Cerebrospinal Fluid Titers Research Articles

Neurocysticercosis Among Children in Chicago

Neurocysticercosis has been diagnosed increasingly in the United States as a consequence of increased immigration from and travel to areas of endemic cysticercosis. We report a retrospective series of 47 pediatric cases of neurocysticercosis in our large children's hospital in Chicago, which has a large immigrant population. Neurocysticercosis was diagnosed on the basis of any of the following three criteria: (1) surgical biopsy findings, (2) radiographic findings consistent with neurocysticercosis as well as diagnostic serum and/or cerebrospinal fluid titers, or (3) consistent radiographic findings and a compatible epidemiologic history (without diagnostic serological findings). Epidemiologic, clinical, laboratory, and radiographic data were analyzed. Neurocysticercosis is a relatively common cause of afebrile seizures in children who present to our emergency department in Chicago. Computed tomography and magnetic resonance imaging are both important modalities in evaluation of children with neurocysticercosis. Laboratory studies are neither sensitive for nor predictive of the diagnosis of neurocysticercosis. Therapy is well tolerated. The long-term prognosis for treated patients appears to be excellent.

Evaluation of new monoclonal antibody-based latex agglutination test for detection of cryptococcal polysaccharide antigen in serum and cerebrospinal fluid

We evaluated the performance of CRYPTO-LEX (Trinity Laboratories, Inc., Raleigh, N. C.), a new mouse immunoglobulin M monoclonal antibody latex agglutination reagent which reacts with the capsular polysaccharide of the four serogroups of Cryptococcus neoformans. This test was compared with CALAS (Meridian Diagnostics, Cincinnati, Ohio) for the ability to detect cryptococcal antigen in serum and cerebrospinal fluid (CSF). A total of 580 clinical specimens (327 serum and 253 CSF samples), primarily from human immunodeficiency virus-infected patients, were tested in this study. Sixty-seven specimens (44 serum and 23 CSF samples) were positive for cryptococcal antigen with both tests, and 511 (282 serum and 229 CSF samples) were negative. The two latex reagents agreed for 326 of 327 serum specimens (44 positives and 282 negatives). One serum specimen with a titer of 1:2 was CALAS positive but CRYPTO-LEX negative. The titer correlation coefficient for the two tests was 0.884 when two highly discordant serum specimens were eliminated from analysis of the data. The two latex tests agreed for 252 of 253 CSF specimens (23 positives and 229 negatives). One specimen with a titer of 1:2 was positive with CALAS and negative by CRYPTO-LEX. The correlation coefficient of the two tests for CSF titers was 0.886. The sensitivity and specificity of CRYPTO-LEX were 97 and 100%, respectively, with a 99.6% correlation with CALAS. These data show that the performance of CRYPTO-LEX is comparable to that of CALAS for detection of cryptococcal antigen in serum and CSF.

Bacterial endotoxins impair electrophysiological properties of cultured astrocytes but not of cultured neurons

The endotoxins of bacteria are lipopolysaccharides which are released in the central nervous system during bacterial meningitis. Endotoxin titers in cerebrospinal fluid correspond to the appearance of severe neurological symptoms like seizures and coma. The pathogenic mechanism, however, by which endotoxins disturb neuronal function, is unclear. The functional deficit may originate either from direct alteration of neuronal excitability or from indirect effects mediated by glial cells. Therefore, we investigated the effects of lipopolysaccharides on electrophysiological properties of cortical neurons and astrocytes in separate cell cultures. Membrane potential, resistance and membrane currents of neurons were unaffected. By contrast, astrocytes depolarized markedly in a dose dependent manner (concentration range 1.0–10.0 μg/ml). The depolarization was Na + dependent and amiloride sensitive (250 μM), both indicating an activation of an electrogenic sodium dependent transport system like the Na + Ca 2+ exchanger as a source of the depolarization. These results suggest that endotoxin induced neurological deficits are not caused by direct effects on neurons, but may result from an impaired glial cell function.

