Skip to main content
Top
Published in: Journal of Neurology 6/2011

Open Access 01-06-2011 | Original Communication

Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases

Authors: Sarah Jesse, Johannes Brettschneider, Sigurd D. Süssmuth, Bernhard G. Landwehrmeyer, Christine A. F. von Arnim, Albert C. Ludolph, Hayrettin Tumani, Markus Otto

Published in: Journal of Neurology | Issue 6/2011

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B, Vanderstichele H, Vanmechelen E, Blennow K (1999) Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol 56:673–680CrossRefPubMed Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B, Vanderstichele H, Vanmechelen E, Blennow K (1999) Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol 56:673–680CrossRefPubMed
2.
go back to reference Apostolski S et al (1991) Serum and CSF immunological findings in ALS. Acta Neurol Scand 83(2):96–98CrossRefPubMed Apostolski S et al (1991) Serum and CSF immunological findings in ALS. Acta Neurol Scand 83(2):96–98CrossRefPubMed
3.
go back to reference Brettschneider J, Claus A, Kassubek J, Tumani H (2005) Isolated blood–cerebrospinal fluid barrier dysfunction: prevalence and associated diseases. J Neurol 252:1067–1073CrossRefPubMed Brettschneider J, Claus A, Kassubek J, Tumani H (2005) Isolated blood–cerebrospinal fluid barrier dysfunction: prevalence and associated diseases. J Neurol 252:1067–1073CrossRefPubMed
4.
go back to reference Brettschneider J, Tumani H, Kiechle U, Muche R, Richards G, Lehmensiek V, Ludolph AC, Otto M (2009) IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One 4:e7638CrossRefPubMed Brettschneider J, Tumani H, Kiechle U, Muche R, Richards G, Lehmensiek V, Ludolph AC, Otto M (2009) IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One 4:e7638CrossRefPubMed
5.
go back to reference Deutsche Gesellschaft für Psychiatrie PuN, Deutsche Gesellschaft für Neurologie (2009) S3-Leitlinie Demenzen. 038/013 Deutsche Gesellschaft für Psychiatrie PuN, Deutsche Gesellschaft für Neurologie (2009) S3-Leitlinie Demenzen. 038/013
6.
go back to reference Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, Jellinger K, Lantos PL, Lippa CF, Mirra SS, Tabaton M, Vonsattel JP, Wakabayashi K, Litvan I (2002) Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 61:935–946PubMed Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, Jellinger K, Lantos PL, Lippa CF, Mirra SS, Tabaton M, Vonsattel JP, Wakabayashi K, Litvan I (2002) Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 61:935–946PubMed
7.
go back to reference Dubois B, Burn D, Goetz C, Aarsland D, Brown RG, Broe GA, Dickson D, Duyckaerts C, Cummings J, Gauthier S, Korczyn A, Lees A, Levy R, Litvan I, Mizuno Y, McKeith IG, Olanow CW, Poewe W, Sampaio C, Tolosa E, Emre M (2007) Diagnostic procedures for Parkinson’s disease dementia: recommendations from the movement disorder society task force. Mov Disord 22:2314–2324CrossRefPubMed Dubois B, Burn D, Goetz C, Aarsland D, Brown RG, Broe GA, Dickson D, Duyckaerts C, Cummings J, Gauthier S, Korczyn A, Lees A, Levy R, Litvan I, Mizuno Y, McKeith IG, Olanow CW, Poewe W, Sampaio C, Tolosa E, Emre M (2007) Diagnostic procedures for Parkinson’s disease dementia: recommendations from the movement disorder society task force. Mov Disord 22:2314–2324CrossRefPubMed
8.
go back to reference Frolich L, Kornhuber J, Ihl R, Fritze J, Maurer K, Riederer P (1991) Integrity of the blood–CSF barrier in dementia of Alzheimer type: CSF/serum ratios of albumin and IgG. Eur Arch Psychiatry Clin Neurosci 240:363–366CrossRefPubMed Frolich L, Kornhuber J, Ihl R, Fritze J, Maurer K, Riederer P (1991) Integrity of the blood–CSF barrier in dementia of Alzheimer type: CSF/serum ratios of albumin and IgG. Eur Arch Psychiatry Clin Neurosci 240:363–366CrossRefPubMed
9.
go back to reference Fuchs A, Rosenthal R (1904) Physikalisch-chemische, zytologische und anderweitige Untersuchungen der Cerebrospinalflüssigkeit. Wien Med Presse 45:2081–2087 Fuchs A, Rosenthal R (1904) Physikalisch-chemische, zytologische und anderweitige Untersuchungen der Cerebrospinalflüssigkeit. Wien Med Presse 45:2081–2087
10.
go back to reference Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Klockgether T, Lang A, Lantos P, Litvan I, Mathias C, Oliver E, Robertson D, Schatz I, Wenning G (1998) Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. Clin Auton Res 8:359–362CrossRefPubMed Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Klockgether T, Lang A, Lantos P, Litvan I, Mathias C, Oliver E, Robertson D, Schatz I, Wenning G (1998) Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. Clin Auton Res 8:359–362CrossRefPubMed
11.
