EFNS guidelines on disease-specific CSF investigations F. Deisenhammer a , R. Egg a , G. Giovannoni b , B. Hemmer c , A. Petzold d , F. Sellebjerg e , C. Teunissen f and H. Tumani g a Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria; b Neuroimmunology Unit, Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, United Kingdom; c Klinikum rechts der Isar der Technischen Universita ¨t Mu ¨nchen, Technische Universita ¨t Mu ¨nchen, Munich, Germany; d Institute of Neurology, University College of London, London, United Kingdom; e Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark; f Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, The Netherlands; and g Neurologische Klinik, Universita ¨t Ulm, Ulm, Germany Keywords: cerebrospinal fluid, diag- nosis, biomarker, testing Received 17 November 2008 Accepted 23 February 2009 We reviewed the literature for disease-specific markers in cerebrospinal fluid (CSF) and evaluated their diagnostic and prognostic relevance in neurological diseases. High tau protein in combination with low amyloid b levels has a high sensitivity (80%) and specificity (90%) for AlzheimerÕs disease (AD) against normal aging and can predict conversion of mild cognitive impairment to AD. The detection of 14-3-3 has a high sensitivity (80–90%) and specificity (90%) for the diagnosis of CJD. Low or unde- tectable CSF hypocretin-1 (orexin-1) levels constitute a diagnostic biomarker for narcolepsy with cataplexy. Detection of beta-2-transferrin indicates CSF contamina- tion in oto- and rhinorrhoe with a sensitivity of >79% at a specificity of 95% similar to the beta-trace protein (sensitivity >90%, specificity 100%). However, beta-trace protein is faster and cheaper to perform. Possible future biomarkers are: elevated levels of vascular endothelial growth factor are relatively sensitive (51–100%) and specific (73–100%) for leptomeningeal metastases from solid tumors and are associ- ated with a poor prognosis in this condition. Elevated CSF neurofilament (Nf) levels probably reflect acute neuronal degeneration. The prognostic value of CSF Nf levels is highest in acute conditions such as subarachnoid hemorrhage, acute optic neuritis and neuromyelitis optica. Introduction Investigation of the cerebrospinal fluid (CSF) in neu- rological diseases has a long history and a small number of molecules have become the standard repertoire in routine CSF work-up such as total protein, glucose, cell count and differentiation, as well as quantitative and qualitative detection of immunoglobulins [1]. In recent years, the search for biomarkers – a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention, as defined by the Biomarkers Definition Working Group [2] – in body fluids including the CSF has in- creased substantially. In addition to the guidelines on routine CSF investigations [1] we wanted to evaluate newer CSF markers with respect to their disease spec- ificity or prognostic relevance. Search strategy Tau protein, amyloid beta, 14-3-3 and myelin basic protein PubMed was searched up to January 2008 for key words including ÔCSFÕ, ÔtauÕ, ÔamyloidÕ, Ô14-3-3Õ, Ômyelin basic proteinÕ, and ÔmbpÕ, which yielded 1785 hits. Only papers in English and relating to adult clinical neurol- ogy were considered for further analysis. Hypocretin A Medline search using the search terms cerebrospinal fluid (CSF), narcolepsy, sleep disorder, hypocretin and orexin was conducted. The search was limited to the time between 1 January 1980 and 1 May 2008. The key words were cross-referenced as follows: (Ôcerebrospinal fluidÕ or ÔCSFÕ) AND (Ôhypocretin or orexinÕ) AND Correspondence: Florian Deisenhammer MD, MSc, Professor of Neurology, Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria (tel.: +43 512 504 24264; fax: +43 512 504 24266; e-mail: florian.deisenhammer@i-med.ac.at). 760 Ó 2009 The Author(s) Journal compilation Ó 2009 EFNS European Journal of Neurology 2009, 16: 760–770 doi:10.1111/j.1468-1331.2009.02595.x