Non-bacterial Meningitis Research Articles

OPSONIC ACTIVITY OF SERUM IN THE ACUTE PHASE OF MENINGITIS

The present study was designed to determine the opsonic activity of serum obtained from meningitis patients in the acute stage of their illness. This study was part of a Danish multicentre prospective study on various aspects of meningitis for a 12-month period. The opsonic activity of serum was determined by a phagocytosis and a chemiluminescence assay using human peripheral blood polymorphonuclear leukocytes. The mean chemiluminescence and phagocytosis indices determined in the sera of 58 patients suffering from various forms of bacterial or non-bacterial meningitis did not differ significantly from that of control sera. Although sera of 4 patients with pneumococcal, 3 with meningococcal, and 1 with streptococcal meningitis exhibited lower opsonic activity than the control sera in the chemiluminescence assay, their values in the phagocytosis assay were similar to control value. It is concluded that serum opsonic activity in meningitis patients is normal and similar to that of healthy individuals.

Report of the Task Force on Diagnosis and Management of Meningitis

Children still die or suffer permanent neurologic sequelae as a result of bacterial meningitis. Prompt diagnosis and aggressive management are the goals, but early signs of meningitis are often subtle and nonspecific and, therefore, may be recognized only in retrospect. The physician must identify among the many febrile children seen every day in office practice—most of whom have spontaneously resolving illnesses usually caused by viruses—the few children who have serious bacterial infection requiring early intervention. No single test or battery of tests replaces the clinical acumen of the physician in identifying the child with early signs of bacterial meningitis. Because of controversies about diagnosis and treatment of meningitis voiced in various forums, including the courtroom, the Task Force on Diagnosis and Management of Meningitis has been asked by the Executive Board of the American Academy of Pediatrics to prepare a report on the causes, diagnosis, management, and outcome of meningitis in infants and children. This task force selected for discussion issues of current relevance and controversy in the diagnosis and treatment of bacterial and nonbacterial meningitis. Many other aspects of meningitis are discussed elsewhere. Commentaries on the prevention of disease by chemoprophylaxis (antimicrobial agents) or immunoprophylaxis (vaccines) have been prepared by the Committee on Infectious Diseases of the American Academy of Pediatrics. In addition the Morbidity and Mortality Weekly Report (Centers for Disease Control, Atlanta) publishes recommendations on vaccine usage and chemoprophylaxis formulated by the Advisory Committee on Immunization Practices. These resources are of value to the practitioner who cares for children and needs information on optimal measures for the treatment and prevention of meningitis.

1104 QUANTITATIVE MEASUREMENT OF C-REACTIVE PROTEIN (CRP) IN CEREBROSPINAL FLUID (CSF) OF PATIENTS WITH BACTERIAL MENINGITIS

The quantitation of CRP in CSF was investigated to aid in distinguishing bacterial from non-bacterial meningitis and other conditions. Previous work has been limited by the lack of a sensitive quantitative assay. This report describes results with a solid-phase sandwich RIA using rabbit antl-CRP coated polystyrene microwells and radiolabeled mouse monoclonal anti-CRP. CRP levels were measured in the CSF of 139 infants and children: 43 had culture-proven bacterial meningitis, 35 had aseptic CNS infections, and 61 had other conditions without CNS involvement. The mean CRP concentration in the bacterial group was 4900 ng/ml (range 0–51,100 ng/ml). This was significantly higher than for the aseptic group (mean 66, range 0–438 ng/ml) and others (mean 141, range 0–1750 ng/ml). Most patients with bacterial meningitis (31/43=72%) had levels >500 ng/ml, whereas those with aseptic (0/35) or other conditions (4/61=7%) were usually <500 ng/ml. In general, there was little correlation between CRP level and CSF protein, glucose, or neutrophil count, but some patients with bacterial meningitis apparently had a poor or delayed inflammatory response, accounting for their low CRP levels. These data suggest that measurement of CRP in CSF may be a useful, though not infallible, predictor of bacterial meningitis, provided that methods for CRP detection are sensitive to <500 ng/ml.