Cryptococcal antigen detection from the urine of AIDS patients

Cryptococcal disease occurs in ≤10% of AIDS patients. Detection of the capsular polysaccharide antigen of the yeast in spinal fluid or serum is used to establish the diagnosis. In addition, cryptococcal antigen (CAg) analysis is used to adjust treatment and evaluate recurrence of active disease. A specimen such as urine, obtained noninvasively, would be optimum for this evaluation. Urine, cerebrospinal fluid (CSF), and serum for CAg analysis, and culture of urine and CSF, were obtained for 103 sets of specimens from 92 patients. CSF and urine specimens for CAg were analyzed with and without pronase treatment; serum was analyzed with pronase only. Twenty percent (21 of 103) of specimen sets showed CAg from eight patients. In all cases, patients with positive CSF and/or serum titers also had positive urine titers. Titers were always serum > CSF > urine, with ranges of 1 : 64–65000; 1 : 64–6250; and 1 : 2–512, respectively. Pronase treatment did not affect CSF titers, but 14 of 23 titers from urine treated with pronase were at least one dilution higher than those without treatment. No false-positive reactions were observed during the study. CSF cultures were positive from seven of eight, and urine cultures were positive from five of eight patients with CAg. These results indicate that urine can be used as a specimen for detection of CAg in AIDS patients and that use of pronase may increase its sensitivity.

Neurological diseases of rottweilers: Neuroaxonal dystrophy and leukoenceph‐ alomalacia

ABSTRACTNeuroaxonal dystrophy (NAD) and leukoencephalomalacia (LEM) are two neurological disorders of the rottweiler that initially present as ataxia of all four limbs. Disorders to be included in the differential diagnosis are caudal cervical spondylomyelopathy, canine distemper virus meningoencephalomyelitis, other nervous system infections or inflammations and spinal cord neoplasia. All diagnostic tests including myelography, cerebrospinal fluid analysis, electrodiagnos‐tic testing and serum and cerebrospinal fluid titres for canine distemper virus are normal in NAD and LEM. There is no treatment for either disease and neurological signs progressively deteriorate. Eventually neurological deficits develop besides ataxia and these help differentiate NAD from LEM. Dogs with NAD develop head tremors and nystagmus while dogs with LEM develop conscious proprioceptive deficits and quadriparesis; the short term prognosis for NAD is better than LEM. Most dogs with LEM are euthanased because of non‐ambulatory tetraparesis within one year.The histopathological lesions associated with NAD include axonal spheroids in many spinal cord and caudal brainstem nuclei and reduced numbers of Purkinje cells in the cerebellum, while in LEM, multifocal areas of demyelination and malacia of the spinal cord and brainstem are the primary histopathological lesions. Both NAD and LEM are suspected to have an autosomal recessive genetic transmission.

Cerebrospinal fluid penetration of cefmenoxime in children with bacterial meningitis

Blood and cerebrospinal fluid (CSF) concentrations of cefmenoxime were determined either microbiologically or by means of HPLC in 20 children with proven or suspected bacterial meningitis. Sixteen children suffered from bacterial meningitis: causative organisms were Haemophilus influenzae type b (n = 10), Streptococcus pneumoniae (n = 4) and Neisseria meningitidis (n = 2). In these patients the cefmenoxime concentration in the CSF ranged from 0.9 to 12.2 mg/l, with a mean concentration of 4.63 mg/l 1.5-3 h after the last intravenous cefmenoxime application and 24-48 h after initiating therapy with 200 mg cefmenoxime/kg/d in four doses. In eight cases the bactericidal titers of the CSF were examined during therapy. Titers between 1:64 and 1:2,048, exceeding the minimal bactericidal concentration, were found. After five doses of cefmenoxime 50 mg/kg, two CSF cultures showed bacterial growth: one H. influenzae (bactericidal titer in CSF 1:256) and one S. pneumoniae.

Anti‐Ri: An antibody associated with paraneoplastic opsoclonus and breast cancer

The serum and cerebrospinal fluid (CSF) of 8 women with ataxia, 6 of whom also had eye movement abnormalities believed to be opsoclonus, were found to contain a highly specific antineuronal antibody we call anti-Ri. Seven of the 8 women also had or developed cancer: carcinoma of the breast in 5, adenocarcinoma in an axillary lymph node in 1, and carcinoma of the fallopian tube in 1. Four patients presented with the neurological disorder; the cancer was diagnosed first in the other 4. Immunohistochemical studies using serum or CSF from all 8 patients revealed a highly specific antibody interaction with central nervous system neuronal nuclei but not with glial or other cells; the titer ranged from 1:5,000 to 1:320,000 in serum and from 1:2,000 to 1:16,000 in CSF. Biotinylated IgG from the patients' serum reacted with the tumors of 3 of 4 patients with anti-Ri antibody but not with breast cancers from patients without anti-Ri antibody. Immunoblots against cerebral cortex neuronal extracts identified protein antigens of 55-kd and 80-kd relative molecular mass. Serum titers by immunoblot ranged from 1:500 to more than 1:40,000 and CSF titers, from 1:10 to 1:2,000. The relative amount of anti-Ri was always higher in CSF than in serum. The antibody was not present in sera from normal individuals; patients with breast cancer without opsoclonus; other patients with opsoclonus; or patients with other paraneoplastic syndromes related to breast, ovarian, or small-cell lung cancer. We conclude that the presence of anti-Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders (opsoclonus) who usually suffer from breast or other gynecological cancer; the antibody when present is a useful marker for an underlying malignancy.

