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Comparison of isolates of Neisseria gonorrhoeae causing meningitis and report of gonococcal meningitis in a patient with C8 deficiency.

We studied a previously healthy 20-year-old woman who presented with gonococcal meningitis. The gonococcal isolate, HT-1, was prototrophic by auxotyping, was protein I serovar IB-1, and agglutinated with wheat germ lectin. This isolate differed from the proline-requiring, serovar IA-1 and IB-4, wheat germ-agglutination-negative gonococcal isolates recovered from three patients during a recent outbreak of gonococcal meningitis in Philadelphia. HT-1 was killed by normal pooled human sera (greater than or equal to 98% at 30 min) but not effectively killed by the convalescent-phase sera of the patient (greater than 30% survival at 30 min). Similar results were obtained when mucosal and cerebrospinal fluid isolates from a Philadelphia patient were exposed to these sera, but mucosal and blood isolates from another Philadelphia case showed increased resistance to killing by normal pooled human sera. Further characterization revealed multiple differences in outer membrane and cellular proteins and lipopolysaccharide between case isolates. Absence of the L8 lipopolysaccharide epitope was noted for all isolates. Sera of our patient were found to have low total hemolytic complement (CH100 = 21 U/ml; normal = 55 to 100 U/ml) due to deficiency of C8 (C8 less than 1,000 CH50 U/ml; normal = greater than or equal to 16,000 CH50 U/ml). This is the first reported case of gonococcal meningitis occurring in a patient with a terminal-complement deficiency. Gonococcal meningitis is a rare complication of gonococcal bacteremia. Both defects in host defenses (e.g., terminal-complement deficiency) and organisms with unusual virulence appear to contribute to the pathogenesis of this complication of gonococcal bacteremia.

Adult↗

Treatment of overt meningeal leukaemia in children: results of second MRC meningeal leukaemia trial.

After induction ofmeningeal remission by a course of intrathecal methotrexate patients were randomly allocated to receive either cranial irradiation or craniospinal irradiation. Patients being treated for their first meningeal relapse were randomised separately from those in their second or subsequent relapse. All eight patients in their first relapse who were given cranial irradiation alone developed further meningeal recurrence (median length of remission 15 weeks) compared with only two out of nine given craniospinal irradiation (median length of remission at least 99 weeks). Four of the nine patients given craniospinal irradiation were alive and without further meningeal relapse two and a half to four years after treatment. Craniospinal irradiation produced no such advantage for patients entering the trial in their second or subsequent meningeal relapse.

Brain↗

Experimental bacterial meningitis in rats: demonstration of hydrocephalus and meningeal enhancement by magnetic resonance imaging.

We investigated whether magnetic resonance imaging (MRI) is able to detect intracranial manifestations of advanced bacterial meningitis in rats. Meningitis was induced in nine animals by injecting 150 microl 10(7) colony forming units per ml of Streptococcus pneumoniae into the cisterna magna. MRI was performed 24 h (n = 5) and 48 h (n = 4) after infection. Controls included (I) animals that were injected intracisternally with 150 microl phosphate-buffered saline or (II) animals without puncture of the cisterna magna. T2-weighted and T1-weighted MR images before and after administration of 0.3 mmol kg(-1) of gadolinium-DTPA were obtained. Hydrocephalus was found in 7 of 9 infected animals, but not in the control group. Abnormal leptomeningeal enhancement was found in all infected animals, but in none of the controls. The animals imaged after 48 h showed a more pronounced hydrocephalus and a more intense leptomeningeal enhancement than animals imaged after 24 h. Even in small animals such as rats, MRI can be used to detect the presence of bacterial meningitis and its associated complications. MRI may be a useful noninvasive method for monitoring the possible effect of adjunctive therapeutic strategies in experimental studies of meningitis.

Animals↗

Case report: greater meningeal inflammation in lumbar than in ventricular region in human bacterial meningitis.

Differences in the composition of ventricular and lumbar cerebrospinal fluid (CSF) based on single pairs of samples have previously been described. We describe a patient that developed post-surgical recurrent meningitis monitored by daily biochemical and bacteriological CSF analysis, simultaneously withdrawn from lumbar space and ventricles. A 20-year-old Caucasian man was admitted to the ICU after a resection of a chordoma that extended from the sphenoidal sinus to the anterior face of C2. CSF was continuously leaking into the pharyngeal cavity after surgery, and three episodes of recurrent meningitis, all due to Pseudomonas aeruginosa O12, occurred. Our case showed permanent ventricular-to-lumbar CSF gradients of leukocytes, protein and glucose that were increased during the acute phase of meningitis, with the greatest amplitude being observed when bacteria were present in both ventricular and lumbar CSF. This might suggest a greater extent of meningeal inflammation in the lumbar than in the ventricular region. Our case also showed that the increase in intravenous antibiotics (cefepim from 8 to 12 g/day and ciprofloxacine from 1.2 to 2.4 g/day) led to an increase in concentration in plasma but not in CSF.

