Cerebrolysin

BACKGROUND: The main objective of the Cerebrolysin REGistry Study in Stroke 2 (C-REGS2) was to systematically record the routine clinical use of Cerebrolysin in patients with moderate ischemic stroke (IS) following the principles of a prospective controlled effectiveness study (CES) to compare its effectiveness in terms of functional recovery to patients treated with standard therapy alone. METHODS: C-REGS2 used an open-label, prospective controlled comparative effectiveness design aligning with the Target Trial Emulation Framework (TTEF) and the GRACE principles for high-quality observational studies based on the principles of high-quality comparative effectiveness research (HQCER) to capture treatment effects in clinical practice. The study was conducted in 16 countries worldwide between April 2018 and April 2024. Moderate IS was defined as baseline NIH Stroke Scale (NIHSS) score 8-15. Treatment modalities and concomitant medications were according to local standards. The methodology included rigorous pre-specified analysis and tight risk-based centralized monitoring, to ensure minimal enrollment bias, maximize data quality and overall reliability of trial results. The compared patient groups were standardized using a restricted cohort design and non-parametric multilevel stratification following the Good Research for Comparative Effectiveness (GRACE) principles. The primary endpoint was ordinal analysis of the modified Rankin Scale (mRS) at 90 days after stroke onset. Secondary endpoints were the ordinal NIH Stroke Scale (NIHSS) at day 21 and 90 after stroke onset, the ordinal mRS at 21 days after IS, the proportion of patients with excellent recovery (mRS 0-1) as well as the proportion of patients with functional independence (mRS 0-2) at 90 days after stroke onset and the ordinal analysis of Montreal Cognitive Assessment (MoCA) scale at 90 days after IS. RESULTS: Out of 1865 enrolled patients, the target population (TP) comprised 1769 patients (1021 Cerebrolysin-treated and 748 controls). The median NIHSS at baseline was 10.0. Median Cerebrolysin dose was 30 ml, median treatment duration was 10 days. Cerebrolysin was superior to standard therapy in the primary endpoint independently to prior thrombolysis (MW 0.6157; confidence interval (CI) 0.5910-0.6404; P < 0.0001) as well as in all secondary endpoints: mRS at day 21 (MW 0.6065, 95% CI 0.5811-0.6319, P < 0.0001), NIHSS at day 21 (MW 0.5792; 95% CI 0.5576-0.6008; P < 0.0001) and NIHSS at day 90 (MW 0.5781; CI 0.5561-0.6002; P < 0.0001). Additional pre-specified secondary endpoints (proportion of patients with excellent recovery and functional independence) showed moderate superiority for Cerebrolysin. The ordinal MoCA showed superiority for Cerebrolysin in the TP (MW 0.5530; CI 0.5282-0.5778; P < 0.0001) with more pronounced effects in the subgroup with cognitive impairments at baseline (Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) ⩾ 3.3). No differences in safety measures were recorded. The study is notable for its robust data integrity, with valid entries of 90.9% for the primary 90 day mRS assessment with multilevel case mix standardization and an overall dropout rate to the final visit of only 5.7%. CONCLUSION: The results of the C-REGS2 study showed the effectiveness and safety of Cerebrolysin treatment for moderate acute IS in real-world clinical practice.

AIM: To evaluate the efficacy and safety of Cerebrolysin (EVER Neuro Pharma GmbH, Austria) in the treatment of patients with multiple sclerosis (MS) in stage of relapse regression. MATERIAL AND METHODS: The study involved 40 patients with remitting MS (McDonald criteria 2010) in stage of MS relapse regression after pulse therapy with methylprednisolone 1000 mg/day 5. Patients randomized into 2 groups: group 1 (G1, n=20) received cerebrolysin 20 ml per 200 ml of 0.9% NaCl solution 1 times per day 10; Group 2 (G2, n=20) - only 200 ml 0.9% NaCl solution on analogical scheme. All patients before and 3-4 weeks after the treatment were carried out assessment of vital signs, routine laboratory tests, tests of cognitive-motor functions (SDMT), visual acuity (LCAT), a comprehensive neurophysiological examinations (CNE). 4 patients in the G1 with presence of previously identified G+ lesions (G+L) were conducted MRI of brain after 3-4 weeks after treatment. RESULTS: In G1 the average age of the patients was 27.35 (5.65) years, the ratio of M/F - 40/60%, the duration of the disease 29.9 (11.01) months, the EDSS in relapse stage - 3.5 [2.0; 4.5] points. The average age of patients in G2 was 26.65 (4.93) years, the ratio of M/F - 35/65%, the duration of the disease - 30.25 (11.98) months, the EDSS in relapse stage - 3.0 [1.5; 4.5] points. Clinical relapse of MS was categorized into groups as follows: optic neuritis (15% vs. 30%; p=0.26), stem dysfunction (15% vs. 25%; p=0.43), hemispheric dysfunction (50% vs. 35%; p=0.34), transverse myelitis (20% vs. 10%; p=0.38). 17 patients (85%) in G1 and 18 patients (90%) in G2 completed a full course of treatment. In both groups showed significant regression estimation EDSS (2.0 [1.75; 2.5] vs. 2.5 [1.75; 2.5]), while significant intergroup differences were not found (p=0.665). In G1 was noted more pronounced dynamics of performance improved in testing MSFC and SDMT (p=0.038 and p=0.026, respectively). Significant intergroup differences in the dynamics of improvement VCAT values were not found (p=0.658). Also in G1 was revealed greater regression of total variance in the CNE than G2 (70.59% vs. 27.78%, p=0.028), while in almost all cases the previously identified neurophysiological abnormalities are not completely regressed. In addition to G1 was marked a tendency to reduce of progressive deterioration of CNE indicators (10% vs. 30%; p=0.228). On MRI cerebrolysin treatment was not associated with an increase of G+L (G+L number before treatment in 4 patients - 14, after treatment - 12), which indicates a potential anti-inducing effect of the drug on the intrathecal inflammation in MS. CONCLUSION: Cerebrolysin positive role in the stimulation of remyelination process in MS has been confirmed by CNE and the selected treatment regimen has demonstrated its safety. Effect of the drug appear to be due to its composition: so according to a group of authors found that investigated the drug contained fragments of tubulin, actin and myelin basic protein, all of which is necessary to ensure non-specific trophic regenerated CNS myelin sheath.

