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Cerebrospinal fluid lactate in 78 cases of adult meningitis.

In a retrospective study of 78 cases of adult meningitis, the CSF lactate was measured on the first spinal tap (ST); 25 had a bacterial meningitis, 28 a viral meningitis; 22 other cases had been on antibiotics prior to admission; 3 cases had meningitis of rare aetiology. The median CSF lactate level among the 25 bacterial cases amounted to 13.6 mmol/l (range: 3.5-24.5) whereas it remained low in the 28 viral cases: 2.7 mmol/l (range: 1.4-4.2). These differences are highly significant. The comparison of the CSF lactate level with the other tests routinely performed showed that the CSF lactate level had the highest sensitivity, specificity and predictive values. The CSF lactate level on the first ST had no prognostic value, but a rapid decrease of the CSF lactate during the treatment is indicative of good prognosis. Among the pretreated cases, a high lactate level could be an indication that bacteria were the causal agents. In conclusion, the measurement of the CSF lactate, quickly performed and inexpensive, is worth performing when a meningitis is suspected, as it appears to be the best way of distinguishing bacterial from non-bacterial meningitis.

Adolescent↗

Penetration of ciprofloxacin into human cerebrospinal fluid in patients with inflamed and non-inflamed meninges.

The penetration of ciprofloxacin into the cerebrospinal fluid (CSF) in 25 patients with non-inflamed meninges and in 9 patients with inflamed meninges was studied. In the patients with non-inflamed meninges plasma and CSF were obtained 1-10 h after the second dose of ciprofloxacin and in the patients with inflamed meninges 1, 2, 3, 5, 7 and 9 h after the second dose. In the first group (non-inflamed meninges) data from 6 patients were obtained 4, 5 and 6 h post-dose. Mean ciprofloxacin concentrations in the CSF ranged from 0.073 mg/l to 0.106 mg/l during this observation time, while in the second group (inflamed meninges) they ranged from 0.089 to 0.260 mg/l. These results demonstrate that ciprofloxacin diffuses into the CSF at concentrations which exceed the MICs of Neisseria meningitidis and most gram-negative aerobic bacilli.

Adolescent↗

Transient diabetes insipidus following Escherichia coli meningitis complicated by ventriculoperitoneal shunt.

Although disorders of ADH secretion associated with meningitis are usually consistent with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), central diabetes insipidus (DI) is an exceptional complication of meningitis. Transient DI as a complication of Escherichia coli (E. coli) meningitis due to ventriculoperitoneal shunt in an 18-month-old boy is presented. Blood and spinal fluid cultures yielded E. coli, sensitive to cefotaxime. The DI arose on the day 3 after admission and continued to the day 20. Treatment comprised cefotaxime, dexamethasone, fluid adjustment and vasopressin. The course of our case supports that in cases of bacterial meningitis, initial fluid restriction may occasionally result in dangerous conditions. Therefore, all children with bacterial meningitis should be followed closely not only in terms of SIADH but also DI. To our knowledge this is the first transient DI associated with E. coli-caused meningitis case reported.

Dandy-Walker Syndrome↗

Dilatation induced by 5-HT in the middle meningeal artery of the anaesthetised cat.

