Identification of Serum Biomarkers for Differentiating Epileptic Seizures from Psychogenic Attacks Using a Proteomic Approach; a Comparative study
Archives of Academic Emergency Medicine,
Vol. 8 No. 1 (2020),
7 January 2020
Introduction: Differentiating actual epileptic seizures (ESs) from psychogenic non-epileptic seizures (PNES) is of great interest. This study compares the serum proteomics of patients diagnosed with ESs and PNES.
Methods: Eight patients with seizure (4 with PNES and 4 with TLE (temporal lope epilepsy)) were enrolled in this comparative study. Venous blood samples were drawn during the first hour following the seizure. Standard protein purification technique was employed and proteins were subsequently separated via 2-D electrophoresis. After comparison of the serum proteomes from the two groups, protein expression was analyzed. The differentially expressed bands were determined using both matrix-assisted laser ionization time-of-flight (MALDI/TOF) and electrospray ionization quadruple mass spectrometry (MS).
Results: This study identified 361 proteins, the expression of 110 proteins increased, and 87 proteins decreased in the PNES group compared with TLE group. Four separate proteins were finally identified with MALDI/TOF MS analysis. Compared with PNES group, alpha 1-acid glycoprotein, ceruloplasmin, and S100-β were down-regulated and malate dehydrogenase 2 was up-regulated in the serum of TLE patients.
Conclusion: Our results indicated that changes in serum levels of S100-β, ceruloplasmin, alpha 1-acid glycoprotein 1, and after seizure could be introduced as potential markers to differentiate ES from PNES; however, more advanced studies are required to reach a better understanding of the underlying mechanisms.
- Epilepsy; Proteomics; Biomarkers; Diagnosis, Differential; Emergency Service, Hospital
How to Cite
Bodde NM, Brooks JL, Baker GA, Boon PA, Hendriksen JG, Aldenkamp AP. Psychogenic non-epileptic seizures—diagnostic issues: a critical review. Clinical neurology and neurosurgery. 2009;111(1):1-9.
Engel J, Wiebe S, French J, Sperling M, Williamson P, Spencer D, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology. 2003;60(4):538-47.
Ogren JA, Bragin A, Wilson CL, Hoftman GD, Lin JJ, Dutton RA, et al. Three‐dimensional hippocampal atrophy maps distinguish two common temporal lobe seizure–onset patterns. Epilepsia. 2009;50(6):1361-70.
Gedzelman ER, LaRoche SM. Long-term video EEG monitoring for diagnosis of psychogenic nonepileptic seizures. Neuropsychiatric disease and treatment. 2014;10:1979.
Gordon PC, Valiengo LdCL, Proença IC, Kurcgant D, Jorge CL, Castro LH, et al. Comorbid epilepsy and psychogenic non-epileptic seizures: how well do patients and caregivers distinguish between the two. Seizure. 2014;23(7):537-41.
Bodde N, Brooks J, Baker G, Boon P, Hendriksen J, Mulder O, et al. Psychogenic non-epileptic seizures—definition, etiology, treatment and prognostic issues: a critical review. Seizure. 2009;18(8):543-53.
LaFrance Jr WC, Reuber M, Goldstein LH. Management of psychogenic nonepileptic seizures. Epilepsia. 2013;54:53-67.
Chmielewska N, Szyndler J, Makowska K, Wojtyna D, Maciejak P, Płaźnik A. Looking for novel, brain-derived, peripheral biomarkers of neurological disorders. Neurologia i neurochirurgia polska. 2018;52(3):318-25.
Hasanzadeh H, Rezaie-Tavirani M, Seyyedi S, Emadi A. Proteomics Study of extremely low frequency electromagnetic field (50 Hz) on human neuroblastoma cells. Koomesh. 2015;17(1):233-8.
D’Alessio L, Giagante B, Oddo S, Silva W, Solís P, Consalvo D, et al. Psychiatric disorders in patients with psychogenic non-epileptic seizures, with and without comorbid epilepsy. Seizure. 2006;15(5):333-9.
