Lectures

The protein concentrations in cerebrospinal fluid depend on blood concentration, blood-CSF barrier function and intrathecal synthesis. Therefore, the interpretation of CSF protein data on the base of absolute CSF concentrations or isolated CSF/serum quotients is not sufficient. The quantitation of intrathecal synthesis in quotient diagrams (Reibergrams) is well established in routine diagnosis of neurological diseases(1,2) with software supported CSF data reports. This diagnostic interpretation method in CSF/Serum quotient diagrams is now supplemented by a new statistics software for the numerical and graphical evaluation of patient groups. This is reached by (i) transfer of Albumin, IgG, IgA and IgM data from tables into Reibergrams; (ii) comparison of patient groups in a single diagram; (iii) group statistics for quantitative intrathecal Ig-synthesis; (iv) disease course for a single patient; and (v) therapy control data in a single diagram together with the easy export of graphical CSF data and statistics into research publication. This communication is to report the mathematical base. With a representative example, we demonstrate the application: a comparison of age-related intrathecal IgG, IgA and IgM synthesis in groups of patients with early onset multiple sclerosis between 7 and 30 years (Reiber H. et al unpublished data). Introduction: As a main target of Cerebrospinal fluid analysis, we detect intrathecal synthesis of the immonuglobulins IgG, IgA and IgM with reference to the albumin quotient, which is the parameter for the individual blood-CSF barrier function. The nonlinear reference range of blood-derived proteins in CSF (Fig.1) is based on the physiologically and theoretically derived hyperbolic functions (2) replacing older linear Index calculations which lead to false interpretations (1). This recent evaluation concept is presented in the CSFdata report to the clinician either graphically in theReibergrams (see Fig. 2) or numerically by calculation of the intrathecally synthesized amount (Igloc) in mg/l CSF or as the relative intrathecal fraction (Ig IF) in % of total Ig CSF concentration (1). Statistics in Reibergrams: The comparison of patient groups in the nonlinear evaluation diagrams needs the reference to the mean values of the reference range in the Reibergrams (Qmean in the Table1 and Fig. 1). This statistical treatment of patient groups is different from the individual data interpretation of a single patient in the routine analysis where we have to detect unambiguously an intrathecal synthesis. In this diagnostic case, the evaluation refers to the upper discrimination line of the reference range (Qlim in the Table1 and Fig.1) Basic calculations: For statistical evaluation this software (3) uses the functions described below. For this purpose in all functions used for routine analysis the values a/b, b, c of Qlim (Reiber 1994, http://www.horeiber.de) are replaced by those for the hyperbolic functions of Qmean. Qmean=a/b (QAlb +b))c The mean intrathecal synthesis is calculated correspondingly with: Igloc (m) = [QIg – Qmean (Ig)] · Ig serum (as mg/l) Ig IF (m) = Ig loc/Ig(CSF) · 100 (in %). The calculation examples in Table1 are performed for patient data with QAlb = 40 · 10 and the corresponding values of a/b, b, c for Qmean functions of IgG, IgA and IgM: Qmean (IgG) = 0.65 (40 2 + 8) -1.4 = 24.66 (·10) Qmean (IgA) = 0.47 (40 2 + 27) -2.1 = 16.86 (·10) Qmean (IgM) = 0.33 (40 2 + 306) -5.7 = 8.71 (·10) IgG loc (m) = (65-24.66) · 12.6 = 508.3 (mg/l) IgG IF(m) = 508.3/819 · 100 = 62 (%) Fig. 1. Hyperbolic functions (2) of the reference range for bloodderived proteins in CSF: QLim = upper border line for diagnostic purpose, Qmean = mean hyperbolic function as reference for statistical evaluation of patient groups. Journal compilation 2008 Blackwell Munksgaard 47 Table 1. Calculation examples with data from a patient with a neuroborreliosis