UKRAINS'KYI VISNYK PSYKHONEVROLOHII

The Scientific and Practical Journal of Medicine
ISSN 2079-0325(p)
DOI 10.36927/2079-0325
Home » Archive of numbers » 2023 » Volume 31, issue 2 (115) » SAFETY OF CEREBROLYSIN FOR NEURORECOVERY AFTER ACUTE ISCHEMIC STROKE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF TWELVE RANDOMIZED-CONTROLLED TRIALS

SAFETY OF CEREBROLYSIN FOR NEURORECOVERY AFTER ACUTE ISCHEMIC STROKE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF TWELVE RANDOMIZED-CONTROLLED TRIALS

Authors

Type of Article

  • Scientific Article

In the Section

  • EVIDENCE-BASED RESEARCH

Key words

Index UDK:
  • 616.831-005.1:616-092.9-036.66:615.217.34

Abstract

We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Database of Systematic Reviews and clinical trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios and their 95 % confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of serious adverse events, as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (risk ratio = 0.6). We observed a tendency of superiority of Cerebrolysin regarding serious adverse events in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.

Pages

  • 84-92

Year / Issue

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References

  1. Gorelick P.B. The Global Burden of  Stroke: Persistent and Disabling. Lancet Neurol. 2019. 18. 417-418.
  2. Markus H.S., Brainin M. COVID-19 and Stroke — A Global World Stroke Organization Perspective. Int. J. Stroke. 2020. 15. 361-364.
  3. Gache K., Leleu H., Nitenberg G., Woimant F., Ferrua M., Minvielle Main Barriers to  Effective Implementation of  Stroke Care Pathways in France: A Qualitative Study. BMC Health Serv. Res. 2014. 14. 95.
  4. Brainin M. Cerebrolysin: A Multi-Target Drug for Recovery after Stroke. Expert Rev. Neurother. 2018. 18. 681-687.
  5. Muresanu D.F., Strilciuc S., Stanу A. Current Drug Treatment of Acute Ischemic Stroke: Challenges and Opportunities. CNS Drugs. 2019. 33. 841-847.
  6. Muresanu D.F. Neuromodulation with Pleiotropic and Multimodal Drugs — Future Approaches to Treatment of Neurological Disorders. In Proceedings of  the Brain Edema XIV. Czernicki Z., Baethmann A., Ito U., Katayama Y., Kuroiwa T., Mendelow D., Eds.; Vienna, Austria: Springer, 2010. Р. 291-294.
  7. Muresanu D.F., Ciurea A.V., Gorgan R.M., Gheorghita E., Florian S.I., Stan H., Blaga A., Ianovici N., Iencean S.M., Turliuc D. et A  Retrospective, Multi-Center Cohort Study Evaluating the Severity-Related Effects of  Cerebrolysin Treatment on  Clinical Outcomes in  Traumatic Brain Injury. CNS Neurol. Disord. Drug Targets. 2015. 14. 587-599.
  8. Taylor E.M. The Impact of  Efflux Transporters in  the Brain on  the Development of  Drugs for CNS Disorders. Clin. Pharm. 2002. 41. 81-92.
  9. Muresanu D.F., Heiss W.-D., Hoemberg V., Bajenaru O., Popescu C.D., Vester J.C., Rahlfs V.W., Doppler E., Meier D., Moessler H. et al. Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial. Stroke. 2016. 47. 151-159.
  10. Stan A., Birle C., Blesneag A., Iancu M. Cerebrolysin and Early Neurorehabilitation in Patients with Acute Ischemic Stroke: A Prospective, Randomized, Placebo-Controlled Clinical Study. J. Med. Life. 2017. 10. 216-222.
  11. Beghi E., Binder H., Birle C., Bornstein N., Diserens K., Groppa S., Homberg V., Lisnic V., Pugliatti M., Randall G. et European Academy of  Neurology and European Federation of  Neurorehabilitation Societies Guideline on  Pharmacological Support in Early Motor Rehabilitation after Acute Ischaemic Stroke. Eur. J. Neurol. 2021. 28. 2831-2845.
  12. Platz T. Rehabilitative Therapy for Arm Paresis Following a Stroke. 2020. Available online: https://www.awmf.org/leitlinien/detail/ll/080-001.html  (accessed on 10 October 2021).
  13. Teasell R., Hussein N., Mirkowski M., Vanderlaan D., Saikaley M., Longval M., Iruthayarajah J. Stroke Rehabilitation Clinician Handbook. 2020. Available online: http://www.ebrsr.com/sites/default/files/EBRSR%20Handbook%20Chapter%204_Upper%20Extremity%20Post%20Stroke_ML.pdf (accessed on 10 October 2021).
