Disease-related data patterns in cerebrospinal fluid diagnostics: medical quality versus analytical quantity.

Cerebrospinal fluid (CSF) diagnostics is characterized by the biologically relevant combination of analytes in order to obtain disease-related data patterns that enable medically relevant interpretations. The necessary change in knowledge bases such as barrier function as a diffusion/CSF flow model and immunological networks of B-cell clones and pleiotropic cytokines is considered. The biophysical and biological principles for data combination are demonstrated using examples from neuroimmunological and dementia diagnostics.

Blood-cerebrospinal fluid (CSF) barrier dysfunction means reduced CSF flow not barrier leakage - conclusions from CSF protein data.

Background: Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such as barrier leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced CSF flow rate as the cause.

Results: Even the severest barrier dysfunctions do not change the molecular size-dependent selectivity or the interindividual variation of the protein transfer across barriers.

Non-linear ventriculo - Lumbar protein gradients validate the diffusion-flow model for the blood-CSF barrier.

Background: Concentrations of blood-derived proteins increase non-linearly between ventricular and lumbar CSF, which could not be satisfactorily explained by known barrier models.

Methods: Protein data analysis with OriginLab. Interpretations with Quotient diagrams by CSF/ Statistics software.

Free light chain kappa and the polyspecific immune response in MS and CIS - Application of the hyperbolic reference range for most reliable data interpretation.

Objectives: Free light chain kappa (FLC-k) in cerebrospinal fluid (CSF) is involved in intrathecal immune responses and is being investigated frequently for its diagnostic sensitivity. The objective of this study was the application and interpretation of FLC-k data in quotient diagrams with a hyperbolic reference range and to confirm the superior evaluation in comparison with another proposed reference method and cut-off values. Secondly, the performance of the FLC-k quotient diagram was analyzed in respect to MS and CIS patients and in relation to the polyspecific immune response.

Diagnostic relevance of free light chains in cerebrospinal fluid - The hyperbolic reference range for reliable data interpretation in quotient diagrams.

Background: Free light chains, type kappa (FLC-K), in cerebrospinal fluid (CSF) were compared to oligoclonal IgG in many studies for sensitive detection of immune reactions in brain. The missing consensus about CSF data interpretation prevents reliable conclusions. This can be overcome by a theory-based hyperbolic reference range in CSF/serum quotient diagrams.

Polyspecific antibodies without persisting antigen in multiple sclerosis, neurolupus and Guillain-Barré syndrome: immune network connectivity in chronic diseases.

The polyspecific antibody synthesis in multiple sclerosis (MS) gained diagnostic relevance with the frequent combination of measles-, rubella- and varicella zoster antibodies (MRZ-antibody reaction) but their pathophysiological role remains unknown. This review connects the data for intrathecal polyspecific antibody synthesis in MS and neurolupus with observations in the blood of patients with Guillain-Barré syndrome (GBS). Simultaneously increased antibody and autoantibody titers in GBS blood samples indicate that the polyspecific antibodies are based on a general property of an immune network, supported by the deterministic day-to-day concentration variation of antibodies in normal blood.

Knowledge-base for interpretation of cerebrospinal fluid data patterns. Essentials in neurology and psychiatry.

The physiological and biophysical knowledge base for interpretations of cerebrospinal fluid (CSF) data and reference ranges are essential for the clinical pathologist and neurochemist. With the popular description of the CSF flow dependent barrier function, the dynamics and concentration gradients of blood-derived, brain-derived and leptomeningeal proteins in CSF or the specificity-independent functions of B-lymphocytes in brain also the neurologist, psychiatrist, neurosurgeon as well as the neuropharmacologist may find essentials for diagnosis, research or development of therapies. This review may help to replace the outdated ideas like "leakage" models of the barriers, linear immunoglobulin Index Interpretations or CSF electrophoresis.

Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry.

The analysis of intrathecal IgG, IgA and IgM synthesis in cerebrospinal fluid (CSF) and evaluation in combined quotient diagrams provides disease-related patterns. The compilation with complementary parameters (barrier function, i.e.

Antibody patterns vary arbitrarily between cerebrospinal fluid and aqueous humor of the individual multiple sclerosis patient: specificity-independent pathological B cell function.

Intrathecal specific antibodies in multiple sclerosis (MS), core of several disease models, are functionally ambiguous. Parallel investigation of cerebrospinal fluid (CSF) and aqueous humor (AH) from 22 MS patients showed similar immune reactions in both compartments but in the individual patient we observed arbitrarily varying differences for specific antibody- (12/14), oligoclonal IgG- (7/8) and isotype patterns. Properties of polyspecific antibodies are consistent with B cells immigrating affinity-maturated, isotype-specific, producing low amounts of antibodies without local target antigen in the brain.

