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H Reiber

Publications and source records attributed to H Reiber.

At least 19 recordsLinked to original sources
PubMed2001

Dynamics of brain-derived proteins in cerebrospinal fluid.

BACKGROUND: The recent theory of blood-cerebrospinal fluid (CSF) barrier function and dysfunction connects molecular flux and CSF flow rate. A reduced CSF flow rate is sufficient to account for the observed hyperbolic relation between different blood-derived protein concentrations in CSF in cases of a blood-CSF barrier dysfunction. METHODS: The dynamics of brain-derived proteins in CSF are investigated with reference to the CSF flow rate measured by CSF/serum albumin concentration quotient. RESULTS: Proteins from neurons or glial cells, tau protein, neuron-specific enolase, S-100 protein, all enter CSF primarily in the ventricular and cisternal space. Their concentration between normal ventricular and lumbar CSF is decreasing (in contrast to blood-derived proteins), and in the case of pathologically decreasing CSF flow rate, the concentration in lumbar CSF remains invariantly constant. Concentrations of the primarily leptomeningeal proteins, beta-trace protein and cystatin C, increase between normal ventricular and lumbar CSF, and in the case of pathologically decreased CSF flow rate they increase linearly in lumbar CSF (concentrations of blood-derived proteins increase non-linearly). CONCLUSIONS: A satisfactory physiological explanation can now be given for the dynamics of proteins in CSF consisting of both brain- and blood-derived fractions (transthyretin, soluble intercellular adhesion molecule (s-ICAM)), as well as the disputed decrease of leptomeningeal protein concentrations (beta-trace protein, cystatin C) in cases of bacterial meningitis is also explained. The biophysical treatment of dynamics in the ventricular and lumbar CSF extends the new theory and shows that CSF flow rate is the most relevant parameter for understanding the pathological changes of both blood- and brain-derived proteins in CSF. The impact on diagnosis of neuro-degenerative diseases is discussed.

Albumins↗
PubMed2001

Tau protein in cerebrospinal fluid (CSF): a blood-CSF barrier related evaluation in patients with various neurological diseases.

Tau protein (tau) is primarily localised in neurons, and after brain parenchymal damage its release into cerebrospinal fluid (CSF) is increased. The particular influences of blood-CSF barrier function and of disease topography on CSF tau levels have not been studied yet. CSF tau concentrations determined by enzyme-immunoassay in various neurological diseases (n = 61) were not dependent upon blood-CSF barrier dysfunction. Significant elevation of tau levels in patients with meningoencephalitis and cerebral hemorrhage indicates brain parenchymal damage. In contrast, tau levels remained normal in patients with bacterial meningitis if encephalitic complications did not occur. In patients with Guillain-Barré syndrome tau levels were low. Increased tau levels in active multiple sclerosis compared to clinically nonactive states indicate axonal pathology in active disease.

Albumins↗
PubMed2001

Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs.

Cerebrospinal fluid (CSF) analysis is a basic tool for diagnosis of neurological diseases. Knowledge regarding blood-CSF barrier function (molecular flux/CSF flow theory) and neuroimmunology is reviewed to aid understanding and evaluation of CSF data. Disease-related immunoglobulin patterns (IgG, IgA, IgM with reference to albumin) are described in CSF/serum quotient diagrams with the hyperbolic reference range for blood-derived protein fractions in CSF. Clinical relevance of complementary analyses (cytology, PCR, oligoclonal IgG, antibody detection and brain-derived proteins) is briefly discussed. Integrated CSF data reports are shown with numerical and graphical data representation, reference range-related interpretation and diagnosis-related comments. The principles and rationale of general CSF analysis reported in this review should enable the reader to accurately interpret CSF data profiles, and to plan a proper evaluation of new brain- or blood-derived analytes in CSF.

Albumins↗
PubMed2001

Reporting cerebrospinal fluid data: knowledge base and interpretation software.