In chloralose-anaesthetised cats, we studied the effects of intravenous and intra-carotid injections of 5-HT on the middle meningeal artery and the way these were modified by 5-HT antagonists. Cats were prepared for blood pressure recording and intravenous injections and a catheter inserted into one carotid artery via a lingual artery. The middle meningeal arteries were exposed and blood flow recorded with laser Doppler probes. Intravenous injections of 5-HT, 2-50 microg kg(-1) (5.2-129 nmole kg(-1)), produced a dose-dependent fall in blood pressure, a rise in meningeal blood flow, and an associated fall in middle meningeal resistance. Resistance changes were the result of a local dilatation and not due to changes downstream of the recording probe. Intracarotid injections of 5-HT produced similar systemic and craniovascular responses, which were larger in the ipsilateral middle meningeal artery. Dose-response curves of vascular resistance changes to intravenous injection of 5-HT were not significantly affected by WAY100635 (5-HT1A antagonist), GR127935 (5-HT(1B/1D) antagonist), methiothepin (5-HT2C and 5-HT7 antagonist), ketanserin (5-HT2A antagonist), SB203186 (5-HT4 antagonist) or cervical sympathectomy, but were blocked by the 5-HT(3/4) antagonist tropisetron, the 5-HT3 antagonist ondansetron, the ganglion-blocking drug hexamethonium and by vagotomy. These drugs and procedures did not significantly antagonise the response to intra-arterially injected 5-HT. We conclude that intravenously-administered 5-HT is a vasodilator in vivo in the cat dural circulation, and that the dilation is not mediated by 5-HT1, 5-HT2, 5-HT4 or 5-HT7 receptors, but is primarily mediated by a vagal reflex, initiated via 5-HT3 receptor activation and brought about by an increase in parasympathetic tone to the middle meningeal artery as part of the von Bezold-Jarisch reflex. There also appears to be a direct vasodilator effect mediated by unknown receptor types, particularly after intra-arterial administration. Neither of these effects is, however, likely to be of importance in the pathophysiology of migraine or other vascular headaches.

Animals↗

Blurring of the vessels of the interhemispheric fissure in multislice CT angiography: a sign of meningeal carcinomatosis.

Meningeal carcinomatosis remains a challenging diagnosis to make, with both cerebrospinal fluid (CSF) analysis and radiological methods having a limited sensitivity. We aimed at describing a possible diagnostic sign of multislice CT angiography (MS-CTA) in the diagnosis of meningeal carcinomatosis. Upon retrospective analysis of MSCT angiographies of the brain, a conspicuous sign of the vessels of the interhemispheric fissure was noted in five patients. Cranial MSCT angiographies were performed with a standardized protocol (120 kV, 200 mA s, collimation of 4x1 mm, table feed per rotation 4 mm). We injected 120 ml of nonionic contrast medium as a bolus, and data acquisition was started after a fixed delay of 35 s. In order to elucidate the finding, correlation with clinical follow-up and/or CSF findings was performed for all patients. In five patients there was a blurring, an increased number, and a pathologic configuration of the vessels of the interhemispheric fissure. All five patients with this sign had clinical signs and symptoms of meningeal carcinomatosis. Three patients had positive CSF cytology, one further patient had follow-up spinal MRI 6 weeks later demonstrating meningeal carcinomatosis. One patient declined lumbar puncture. MS-CTA has the capacity to demonstrate a pathologic configuration of the vessels of the interhemispheric fissure in patients with meningeal carcinomatosis. This sign may serve as an indicator of meningeal carcinomatosis and should raise the suspicion of this disease entity.

Cerebral Angiography↗

Malignant solitary fibrous tumor of the meninges.

Increasing numbers of solitary fibrous tumors (SFTs) in the meninges have been reported since this entity was first recognized. While most cases previously reported were considered to be benign, the malignant potential of extrathoracic SFTs has not been excluded. The authors report a rare case of a meningeal SFT with malignant behavior occurring in a Japanese female patient, initially resected when she was 44 years old and recurring in the same place four times during a 26-year follow-up period. A metastatic tumor to the right lung arose 25 years after the resection of the first meningeal tumor and focal invasion into the cerebellum was also observed with her last (5th) meningeal tumor. Immunohistochemical analysis showed all tumors to be diffusely positive for CD34 and negative for EMA, with a so-called "patternless" histological pattern, featuring thin collagen fibers between tumor cells. A focal "staghorn" vascular pattern was also observed. Ki67 (MIB-1) labeling indices and mitosis rates were 3.1+/-1.2% and less than 1/10 high power fields (HPF) in the first meningeal tumor and 16.1+/-6.4% and 6/10HPF in the last (5th) one, respectively. Thus, the present case suggests that meningeal SFTs possess malignant potential so that careful long-term follow up is required.

Adult↗

Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis.

