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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


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1437-4331
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Volume 53, Issue 10

Issues

Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury

Eduardo Martínez-Morillo
  • Lunenfeld-Tanenbaum Research Institute, Joseph and Wolf Lebovic Health Complex, Mount Sinai Hospital, Toronto, ON, Canada
  • Department of Clinical Biochemistry, Laboratory of Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
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/ Charmaine Childs
  • Centre for Health and Social Care Research, Faculty of Health and Wellbeing, Sheffield Hallam University, Sheffield, UK
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/ Belén Prieto García
  • Department of Clinical Biochemistry, Laboratory of Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
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/ Francisco V. Álvarez Menéndez
  • Department of Clinical Biochemistry, Laboratory of Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
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/ Alexander D. Romaschin
  • Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
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/ Gianfranco Cervellin / Giuseppe LippiORCID iD: http://orcid.org/0000-0001-9523-9054 / Eleftherios P. Diamandis
  • Corresponding author
  • Pathology and Laboratory Medicine Department, Mount Sinai Hospital, Suite 6-201, Box 32, 60 Murray Street, Toronto, ON M5T 3L9, Canada
  • Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada
  • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-02-07 | DOI: https://doi.org/10.1515/cclm-2014-0908

Abstract

Background: Brain injury is a medical emergency that needs to be diagnosed and treated promptly. Several proteins have been studied as biomarkers of this medical condition. The aims of this study were to: 1) evaluate the selectivity and precision of a commercial ELISA kit for neurofilament medium polypeptide (NFM) protein; and 2) evaluate the concentration in cerebrospinal fluid (CSF) and serum of healthy individuals and patients with brain damage.

Methods: An ELISA from Elabscience was used. The selectivity was evaluated using size-exclusion chromatography and mass spectrometry. Intra- and inter-batch coefficients of variation (CV) were also studied. Fifty-one CSF samples from 36 age-matched patients with hemorrhagic stroke (HS) (n=30), ischemic stroke (IS) (n=11) and healthy individuals (n=10) were assayed. In addition, serum samples from healthy volunteers (n=47), 68 serum samples from seven patients with HS, 106 serum samples from 12 patients with traumatic brain injury (TBI) and 68 serum samples from 68 patients with mild traumatic brain injury (mTBI) were also analyzed.

Results: NFM was identified in the chromatographic fraction with highest immunoreactivity. The intra- and inter-batch CVs were ≤10% and ≤13%, respectively. The CSF-NFM concentration in HS was significantly higher (p<0.0001) than in IS and controls. Serum NFM concentration ranged from 0.26 to 8.57 ng/mL in healthy individuals (median=2.29), from 0.97 to 42.4 ng/mL in HS (median=10.8) and from 3.48 to 45.4 ng/mL in TBI (median=14.7). Finally, 44% of patients with mTBI had increased NFM concentration, with significantly higher levels (p=0.01) in patients with polytrauma.

Conclusions: To our knowledge this is the first study describing increased NFM levels in CSF and serum from patients with brain damage.

This article offers supplementary material which is provided at the end of the article.

Keywords: biomarker; brain injury; cerebrospinal fluid; neurofilament; serum; stroke

References

  • 1.

    Mondello S, Schmid K, Berger RP, Kobeissy F, Italiano D, Jeromin A, et al. The challenge of mild traumatic brain injury: role of biochemical markers in diagnosis of brain damage. Med Res Rev 2014;34:503–31.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 2.

    Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics – 2013 update: a report from the American Heart Association. Circulation 2013;127:e6–245.Google Scholar

  • 3.

    Schiff L, Hadker N, Weiser S, Rausch C. A literature review of the feasibility of glial fibrillary acidic protein as a biomarker for stroke and traumatic brain injury. Mol Diagn Ther 2012;16:79–92.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 4.

    Schiavi P, Laccarino C, Servadei F. The value of the calcium binding protein S100 in the management of patients with traumatic brain injury. Acta Biomed 2012;83:5–20.Google Scholar

  • 5.

    Moritz S, Warnat J, Bele S, Graf BM, Woertgen C. The prognostic value of NSE and S100B from serum and cerebrospinal fluid in patients with spontaneous subarachnoid hemorrhage. J Neurosurg Anesthesiol 2010;22:21–31.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 6.

    Brea D, Sobrino T, Blanco M, Cristobo I, Rodriguez-Gonzalez R, Rodriguez-Yanez M, et al. Temporal profile and clinical significance of serum neuron-specific enolase and S100 in ischemic and hemorrhagic stroke. Clin Chem Lab Med 2009;47:1513–8.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 7.

    Martinez-Morillo E, Garcia Hernandez P, Begcevic I, Kosanam H, Prieto Garcia B, Alvarez Menendez FV, et al. Identification of novel biomarkers of brain damage in patients with hemorrhagic stroke by integrating bioinformatics and mass spectrometry-based proteomics. J Proteome Res 2014;13:969–81.CrossrefWeb of ScienceGoogle Scholar

  • 8.