The compilation of cerebrospinal fluid (CSF) patient data together with a graphic display of immunoglobulin patterns in a single CSF report has two main advantages: analytical and clinical plausibility control of a complex set of data improves quality assessment and allows improved clinical specificity and sensitivity for recognition of disease-related "typical" data patterns. The widespread use of automated on-line evaluation programs can now be combined with knowledge-based programs for interpretation by clinical chemists and neurologists. These programs are based on knowledge of neuroimmunology, blood-CSF barrier function and dysfunction, influence of CSF flow on concentrations of blood-derived and brain-derived proteins in CSF, specific intrathecal antibody synthesis and relevance of brain proteins for differential diagnosis of degenerative diseases. The relevance of hyperbolic discrimination functions in quotient diagrams for the detection of intrathecal immunoglobulin synthesis is compared with earlier, still frequently used, linear interpretation functions. Differences found in commercially available interpretation software are discussed.

Brain↗
PubMed2000

Intrathecal release of sICAM-1 into CSF in neuroborreliosis--increased brain-derived fraction.

In the present study, we report sICAM-1 concentration in the cerebrospinal fluid (CSF) and serum of patients with neuroborreliosis (NB, n = 11), compared to the data from a control group of patients with corresponding blood/CSF barrier dysfunction but without inflammation in the central nervous system (disc prolaps, DP, n = 11). In NB, the sICAM-1 concentration in CSF was increased up to six-fold (ranges: 6.6-42.8 ng/ml and 2.2-9.8 ng/ml for NB and DP respectively) with no change in serum sICAM-1. The corresponding sICAM-1 CSF/serum concentration quotients (Q(ICAM)) were in the ranges: 22.5-171.3 X 10(-3), and 8.8-27.8 X 10(-3) for NB and DP respectively. This finding can be explained by increase of the brain-derived fraction of sICAM-1 in NB. In one case we observed increased Q(ICAM) on 6th day after admission to the hospital (171.3 X 10(-3) at the time of the first lumbar puncture slightly increasing to 243.6 x 10(-3) five days later), followed by normalization, in two remaining repunctured patients we observed decreasing QICAM with normalizing Q(Alb).

Adolescent↗
PubMed2000

European cerebrospinal fluid consensus group--a TeamRoom (Lotus Notes)-based communication network.

A group of clinical neurochemists from all over Europe used TeamRoom to share information and to trace their discussions in a computer network. TeamRoom is a Lotus Notes based groupware tool enabling collaboration amongst geographically dispersed teams. As a result of this work a picture is emerging in the virtual TeamRoom space that represents a new kind of consensus in the use of cerebrospinal fluid analysis for diagnosis of neurological diseases. This kind of consensus differs from the conventional written report in giving a more complex and potentially richer representation of the field, in which both common views and minority perspectives are revealed. If direct access to this work is made available to other clinical neurochemists for consultation via a website, they may see their own practice in a wider context. This approach to improving different evolving traditions is more suitable for a global multicultural environment than a singular view of best practice produced by a more traditional process of group discussion. We refer to the benefits of a mixture of face to face meetings, collaboration in TeamRoom and teleconferencing for work in a non-hierarchical, multicultural and multilingual group. We suggest that the TeamRoom concept is a valuable model for enhancing self-organized harmonization across the developing European Union.

Computer Communication Networks↗
PubMed1999

Prothrombin concentration in the cerebrospinal fluid is not altered in Alzheimer's disease.

Prothrombin, known to be expressed in brain and to possess growth modulating properties, has been suggested to be involved in the pathogenesis of Alzheimer's disease (AD). We studied prothrombin concentration in lumbar CSF (L-CSF) in patients with AD (n = 25), neurologic disease controls (NDC; n = 33) covering a wide range of neurologic disorders, and subjects with Guillain-Barre syndrome (GBS; n = 4) as well as in samples of non-pathological ventricular CSF (V-CSF; n = 4). The results were evaluated with respect to CSF flow rate, as indicated by the albumin quotient (Q(Alb)). The concentrations of prothrombin in L-CSF in NDC (mean: 0.46 mg/l, range: 0.21-0.96), and AD (mean: 0.6 mg/l, range: 0.19-1.2) were in the normal range reported previously. Expectedly, prothrombin concentration in L-CSF of GBS was increased (mean: 6.3 mg/l, range: 2.3-9.7) corresponding to the increased Q(Alb) in this group (mean 54.6x10(-3), range: 17-88.1). The concentrations of both prothrombin and albumin were 5.5-fold higher in L-CSF than in V-CSF (mean Q(Alb) : 1.1x10(-3), mean concentration of prothrombin: 0.088 mg/l). In conclusion, CSF prothrombin in all conditions evaluated here is exclusively derived from blood.

