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Elevated levels of beta 2-microglobulin and neopterin in cerebrospinal fluid (CSF) have been associated with neurologic complications of infection with the human immunodeficiency virus (HIV). The effect of zidovudine (ZDV) on these markers was assessed by studying the effect of ZDV treatment duration on CSF levels in a cohort of 145 HIV-positive men who were receiving ZDV. CSF beta 2-microglobulin and neopterin levels were significantly lower in those who had been taking ZDV for an intermediate period of time (46-365 days) than in those who had received ZDV either long term (> 365 days) or short term (1-45 days). CSF quinolinic acid levels were independent of duration of ZDV administration. A second CSF evaluation was available after 1 year for 54 HIV-positive men (19 of whom were also in the first cohort) and 11 HIV-negative controls. Patients who had started ZDV between lumbar punctures showed a significant decrease in CSF beta 2-microglobulin, but in those who had been receiving ZDV for > 1 year beta 2-microglobulin increased (p = 0.001). The effect was not observed with neopterin (p = 0.14). (Quinolinic acid levels were not studied longitudinally.) Finally, we observed that CSF levels of beta 2-microglobulin, neopterin, and quinolinic acid correlated strongly with each other in HIV-positive individuals (r = 0.7, p < 0.0001), even though ZDV might have different effects on these markers. In conclusion, we report that initiation of ZDV therapy is associated with a transient decrease in CSF levels of beta 2-microglobulin and neopterin.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

The effect of zidovudine on beta 2-microglobulin and neopterin in the cerebrospinal fluid (CSF) was studied in ten HIV-seropositive neurologically healthy individuals. CSF concentrations of neopterin decreased by 53% (from 20.3 to 9.5 nmol/l, p < 0.01) and beta 2-microglobulin by 36% (from 2.8 to 1.8 mg/l, p < 0.01) four to eight months after initiation of therapy.

Objectives and Design: Because macrophages are the predominant immune cell and the predominant infected cell in the brains of patients with HIV encephalitis, we studied macrophage and immune activation-associated factors in the cerebrospinal fluid (CSF) from 39 autopsied AIDS cases for whom complete neuropathologic evaluation of the brain was available., Results: CSF HIV p24 antigen was present in less than one-third of cases (11 out of 39). Less than half of the autopsies with moderate to severe parenchymal infection by HIV had high levels of CSF p24, although all autopsies with elevated levels of HIV p24 had moderate to severe HIV encephalitis. Elevated levels of cytokines, beta 2-microglobulin, neopterin, and quinolinic acid were observed., Conclusions: Although many of the CSF findings showed a strong correlation with each other, none showed a strong correlation with the severity of HIV infection of the brain itself. The absence of a close association between CSF abnormalities and HIV encephalitis could reflect the abundance of complicating opportunistic infections in these terminally ill patients or the inadequacy of CSF as a marker of basal ganglia involvement in HIV encephalitis. These findings complicate interpretation of clinical studies of CSF in patients with AIDS where neuropathologic evaluation is unavailable.

Beta 2-microglobulin (beta 2m) is a small protein that forms the light chain of the class I major histocompatibility molecule and is also present in soluble form in serum and cerebrospinal fluid (CSF). Measles is associated with immune activation and evidence of immunologic abnormalities that persist for several weeks. To assess further the immunologic changes occurring during measles, beta 2m was measured in plasma and CSF. beta 2m became elevated during measles before the onset of the rash and was highest during the rash. Elevations persisted for several weeks and correlated well with levels of soluble interleukin-2 receptor and neopterin and less well with soluble CD8. CSF beta 2m was elevated in postmeasles encephalomyelitis. Plasma levels of beta 2m did not correlate with spontaneous proliferation of peripheral blood mononuclear cells (PBMC) or with in vitro production of beta 2m by cultured PBMC. The data suggest that increases in beta 2m in measles correlate better with cytokine production than with cell proliferation.

