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Inappropriate antidiuretic hormone in children with viral meningitis.

Urinary excretion rates of antidiuretic hormone were determined by radioimmunoassay in children with bacterial (6) and viral (11) meningitis, and in children with other febrile illnesses (7). These values were compared to normal data obtained from 50 healthy, normally hydrated children ranging in age from 1 week to 9 years. Plasma sodium concentrations were measured in the sick children; urine osmolality and creatinine concentrations were measured in all children. Upon admission, all children with bacterial meningitis and 64% of those with viral meningitis had urinary antidiuretic hormone excretion rates greater than 2 S.D. above values obtained from age-matched controls. Fifty-seven percent of children with other febrile illnesses had similarly elevated antidiuretic hormone values; however, only in the bacterial and viral meningitis groups were antidiuretic hormone excretion rates inappropriate because they occurred when serum sodium concentrations were found to be normal or low normal (i.e., 136 +/- 2 mEq/L and 137 +/- 1 mEq/L, respectively). The average serum sodium in the group with other febrile illnesses was higher (146 +/- 5 mEq/L; p less than 0.05) and could represent an appropriate stimulus for antidiuretic hormone release. In spite of high levels of antidiuretic hormone, most viral meningitis patients did not concentrate their urine, probably because all except 2 were younger than 2 months of age. We conclude that viral meningitis, like bacterial meningitis, frequently is associated with inappropriate antidiuretic hormone secretion; however, most children with viral meningitis may be protected from developing hyponatremia because of their inability to concentrate their urine.

Child↗

[Serum procalcitonin levels in children with bacterial or viral meningitis].

OBJECTIVE: To investigate the ability of serum procalcitonin (PCT) to differentiate between bacterial and viral meningitis. METHODS: The serum PCT levels were measured in 41 children with acute bacterial (n=18) or viral (n=23) meningitis by immunoluminometric assay. Meanwhile serum CRP levels and erythrocyte sedimentation rate (ESR) were measured. RESULTS: The children with acute bacterial meningitis had higher levels of PCT (51.73 +/- 30.75 microg/L) and CRP(182.36 +/- 54.5 mg/L) and ESR (50.44 +/- 8.95 mm/h) than those with viral meningitis (0.84 +/- 0.99 microg/L, 8.90 +/- 10.66 mg/L and 16.75 +/- 13.23 mm/h respectively, P < 0.01). Both PCT and CRP had high predictive value for bacterial meningitis based on the area under curve of the receiver operating characteristics curves, 0.984 for PCT (95% confidence interval 0.953-1.013) and 0.983 for CRP (95% confidence interval 0.954-1.012) (P > 0.05). All of the children with bacterial meningitis had serum PCT levels above 0.5 microg/L, but only 2 patients with viral meningitis exceeded this value. CONCLUSIONS: The measurement of serum PCT levels may be of value in the differential diagnosis of meningitis due to either bacterial or viruses.

Blood Sedimentation↗

Application of PCR for various neurotropic viruses on the diagnosis of viral meningitis.

BACKGROUND: Epidemiological studies have indicated that the majority of cases of aseptic meningitis result from viral infections. However, specific viral pathogens for aseptic meningitis can be identified in only some cases even if consistent conventional diagnostic methodologies rare used. OBJECTIVES: To clarify the etiological agents of aseptic meningitis by means of polymerase chain reaction (PCR) for various neurotropic viruses. STUDY DESIGN: Cerebrospinal fluid (CSF) samples were collected from 73 children suspected of having meningitis from November 1991 to December 1994. The samples were examined for infectious viruses by cell culture and for viral genomes by PCR. RESULTS AND CONCLUSIONS: Of 45 samples from patients diagnosed with aseptic meningitis, positive PCR results for enterovirus, mumps virus, cytomegalovirus, and varicella-zoster virus were obtained from respectively 25, 14, 1, and 1. Viral pathogens were thus identified in 41 (91.1%) of the 45 CSF samples. By the combination of PCR methods with conventional virological methods, the diagnosis of viral meningitis was established in 97.8% of the 45 cases. Our findings prove that the application of PCR methods is useful for etiological study of aseptic meningitis, and that the vast majority of cases of aseptic meningitis result from viral infection.

