Discussion
post-stroke, axonal and myelin damage, stroke, AIS, neurological deficit, HT, rtPA, intracranial hemorrhagic
DRUG-DRUG INTERACTION, STROKE, SECONDARY, EVENTS
The results of this randomized, open-label, multicenter pilot trial in stroke patients demonstrate beneficial effects of Cerebrolysin as an early add-on to IVT on the primary (the rate of symptomatic HT) and secondary (early neurological recovery) endpoints. Although we found a significant improvement in the DTI and PS values of the infarcted area, this treatment approach did not affect the long-term functional outcome.A variety of composite scores to predict HT in AIS patients have been published [The risk of HT is established to be the highest on day 1 after stroke onset, and it keeps being significant for the next 14 days [Cerebrolysin treatment was started simultaneously with IVT and continued for 2 weeks. This approach seems to be safe and could alleviate symptomatic intracranial hemorrhagic events and early neurological deficit. Moreover, the beneficial effects correlated with the positive changes in the imaging metrics, supporting the neuroprotective and BBB stabilizing activity of Cerebrolysin. Thus, our findings are strongly coherent with the initial rationale.However, the rate of symptomatic HT observed in our study was higher than it was reported in other IVT clinical trials [In a prospective open-label study of AIS patients with futile recanalization after rtPA, Poljakovic et al. have demonstrated a clear trend towards HT rate reduction in patients treated with Cerebrolysin [In a previous trial by Lang et al. (CERE-LYSE-1), the authors looked at the safety of Cerebrolysin administered 1 h after rtPA infusion for 10 consecutive days as well as at short- and long-term functional outcomes in AIS patients, but not at HT [While our data on short-term neurological recovery confirms the results of previous trials [The ESCAPE-NA1 trial, a large-scale study of the neuroprotective agent nerinetide, failed to demonstrate an improvement in the long-term post-stroke functional outcome due to a possible drug-drug interaction with alteplase [AD and RD could serve as in vivo surrogate markers of axonal and myelin damage, respectively [PS is a known imaging marker of BBB permeability. The more PS rises following AIS, the higher the risk of HT [The strength of the study came in simultaneous use of Cerebrolysin and rtPA followed by a combined assessment of clinical and advance brain imaging data in AIS patients, which has demonstrated multimodal effects of Cerebrolysin on brain recovery and HT prevention in the clinical settings.However, our research had several limitations. It was not blinded, and standard medical care was applied to both groups.Moreover, the sample size was relatively small. As a consequence, the imbalance in some covariates did occur which could be expected since exact balance is a large-sample property [The study was also limited in terms of ethnic and racial diversity. The majority of the participants were of Russian, Tatar, and Jewish ethnic groups with no patients of African, Asian or Hispanic origin.The analysis of DTI and CTP data was confined to a single slice. As a result, our assessment of the infarcted area was restricted. Moreover, our selection criteria for the advanced brain imaging could be a source of potential bias.Therefore, additional large-scale clinical trials are warranted to confirm our findings.