Skip to main content

Advertisement

Log in

Recommendations for cerebrospinal fluid analysis

  • Review
  • Published:
Folia Microbiologica Aims and scope Submit manuscript

Abstract

Diseases of the central nervous system (CNS) mean for the human organism a potentially dangerous situation. An investigation of cerebrospinal fluid (CSF) provides important information about a character of CNS impairment in the decision-making diagnostic and therapeutic algorithm. The authors present a brief overview of available cerebrospinal fluid assays, shortened indication criteria, a recommended algorithm of CSF assessment in different suspected diseases, and a view of the external quality system. The whole portfolio of obtainable CSF methodology is further subdivided according to the adequate choice into the first and inevitable basic routine panel, and following complicated analyses of highly specialized character. The basic panel is considered for standard laboratories, the complete specialized assessment should be provided by a super-consulting laboratory.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AB:

β-amyloid

AIDP/CIDP:

Acute/chronic inflammatory demyelinating polyneuropathy

anti-AMPA:

Anti-glutamate receptor antibodies

anti-GAG:

Antiganglioside antibodies

anti-NMDAR:

Antibodies for detection of glutamate NMDA (N-methyl-D-aspartate) receptors

anti-VGKC:

Antibodies against Voltage-Gated Potassium (Kalium) channels

APP:

Acute phase proteins

BBR, BM:

Reaction for Berlin blue., i.e. cytological staining for iron detection using Prussian blue

CARS:

Compensatory anti-inflammatory response syndrome

CJD:

Creutzfeldt-Jakob disease

CMV:

Cytomegalovirus

CNS/PNS:

Central/peripheral nervous system

CSF:

Cerebrospinal fluid

EBV:

Epstein-Barr virus

EFNS:

European Federation of Neurological Societies

EQA:

External quality assessment

ELISA:

Enzyme-Linked Immuno-Sorbent Assay

HSV:

Herpes simplex virus

HZV:

Herpes zoster virus

GAD:

Acid decarboxylase of gamma aminobutyric acid

IL(s):

Interleukin(s)

JCV:

John Cunningham virus

LGI1:

Leucine-rich glioma inactivated protein 1

ME:

Viral meningoencephalitis

MRZH:

Antibodies against neurotropic viruses like measles, rubella, varicella zoster and herpes simplex

NMO:

Neuromyelitis optica

NMO-IgG:

IgG auto-antibodies against AQP-4 water channel

MS:

Multiple sclerosis

NSE:

Neuron-specific enolase

OCB:

Oligoclonal bands of immunoglobulins

ORO:

cytological staining for lipids (oil red O)

PACNS:

Primary angiitis of the CNS

PAP:

Papanicolaou cytological staining

PAS:

Cytological staining with periodic acid + Schiffs reagent on mucopolysaccharides

PCR:

Polymerase chain reaction

Pentraxins:

Pentagonal acute phase proteins, both of hepatic and extrahepatic (e.g. CNS, placenta) origin

PML:

Progressive multifocal leucoencephalopathy

RR MS:

Relapsing–remitting multiple sclerosis

SAH:

Subarachnoid haemorrhage

SERPIN(s):

Serin proteinase inhibitor(s)

SIRS:

Systemic inflammatory response syndrome

Tc:

CD8+ T cytotoxic cell

Th:

CD4+ T helper cell

Treg:

T regulatory cell

VZV:

Varicella zoster virus

WB:

Western blot

ᅟ:

All remaining abbreviations are explained in the text.

References

  • Adam P, Taborský L, Sobek O, Hildebrand T, Kelbich P, Průcha M, Hyanek J (2001) Cerebrospinal fluid. Adv Clin Chem 36:1–62

    Article  CAS  PubMed  Google Scholar 

  • Adam P, Táborský L, Sobek O, Kelbich P, Průcha M (2002) Proteinology of cerebrospinal fluid. Medica News Publishers, Prague, Czech Republic

    Google Scholar 

  • Adam P, Sobek O, Táborský L, Hildebrand T, Tutterová O, Žáček P (2003a) Orosomucoid (alpha-1-glykoprotein) levels in MS patients subgroups. Clin Chim Acta 334(1–2):107–110

    Article  CAS  PubMed  Google Scholar 

  • Adam P, Taborský L, Průcha M, Sobek O, Kratochvíla J, Zeman D (2003b) Cytology of cerebrospinal fluid. Medica News Publishers (1st ed), Prague, Czech Republic

  • Adam P, Sobek O, Scott CS (2007) Analysis of cerebrospinal fluid cell populations with monoclonal antibodies. Folia Microbiol 52:529–534

