Download PDF
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2020; 78(07): 424-429
DOI: 10.1590/0004-282X20200040
Original Article

Evaluation of ubiquitin C-terminal hydrolase-L1 enzyme levels in patients with epilepsy

Avaliação dos níveis de enzima ubiquitina C-terminal hidrolase-L1 em pacientes com epilepsia
Ibrahim Halil YASAK 
1   Harran University, Emergency Deparment of Medicine, Sanliurfa, Turkey.
,
Mustafa YILMAZ 
2   University of Firat, Emergency Medicine, Elazig, Turkey.
,
Murat GÖNEN 
3   Firat Universitesi Tip Fakultesi, Neurology, Elazig, Turkey.
,
Metin ATESCELIK 
2   University of Firat, Emergency Medicine, Elazig, Turkey.
,
Mehtap GURGER 
2   University of Firat, Emergency Medicine, Elazig, Turkey.
,
Nevin ILHAN 
4   Firat Universitesi, Biochemistry Department, Elazig, Turkey.
,
Mehmet Cagri GOKTEKIN 
2   University of Firat, Emergency Medicine, Elazig, Turkey.
› Author AffiliationsSupported by: University Scientific Research Projects Coordination Unit TF 1538
› Further Information
Also available at
   Permissions and Reprints

ABSTRACT

Objective: Ubiquitin C-terminal Hydrolase-L1 (UCH-L1) enzyme levels were investigated in patients with epilepsy, epileptic seizure, remission period, and healthy individuals. Methods: Three main groups were evaluated, including epileptic seizure, patients with epilepsy in the non-seizure period, and healthy volunteers. The patients having a seizure in the Emergency department or brought by a postictal confusion were included in the epileptic attack group. The patients having a seizure attack or presenting to the Neurology outpatient department for follow up were included in the non-seizure (remission period) group. Results: The UCH-L1 enzyme levels of 160 patients with epilepsy (80 patients with epileptic attack and 80 patients with epilepsy in the non-seizure period) and 100 healthy volunteers were compared. Whereas the UCH-L1 enzyme levels were 8.30 (IQR=6.57–11.40) ng/mL in all patients with epilepsy, they were detected as 3.90 (IQR=3.31–7.22) ng/mL in healthy volunteers, and significantly increased in numbers for those with epilepsy (p<0.001). However, whereas the UCH-L1 levels were 8.50 (IQR=6.93–11.16) ng/mL in the patients with epileptic seizures, they were 8.10 (IQR=6.22–11.93) ng/mL in the non-seizure period, and no significant difference was detected (p=0.6123). When the UCH-L1 cut-off value was taken as 4.34 mg/mL in Receiver Operating Characteristic (ROC) Curve analysis, the sensitivity and specificity detected were 93.75 and 66.00%, respectively (AUG=0.801; p<0.0001; 95%CI 0.747–0.848) for patients with epilepsy. Conclusion: Even though UCH-L1 levels significantly increased more in patients with epilepsy than in healthy individuals, there was no difference between epileptic seizure and non-seizure periods.

RESUMO

Objetivo: Níveis da enzima ubiquitina C-terminal hidrolase-L1 (UCH-L1) foram investigados em pacientes com epilepsia, crise epiléptica, período de remissão e indivíduos saudáveis. Método: Foram avaliados três grupos principais, incluindo crise epiléptica, epilepsia no período não convulsivo e voluntários saudáveis. Pacientes com convulsão no departamento de emergência ou trazidos por confusão pós-ictal foram incluídos no grupo de crise epiléptica. Os pacientes que tiveram crise epiléptica ou foram ao ambulatório de Neurologia para acompanhamento foram incluídos no grupo não convulsivo (período de remissão). Resultados: Os níveis da enzima UCH-L1 de 160 pacientes com epilepsia (80 pacientes com crise epiléptica e 80 pacientes com epilepsia no período não convulsivo) e 100 voluntários saudáveis foram comparados. Enquanto os níveis da enzima UCH-L1 foram 8,30 (IQR=6,57–11,40) ng/mL em todos os pacientes com epilepsia, os níveis detectados foram de 3,90 (IQR=3,31–7,22) ng/mL em voluntários saudáveis e aumentaram significativamente na epilepsia (p<0,001). No entanto, ao passo que os níveis de UCH-L1 foram 8,50 (IQR=6,93–11,16) ng/mL nos pacientes com crise epiléptica, foram 8,10 (IQR=6,22–11,93) ng/mL no período não convulsivo, e nenhuma diferença significativa foi detectada (p=0,6123). Quando o valor de corte de UCH-L1 foi considerado 4,34 mg/mL com base na análise da curva ROC, sensibilidade e especificidade foram detectadas como 93,75 e 66,00%, respectivamente (AUG=0,801; p<0,0001; IC95% 0,747–0,848) para os pacientes com epilepsia. Conclusão: Embora os níveis de UCH-L1 tenham aumentado significativamente nos pacientes com epilepsia em relação aos indivíduos saudáveis, não foi observada diferença entre crise epiléptica e períodos não convulsivos.

