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Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases.

Jesse S, Brettschneider J, SĂĽssmuth SD, Landwehrmeyer BG, von Arnim CA, Ludolph AC, Tumani H, Otto M - J. Neurol. (2010)

Bottom Line: Mildly elevated Q (alb) were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND.With the exception of 1 MND patient, no intrathecal Ig synthesis was observed.Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Ulm, Steinhövelstr. 1, 89075, Ulm, Germany. sarah.jesse@uni-ulm.de

ABSTRACT
In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However, large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define a normal reference spectrum of routine CSF parameters in neurodegenerative diseases. Routine CSF parameters (white cell count, lactate and albumin concentrations, CSF/serum quotients of albumin (Q (alb)), IgG, IgA, IgM, and oligoclonal IgG bands (OCB)) were retrospectively analyzed in an academic research setting. A total of 765 patients (Alzheimer's disease (AD), Parkinson's disease (PD), Parkinson's disease dementia (PDD), vascular dementia (VD), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), motor neuron diseases (MND), spinocerebellar ataxia (SCA), Huntington's disease (HD)) and non-demented control groups including a group of patients with muscular disorders (MD). The main outcome measures included statistical analyses of routine CSF parameters. Mildly elevated Q (alb) were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND. With the exception of 1 MND patient, no intrathecal Ig synthesis was observed. Isolated OCBs in CSF were sometimes found in patients with neurodegenerative diseases without elevated cell counts; lactate levels were always normal. A slightly elevated Q (alb) was observed in a subgroup of patients with neurodegenerative diseases and does not exclude the diagnosis. Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis.

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Illustration of Reibergrams for all patient groups. Q–IgG, Q–IgA, and Q–IgM are indicated in relation to the CSF–blood barrier function, represented by Qalb. For interpretation of the Reibergrams, see Fig. 1
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Fig3: Illustration of Reibergrams for all patient groups. Q–IgG, Q–IgA, and Q–IgM are indicated in relation to the CSF–blood barrier function, represented by Qalb. For interpretation of the Reibergrams, see Fig. 1

Mentions: Intrathecal synthesis of IgG, IgA, and IgM was detected based on the method of Reiber referring the IgG, IgA, and IgM quotients to Qalb, with a nonlinear reference range of blood-derived proteins in CSF (see Fig. 1) based on the physiologically and theoretically derived hyperbolic functions [24, 26]. The data are presented to the clinician either graphically in the diagrams by Reiber, so called Reibergrams (see Fig. 3) or numerically by calculation of the intrathecally synthesized amount (Igloc) in mg/l CSF or as the relative intrathecal fraction (IgIF) in % of the total Ig CSF concentration. To ensure maximal sensitivity, the interpretation of an intrathecal synthesis refers to the upper border line of the reference range (Qlim in the quotient diagrams). This line is based on Qmean + 3s (or a reference range including 99% of the noninflammatory cases). The comparison of different patient groups in the nonlinear evaluation diagrams needs the reference to the mean values of the reference range in the Reibergrams (Qmean) as evaluated in the CSF statistics tool (“Protein Statistics in CSF Analysis with Reibergrams”, Version 3.0, COMED). Intrathecal Ig synthesis is calculated with Igloc in mg/l replacing Qlim by Qmean. IgIF, the relative intrathecal fraction is not useful for statistics of groups.Intrathecal Ig synthesis with reference to Qmean is calculated according to:\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\text{Ig}}_{\text{loc}} \left( {\text{mean}} \right) = \left( {Q_{\text{Ig}} - \, Q_{\text{Ig}} \left( {\text{mean}} \right)} \right) \, \times {\text{ Ig serum }}\left[ {{\text{mg}}/{\text{l}}} \right].$$\end{document}Fig. 1


Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases.

Jesse S, Brettschneider J, SĂĽssmuth SD, Landwehrmeyer BG, von Arnim CA, Ludolph AC, Tumani H, Otto M - J. Neurol. (2010)

Illustration of Reibergrams for all patient groups. Q–IgG, Q–IgA, and Q–IgM are indicated in relation to the CSF–blood barrier function, represented by Qalb. For interpretation of the Reibergrams, see Fig. 1
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101362&req=5

Fig3: Illustration of Reibergrams for all patient groups. Q–IgG, Q–IgA, and Q–IgM are indicated in relation to the CSF–blood barrier function, represented by Qalb. For interpretation of the Reibergrams, see Fig. 1
Mentions: Intrathecal synthesis of IgG, IgA, and IgM was detected based on the method of Reiber referring the IgG, IgA, and IgM quotients to Qalb, with a nonlinear reference range of blood-derived proteins in CSF (see Fig. 1) based on the physiologically and theoretically derived hyperbolic functions [24, 26]. The data are presented to the clinician either graphically in the diagrams by Reiber, so called Reibergrams (see Fig. 3) or numerically by calculation of the intrathecally synthesized amount (Igloc) in mg/l CSF or as the relative intrathecal fraction (IgIF) in % of the total Ig CSF concentration. To ensure maximal sensitivity, the interpretation of an intrathecal synthesis refers to the upper border line of the reference range (Qlim in the quotient diagrams). This line is based on Qmean + 3s (or a reference range including 99% of the noninflammatory cases). The comparison of different patient groups in the nonlinear evaluation diagrams needs the reference to the mean values of the reference range in the Reibergrams (Qmean) as evaluated in the CSF statistics tool (“Protein Statistics in CSF Analysis with Reibergrams”, Version 3.0, COMED). Intrathecal Ig synthesis is calculated with Igloc in mg/l replacing Qlim by Qmean. IgIF, the relative intrathecal fraction is not useful for statistics of groups.Intrathecal Ig synthesis with reference to Qmean is calculated according to:\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\text{Ig}}_{\text{loc}} \left( {\text{mean}} \right) = \left( {Q_{\text{Ig}} - \, Q_{\text{Ig}} \left( {\text{mean}} \right)} \right) \, \times {\text{ Ig serum }}\left[ {{\text{mg}}/{\text{l}}} \right].$$\end{document}Fig. 1

Bottom Line: Mildly elevated Q (alb) were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND.With the exception of 1 MND patient, no intrathecal Ig synthesis was observed.Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Ulm, Steinhövelstr. 1, 89075, Ulm, Germany. sarah.jesse@uni-ulm.de

ABSTRACT
In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However, large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define a normal reference spectrum of routine CSF parameters in neurodegenerative diseases. Routine CSF parameters (white cell count, lactate and albumin concentrations, CSF/serum quotients of albumin (Q (alb)), IgG, IgA, IgM, and oligoclonal IgG bands (OCB)) were retrospectively analyzed in an academic research setting. A total of 765 patients (Alzheimer's disease (AD), Parkinson's disease (PD), Parkinson's disease dementia (PDD), vascular dementia (VD), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), motor neuron diseases (MND), spinocerebellar ataxia (SCA), Huntington's disease (HD)) and non-demented control groups including a group of patients with muscular disorders (MD). The main outcome measures included statistical analyses of routine CSF parameters. Mildly elevated Q (alb) were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND. With the exception of 1 MND patient, no intrathecal Ig synthesis was observed. Isolated OCBs in CSF were sometimes found in patients with neurodegenerative diseases without elevated cell counts; lactate levels were always normal. A slightly elevated Q (alb) was observed in a subgroup of patients with neurodegenerative diseases and does not exclude the diagnosis. Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis.

Show MeSH
Related in: MedlinePlus