Cerebrospinal fluid (CSF) proteins with molecular masses of < 150,000 Da were identified by immunoblotting after two kinds of nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). With PAGE 1 (17-27% gradient gel), CSF proteins were clearly separated into seven to nine bands with molecular masses of 3000-67,000 Da; seven bands were identified as beta 2-microglobulin, lysozyme, prealbumin, free kappa and lambda chain, apolipoprotein A-I, glycoproteins, and albumin by immunoblotting. With PAGE 2 (10-20% gradient gel), proteins were clearly separated into 11-16 bands with molecular masses of 15,000-150,000 Da; 11 were identified as prealbumin, free kappa and lambda chain, apolipoprotein A-I, glycoproteins, albumin, alpha 1-antitrypsin, transferrin (separated into two bands), immunoglobulin fragments, haptoglobin, and IgG. We analyzed CSF samples collected from 81 patients with cerebrospinal signs by these SDS-PAGE methods and observed prominent bands in some cases.

Quinolinic acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway. Increased concentrations of QUIN occur in both cerebrospinal fluid (CSF) and blood of patients infected with human immunodeficiency virus (HIV)-1, particularly those with neurologic disturbances. In the present study of HIV-1 infected patients in Walter Reed stages 4, 5 and 6, reductions in L-tryptophan accompanied proportional increases in L-kynurenine and QUIN in both serum and CSF. Further, close inter-correlations exist between QUIN kynurenic acid and L-kynurenine with both beta 2-microglobulin and neopterin in CSF and serum. These correlations support the hypotheses that the kynurenine pathway is activated in association with inflammation and induction of indoleamine-2,3-dioxygenase. There were no relationships between CSF QUIN, L-kynurenine or kynurenic acid with the ratio of serum:CSF albumin concentrations, which indicates that the increases in CSF QUIN, L-kynurenine or kynurenic acid were not dependent on a breakdown of the blood-brain barrier. Kynurenic acid is also a kynurenine pathway metabolite that can attenuate the excitotoxic effects of QUIN when present in higher molar concentrations. While CSF kynurenic acid levels were increased in HIV-1-infected patients, the magnitude of the increases were smaller than those of QUIN and the molar concentrations of kynurenic acid were consistently lower than QUIN by at least one order of magnitude. We conclude that immune activation increases the levels of neuroactive kynurenines within the central nervous system of HIV-1-infected patients secondary to activation of indoleamine-2,3-dioxygenase.

We measured serum and CSF beta 2-microglobulin (beta 2M) levels in HIV-1 seropositive individuals with and without dementia to determine the frequency and diagnostic utility of elevation of CSF beta 2M. We compared 34 samples from 27 patients with HIV-1 dementia with 110 samples from 54 HIV-1 seropositive participants in the Multicenter AIDS Cohort Study, none of whom had progressive dementia. Neurosyphilis and CNS opportunistic processes were excluded in all subjects. We stratified the nondemented subjects by duration of HIV seropositivity and peripheral blood CD4 count. Compared with the nondemented group, demented subjects had significantly higher CSF total protein, IgG%, and CSF albumin/serum albumin ratios. A highly significant association was found between elevated CSF beta 2M and reduced CD4 count (p less than 0.0001). No significant differences were noted between the demented and nondemented groups in CSF WBC count or in the frequency of CSF HIV-1 isolation. The mean CSF beta 2M was 1.9 mg/l in the nondemented subjects compared with 4.2 mg/l in those with dementia (p less than 0.0001). We derived a cutoff of 3.8 mg/l from the distribution of CSF beta 2M in the nondemented group. The determination of CSF beta 2M had a sensitivity of 44%, specificity of 90%, and a positive predictive value of 88% for diagnosis of HIV dementia when compared with nondemented subjects with CD4 counts less than 200. In those without dementia, there was a strong correlation between serum and CSF beta 2M (r = 0.50, p less than 0.0001), but in demented subjects CSF beta 2M was elevated independently of serum levels, suggesting that CSF beta 2M is produced within the brain in HIV dementia. In the absence of CNS opportunistic processes, elevated CSF beta 2M greater than 3.8 mg/l is a clinically useful marker for HIV dementia.