Adenosine deaminase activity (ADA) determination in cerebrospinal fluid (CSF) is considered a specific test for the diagnosis of tuberculous meningitis. In order to study the variability of this marker in patients with different neurological disorders associated with HIV infection, and its utility for the diagnosis of tuberculous meningitis in these patients, the ADA levels in 417 CSF samples from HIV-infected patients with neurological symptoms were reviewed. HIV infection, HIV-associated neurological disorders, and progressive multifocal leukoencephalopathy were not associated with elevated ADA in CSF. Among patients with meningitis, receiver operating characteristic curve analysis gave an optimal ADA cut-off point of 8.5 IU/l for the diagnosis of tuberculous meningitis, with 57% sensitivity, 87% specificity, and an area under the curve of 0.747 (similar to that for CSF glucose concentration). False-positive results were found in patients with neurological CMV disease and cryptococcal, lymphomatous, and probable candidal meningitis. The results of this study indicate that ADA determination in CSF has limited utility for the diagnosis of tuberculous meningitis in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Cerebrospinal fluid leakage during transsphenoidal surgery: postoperative external lumbar drainage reduces the risk for meningitis.

Postoperative meningitis is a well known complication of transsphenoidal surgery (TSS). The objective of this study was to evaluate whether postoperative external cerobrospinal fluid (CSF) drainage in case of intraoperative CSF-leakage, reduces the risk of postoperative meningitis. We retrospectively reviewed a series of 278 consecutive transsphenoidal operations. In all operations with intraoperative CSF leakage, an external lumbar drain (ELD) was inserted directly postoperatively, and removed after at least 5 days. The incidence of postoperative meningitis was compared with that in a previously studied series of 228 consecutive transsphenoidal operations, without insertion of an ELD in cases with intraoperative CSF leakage. In the present series, postoperative meningitis occurred in 2/278 (0.7%) operations, compared to 7/228 (3.1%) operations in the previous study period (P < 0.05). Intraoperative CSF leakage was noted in 70/278 (25.2%) operations. All these patients received an ELD immediately after surgery for at least 5 days. There were no reported complications of ELD insertion. In the present series, 1 of 70 (1.4%) patients with intraoperative CSF leakage developed meningitis, compared to 3 of 22 (13.6%) patients in the previous study (P < 0.05). The present report on 278 consecutive transsphenoidal operations shows that the routine insertion of an ELD in patients in whom intraoperative CSF leakage is observed significantly reduces the incidence of postoperative meningitis. Possibly, diversion of CSF prevents the formation of a CSF fistula and thereby the risk of infection. The role of prophylactic antibiotic treatment in patients with CSF rhinorrhea after TSS remains to be established.

Drainage↗

Meningeal carcinomatosis in small cell carcinoma of the lung.

Cerebral and meningeal metastases are increasingly important complications in small cell anaplastic carcinoma of the lung. In a study at this institution, 60 evaluable patients received intensive chemotherapy without prophylactic cranial irradiation or other prophylactic measures. The complete plus partial remission rate was 78 percent with a median survival of 49+ weeks (range eight to 106+ weeks) for those with a complete response and 18+ weeks (range six to 67 weeks) for those with a partial response, all of which are comparable to other reported series. In 11 patients (18 percent) meningeal carcinomatosis has developed. Forty-two percent of the patients with a relapse have exhibited meningeal carcinomatosis and in 27 percent of the patients with a relapse it was the only site of relapse. Cerebral metastases occurred in 27 percent of those who had a relapse, and in 12 percent this was the sole site of relapse. Simultaneous meningeal carcinomatosis and cerebral metastases occurred in 8 percent of the patients with a relapse. The median time to meningeal relapse was 27 weeks (range 12 to 60 weeks) compared with 25+ weeks (six to 106+ weeks) over-all, and the median survival was 28 weeks (range 14 to 82 weeks) compared with 25+ weeks (two to 106+ weeks) for the whole group with small cell carcinoma of the lung. Meningeal involvement in small cell carcinoma of the lung must now be considered a sanctuary site of equal importance to cerebral metastases. To prevent and treat this complication will necessitate evaluation of all available modalities, including cranial and spinal irradiation, intrathecal chemotherapy and systemic agents that readily cross the blood-brain barrier.

Adult↗

Gamma delta T lymphocytes and proinflammatory cytokines in bacterial meningitis.

