Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2015

Open Access 01-12-2015 | Research article

No prognostic value of routine cerebrospinal fluid biomarkers in a population-based cohort of 407 multiple sclerosis patients

Authors: Madlyne Becker, Clotilde Latarche, Emilie Roman, Marc Debouverie, Catherine Malaplate-Armand, Francis Guillemin

Published in: BMC Neurology | Issue 1/2015

Login to get access

Abstract

Background

We aimed to determine the association of clinical and routine cerebrospinal fluid biochemical markers (total protein, IgG index and oligoclonal bands) with disability in multiple sclerosis and whether these biomarkers assessed at diagnosis add prognostic value.

Methods

We followed a cohort of patients included in the Multiple Sclerosis Lorraine Register (eastern France) who had a diagnosis of multiple sclerosis for at least 5 years, as well as biological markers values and MRI findings (Barkhof’s criteria). In a Cox regression model, endpoint was time to score of 4 on the Expanded Disability Status Scale (EDSS) (i.e., limited time walking without aid or rest for more than 500 m).

Results

For 407 patients included, the median time from multiple sclerosis onset to EDSS score 4 was 4.5 years [2.2–7.2]. Cerebrospinal fluid total protein factor < 500 mg/L was associated with EDSS score 4 on bivariate analysis (hazard ratio 0.66, 95% confidence interval 0.46–0.95, p = 0.02). On multivariate analysis, older age at disease onset (≥50 years) and initial primary progressive course of MS but not biological markers predicted worse prognosis.