Cerebrospinal fluid (CSF) and serum samples of 20 patients with central nervous system manifestations of hematological malignancies including primary cerebral lymphoma (n = 5) and disseminated non-Hodgkin lymphoma (n = 7) were examined for albumin, IgG, IgM, fibronectin, beta 2-microglobulin, interleukin-6, soluble interleukin-2 receptor, tumor necrosis factor alpha, and oligoclonal immunoglobulin bands. Although a broad range of abnormalities were detected, no reliable CSF parameter for the diagnosis of leptomeningeal spread from hematological neoplasias could be identified. An analysis of 61 repeat lumbar punctures added little to the findings of the first CSF examinations. Currently, immunochemical studies of CSF cell surface markers and early biopsy have probably more clinical value than the determination of the humoral CSF parameters included in this study. However, analysis of cytokine synthesis by single CSF cells using molecular biology techniques may improve the differential diagnosis of hematological neoplasia of the brain and spinal cord in the future.

Elevated cerebrospinal fluid (CSF) levels of neopterin and beta 2-microglobulin (beta 2MG) reflect activation of the cellular immune response in the central nervous system (CNS). In 118 consecutive subjects [15 controls and 103 patients with human immunodeficiency virus (HIV) infection classified according to the Walter Reed staging system (WR)], neopterin and beta 2MG were determined in paired samples of CSF and serum. The permeability of the blood-CSF barrier and local release of neopterin and beta 2MG were taken into account: The molecular weight and diameter were used to determine filtration at the blood-CSF barrier. CSF neopterin levels were increased in all stages of HIV infection. beta 2MG levels were elevated in WR2 and later stages. Neopterin, beta 2MG, and cell counts similarly showed peaks in WR2, as did neopterin and beta 2MG also in the later stages WR5 and WR6. Neurologically asymptomatic patients exhibited higher neopterin CSF levels than did controls (12.67 +/- 11.6 vs. 2.34 +/- 1.05 nmol/l, P less than 0.001) and higher CSF beta 2MG (2.12 +/- 1.25 vs. 1.3 +/- 0.37 mg/l, P = 0.001). Patients with HIV encephalopathy had higher levels of beta 2MG (3.75 +/- 1.83 mg/l) than asymptomatic patients (P less than 0.01). CSF levels of neopterin were markedly different in patients with HIV encephalopathy and toxoplasmosis (P less than 0.01). A high quantity of local release of the markers neopterin and beta 2MG may reflect HIV infection of the CNS in early and late stages and additional release upon opportunistic infections.

Cerebrospinal fluid (CSF) and serum concentrations of beta-2-microglobulin (beta-2-m) were evaluated in 19 patients with clinically definite multiple sclerosis (MS), in 21 with AIDS dementia complex (ADC), and in 20 subjects with other neurological diseases (OND). CSF beta-2-m and CSF/serum beta-2-m ratio were significantly higher in the patients with ADC than in the MS and OND patients. The CSF and serum levels of beta-2-m in MS patients were not significantly different from those of OND patients. These findings indicate that CSF beta-2-m and CSF/serum ratio may be a useful marker in the diagnosis of ADC. In MS patients the beta-2-m CSF determinations are of no value.

Objective: To determine the relationship between cerebrospinal fluid (CSF) beta 2-microglobulin (beta 2M) and severity of AIDS dementia complex (ADC), and between CSF beta 2M and response of ADC to zidovudine., Design: A prospective study., Setting: Tertiary referral hospital., Patients, Participants: Seventy-eight patients with varying stages of ADC were selected from a subgroup of a cohort of HIV-seropositive patients who are being studied prospectively for the neurological complications of HIV-1 infection. To enter our study, patients had to have an ADC stage of at least 0.5 (equivocal symptoms or abnormal neurological signs in the absence of functional impairment). A control group of 11 HIV-1-seropositive, neurologically normal patients was chosen randomly from the patients followed in the Multicenter AIDS Cohort Study., Interventions: Patients were assessed neurologically and neuropsychologically and computed tomography of the brain and CSF studies were performed., Main Outcome Measures: Patients were staged according to severity of ADC on clinical criteria. Neuropsychological test scores were converted to an impairment score. CSF beta 2M was quantified in both serum and CSF of all patients and in 10 patients with pre- and post-zidovudine assessments., Results: There was a high correlation between CSF beta 2M concentration and severity of ADC (P less than 0.0001); treatment with zidovudine significantly reduced these concentrations (P = 0.013). CSF beta 2M concentration was independent of CSF white-cell count and blood-brain barrier impairment. Other CSF changes in the same patients (including blood-brain barrier permeability to albumin, intrathecal synthesis of immunoglobulin G and HIV-1-p24-antigen levels) were less useful as objective correlates of ADC severity and response to zidovudine therapy., Conclusions: CSF beta 2M may be a valuable marker of ADC severity and response to antiviral therapy.