Adolescent↗
PubMed1998

Intercellular adhesion molecule-1 in cerebrospinal fluid--the evaluation of blood-derived and brain-derived fractions in neurological diseases.

The soluble intercellular adhesion molecule-1 (sICAM-1) was measured in paired CSF and serum samples from 128 patients with different neurological diseases. The reference range of blood-derived sICAM-1 fractions in CSF was characterized with reference to the albumin CSF/serum quotients. The low mean concentrations of sICAM-1 of normal controls (n=33) in CSF (1.5 ng/ml; C.V.=40%) compared to serum (285.1 ng/ml; C.V.=32%) indicate that about 60% to 80% of sICAM-1 in normal lumbar CSF derives from blood. This calculation is based on the theoretically expected molecular size-dependent blood-CSF gradient between 300:1 to 250:1. In patients with non-inflammatory diseases (n=21) the sICAM-1 CSF/serum quotient increased non-linearly with increasing albumin CSF/serum quotient (blood-CSF barrier dysfunction) displaying the shape of a saturation-like curve in contrast to hyperbolic curves of other blood-derived proteins in CSF. This non-linear relation between sICAM-1 and albumin quotients does not allow a linear index evaluation reported in earlier studies. In bacterial meningitis (n=31) and viral meningoencephalitis (n=28) in addition to the increased blood-derived fraction, the brain-derived fraction of sICAM-1 in CSF was up to 12-fold higher than that in controls. The sICAM-1 CSF/serum quotients in MS (n=15) did not differ from non-inflammatory controls, i.e., there was no brain-dependent sICAM-1 fluctuation in CSF in contrast to the known fluctuations in blood. Earlier published reports on sICAM-1 have been controversial due to less sensitive assays and unsuitable linear evaluation concepts for blood-CSF barrier dysfunction.

Blood-Brain Barrier↗
PubMed1998

Beta-trace protein concentration in cerebrospinal fluid is decreased in patients with bacterial meningitis.

Although meninges represent a major site of biosynthesis, beta-trace protein (beta-trace) has not been studied in the cerebrospinal fluid (CSF) of meningitis patients. We measured beta-trace in lumbar CSF of normal controls (n = 27) and in patients with various neurological diseases (n = 92) by an immunonephelometric assay. The mean concentration of beta-trace in CSF of control patients was 16.6+/-3.6 mg/l. In bacterial meningitis (n = 41), CSF beta-trace was significantly decreased (8.7+/-3.9 mg/l; P< 0.001), whereas in spinal canal stenosis it was elevated (29.2+/-10.3 mg/l; P= 0.002). In viral meningoencephalitis (n = 12), beta-trace CSF concentrations were normal. Beta-trace concentrations remained below the normal range even after curing of bacterial meningitis, and normalisation of CSF leucocytes and blood-CSF barrier function. Beta-trace may be a useful tool for studying the pathophysiology of bacterial meningitis.

Adult↗
PubMed1998

Prothrombin in normal human cerebrospinal fluid originates from the blood.

In spite of the fact that prothrombin is produced by cells within the central nervous system, its presence in the cerebrospinal fluid (CSF) has not been investigated. We determined the concentration of prothrombin in CSF with reference to the concentration in plasma in paired samples from 18 "normal" control patients and 4 patients with relapsing-remitting type of multiple sclerosis (MS). The newly developed ELISA was very specific (no cross-reactivity with thrombin) and sensitive (detection limit--0.7 ng/ml) with an imprecision of CV = 8.3% (intraseries) and 7.0% (interassay). The mean prothrombin concentration in normal CSF was 0.55 mg/l (CV +/- 33%, range: 0.28-0.93 mg/l), in normal plasma 121.8 mg/l +/- 21%, resulting in a mean CSF/plasma concentration quotient (Q(Proth)--4.5 x 10(-3) (CV +/- 35%, range: 2.1-8.3 x 10(-3)) corresponding to a mean albumin quotient in this group of subjects of Q(Alb) = 5.8 x 10(-3). Due to the Q(Proth) and the molecular weight of prothrombin (72 kDa)--similar to that of albumin--we conclude that prothrombin in normal human CSF originates predominantly (>95%) from blood. The enzymatic activity in CSF is conserved. Comparable results obtained in MS patients with only few small MRI lesions suggest that local chronic inflammatory disease of the central nervous system does not influence prothrombin concentration in the CSF if the blood-CSF barrier function is normal.

