psychoneuro 2008; 34(6/07): 293-305
DOI: 10.1055/s-0028-1083831
Schwerpunkt

© Georg Thieme Verlag Stuttgart · New York

Liquordiagnostik der Multiplen Sklerose – Diagnose und Differenzialdiagnose

Modern cerebrospinal fluid analysis of Multiple Sclerosis – Diagnosis and differential diagnosisRegina Schläger1 , Matthias Mehling1 , 2 , Achim Gass1 , Jens Kuhle1 , 2
  • 1Neurologische Klinik, Universitätsspital, Basel (Schweiz)
  • 2Departement Biomedizin, Universitätsspital, Basel (Schweiz)
Further Information

Publication History

Publication Date:
31 July 2008 (online)

Bei der Multiplen Sklerose handelt es sich um eine chronisch–entzündliche Erkrankung des zentralen Nervensystems mit funktionellen Defiziten vorwiegend aufgrund multipler demyelinisierender Läsionen unterschiedlichen Alters. Grundkonzept der Diagnosestellung ist der Nachweis einer Dissemination des Krankheitsprozesses in Bezug auf Ort und Zeit. Die diagnostischen Kriterien der Multiplen Sklerose wurden wiederholt revidiert. Der Artikel gibt einen Überblick über verschiedene Kriteriensysteme und diskutiert die derzeit verwendeten McDonald–Kriterien in ihrer revidierten Fassung von 2005. Die Diagnosestellung der Multiplen Sklerose beruht auf dem Ausschluss anderer entzündlicher, infektiöser, granulomatöser und hereditärer Erkrankungen, die nachfolgend skizziert werden. Ein klinischer Abklärungsalgorithmus bei Verdacht auf Multiple Sklerose wird vorgestellt. Im Rahmen der Diagnosestellung ist die Liquoranalyse essenziell, charakteristische Liquorbefunde und ihre Bedeutung werden diskutiert.

Multiple Sclerosis (MS) is defined as a chronic inflammatory disease of the central nervous system with functional deficits predominantly due to multiple demyelinated and axonal lesions of different age. The basic concept of diagnosis relies on confirming dissemination of the disease process in time and space. The diagnostic criteria of MS were revised several times, the article gives an overview over different sets of diagnostic criteria and discusses the most recent version of the McDonald criteria, 2005. Several inflammatory, infectious, granulomatous and hereditary diseases may resemble MS and have to be excluded in the diagnostic process. An algorithmic approach to patients with suspected MS is described. In diagnosing MS analysis of the cerebrospinal fluid (CSF) plays an essential role, characteristic findings in CSF and their significance are discussed.