Beta-2-microglobulin (B2m) was measured in the cerebrospinal fluid (CSF) and serum from 18 adults with acute lymphoblastic leukemia, acute myeloblastic leukemia or lymphoma in order to detect early central nervous system (CNS) involvement or relapse. Six had CNS-involvement documented by neurologic symptoms and tumor cells in the CSF. Their CSF-B2m-concentrations were significantly higher before intrathecal chemotherapy than in those without this complication (P less than 0.01). During therapy CSF-B2m levels fell rapidly to normal values on repeated measurements. The study demonstrates that serial determination of CSF-B2m alone may be a useful and sensitive marker of CNS-dissemination in acute leukemia and malignant lymphoma. Using the criteria of CSF-B2m greater than 160 nmol/l as a positive diagnostic test the sensitivity of the test was 100%, the specificity was 76%. The same values for the CSF/serum-ratio greater than 1 were 75% and 64%, respectively.

We measured cerebrospinal fluid (CSF) and serum beta 2-microglobulin (beta 2-M) in Acquired Immunodeficiency Syndrome (AIDS) patients with or without clinical evidence of central nervous system (CNS) involvement. The CSF beta 2-M level was significantly higher than the serum level in AIDS patients with neurological symptoms, but not in AIDS without neurological symptoms, suggesting an increased shedding of this protein in CSF, as a result of rapid cellular turnover within CNS. CSF beta 2-M level increases both in Human Immunodeficiency Virus type 1 (HIV-1) related and in opportunistic CNS syndromes, confirming that beta 2-M is a non specific marker of CNS involvement in AIDS. Nevertheless, the highest CSF beta 2-M values were observed in patients with severe dementia and autoptic diagnosis of multifocal giant cells encephalitis (MGCE) without other opportunistic diseases. This observation could have important implications for monitoring AIDS dementia complex in AIDS patients. Finally, 5 out of 7 (71%) AIDS patients with cryptococcal meningitis showed a decline in CSF beta 2-M level well related to the decrease of cryptococcal antigen (Crypto-Ag) titres and the clinical remission. This data suggests that CSF beta 2-M determination could be used as a useful test in monitoring efficacy of therapy of CNS pathologies in AIDS patients.

Cerebrospinal fluid (CSF) and serum concentration of beta-2-microglobulin (beta-2-m) were evaluated in 30 patients in various stages of HIV-1 infection. CSF beta-2-m and CSF/serum ratio were significantly higher in patients with neurological complications respect to asymptomatic subjects. These findings indicate that CSF beta-2-m and CSF/serum ratio may be a useful marker of neurological involvement in HIV-1 infection.

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.

The results of cerebrospinal fluid (CSF) biochemical markers were compared with conventional CSF cytology in patients treated for leptomeningeal metastases from extra cranial malignancies. For lumbar CSF, before treatment, no statistically significant difference of the probabilities of being positive was found between CSF cytology and a classification by linear discriminant analysis, based on patient's age, of beta-glucuronidase and beta 2-microglobulin. During treatment, classification by linear discriminant analysis was found more often positive than cytology. Possible mechanisms for this difference are discussed. For ventricular CSF a correlation was found between CSF cytology and beta-glucuronidase for solid tumours, and between CSF cytology and beta 2-microglobulin for haematological malignancies. Reference values for ventricular protein, CEA beta-glucuronidase and beta 2-microglobulin were obtained for cytological negative samples.