go back to reference H Hampel, Müller-Spahn F, Berger C, Haberl A, Ackenheil M, Hock C (1995) Evidence of blood–cerebrospinal fluid-barrier impairment in a subgroup of patients with dementia of the Alzheimer type and major depression: a possible indicator for immunoactivation. Dementia 6:348–354 H Hampel, Müller-Spahn F, Berger C, Haberl A, Ackenheil M, Hock C (1995) Evidence of blood–cerebrospinal fluid-barrier impairment in a subgroup of patients with dementia of the Alzheimer type and major depression: a possible indicator for immunoactivation. Dementia 6:348–354
12.
go back to reference Hampel H, Kotter HU, Padberg F, Korschenhausen DA, Moller HJ (1999) Oligoclonal bands and blood–cerebrospinal-fluid barrier dysfunction in a subset of patients with Alzheimer disease: comparison with vascular dementia, major depression, and multiple sclerosis. Alzheimer Dis Assoc Disord 13:9–19CrossRefPubMed Hampel H, Kotter HU, Padberg F, Korschenhausen DA, Moller HJ (1999) Oligoclonal bands and blood–cerebrospinal-fluid barrier dysfunction in a subset of patients with Alzheimer disease: comparison with vascular dementia, major depression, and multiple sclerosis. Alzheimer Dis Assoc Disord 13:9–19CrossRefPubMed
13.
go back to reference Harbo HF, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, De Jonghe P, Lossos A, Lynch T, Mariotti C, Schols L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen C, Zeviani M, Burgunder JM, Gasser T (2009) EFNS guidelines on the molecular diagnosis of neurogenetic disorders: general issues, Huntington’s disease, Parkinson’s disease and dystonias. Eur J Neurol 16:777–785CrossRefPubMed Harbo HF, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, De Jonghe P, Lossos A, Lynch T, Mariotti C, Schols L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen C, Zeviani M, Burgunder JM, Gasser T (2009) EFNS guidelines on the molecular diagnosis of neurogenetic disorders: general issues, Huntington’s disease, Parkinson’s disease and dystonias. Eur J Neurol 16:777–785CrossRefPubMed
14.
go back to reference Janssen JC, Godbolt AK, Ioannidis P, Thompson EJ, Rossor MN (2004) The prevalence of oligoclonal bands in the CSF of patients with primary neurodegenerative dementia. J Neurol 251:184–188CrossRefPubMed Janssen JC, Godbolt AK, Ioannidis P, Thompson EJ, Rossor MN (2004) The prevalence of oligoclonal bands in the CSF of patients with primary neurodegenerative dementia. J Neurol 251:184–188CrossRefPubMed
15.
go back to reference Keir G, Luxton RW, Thompson L (1990) Isoelectric focusing of cerebrospinal fluid immunoglobulin G: an annotated update. Ann Clin Biochem 27:436–443PubMed Keir G, Luxton RW, Thompson L (1990) Isoelectric focusing of cerebrospinal fluid immunoglobulin G: an annotated update. Ann Clin Biochem 27:436–443PubMed
16.
go back to reference Klockgether T (2005) Ataxias Diagnostic procedure and treatment. Nervenarzt 76:1275–1283 quiz 1284-1275CrossRefPubMed Klockgether T (2005) Ataxias Diagnostic procedure and treatment. Nervenarzt 76:1275–1283 quiz 1284-1275CrossRefPubMed
17.
go back to reference Leonardi A, Abbruzzese G, Arata L, Cocito L, Vische M (1984) Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis. J Neurol 231:75–78CrossRefPubMed Leonardi A, Abbruzzese G, Arata L, Cocito L, Vische M (1984) Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis. J Neurol 231:75–78CrossRefPubMed
18.
go back to reference Lewczuk P, Esselmann H, Bibl M, Beck G, Maler JM, Otto M, Kornhuber J, Wiltfang J (2004) Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer’s disease: original data and review of the literature. J Mol Neurosci 23:115–122CrossRefPubMed Lewczuk P, Esselmann H, Bibl M, Beck G, Maler JM, Otto M, Kornhuber J, Wiltfang J (2004) Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer’s disease: original data and review of the literature. J Mol Neurosci 23:115–122CrossRefPubMed
19.
go back to reference Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47:1–9PubMed Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47:1–9PubMed
20.
go back to reference McKeith IG (2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. J Alzheimers Dis 9:417–423PubMed McKeith IG (2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. J Alzheimers Dis 9:417–423PubMed
21.
go back to reference McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944PubMed McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944PubMed
22.
go back to reference Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546–1554PubMed Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546–1554PubMed
23.
go back to reference Otto M (2010) Dementia diagnostics 2.0–transfer from research studies into routine clinical practice. Clin Chem 56:152–153CrossRefPubMed Otto M (2010) Dementia diagnostics 2.0–transfer from research studies into routine clinical practice. Clin Chem 56:152–153CrossRefPubMed
24.
go back to reference Reiber H (1994) Flow rate of cerebrospinal fluid (CSF)- a concept common to normal blood–CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122:189–203CrossRefPubMed Reiber H (1994) Flow rate of cerebrospinal fluid (CSF)- a concept common to normal blood–CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122:189–203CrossRefPubMed