Keywords:

Epilepsy - Ubiquitin - Seizures

Palavras-chave:

Epilepsia - Ubiquitinas - Convulsões


Publication History

Received: 26 December 2019

Accepted: 26 February 2020

Article published online:
13 June 2023

© 2020. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Pitkänen A, Lukasiuk K. Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy Behav. 2009 Jan;14 Suppl 1:16-25. https://doi.org/10.1016/j.yebeh.2008.09.023
  • 2 Engel J Jr, Starkman S. Overview of seizures. Emergency medicine clinics of North America. 1994;12(4):895-923.
  • 3 Huff JS, Melnick ER, Tomaszewski CA, Thiessen ME, Jagoda AS, Fesmire FM, et al. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2014 Apr;63(4):437-47.e15. https://doi.org/10.1016/j.annemergmed.2014.01.018
  • 4 Diaz-Arrastia R, Wang KK, Papa L, Sorani MD, Yue JK, Puccio AM, et al. Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J Neurotrauma. 2014 Jan;31(1):19-25. https://doi.org/10.1089/neu.2013.3040
  • 5 Papa L, Akinyi L, Liu MC, Pineda JA, Tepas III JJ 3rd, Oli MW, et al. Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit Care Med. 2010 Jan;38(1):138-44. https://doi.org/10.1097/CCM.0b013e3181b788ab
  • 6 Chen F, Sugiura Y, Myers KG, Liu Y, Lin W. Ubiquitin carboxyl-terminal hydrolase L1 is required for maintaining the structure and function of the neuromuscular junction. Proc Natl Acad Sci U S A. 2010 Jan;107(4):1636-41. https://doi.org/10.1073/pnas.0911516107
  • 7 Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, et al. Ubiquitin hydrolase Uch-L1 rescues β-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006 Aug;126(4):775-88. https://doi.org/10.1016/j.cell.2006.06.046
  • 8 Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, et al. The ubiquitin pathway in Parkinson's disease. Nature. 1998 Oct;395(6701):451-2. https://doi.org/10.1038/26652
  • 9 Castegna A, Aksenov M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, α-enolase and heat shock cognate 71. J Neurochem. 2002 Sep;82(6):1524-32. https://doi.org/10.1046/j.1471-4159.2002.01103.x
  • 10 Choi J, Levey AI, Weintraub ST, Rees HD, Gearing M, Chin LS, et al. Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases. J Biol Chem. 2004 Mar 26;279(13):13256-64. https://doi.org/10.1074/jbc.M314124200
  • 11 Ren C, Zoltewicz S, Guingab-Cagmat J, Anagli J, Gao M, Hafeez A, et al. Different expression of ubiquitin C-terminal hydrolase-L1 and αII-spectrin in ischemic and haemorrhagic stroke: potential biomarkers in diagnosis. Brain Res. 2013 Dec;1540:84-91. https://doi.org/10.1016/j.brainres.2013.09.051
  • 12 ACEP Clinical Policies Committee; Clinical Policies Subcommittee on Seizures. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2004 May;43(5):605-25. https://doi.org/10.1016/S019606440400068X
  • 13 Nicoletti A, Reggio A, Bartoloni A, Failla G, Sofia V, Bartalesi F, et al. Prevalence of epilepsy in rural Bolivia: a door-to-door survey. Neurology. 1999 Dec;53(9):2064-9. https://doi.org/10.1212/wnl.53.9.2064