In HIV-seropositive patients, we evaluated the clinical utility of measuring combinations of serum and CSF levels of neopterin and beta 2-microglobulin (beta 2-M) (by RIA), as well as the intra-blood-brain-barrier (IBBB) IgG synthesis rate, IgG index, and HIV antibody index (by rate nephelometry, EIA, and formulae) for the assessment of HIV infection of the CNS. We studied paired sera and CSF from 31 HIV-seropositive patients: asymptomatic (16), ARC (12), and AIDS (3). A normal serum neopterin level predicts normal levels of serum beta 2-M, CSF neopterin, or CSF beta 2-M in 90%, 100%, and 100%, respectively, of our patients. An elevated serum neopterin level predicts an elevated level of serum beta 2-M or CSF neopterin in 81% and 62%, respectively, of cases. The HIV antibody index and IBBB IgG synthesis rate or IgG index must be determined separately because they do not predict each other and are not predicted by levels of neopterin or beta 2-M.

Increased concentrations of beta 2-microglobulin in cerebrospinal fluid have been used to detect central nervous system involvement with metastatic cancer and with neurological complications of AIDS. However, no adequate reference interval study has been reported for beta 2-microglobulin in cerebrospinal fluid. We established a reference interval with both the Abbott IMx microparticle enzyme-linked immunoassay (EIA) (0.6-2.0 mg/L) and the Pharmacia beta 2-micro EIA 96 method (0.8-2.2 mg/L) for beta 2-microglobulin in cerebrospinal fluid. The two methods correlate well, with the latter method giving slightly higher values. beta 2-Microglobulin increases with age in adults by about 0.1 mg/L every 7.5 years, with no significant difference between genders.

The usefulness of measuring beta 2-microglobulin levels in the cerebrospinal fluid (CSF) in neurological diseases is discussed and the relevant literature is reviewed in this article. An elevation of this protein in the CSF is particularly indicative of disease activity in multiple sclerosis, neuro-Behçet's disease, sarcoidosis, acquired immunodeficiency syndrome-dementia complex and meningeal metastasis of malignant tumors, especially the meningeal dissemination of acute leukemia and malignant lymphoma.

Two cases of HIV infection associated with neurological complications are described. The patients had been followed with repeated cerebrospinal fluid (CSF) analyses 1-3 years before the neurological disease and 5 months after zidovudine treatment. CSF mononuclear cell count and the AIDS predictors beta 2-microglobulin and neopterin decreased in CSF after treatment and were lower or at the level seen 1-3 years before treatment. The results suggest that zidovudine has a suppressive effect on the HIV infection in CNS at least for 5 months, even when low zidovudine doses (500 mg daily) were used.

In 60 patients with tumours of the central nervous system (50 intracranial, 10 intraspinal) the beta 2-microglobulin in serum and cerebrospinal fluid was examined. The frequency of pathological finding was in both examined fluids considerable and differed with regard to the type and site of the tumours; it was particularly high in intracranial gliomas (in serum 87.1%, in cerebrospinal fluid 74.2%). For comparison a group of 55 patients with multiple sclerosis was examined where the incidence of elevated beta 2-microglobulin was markedly lower (in serum 29.1%, in cerebrospinal fluid 20%). Normal values in serum and cerebrospinal fluid were obtained in 50 subjects without organic lesions of the nervous system.

