Journal of Neurology

, Volume 257, Issue 10, pp 1708–1712 | Cite as

Serum neuron-specific enolase level as a biomarker in differential diagnosis of seizure and syncope

  • Seung-Yeob Lee
  • Young-Chul Choi
  • Jeong-Ho Kim
  • Won-Joo KimEmail author
Original Communication


Patients who experience a single generalized tonic–clonic seizure or syncope may have similar clinical symptoms, which can cause difficulty in the differential diagnosis. The aim of this study was to examine whether serum neuron-specific enolase (NSE) has diagnostic relevance as a biochemical marker for these disorders. Serum NSE levels were analyzed following a loss of consciousness in patients who were diagnosed with a seizure (n = 52) and syncope (n = 42) compared with normal controls (n = 91). NSE was 14.97 ± 7.57 ng/dl for the seizure group, 10.15 ± 3.22 ng/dl for the syncope group, and 10.03 ± 1.28 ng/dl for the control group. The seizure group showed a significantly increased serum NSE (p < 0.05) compared to the syncope and control groups. By receiver operating characteristic (ROC) curve analysis, the cut-off value with the highest diagnostic accuracy was defined as 11.5 ng/ml with a sensitivity of 0.58 and specificity of 0.91. The NSE values of the syncope and control groups showed no significant differences. Syncope may not influence diffuse brain damage. Serum NSE measurement may be a helpful test for the identification and diagnosis of a seizure rather than syncope.