  • 14 Dent W, Helbok R, Matuja WBP, Scheunemann S, Schmutzhard E. Prevalence of active epilepsy in a rural area in South Tanzania: a door-to-door survey. Epilepsia. 2005 Dec;46(12):1963-9. https://doi.org/10.1111/j.1528-1167.2005.00338.x
  • 15 Pitkänen A, Sutula TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol. 2002 Jul;1(3):173-81. https://doi.org/10.1016/s1474-4422(02)00073-x
  • 16 Palmio J, Peltola J, Vuorinen P, Laine S, Suhonen J, Keränen T. Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures. J Neurol Sci. 2001 Jan;183(1):27-31. https://doi.org/10.1016/s0022-510x(00)00478-0
  • 17 Palmio J, Suhonen J, Keränen T, Hulkkonen J, Peltola J, Pirttilä T. Cerebrospinal fluid tau as a marker of neuronal damage after epileptic seizure. Seizure. 2009 Sep;18(7):474-7. https://doi.org/10.1016/j.seizure.2009.04.006
  • 18 Thompson R, Doran J, Jackson P, Dhillon A, Rode J. PGP 9.5-a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983 Nov;278(1-2):224-8. https://doi.org/10.1016/0006-8993(83)90241-x
  • 19 Wilkinson KD. Roles of ubiquitinylation in proteolysis and cellular regulation. Annu Rev Nutr. 1995;15:161-89. https://doi.org/10.1146/annurev.nu.15.070195.001113
  • 20 Gong B, Leznik E. The role of ubiquitin C-terminal hydrolase L1 in neurodegenerative disorders. Drug News Perspect. 2007 Jul-Aug;20(6):365-70. https://doi.org/10.1358/dnp.2007.20.6.1138160
  • 21 Setsuie R, Wada K. The functions of UCH-L1 and its relation to neurodegenerative diseases. Neurochem Int. 2007 Jul-Sep;51(2-4):105-11. https://doi.org/10.1016/j.neuint.2007.05.007
  • 22 Mondello S, Constantinescu R, Zetterberg H, Andreasson U, Holmberg B, Jeromin A. CSF α-synuclein and UCH-L1 levels in Parkinson's disease and atypical parkinsonian disorders. Parkinsonism Relat Disord. 2014 Apr;20(4):382-7. https://doi.org/10.1016/j.parkreldis.2014.01.011
  • 23 Li Y, Wang Z, Zhang B, Zhe X, Wang M, Bai J, et al. Cerebrospinal fluid ubiquitin C-terminal hydrolase as a novel marker of neuronal damage after epileptic seizure. Epilepsy Res. 2013 Feb;103(2-3):205-10. https://doi.org/10.1016/j.eplepsyres.2012.08.001
  • 24 Bradley WG, Daroff RB, Fenichel GM, Jankovic J. Neurology in clinical practice (principles of diagnosis and management). 4th ed. Philadelphia: Butterworth Heinemann, 2004.
  • 25 Lancman ME, Brotherton TA, Asconapé JJ, Penry JK. Psychogenic seizures in adults: a longitudinal study. Seizure 1993;2(4):281-6. http://dx.doi.org/10.1016/S1059-1311(05)80141-4
  • 26 Chen DK, So YT, Fisher RS. Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcomittee of the American Academy of Neurology. Neurology 2005;65(5):668-75. ttp://dx.doi.org/10.1212/01.wnl.0000178391.96957.d0
  • 27 Shah AK, Shein N, Fuerst D, Yangala R, Shah J, Watson C. Peripheral WBC count and serum prolactin level in various seizure types and nonepileptic events. Epilepsia 2001;42(11):1472-5. http://dx.doi.org/10.1046/j.1528-1157.2001.11901.x