Skip to main content
SpringerLink
Log in

Axonal damage is remarkable in patients with acutely worsening symptoms of compression myelopathy: biomarkers in cerebrospinal fluid samples

  • Original Article
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

Purpose

To determine levels of biomarkers reflecting damage to axon, myelin, astrocytes, and neuron in cerebrospinal fluid (CSF) of patients with cervical compression myelopathy.

Methods

We collected 69 CSF samples from patients before spinal surgery for acutely worsening compression myelopathy (AM, 20), chronic compression myelopathy (CM, 20), and lumbar canal stenosis (LCS 29; control). We measured levels of phosphorylated neurofilament subunit H (pNF-H), tau (reflecting axonal damage), myelin basic protein (MBP) (reflecting demyelination), S100b (reflecting astrocyte damage), and neuron-specific enolase (NSE) (reflecting neuronal damage). Change of neurological function by surgery was determined using a Japanese Orthopaedic Association (JOA) score for cervical myelopathy.

Results

Significantly higher levels of pNF-H were detected in AM compared with those in either CM or LCS (P < 0.01). Significantly higher levels of tau were detected in AM compared with those in CM (P < 0.05). Levels of MBP were undetectable in almost all the patients. Levels of S100b were equivalent in the three groups. Levels of NSE in AM and CM were significantly lower than those in LCS (P < 0.01). The recovery rate of JOA score was significantly greater for patients with AM than CM. We found a positive correlation between pNF-H and recovery of JOA score (r = 0.381, P = 0.018).

Conclusion

The present results suggest that axonal damage is remarkable compared with demyelination, astrocytic, and neuronal damage in AM. Better clinical outcome in AM with high CSF levels of pNF-H indicates that axonal compensatory plasticity in spinal cord is preserved, and pNF-H can be predictive of good surgical outcome for AM.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ahadi R, Khodagholi F, Daneshi A et al (2015) Diagnostic value of serum levels of GFAP, pNF-H, and NSE compared with clinical findings in severity assessment of human traumatic spinal cord injury. Spine (Phila Pa 1976) 40:E823–E830. https://doi.org/10.1097/brs.0000000000000654

    Article  Google Scholar 

  2. Anderson KJ, Scheff SW, Miller KM et al (2008) The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a blood biomarker of traumatic brain injury. J Neurotrauma 25:1079–1085. https://doi.org/10.1089/neu.2007.0488

    Article  PubMed  PubMed Central  Google Scholar 

  3. Baba H, Maezawa Y, Imura S et al (1996) Quantitative analysis of the spinal cord motoneuron under chronic compression: an experimental observation in the mouse. J Neurol 243:109–116

    Article  PubMed  CAS  Google Scholar 

  4. Cao F, Yang XF, Liu WG et al (2008) Elevation of neuron-specific enolase and S-100beta protein level in experimental acute spinal cord injury. J Clin Neurosci 15:541–544. https://doi.org/10.1016/j.jocn.2007.05.014

    Article  PubMed  CAS  Google Scholar 

  5. Casmiro M, Maitan S, De Pasquale F et al (2005) Cerebrospinal fluid and serum neuron-specific enolase concentrations in a normal population. Eur J Neurol 12:369–374. https://doi.org/10.1111/j.1468-1331.2004.01021.x

    Article  PubMed  CAS  Google Scholar 

  6. Haque A, Ray SK, Cox A et al (2016) Neuron specific enolase: a promising therapeutic target in acute spinal cord injury. Metab Brain Dis. https://doi.org/10.1007/s11011-016-9801-6

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hayakawa K, Okazaki R, Ishii K et al (2012) Phosphorylated neurofilament subunit NF-H as a biomarker for evaluating the severity of spinal cord injury patients, a pilot study. Spinal Cord 50:493–496. https://doi.org/10.1038/sc.2011.184

    Article  PubMed  CAS  Google Scholar 

  8. Heizmann CW, Fritz G, Schafer BW (2002) S100 proteins: structure, functions and pathology. Front Biosci J Virtual Libr 7:d1356–d1368

    CAS  Google Scholar 

  9. Jimenez-Jimenez FJ, Hernanz A, Medina-Acebron S et al (2005) Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neurol Scand 111:114–117. https://doi.org/10.1111/j.1600-0404.2005.00370.x

    Article  PubMed  CAS  Google Scholar 

  10. Koda M, Mochizuki M, Konishi H et al (2016) Comparison of clinical outcomes between laminoplasty, posterior decompression with instrumented fusion, and anterior decompression with fusion for K-line (–) cervical ossification of the posterior longitudinal ligament. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 25:2294–2301. https://doi.org/10.1007/s00586-016-4555-8

    Article  Google Scholar 

  11. Lima JE, Takayanagui OM, Garcia LV et al (2004) Use of neuron-specific enolase for assessing the severity and outcome in patients with neurological disorders. Braz J Med Biol Res 37:19–26

    Article  PubMed  CAS  Google Scholar 

  12. Masaki Y, Yamazaki M, Okawa A et al (2007) An analysis of factors causing poor surgical outcome in patients with cervical myelopathy due to ossification of the posterior longitudinal ligament: anterior decompression with spinal fusion versus laminoplasty. J Spinal Disord Tech 20:7–13. https://doi.org/10.1097/01.bsd.0000211260.28497.35

    Article  PubMed  Google Scholar 

  13. Murphy RK, Sun P, Xu J et al (2016) Magnetic resonance imaging biomarker of axon loss reflects cervical spondylotic myelopathy severity. Spine (Phila Pa 1976) 41:751–756. https://doi.org/10.1097/brs.0000000000001337