BACKGROUND: Patients with bacterial meningitis have a T-cell defect and impaired cytokine production. METHODS: The phenotype and percentage of circulating alpha beta and gamma delta T-cell receptor-bearing lymphocytes were determined from patients with bacterial meningitis (Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis), patients with bacterial infection but without meningitis, and healthy control subjects by a monoclonal antibody staining method. The in vitro production of cytokines, interleukins (IL-2, IL-6), interferon-gamma and tumor necrosis factor-alpha was measured by the bioassay or ELISAs. RESULTS: The percentage of circulating gamma delta T cells with a CD3+CD4+CD8- phenotype was significantly (p < 0.001) increased in all patients with bacterial meningitis compared with patients with bacterial infection and healthy control subjects. The CD3+ gamma delta T cells from patients with meningitis produced highly elevated levels of two proinflammatory cytokines, tumor necrosis factor-alpha and IL-6. However, interferon-gamma production was enhanced by CD3+ alpha beta T cells. CONCLUSION: The increased percentage of circulating T-cell receptor gamma delta T cells and their in vitro production of tumor necrosis factor-alpha and IL-6 cytokines may play an important role in the pathogenesis and inflammatory response in bacterial meningitis.

Antibodies, Monoclonal↗

Rapid disappearance of Haemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines.

Mortality from meningitis caused by Haemophilus influenzae type b (Hib), a disease that affects mainly infants and young children, can reach 5% in industrialised countries and ten times that in non-industrialised countries. To determine the efficacy of vaccination against Hib, we carried out a retrospective survey of the incidence of Hib meningitis over five decades in the Greater Helsinki area of Finland, where all children with bacterial meningitis are treated in one of three centres. Except for a meningococcal epidemic in the early 1970s, Hib was the leading cause of childhood bacterial meningitis until the Hib conjugate vaccines changed the picture profoundly. In 1986-87 the polysaccharide-diphtheria toxoid conjugate (PRP-D) was given experimentally to 50% of infants. In 1988-89 all infants were vaccinated, 50% with PRP-D, 50% with another conjugate vaccine, the oligosaccharide-CRM197 protein conjugate (HbOC). Since 1990 a third conjugate vaccine, the polysaccharide-tetanus toxoid (PRP-T), has been administered routinely to all infants. The vaccines were administered at age 3-6 months, with a booster dose at 14-18 months. In the first 5 years of the Hib vaccination programme the number of cases of Hib meningitis in children aged 0-4 years fell sharply, from 30 in 1986 (the first year of the programme) to none in 1991. The decline contrasts sharply with the rising trend up to the mid 1980s. Vaccination seems to be the only explanation for the observed change in the epidemiology of Hib meningitis.

Adolescent↗

Risk of aseptic meningitis after measles, mumps, and rubella vaccine in UK children.

Cases of aseptic meningitis associated with measles/mumps/rubella vaccine were sought in thirteen UK health districts following a reported cluster in Nottingham which suggested a risk of 1 in 4000 doses, substantially higher than previous estimates based on cases reported by paediatricians (4 per million). Cases were ascertained by obtaining vaccination records of children with aseptic meningitis diagnosed from cerebrospinal fluid samples submitted to Public Health Laboratories or discharged from hospital with a diagnosis of viral meningitis. Both methods identified vaccination 15-35 days before onset as a significant risk factor and therefore indicative of a causal association. With both, half the aseptic meningitis cases identified in children aged 12-24 months were vaccine-associated with onset 15-35 days after vaccine. The study confirmed that the true risk was substantially higher than suggested by case reports from paediatricians, probably about 1 in 11,000 doses. However, the possibility that the aseptic meningitis induced by vaccination was largely asymptomatic and a chance laboratory finding in children investigated for other clinical conditions, particularly febrile convulsions, could not be excluded. Comparison of national reports of virus-positive mumps meningitis cases before and after the introduction of this vaccine indicated that the risk from wild mumps was about 4-fold higher than from vaccine. Altogether, 28 vaccine-associated cases were identified, all in recipients of vaccines containing the Urabe mumps strain. The absence of cases in recipients of vaccine containing the Jeryl Lynn strain, despite its 14% market share, suggested a higher risk from Urabe vaccine. A prospective adverse event surveillance system using the study methods is currently being established to assess the risk, if any, from the Jeryl Lynn strain which is now the only mumps vaccine used in the UK.