Elevated levels of interleukin-6 in serum and cerebrospinal fluid of HTLV-I-associated myelopathy/tropical spastic paraparesis

A significant elevation of interleukin-6 (IL-6) level was observed both in serum (mean 0.455 ± 0.251) and in cerebrospinal fluid (CSF) (mean 0.043 ± 0.016) obtained from 13 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) when compared to that of either asymptomatic carriers (mean 0.181 ± 0.074 and 0.021 ± 0.015, respectively) or controls (mean 0.208 ± 0.119 and 0.021 ± 0.015, respectively). The differences were statistically significant between HAM/TSP and asymptomatic carrier for serum ( P < 0.05) or CSF ( P < 0.01). The correlation indexes between serum IL-6 and anti-HTLV-I antibody titers in serum and CSF were 0.61 ( P < 0.06) and 0.67 ( P < 0.05), respectively. Both the cell count and protein level in CSF correlated with CSF IL-6 activity at 0.68 ( P < 0.01) and 0.56 ( P < 0.05), respectively. The results demonstrate that IL-6 may contribute to the production of anti-HTLV-I antibody, and signs of slight inflammation are present in the central nervous system in HAM/TSP.

Influence of antibiotic dose, dosing interval, and duration of therapy on outcome in experimental pneumococcal meningitis in rabbits.

We examined the influence of several pharmacokinetic parameters on cure rates in rabbits with experimental pneumococcal meningitis. When the duration of treatment was kept constant, cure rates improved as the individual dose of ampicillin was increased. On the other hand, when four doses of ampicillin at 60 mg/kg of body weight, producing peak concentrations in cerebrospinal fluid (CSF) of approximately 40 times the MBC, were administered at intervals of 24 instead of 4 h and the duration of therapy was thus prolonged from 12 to 72 h, cure rates also increased (85 versus 25%; P less than 0.01). These high cure rates were achieved even though bacterial titers in CSF 24 h after the first dose had reached levels similar to those present at the beginning of therapy. Cure in these animals was explained by the fact that the second ampicillin dose reduced bacterial titers in CSF significantly more than did the first dose (5.2 versus 2.5 log10 CFU/ml; P less than 0.02). The clinical relevance of these observations remains to be determined.

Acute cerebellar swelling in varicella encephalitis

A 4-year-old male developed encephalitis 2 weeks after the onset of varicella. During his evaluation neuroradiologic procedures documented cerebellar edema and demyelination. Cerebrospinal fluid titers confirmed varicella encephalitis. To our knowledge, this patient is the first reported with focal cerebellar edema, an expected finding, with a clinical varicella infection as documented by computed tomography and magnetic resonance imaging.

Immunodiagnosis of neurocysticercosis: immunoenzymatic assay with antigens chemically bound to supports to detect antibodies in serum and cerebrospinal fluid

Foi padronizado o teste imunoenzimático, ELISA, utilizando-se componentes antigênicos de Cysticercus cellulosae quimicamente ligados a suportes sólidos constituídos de discos de tecido-resina (ELISA-d), para pesquisa de anticorpos em soro líquido cefalorraquiano (LCR), ensaiando-se uma única diluição do espécime clínico. O suporte tecido-resina foi composto de tecido de poliéster impregnado com resina polimerizada de N-metilol-acrilamida, apresentando grupos N-metilol livres, capazes de reagir covalentemente com grupos funcionais de proteínas e polissacarídeos presentes no extrato antigênico salino total obtido de cisticercos. Foram ensaiados 38 soros e 74 LCR de pacientes com neurocisticercose comprovada e 50 soros e 107 LCR do grupo controle (pacientes com quadros clínicos neurológicos diversos e indivíduos supostamente normais). Obtivemos os seguintes índices de sensibilidade e especificidade: 94,7% e 92,0% para o teste realizado no soro e 98,6% e 100% para o teste realizado no LCR. O teste ELISA-d mostrou-se eficiente para o diagnóstico da neurocisticercose, principalmente quando realizado no LCR, com vantagens de estabilidade, facilidade de execução e baixo custo.

The clinical laboratory evaluation of cryptococcal infections in the acquired immunodeficiency syndrome.