Adult↗

Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group.

OBJECTIVE: To determine whether treatment with dexamethasone and ceftriaxone for children with bacterial meningitis reduces the frequency of either sensorineural hearing loss or other neurologic sequelae. DESIGN: This was a prospective, multicentered, placebo-controlled clinical trial. Subjects were followed for 1 year. SETTING: The study was conducted in six children's hospitals located in Pittsburgh, Houston, Los Angeles, Chicago, Washington, D.C., and Columbus, Ohio. PATIENTS: Enrolled were 173 children, 8 weeks to 12 years of age, with suspected bacterial meningitis; 143 children were evaluable. Eighty-seven percent of patients were followed for at least 6 weeks to 3 months, and 67% were followed for 1 year. INTERVENTIONS: Subjects were randomized to receive ceftriaxone with or without dexamethasone (0.15 mg/kg every 6 hours for 4 days). Auditory brainstem responses (ABR) were measured within 24 hours of admission. MAIN OUTCOME MEASURES: Hearing, development, and neurologic sequelae were assessed at the time of discharge and 6 weeks and 1 year later. MAIN RESULTS: One hundred forty-three patients (69 received dexamethasone and 74 received placebo) with bacterial meningitis were evaluable: Haemophilus influenzae type b (83), Streptococcus pneumoniae (33), Neisseria meningitidis (24), and three others. Overall, there was no significant difference in auditory outcome between dexamethasone and placebo recipients. Twenty-two children had bilateral moderate or more severe hearing loss at the time of the first ABR. At follow-up, the resolution of hearing impairment was nearly identical for each group. Nine of ten children who remained persistently deaf were deaf at the time of the first ABR. There were no differences in neurologic or developmental outcome between groups. CONCLUSION: All but one child with persistent bilateral moderate or more severe hearing loss had demonstrable deafness at the time of the first ABR. Dexamethasone did not significantly improve audiologic, neurologic, or developmental outcome in children with bacterial meningitis.

Ceftriaxone↗

Epidemiology of pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel: a 3-year nationwide prospective study. Israeli Pediatric Bacteremia and Meningitis Group.

In a 3-year nationwide prospective study on pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel, 1258 invasive infections with a known focus were observed. Meningitis was found in 482 (38%): 56%, 16%, and 76% of all infections by H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. The incidence of meningitis during the first year of life was 67.1, 17.5, and 9.5/100,000 for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively, and in children < 5 years old it was 18.5, 5.3, and 5.2. Extrapolated for a population in which 100,000 live births occur yearly, 2097 hospital days were required. The case fatality rate was 2.2%, 5.9%, and 6.3% for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. Boys were affected significantly more often than girls, but mortality was higher among girls. On the basis of the observed serotypes and age distribution, even with optimal vaccine development in the next 5 years, it is not likely that > 50% of all cases will be prevented.

Age Distribution↗

Cerebrospinal fluid and serum immunoglobulins and antibody titers in mumps meningitis and aseptic meningitis of other etiology.

Cerebrospinal fluid (CSF) and serum from 19 patients with mumps meningitis and 19 patients with meningitis of other etiology were investigated on two or more occasions for at least 1 month after onset. Intrathecal synthesis of immunoglobulin (Ig) G was found in 55%, of IgA in 26%, and of IgM in 24% of the patients. Oligoclonal Ig was demonstrable by agarose gel electrophoresis in 37% of the patients, mostly already during the first week after onset, and could persist for years. Mumps virus antibody synthesis within the central nervous system occurred in 37% of the mumps meningitis patients. The inflammatory reaction within the central nervous system as reflected by mononuclear pleocytosis, Ig synthesis, and oligoclonal Ig was not correlated to the clinical course. The blood-brain barrier was evaluated by determination of the CSF total protein, CSF/serum albumin ratio, and CSF/serum alpha2-macroglobulin ratio. A significant correlation was found among these three parameters. Persistence of the elevated CSF/serum albumin ratio seems to influence prognosis, and this parameter is recommended for evaluation of the blood-brain barrier function.

Antibodies, Viral↗

Rapid diagnosis of lymphocytic meningitis by frequency-pulsed electron capture gas-liquid chromatography: differentiation of tuberculous, cryptococcal, and viral meningitis.

