Assessment of Serum Cystatin C Level and Neuroprotection Under Levetiracetam Monotherapy in Patients with Epilepsy

Year 2022, Volume: 3 Issue: 2, 98 - 104, 16.09.2022

Fatma Şimşek , Seda Aşkın

https://doi.org/10.56766/ntms.1108819

Abstract

Aim: Cystatin C is a cysteine protease inhibitor that has been shown to have antiviral, antibacterial and neuroprotective efficacy. The aim of this study is to assess the effect of levetiracetam monotherapy on serum cystatin C levels and the neuroprotective efficacy thereof in patients with epilepsy.
Material and Methods: 30 patients, who were diagnosed with epilepsy for the first time and subsequently started on levetiracetam monotherapy, were included in the study as the study group, whereas 30 healthy volunteers were included in the study as the control group. Serum cystatin C and creatinine levels of patients were measured twice, once before they were started on the levetiracetam treatment and once after the completion of six months of treatment levetiracetam, whereas the serum cystatin C and creatinine levels of the healthy control subjects were measured once.
Results: Both the pre-treatment and post-treatment creatinine levels of epilepsy patients were found to be statistically significantly higher compared to the creatinine levels of the healthy control subjects. The pre-treatment and post-treatment serum cystatin C levels of epilepsy patients were found to be lower compared to the serum cystatin C levels of the healthy control subjects, albeit not statistically significantly. Additionally, serum cystatin C levels of epilepsy patients were found to have increased after the completion of the levetiracetam treatment, even though not statistically significantly.
Conclusion: The increase observed in the cystatin C levels, which is a neuroprotective agent, in epilepsy patients following the completion of the levetiracetam treatment indicates that levetiracetam has neuroprotective activity.

Keywords

Levetiracetam, epilepsy, cystatin c

References

• 1. Wakita M, Kotani N, Kogure K, Akaike N. Inhibition of Excitatory Synaptic Transmission in Hippocampal Neurons by Levetiracetam Involves Zn2+-Dependent GABA Type A Receptor–Mediated Presynaptic Modulation. J Pharmacol Exp Ther 2014;348(2):246–59.
• 2. Carunchio I, Pieri M, Ciotti MT, Albo F, Zona C. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia 2007;48(4):654–62.
• 3. Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 2004;43(11):707–24.
• 4. Bobek LA, Levine MJ. Cystatins - Inhibitors of Cysteine Proteinases. Crit Rev Oral Biol Med 1992;3(4):307–32. 5. Rule AD, Bailey KR, Lieske JC, Peyser PA, Turner ST. Estimating the glomerular filtration rate from serum creatinine is better than from cystatin C for evaluating risk factors associated with chronic kidney disease. Kidney Int 2013;83(6):1169–76.
• 6. Shardlow A, McIntyre NJ, Fraser SDS, et al. The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: A primary care cohort study. PLoS Med 2017;14(10):e1002400. 7. Kyhse-Andersen J, Schmidt C, Nordin G, et al. Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem 1994;40(10):1921–6.
• 8. Levy E, Jaskolski M, Grubb A. The role of cystatin C in cerebral amyloid angiopathy and stroke: cell biology and animal models. Brain Pathol 2006;16(1):60–70.
• 9. Sundelof J, Arnlov J, Ingelsson E, et al. Serum cystatin C and the risk of Alzheimer disease in elderly men. Neurology 2008;71(14):1072–9.
• 10. Ishimaru H, Ishikawa K, Ohe Y, Takahashi A, Maruyama Y. Cystatin C and apolipoprotein E immunoreactivities in CA1 neurons in ischemic gerbil hippocampus. Brain Res 1996;709(2):155–62.
• 11. Lukasiuk K, Pirttila TJ, Pitkanen A. Upregulation of cystatin C expression in the rat hippocampus during epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy. Epilepsia 2002;43 Suppl 5:137–45.
• 12. Aronica E, van Vliet EA, Hendriksen E, Troost D, da Silva FHL, Gorter JA. Cystatin C, a cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy. Eur J Neurosci 2001;14(9):1485–91.
• 13. Tizon B, Sahoo S, Yu H, et al. Induction of Autophagy by Cystatin C: A Mechanism That Protects Murine Primary Cortical Neurons and Neuronal Cell Lines. PLoS One 2010;5(3):e9819.
• 14. Dulinska J, Setkowicz Z, Janeczko K, et al. Synchrotron radiation Fourier-transform infrared and Raman microspectroscopy study showing an increased frequency of creatine inclusions in the rat hippocampal formation following pilocarpine-induced seizures. Anal Bioanal Chem 2012;402(7):2267–74.
• 15. Rambo LM, Ribeiro LR, Schramm VG, et al. Creatine increases hippocampal Na(+),K(+)-ATPase activity via NMDA-calcineurin pathway. Brain Res Bull 2012;88(6):553–9.
• 16. Lee DH, Lee DW, Kwon JI, et al. In Vivo Mapping and Quantification of Creatine Using Chemical Exchange Saturation Transfer Imaging in Rat Models of Epileptic Seizure. Mol imaging Biol 2019;21(2):232–9.
• 17. Grubb A. Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clin Nephrol 1992;38 Suppl 1:S20-7.
• 18. Mecarelli O, Vicenzini E, Pulitano P, et al. Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. Ann Pharmacother 2004;38(11):1816–22.
• 19. Meador KJ, Gevins A, Loring DW, et al. Neuropsychological and neurophysiologic effects of carbamazepine and levetiracetam. Neurology 2007;69(22):2076–84.
• 20. Chuo LJ, Sheu WH, Pai MC, Kuo YM. Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease. Dement Geriatr Cogn Disord 2007;23(4):251–7.
• 21. Palmer S, Vecchio M, Craig JC, et al. Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Kidney Int 2013;84(1):179–91.
• 22. Wu L, Yan ZR, Jiang H, Xing HM, Li HH, Qiu CX. Serum cystatin C, impaired kidney function, and geriatric depressive symptoms among older people living in a rural area: a population-based study. BMC Geriatr 2018;18(1):1–8.
• 23. Minev E, Unruh M, Shlipak MG, et al. Association of cystatin C and depression in healthy elders: the health, aging and body composition study. Nephron Clin Pr 2010;116(3):c241-6.
• 24. Li HB, Wang AX, Qi G, et al. Cystatin C and risk of new-onset depressive symptoms among individuals with a normal creatinine-based estimated glomerular filtration rate: A prospective cohort study. Psychiatry Res 2019;273:75–81.
• 25. Fliser D, Ritz E. Serum cystatin C concentration as a marker of renal dysfunction in the elderly. Am J kidney Dis 2001;37(1):79–83.