Cerebrospinal fluid (CSF) and serum B2-microglobulin (B2m) levels were measured prospectively in 63 patients with hematological malignancies and 14 patients with solid tumours to evaluate the correlation between elevated levels and malignant infiltration of meninges. Serial CSF B2-m levels were also measured in 18 patients who received prophylactic intrathecal cytotoxic treatment. CSF B2-m levels were significantly higher in patients with central nervous system (CNS) involvement than in those without (p less than 0.001). A CSF B2-m level greater than 1.80 mg/L was closely associated with CNS disease (specificity 96%, sensitivity 76%) and CNS infiltration was also likely when the CSF B2-m level exceeded a simultaneously drawn serum level (specificity 98%, sensitivity 46%). Intrathecal methotrexate prophylaxis resulted in a consistent and significant rise in CSF B2-m levels with an average increase of 96% during a course of intrathecal injections. These results suggest that CSF B2-m levels may not be helpful for predicting early CNS relapse in these patients. However the CSF B2-m level and the corresponding serum B2-m level is a useful adjunct to the cytological diagnosis of CNS involvement by malignancy at presentation. Its value in predicting early CNS relapse and documenting response to CNS treatment requires further clarification.

Beta 2-Microglobulin levels in the CSF and serum of 125 neurological patients were determined. The concentration of beta 2-microglobulin in CSF and serum is approximately the same, ranging from 0.6--2.3 mg/l. No clear relationship could be found between the CSF beta 2-microglobulin level on the one hand and the total protein content and white cell count on the other. There was no clear relationship between the serum beta 2-microglobulin and CSF microglobulin content. An increase of beta 2-microglobulin in CSF was found most often in cases of serious infection of the meninges or of the central nervous system. An elevated beta 2-microglobulin content can occur as the only abnormal feature of the CSF.

This study presents results of investigations of lumbar and ventricular cerebrospinal fluid (CSF) biochemical markers (Beta-glucuronidase (B-gluc), Beta-2-microglobulin (B2-m), and carcinoembrionic antigen (CEA] in 28 patients with five different tumor types with leptomeningeal metastasis diagnosed by CSF cytology and/or autopsy. All received methotrexate and radiotherapy at some stage. Decadron or other symptomatic treatments were not used. Measurements of the concentrations of B-gluc, B2-m and CEA were evaluated with the aim of correlating the results of these measurements to site of disease, of monitoring response and early relapse of leptomeningeal disease, and of establishing the duration of survival. In almost all our patients the results of ventricular CSF B-gluc, B2-m and CEA measurements were lower than those obtained from lumbar CSF. The markers did not correlate with site of disease or CSF cytology. A clear relationship was found between pretreatment lumbar CSF B2-m and CEA levels, response to therapy and survival. The markers are also useful for monitoring response. The findings of this study indicate that B2-m and CEA levels have a prognostic value with regard to response to therapy and time of survival.

Beta 2 microglobulin is a low molecular weight protein integrating the light chain HLA antigens. Its serum concentration is increased in different neoplasias and in renal failure. Using solid phase RIA we determined the concentration of beta 2 microglobulin in plasma and spinal fluid of 57 healthy individuals and patients with hematologic neoplasia. Serum levels were 1.34 +/- 0.34 mg/l and spinal fluid levels were 1.3 +/- 0.7 mg/l in healthy subjects. Serum levels in 29 patients with myeloma was 7.51 mg/l, significantly higher in those with renal failure (12.35 mg/l) compared to those without (4.54). In 30 patients with non-Hodgkin lymphoma the mean serum levels were 2.90 mg/l, significantly greater in those with active disease (3.18) than in those with remission (1.5). No difference was found according to the degree of malignancy. Patients with acute lymphatic leukemia had elevated values of beta 2 microglobulin while the disease was active (3.37 mg/l), decreasing to normal levels after remission (1.79 mg/l). Spinal fluid levels of beta 2 microglobulin were elevated only in patients with central nervous system involvement. Our results indicate that serum levels of beta 2 microglobulin are helpful in patients with hematologic neoplasia in assessing the activity of the disease and tumor mass, especially in multiple myeloma.

The value of serial determination of the cerebrospinal fluid (CSF) beta-2-microglobulin (Beta 2m) level for early detection of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) has been prospectively studied in 30 children. Beta 2m was determined by micro-ELISA assay. Results demonstrated a sensitivity of 40% (95% confidence interval, 5.3-85.3%) and a predictive value of 8% (95% confidence interval, 1.0-26.0%). In post-irradiation syndrome, as well as in viral infection with cytopathological changes of white cells in CSF, beta 2m values proved to be significantly higher than in incipient CNS relapse, and these conditions, or an unknown cause, are more often associated with beta 2m elevation than CNS relapse. No relation was found between CSF white cell counts and beta 2m levels. It is concluded that beta 2m is not an appropriate test for early detection of CNS involvement in children with acute lymphoblastic leukemia.