Oto M, Reuber M. Psychogenic non-epileptic seizures: aetiology, diagnosis and management. Advances in psychiatric treatment. 2014;20(1):13-22.
Angus-Leppan H. Diagnosing epilepsy in neurology clinics: a prospective study. Seizure. 2008;17(5):431-6.
Tunca Z, Ergene U, Fidaner H, Cimilli C, Ozerdem A, Alkin T, et al. Reevaluation of serum cortisol in conversion disorder with seizure (pseudoseizure). Psychosomatics. 2000;41(2):152-3.
Bakvis P, Spinhoven P, Giltay EJ, Kuyk J, Edelbroek PM, Zitman FG, et al. Basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures. Epilepsia. 2010;51(5):752-9.
Ehsan T, Fisher RS, Johns D, Lukas RJ, Blum D, Eskola J. Sensitivity and specificity of paired capillary prolactin measurement in diagnosis of seizures. Journal of Epilepsy. 1996;9(2):101-5.
Anzola GP. Predictivity of plasma prolactin levels in differentiating epilepsy from pseudoseizures: a prospective study. Epilepsia. 1993;34(6):1044-8.
Willert C, Spitzer C, Kusserow S, Runge U. Serum neuron‐specific enolase, prolactin, and creatine kinase after epileptic and psychogenic non‐epileptic seizures. Acta neurologica scandinavica. 2004;109(5):318-23.
Rabinowicz AL, Correale J, Boutros RB, Couldwell WT, Henderson CW, DeGiorgio CM. Neuron‐specific enolase is increased after single seizures during inpatient video/EEG monitoring. Epilepsia. 1996;37(2):122-5.
LaFrance W, Leaver K, Stopa E, Papandonatos G, Blum A. Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures. Neurology. 2010;75(14):1285-91.
Aydin S, Dag E, Ozkan Y, Arslan O, Koc G, Bek S, et al. Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients. Peptides. 2011;32(6):1276-80.
Pritchard III PB, Wannamaker BB, Sagel J, Daniel CM. Serum prolactin and cortisol levels in evaluation of pseudoepileptic seizures. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1985;18(1):87-9.
Bauer J, Stefan H, Schrell U, Uhlig B, Landgraf S, Neubauer U, et al. Serum prolactin concentrations and epilepsy. European archives of psychiatry and clinical neuroscience. 1992;241(6):365-71.
Fountain N, Van Ness P, Swain-Eng R, Tonn S, Bever C. Quality improvement in neurology: AAN epilepsy quality measures: report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology. Neurology. 2011;76(1):94-9.
Nass RD, Sassen R, Elger CE, Surges R. The role of postictal laboratory blood analyses in the diagnosis and prognosis of seizures. Seizure. 2017;47:51-65.
Brigo F, Igwe SC, Erro R, Bongiovanni LG, Marangi A, Nardone R, et al. Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review. Journal of neurology. 2015;262(2):251-7.
Kyriakides T, Angelini C, Schaefer J, Sacconi S, Siciliano G, Vilchez J, et al. EFNS guidelines on the diagnostic approach to pauci‐or asymptomatic hyperCKemia. European Journal of Neurology. 2010;17(6):767-73.
Silvestri NJ, Wolfe GI. Asymptomatic/pauci‐symptomatic creatine kinase elevations (hyperckemia). Muscle & nerve. 2013;47(6):805-15.
Hamrah MP, Tavirani MR, Movahedi M, Karvigh SA. Proteomic Analysis of patients with Epileptic Seizure and Psychogenic Non-epileptic Seizure; a Cross-Sectional Study. Archives of Academic Emergency Medicine. 2020;8(1).
Rydén L. Ceruloplasmin. Copper proteins and copper enzymes: CRC Press; 2018. p. 37-100.
Rahman H, Jahan I, Ahmed MR. The Effects of Antiepileptic Drugs (AED) on Serum Copper Level in Children with Epilepsy. Journal of Pharmaceutical Research International. 2019:1-7.