The medical and laboratory records were reviewed in 37 acquired immunodeficiency syndrome (AIDS) patients with cryptococcal infections. In 24 patients with the presentation of cryptococcal meningitis, the initial cerebrospinal fluid (CSF) culture was positive. The initial India ink mount demonstrated organisms in 79% of culture positive CSF specimens. After therapy the subsequent India ink mounts demonstrated 84% sensitivity and 53% specificity with respect to culture outcome. Cultures of blood, bronchoalveolar lavage fluid, and brain were more likely to be positive than cultures from other sites. The initial blood cultures were positive in eight of eight patients at presentation of cryptococcal meningitis. When the initial CSF titer was greater than 1:2, the corresponding CSF culture was always positive. A negative culture during therapy did not necessarily indicate eradication of infection. The initial cerebrospinal fluid and serum cryptococcal antigen titers varied significantly and could not be correlated with survival. In three instances when the CSF cryptococcal antigen titers and cultures were negative, a positive serum cryptococcal antigen greater than 1:8 suggested disseminated infection.

Ceftriaxone Therapy for Asymptomatic Neurosyphilis

A 27-year-old man with documented hypersensitivity to penicillin was treated intramuscularly for asymptomatic neurosyphilis with ceftriaxone (1 g daily for 14 days). After treatment the serum titer in the VDRL (Venereal Disease Research Laboratory) test declined from 32 to four dilutions. Lumbar punctures at months 3, 6, 9, and 28 after treatment revealed normalization of the cell count in cerebrospinal fluid and a decline in the VDRL titer in cerebrospinal fluid from four to one dilution(s). Western blot analysis revealed the presence in serum of IgG antibodies to at least 17 treponemal antigens and in cerebrospinal fluid of antibodies to at least ten treponemal antigens. Following ceftriaxone therapy serum and cerebrospinal fluid IgG reactivity to all antigens steadily decreased in intensity. These results indicate that ceftriaxone may provide a useful alternative therapy for penicillin-allergic patients with neurosyphilis.

Effect of Methylprednisolone on CSF IgG Parameters, Myelin Basic Protein and Anti-Myelin Basic Protein in Multiple Sclerosis Exacerbations

Clinical exacerbations of multiple sclerosis (MS) are characterized by elevated levels of cerebrospinal fluid (CSF) myelin basic protein (MBP). The purposes of this study were to determine whether anti-MBP antibodies are present in increased titer in CSF of MS patients with exacerbations, and whether they can be suppressed by the administration of immunosuppressive dosages of methylprednisolone (MP). A solid phase radio-immunoassay (RIA) was used to detect free and total anti-MBP antibodies before and after acid hydrolysis of CSF. In MS exacerbations, the majority of elevated anti-MBP is in the free form. With the exception of subacute sclerosing panencephalitis (SSPE) and some cases of post infectious encephalomyelitis, anti-MBP antibodies are not present in either MS patients in remission or in non-MS controls. Anti-MBP levels remained elevated over a 10 day period when patients are managed by bed rest only or when treated with intravenous (IV) ACTH. IV administration of MP in "high" (160 mg/day) or "mega" (2 g/day) dosages produces a highly significant reduction of both MBP (p less than 0.01) and anti-MBP (p less than 0.001) levels. Total intrathecal IgG synthesis is also significantly suppressed by IV-MP but not by ACTH.

Vestibular Neuronitis —Serum and CSF Virus Antibody Titer—

The cerebrospinal fluid (CSF) findings of patients with vestibular neuronitis were virologically evaluated and discussed in contrast to those of herpes zoster. CSF samples obtained from seven patients with vestibular neuronitis, aged 28 to 55 years, were examined. The results were as follows: The CSF protein level in the vestibular neuronitis showed the peculiar change; i.e. its level was normal at the onset period of vertigo, but it rose to abnormal levels mostly in the period of two weeks, while the cell count remained normal throughout all phases of our study. Herpes simplex virus (HSV) type 1 IgG antibody titers measured by indirect immunofluorescent antibody technique (IF) in paired sera rose in one of the seven cases of vestibular neuronitis, but the antibody titers of the same virus in the CSF were not detected. HSV type 1 IgG antibody titers measured by IF in the CSF were detected in two of seven cases of vestibular neuronitis, but not significant. The ratio of EB virus (EBV) capsid antigen IgG antibody titers in CSF to that in serum ranged from 1:160 to 1:80 in vestibular neuronitis. There was no direct available evidence that vestibular neuronitis caused a break in blood-CSF barrier, an increase in IgG synthesis in the central nervous system or active infection with HSV, varicella zoster virus (VZV), or EBV. In this paper, we summarized the recent information on studies of the CSF and a latent herpes virus infection in order to give perspective to the pathogenesis of vestibular neuronitis.