The concentrations of immuno-reactive beta2-microglobulin (beta2m) were measured in the cerebrospinal fluid (CSF) and the cystic fluid (CF) of Central Nervous System (CNS) tumours (gliomas, n = 5; craniopharyngiomas, n = 5) and in the culture medium of established cell lines derived from CNS tumors. These data are compared with plasma and CSF values of beta2m in normal subjects (n = 15) and in a group of peripheral solid tumors (metastatic breast carcinomas, n = 9). In the control group the absence of correlation between plasma and CSF values, suggests an independant production of beta2m in the two compartments considered. The capacity of CNS tumor cells to synthesize beta2m is demonstrated in vitro. In vitro beta-2m concentrations in the CF embryonic tumors (craniopharyngiomas) is significantly more elevated than in non malignant astrocytomas.

Beta-2-microglobulin was determined in 147 patients admitted to hospital because of suspicion of CNS disease. Patients with meningism were chosen as control group. The concentration of beta-2-microglobulin in the spinal fluid of control patients was correlated with age. Reference values for 0-40 years were 0.34-1.58 mg/l. Above 40 years of age the values were 0.46-3.14 mg/l. CSF beta-2-microglobulin levels of patients with meningism, aseptic and bacterial meningitis overlap too much to be relevant in distinguishing between these entities. Five patients with herpes simplex encephalitis had markedly elevated levels ranging from 4.4 to 9.0 mg/l. Ten patients with herpes zoster-associated encephalitis had values from 1.1 to 6.1 mg/l. In the patient groups with CNS infections, the ratio of serum to spinal fluid beta-2-microglobulin was significantly more frequently less than 1 as compared with the meningism group, indicating intrathecal production of the protein. Further studies on the clinical relevance of CSF beta-2-microglobulin in the diagnosis of encephalitis seem warranted.

Central nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as beta 2-microglobulin (beta 2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty-two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased beta 2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25, beta 2m in three of 21, LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of beta 2m, LYS and LF but not of total protein, which may reflect a drug-induced inflammatory reaction in the CNS. We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.

To detect early relapse in the central nervous systems (CNS) of patients with acute leukemia or lymphoma, we measured levels of beta 2-microglobulin (beta 2 m) in serum and cerebrospinal fluid (CSF). CSF levels were significantly higher in patients with leukemia (P < 0.001) or lymphoma (P < 0.02) with clinical evidence of CNS involvement than in those without this complication. When serum and CSF levels were measured simultaneously, the CSF level of beta 2 m was significantly higher than the serum level in patients with acute leukemia and lymphoma with CNS involvement (P = 0.05), but not in patients without CNS involvement. Serial determination of CSF beta 2 m correlated well with the clinical appearance and disappearance of CNS involvement. These data suggest that serial and simultaneous determination of beta 2 m in serum and CSF may be useful in early diagnosis of CNS involvement and in monitoring intrathecal therapy in patients with acute leukemia or lymphoma.

Immunochemical identification of neurospecific beta 2-globulin (N beta G) in the cerebrospinal fluid (CSF) of mentally healthy subjects and mental patients showed its immunochemical identity in both group. A comparative immunochemical analysis revealed considerable differences in N beta G levels in the CSF in patients with neuropsychic diseases as compared with the control group. The content of N beta G was found to vary in different psychopathological syndromes. It is suggested that variations in N beta G levels in the CSF may be related to psychomotor activity.