Cerebrospinal Fluid↗

[Outpatient management of children with viral meningitis].

OBJECTIVE: To describe our experience in the extrahospitalary management of children with suspected viral meningitis (YM). METHOD: Between April and July 1997. 156 children were diagnosed of YM in our hospital and 150 managed as outpatients, after being a few hours in our emergency department. All of them were suspected to have VM attending usual clinical and laboratory findings and were discharged with cautious instructions to demand a new assessment. We contacted telephonically with them one month and six months later. RESULTS: All the children with suspected viral meningitis and managed as outpatients had negative blood and CSF cultures and all of them did well. Telephonically, 104 children (69.3%) referred transient headache or back pain. and 20 of these (13.3% of all the 150) came again to our hospital, and 4 required rest for a few hours (4-12 hours) in our observation setting. Children with suspected VM didn't go to school during 5.9 x 6.1 days (1-30 days) and 71 (47.3%) were absent less than 3 days. CONCLUSION: Outpatient management of most of the children with suspected VM is possible. When a patient is sent home, detailed instructions must be given to the family.

Adolescent↗

Viral meningitis and encephalitis: traditional and emerging viral agents.

In the United States, the annual number of central nervous system (CNS) infections that occur as a result of viral agents far exceeds that of infections caused by bacteria, yeast, molds, and protozoa combined. The recent incursion of West Nile virus (WNV) into North America has led to a dramatic change in the incidence and epidemiology of summer-associated viral CNS disease. As a result of increased testing for WNV, lesser known viral causes of CNS infection have been identified. Even the epidemiology of such traditional viral neuropathogens as rabies has changed in recent years. This review provides an overview of viruses traditionally associated with meningitis and encephalitis (enteroviruses, La Crosse virus, St. Louis encephalitis virus, eastern and western equine viruses, varicella-zoster virus), as well as several of the less common (Powassan virus, lymphocytic choriomeningitis virus, Colorado tick fever virus, rabies virus, influenza viruses, etc.) and emerging (West Nile virus) viral pathogens.

Communicable Diseases, Emerging↗

Interferon induction and granulocyte function in patients with viral meningitis.

In 22 consecutive patients with acute viral meningitis we studied the ability of neutrophilic granulocytes to phagocytize yeast particles, the interferon (IFN) levels in serum and cerebrospinal fluid as well as the activity of the enzyme 2'-5' oligoadenylate synthetase in peripheral lymphoid cells. During the acute stage of illness a decreased phagocytosis of the neutrophils was demonstrated, while the adherence of yeast particles to the cells was increased. This was accompanied by the presence of IFN in the cerebrospinal fluid and an increase in the 2'-5' oligoadenylate synthetase activity of peripheral lymphoid cells. About two months after onset of symptoms the synthetase activity and the phagocytic activity of granulocytes were restored to normal levels. The results of this study may indicate that the impaired neutrophil function in viral disease is influenced by increases in IFN levels in vivo.

2',5'-Oligoadenylate Synthetase↗

[A score for the differential diagnosis of bacterial and viral meningitis].

The purpose of this study was to verify the statistical validity of the score proposed by Thomé et al. for the differential diagnosis between bacterial and viral meningitis and to study the utility of two new parameters (CRP and the patient's age). A retrospective review of 136 consecutive cases of meningitis was made. The cases were classified into three groups according to the culture results and the use or not of intravenous antibiotics. There were 20 cases of bacterial meningitis, 60 non-bacterial and 56 cases of meningitis of uncertain etiology. Considering only the patients in the first two groups, the capacity for differential diagnosis between bacterial and non-bacterial meningitis of the 8 parameters in the original score, the CRP and the patient's age was analyzed with a numeric value of 0, 1, or 2 assigned to each parameter. Finally, the results of applying the score that includes the two new parameters with the original score are compared. We found that all parameters showed statistical significance for the differential diagnosis between bacterial and viral meningitis. The resulting score can be used in order to decide the need for intravenous antibiotic therapy, with only a few cases being uncertain. The score with the two new parameters correctly classified 78 of the 80 cases, while leaving only two case uncertain as compared to the four that remained unclassified with the original score. We conclude that the score is a useful instrument in the differential diagnosis between bacterial and viral meningitis. Furthermore, the introduction of CRP and the patient's age improves the diagnostic value of the test.