Conclusion

Routine cerebrospinal fluid biological markers at diagnosis were not prognostic factors of multiple sclerosis progression.
Literature
1.
Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol. 2005;62(6):865–70.CrossRefPubMed
2.
Deisenhammer F, Bartos A, Egg R, Gilhus NE, Giovannoni G, Rauer S, et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol. 2006;13(9):913–22.CrossRefPubMed
3.
Link H, Huang YM. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol. 2006;180(1-2):17–28.CrossRefPubMed
4.
Villar LM, Masterman T, Casanova B, Gomez-Rial J, Espino M, Sadaba MC, et al. CSF oligoclonal band patterns reveal disease heterogeneity in multiple sclerosis. J Neuroimmunol. 2009;211(1-2):101–4.CrossRefPubMed
5.
Awad A, Hemmer B, Hartung HP, Kieseier B, Bennett JL, Stuve O. Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis. J Neuroimmunol. 2010;219(1-2):1–7.CrossRefPubMed
6.
Izquierdo G, Angulo S, Garcia-Moreno JM, Gamero MA, Navarro G, Gata JM, et al. Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients. Acta Neurol Scand. 2002;105(3):158–63.CrossRefPubMed
7.
Olsson JE, Link H, Muller R. Immunoglobulin abnormalities in multiple sclerosis. Relation to clinical parameters: disability, duration and age of onset. J Neurol Sci. 1976;27(2):233–45.CrossRefPubMed
8.
Stendahl-Brodin L, Link H. Relation between benign course of multiple sclerosis and low-grade humoral immune response in cerebrospinal fluid. J Neurol Neurosurg Psychiatry. 1980;43(2):102–5.CrossRefPubMedPubMedCentral
9.
Avasarala JR, Cross AH, Trotter JL. Oligoclonal band number as a marker for prognosis in multiple sclerosis. Arch Neurol. 2001;58(12):2044–5.CrossRefPubMed
10.
Joseph FG, Hirst CL, Pickersgill TP, Ben Shlomo Y, Robertson NP, Scolding NJ. CSF oligoclonal band status informs prognosis in multiple sclerosis: a case control study of 100 patients. J Neurol Neurosurg Psychiatry. 2009;80(3):292–6.CrossRefPubMed
11.
Rojas JI, Patrucco L, Cristiano E. Oligoclonal bands and MRI in clinically isolated syndromes: predicting conversion time to multiple sclerosis. J Neurol. 2010;257(7):1188–91.CrossRef
12.
Verjans E, Theys P, Delmotte P, Carton H. Clinical parameters and intrathecal IgG synthesis as prognostic features in multiple sclerosis. Part I J Neurol. 1983;229(3):155–65.CrossRefPubMed
13.
Idiman E, Ozakbas S, Dogan Y, Kosehasanogullari G. The significance of oligoclonal bands in multiple sclerosis: relevance of demographic and clinical features, and immunogenetic backgrounds. J Neuroimmunol. 2009;212(1-2):121–4.CrossRefPubMed
14.
Siritho S, Freedman MS. The prognostic significiance of cerebrospinal fluid in multiple sclerosis. J Neurol Sci. 2009;15(279(1-2):21–5.CrossRef
15.
Tumani H, Hartung HP, Hemmer B, Teunissen C, Deisenhammer F, Giovannoni G, et al. Cerebrospinal fluid biomarkers in multiple sclerosis. Neurobiol Dis. 2009;35(2):117–27.CrossRefPubMed
16.
Annunziata P, Giorgio A, De Santi L, Zipoli V, Portaccio E, Amato MP, et al. Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients treated with interferon-beta. J Neurol Sci. 2006;244(1-2):97–102.CrossRefPubMed
17.
Zeman AZJ, Kidd D, McLean BN, Kelly MA, Francis DA, Miller DH, et al. A study of oligoclonal band negative multiple sclerosis. J Neurol Neurosurg Psychiatry. 1996;60:27–30.CrossRefPubMedPubMedCentral
18.
Mayringer I, Timeltaler B, Deisenhammer F. Correlation between the IgG index, oligoclonal bands in CSF, and the diagnosis of demyelinating diseases. Eur J Neurol. 2005;12(7):527–30.CrossRefPubMed
19.
Imrell K, Greiner E, Hillert J, Masterman T. HLA-DRB115 and cerebrospinal-fluid-specific oligoclonal immunoglobulin G bands lower age at attainment of important disease milestones in multiple sclerosis. J Neuroimmunol. 2009;210(1-2):128–30.CrossRefPubMed
20.
Rojas JI, Tizio S, Patrucco L, Cristiano E. Oligoclonal bands in multiple sclerosis patients: worse prognosis? Neurol Res. 2012;34(9):889–92.CrossRefPubMed
21.
Gajofatto A, Bongianni M, Zanusso G, Benedetti MD, Monaco S. Are cerebrospinal fluid biomarkers useful in predicting the prognosis of multiple sclerosis patients? Int J Mol Sci. 2011;12(11):7960–70.CrossRefPubMedPubMedCentral
22.
Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med. 2000;343(20):1430–8.CrossRefPubMed
23.
Debouverie M, Pittion-Vouyovitch S, Louis S, Guillemin F. Natural history of multiple sclerosis in a population-based cohort. Eur J Neurol. 2008;15(9):916–21.CrossRefPubMed
24.
Brex PA, Ciccarelli O, O’Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med. 2002;346(3):158–64.CrossRefPubMed
25.
Leibowitz U, Alter M. Clinical factors determining prognosis in multiple sclerosis. Neurology. 1968;18(3):286–7.CrossRefPubMed
26.
Confavreux C, Aimard G, Devic M. Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain. 1980;103(2):281–300.CrossRefPubMed
27.
Detels R, Clark VA, Valdiviezo NL, Visscher BR, Malmgren RM, Dudley JP. Factors associated with a rapid course of multiple sclerosis. Arch Neurol. 1982;39(6):337–41.CrossRefPubMed
28.
29.
Vukusic S, Confavreux C. Natural history of multiple sclerosis: risk factors and prognostic indicators. Curr Opin Neurol. 2007;20(3):269–74.CrossRefPubMed
30.
Debouverie M, Pittion-Vouyovitch S, Louis S, Roederer T, Guillemin F. Increasing incidence of multiple sclerosis among women in Lorraine. Eastern France Mult Scler. 2007;13(8):962–7.CrossRefPubMed
31.
Debouverie M, Lebrun C, Jeannin S, Pittion-Vouyovitch S, Roederer T, Vespignani H. More severe disability of North Africans vs Europeans with multiple sclerosis in France. Neurology. 2007;68(1):29–32.CrossRefPubMed
32.