The cerebrospinal fluid anion gap

A L T H O U G H M O S T P A T I E N T S with acute bacterial meningitis have well-defined abnormalities in their cerebrospinal fluid, a few do not.' This fact, coupled with the knowledge that certain patients with aseptic (nonbacterial) meningitis have CSF changes similar to those typically seen in bacterial diseases demonstrates the need for a rapid means of differentiating the two conditions. Recently, the enzymatic determination of CSF lactate has been suggested to be useful in this regard? Although this test is not readily available in all hospitals, Pavlakis and colleagues ~ found that calculation of the CSF anion gap was an alternative means of ascertaining this abnormality and that it reliably discriminated viral from bacterial meningitis. More recently, however, Rutledge et al' found that CSF lactate measurements were not, after all, helpful. Here we report !hat determination of the CSF anion gap also fails to provide the required specificity.

C-Reactive protein in spinal fluid of children with meningitis

We have evaluated a commercially available latex agglutination system for the detection of C-reactive protein in CSF by a prospective study of 56 patients with CSF pleocytosis. On initial lumbar puncture, C-RP was detected in 100% (24/24) of patients with culture-proven bacterial meningitis, compared to 6% (2/32) of patients in the nonbacterial group (chi 2 c = 44.8, P less than 0.0001). C-RP in CSF had a sensitivity of 1.0 and a specificity of 0.94 for detecting culture-positive, bacterial meningitis. It was a more sensitive test for differentiating bacterial from nonbacterial meningitis on initial CSF examination than was the number of CSF leukocytes, the absolute number of CSF polymorphonuclear leukocytes, CSF glucose concentration, CSF protein concentration, or Gram staining of CSF. Detection of C-RP by latex agglutination may prove to be a practical and reliable method for differentiating bacterial from nonbacterial meningitis.

1089 OEREBROSPINAL FLUID LACTIC ACID DEHYDROGENASE LEVELS IN MENINGITIS

Cerebrospinal fluid (CSF) lactic acid dehydrogenase (LDH) has been utilized to help distinguish bacterial from non-bacterial meningitis. We reviewed the initial lumbar puncture (LP) results in 45 pediatric patients with documented bacterial meningitis seen between 1977-80. Patients ranged in age from 1 month to 16 years. No CSF specimens contained significant numbers of RBC's. Nine of the 45 patients had received oral antibiotics prior to admission. A CSF LDH value of more than 20 IU/L (40 units/ml) was considered presumptive evidence of bacterial meningitis, although antibiotics were begun in all patients immediately following the initial LP. A total of 9 patients (20%) had CSF LDH values < 20 IU/L: 1 of 4 patients with meningitis due to S. pneumoniae, 3 of 23 with H. influenzae, type b, meningitis, and 5 of 18 patients with N. meningitidis meningitis. There were no clinically distinguishing features of these 9 patients, and they were not among the patients who received oral antibiotics. During the same period of time, 29 patients found to have non-bacterial meningitis had CSF LDH determinations performed on their initial LP's. Of those 29, 13 (45%) had CSF LDH values >20 IU/L. For this group of 74 patients with meningitis encountered during a 3 year period, initial CSF LDH did not prove helpful in distinguishing bacterial from non-bacterial disease.

Management of presumptive bacterial meningitis in childhood: A practical approach

Precise bacteriological diagnosis in acute meningitis is sometimes difficult. The present study, in which 59 of 97 children received chemotherapy for presumptive bacterial meningitis and of whom only 40 were subsequently proved to have a bacterial aetiology, reflects this. The diagnostic data from these 97 patients have therefore been reviewed in an attempt to identify factors which may assist discrimination of bacterial from non-bacterial meningitis. A decision plan for the management of suspected bacterial meningitis, based on these results, is suggested.

Occurrence of oligoclonal gammaglobulin in the CSF of children with prolonged and chronic CNS-infections.