    Article  Google Scholar 

  14. Nagashima H, Morio Y, Yamane K et al (2009) Tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 18:1946–1950. https://doi.org/10.1007/s00586-009-1069-7

    Article  Google Scholar 

  15. Nygaard O, Langbakk B, Romner B (1998) Neuron-specific enolase concentrations in serum and cerebrospinal fluid in patients with no previous history of neurological disorder. Scand J Clin Lab Investig 58:183–186

    Article  CAS  Google Scholar 

  16. Ohya J, Chikuda H, Kato S et al (2015) Elevated levels of phosphorylated neurofilament heavy subunit in the cerebrospinal fluid of patients with lumbar spinal stenosis: preliminary findings. Spine J Off J N Am Spine Soc 15:1587–1592. https://doi.org/10.1016/j.spinee.2015.03.013

    Article  Google Scholar 

  17. Pouw MH, Kwon BK, Verbeek MM et al (2014) Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects. Spinal Cord 52:428–433. https://doi.org/10.1038/sc.2014.26

    Article  PubMed  CAS  Google Scholar 

  18. Raabe A, Seifert V (2000) Protein S-100B as a serum marker of brain damage in severe head injury: preliminary results. Neurosurg Rev 23:136–138

    Article  PubMed  CAS  Google Scholar 

  19. Sakuma T, Yamazaki M, Okawa A et al (2012) Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, part 1: a phase I and IIa clinical trial. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 21:482–489. https://doi.org/10.1007/s00586-011-2020-2

    Article  Google Scholar 

  20. Sampath P, Bendebba M, Davis JD et al (2000) Outcome of patients treated for cervical myelopathy. A prospective, multicenter study with independent clinical review. Spine (Phila Pa 1976) 25:670–676

    Article  CAS  Google Scholar 

  21. Schmidt MH, Quinones-Hinojosa A, Rosenberg WS (2002) Cervical myelopathy associated with degenerative spine disease and ossification of the posterior longitudinal ligament. Semin Neurol 22:143–148. https://doi.org/10.1055/s-2002-36537

    Article  PubMed  Google Scholar 

  22. Shaw G, Yang C, Ellis R et al (2005) Hyperphosphorylated neurofilament NF-H is a serum biomarker of axonal injury. Biochem Biophys Res Commun 336:1268–1277. https://doi.org/10.1016/j.bbrc.2005.08.252

    Article  PubMed  CAS  Google Scholar 

  23. Shibahashi K, Doi T, Tanaka S, Hoda H et al (2016) The serum phosphorylated neurofilament heavy subunit as a predictive marker for outcome in adult patients after traumatic brain injury. J Neurotrauma 33:1826–1833. https://doi.org/10.1089/neu.2015.4237

    Article  PubMed  Google Scholar 

  24. Takahashi H, Aoki Y, Nakajima A et al (2014) Phosphorylated neurofilament subunit NF-H becomes elevated in the cerebrospinal fluid of patients with acutely worsening symptoms of compression myelopathy. J Clin Neurosci 21:2175–2178. https://doi.org/10.1016/j.jocn.2014.04.021

    Article  PubMed  CAS  Google Scholar 

  25. Van Engelen BG, Lamers KJ, Gabreels FJ et al (1992) Age-related changes of neuron-specific enolase, S-100 protein, and myelin basic protein concentrations in cerebrospinal fluid. Clin Chem 38:813–816

    PubMed  Google Scholar 

  26. Vidal PM, Karadimas SK, Ulndreaj A et al (2017) Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy. JCI Insight. https://doi.org/10.1172/jci.insight.92512

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yokobori S, Zhang Z, Moghieb A et al (2015) Acute diagnostic biomarkers for spinal cord injury: review of the literature and preliminary research report. World Neurosurg 83:867–878. https://doi.org/10.1016/j.wneu.2013.03.012

    Article  PubMed  Google Scholar 

  28. Zhu B, Xu Y, Liu X et al (2013) Anterior approach versus posterior approach for the treatment of multilevel cervical spondylotic myelopathy: a systemic review and meta-analysis. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 22:1583–1593. https://doi.org/10.1007/s00586-013-2817-2

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported in part by JSPS KAKENHI Grant Number 25861346.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Toho University Sakura Medical Center, 564-1, Shimoshizu, Sakura, Chiba, 285-8741, Japan

    Hiroshi Takahashi, Arata Nakajima, Masato Sonobe, Fumiaki Terajima, Masahiko Saito, Takuya Miyamoto, Keita Koyama, Keiichiro Yamamoto & Koichi Nakagawa

  2. Department of Orthopaedic Surgery, Chiba Eastern Medical Center, Togane, Japan

    Yasuchika Aoki

  3. Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

    Takeo Furuya, Masao Koda & Seiji Ohtori

  4. Department of Orthopaedic Surgery, University of Tsukuba, Tsukuba, Japan

    Masashi Yamazaki

Authors
  1. Hiroshi Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuchika Aoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arata Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masato Sonobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fumiaki Terajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masahiko Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takuya Miyamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Keita Koyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Keiichiro Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takeo Furuya
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masao Koda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Seiji Ohtori
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Masashi Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Koichi Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroshi Takahashi.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 146 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takahashi, H., Aoki, Y., Nakajima, A. et al. Axonal damage is remarkable in patients with acutely worsening symptoms of compression myelopathy: biomarkers in cerebrospinal fluid samples. Eur Spine J 27, 1824–1830 (2018). https://doi.org/10.1007/s00586-018-5549-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-018-5549-5

Keywords

Search

Navigation