Cerebrospinal Fluid IgG Synthesis Research Articles

Clinical Significance of MRI Contrast Enhancement of the Oculomotor Nerve in Ischemic Isolated Oculomotor Nerve Palsy.

Background and PurposeContrast enhancement of the oculomotor nerve in MRI was recently noticed in patients with clinical ischemic isolated oculomotor nerve palsy (iIONP). The opinions about whether this is a sign of inflammation and whether or not to administer steroids vary between doctors. The study aimed to determine the associations between this enhancement and vascular-disease risk factors (VRFs) and inflammatory factors in iIONP patients.MethodsThe study recruited patients who had experienced iIONP during the previous 2 years. They were divided into groups A and B based on whether or not they exhibited an enhanced oculomotor nerve in MRI of the cavernous sinus using thin-section, fat-suppressed, and contrast-enhanced sequences. VRFs, inflammatory factors, and improvement scores were compared between the two groups.ResultsMost (71.1%) of the 45 included iIONP patients had enhanced oculomotor nerves in MRI. VRFs, periorbital pain, elevated C-reactive protein and erythrocyte sedimentation rate, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not significantly associated with the enhancement. Four of the five patients in group A exhibited an elevated cerebrospinal fluid (CSF) IgG synthesis rate. The improvement score of eight patients who received 80 mg of methylprednisolone in addition to the routine therapy was not significantly different from the scores of the other patients (p=0.485).ConclusionsMore than half of the iIONP patients had an enhanced oculomotor nerve in MRI. A few of them also had elevated CSF IgG synthesis rate, but no further evidence for inflammation was found. The administration of steroids seemed to have no benefit other than increasing the blood glucose level.

CD24 Gene Allele Variation Is Not Associated with Oligoclonal IgG Bands and IgG Index of Multiple Sclerosis Patients

Objective: Multiple sclerosis (MS) shows evidence of many distinctive aspects of an autoimmune disorder, including a polygenic inheritance. A recent candidate gene for susceptibility to MS is CD24, which has also been shown to be associated with disease progression. This study was designed to examine whether there is a relationship between the CD24 genotype, oligoclonal band (OCB) status and IgG index in the cerebrospinal fluid (CSF) of MS patients. Methods: A total of 27 definite MS patients were enrolled in this cross-sectional study. Blood samples were collected from a peripheral vein, and CSF was obtained by lumbar puncture. The CD24 gene was sequenced in the blood specimen, and albumin and IgG concentrations were measured in both CSF and serum. We compared both IgG index and OCB status in patients with and without CD24V/V. The correlation between MS severity score (MSSS), OCB status, CD24 genotype and IgG index was studied. Results: Only 15 patients were OCB positive. Among patients with negative OCBs, only 2 patients had the V/V genotype. Furthermore, in those with the V/V genotype, IgG index was not significantly elevated (p = 0.322). Patients with the V/V genotype had a significantly higher MSSS (p = 0. 04), but neither the presence of OCBs nor the IgG index showed significant correlation with MSSS (p = 0.379 and 0.20, respectively). Conclusion: We could not show any relationship between the CD24V/V genotype, OCB status and IgG index. This could be interpreted as indicating that the CD24V/V allele exerts its effects on the disease course independently of CSF IgG synthesis.

CSF follow-up in HIV-1 infection: intrathecal production of HIV-specific and unspecific IGG, and beta-2-microglobulin increase with duration of HIV-1 infection.

Ninety-nine sequential cerebrospinal fluid (CSF) samples from 28 human immunodeficiency virus-1 (HIV-1)-infected patients were analyzed during the follow-up of 9 months to 4 years. Intrathecal synthesis of HIV-antibodies and IgG (p < 0.01), and the levels of beta-2-microglobulin (beta 2m) in the CSF (p < 0.05) and serum (p < 0.01) increased with duration of HIV-1 infection. No effect of duration of HIV-1 infection was observed on the individual CSF white cell counts and the levels of blood-brain-barrier (BBB) permeability. In 13 patients with HIV-1-associated central nervous system (CNS) disease, the effect of duration was seen as an increase of the individual beta 2m levels in serum (p < 0.01). Moreover, 7 of 9 patients who developed neurological disease or showed its progression during the study increased the level of beta 2m in the CSF. All of them increased the level of beta 2m in serum. In 15 neurologically healthy subjects, the effect of duration was expressed as an increase of the level of individual beta 2m in CSF (p < 0.05) and intrathecal IgG synthesis (p < 0.01). In the AIDS group, the level of beta 2m in the CSF increased, but in less severe stages the dependency of the individual CSF parameters on disease duration was not found. Our results indicate that elevated levels of beta 2m in CSF and serum appear to predict progression of neurological and systemic diseases, respectively. Elevated beta 2m in the CSF of clinically intact individuals may indicate subclinical neurological disease caused by HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of formulae for CSF IgG synthesis using data obtained from two methods: importance of receiver operator characteristic curve analysis.

