The Possible Role of Cerebrolysin in Prevention of Hemorrhagic Transformation after Acute Ischemic Stroke
International Neuropsychiatric Disease Journal, Volume 19, Issue 1,
Hemorrhagic transformation (HT) is one of the most feared challenges in management of acute ischemic stroke (AIS) that affects both the treatment plan and the clinical prognosis. The risk for HT is not monocausal and it is almost impossible to define a single target for prevention of HT. Thus, we consider that it is worthwhile to investigate and review the possible role of Cerebrolysin as a multimodal, pleiotropic neuroprotective and neurotrophic agent in the prevention of HT. Cerebrolysin has been the subject of multiple animal and in vitro studies, the majority of which have yielded encouraging results in terms of pleiotropic and multimodal neuroprotective and neurorestorative activity.
Cerebrolysin has been investigated in multiple clinical trials. Over the past 10 years, among the studies investigating the effect of Cerebrolysin in acute ischemic stroke, 5 studies have reported the extent of hemorrhagic transformation as a part of the outcome. Lower HT rates were reported for Cerebrolysin treated patients versus controls across all studies. Thus, the reported results are consistent across all studies, however, the differences did not reach the level of statistical significance except for one study.
The interpretation of these results is limited by several considerations. Despite these limitations, in the light of the clearly positive clinical results of Cerebrolysin on functional recovery and its favorable safety profile, a dose of 30 ml/day for 10-21 days may be given to reduce the risk of HT. This observation should be confirmed by further large randomized controlled clinical trials with standardization of the HT definition.
- hemorrhagic transformation
- acute ischemic stroke
How to Cite
Poljakovic Z, Supe S, Ljevak J, Starcevic K, Peric I, Blazevic N, Krbot-Skoric M, Jovanovic I, Ozretic D. Efficacy and safety of Cerebrolysin after futile recanalisation therapy in patients with severe stroke. Clinical Neurology and Neurosurgery. 2021 Aug 1;207:106767.
Elsaid N, Mustafa W, Saied A. Radiological predictors of hemorrhagic transformation after acute ischemic stroke: An evidence-based analysis. The Neuroradiology Journal. 2020;33(2):118-133. DOI:10.1177/1971400919900275
Yassi N, Parsons M, Christensen S, et al. Prediction of poststroke hemorrhagic transformation using computed tomography perfusion. Stroke. 2013;44: 3039–3043.
Zhang J, Yang Y, Sun H, et al. Hemorrhagic transformation after cerebral infarction: Current concepts and challenges. Ann Transl Med. 2014; 2: 81.
Arboix A, Jiménez C, Massons J, Parra O, Besses C. Hematological disorders: a commonly unrecognized cause of acute stroke. Expert review of Hematology. 2016 Sep 1;9(9):891-901.
Elsaid N, Bigliardi G, Dell’Acqua ML, et al. The role of automated computed topography perfusion in prediction of hemorrhagic transformation after acute ischemic stroke. The Neuroradiology Journal. 2022;0(0). DOI:10.1177/19714009221111084
Staszewski J, Ste¸ pien´ A, Piusin´ ska-Macoch R, De¸ biec A, Gniadek-Olejniczak K, Frankowska E, Maliborski A, Chadaide Z, Balo D, Król B, Namias R, Harston G, Mróz J and Piasecki P. Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion: Study Protocol for a Prospective, Open Label, Single-Center Study With 12 Months of Follow-Up. Front. Neurol. 2022;13:910697. DOI: 10.3389/fneur.2022.910697
Otero-Ortega L, Gutiérrez-Fernández M, Díez-Tejedor E. Recovery after stroke: new insight to promote brain plasticity. Front Neurol. 2021;12:768958. DOI: 10.3389/fneur.2021.768958
Philip M, Benatar M, Fisher M, Savitz SI. Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials. Stroke. 2009;40:577–81. DOI: 10.1161/STROKEAHA.108.524330
Xiong XY, Liu L, Yang QW. Refocusing neuroprotection in cerebral reperfusion era: new challenges and strategies. Front Neurol. 2018;9:249. DOI: 10.3389/fneur.2018.00249
Ayer A, Hwang BY, Appelboom G, Connolly ES Jr. Clinical trials for neuroprotective therapies in intracerebral hemorrhage: a new roadmap from bench to bedside. Transl Stroke Res. (2012) 3:409–17. DOI: 10.1007/s12975-012-0207-4
Wang L, Xiong X, Zhang L, Shen J. Neurovascular unit: a critical role in ischemic stroke. CNS Neurosci Ther. 2021;27:7–16. DOI: 10.1111/cns.13561
Heiss WD, Brainin M, Bornstein NM, Tuomilehto J, Hong Z. Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Stroke. 2012 Mar;43(3):630-6.
