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Cited by 741Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersClinical Laboratory Practices and Quality Control

Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report.

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Andersson, M., Alvarez-Cermeno, J., Bernardi, G., Cogato, I., Fredman, P., Frederiksen, J., Fredrikson, S., Gallo, P. +16 more·1994·Journal of Neurology, Neurosurgery & Psychiatry
DOI 10.1136/jnnp.57.8.897PMC PMC1073070
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Abstract

The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organised five workshops to discuss CSF analytical standards in the diagnosis of multiple sclerosis. This consensus report from 12 European countries summarises the results of those workshops. It is hoped that neurologists will confer with their colleagues in clinical chemistry to arrange the best possible local practice. The most sensitive method for the detection of oligoclonal immunoglobulin bands is isoelectric focusing. The same amounts of IgG in parallel CSF and serum samples are used and oligoclonal bands are revealed with IgG specific antibody staining. All laboratories performing isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and serum patterns. Quantitative measurements of IgG production in the CNS are less sensitive than isoelectric focusing. The preferred method for detection of blood-CSF barrier dysfunction is the albumin quotient. The CSF albumin or total protein concentrations are less satisfactory. These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/microliters. Among evolving optional tests, measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free light chains, IgM, IgA, or myelin basic protein concentrations.

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  • Multiple studies provide evidence that in adult patients with CIS, CSF OCBs are an independent predictor of the risk of a second attack when controlling for demographic, clinical, treatment, and MRI variables.

    “Multiple studies provide evidence that in adult patients with CIS, CSF OCBs are an independent predictor of the risk of a second attack when controlling for demographic, clinical, treatment, and MRI variables. 61-69”

    From Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria (2018) · cites this paper as [62]

    The consensus report’s Abstract and “Diagnosis of multiple sclerosis” section discuss oligoclonal bands as a diagnostic finding, not as a predictor of a second attack. Searches for clinically isolated syndrome, second attacks, and prediction after adjustment for MRI or other variables found no passage addressing the claimed association. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 62