    Zanier ER, Refai D, Zipfel GJ, Zoerle T, Longhi L, Esparza TJ, et al. Neurofilament light chain levels in ventricular cerebrospinal fluid after acute aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 2011;82:157–9.Web of ScienceCrossrefPubMedGoogle Scholar

  • 9.

    Kuhle J, Regeniter A, Leppert D, Mehling M, Kappos L, Lindberg RL, et al. A highly sensitive electrochemiluminescence immunoassay for the neurofilament heavy chain protein. J Neuroimmunol 2010;220:114–9.Web of ScienceGoogle Scholar

  • 10.

    Petzold A, Keir G, Kay A, Kerr M, Thompson EJ. Axonal damage and outcome in subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 2006;77:753–9.Google Scholar

  • 11.

    Petzold A, Rejdak K, Belli A, Sen J, Keir G, Kitchen N, et al. Axonal pathology in subarachnoid and intracerebral hemorrhage. J Neurotrauma 2005;22:407–14.PubMedCrossrefGoogle Scholar

  • 12.

    Prassas I, Diamandis EP. Translational researchers beware! Unreliable commercial immunoassays (ELISAs) can jeopardize your research. Clin Chem Lab Med 2014;52:765–6.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 13.

    Rifai N, Watson ID, Miller WG. Commercial immunoassays in biomarkers studies: researchers beware! Clin Chem 2012;58:1387–8.Web of ScienceCrossrefPubMedGoogle Scholar

  • 14.

    Martinez-Morillo E, Diamandis A, Romaschin AD, Diamandis EP. Kallikrein 6 as a serum prognostic marker in patients with aneurysmal subarachnoid hemorrhage. PLoS One 2012;7:e45676.Web of ScienceGoogle Scholar

  • 15.

    Childs C, Martinez-Morillo E, Wai AP, Zu MM, Diamandis A, Diamandis EP. Exploring the relationship between serum biomarkers, acute intracerebral changes and outcome after severe traumatic brain injury (TBI). Clin Chem Lab Med 2013;51:e195–7.Web of ScienceCrossrefGoogle Scholar

  • 16.

    Cervellin G, Benatti M, Carbucicchio A, Mattei L, Cerasti D, Aloe R, et al. Serum levels of protein S100B predict intracranial lesions in mild head injury. Clin Biochem 2012;45:408–11.Web of ScienceCrossrefPubMedGoogle Scholar

  • 17.

    Arlen RK, editor. New research on neurofilament proteins. Hauppauge NY: Nova Science Publishers, Inc, 2007.Google Scholar

  • 18.

    Liem RK, Messing A. Dysfunctions of neuronal and glial intermediate filaments in disease. J Clin Invest 2009;119: 1814–24.Web of ScienceGoogle Scholar

  • 19.

    Kuhle J, Gaiottino J, Leppert D, Petzold A, Bestwick JP, Malaspina A, et al. Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome. J Neurol Neurosurg Psychiatry [Epub ahead of print 2014 Jun 16]. pii: jnnp-2013-307454. doi: 10.1136/jnnp-2013-307454.Web of ScienceCrossrefGoogle Scholar

  • 20.

    Gaiottino J, Norgren N, Dobson R, Topping J, Nissim A, Malaspina A, et al. Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS One 2013;8:e75091.Web of SciencePubMedGoogle Scholar

  • 21.

    Cai JY, Lu C, Chen MH, Ba HJ, Chen XD, Lin JH, et al. Predictive value of phosphorylated axonal neurofilament subunit H for clinical outcome in patients with acute intracerebral hemorrhage. Clin Chim Acta 2013;424:182–6.Web of ScienceGoogle Scholar

  • 22.

    Gresle MM, Liu Y, Dagley LF, Haartsen J, Pearson F, Purcell AW, et al. Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients. J Neurol Neurosurg Psychiatry 2014;85:1209–13.Google Scholar

  • 23.

    Uhlen M, Oksvold P, Fagerberg L, Lundberg E, Jonasson K, Forsberg M, et al. Towards a knowledge-based Human Protein Atlas. Nat Biotechnol 2010;28:1248–50.CrossrefGoogle Scholar

About the article

Corresponding author: Eleftherios P. Diamandis, MD, PhD, FRCPC, FRSC, Pathology and Laboratory Medicine Department, Mount Sinai Hospital, Suite 6-201, Box 32, 60 Murray Street, Toronto, ON M5T 3L9, Canada, Phone: +1 416 586 8443, Fax: +1 416 619 5521, E-mail: ; Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada; and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada


Received: 2014-09-14

Accepted: 2015-01-06

Published Online: 2015-02-07

Published in Print: 2015-09-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 53, Issue 10, Pages 1575–1584, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2014-0908.

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