Cerebrospinal fluid neopterin is brain-derived and not associated with blood-CSF barrier dysfunction in non-inflammatory affective and schizophrenic spectrum disorders.

Many psychiatric patients have a minor blood-CSF barrier dysfunction and increased Cerebrospinal fluid (CSF) neopterin concentrations. The source of normal CSF neopterin, a biomarker in inflammatory and non-inflammatory neurological diseases, has never been shown explicitly, a precondition for sensitive detection of pathologically increased CSF neopterin. Neopterin concentrations (ELISA) in CSF and serum of normal controls (n = 26) are evaluated by inter-individual variation propagation.

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response.

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance.

Methodology/principal Findings: This was a retrospective study on a cohort of 115 T.

Mannan-binding lectin in cerebrospinal fluid: a leptomeningeal protein.

Background: Mannan-binding lectin (MBL), a protein of the innate immune response is attracting increasing clinical interest, in particularly in relation to its deficiency. Due to its involvement in brain diseases, identifying the source of MBL in CSF is important. Analysis of cerebrospinal fluid (CSF) can provide data that discriminates between blood-, brain-, and leptomeninges-derived proteins.

Mannose-binding lectin deficiency with eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in children: a case series.

Introduction: Eosinophilic meningitis, a potentially fatal disease caused by Angiostrongylus cantonensis, is considered an emerging infectious disease.

Case Presentation: Three Caucasian boys (aged five-years-old, 10-years-old and six-years-old) with a diagnosis of eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis were studied. Serum immunoglobulin A (IgA), IgM, IgG, and complements C3c and C4 levels were quantified by using an immunodiffusion technique.

Clinical and neurochemical characteristics of pediatric multiple sclerosis - CSF analysis as knowledge base for differential diagnosis and pathophysiology.

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system affecting young adults. Although adults and children share important features of the disease, they also differ in some clinical, radiological and laboratory aspects. This review focuses on the neuroimmunological findings in the cerebrospinal fluid of children with MS pointing out that there is already at earliest time of clinical manifestation a neuroimmunological pattern, which differs only in intensity of the humoral immune response but not in frequency and does not support a neuroimmunological difference between early onset from adult onset MS.

Treatment failure related to intrathecal immunoglobulin M (IgM) synthesis, cerebrospinal fluid IgM, and interleukin-10 in patients with hemolymphatic-stage sleeping sickness.

Human African trypanosomiasis treatment is stage dependent, but the tests used for staging are controversial. Central nervous system involvement and its relationship with suramin treatment failure were assessed in 60 patients with parasitologically confirmed hemolymphatic-stage Trypanosoma brucei gambiense infection (white blood cell count of View Article and Find Full Text PDF

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.

Fuchs heterochromic cyclitis: rubella virus antibodies and genome in aqueous humor.

Purpose: To characterize the polyspecific intraocular antibody synthesis in aqueous humor of patients with chronic inflammatory diseases of the eye and to detect the causative antigen in Fuchs heterochromic cyclitis (FHC).

Design: Retrospective case-control study.

Methods: Intraocular antibody synthesis is detected in aqueous humor with the Antibody Index [AI] (improved Goldmann-Witmer Index) and quantified as specific antibody fraction, F(s) (intraocular specific antibody concentration in percent of intraocular total immunoglobulin G in aqueous humor).

Proteins in cerebrospinal fluid and blood: barriers, CSF flow rate and source-related dynamics.

Cerebrospinal fluid (CSF) routine analysis for diagnosis of neurological diseases is based on the concepts for discrimination of blood-derived and brain-derived immunoglobulin fractions in CSF. The actual molecular flux/CSF flow theory of the blood/CSF barrier function, which founded the hyperbolic discrimination lines in quotient diagrams, is derived from the laws of molecular diffusion combined with CSF flow rate. It emerged from this theory that the decrease of CSF flow rate is sufficient to explain quantitatively the increase of CSF protein concentrations as observed in many neurological diseases.

Intrathecal immune response pattern for improved diagnosis of central nervous system involvement in trypanosomiasis.

Diagnosis of central nervous system (CNS) involvement in human African trypanosomiasis is crucial in determination of therapy. Cerebrospinal fluid (CSF) and serum immunoglobulin concentrations, blood-CSF barrier dysfunction, pattern of intrathecal immunoglobulin synthesis, trypanosome-specific antibody synthesis, and CSF lactate concentrations were analyzed in 272 patients with Trypanosoma brucei gambiense infection. As part of the 2- or 3-class immune response, the predominant intrathecal IgM synthesis was the most sensitive (95%) marker for inflammation of the brain.

Quality assurance for cerebrospinal fluid protein analysis: international consensus by an Internet-based group discussion.

A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This new approach respecting multicultural differences, common views, and minority opinions, is available in http://www.