Literatur

  • 1 Allison RS, Millar JH.. Prevalence of disseminated sclerosis in Northern Ireland.  Ulster Med J. 1954;  23 1-27
  • 2 Andersson M, Alvarez–Cermeño J, Bernardi G. et al. . Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report.  J Neurol Neurosurg Psychiatry. 1994;  57 897-902
  • 3 Annunziata P, Giorgio A, De Santi L. 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 97-102
  • 4 Baranzini SE, Jeong MC, Butunoi C. et al. . B cell repertoire diversity and clonal expansion in multiple sclerosis brain lesions.  J Immunol. 1999;  163 5133-5144
  • 5 Barkhof F, Rocca M, Francis G. et al. . Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon beta1a.  Ann Neurol. 2003;  53 718-724
  • 6 Charil A, Yousry TA, Rovaris M. et al. . MRI and the diagnosis of multiple sclerosis: expanding the concept of „no better explanation”.  Lancet Neurol. 2006;  5 841-852
  • 7 Cole SR, Beck RW, Moke PS. et al. . The predictive value of CSF oligoclonal banding for MS 5 years after optic neuritis. Optic Neuritis Study Group.  Neurology. 1998;  51 885-887
  • 8 Colombo M, Dono M, Gazzola P. et al. . Accumulation of clonally related B lymphocytes in the cerebrospinal fluid of multiple sclerosis patients.  J Immunol. 2000;  164 2782-2789
  • 9 Comi G, Filippi M, Barkhof F. et al. . Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study.  Lancet. 2001;  357 1576-1582
  • 10 Dalton CM, Brex PA, Miszkiel KA. et al. . Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis.  Ann Neurol. 2002;  52 47-53
  • 11 Dujmovic I, Mesaros S. et al. . Primary progressive multiple sclerosis: clinical and paraclinical characteristics with application of the new diagnostic criteria.  Eur J Neurol. 2004;  11 439-444
  • 12 Fassas A, Passweg JR, Pekmezovic T. et al. . Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study.  J Neurol. 2002;  249 1088-1097
  • 13 Felgenhauer K, Reiber H.. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system.  Clin Investig. 1992;  70 28-37
  • 14 Filippi M, Rovaris M, Inglese M. et al. . Interferon beta–1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double–blind, placebo–controlled trial.  Lancet. 2004;  364 1489-1496
  • 15 Filippini G, Comi GC, Cosi V. et al. . Sensitivities and predictive values of paraclinical tests for diagnosing multiple sclerosis.  J Neurol. 1994;  241 132-137
  • 16 Freedman MS, Thompson EJ, Deisenhammer F. et al. . Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement.  Arch Neurol. 2005;  62 865-870
  • 17 Giovannoni G, Kieseier B, Hartung HP.. Correlating immunological and magnetic resonance imaging markers of disease activity in multiple sclerosis.  J Neurol Neurosurg Psychiatry. 1998;  64
  • 18 Hickey WF.. Migration of hematogenous cells through the blood–brain barrier and the initiation of CNS inflammation.  Brain Pathol. 1991;  1 97-105
  • 19 Jacobs LD, Beck RW, Simon JH. et al. . Intramuscular interferon beta–1a therapy initiated during a first demyelinating event in multiple sclerosis.  N Engl J Med. 2000;  343 898-904
  • 20 Kappos L, Polman CH, Freedman MS. et al. . Treatment with interferon beta–1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.  Neurology. 2006;  67 1242-1249
  • 21 Keren FK.. College of American Pathologists. Cerebrospinal Fluid Survey M–B: Participant Summary Report. Northfield,IL: College of American Pathologists 2002: 6
  • 22 Korteweg T, Tintoré M, Uitdehaag B. et al. . MRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow–up study.  Lancet Neurol. 2006;  5 221-227
  • 23 Lefvert AK, Link H.. IgG production within the central nervous system: a critical review of proposed formulae.  Ann Neurol. 1985;  17 13-20
  • 24 Link H, Tibbling G.. Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis.  Scand J Clin Lab Invest. 1977;  37 397-401
  • 25 Link H, Huang YM.. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness.  J Neuroimmunol. 2006;  180 17-28
  • 26 Mancardi GL, Saccardi R, Filippi M. et al. . Autologous hematopoietic stem cell transplantation suppresses Gd–enhanced MRI activity in MS.  Neurology. 2001;  57 62-68
  • 27 Martinelli V, Comi G, Filippi M. et al. . Paraclinical tests in acute–onset optic neuritis: basal data and results of a short follow–up.  Acta Neurol Scand. 1991;  84 231-236
  • 28 McDonald WI, Compston A, Edan G. et al. . Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.  Ann Neurol. 2001;  50 121-127
  • 29 Miller DH, Ormerod IE, Rudge P. et al. . The early risk of multiple sclerosis following isolated acute syndromes of the brainstem and spinal cord.  Ann Neurol. 1989;  26 635-639