  1. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 1983;13:227-31.
  2. Bradbury M. The concept of a blood-brain bamer. Chichester; John Wiley and Sons, 1979.
  3. Fishman RA. Cerebrospinal fluid in diseases of the nervous system. 2nd ed. Philadelphia: WB Saunders and Co, 1992.
  4. Kostulas VK. Oligoclonal IgG bands in cerebrospinal fluid. Acta Neurol Scand (suppl 103) 1985;72:1-112.
  5. Schuller E. A new strategy for the study of intrathecal immunity. In: Marrosu MG, Cianchetti C, Tavolato B. eds. Trends in neuroimmunology. New York: Plenum Press, 1990:3-12.
  6. Thompson EJ. The CSF proteins: a biochemical approach. Amsterdam: Elsevier, 1988.
  7. Tourtellotte WW. The cerebrospinal fluid in multiple sclerosis. In: Vinken PJ, Bruyn GW, Klawans HS, eds. Handbook of clinical neurology. Amsterdam: Elsevier, 1985:79-130.
  8. Felgenhauer K. Protein size and cerebrospinal fluid composition. Klin Wochenschr 1974;52: 1158-64.
  9. Tourtellotte WW, Potvin AR, Fleming JO, et al. Multiple sclerosis: measurement and validation of central nervous system IgG synthesis rate. Neurology 1980;30:240-4.
  10. Schuller EAC, Benabdallah S, Sagar HJ, Reboul JAM, Tompe LC. IgG synthesis within the central nervous system. Arch Neurol 1987;44:600-4.
  11. Schuller E, Sagar HJ. Local synthesis of CSF immunoglobulins. _.7Neurol Sci 1981;51:361-70.
  12. Tibbling G, Link H, Ohman S. Principles of albumin and IgG analyses in neurological disorders. 1. Establishment of reference values. Scand _7 Clin Lab Invest 1977;37: 385-90.
  13. Blennow K, Fredman P, Wallin A, et al. Protein analyses in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age. Eur Neurol 1993; 33:129-33.
  14. Link H, Tibbling G. Principles of albumin and IgG analy- sis in neurological disorders: III. Evaluation of IgG syn- thesis within the central nervous system in multiple sclerosis. Scand j Clin Lab Invest 1977;37:397-401.
  15. Lolli F, Halawa I, Link H. Intrathecal synthesis of IgG, IgA, IgM and IgD in untreated multiple sclerosis and controls. Acta Neurol Scand 1989;80:238-47.
  16. Reiber H, Felgenhauer K. Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 1987;163:319-28.
  17. Laurell C-B. On the origin of major CSF proteins. In: Thompson EJ, ed. Advances in CSF protein research and diagnosis. Lancaster: MTP Press Ltd, England. 1987: 123-8.
  18. Luxton RW, McLean BN, Thompson EJ. Isoelectric focusing versus quantitative measurements in the detec- tion of intrathecal local synthesis of IgG. Clin Chim Acta 1990;187:297-308.
  19. Ohman S, Ernerudh J, Forsberg P, Henriksson A, von Schenk H, Vrethem M. Comparison of seven formulae and isoelectrofocusing for deternination of intrathecally produced IgG in neurological disease. Ann Clin Biochem 1992;29:405-1 0.
  20. Felgenhauer K, Schadlich H-J. The compartmental IgM and IgA response within the central nervous system. .7 Neurol Sci 1987;77:125-35.
  21. Felgenhauer K, Reiber H. The diagnostic relevance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. CGin Invest 1992;70:28-37.
  22. Felgenhauer K, Schadlich H-J, Nekic M, Ackermann R. Cerebrospinal fluid virus antibodies. A diagnostic indi- cator for multiple sclerosis? .7 Neurol Sci 1985;71:291-9.
  23. Reiber H, Lange P. Quantitation of virus-specific antibody concentration in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem 1991;37:1153-60.
  24. Sindic CJM, Laterre EC. Oligoclonal free kappa and lambda bands in the cerebrospinal fluid of patients with MS and CNS infections. An immunoaffinity-mediated capillary blot study. _7 Neuroimmunol 1991;33:63-72.
  25. Luxton RW, Thompson EJ. Affinity distributions of anti- gen-specific IgG in patients with multiple sclerosis and in patients with viral encephalitis. .7 Immunol Method 1990;13:277-82.
  26. Frequin STFM, Barkhof F, Lamers KJB, Hommes OR, Borm GF. CSF myelin basic protein, IgG and IgM lev- els in 101 MS patients before and after treatment with high-dose intravenous methylprednisolone. Acta Neurol Scand 1992;86:291-7.
  27. Gallo P, Tavolato B, Bergenbrant S, Siden A. Immunoglobulin light chain patterns in the cere- brospinal fluid. A study with special reference to the occurrence of free light chains in cerebrospinal fluid with and without oligoclonal immunoglobulin G. 7 Neurol Sci 1989;94:241-53.
  28. Livrea P, Trojano M, Simone IL, Zimatore GB, Lamontanara G. Intrathecal IgG synthesis in multiple sclerosis: comparison between isoelectric focusing and quantitative estimation of cerebrospinal fluid IgG. _7 Neurol 1981;224:159-69.
  29. Nespolo A, Bianchi G, Salmaggi A, Lazzaroni M, Cerrato D, Tajoli LM. Immunoblotting techniques with picogram sensitivity in cerebrospinal fluid protein detec- tion. Electrophoresis 1989;10:34-40.
  30. Olsson T, Kostulas V, Link H. Improved detection of oligoclonal IgG in cerebrospinal fluid by isoelectric focusing in agarose, double-antibody peroxidase labelling, and avidin-biotin amplification. Clin Chem 1984;30:409-21.
  31. Souverijn JHM, Serree HMP, Peet R, Grenzebach Smit W, Bruyn GW. Intrathecal immunoglobulin synthesis. Comparison of various formulae with the "gold standard" of isoelectric focussing. _7 Neurol Sci 1991; 102:11-6.