El Adssi H, Debouverie M, Guillemin F. Estimating the prevalence and incidence of multiple sclerosis in the Lorraine region, France, by the capture-recapture method. Mult Scler. 2012;18(9):1244–50.CrossRefPubMed
33.
Cortese I, Capone S, Luchetti S, Grimaldi LM, Nicosia A, Cortese R. CSF-enriched antibodies do not share specificities among MS patients. Mult Scler. 1998;4(3):118–23.CrossRefPubMed
34.
Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler. 1998;4(3):111–7.CrossRefPubMed
35.
Walsh MJ, Tourtellotte WW. Temporal invariance and clonal uniformity of brain and cerebrospinal IgG, IgA, and IgM in multiple sclerosis. J Exp Med. 1986;163:41–53.CrossRefPubMed
36.
Confavreux C, Compston DA, Hommes OR, McDonald WI, Thompson AJ. EDMUS, a European database for multiple sclerosis. J Neurol Neurosurg Psychiatry. 1992;55:671–6.CrossRefPubMedPubMedCentral
37.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444–52.CrossRefPubMed
38.
Barkhof F, Filippi M, Miller DH, Scheltens P, Campi A, Polman CH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain. 1997;120(Pt 11):2059–69.CrossRefPubMed
39.
Hosmer DW, Lemeshow S, May S. Applied Survival Analysis. 2nd ed. Hoboken: John Wiley & Sons; 2008.CrossRef
40.
Lourenco P, Shirani A, Saeedi J, Oger J, Schreiber WE, Tremlett H. Oligoclonal bands and cerebrospinal fluid markers in multiple sclerosis: associations with disease course and progression. Mult Scler. 2012;0(0):1–8.
41.
Debouverie M. Gender as a prognostic factor and its impact on the incidence of multiple sclerosis in Lorraine. France J Neurol Sci. 2009;286(1-2):14–7.CrossRefPubMed
42.
Vukusic S, Confavreux C. Prognostic factors for progression of disability in the secondary progressive phase of multiple sclerosis. J Neurol Sci. 2003;206(2):135–7.CrossRefPubMed
43.
Abraira V, Alvarez-Cermeno JC, Arroyo R, Camara C, Casanova B, Cubillo S, et al. Utility of oligoclonal IgG band detection for MS diagnosis in daily clinical practice. J Immunol Methods. 2011;371(1-2):170–3.CrossRefPubMed
44.
Hintzen RQ, Giovannoni G. CSF analysis in suspected MS: do bands aid? Neurology. 2008;70:1059–60.CrossRefPubMed
45.
Cepok S, Jacobsen M, Schock S, Omer B, Jaekel S, Boddeker I, et al. Patterns of cerebrospinal fluid pathology correlate with disease progression in multiple sclerosis. Brain. 2001;124(Pt 11):2169–76.CrossRefPubMed
46.
Binquet C, Quantin C, Le TG, Pagliano JF, Abrahamowicz M, Moreau T. The prognostic value of initial relapses on the evolution of disability in patients with relapsing-remitting multiple sclerosis. Neuroepidemiology. 2006;27(1):45–54.CrossRefPubMed
47.
Hecker M, Paap BK, Goertsches RH, Kandulski O, Fatum C, Koczan D, et al. Reassessment of blood gene expression markers for the prognosis of relapsing-remitting multiple sclerosis. PLoS One. 2011;6(12), e29648.CrossRefPubMedPubMedCentral
48.
Mandrioli J, Sola P, Bedin R, Gambini M, Merelli E. A multifactorial prognostic index in multiple sclerosis. Cerebrospinal fluid IgM oligoclonal bands and clinical features to predict the evolution of the disease. J Neurol. 2008;255(7):1023–31.CrossRefPubMed
49.
Calabrese M, Federle L, Bernardi V, Rinaldi F, Favaretto A, Varagnolo MC, et al. The association of intrathecal immunoglobulin synthesis and cortical lesions predicts disease activity in clinically isolated syndrome and early relapsing-remitting multiple sclerosis. Mult Scler. 2012;18(2):174–80.CrossRefPubMed
50.
Bejarano B, Bianco M, Gonzalez-Moron D, Sepulcre J, Goni J, Arcocha J, et al. Computational classifiers for predicting the short-term course of Multiple sclerosis. BMC Neurol. 2011;11:67.CrossRefPubMedPubMedCentral
51.
Huttner HB, Schellinger PD, Struffert T, Richter G, Engelhorn T, Bassemir T, et al. MRI criteria in MS patients with negative and positive oligoclonal bands: equal fulfillment of Barkhof’s criteria but different lesion patterns. J Neurol. 2009;256(7):1121–5.CrossRefPubMed
52.
Andreadou E, Chatzipanagiotou S, Constantinides VC, Rombos A, Stamboulis E, Nicolaou C. Prevalence of cerebrospinal fluid oligoclonal IgG bands in Greek patients with clinically isolated syndrome and multiple sclerosis. Clin Neurol Neurosurg. 2013;115:2094–8.CrossRefPubMed
53.
Debouverie M, Laforest L, Van Ganse E, Guillemin F, LORSEP Group. Earlier disability of the patients followed in multiple Sclerosis centers compared to outpatients. Mult Scler. 2009;15(2):251–7.CrossRefPubMed
Metadata
Title
No prognostic value of routine cerebrospinal fluid biomarkers in a population-based cohort of 407 multiple sclerosis patients
Authors
Madlyne Becker
Clotilde Latarche
Emilie Roman
Marc Debouverie
Catherine Malaplate-Armand
Francis Guillemin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2015
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-015-0330-4

Other articles of this Issue 1/2015

BMC Neurology 1/2015 Go to the issue

Study protocol

Testing the efficacy of web-based cognitive behavioural therapy for adult patients with chronic fatigue syndrome (CBIT): study protocol for a randomized controlled trial

Research article

Rate of aspiration pneumonia in hospitalized Parkinson’s disease patients: a cross-sectional study

Case report

Report of cold agglutinins in a patient with acute ischemic stroke

Research article

The economic impact of epilepsy: a systematic review

Research article

Association between changes in brain microstructure and cognition in older subjects at increased risk for vascular disease

Research article

A comparison of the brief international cognitive assessment for multiple sclerosis and the brief repeatable battery in multiple sclerosis patients