Cerebrospinal fluid specimens from patients with tuberculous (17 cases), cryptococcal (15 cases), and viral (14 cases) meningitis were analyzed by frequency-pulsed electron capture gas-liquid chromatography and mass spectrometry. Compounds that disappeared after therapy were found to be present in each of these specimens and were not detected in controls. They occurred in repetitive patterns such that these three types of meningitis could be rapidly distinguished. The compound associated with tuberculous meningitis has been tentatively identified. These finding have implications for rapid diagnosis, pathophysiological studies, and possible new therapeutic approaches.

Chromatography, Gas↗

Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group.

OBJECTIVE: To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults. DESIGN: Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30. RESULTS: Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion. CONCLUSION: Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae.

Adult↗

Mycobacterium tuberculosis meningitis and other etiologies of the aseptic meningitis syndrome.

Mycobacterium tuberculosis is one of the most common infectious agents in the world. It causes an insidious form of meningitis characterized by headache, low-grade fever, stiff neck and cranial nerve palsies, and an acute meningoencephalitis characterized by coma, raised intracranial pressure, seizures, and focal neurological deficits. This review focuses on the diagnosis and therapy of the insidious form of tuberculous meningitis and discusses the differential diagnosis of infectious and noninfectious etiologies of the aseptic meningitis syndrome.

Behcet Syndrome↗

Listeria meningitis during treatment of a meningococcal meningitis in an immunocompetent infant.

A case report of a listeria meningitis 5 days after diagnosis of meningococcal meningitis in a immunocompetent child of 2 years is presented. The infection occurred during hospital admission. Culture results of cerebrospinal fluid (CSF) were confirmed by a listeria-specific polymerase chain reaction in 2 CSF specimens. The listeria meningitis quickly responded to antimicrobial treatment with intravenous amoxicillin combined with tobramycin.

Amoxicillin↗

[Meningeal melanocytoma: a rare meningeal tumor].

Meningeal melanocytoma is a rare benign pigmented tumor. It develops from melanocytes normally present in the meninges of the posterior fossa and medulla. It is an extra axial tumor, that manifests due to compression of adjacent structures. The authors report a case of meningeal melanocytoma located at the foramen magnum. They insist on the characteristic paramagnetic signal of the tumor on the different MRI sequences.

Cerebral Angiography↗

Detection of bacterial antigens in cerebrospinal fluid by a latex agglutination test in 'septic unknown' meningitis and serogroup B meningococcal meningitis.

The latex agglutination test (Wellcogen) was evaluated specifically in cases of 'septic unknown' meningitis, with CSF findings characteristic of bacterial meningitis but with no bacterial organisms grown on CSF culture or seen on microscopy after Gram staining. In only 4 (12%) of 33 cases of 'septic unknown' meningitis were antigens identified in the CSF. This kit contains for the first time reagents for the detection of serogroup B Neisseria meningitidis antigens and was also evaluated for this bacteria. Only 6 (27%) of 22 serogroup B N. meningitidis cases were identified.

Antigens, Bacterial↗

[Cervico-mimetic meningeal symptom in acute diffuse lesions of the cerebral meninges].

The response of a patient in the form of a painful grimace at the examination of occipital rigidity is considered as an objective positive cervical-mimic symptom. Its informative value increases when diffuse muscular hypertonus and restlessness compound the study and interpretation of the major classic meningeal symptoms. In seven patients, a positive symptom made it possible to connect their state with acute diffuse meningeal pathology prior to a cerebrospinal fluid examination; a negative symptom allowed the exclusion of meningeal pathology in 13 patients which was confirmed by CSF examination. The author failed to find any reported data on this symptom.

Acute Disease↗

Experimental pneumococcal meningitis: cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitric oxide.

We investigated whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA) and the free radical scavenger superoxide dismutase influences cerebral blood flow changes, brain edema, and cerebrospinal fluid pleocytosis in early experimental pneumococcal meningitis. Compared to untreated infected rats, superoxide dismutase given 3 hours after infection significantly attenuated the increase of brain water content, intracranial pressure, and cerebrospinal fluid white blood cell count, but did not modulate the increase in regional cerebral blood flow. N-Nitro-L-arginine treatment (5 mg/kg intravenously, followed by 5 mg/kg/hour) reversed the increase in regional cerebral blood flow; prevented an increase in brain water content, intracranial pressure, and cerebrospinal fluid nitrite concentrations; and reduced cerebrospinal fluid white blood cell count. With a closed cranial window preparation, N-nitro-L-arginine prevented pneumococci-induced dilatation of pial arterioles. When the effective dose was increased twofold, the effects of N-nitro-L-arginine became more pronounced but resulted in the death of 4 of 5 rats, probably due to hemodynamic side effects. In primary cultures of rat cerebral endothelial cells, nitrite concentrations increased after pneumococcal stimulation, which could be prevented by N-nitro-L-arginine and cycloheximide. These data suggest that (a) nitric oxide accounts for regional cerebral blood flow changes and pial arteriolar dilatation in the early phase of experimental pneumococcal meningitis; (b) both superoxide radical and nitric oxide are involved as mediators of brain edema and meningeal inflammation; and (c) cerebral endothelial cells can be stimulated by pneumococci to release nitric oxide presumably via the inducible nitric oxide synthase.