  32. Staugaitis SM, Shapack P, Tourtellotte WW, Lee MM, Reiber H-O. Isoelectric focusing of unconcentrated cerebrospinal fluid: applications to ultrasensitive analy- sis of oligoclonal immunoglobulin G. Electrophoresis 1985;6:287-91.
  33. Walker RWH, Keir G, Johnson MH, Thompson EJ. A rapid method for detecting oligoclonal IgG in uncon- centrated CSF by agarose isoelectric focusing, transfer to cellulose nitrate and immunoperoxidase staining. _7 Neuroimmunol 1983;4: 141-8.
  34. Wikkelso C, Andersson M, Andersson R, Blomstrand C. Isoelectric focusing followed by silver staining: a suitable method for routine investigation of cerebrospinal fluid proteins. Eur Neurol 1984;23:306-12.
  35. Martino G, Servalli C, Filippi M, et al. Absence of oligoclonally restricted immunoglobulins in tears from multiple sclerosis patients. _7 Neuroimmunol 1993;4: 149-56.
  36. Sindic CJM, Delacroix DL, Vaerman JP, Laterre EC, Masson PL. Study of IgA -in the cerebrospinal fluid of neurological patients with special reference to size, sub- class and local production. T7 Neuroimmunol 1984;7: 65-75.
  37. Mehta PD, Patrick BA, Miller JA. Absence of oligoclonal IgA in CSF and serum of multiple sclerosis patients. .7 Neuroimmunol 1984;6:67-9.
  38. Sharief MK, Thompson EJ. Distribution of cerebrospinal fluid oligoclonal IgM bands in neurological diseases: a comparison between agarose electrophoresis and iso- electric focusing. .7 Neurol Sci 1992;109:83-7.
  39. Sharief MK, Thompson EJ. Intrathecal immunoglobulin M synthesis in multiple sclerosis. Brain 1991;114: 181-95.
  40. Lolli F, Siracusa G, Amato MP, et al. Intrathecal synthesis of free immunoglobulin light chains and IgM in initial multiple sclerosis. Acta Neurol Scand 1991;83:239-43.
  41. Sharief MK, Thompson EJ. The predictive value of intrathecal immunoglobulin synthesis and magnetic resonance imaging in acute isolated syndromes for subsequent development of multiple sclerosis. Ann Neurol 1991;29:147-51.
  42. Massaro AR, Scivoletto G, Tonali P. Cerebrospinal fluid markers in neurological disorders. Ital 7 Neurol Sci 1990; 11:537-47.
  43. Vakaet A, Thompson EJ. Free light chains in cere- brospinal fluid: an indicator of recent immunological stimulation. .7 Neurol Neurosurg Psychiatry 1985;48: 995-8.
  44. Vandvik B. Oligoclonal IgG and free light chains in the cerebrospinal fluid of patients with multiple sclerosis and infectious diseases of the central nervous system. Scand _j Immunol 1977;6:913-22.
  45. Fagnart OC, Sindic CJM, Laterre C. Free kappa and lambda light chain levels in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. .7 Neuroimmunol 1988;19: 119-32.
  46. Keir G, Luxton RW, Thompson EJ. Isoelectric focusing of cerebrospinal fluid immunoglobulin G: an annotated update. Ann Clin Biochem 1990;27:436-43.
  47. Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry 2007;78:644e6.
  48. Carroll LJ, Holm L, Ferrari R, et al. Recovery in whiplash-associated disorders: do you get what you expect? J Rheumatol 2009;36:1063e70.
  49. Ozegovic D, Carroll LJ, David Cassidy J. Does expecting mean achieving? The association between expecting to return to work and recovery in whiplash associated disorders: a population-based prospective cohort study. Eur Spine J 2009;18:893e9.
  50. Crooks J, Milner R, Schultz IZ, et al. Determinants of occupational disability following a low back injury: a critical review of the literature. J Occup Rehabil 2002;12:277e95.
  51. Linton SJ. A review of psychological risk factors in back and neck pain. Spine 2000;25:1148e56.
  52. Sullivan MJ, Stanish W, Waite H, et al. Catastrophizing, pain, and disability in patients with soft-tissue injuries. Pain 1998;77:253e60.
  53. Sullivan MJ, Rodgers WM, Kirsch I. Catastrophizing, depression and expectancies for pain and emotional distress. Pain 2001;91:147e54.
  54. Truchon M, Fillion L. Biopsychosocial determinants of chronic disability and low-back pain: a review. J Occup Rehabil 2000;10:117e42.
  55. Bostick GP, Ferrari R, Carroll LJ, et al. A population- based survey of beliefs about neck pain from whiplash injury, work-related neck pain, and work- related upper extremity pain. Eur J Pain 2009;13:300e4.
  56. Ferrari R, Lang CGJ. Symptom expectation for minor head injury in Canada versus Germany. Clin Neurol Neurosurg 2003;105:146e7.
  57. Mickeviciene D, Schrader H, Obelieniene D, et al. A controlled prospective inception cohort study on the post-concussion syndrome outside the medicolegal context. Eur J Neurol 2004;11:411e19.
  58. Ferrari R, Obelieniene D, Russell AS, et al. Symptom expectation after minor head injury. A comparative study between Canada and Lithuania. Clin Neurol Neurosurg 2001;103:184e90.
  59. Buchbinder R, Jolley D. Population based intervention to change back pain beliefs: three year follow up population survey. BMJ 2004;328:321.
  60. Buchbinder R, Jolley D, Wyatt M. Population based intervention to change back pain beliefs and disability: three part evaluation. BMJ 2001;322:1516e20.
  61. Buchbinder R, Jolley D, Wyatt M. 2001 Volvo award winner in clinical studies: effects of a media campaign on back pain beliefs and its potential influence on management of low back pain in general practice. Spine 2001;26:2535e42.
  62. Buchbinder R, Jolley D. Effects of a media campaign on back beliefs is sustained 3 years after its cessation. Spine 2005;30:1323e30.