CSF-proteins of 1770 children and adolescents with different neurological diseases and of 75 controls were examined by zone electrophoresis in agarose gel electrophoresis and by immunofixation electrophoresis. The quantitative evaluation of the phoretograms by an analog computer revealed oligoclonal changes of the gamma-globulin profile in 53 patients with subacute or chronic CNS-infections and in 5 children with a medulloblastoma. Seventeen of 37 children with congenital infections had 1--5 oligoclonal gamma-fractions consisting of IgG. Five to seven oligoclonal IgG fractions were detected in each of 16 children with SSPE. All 6 adolescents with multiple sclerosis had 2--5 oligoclonal IgG fractions. One to five oligoclonal gamma-bands occurred transiently in the CSF of 4 children with prolonged meningoencephalitis caused by different viruses, in 3 children with a prolonged non-bacterial meningitis of probable viral origin, in 2 infants with prolonged bacterial meningitis after corticosteroid therapy, and in 1 child with prolonged bacterial meningitis during cytostatic therapy. Four to six oligoclonal gamma-subfractions were found at different times during progressive viral encephalitis that developed during maintenance therapy of acute lymphoblastic leukaemia, and in 2 patients with chronic meningoencephalitis of unknown origin. Since oligoclonal gamma-globulin was detected almost invariably in the CSF of patients with prolonged or chronic neurologic infections, this finding implies persistence of antigens in the CNS and pathologic invasion of lymphocytes with selective proliferation of antigen-stimulated clones.

Determination of Oligoclonal Gammaglobulin in the CSF of Children with Subacute and Chronic CNS-Infections by Quantitative Agarosegel Electrophoresis: 44

CSF-proteins of 13oo children and adolescents with different neurologic diseases and of 75 normal controls were examined by zone electrophoresis in agarosegel and by immunologic techniques. The quantitative evaluation of the phoretogramms by an analog computer revealed in 68 patients who suffered from subacute or chronic CNS-infections marked changes of the γ-globulin profile. 32 out of 37 children with congenital infections showed a marked increase of γ-globulin during the first two years. One half of these patients revealed 1-5 oligoclonal IgG-fractions (comprising 0.6 - 15.5 % of total protein), that persisted for at least several months.Though γ-globulin was increased only in 3 out of 6 patients with multiple sclerosis, 2-5 oligoclonal IgG-fractions (5.5 -20.4 % of total protein) appeared in all cases. In 16 children suffering from subacute sclerosing panencephalitis oligoclonal IgG (5-7 subfractions) amounted to 20.1 - 56.1 % of total protein. Furthermore, 1-5 oligoclonal IgG bands (8.2 - 35.5 % of total protein) were found in the CSF of 5 children during prolonged non-bacterial meningitis, in 2 patients with chronic aseptic meningoencephalitis, and in 2 cases of subacute bacterial meningitis. Since oligoclonal IgG occurred only in the CSF of cases of subacute or chronic neurologic infections (with the exception of leukemia and medulloblastoma) this finding could mean persistance of antigen in the CNS and pathologic invasion of lymphocytes into the CNS with selective proliferation of antigen-stimulated clones.

Immunoglobulins in cerebrospinal fluid in various neurologic disorders.

Abstract We determined the concentrations of immunoglobulins A, G, and M in cerebrospinal fluid of 16 patients suffering from multiple sclerosis, 13 with non-bacterial meningitis, 10 with stroke syndrome, and 13 with epilepsy. The differences in concentrations of immunoglobulins in these groups were remarkable in the patients with multiple sclerosis, meningitis, or stroke syndrome. We propose that the determination of the absolute immunoglobulin content in cerebrospinal fluid is of greater significance than the relative immunoglobulin concentration.

Immunoglobulins in cerebrospinal fluid in various neurologic disorders.

We determined the concentrations of immunoglobulins A, G, and M in cerebrospinal fluid of 16 patients suffering from multiple sclerosis, 13 with non-bacterial meningitis, 10 with stroke syndrome, and 13 with epilepsy. The differences in concentrations of immunoglobulins in these groups were remarkable in the patients with multiple sclerosis, meningitis, or stroke syndrome. We propose that the determination of the absolute immunoglobulin content in cerebrospinal fluid is of greater significance than the relative immunoglobulin concentration.