Neuron-specific enolase Seizure Syncope 


  1. 1.
    Aksamit AJ Jr, Preissner CM, Homburger HA (2001) Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt–Jakob disease. Neurology 57:728–730PubMedGoogle Scholar
  2. 2.
    Anand N, Stead LG (2005) Neuron-specific enolase as a marker for acute ischemic stroke: a systematic review. Cerebrovasc Dis 20:213–219CrossRefPubMedGoogle Scholar
  3. 3.
    Bandyopadhyay S, Hennes H, Gorelick MH, Wells RG, Walsh-Kelly CM (2005) Serum neuron-specific enolase as a predictor of short-term outcome in children with closed traumatic brain injury. Acad Emerg Med 12:732–738CrossRefPubMedGoogle Scholar
  4. 4.
    Berger RP, Pierce MC, Wisniewski SR, Adelson PD, Clark RS, Ruppel RA, Kochanek PM (2002) Neuron-specific enolase and S-100B in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatrics 109:E31CrossRefPubMedGoogle Scholar
  5. 5.
    Bergfeldt L (2003) Differential diagnosis of cardiogenic syncope and seizure disorders. Heart 89:353–358CrossRefPubMedGoogle Scholar
  6. 6.
    Britton JW (2004) Syncope and seizures-differential diagnosis and evaluation. Clin Auton Res 14:148–159CrossRefPubMedGoogle Scholar
  7. 7.
    Britton JW, Benarroch E (2006) Seizures and syncope: anatomic basis and diagnostic considerations. Clin Auton Res 16:18–28CrossRefPubMedGoogle Scholar
  8. 8.
    Buttner T, Lack B, Jager M, Wunsche W, Kuhn W, Muller T, Przuntek H, Postert T (1999) Serum levels of neuron-specific enolase and s-100 protein after single tonic–clonic seizures. J Neurol 246:459–461CrossRefPubMedGoogle Scholar
  9. 9.
    Chen DK, So YT, Fisher RS, Technology Therapeutics Assessment Subcommittee of the American Academy of Neurology (2005) Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 65:668–675CrossRefPubMedGoogle Scholar
  10. 10.
    Cuthill FM, Espie CA (2005) Sensitivity and specificity of procedures for the differential diagnosis of epileptic and non-epileptic seizures: a systematic review. Seizure 14:293–303CrossRefPubMedGoogle Scholar
  11. 11.
    DeGiorgio CM, Heck CN, Rabinowicz AL, Gott PS, Smith T, Correale J (1999) Serum neuron-specific enolase in the major subtypes of status epilepticus. Neurology 52:746–749PubMedGoogle Scholar
  12. 12.
    Francis A, Rivett AJ, Roth JA (1983) Activity of neuron-specific enolase in normal and lesioned rat brain. Brain Res 263:89–95CrossRefPubMedGoogle Scholar
  13. 13.
    Hardemark HG, Ericsson N, Kotwica Z, Rundstrom G, Mendel-Hartvig I, Olsson Y, Pahlman S, Persson L (1989) S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage. J Neurosurg 71:727–731CrossRefPubMedGoogle Scholar
  14. 14.
    Hardemark HG, Persson L, Bolander HG, Hillered L, Olsson Y, Pahlman S (1988) Neuron-specific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid. Stroke 19:1140–1144PubMedGoogle Scholar
  15. 15.
    Kohira I, Tsuji T, Ishizu H, Takao Y, Wake A, Abe K, Kuroda S (2000) Elevation of neuron-specific enolase in serum and cerebrospinal fluid of early stage Creutzfeldt–Jakob disease. Acta Neurol Scand 102:385–387CrossRefPubMedGoogle Scholar
  16. 16.
    Marangos PJ, Schmechel DE (1987) Neuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells. Annu Rev Neurosci 10:269–295CrossRefPubMedGoogle Scholar
  17. 17.
    Massabki PS, Silva NP, Lourenco DM, Andrade LE (2003) Neuron specific enolase concentration is increased in serum and decreased in platelets of patients with active systemic sclerosis. J Rheumatol 30:2606–2612PubMedGoogle Scholar
  18. 18.
    McKeon A, Vaughan C, Delanty N (2006) Seizure versus syncope. Lancet Neurol 5:171–180CrossRefPubMedGoogle Scholar
  19. 19.
    Oh SH, Lee JG, Na SJ, Park JH, Choi YC, Kim WJ (2003) Prediction of early clinical severity and extent of neuronal damage in anterior-circulation infarction using the initial serum neuron-specific enolase level. Arch Neurol 60:37–41CrossRefPubMedGoogle Scholar
  20. 20.
    Pahlman S, Esscher T, Bergvall P, Odelstad L (1984) Purification and characterization of human neuron-specific enolase: radioimmunoassay development. Tumour Biol 5:127–139PubMedGoogle Scholar
  21. 21.
    Petramfar P, Yaghoobi E, Nemati R, Asadi-Pooya AA (2009) Serum creatine phosphokinase is helpful in distinguishing generalized tonic–clonic seizures from psychogenic nonepileptic seizures and vasovagal syncope. Epilepsy Behav 15:330–332CrossRefPubMedGoogle Scholar
  22. 22.
    Prinz RA, Marangos PJ (1982) Use of neuron-specific enolase as a serum marker for neuroendocrine neoplasms. Surgery 92:887–889PubMedGoogle Scholar
  23. 23.
    Rabinowicz AL, Correale J, Boutros RB, Couldwell WT, Henderson CW, DeGiorgio CM (1996) Neuron-specific enolase is increased after single seizures during inpatient video/EEG monitoring. Epilepsia 37:122–125CrossRefPubMedGoogle Scholar
  24. 24.
    Schreiber SS, Sun N, Tocco G, Baudry M, DeGiorgio CM (1999) Expression of neuron-specific enolase in adult rat brain following status epilepticus. Exp Neurol 159:329–331CrossRefPubMedGoogle Scholar
  25. 25.
    Sheldon R, Rose S, Ritchie D, Connolly SJ, Koshman ML, Lee MA, Frenneaux M, Fisher M, Murphy W (2002) Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol 40:142–148CrossRefPubMedGoogle Scholar
  26. 26.
    Sulter G, Elting JW, De Keyser J (1998) Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke. Neurosci Lett 253:71–73CrossRefPubMedGoogle Scholar
  27. 27.
    Tumani H, Otto M, Gefeller O, Wiltfang J, Herrendorf G, Mogge S, Steinhoff BJ (1999) Kinetics of serum neuron-specific enolase and prolactin in patients after single epileptic seizures. Epilepsia 40:713–718CrossRefPubMedGoogle Scholar
  28. 28.
    Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S (2006) Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 67:203–210CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Seung-Yeob Lee
    • 1
  • Young-Chul Choi
    • 1
  • Jeong-Ho Kim
    • 2
  • Won-Joo Kim
    • 1
    Email author
  1. 1.Department of NeurologyGangnam Severance Hospital, Yonsei University College of MedicineSeoulKorea
  2. 2.Department of Clinical PathologyGangnam Severance Hospital, Yonsei University College of MedicineSeoulKorea

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