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Authors
Andersson, M., Alvarez-Cermeno, J., Bernardi, G., Cogato, I., Fredman, P., Frederiksen, J., Fredrikson, S., Gallo, P., Grimaldi, L. M., Gronning, M., Keir, G., Lamers, K., Link, H., Magalhaes, A., Massaro, A. R., Ohman, S., Reiber, H., Ronnback, L., Schluep, M., Schuller, E., Sindic, C. J. M., Thompson, E. J., Trojano, M., & Wurster, U.
Affiliations
  • Sahlgrenska University Hospital (SE)
  • University of Copenhagen (DK)
  • Vita-Salute San Raffaele University (IT)
  • Radboud University Nijmegen (NL)
  • Linköping University (SE)
ORCID
Venue
Journal of Neurology, Neurosurgery & Psychiatry
Publisher
BMJ
Published
1994-08-01
Volume
57
Issue
8
Pages
897-902
ISSN
0022-3050 (ISSN-L)
DOI
10.1136/jnnp.57.8.897
PMC
PMC1073070
OpenAlex
W2143255467
Cited by
741
References
0
Citations by year
2026: 28 · 2025: 33 · 2024: 26 · 2023: 31 · 2022: 29 · 2021: 36 · 2020: 42 · 2019: 38 · 2018: 27 · 2017: 22 · 2016: 28 · 2015: 24 · 2014: 17 · 2013: 23 · 2012: 24
FWCI
6.68
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • DIAL (Catholic University of Leuven) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
multiple sclerosis, cerebrospinal fluid analysis, oligoclonal bands, isoelectric focusing, blood-CSF barrier dysfunction, albumin quotient, CSF cell count, CSF IgG, myelin basic protein, diagnostic criteria
MeSH terms
Acute Disease, Adolescent, Adult, Age Factors, Albumins, Cell Count, Cerebrospinal Fluid, Cerebrospinal Fluid Proteins, Chronic Disease, Humans, Immunoglobulin G, Isoelectric Focusing, Middle Aged, Multiple Sclerosis, Quality Control, Sensitivity and Specificity, Specimen Handling

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