Amino Acid Oxidoreductases↗

Analysis of cytokine levels in cerebrospinal fluid in mumps meningitis: comparison with echovirus type 30 meningitis.

BACKGROUND: It is unclear whether or not the CSF cytokine profiles in viral meningitis differ with the kind of causative virus. METHODS: We measured the concentrations of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, and IL-10 in CSF during the acute stage in 15 children with mumps meningitis (MM), and 34 with echovirus type 30 meningitis (EM). RESULTS: The CSF IFN-gamma, IL-2, IL-6, and IL-10 levels were elevated in MM, and the CSF IFN-gamma, IL-2, and IL-6 levels were elevated in EM. The CSF IFN-gamma, IL-2, and IL-10 levels in MM were significantly higher than those in EM (p<0.0001, p<0.0001, and p<0.0001, respectively). The CSF IL-6 levels in EM were significantly higher than those in MM (p=0.0255). The CSF TNF-alpha and IL-4 levels were not elevated in MM or EM. In MM, the IL-6 level was correlated with the IL-2 and IL-10 levels in CSF (p=0.0347 and p=0.0120, respectively). In EM, the IFN-gamma level was correlated with the IL-10 level in CSF (p=0.0002). CONCLUSION: CSF cytokine profiles in MM were different from those in EM. Therefore, it is likely that the pathogenesis of MM is different from that of EM.

Adolescent↗

Acute meningococcal meningitis: analysis of features of the disease according to the age of 255 patients. Copenhagen Meningitis Study Group.

Clinical and laboratory features of acute meningococcal meningitis according to age were studied in 255 patients. Whereas males accounted for three out of five patients aged 0-4 years, females accounted for three out of four patients older than 50 years of age. All patients had clinical signs of nuchal rigidity and fever. Patients older than 30 years of age had less frequent petechiae (62%) than younger patients (81%). Furthermore, elderly patients above 50 years of age were prone to an obtunded mental state and a prolonged disease course with fever. Without relation to age, 2/3 had purulent meningitis and 2/3 had marked peripheral leucocytosis (> 15 x 10(9) cells/l); 90% of patients had at least one of these findings. The cellular inflammatory response in peripheral blood indicated a bacterial aetiology in > 95% of the cases. More than 80% of children and adults had abnormal CSF biochemical findings, but the level of protein and the glucose ratio (CSF/serum) were positively and negatively correlated to increasing age of the patient, respectively: thus, in children these biochemical markers may be unreliable in the differentiation between a bacterial and non-bacterial aetiology. Thrombocytopenia (< 100.000 x 10(9)/I) was not associated with age, though the lowest platelet count was found in elderly patients. The case fatality rate was 7.5%, but neither age, sex nor sign of septicaemia was associated with fatality. Thrombocytopenia, a lowered coagulation index (< 0.5, factors II, VII, X), a moderate anaemia (haemoglobin < 11 g/dl), an obtunded mental state and a history of convulsions were poor prognostic factors; only anaemia was independently correlated to fatality so this should be considered as an important prognostic marker in the acute phase of meningococcal meningitis.

Acute Disease↗

Recurring aseptic meningitis after travel to the tropics: a case of Mollaret's meningitis? Case report with review of the literature.

Recurrent aseptic meningitis in a 35-year-old caucasian woman is described. She had many attacks over a period of 9 years. The first attack occurred after travel in the tropics. In spite of extensive examinations no cause could be found for the recurrent attacks. Both the clinical presentation and characteristics of the cerebrospinal fluid are compatible with the diagnosis of Mollaret's meningitis. There is no known cure for this condition, although colchicine and indomethacin have been mentioned to relieve symptoms. In our patient, a treatment with indomethacin during the last attack resulted in a clear and rapid improvement of symptoms. Since this episode only mild relapses have occurred, all of which responded well to the same treatment. This case highlights the long time span in which attacks of Mollaret's meningitis can occur, and the spectacular benefit of indomethacin.

Adult↗