    Article  CAS  Google Scholar 

  • Adam P, Sobek O, Hybelová M, Doležil D, Kasík J, Hajduková L, Adam D, Svatoňová J (2009) Eosinophilic meningitis–an immunophenotyping recording of a very rare clinical entity. Folia Microbiol 54:257–260

    Article  CAS  Google Scholar 

  • Adam P, Sobek O, Scott CS, Doležil D, Kasík J, Hajduková L, Adam D (2010) Immunophenotypic analysis of cerebrospinal fluid cell populations with the CELL-DYN Sapphire haematology analyser: method feasibility and preliminary observations. Internat J Lab Hematol 32:22–32

    Article  CAS  Google Scholar 

  • Aksamit AJ Jr, Preissner CM, Homburger HA (2001) Quantification of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt–Jakob disease. Neurology 57:728–730

    Article  PubMed  Google Scholar 

  • Bednářová J, Štourač P, Adam P (2005) The diagnostical relevance of immunological variables in neuroborreliosis and multiple sclerosis. Acta Neurol Scandinavica 112:97–102

    Article  CAS  Google Scholar 

  • Bořecká K, Adam P, Sobek O, Hajduková L, Lánská V, Nekola O (2013) Coefficient of energy balance: effective tool for early differential diagnosis of CNS diseases, BioMed Res Internat 2013; article ID 745943

  • Deisenhammer F, Bartoš A, Egg R, Gilhus NE, Giovannoni G, Rauer S, Sellebjerg F (2006) Guidelines on routine cerebrospinal fluid analysis. Report from EFNS task force. Eur J Neurol 13:913–922

    Article  CAS  PubMed  Google Scholar 

  • Deisenhammer F, Egg R, Giovannoni G, Hemmer B, Petzold A, Sellebjerg F, Teunissen C, Tumani H (2009) EFNS guidelines on disease-specific CSF investigations. Eur J Neurol 16:760–770

    Article  CAS  PubMed  Google Scholar 

  • Deinsenhemmer F, Sellebjerg F, Teunissen CE, Tumani H (2015) Cerebrospinal fluid in clinical neurology. Springer

  • Dušková J, Sobek O (2018) Assisting the neurologist in diagnosis of CNS malingnancies – current possibilities and limits of cerebrospinal fluid cytology and immunocytochemistry. Brain and Behavior DOI 7:e00805. https://doi.org/10.1002/brb3.805

    Article  Google Scholar 

  • Felgenhauer K (1998) Laboratory of neurological diseases, in clinical laboratory diagnostics. Use and assessment of clinical laboratory results, L. Thomas (Ed.), pp. 1308–1326; TH-Books Verlagsgesellschaft mbH, Franfurkt, Germany

  • Fernandez O (2013) Best practice in the use of natalizumab in multiple sclerosis. Therapeut Adv Neurol Disorders 6(2):69–79

    Article  CAS  Google Scholar 

  • Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G, Öhman S, Racke MK, Sharief M, Sindic CJM, Sellebjerg F, Tourtellotte WW (2005) Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis. A concensus statement. Arch Neurol 62:865–870

    Article  PubMed  Google Scholar 

  • Fujimori J, Nakashima I, Kuroda H, Fujihara K, Aoki M (2014) Cerebrospinal fluid CXCL 13 is a prognostic marker for aseptic meningitis. J Neuroimmunol 273(1–2):77–84

    Article  CAS  PubMed  Google Scholar 

  • Graber DJ, Levy M, Kerr D, Wade WF (2008) Neuromyelitis optica pathogenesis and aquaporin 4. J Neuroinflammat 5:22

    Article  CAS  Google Scholar 

  • Grisold W, Giometto B, Vitaliani R, Oberndorfer S (2011) Current approaches to the treatment of paraneoplastic encephalitis. Therapeut Adv Neurological Disorders 4(4):237–248

    Article  CAS  Google Scholar 

  • Hajduková L et al. (2014) Biomarkers of brain damage: S100 and NSE concentrations in cerebrospinal fluid – a normative study BioMed Res Int Article ID 379071

  • Hořejší V, Bartůňková J (2005) Basic immunology (in Czech). Triton, Prague, Czech Republic

  • Irani DN (2009) Cerebrospinal fluid in clinical practice. Elsevier, Saunders

    Google Scholar 

  • Kaida K, Kusunoki S (2010) Antibodies to gangliosides and ganglioside complexes in Guillain-Barré syndrome and Fisher syndrome: mini-review. J Neuroimmunol 223(1–2):5–12