Child, Preschool↗

CSF findings in Lyme meningitis.

The results of cerebrospinal fluid examination in 59 cases of meningitis caused by Borrelia burgdorferi were analysed and compared with 73 non-Lyme meningitis cases. There was no statistically significant difference in the median cell count of 160 x 10(6)/l in the Lyme meningitis patients and the 150 x 10(6)/l in the non-Lyme cases. The protein level was elevated in both patients groups to 0.9 g/l and 0.8 g/l, respectively. The glucose level of 2.9 mmol/l (1.0-6.1) was, however, significantly (P = 0.005) lower in Lyme meningitis than the 3.3 mmol/l (1.6-5.4) in the non-Lyme cases. The most important observation of the study was the finding of a combination of pleocytosis, elevated protein (greater than 0.6 g/l) and low glucose levels (less than 2.1 mmol/l) (considered to be pathognostic for tuberculous meningitis) in six of 59 cases of Lyme meningitis.

Animals↗

Bacterial meningitis in Hong Kong: 10-years' experience.

OBJECTIVE: We studied the etiology, clinical features and outcome of patients with bacterial meningitis from an urban Chinese city over a 10-years period. METHODS: We reviewed the files of all persons aged 15-years old or above diagnosed with community-acquired bacterial meningitis from a regional hospital. The clinical findings, relevant laboratory and imaging results as well as outcome were recorded in cases with microbiological evidence of meningitis. Neurosurgical and pediatric patients were excluded. RESULTS: Sixty-five patients between the ages of 15 and 86 years of age (mean 52 years) were identified of whom 18 (28%) died. The four most common causes were Mycobacteria tuberculosis (46%), Streptococcus pneumoniae (11%), Streptococcus suis (9%) and Klebsiella pneumoniae (8%). Neisseria meningitidis and Haemophilus influenzae were rare pathogens. The annual incidence of community-acquired bacterial meningitis was 1.27/100,000 adults. Delay in treatment was associated with a poorer prognosis (p<0.001, OR=38.84, CI=7.33-205.80). CONCLUSION: The causative organisms found in this region of China differ from that reported from Europe and the US; tuberculous meningitis is the most common cause of bacterial meningitis.

Adolescent↗

Ten years of clinical experience with adult meningitis at an urban academic medical center.

The purpose of this study is to describe the clinical presentation and bacteriology of adult patients admitted to an urban academic medical center with bacterial meningitis over a 10-year period. In this retrospective review, we identified all adult patients discharged from a tertiary care facility between November 1992 and March 2003 with a diagnosis of bacterial meningitis. Data regarding demographics, vital signs, presenting symptoms, seven predisposing factors, body fluid cultures, cerebrospinal fluid (CSF) findings, and mortality were abstracted. Data were analyzed using descriptive methods. We identified 38 cases. Overall mortality rate was 18.4% (95% confidence interval 7.7-34.3%). The most common of the seven predisposing factors was an immunocompromised state (31.6%). Streptococcus pneumoniae (24.3%), other streptococcus species (24.3%), and Gram-negative rods (16.2%) were the most commonly identified organisms. The classic meningitis triad (fever, neck stiffness, mental status change or headache) was present in only 21.1% of cases. CSF analysis demonstrated WBC >or= 100/mm3 in 81.3%, decreased glucose (< 50 mg/dL) in 50%, and elevated protein (> 45 mg/dL) in 91.2%. With increasing numbers of immunocompromised patients, atypical presentations of bacterial meningitis seem to be more common. A higher percentage of bacterial meningitis cases seem to be caused by Gram-negative rods and Streptococcus species other than Streptococcus pneumoniae. The classic meningitis triad occurred in fewer cases than previously described.

Academic Medical Centers↗

Seizures complicating infantile and childhood bacterial meningitis.