25.
go back to reference Reiber H (1995) External quality assessment in clinical neurochemistry: survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF/serum quotients. Clin Chem 41:256–263PubMed Reiber H (1995) External quality assessment in clinical neurochemistry: survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF/serum quotients. Clin Chem 41:256–263PubMed
26.
go back to reference Reiber H (2003) Proteins in cerebrospinal fluid and blood: barriers, CSF flow rate and source-related dynamics. Restor Neurol Neurosci 21:79–96PubMed Reiber H (2003) Proteins in cerebrospinal fluid and blood: barriers, CSF flow rate and source-related dynamics. Restor Neurol Neurosci 21:79–96PubMed
27.
go back to reference Reiber H, Peter JB (2001) Cerebrospinal fluid analysis—disease-related data patterns and evaluation programs. J Neurol Sci 184:101–122CrossRefPubMed Reiber H, Peter JB (2001) Cerebrospinal fluid analysis—disease-related data patterns and evaluation programs. J Neurol Sci 184:101–122CrossRefPubMed
28.
go back to reference Reiber H, Ungefehr S, Jacobi C (1998) The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler 4:111–117PubMed Reiber H, Ungefehr S, Jacobi C (1998) The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler 4:111–117PubMed
29.
go back to reference Reiber H, Otto M, Trendelenburg C, Wormek A (2001) Reporting cerebrospinal fluid data: knowledge base and interpretation software. Clin Chem Lab Med 39:324–332CrossRefPubMed Reiber H, Otto M, Trendelenburg C, Wormek A (2001) Reporting cerebrospinal fluid data: knowledge base and interpretation software. Clin Chem Lab Med 39:324–332CrossRefPubMed
30.
go back to reference Skoog I, Wallin A, Fredman P, Hesse C, Aevarsson O, Karlsson I, Gottfries CG, Blennow K (1998) A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology 50:966–971PubMed Skoog I, Wallin A, Fredman P, Hesse C, Aevarsson O, Karlsson I, Gottfries CG, Blennow K (1998) A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology 50:966–971PubMed
31.
32.
go back to reference The EFNS Task Force on Diagnosis, Management of Amyotrophic Lateral Sclerosis (2005) Guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol 12:921–938CrossRef The EFNS Task Force on Diagnosis, Management of Amyotrophic Lateral Sclerosis (2005) Guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol 12:921–938CrossRef
33.
go back to reference Tumani H, Teunissen C, Sussmuth S, Otto M, Ludolph AC, Brettschneider J (2008) Cerebrospinal fluid biomarkers of neurodegeneration in chronic neurological diseases. Expert Rev Mol Diagn 8:479–494CrossRefPubMed Tumani H, Teunissen C, Sussmuth S, Otto M, Ludolph AC, Brettschneider J (2008) Cerebrospinal fluid biomarkers of neurodegeneration in chronic neurological diseases. Expert Rev Mol Diagn 8:479–494CrossRefPubMed
34.
go back to reference Upton ML, Weller RO (1985) The morphology of cerebrospinal fluid drainage pathways in human arachnoid granulations. J Neurosurg 63:867–875CrossRefPubMed Upton ML, Weller RO (1985) The morphology of cerebrospinal fluid drainage pathways in human arachnoid granulations. J Neurosurg 63:867–875CrossRefPubMed
35.
go back to reference Vandermeeren M, Mercken M, Vanmechelen E, Six J, van de Voorde A, Martin JJ, Cras P (1993) Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 61:1828–1834CrossRefPubMed Vandermeeren M, Mercken M, Vanmechelen E, Six J, van de Voorde A, Martin JJ, Cras P (1993) Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 61:1828–1834CrossRefPubMed
36.
go back to reference Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B (2007) Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol 14:e1–26CrossRefPubMed Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B (2007) Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol 14:e1–26CrossRefPubMed
37.
go back to reference Zimmermann R, Beck G, Knispel S, Maler JM, Weih M, Wiltfang J, Kornhuber J, Lewczuk P (2010) Intrathecal IgG synthesis in patients with alterations in the neurochemical dementia diagnostics. J Alzheimers Dis 19:1199–1203 Zimmermann R, Beck G, Knispel S, Maler JM, Weih M, Wiltfang J, Kornhuber J, Lewczuk P (2010) Intrathecal IgG synthesis in patients with alterations in the neurochemical dementia diagnostics. J Alzheimers Dis 19:1199–1203
Metadata
Title
Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases
Authors
Sarah Jesse
Johannes Brettschneider
Sigurd D. Süssmuth
Bernhard G. Landwehrmeyer
Christine A. F. von Arnim
Albert C. Ludolph
Hayrettin Tumani
Markus Otto
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Journal of Neurology / Issue 6/2011
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-010-5876-x

Other articles of this Issue 6/2011

Journal of Neurology 6/2011 Go to the issue