Adolescent↗

Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study.

OBJECTIVE: To test the hypotheses that patients exposed to viral meningitis would be at an increased risk of developing chronic fatigue syndrome and would have an excess of neurological symptoms and physical impairment. METHODS: Eighty three patients were followed up 6-24 months after viral meningitis and a postal questionnaire was used to compare outcome with 76 controls who had had non-enteroviral, non-CNS viral infections. RESULTS: For the 159 patients and controls the prevalence of chronic fatigue syndrome was 12.6%, a rate higher than previously reported from primary care attenders, suggesting that moderate to severe viral infections may play a part in the aetiology of some fatigue states. Those with a history of meningitis showed a slight, non-significant increase in prevalence of chronic fatigue syndrome (OR 1.4; 95% CI 0.5-3.6) which disappeared when logistic regression and analysis was used to correct for age, sex, and duration of follow up (OR 1.0; 95% CI 0.3-2.8). Controls showed marginally higher psychiatric morbidity measured on the general health questionnaire-12 (adjusted OR 0.6; 95% CI 0.3-1.3) Both groups had similar rates of neurological symptoms and physical impairment. The best predictor of chronic fatigue was a prolonged duration time of off work after the illness (OR 4.93, 95% CI 1.3-18.8). The best predictor of severe chronic fatigue syndrome diagnosed by Center for Disease Control criteria was past psychiatric illness (OR 7.82, 95% CI 1.8-34.3). Duration of viral illness, as defined by days in hospital, did not predict chronic fatigue syndrome. CONCLUSIONS: (1) The prevalence of chronic fatigue syndrome is higher than expected for the range of viral illnesses examined; (2) enteroviral infection is unlikely to be a specific risk factor for its development; (3) onset of chronic fatigue syndrome after a viral infection is predicted by psychiatric morbidity and prolonged convalescence, rather than by the severity of the viral illness itself.

Adolescent↗

Cerebrospinal fluid levels of soluble CD14 in inflammatory and non-inflammatory diseases of the CNS: upregulation during bacterial infections and viral meningitis.

The CD14 antigen, an important cell surface molecule of monocytic cells, is involved in cellular activation: it binds lipopolysaccharide and other cellular lipid structures. Brain macrophages play a pivotal role during inflammatory reactions of the CNS parenchyma, ventricles and meninges. A soluble form of CD14 (sCD14) was measured in paired cerebrospinal fluid (CSF) and serum samples from 91 patients with different neurological diseases. Mean levels of circulating sCD14 in CSF in a control group of 22 patients with neurologic complaints but no neurological deficit on clinical examination were 0.19 +/- 0.06 (mean +/- SD) mg/l. The CSF/blood ratios of sCD14 was 49 +/- 16 x 10(-3), while those of albumin were 4.4 +/- 1.4 x 10(-3). These extremely high CSF/blood ratios of the sCD14 molecule compared to albumin indicate a local cerebral production. No significant changes in CSF sCD14 levels were found in patients with non-inflammatory neurological diseases (NID). In contrast, CSF sCD14 levels were markedly elevated during acute meningitis, but there was no direct correlation between sCD14 and monocyte count in the CSF. Thus, sCD14 could not originate in the CSF compartment from monocytes alone. The highest values for sCD14 were found in CSF during infections with various pathogens such as Staphylococcus aureus or Listeria monocytogenes. While sCD14 serum levels dramatically increased during acute bacterial meningitis, sCD14 ratios did not correlate with albumin ratios during the course of disease. Therefore, increased CSF sCD14 may originate from cerebral production by activated or infiltrated macrophages rather than passive diffusion from the blood, while elevated sCD14 serum levels resulted from enhanced local production. Increased CSF and serum sCD14 values were also observed in meningitis caused by viral infection. As in bacterial meningitis, sCD14 in CSF specimens did not correlate with the function of the blood/CSF barrier. Repeated lumbar punctures revealed a normalization of CSF sCD14 levels during clinical recovery. These results provide the first evidence for local production of sCD14 within the CNS. Our findings further indicate that sCD14 in CSF is a reliable marker for activation of macrophages within the CNS during inflammatory processes.

