Document Type : Original Article

Authors

1 Assistant Professor of Neurology, Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

2 Professor of Neurology, Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Professor of Neurology, Stroke Fellowship, Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

4 Resident of Neurology, Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

5 Ph.D. Candidate in Epidemiology, School of Public Health, Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Introduction: Some recent studies have shown that citicoline improves clinical symptoms in patients with stroke. Citicoline's mechanism of action in improving the clinical symptoms is not recognized yet. The aim of this study was to evaluate the cerebrovascular hemodynamic status in patients with ischemic stroke treated with citicoline compared with the control group.
Methods: In this study, 64 patients (20 male, 44 female) with supratentorial ischemic stroke were included. Patients underwent transcranial and extra cranial ultrasonography within 24 hours of admission and were divided into two equal groups (32 patients per group). One group was treated with citicoline (500 mg/day) and the second group was treated with placebo for one week. Then, patients underwent transcranial and extra cranial ultrasonography again. Data were analyzed by paired t-test and independent t-test.
Results: In this study, no significant difference between the groups in terms of age, gender, cardiovascular factors and NIHSS was observed. Peak systolic velocity (PSV) in RCCA, RICA, RVA, LVA, and mean flow velocity (MFV) in RICA and LACA were significantly different between two groups. As there was no significant difference in confounding variables between the two groups, therefore, the difference in PSV and MFV between the groups may be due to citicoline.
Conclusion: Prescription of citicoline for treatment of acute ischemic stroke is associated with hemodynamic changes in cerebral arteries. This finding can be one of the citicoline's mechanisms of action in ischemic stroke process.
 

Keywords

  1. Overgaard K. The effects of citicoline on acute ischemic stroke: a review. J Stroke Cerebrovasc Dis 2014; 23(7):1764-9.
  2. Mousavi SA, Khorvash F, Hoseini T. The efficacy of citroline in the treatment of ischemic stroke and primary hypertensive intracereral hemorrhage; a review article. ARYA Atheroscler 2010; 6(3):122-5.
  3. Bustamante A, Giralt D, Garcia-Bonilla L, Campos M, Rosell A, Montaner J. Citicoline in pre-clinical animal models of stroke: a meta-analysis shows the optimal neuroprotective profile and the missing steps for jumping into a stroke clinical trial. J Neurochem 2012; 123(2):217-25.
  4. Hurtado O, Hernandez-Jimenez M, Zarruk JG, Cuartero MI, Ballesteros I, Camarero G, et al. Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke. J Neurochem 2013; 126(6):819-26.
  5. Sobrino T, Rodriguez-Gonzalez R, Blanco M, Brea D, Perez-Mato M, Rodriguez-Yanez M, et al. CDP-choline treatment increases circulating endothelial progenitor cells in acute ischemic stroke. Neurol Res 2011; 33(6):572-7.
  6. Alvarez-Sabin J, Roman GC. The role of citicoline in neuroprotection and neurorepair in ischemic stroke. Brain Sci 2013; 3(3):1395-414.
  7. Cho HJ, Kim YJ. Efficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases. Methods Find Exp Clin Pharmacol 2009; 31(3):171-6.
  8. Alvarez-Sabin J, Ortega G, Jacas C, Santamarina E, Maisterra O, Ribo M, et al. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovasc Dis 2013; 35(2):146-54.
  9. Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, Sabounjian L, et al. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol 2000; 48(5):713-22.
  10. Kern R, Nagayama M, Toyoda K, Steiner T, Hennerici MG, Shinohara Y. Comparison of the European and Japanese guidelines for the management of ischemic stroke. Cerebrovasc Dis 2013; 35(5):402-18.
  11. Mitta M, Goel D, Bansal KK, Puri P. Edaravone - citicoline comparative study in acute ischemic stroke (ECCS-AIS). J Assoc Physicians India 2012; 60:36-8.
  12. Secades JJ, Alvarez-Sabin J, Castillo J, Diez-Tejedor E, Martinez-Vila E, Rios J, et al. Citicoline for acute ischemic stroke: a systematic review and formal meta-analysis of randomized, double-blind, and placebo-controlled trials. J Stroke Cerebrovasc Dis 2016; 25(8):1984-96.
  13. Davalos A, Alvarez-Sabin J, Castillo J, Diez-Tejedor E, Ferro J, Martinez-Vila E, et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet 2012; 380(9839):349-57.
  14. Lee W. General principles of carotid Doppler ultrasonography. Ultrasonography 2014; 33(1):11-7.
  15. Hamzei-Moghaddam A, Shafa MA, Khanjani N, Farahat R. Frequency of opium addiction in patients with ischemic stroke and comparing their cerebrovascular Doppler ultrasound changes to non-addicts. Addiction & Health 2013; 5(3-4):95-101.
  16. Shafa MA, Seifaddini R, Iranmanesh F. Association between serum uric acid level and stenosis in Atherothrombotic infarction. Journal of Kerman University of Medical Sciences 2017; 24(1):68-77.
  17. Iranmanesh F, Vakilian A. Efficiency of citicoline in increasing muscular strength of patients with nontraumatic cerebral hemorrhage: a double-blind randomized clinical trial. J Stroke Cerebrovasc Dis 2008; 17(3):153-5.
  18. Clark WM, Williams BJ, Selzer KA, Zweifler RM, Sabounjian LA, Gammans RE. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 1999; 30(12):2592-7.
  19. Dávalos A, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Ferro J, Martínez-Vila E, et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). The Lancet 2012; 380(9839):349-57.
  20. Alvarez-Sabin J, Ortega G, Jacas C, Santamarina E, Maisterra O, Ribo M, et al. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovasc Dis 2013; 35(2):146-54.
  21. Clark WM, Wechsler LR, Sabounjian LA, Schwiderski UE. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 2001; 57(9):1595-602.
  22. Casado A, Secades JJ, Ibarz R, Herdman M, Brosa M. Cost-effectiveness of citicoline versus conventional treatment in acute ischemic stroke. Expert Rev Pharmacoecon Outcomes Res 2008; 8(2):151-7.
  23. Diederich K, Frauenknecht K, Minnerup J, Schneider BK, Schmidt A, Altach E, et al. Citicoline enhances neuroregenerative processes after experimental stroke in rats. Stroke 2012; 43(7):1931-40