Diagnosis of spirochetal meningitis by enzyme-linked immunosorbent assay and indirect immunofluorescence assay in serum and cerebrospinal fluid.

The antibody response against a spirochetal strain isolated from Swedish Ixodes ricinus ticks was determined by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay of cerebrospinal fluid (CSF) and serum specimens from 45 patients with chronic meningitis. Samples of CSF, serum, or both from patients with various infections of the central nervous system, multiple sclerosis, syphilis, or infectious mononucleosis and from healthy individuals served as control samples. Probable spirochetal etiology could be demonstrated for 41 of 45 (91%) patients with clinical symptoms of chronic meningitis. Approximately 25% of the patients had significantly elevated titers of antibody to the spirochete in CSF but not in serum. The highest diagnostic sensitivity, 91%, was demonstrated by measurement of CSF antibodies and calculation of a spirochetal CSF titer index, which is the ratio of (ELISA titer in CSF/ELISA titer in serum) to (albumin in CSF/albumin in serum) and which also considers the degree of blood-CSF barrier damage. The highest specificity, 98%, was obtained by calculation of a CSF titer index. Patients with short duration of disease were especially prone to be antibody negative in serum but positive in CSF. Significant rise in serum antibody titers was seldom demonstrated in patients treated with antibiotics. It is concluded that measurement of CSF antibodies, especially by ELISA, is a highly sensitive and specific method for the immunological diagnosis of spirochetal meningitis.

Aztreonam therapy in experimental meningitis due to Haemophilus influenzae type b and Escherichia coli K1.

The penetration of aztreonam into cerebrospinal fluid was 7 to 15% and 9 to 25%, respectively, in experimental Haemophilus influenzae type b and Escherichia coli K1 meningitis. Aztreonam was effective in reducing the number of organisms in cerebrospinal fluid after single-dose and continuous infusion administration, and the median bactericidal titers in cerebrospinal fluid were 1:32 against both meningeal pathogens.

Pharmacokinetics and bacteriological efficacy of mezlocillin in experimental Escherichia coli and Listeria monocytogenes meningitis.

The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were less than 1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony counts of of susceptible E. coli in CSF by 90% or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of less than 1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56 degrees C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.

Pharmacokinetics of interferon in blood, cerebrospinal fluid, and brain after administration of modified polyriboinosinic-polyribocytidylic acid and amphotericin B.

Polyriboinosinic-polyribocytidylic acid (with a sedimentation coefficient of 9S) prepared in a complex with poly-L-lysine and carboxymethylcellulose (poly ICLC) was given intravenously to rabbits in a priming technique with two infusions 4 hr apart; and with low-dose amphotericin B (AmB, 0.5 mg) to trace the transfer of interferon (IFN) in serum to cerebrospinal fluid (CSF) and brain. Peak titers of IFN in serum were at 4 hr, but peak titers of IFN in CSF and brain occurred at 8 hr. At 4 hr, CSF IFN was 0.6%-2.7% of serum titers but at 8 hr had increased to 11.7%-51.1%. IFN was uniformly distributed to all areas of the brain and spinal cord at 8 hr. Titers of IFN in the brain were independent of CSF values, and varied from 5.9%-44.1% of the serum titers. When two injections of poly ICLC were given 4 hr apart, IFN titers in serum, CSF, and brain were significantly raised. Poly ICLC together with AmB increased serum IFN.

Local production of mumps IgG and IgM antibodies in the cerebrospinal fluid of meningitis patients.

Immunoglobulin G (IgG) and M (IgM) antibodies against mumps virus were measured by an enzyme-linked immunosorbent assay (ELISA) in the serum and cerebrospinal fluid (CSF) specimens of patients with mumps meningitis. The CSF IgG antibodies correlated well with the respective antibody titers in serum. On the contrary, in only about half of the patients a moderate correlation was found between the CSF and serum IgM antibody titers, while the other patients did not have detectable mumps IgM antibodies in CSF irrespective of intermediate to high titers in serum. Two different immunologic mechanisms may be involved in these two groups which, however, did not show any clinical differences. The lack of IgM antibodies in the CSF of many patients diminished the value of CSF in the laboratory diagnosis of mumps meningitis compared to use of serum specimens. Intrathecal synthesis of mumps IgG antibodies was demonstrated in 83% of the patients, and of IgM antibodies in at least 67% of those patients with detectable IgM antibodies in CSF. The ratio between mumps IgG and IgM antibodies was higher in CSF than in serum, suggesting that the synthesis of IgG antibodies in central nervous system was more efficient than that of IgM antibodies.