Brainin M. Cerebrolysin: A multi-target drug for recovery after stroke. Expert Rev Neurother. (2018) 18:681–7. DOI: 10.1080/14737175.2018.1500459
Zhang L, Chopp M, Meier DH, Winter S, Wang L, Szalad A, et al. Sonic hedgehog signaling pathway mediates cerebrolysin improved neurological function after stroke. Stroke. 2013;44:1965–72. DOI: 10.1161/str.44.suppl_1.AWMP36
Muresanu DF, Livint Popa L, Chira D, Dabala V, Hapca E, Vlad I, et al. Role and impact of cerebrolysin for ischemic stroke care. J Clin Med. 2022;11:1273. DOI: 10.3390/jcm11051273
Teng H, Li C, Zhang Y, Lu M, Chopp M, Zhang ZG, et al. Therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability. Neuroreport. 2021;32:359–66. DOI: 10.1097/WNR.0000000000001598
Chang WH; Lee J, Shin YI, Ko MH, Kim DY, Sohn MK, Kim J, Kim YH. Cerebrolysin Combined with Rehabilitation Enhances Motor Recovery and Prevents Neural Network Degeneration in Ischemic Stroke Patients with Severe Motor Deficits. J. Pers. Med. 2021;11:545.
Chang WH, Park C, Kim DY, Shin YI, Ko MH, Lee A, Jang SY, Kim YH. Cerebrolysin Combined with Rehabilitation Promotes Motor Recovery in Patients with Severe Motor Impairment after Stroke. BMC Neurol. 2016;16:31.
Xue LX, Zhang T, Zhao YW, Geng Z, Chen JJ, Chen H. Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: effects on neurological and behavioral outcomes in acute ischemic stroke. Experimental and Therapeutic Medicine. 2016;11(5):2015-20.
Lang W, Stadler CH, Poljakovic Z, Fleet D, Lyse Study Group. A prospective, randomized, placebo-controlled, double-blind trial about safety and efficacy of combined treatment with alteplase (rt-PA) and Cerebrolysin in acute ischaemic hemispheric stroke. International Journal of Stroke. 2013 Feb;8(2):95-104.
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. Journal of medicine and life. 2017 Oct;10(4):216.
Tran L, Alvarez XA, Le HA, Nguyen DA, Le T, Nguyen N, Nguyen T, Nguyen T, Vo T, Tran T, Duong C. Clinical Efficacy of Cerebrolysin and Cerebrolysin plus Nootropics in the Treatment of Patients with Acute Ischemic Stroke in Vietnam. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2022 Aug 1;21(7):621-30.
Muresanu DF, Heiss WD, Hoemberg V, Bajenaru O, Popescu CD, Vester JC, Rahlfs VW, Doppler E, Meier D, Moessler H, Guekht A. Cerebrolysin and Recovery After Stroke (CARS) A randomized, placebo-controlled, double-blind, multicenter trial. Stroke. 2016 Jan; 47(1):151-9.
Guekht A, Heiss D, Gusev E, Vester J, Doppler E, Muresanu D. Cerebrolysin and recovery after stroke (CARS 2): a randomized, placebo-controlled, double-blind, multicenter clinical study. Journal of the Neurological Sciences. 2015 Oct 15;357:e103.
Rezaei Y, Amiri-Nikpour MR, Nazarbaghi S, Ahmadi-Salmasi B, Mokari T, Tahmtan O. Cerebrolysin Effects on Neurological Outcomes and Cerebral Blood Flow in Acute Ischemic Stroke. Neuropsychiatr. Dis. Treat. 2014;10: 2299.
Rudilosso S, Rodríguez-Vázquez A, Urra X, Arboix A. The potential impact of neuroimaging and translational research on the clinical management of lacunar stroke. International journal of molecular sciences. 2022;23(3):1497.
Abstract View: 34 times
PDF Download: 10 times