Neurochemical Research

, Volume 34, Issue 11, pp 1969–1974 | Cite as

The Value of the Serum Neurofilament Protein Heavy Chain as a Biomarker for Peri-operative Brain Injury After Carotid Endarterectomy

  • Johann Sellner
  • Axel Petzold
  • Suwad Sadikovic
  • Lorena Esposito
  • Martin S. Weber
  • Peter Heider
  • Hans-Henning Eckstein
  • Bernhard Hemmer
  • Holger Poppert
Original Paper


This prospective study examined the value of serum neurofilament protein levels for detecting peri-operative brain damage following carotid endarterectomy. An ELISA was used for quantification of neurofilament protein heavy chain (NfHSMI35) levels from patients undergoing endarterectomy for symptomatic (n = 17) and asymptomatic high-grade internal carotid artery stenosis (n = 30). All patients underwent diffusion-weighted brain imaging before and after the procedure. NfHSMI35 levels were significantly higher in patients with a symptomatic carotid artery stenosis (0.131 ng/ml) if compared to asymptomatic patients (0.055 ng/ml, P = 0.01). However, serum NfHSMI35 levels were not related to signs of brain ischemia on routine brain imaging techniques. Our pilot data suggests that raised NfHSMI35 serum levels in patients with symptomatic carotid artery disease may be a sensitive biomarker for diffuse ischemic damage to the CNS. We conclude that NfHSMI35 failed to qualify as a biomarker for peri-operative brain injury in CEA and factors that may have compromised the validation of this biomarker are discussed and need to be taken into account for the design of further studies.