Beta-2-microglobulin determinations in cerebrospinal fluid (CSF) of patients with leukemia, lymphoma, and oat cell carcinoma were performed to evaluate the utility of this test in early detection of metastasis to the central nervous system (CNS). In the presence of CNS disease, significantly higher levels (P less than 0.001) were found than in normals or patients without CNS disease. Serial measurements were performed on two patients, and in all cases beta-2-microglobulin became elevated coincident with CNS relapse, and returned to normal as remission was achieved. Serial testing of CSF beta-2-microglobulin, in patients with cancers known to invade the CNS, should facilitate prompt treatment of CNS metastasis.

The levels of lysozyme (LZM) and beta 2-microglobulin (beta 2m) were measured in the cerebrospinal fluid (CSF) and serum of 32 patients with sarcoidosis, 20 of whom had neurosarcoidosis. LZM was analyzed by a new radioimmunoassay (RIA) modification. CSF LZM was elevated in 15 of 20 patients with neurosarcoidosis but in only 4 of 12 patients with extraneural sarcoidosis. CSF beta 2m values were elevated in 13 of 19 and in one of 11 patients, respectively. In neurosarcoidosis, both CSF LZM and beta 2m correlated to CSF leucocytes but not significantly to CSF albumin thus suggesting that LZM and beta 2m were secreted from cells within the central nervous system (CNS). In patients with sarcoidosis, elevations of CSF LZM and beta 2m revealed disease activity in the CNS. Both analyses were also useful in the follow-up of neurosarcoidosis.

A case of primary malignant lymphoma involving the hypothalamus is reported. A 31-year-old man was admitted with progressive disorientation. A computed tomography (CT) scan demonstrated a normodense, homogenously enhanced, and nodular shaped mass lesion involving the suprasellar region and extending to the third ventricle. In view of marked cerebral edema, dexamethasone was intravenously administered, at a dose of 4 mg/4 hr, and gradually tapered off. CT scans obtained 10 days after the admission revealed dramatic regression of the lesion, which corresponded with the clinical remission. However, on the 4th day after the discontinuance of corticosteroid, a CT scan demonstrated the recurrence of the mass lesion. Because of the rapid deterioration of consciousness and the progressive enlargement of the mass and dilatation of the ventricles, partial removal of tumor and ventricular drainage were carried out on the 24th day after admission. Dexamethasone was intravenously administered again at a dose of 4 mg/4 hr. A CT scan obtained five days after the operation showed complete disappearance of the lesion, and the patient had became almost alert. CT scans obtained on the 18th day and the 35th day after the operation showed complete disappearance of the mass. However, Magnetic Resonance Imaging revealed a localized area of abnormal signal intensity in the hypothalamus. Diabetes insipidus was continuously observed from the time of admission. A concomitant change of beta-2-microglobulin (beta-2-MG) and immunoglobulin (IgA, IgG, IgM) concentrations in serum and cerebrospinal fluid (CSF) with clinical profiles and CT findings were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial determinations of beta 2-microglobulin, lactoferrin and lysozyme in CSF were performed in 14 patients with acute cerebrovascular lesions. Marked elevations were noted in patients with cerebral bleeding or hemorrhagic infarction. Patients with infarction without signs of bleeding or with cerebrovascular lesions undetectable by computed tomography also had an increase in these proteins. The increases in CSF of beta 2-microglobulin, lactoferrin and lysozyme could not be explained by a damaged blood-brain barrier but was believed to be a local product of the central nervous system. Peak levels of lactoferrin and lysozyme were noted on day 2-3 after onset of symptoms. Lactoferrin then declined while lysozyme remained elevated for another few days. beta 2-microglobulin gradually increased reaching peak levels on day 4-5 and remained elevated even 2 weeks after the onset of symptoms. We suggest that the increases of lactoferrin, lysozyme and beta 2-microglobulin reflect various inflammatory reactions mediated by granulocytes, macrophages and lymphocytes, respectively.

beta 2-microglobulin was measured in the CSF of 33 MS patients (age range 26-66 years) and compared with the 95% confidence interval determined in an age-matched reference group of 32 patients without neurologic disease. Six MS (18%) had moderately increased concentrations and this subgroup was characterized by severe neurologic impairment according to Kurtzke's expanded disability scale. Increased CSF beta 2-microglobulin concentration in MS may reflect lesion formation.