Die Analytik des Liquor cerebrospinalis ist von zentraler Bedeutung in der frühen Diagnosestellung erregerbedingter neurologischer Erkrankungen. Neben der Bestimmung grundlegender liquoranalytischer Parameter wie Zellzahl, Proteine und Laktat, ist die gezielte Suche nach Erregern bakterieller, viraler oder pilzbedingter Infektionen des ZNS entscheidend. Dies kann direkt mittels mikrobiologischer Spezialfärbungen, Kulturmethoden, Nukleinsäure- oder Antigennachweis erfolgen oder indirekt serologisch im Blut oder mittels Nachweis einer erregerspezifischen Antikörpersynthese im Liquor. Neben der Vermittlung von Grundlagen der klinischen Liquordiagnostik soll dieser Fortbildungsartikel den Blick für die speziellen Aspekte der Erregerdiagnostik schärfen. Auf diese Weise soll ermöglicht werden, durch konkrete Fragestellungen an das Labor eine zielgerichtete Analytik zu veranlassen und deren Ergebnisse kritisch zu interpretieren, um dem Patienten die bestmögliche Behandlung zukommen lassen zu können.
Abstract
Cerebrospinal fluid analysis is of prime importance to establish an early diagnosis of central nervous system infections. Beside the basic diagnostics containing CSF white cell count, lactate concentration and protein analysis, the targeted search for agents of bacterial, viral or fungal CNS infectious diseases is essential. Decisive methods are bacterial and fungal staining techniques, microbiological culture methods, nucleic acid amplification and antigen detection methods or indirect identification of pathogens by serologic testings including the determination of pathogen-specific intrathecal immunoglobulin synthesis. Besides imparting basic principles of cerebrospinal fluid analysis, this article focuses on special aspects of detection of infectious agents. Well-directed questions and a close communication between clinician and laboratory allow optimal diagnostic analysis for successful confirmation of the diagnosis and for optimal treatment of the patient.
Literatur
1 Quincke H. Die Lumbalpunction des Hydrocephalus. Berliner klinische Wochenschrift 1891; 891: 929-933
4 Woitalla D, Otto M, von Stuckrad-Barre S et al. Diagnostische Liquorpunktion. In: Diener H, Weimar C, eds Leitlinien für Diagnostik und Therapie in der Neurologie. 5. ed. Stuttgart: Thieme; 2012: 1017-1023
7 Popp J, Riad M, Freymann K et al. Diagnostic lumbar puncture performed in the outpatient setting of a memory clinic. Frequency and risk factors of post-lumbar puncture headache. Nervenarzt 2007; 78: 547-551
8 Anforderungen an die Hygiene bei Punktionen und Injektionen – Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention beim Robert Koch-Institut. Bundesgesundheitsblatt 2011; 54: 1135-1144
9 Petereit H, Sindern E, Wick M. Leitlinien der Liquordiagnostik und Methodenkatalog der Deutschen Gesellschaft für Liquordiagnostik und Klinische Neurochemie. Heidelberg: Springer Medizin; 2007
14 Tumani H, Kluge H. Anatomie und Physiologie des Liquorsystems. In: Zettl UK, Lehmitz R, Mix E, eds Klinische Liquordiagnostik. 2. ed. Berlin: de Gruyter; 2005: 39-55
15 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
16 Andersson M, Alvarez-Cermeno J, Bernardi G et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994; 57: 897-902
17 Wurster U, Stachan R, Windhagen A et al. Reference values for standard cerebrospinal fluid examinations in multiple sclerosis. Results from 99 healthy volunteers. In: ECMID:Multiple Sclerosis. 2006: 228
19 La Scolea Jr LJ, Dryja D. Quantitation of bacteria in cerebrospinal fluid and blood of children with meningitis and its diagnostic significance. J Clin Microbiol 1984; 19: 187-190
20 Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2004; 39: 1267-1284
21 van de Beek D, de Gans J, Spanjaard L et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004; 351: 1849-1859
22 Nigrovic LE, Malley R, Macias CG et al. Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis. Pediatrics 2008; 122: 726-730
24 Perfect JR. Cryptococcus neoformans. In: Mandell GL, Bennett JE, Dolin R, eds Principles and Practice of Infectious Diseases. Philadelphia, Pennsylvania: Elsevier; 2005: 2997-3011
25 Marchetti O, Lamoth F, Mikulska M et al. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant 2012; 47: 846-854
26 Portegies P, Solod L, Cinque P et al. Guidelines for the diagnosis and management of neurological complications of HIV infection. Eur J Neurol 2004; 11: 297-304
27 Arendt G, Eggers C, Furrer H et al. Diagnostik und Therapie HIV-1-assoziierter neurologischer Erkrankungen. In: Diener H, Weimar C, eds Leitlinien für Diagnostik und Therapie in der Neurologie. 5. ed. Stuttgart: Thieme; 2012: 560-569
28 Bennett JE, Hasenclever HF, Tynes BS. Detection of Cryptococcal Polysaccharide in Serum and Spinal Fluid: Value in Diagnosis and Prognosis. Trans Assoc Am Physicians 1964; 77: 145-150
30 Chaudhuri A, Martinez-Martin P, Kennedy PG et al. EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults. Eur J Neurol 2008; 15: 649-659
31 Greisen K, Loeffelholz M, Purohit A et al. PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid. J Clin Microbiol 1994; 32: 335-351
32 Srinivasan L, Pisapia JM, Shah SS et al. Can broad-range 16S ribosomal ribonucleic acid gene polymerase chain reactions improve the diagnosis of bacterial meningitis? A systematic review and meta-analysis. Ann Emerg Med 2012; 60: 609-620 e602
33 Steiner I, Schmutzhard E, Sellner J et al. EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system. Eur J Neurol 2012; 19: 1278-1291
34 Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem 1991; 37: 1153-1160
38 Proulx N, Frechette D, Toye B et al. Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis. QJM 2005; 98: 291-298
40 McGrath N, Anderson NE, Croxson MC et al. Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry 1997; 63: 321-326
41 Raschilas F, Wolff M, Delatour F et al. Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2002; 35: 254-260
42 Tyler KL. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret’s. Herpes 2004; 11 (Suppl. 02) 57A-64A
43 Aurelius E, Johansson B, Skoldenberg B et al. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet 1991; 337: 189-192
44 Revello MG, Baldanti F, Sarasini A et al. Quantitation of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis by the polymerase chain reaction. Clinical and diagnostic virology 1997; 7: 183-191
45 Weil AA, Glaser CA, Amad Z et al. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2002; 34: 1154-1157
46 Rauer S, Kaiser R, Kölmel HW et al. Neuroborreliose. In: Diener H, Weimar C, eds Leitlinien für Diagnostik und Therapie in der Neurologie. 5. ed. Thieme: 2012: 513-522
47 Mygland A, Ljostad U, Fingerle V et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 2010; 17: 8-16, e11 – e14
52 Kaiser R, Archelos-Garcia J, Jilg W et al. Frühsommer-Meningoenzephalitis (FSME). In: Diener H, Weimar C, eds Leitlinien für Diagnostik und Therapie in der Neurologie. 5. ed. Stuttgart: Thieme; 2012: 554-559
54 Nau R, Behnke-Mursch J, Eiffert H et al. Hirnabszess. In: Diener H, Weimar C, eds, Leitlinien für Diagnostik und Therapie in der Neurologie. 5. ed. Stuttgart: Thieme; 2012: 505-512
55 Bitsch A, Nau R, Hilgers R et al. Focal neurologic deficits in infective endocarditis and other septic diseases. Acta Neurol Scnad 1996; 94: 279-286
