by rapid neurologic deterioration and death. Thus, the diagnosis and treatment of neoplastic meningitis present challenges for the clinical oncologist. The diagnosis of neoplastic meningitis is based on clinical signs and symptoms, laboratory analysis of cerebrospinal fluid to determine cell count and cytology, and analysis of neuroimaging studies for evidence of leptomeningeal or cranial nerve enhancement. Once diagnosed, conventional treatment regimens may include radiotherapy combined with systemic or intrathecal chemotherapy, often with the antimetabolites cytarabine and/or methotrexate. However, the prognosis for neoplastic meningitis secondary to an underlying solid tumor or recurrent leukemia is poor with conventional treatment regimens. Therefore, novel agents for intrathecal administration, including DepoCyttrade mark, mafosfamide, and topotecan, or novel therapeutic approaches, including conjugated monoclonal antibodies and immunotoxins or gene therapy, are currently under investigation. Such new agents and therapeutic approaches will facilitate the development of effective treatment strategies and will ultimately improve the outcome for patients with this devastating disease. This article provides an overview of the approaches to the diagnosis, evaluation, and treatment of neoplastic meningitis.

Antineoplastic Combined Chemotherapy Protocols↗