    Article  CAS  PubMed  Google Scholar 

  • Kelbich P, Koudelková M, Machová H, Tomaškovič M, Vachata P, Kotalíková P, Chmelíková V, Hanuljaková E (2007) Importance of urgent cerebrospinal fluid examination for early diagnosis of central nervous system infections. Klin Mikrobiol Inf Lek 13:9–20

    Google Scholar 

  • Kelbich P, Adam P, Sobek O, Koudelková M, Procházka J, Hanuljaková E, Válková R, Tomaškovič M, Krušina M (2009) Basic cerebrospinal fluid test in diagnosing central nervous system involvement (in Czech). Neurologie pro praxi 10(5):285–289

    Google Scholar 

  • Kepa L, Oczko-Grzesik, Sobala-Scigiel Bm Boroń-Kaczmarska A (2015) Chemokine CXCL13 concentration in cerebrospinal fluid in patients with neuroborreliosis – own observations. Przegl Epidemiol 69:705–710

    PubMed  Google Scholar 

  • Kleine TO, Damm T, Althaus H (2000) Quantification of β-trace protein and detection of transferrin isoforms in mixtures of cerebrospinal fluid and blood serum as models of rhinorrhea and otorrhea diagnosis. Fresenius J Anal Chem 366(4):382–386

    Article  CAS  PubMed  Google Scholar 

  • Kollewe K, Wurster U, Sinzenich T, Körner S, Dengler R, Mohammadi B, Petri S (2015) Anti-ganglioside antibodies in amyotrophic lateral sclerosis revisited. Plos One 10(4):e0125339. 10.1371

  • Krejsek J, Kopecký O (2004) Klinická imunologie (In Czech) Nucleus. Czech Republic, Hradec Králové

    Google Scholar 

  • Maier B, Laurer HL, Rose S, Buurman WA, Marzi I (2005) Physiological levels of pro- and anti-inflammatory mediators in cerebrospinal fluid and plasma: a normative study. J Neurotrauma 22:822–835

    Article  PubMed  Google Scholar 

  • Mellergard J, Edstrom M, Vrethem M, Ernerudh J, Dahle C (2010) Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluid. Mult Scler 16(2):208–217

    Article  CAS  PubMed  Google Scholar 

  • Myglanda A, Ljøstada U, Fingerled V, Rupprechte T, Schmutzhardf E, Steiner I (2010) EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol 17:8–16

  • Prasad R, Kapoor R, Srivastava R, Mishra OP, Singh TB (2014) Cerebrospinal fluid TNF alpha, IL-6, and IL-8 in children with bacterial meningitis. Pediatr Neurol 50(1):60–65

    Article  PubMed  Google Scholar 

  • Prüss H, Dalmau J, Harms L, Höltje M, Ahnert-Hilger G, Borowski K, Stoecker W, Wandinger KP (2010) Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 75(19):1735–1739

    Article  CAS  PubMed  Google Scholar 

  • Reiber H (1994) The hyperbolic function: a mathematical solution of the protein flux/CSF flow model for blood-CSF barrier function. J Neurol Sci 126:243–245

    Article  Google Scholar 

  • Reiber H, Thompson EJ, Grimsley G, Bernardi G, Adam P, Monteiro de Almeida S, Freedman P, Keir G, Lammers L, Liblau R, Menna-Barreto M, Sa MJ, Seres E, Sindic CJM, Teelken A, Trendelenburg C, Trojano M, van Antwerpen M, Verbeek MM (2003) quality assurance for cerebrospinal fluid analysis: international consensus by an internet-based group discussion. Clin Chem Lab Med 41(3):331–337

    Article  CAS  PubMed  Google Scholar 

  • Roine I, Saukkoriipi A, Leinonen M, Peltola H (2008) LatAm meningitis study group. Microbial genome count in cerebrospinal fluid compared with clinical characteristics in pneumococcal and Haemophilus influenzae type b meningitis in children, Diagnostic Microbiol Infectious Dis 63(1):16–23

  • Sillanpää H, Skogman BH, Sarvas H, Seppälä IJT, Lahdenne P (2013) Cerebrospinal fluid chemokine CXCL13 in the diagnosis of neuroblorreliosis in children. Scand J Infect Dis 45(7):526–530

    Article  CAS  PubMed  Google Scholar 

  • Seyfert S, Kunzmann V, Schwertfeger N, Koch HC, Faulstich A (2002) Determinants of lumbar CSF protein concentration. Eur J Neurol 249(8):1021–2016