  • 30 Ohman S, Ernerudh J, Forsberg P. et al. . Comparison of seven formulae and isoelectrofocusing for determination of intrathecally produced IgG in neurological diseases.  Ann Clin Biochem. 1992;  29 405-410
  • 31 Polman CH, Reingold SC, Edan G. et al. . Diagnostic criteria for multiple sclerosis: 2005 revisions to the „McDonald Criteria”.  Ann Neurol. 2005;  58 840-846
  • 32 Poser CM, Paty DW, Scheinberg L. et al. . New diagnostic criteria for multiple sclerosis: guidelines for research protocols.  Ann Neurol. 1983;  13 227-231
  • 33 Qin Y, Duquette P, Zhang Y. et al. . Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis.  J Clin Invest. 1998;  102 1045-1050
  • 34 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;  163 319-328
  • 35 Reiber H.. Flow rate of cerebrospinal fluid (CSF) – a concept common to normal blood–CSF barrier function and to dysfunction in neurological diseases.  J Neurol Sci. 1994;  122 189-203
  • 36 Reiber H.. Die diagnostische Bedeutung neuroimmunologischer Reaktionsmuster im Liquor cerebrospinalis.  Lab Med. 1995;  19 444-462
  • 37 Reiber H, Ungefehr S, Jacobi C.. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis.  Mult Scler. 1998;  4 111-117
  • 38 Reiber H, Peter JB.. Cerebrospinal fluid analysis: disease–related data patterns and evaluation programs.  J Neurol Sci. 2001;  184 101-122
  • 39 Roström B, Link H, Norrby E.. Antibodies in oligoclonal immunoglobulins in CSF from patients with acute cerebrovascular disease.  Acta Neurol Scand. 1981;  64 225-240
  • 40 Schumacker GA, Beebe G, Kibler RF. et al. . Problems of experimental trials of therapy in multiple sclerosis.  Ann NY Acad Sci. 1965;  122 552-568
  • 41 Sindic CJ.. CSF analysis in multiple sclerosis.  Acta Neurol Belg. 1994;  94 103-111
  • 42 Sindic CJ, Van Antwerpen MP, Goffette S.. The intrathecal humoral immune response: laboratory analysis and clinical relevance.  Clin Chem Lab Med. 2001;  39 333-340
  • 43 Söderström M, Ya–Ping J, Hillert J, Link H.. Optic neuritis: prognosis for multiple sclerosis from MRI, CSF, and HLA findings.  Neurology. 1998;  50 708-714
  • 44 Stachan R, Wurster U.. Frequency of virus specific antibodies in clinically definite multiple sclerosis versus acute monosymptomatic opticus neuritis.  J lab Med. 1996;  20 515
  • 45 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;  43 102-105
  • 46 Thompson EJ.. Proteins of the Cerebrospinal Fluid. New York: Elsevier, Academic Press 2005
  • 47 Thompson EJ, Keir G.. Laboratory investigation of cerebrospinal fluid proteins.  Ann Clin Biochem. 1990;  27 425-435
  • 48 Thompson EJ.. Cerebrospinal fluid.  J Neurol Neurosurg Psychiatry. 1995;  59 349-357
  • 49 Tintoré M, Rovira A, Río J. et al. . New diagnostic criteria for multiple sclerosis: application in first demyelinating episode.  Neurology. 2003;  60 27-30
  • 50 Tourtellotte W.. On cerebrospinal fluid immunoglobulin–G (IgG) quotients in multiple sclerosis and other diseases. A review and a new formula to estimate the amount of IgG synthesized per day by the central nervous system.  J Neurol Sci. 1970;  10 279-304
  • 51 Tourtellotte WW, Potvin AR, Fleming JO. et al. . Multiple sclerosis: measurement and validation of central nervous system IgG synthesis rate.  Neurology. 1980;  30 240-244
  • 52 Tumani H, Tourtellotte WW, Peter JB, Felgenhauer K.. Acute optic neuritis: combined immunological markers and magnetic resonance imaging predict subsequent development of multiple sclerosis. The Optic Neuritis Study Group.  J Neurol Sci. 1998;  155 44-49
  • 53 Wiendl H, Kieseier BC, Gold R. et al. . Multiple Sklerose – Revision der neuen McDonald–Diagnosekriterien.  Nervenarzt. 2006;  1235 1235-1245
  • 54 Wolinsky JS. PROMiSe Study Group. . The diagnosis of primary progressive multiple sclerosis.  J Neurol Sci. 2003;  206 145-152
  • 55 Wurster U.. Protein gradients in the cerebrospinal fluid and the calculation of intracerebral IgG synthesis.  J Neuroimmunol. 1988;  20 233-235
  • 56 Wurster U, Rinke M.. Does glycosilation contribute to the oligoclonal appearance of intracerebrally synthesized IgG?.  Can J Neurol Sci. 1993;  4
  • 57 Wurster U.. Elektrophoreseverfahren – Nachweis und Bedeutung von oligoklonalen Banden. In: Zettl K, Lehmitz R, and Eilhard M, Hrsg. Klinische Liquordiagnostik. 2. Aufl. Berlin: de Gruyter 2005: 208-238
  • 58 Zeman AZ, Kidd D, McLean BN. et al. . A study of oligoclonal band negative multiple sclerosis.  J Neurol Neurosurg Psychiatry. 1996;  60 27-30

Korrespondenz

Dr. med. Regina Schlaeger

Universitätsspital Basel Abteilung für Neurologie

Petersgraben 4

4031 Basel (Schweiz)

Email: schlaegerr@uhbs.ch

    >