In this study, 116 patients, at least 1 month of age but younger than 5 years, were identified with culture-proven bacterial meningitis. A comparison was made between the clinical data of the patients with and without seizures during hospitalization. Seizures during acute bacterial meningitis accounted for 47% (55/116) of the episodes. Time interval between the onset of bacterial meningitis and that of seizures was 1 to 20 days (mean, 4 days). Twelve of these 55 patients had one or more afebrile seizures after completing the treatment. At follow-up of at least 1 year after completing treatment, 26 patients had good outcomes, whereas the other 29 patients had poor outcomes. A strong correlation between the findings of abnormalities through neuroimaging and the occurrence of seizures during hospitalization was observed. The long-term outcomes of patients with infantile and childhood bacterial meningitis, who had seizures during the acute phase of bacterial meningitis, were worse than the outcomes of those who did not have such seizures. No child developed late seizures unless there were acute seizures. Factors associated with seizures during acute bacterial meningitis include disturbed consciousness on admission, abnormal neuroimaging findings, and low glucose and high concentration of total proteins in cerebrospinal fluid.

Chi-Square Distribution↗

Ultrastructure of canine meninges after repeated epidural injection of S(+)-ketamine.

BACKGROUND: The safety of ketamine when administered by the spinal route must be confirmed in various animal species before it is approved for use in humans. This study evaluates the ultrastructure of canine meninges after repeated doses of epidural S(+)-ketamine. METHODS: Five dogs received S(+)-ketamine 5%, 1 mg/kg, twice a day for 10 days through an epidural catheter with its tip located at the L5 level. One dog received the same volume of normal saline at the same times. The spinal cord and meninges were processed for histopathological and ultrastructural studies. Clinical effects were assessed after each injection. RESULTS: Motor and sensory block appeared after each injection of S(+)-ketamine, but not in the dog receiving saline. No signs of clinical or neurologic alterations were observed. Using light microscopy, no meningeal layer showed alterations except focal infiltration at the catheter tip level by macrophages, lymphocytes, and a few mast cells. The cells of different layers were studied by electron microscopy and interpreted according to data from human and other animal species because no ultrastructural description of the canine meninges is currently available. There were no cellular signs of inflammation, phagocytosis, or degeneration in meningeal layers and no signs of atrophy, compression, or demyelinization in the areas of dorsal root ganglia and spinal cord around the arachnoid. These findings were common for dogs receiving S(+)-ketamine and the dog receiving saline. CONCLUSION: Repeated doses of epidural S(+)-ketamine 5%, 1 mg/kg, twice a day for 10 days was not associated to cellular alterations in canine meninges.

Animals↗

The significance of seizures and other predictive factors during the acute illness for the long-term outcome after bacterial meningitis.

BACKGROUND: Seizures are important neurological complications of bacterial meningitis, but no information about its epidemiology and the outcomes of seizures after community-acquired bacterial meningitis (CABM) in an adult population have been reported. AIMS: To determine the frequency, clinical relevance, subtypes of seizures during the acute phase of bacterial meningitis, and the long-term outcomes of seizure complicating adult CABM. METHODS: In this 12-year retrospective study, 117 adult patients were identified with culture-proven CABM. A comparison was made between the clinical data of the patients with and without seizures during hospitalization. RESULTS: Thirty-one patients had seizures during CABM, accounting for 27% (31/117) of the episodes. The time interval between the onset of bacterial meningitis and the seizures was 1-21 days (mean, 4 days). Furthermore, 80% (25/31) of the episodes occurred within 24 h of presentation. Ten patients who had seizures progressed to status epilepticus. At follow-up after completing treatment, 10 patients completely recovered and were seizure-free, 19 died of meningitis during the acute stage and the other two progressed to chronic epilepsy. CONCLUSION: A log-rank test demonstrated that the long-term outcome of adult CABM with acute seizures produced worse outcomes than for those who had no seizures, though no difference was noted between focal and generalized seizures. None of our patients without seizures in the acute phase of bacterial meningitis developed late seizures during the follow-up periods. Poor outcome in this study may attribute to neurological complications such as seizure, hydrocephalus, infection itself, or a combination of complications.

Aged↗