To determine the clinical performance of three cerebrospinal fluid (CSF) IgG synthesis formulae using data obtained from two quantitation methods. Receiver operator characteristic (ROC) analysis and decision index plots were used to compare a rate nephelometric (RN) and a rocket immunoelectrophoretic (RIEP) method for quantitating albumin and IgG for use in CSF IgG synthesis formulae. Further analysis was used to determine the most clinically accurate of these formulae for a diagnosis of multiple sclerosis with regard to technical accuracy and cost effectiveness. Values for albumin and IgG determined by RN gave better sensitivities and specificities than the RIEP method when applied to all three formulae; however, when the 95% confidence limits were considered, the difference was not significant. Using the RN method with an agreed "rule in" threshold value of 90% specificity, the IgG index gave the best clinical performance. ROC curve analysis and decision index plots provide valuable tools in assessing and comparing the clinical performance of new and existing laboratory assays.

Cerebrospinal Fluid Neopterin Levels in 159 Neurologically Asymptomatic Persons Infected with the Human Immunodeficiency Virus (HIV-1): Relationship to Immune Status

Monocytes and brain macrophage-microglial cells are thought to play a crucial role in the neurologic dysfunction associated with HIV-1 disease. Since neopterin is produced by monocytes-macrophages, we asked whether cerebrospinal fluid (CSF) neopterin levels increase before the onset of HIV-1 neurologic disease and whether they correlate with other CSF and peripheral blood immunologic parameters. In this study, CSF neopterin levels from 159 neurologically asymptomatic HIV-positive persons were found to increase as the blood CD4+ T-cell count decreased and as CSF IgG, IgG synthesis, IgG index, and beta 2-microglobulin increased. Neopterin levels in the CSF exceeded those in the serum in 32% of patients, while 25% had CSF levels > 13.5 nmol/liter. CSF neopterin levels vary with immune status, may reflect intrathecal production, and can be elevated in asymptomatic HIV-positive patients with normal neurologic examinations. Long-term follow-up of this patient population should be able to define the clinical correlation between CSF neopterin levels during the asymptomatic phase of HIV-1 disease and the risk of subsequent neurologic disease.

Effect of treatment on oligoclonal IgG bands and intrathecal IgG synthesis in sequential cerebrospinal fluid and serum from patients with subacute sclerosing panencephalitis

Oligoclonal IgG bands were analyzed in matching pairs of cerebrospinal fluid (CSF) and serum from 12 subacute sclerosing panencephalitis (SSPE) patients, using isoelectric focusing and immunofixation. Each patient was given isoprinosine, and four of the 12 patients were given alpha-interferon in addition. Two to 4 serial CSF and serum samples were collected from each SSPE patient during periods ranging from 1 to 16 months. In 3 SSPE patients in a small number of new oligoclonal bands were seen in the follow-up CSF samples. In the other 9 SSPE patients there was no change in CSF band patterns between initial and follow-up specimens. Band patterns in serum remained unchanged between initial and follow-up samples. Although all 12 SSPE cases had higher IgG indices and increased rate of intra blood-brain barrier (BBB) IgG synthesis in comparison to patients with other neurological diseases, the values did not significantly differ between the first and follow-up specimens. We conclude that treatment of SSPE patients with isoprinosine or with isoprisonine and alpha-interferon had no significant effect on the CSF oligoclonal band profiles or IgG synthesis within the central nervous system.

Comparison of spinal fluid beta 2-microglobulin levels with CD4+ T cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the human immunodeficiency virus type 1.

Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.

Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus infection.

This report summarizes the results of neurologic and cerebrospinal fluid (CSF) study findings in over 400 of the 649 human immunodeficiency virus-infected US Air Force personnel, evaluated as of Dec 31, 1987. Eighty percent of these patients were entirely asymptomatic and immunologically normal, 13% had low T-helper lymphocyte counts and/or cutaneous anergy, and only 7% had opportunistic infection. Sixty-three percent of all patients had some CSF abnormality. Sixty percent of the asymptomatic group had at least one abnormal result, over 25% had three or four CSF abnormalities, and over 7% had five or six abnormal values. When patients with evidence of blood-brain barrier leak were excluded, significant differences were seen between disease groups with regard to CSF glucose, CSF IgG levels, and CSF IgG synthesis. No human immunodeficiency virus-related central nervous system abnormalities were found on neurologic examination in immunologically intact asymptomatic patients regardless of CSF findings. No clear-cut predictor of impending central nervous system complications has, as yet, been identified from the CSF parameters studied.