Acute Disease↗

Laboratory surveillance of viral meningitis by examination of cerebrospinal fluid in Cape Town, 1981-9.

Nine years accumulated laboratory data derived from the culture of the cerebrospinal fluid of 11,360 aseptic meningitis cases were retrospectively reviewed to establish the epidemiology of viral meningitis in Cape Town. Virus was isolated from 3406 of the cases (91% enteroviruses and 9% mumps). Five major summer viral meningitis episodes were documented: two of echovirus 4 (706 and 445 cases), echovirus 9 (223), coxsackie A9 (104) and one of unidentified enterovirus (324 cases--probably echo 9). Although coxsackie B was endemic, clusters of one or other type were dominant at any one time. Mumps was endemic. Sixty-two percent of all viral cases were < 5 years old. The median ages of 4 and 5 years in echoviruses 9 and 4 (the epidemic strains) contrasted with that of 1 year in coxsackie B (with many cases < 3 months old). Mumps peaked at 3-4 years of age. Males dominated overall, particularly in mumps.

Adolescent↗

[Procalcitonin, C-reactive protein and interleukin 6 in bacterial and viral meningitis in children].

OBJECTIVES: In young children with meningitis, blood or cerebrospinal fluid (CSF) analysis cannot differentiate all cases of viral meningitis (VM) from bacterial meningitis (BM). Empirical antibiotic therapy is often given. As new markers are needed, we compared serum proCalcitonin (PCT) with CSF analysis for C-reactive protein (CRP) and interleukin-6 (IL6). PATIENTS AND METHODS: PCT was measured with a chemoluminescent assay in the sera of 23 children (aged 3 months to 14 years) hospitalized for BM and in 51 patients with VM. RESULTS: Initial CRP (mean 143.3 mg/l, range 28-351 and mean 13.9, range 1-48), CSF proteins (mean 2.2, range 0.4-4.74 and mean 0.57, range 0.12-2.72) and white blood cell count in CSF (range 240-17500 and 20-3200) in BM and VM respectively, were not sufficiently discriminative to distinguish between BM and VM. Twenty-four of the 51 patients with VM were given antibiotics. IL6 values at admission showed an overlap zone (> 100 pg/ml in 7/19 patients with VM and < 100 pg/ml in 1/8 patients with BM. PCT was discriminative in all cases: mean PCT in BM was 61 micrograms/l (range 4.8-335) and 0.33 in VM (range 0-1.7; p < 0.001). No production of PCT was detected in CSF. After antibiotic therapy, PCT decreased and reached undetectable levels after recovery. CONCLUSION: PCT is a sensitive and specific marker for early diagnosis of viral meningitis versus bacterial meningitis in children.

Adolescent↗

Measurement of procalcitonin levels in children with bacterial or viral meningitis.

We measured the plasma procalcitonin levels in 59 children who were admitted to the hospital because of bacterial or viral meningitis. Eighteen children with acute bacterial meningitis had elevated procalcitonin levels (mean level, 54.5 micrograms/L; range, 4.8-110 micrograms/L). The procalcitonin levels in 41 children with viral meningitis were low (mean level, 0.32 micrograms/L; range, 0-1.7 micrograms/L; P < .0001). Assay of cerebrospinal fluid (CSF) cells and proteins and serum C-reactive protein showed a zone of overlapping values between the two groups. Procalcitonin was not produced in CSF. Plasma procalcitonin levels decreased rapidly during antibiotic therapy. These data suggest that the measurement of plasma procalcitonin might be of value in the differential diagnosis of meningitis due to either bacteria or viruses.

Adolescent↗

Immunologic defense in bacterial and viral meningitis in children.

The investigation of a number of parameters of nonspecific and specific defense in 13 purulent and 18 mumps meningitides gave no indication of underlying primary immunodeficiencies. Only in the acute phase of mumps meningitis did we find a temporary suppression of cellular immune reactions measured as diminished rate of incorporation of thymidine by phytohemagglutinin-stimulated peripheral blood lymphocytes.

Humans↗