  14. Bornstein N.M., Guekht A., Vester J., Heiss W.-D., Gusev E., Homberg V., Rahlfs V.W., Bajenaru O., Popescu B.O., Muresanu D. Safety and Efficacy of Cerebrolysin in Early Post-Stroke Recovery: A Meta-Analysis of  Nine Randomized Clinical Trials. Neurol. Sci. 2018. 39. 629-640.
  15. Ziganshina L.E., Abakumova T., Vernay L. Cerebrolysin for Acute Ischaemic Stroke. Cochrane Database Syst. Rev. 2016. 12. CD007026.
  16. Strilciuc S. Safety of Cerebrolysin for Neurorecovery after Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Twelve Randomized-Controlled Trials. OSF Registry. 2021.
  17. Gharagozli K., Harandi A.A., Houshmand S., Akbari N., Muresanu D.F., Vester J., Winter S., Moessler H. Efficacy and Safety of Cerebrolysin Treatment in Early Recovery after Acute Ischemic Stroke: A Randomized, Placebo-Controlled, Double-Blinded, Multicenter Clinical Trial. J. Med. Life. 2017. 10. 153-160.
  18. Heiss W.-D., Brainin M., Bornstein N.M., Tuomilehto J., Hong Cerebrolysin Acute Stroke Treatment in  Asia (CASTA) Investigators Cerebrolysin in Patients with Acute Ischemic Stroke in Asia: Results of a Double-Blind, Placebo-Controlled Randomized Trial. Stroke. 2012. 43. 630-636.
  19. Lang W., Stadler C.H., Poljakovic Z., Fleet D.; Lyse Study Group. A Prospective, Randomized, Placebo-Controlled, DoubleBlind Trial about Safety and Efficacy of Combined Treatment with Alteplase (Rt-PA) and Cerebrolysin in Acute Ischaemic Hemispheric Stroke. Int. J. Stroke. 2013. 8. 95-104.
  20. Guekht A., Vester J., Heiss W.-D., Gusev E., Hoemberg V., Rahlfs V.W., Bajenaru O., Popescu B.O., Doppler E., Winter S. et al. Safety and Efficacy of Cerebrolysin in  Motor Function Recovery after Stroke: A Meta-Analysis of the CARS Trials. Neurol. Sci. 2017. 38. 1761-1769.
  21. Ladurner G., Kalvach P., Moessler H., Cerebrolysin Study Group. Neuroprotective Treatment with Cerebrolysin in Patients with Acute Stroke: A Randomised Controlled Trial. J. Neural. Transm. 2005. 112. 415-428.
  22. Skvortsova V.I., Stakhovskaia L.V., Gubskii L.V., Shamalov N.A., Tikhonova I.V., Smychkov A.S. A randomized, double-blind, placebo-controlled study of  Cerebrolysin safety and efficacy in  the treatment of acute ischemic stroke. Zhurnal Nevrol. I Psikhiatrii Im. S.S. Korsakova. 2004. 104. 51-55.
  23. Shamalov N.A., Stakhovskaia L.V., Burenchev D.V., Kichuk I.V., Tvorogova T.V., Botsina A.I., Smychkov A.S., Kerbikov O.B., Moessler H., Novak P. et al. The effect of cerebrolysin in dosage 50 ml on the volume of lesion in ischemic stroke. Zhurnal Nevrol. I Psikhiatrii Im. S.S. Korsakova. 2010. 110. 34-37.
  24. Amiri-Nikpour M.R., Nazarbaghi S., Ahmadi-Salmasi B., Mokari T., Tahamtan U., Rezaei Y. Cerebrolysin Effects on Neurological Outcomes and Cerebral Blood Flow in Acute Ischemic Stroke. Neuropsychiatr. Dis. Treat. 2014. 10. 2299-2306.
  25. Chang W.H., Park C., Kim Y., Shin Y.-I., Ko  M.-H., Lee  A., Jang  S.Y., Kim Y.-H. Cerebrolysin Combined with Rehabilitation Promotes Motor Recovery in Patients with Severe Motor Impairment after Stroke. BMC Neurology. 2016. 16. 31.
  26. Xue L.-X., Zhang T., Zhao Y.-W., Geng Z., Chen J.-J., Chen H. Efficacy and Safety Comparison of DL-3-n-Butylphthalide and Cerebrolysin: Effects on  Neurological and Behavioral Outcomes in Acute Ischemic Stroke. Exp. Ther. Med. 2016. 11. 2015-2020.
  27. Nilanont Y., Komoltri C., Saposnik G., Cote R., Di Legge S., Jin Y., Prayoonwiwat N., Poungvarin N., Hachinski V. The Canadian Neurological Scale and the NIHSS: Development and Validation of a Simple Conversion Model. Cereb. Dis. 2010. 30. 120-126.
  28. Popa-Wagner Dietary Habits, Lifestyle Factors and Neurodegenerative Diseases. Available online: https://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=3;spage=394;epage=400;aulast=Popa%2DWagner (accessed on 3 December 2021).

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UKRAINS'KYI VISNYK PSYKHONEVROLOHII

The Scientific and Practical Journal of Medicine

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