Mbbs AP, Kumar I, Dm S, Gahlot A, Dm S, Singh P. Epilepsy and Neurodegeneration: Clues in the Hair and Blood Vessels! 2019.
Hamed SA, Abdellah MM, El-Melegy N. Blood levels of trace elements, electrolytes, and oxidative stress/antioxidant systems in epileptic patients. Journal of pharmacological sciences. 2004;96(4):465-73.
Chen Y-H, Liu S-J, Gao M-M, Zeng T, Lin G-W, Tan N-N, et al. MDH2 is an RNA binding protein involved in downregulation of sodium channel Scn1a expression under seizure condition. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2017;1863(6):1492-9.
Lerche H, Jurkat‐Rott K, Lehmann‐Horn F. Ion channels and epilepsy. American journal of medical genetics. 2001;106(2):146-59.
Xu X, Guo F, Lv X, Feng R, Min D, Ma L, et al. Abnormal changes in voltage-gated sodium channels NaV1. 1, NaV1. 2, NaV1. 3, NaV1. 6 and in calmodulin/calmodulin-dependent protein kinase II, within the brains of spontaneously epileptic rats and tremor rats. Brain research bulletin. 2013;96:1-9.
Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, et al. S100B's double life: intracellular regulator and extracellular signal. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2009;1793(6):1008-22.
Riuzzi F, Sorci G, Arcuri C, Giambanco I, Bellezza I, Minelli A, et al. Cellular and molecular mechanisms of sarcopenia: the S100B perspective. Journal of cachexia, sarcopenia and muscle. 2018;9(7):1255-68.
Walker LE, Janigro D, Heinemann U, Riikonen R, Bernard C, Patel M. WONOEP appraisal: Molecular and cellular biomarkers for epilepsy. Epilepsia. 2016;57(9):1354-62.
Sendrowski K, Sobaniec W, Sobaniec-Lotowska M, Lewczuk P. S-100 protein as marker of the blood-brain barrier disruption in children with internal hydrocephalus and epilepsy--a preliminary study. Roczniki Akademii Medycznej w Bialymstoku (1995). 2004;49:236-8.
Kaciński M, Budziszewska B, Lasoń W, Zając A, Skowronek-Bała B, Leśkiewicz M, et al. Level of S100B protein, neuron specific enolase, orexin A, adiponectin and insulin-like growth factor in serum of pediatric patients suffering from sleep disorders with or without epilepsy. Pharmacological Reports. 2012;64(6):1427-33.
Dyck RH, Bogoch II, Marks A, Melvin NR, Teskey GC. Enhanced epileptogenesis in S100B knockout mice. Molecular brain research. 2002;106(1-2):22-9.
Chang C-C, Lui C-C, Lee C-C, Chen S-D, Chang W-N, Lu C-H, et al. Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy. BMC neurology. 2012;12(1):15.
DeGiorgio C, Correale J, Gott P, Ginsburg D, Bracht K, Smith T, et al. Serum neuron‐specific enolase in human status epilepticus. Neurology. 1995;45(6):1134-7.
Leutmezer F, Wagner O, Baumgartner C. Serum S‐100 Protein Is Not a Suitable Seizure Marker in Temporal Lobe Epilepsy. Epilepsia. 2002;43(10):1172-4.
Asadollahi M, Simani L. The diagnostic value of serum UCHL-1 and S100-B levels in differentiate epileptic seizures from psychogenic attacks. Brain research. 2019;1704:11-5.
Fournier T, Medjoubi-N N, Porquet D. Alpha-1-acid glycoprotein. Biochimica et Biophysica Acta (BBA)-Protein Structure and Molecular Enzymology. 2000;1482(1-2):157-71.
Morita K, Yamaji A. Changes in the concentration of serum alpha 1-acid glycoprotein in epileptic patients. European journal of clinical pharmacology. 1994;46(2):137-42.
DeVane CL, Lim C, Carson SW, Tingle D, Hackett L, Ware MR. Effect of electroconvulsive therapy on serum concentration of alpha-1-acid glycoprotein. Biological psychiatry. 1991;30(2):116-20.
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