    Article  CAS  Google Scholar 

  • Schoonenboom SNM, Pijnenburg YAL, Mulder C, Rosso SM, Van Elk EJ, Van Kamp GJ, Van Swieten JC, Scheltens P (2004) Amyloid (1–42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease. Neurology 62:1580–1584

    Article  CAS  PubMed  Google Scholar 

  • Slack SD, Turley P, Allgar V, Holbrook IB, (2016) Cerebrospinal fluid lactate: measurement of an adult reference interval, An Clin Biochem 2016, 53(1) 164–167

  • Smagina IV, El’chaninova SA (2013) Relationship between biochemical parameters of cerebrospinal fluid and the course of multiple sclerosis. Zh Nevrol Psikhiatr S S Korsakova 113:43–46

    CAS  Google Scholar 

  • Sobek O, Adam P (2003) Letter to the editors: on published article by S. Seyfert, V. Kunzmann, N. Schwertfeger, H. C. Koch, A. Faulstich: Determinants of lumbar CSF protein concentration. Eur J Neurol 250(3):371–372

    Article  CAS  Google Scholar 

  • Sobek O, Adam P, Svatoňová J (2007) Letter to the editor – comments on published article by F. Deisenhammer et al. Eur J Neurol 14(6):1468

    Article  Google Scholar 

  • Sobek O, Adam P, Kelbich P, Koudelková M, Doležil D, Kasík J, Hajduková L, Krušina M, Hybelová M (2009) Evaluation of cerebrospinal fluid – current potentials (in Czech). Neurológia pre prax 10(5):261–265

    Google Scholar 

  • Sobek O, Adam P, Koudelková M, Štourač P, Mareš J (2012) The algorithm of CSF examination according to the recommendation of the Committee of CSF and Neuroimmunology of the Czech Neurological Society. Česká a Slovenská Neurologie 108(2):159–163

    Google Scholar 

  • Stoeck K, Bodemer M, Zerr I (2006) Pro- and anti-inflammatory cytokines in the CSF of patients with Creutzfeld-Jacob disease. J Neuroimmunol 172(1–2):175–181

    Article  CAS  PubMed  Google Scholar 

  • Stork AC, Jacobs BC, Tio-Gillen AP, Eurelings M, Jansen MD, van den Berg LH, Notermans NC, van der Pol WL (2014) Prevalence, specificity and functionality of anti-ganglioside antibodies in neuropathy associated with IgM monoclonal gammopathy. J. Neuroimmunol 268(1–2):89.94

    PubMed  Google Scholar 

  • Sulik A, Kroten A, Wojtkowska M, Oldak E (2014) Increased levels of cytokines in cerebrospinal fluid of children with aseptic meningitis caused by mumps virus and echovirus 30. Scand J Immunol 79(1):68–72

    Article  CAS  PubMed  Google Scholar 

  • Tavakoli NP, Wang H, Nattanmai S, Dupuis M, Fusco H, Hull R (2008) Detection and typing of enteroviruses from CSF specimens from patients diagnosed with meningitis/encephalitis. J Clin Virol 43(2):207–211

    Article  CAS  PubMed  Google Scholar 

  • Voltz R (2004) Paraneoplastic neurological syndromes. An update on diagnosis, pathogenesis and therapy. The Lancet Neurology 1(5):294–305

    Article  Google Scholar 

  • Wildemann B, Oschmann P, Reiber H (Eds) (2006) Neurologische Labordiagnostik. Georg Thieme Verlag, Stuttgart

  • Zeman D, Adam P, Kalistová H, Sobek O, Kelbich P, Anděl J, Anděl M (2000) Transferrin in patients with multiple sclerosis: a comparison among various subgroups of multiple sclerosis patients. Acta Neurol Scand 101:89–94

    Article  CAS  PubMed  Google Scholar 

  • Zeman D, Adam P, Kalistová H, Sobek O, Anděl J, Anděl M (2001) Cerebrospinal fluid cytological findings in multiple sclerosis: a comparison between patient subgroups. Acta Cytol 45(1):51–59

    Article  CAS  PubMed  Google Scholar 

  • Zeman D, Vaníčková Z, Benáková H, Havrdová E (2002) Free kappa light chains in cerebrospinal fluid and serum, Klinická Biochemie a Metabolismus 10(31) (no. 2):98-102

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. Adam.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hepnar, D., Adam, P., Žáková, H. et al. Recommendations for cerebrospinal fluid analysis. Folia Microbiol 64, 443–452 (2019). https://doi.org/10.1007/s12223-018-0663-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12223-018-0663-7

Navigation