Measurement of lactic acid in cerebrospinal fluid of patients with infections of the central nervous system.

The concentration of lactic acid in cerebrospinal fluid (CSF) was determined by gas-liquid chromatography in 205 samples of CSF from 97 patients with or without infections of the central nervous system. Patients without infection or those with nonbacterial (presumably viral) meningitis consistently had low concentrations of lactic acid in CSF (i.e., less than or equal to 35 mg/100 ml), whereas patients with bacterial or tuberculosis meningitis consistently had concentrations of lactic acid in CSF of greater than 35 mg/100 ml. There was no overlap in concentrations of lactic acid between these two groups. Further, lactic acid concentrations in CSF from patients partially treated for meningitis were generally greater than 35 mg/100 ml through the third day of therapy and, thereafter, progressively declined to less than 20 mg/100 ml by the seventh to 10th day of therapy. Relapse of bacterial infection was consistently documented by a recurrence of an increased concentration of lactic acid in CSF. Preliminary experience with determination of the concentration of lactic acid in CSF suggests that it may be useful in distinguishing bacterial (with or without positive cultures) and tuberculous meningitis from meningitis due to nonbacterial causes.

Leukocyte Lactate Dehydrogenase in Bacterial Meningitis

Lactate dehydrogenase (LDH) was assayed in peripheral leukocytes of 32 children with bacterial meningitis, nine children with nonbacterial meningitis, and 24 age-matched, healthy controls. Leukocyte LDH activity in patients with bacterial meningitis was significantly higher than in patients with nonbacterial meningitis (p &amp;lt; 0.01) and normal controls (p &amp;lt; 0.001). Eighty-eight percent of the patients with bacterial meningitis had leukocyte LDH values exceeding, 150 units/106 WBC, the upper limit of normal value for controls. Nitroblue tetrazolium (NBT) dye tests performed on 23 patients with bacterial meningitis were elevated in ten patients (43%). The elevation of leukocyte LDH activity in patients with bacterial meningitis appears to be independent of the number of circulating granulocytes or the presence of bacteremia. A major factor which appeared to influence the leukocyte LDH activity was the duration of adequate antibiotic therapy. Sequential determinations showed a return of the LDH values to normal approximately ten days after the initiation of therapy. A rise in leukocyte LDH was encountered in two patients with subdural effusion. The finding of significantly elevated leukocyte LDH values in three newborn infants with neonatal meningitis and sepsis suggests that this test may be of value in the diagnosis of neonatal sepsis.

The Significance of Proplasmocytes and Atypical Plasma Cells in the Benign Lymphocytic Meningitis Syndrome

Abstract A nontuberculous, lymphocytic meningitis with a low C.S.F. sugar level may be confused with a tuberculous meningitis. Additional diagnostic help may be obtained from examination of the blood. The blood pictures of twelve patients with tuberculous meningitis were compared with those from ten patients with a nontuberculous, nonbacterial lymphocytic meningitis, four of whom had low C.S.F. sugar levels. These ten patients appeared clinically to be suffering from the same disease and only the serum complement fixation test for lymphocytic choriomeningitis showed them to be a heterogeneous group. The main differences in the blood were (1) a uniformly low total white cell count in the benign meningitis group as opposed to a widely varying total white cell count in tuberculous meningitis; (2) a lower percentage count of polymorphs in the benign lymphocytic meningitis group; (3) the presence of atypical plasma cells in nine of the ten patients in the benign, lymphocytic meningitis group. Two of the patients with benign meningitis, who had repeatedly given negative Paul-Bunnell tests showed a blood picture indistinguishable from that of glandular fever. Although these atypical plasma cells are not specific for lymphocytic choriomeningitis or for virus diseases in general, they were found in no case of tuberculous meningitis. The presence of these cells is therefore of considerable aid in excluding a diagnosis of tuberculous meningitis.

Three cases of non-bacterial meningitis

Three cases of non-bacterial meningitis