Neurofilaments Biomarker Stroke Carotid-endarterectomy Brain injury 


  1. 1.
    Feigin VL, Lawes CM, Bennett DA et al (2003) Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2:43–53. doi: 10.1016/S1474-4422(03)00266-7 PubMedCrossRefGoogle Scholar
  2. 2.
    Halliday A, Mansfield A, Marro J et al (2004) Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 363:1491–1502. doi: 10.1016/S0140-6736(04)16146-1 PubMedCrossRefGoogle Scholar
  3. 3.
    ECST Trial (1998) Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 351:1379–1387. doi: 10.1016/S0140-6736(97)09292-1 CrossRefGoogle Scholar
  4. 4.
    Schnaudigel S, Groschel K, Pilgram SM et al (2008) New brain lesions after carotid stenting versus carotid endarterectomy: a systematic review of the literature. Stroke 39:1911–1919. doi: 10.1161/STROKEAHA.107.500603 PubMedCrossRefGoogle Scholar
  5. 5.
    Petzold A, Rejdak K, Belli A et al (2005) Axonal pathology in subarachnoid and intracerebral hemorrhage. J Neurotrauma 22:407–414. doi: 10.1089/neu.2005.22.407 PubMedCrossRefGoogle Scholar
  6. 6.
    Guy J, Shaw G, Ross-Cisneros FN et al (2008) Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON). Mol Vis 14:2443–2450PubMedGoogle Scholar
  7. 7.
    Petzold A, Rejdak K, Plant GT (2004) Axonal degeneration and inflammation in acute optic neuritis. J Neurol Neurosurg Psychiatry 75:1178–1180. doi: 10.1136/jnnp.2003.017236 PubMedCrossRefGoogle Scholar
  8. 8.
    Chaturvedi S, Bruno A, Feasby T et al (2005) Carotid endarterectomy—an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 65:794–801. doi: 10.1212/01.wnl.0000176036.07558.82 PubMedCrossRefGoogle Scholar
  9. 9.
    Poppert H, Wolf O, Resch M et al (2004) Differences in number, size and location of intracranial microembolic lesions after surgical versus endovascular treatment without protection device of carotid artery stenosis. J Neurol 251:1198–1203. doi: 10.1007/s00415-004-0502-4 PubMedCrossRefGoogle Scholar
  10. 10.
    Petzold A, Keir G, Green AJ et al (2003) A specific ELISA for measuring neurofilament heavy chain phosphoforms. J Immunol Methods 278:179–190. doi: 10.1016/S0022-1759(03)00189-3 PubMedCrossRefGoogle Scholar
  11. 11.
    Whiteley W, Tseng MC, Sandercock P (2008) Blood biomarkers in the diagnosis of ischemic stroke: a systematic review. Stroke 39:2902–2909. doi: 10.1161/STROKEAHA.107.511261 PubMedCrossRefGoogle Scholar
  12. 12.
    Petzold A, Gveric D, Groves M et al (2008) Phosphorylation and compactness of neurofilaments in multiple sclerosis: indicators of axonal pathology. Exp Neurol 213:326–335. doi: 10.1016/j.expneurol.2008.06.008 PubMedCrossRefGoogle Scholar
  13. 13.
    Engelter S, Wetzel S, Bonati LH et al (2008) The clinical significance of diffusion-weighted imaging in stroke and TIA patients. Swiss Med Wkly 138:729–740PubMedGoogle Scholar
  14. 14.
    Wolf O, Heider P, Heinz M et al (2004) Frequency, clinical significance and course of cerebral ischemic events after carotid endarterectomy evaluated by serial diffusion weighted imaging. Eur J Vasc Endovasc Surg 27:167–171. doi: 10.1016/j.ejvs.2003.11.002 PubMedCrossRefGoogle Scholar
  15. 15.
    Chida K, Ogasawara K, Suga Y et al (2009) Postoperative cortical neural loss associated with cerebral hyperperfusion and cognitive impairment after carotid endarterectomy: 123I-iomazenil SPECT study. Stroke 40:448–453. doi: 10.1161/STROKEAHA.108.515775 PubMedCrossRefGoogle Scholar
  16. 16.
    Soinne L, Helenius J, Tikkala I et al (2009) The effect of severe carotid occlusive disease and its surgical treatment on cognitive functions of the brain. Brain Cogn 69:353–359. doi: 10.1016/j.bandc.2008.08.010 PubMedCrossRefGoogle Scholar
  17. 17.
    Unden J, Strandberg K, Malm J et al (2009) Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation. J Neurol 256:72–77. doi: 10.1007/s00415-009-0054-8 PubMedCrossRefGoogle Scholar
  18. 18.
    Petzold A, Baker D, Pryce G et al (2003) Quantification of neurodegeneration by measurement of brain-specific proteins. J Neuroimmunol 138:45–48. doi: 10.1016/S0165-5728(03)00092-4 PubMedCrossRefGoogle Scholar
  19. 19.
    Petzold A, Michel P, Stock M et al (2008) Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome. J Stroke Cerebrovasc Dis 17:196–203. doi: 10.1016/j.jstrokecerebrovasdis.2008.02.002 PubMedCrossRefGoogle Scholar
  20. 20.
    Jordan W, Hagedohm J, Wiltfang J et al (2002) Biochemical markers of cerebrovascular injury in sleep apnoea syndrome. Eur Respir J 20:158–164. doi: 10.1183/09031936.02.00862001 PubMedCrossRefGoogle Scholar
  21. 21.
    Sellner J, Leyssen P, Heiland S et al (2004) In vivo monitoring of acute flavivirus (Modoc) encephalitis with regional and whole-brain quantitative diffusion magnetic resonance imaging. J Neurovirol 10:255–259. doi: 10.1080/13550280490463479 PubMedCrossRefGoogle Scholar
  22. 22.
    Kosior RK, Wright CJ, Kosior JC et al (2007) 3-Tesla versus 1.5-Tesla magnetic resonance diffusion and perfusion imaging in hyperacute ischemic stroke. Cerebrovasc Dis 24:361–368. doi: 10.1159/000106983 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Johann Sellner
    • 1
  • Axel Petzold
    • 2
  • Suwad Sadikovic
    • 1
  • Lorena Esposito
    • 1
  • Martin S. Weber
    • 1
  • Peter Heider
    • 3
  • Hans-Henning Eckstein
    • 3
  • Bernhard Hemmer
    • 1
  • Holger Poppert
    • 1
  1. 1.Department of Neurology, Klinikum rechts der IsarTechnische Universität MünchenMunichGermany
  2. 2.Department of Neuroimmunology, Institute of Neurology, The National Hospital for Neurology and NeurosurgeryUniversity College London HospitalsLondonUK
  3. 3.Department of Vascular Surgery, Klinikum rechts der IsarTechnische Universität MünchenMunichGermany

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