Biological Transport↗
PubMed1998

Intrathecal synthesis of immunoglobulins in eosinophilic meningoencephalitis due to Angiostrongylus cantonensis.

Eosinophilic meningoencephalitis due to the nematode Angiostrongylus cantonensis, which is endemic to Cuba, occurs in children and is due to accidental contact with soil snails. The course is less often fatal than in adult patients in southeastern Asia. Cerebrospinal fluid (CSF) and serum samples from 24 pediatric patients were analyzed and evaluated in CSF/serum quotient diagrams (Reiber graphs) to characterize the neuroimmunological response and the blood-CSF barrier dysfunction that occur in the course of the disease. At the time of the first diagnostic lumbar puncture, together with eosinophilic pleocytosis (1,920 +/- 400 cells/microl), intermediate blood-CSF barrier dysfunction (i.e., an increased CSF/serum albumin quotient) with no intrathecal immunoglobulin G (IgG), IgA, and IgM class response was observed in all cases. Seven days later, at the time of early clinical recovery, the blood-CSF barrier dysfunction was normalized in 75% of the patients, but meanwhile, intrathecal immunoglobulin synthesis emerged in all cases, as either a two-class response (IgG and IgA in 85% of the patients) or a three-class response (IgG, IgA, and IgM; 30%). The fraction of eosinophilic cells (40%) remained large despite a decreasing total cell count. The neuroimmunological pattern of this inflammatory response to the parasite and its toxins is discussed with regard to the CSF patterns of other infectious diseases caused by bacteria or viruses.

Adolescent↗
PubMed1998

Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases.

The state of the art in routine CSF analysis is reviewed with particular reference to multiple sclerosis regarding: (1) The physiology and pathophysiology of blood-CSF barrier function and dysfunction with the CSF flow rate as main modulator of blood- and brain-derived protein concentrations in CSF; (2) The neuroimmunological aspects regarding (a) patterns of disease-related immunoglobulin class response (IgG, IgA, IgM) in actual Reiber graphs with reference to specific parameters and optional tests, and (b) the oligoclonal, polyspecific antibody synthesis in brain; (3) Particular marker proteins in CSF and blood for differential diagnosis of neurological diseases; (4) Mathematical base for evaluations of CSF data with an example of a multiple sclerosis patient for calculation of intrathecal immunoglobulin and antibody synthesis as well as Antibody Index.

Biomarkers↗
PubMed1998

The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis.

We report an extended set of neuroimmunological data detected in cerebrospinal fluid (CSF) from n = 267 patients with definite multiple sclerosis (MS). Known frequencies of oligoclonal IgG (98%), frequencies of intrathecal fractions of IgG, IgA and IgM (72%, 9% and 20%, respectively) were confirmed and quantitated as intrathecal fractions, IgIF or CSF concentrations, IgLOC. Eighty-nine per cent of the patients had a combined 'MRZ-reaction', i.e. intrathecal antibody synthesis (Antibody Index, AI > 1.4) against measles, rubella and/or varicella zoster virus. Frequencies of single antibodies decreased from measles (78%) to rubella (60%), VZV (55%) and HSV (28%). This MRZ-reaction, indicating a chronic autoimmune type disease already at time of first clinical symptoms, is less sensitive but more specific than detection of oligoclonal IgG. With increasing intrathecal IgG synthesis the number of different locally synthesized antibody species were increased as well as the amount per species (increased mean AI values). The concentration of MRZ antibodies in CSF represents together about 2% of intrathecally synthesized total IgG. But, as a very particular result the ratio of intrathecally synthesized specific antibody/intrathecally synthesized JgG was 5-fold higher (0.24-0.85%) compared to the corresponding ratio in blood (0.06-0.17%) of MS patients. This difference between brain ratio and blood ratio is discussed to be indicative for the anti-MRZ antibody forming B-lymphocyte subset in blood migrating into brain at earlier time of pathophysiological start of disease. These results give a concise explanation of neuroimmunological aspects in MS, not understood so far.

Antibodies, Viral↗
PubMed1998

Non increased neuron-specific enolase concentration in cerebrospinal fluid during first febrile seizures and a year follow-up in pediatric patients.

Febrile seizures are the commonest acute neurological disorder of early childhood. Studies suggested that febrile seizures are previous acute events from a more serious neurological problem. Due to neuron-specific enolase is generally accepted as a marker for neuropathological processes in the brain, 16 pediatric patients were studied during their first seizures and a year after it. Neuron-specific enolase in cerebrospinal fluid and blood were analysed by an immune enzyme assay. Non pathological neuron-specific enolase values were obtained in both periods in the group of patients. There were no significative differences when paired series statistics test was performed with 95% of confidence. Neuron-specific enolase appears not to be a marker for febrile seizures because its concentration not be increased in cerebrospinal fluid in this group of patients.

Cerebrospinal Fluid↗
PubMed1998

[Beta trace protein in the cerebrospinal fluid and serum in meningoencephalitis].

INTRODUCTION: beta-trace protein or D2 prostaglandin synthase is a dual functional protein. Its role and clinical value in cerebrospinal fluid is under study. MATERIAL AND METHODS: Seventy four pediatric patients suffering from viral meningoencephalitis and 7 with bacterial meningoencephalitis were studied. Sera and cerebrospinal fluid samples were taken. Albumin and beta-trace protein were quantified by immunodiffusion and nephelometry respectively. RESULTS: Increased cerebrospinal fluid beta-trace protein levels in comparison with normal value were observed. Nevertheless such expected increment was no possible seen in bacterial meningoencephalitis. CONCLUSIONS: beta-trace protein may contribute with the etiological diagnosis in meningoencephalitis.

Albumins↗
PubMed1997

[Analysis of aqueous humor in intraocular toxoplasmosis].

BACKGROUND: Despite many clinical examinations and laboratory tests, the cause of uveitis is very often not discovered. The examination of local intraocular antibody production is a valuable additional diagnostic means. PATIENTS AND METHODS: Aqueous humor was obtained from 46 eyes with severe uveitis: retinochorioiditis (n = 27), intermediate uveitis (n = 11), iridocyclitis (n = 5), and panuveitis (3). With the enzyme-linked immunosorbent assay (ELISA) the antibodies against Toxoplasma gondii were measured in aqueous humor and serum and the intraocular antibody production was calculated by the formation of an antibody index (AI). As the AI values are corrected for possible polyspecific immune response, the AI index is more sensitive than the Goldmann-Witmer index. RESULTS: An intraocular antibody synthesis against T. gondii could be confirmed in 20 eyes. The serum antibody concentration against T. gondii was in the reference range in 45 patients and only one patient had a very high increase of antibodies. In nine of 20 eyes, intraocular synthesis of antibodies against T. gondii was unexpected due to the lack of clinical evidence. CONCLUSIONS: The aqueous humor analysis is more reliable than the proof of serum antibodies, and it helps to increase the number of eyes with uveitis in which a specific therapy can be established.

Animals↗
PubMed1997

Intrathecal IgA synthesis in X-linked cerebral adrenoleukodystrophy.

Cerebrospinal fluid data on 25 patients suffering from various phenotypes of X-linked adrenoleukodystrophy have been evaluated neurochemically including cerebrospinal fluid/serum quotient diagrams. Intrathecal IgA production in 13 of 14 patients with cerebral adrenoleukodystrophy was the most sensitive parameter in cerebrospinal fluid and was not seen in any of the neurologically asymptomatic patients or in the patients with adrenomyeloneuropathy. A blood-cerebrospinal fluid barrier dysfunction was found in 9 of these 14 patients. Additional intrathecal IgG or IgM synthesis was observed in 3 patients each. In 1 patient with lumbar punctures before and after onset of neurologic symptoms intrathecal IgA synthesis was seen only after the appearance of neurologic symptoms. Repetition of lumbar punctures in 5 neurologically symptomatic patients with cerebral adrenoleukodystrophy revealed a similar pattern of intrathecal IgA synthesis with a tendency of decreasing IgA concentration. The pathophysiologic aspects of intrathecal IgA synthesis are discussed in relation to other demyelinating and inflammatory neurologic diseases.

Adolescent↗