BACKGROUND: Cerebrolysin could mitigate reperfusion injury and hemorrhagic transformation (HT) in animal models of acute ischemic stroke. METHODS: This was a prospective, randomized, open-label, parallel-group with active control, multicenter pilot study. Cerebrolysin (30 mL/day over 14 days) was administered concurrently with alteplase (0.9 mg/kg) in 126 patients, whereas 215 control patients received alteplase alone. The primary outcomes were the rate of any and symptomatic HT assessed from day 0 to 14. The secondary endpoints were drug safety and functional outcome measured with the National Institutes of Health Stroke Scale (NIHSS) on day 1 and 14, and the modified Rankin scale (mRS) on day 90. Advanced brain imaging analysis was applied on day 1 and 14 as a marker for in vivo pharmacology of Cerebrolysin. RESULTS: Cerebrolysin treatment resulted in a substantial decrease of the symptomatic HT rate with an odds ratio (OR) of 0.248 (95% CI: 0.072-0.851; p = 0.019). No serious adverse events attributed to Cerebrolysin occurred. On day 14, the Cerebrolysin arm showed a significant decrease in the NIHSS score (p = 0.045). However, no difference in the mRS score was observed on day 90. A substantial improvement in the advanced brain imaging parameters of the infarcted area was evident in the Cerebrolysin group on day 14. CONCLUSIONS: Early add-on of Cerebrolysin to reperfusion therapy was safe and significantly decreased the rate of symptomatic HT as well as early neurological deficit. No effect on day 90 functional outcome was detected. Improvements in the imaging metrics support the neuroprotective and blood-brain barrier stabilizing activity of Cerebrolysin. TRIAL REGISTRATION: Name of Registry: ISRCTN. TRIAL REGISTRATION NUMBER: ISRCTN87656744 . Trial Registration Date: 16/02/2021.

STUDY DESIGN: Prospective randomized control trial. OBJECTIVE: To analyze outcomes following the injection of cerebrolysin in surgically treated patients with degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Previous research has concluded that superior functional outcomes are achieved with the use of cerebrolysin in surgically treated patients of DCM for 21 days. Our study has been conducted to analyze the use of this drug for a shorter duration (10 days) and compare its clinical efficacy. METHODS: Ninety operated cases of mild to severe DCM were randomized into two groups. Sixty patients received the injection Cerebrolysin for 10 days postoperatively. The remaining 30 patients received a placebo. Functional outcomes were measured using modified Japanese Orthopaedic Association (mJOA) scores and visual analogue scale (VAS). The American Spinal Injury Association (ASIA) scale was used to document neurological recovery. Hand function was assessed by measuring the grip strength and the upper limb function score the upper extremity motor mJOA plus upper extremity sensory mJOA score. Assessments were performed and preoperatively and postoperatively and at one-month, three-month, six-month, and one-year following surgery. RESULTS: Preoperative mJOA and VAS scores were comparable in both groups ( P >0.05). Both groups experienced an improvement in mJOA and VAS scores at all time-points during follow-up as compared with preoperative scores. However, the cerebrolysin group demonstrated significantly greater mJOA scores (16.37±1) when compared with the placebo (15.2±1.8) at one-year follow-up ( P <0.0001). Neurological improvement with cerebrolysin therapy was also superior ( P =0.04). No significant adverse reactions were documented. CONCLUSION: Injection cerebrolysin, when administered for 10 days postoperatively, can result in significantly greater neurological improvement and hand function in patients with DCM who also receive surgery.

STUDY DESIGN: Prospective randomized control trial. OBJECTIVE: The aim of this study was to analyze role of cerebrolysin in patients of degenerative cervical myelopathy (DCM) managed by surgical modalities. SUMMARY OF BACKGROUND DATA: Cerebrolysin has been extensively researched with variable success in neurodegenerative pathologies. There has been only one study in published literature till date that has studied role of cerebrolysin in DCM in conservatively managed patients but none in the patients treated surgically. We present our pilot study which analyzes the role of cerebrolysin in patients of DCM managed by surgical modalities. METHODS: This prospective randomized control trial was conducted at a tertiary care institute in Mumbai. Sixty operated cases of DCM were randomly divided into 2 groups. The first group was given Injection Cerebrolysin 5 mL diluted in 100 mL Normal Saline over 30 minutes once a day for 21 days postoperatively. The second group was given placebo. Modified Japanese Orthopedic Association scores (mJOA) and visual analog scale (VAS) were used to document functional outcomes at 3 weeks, 3 months, 6 months, and 1 year. Recovery of hand function was separately accessed by improvement in hand power and sensations. RESULTS: Preoperative mJOA and VAS scores were comparable between 2 groups. Both groups showed significant improvement in both mJOA and VAS scores at 3weeks, 3 months, 6 months and 1-year follow-up (P < 0.01). In comparing the two groups, there was no difference in improvement of mJOA and VAS scores. However, cerebrolysin group showed significant improvement in hand function at 1 year compared to the placebo. Postoperative neurological recovery was better in the cerebrolysin group with 66.7% patients showing complete neurological recovery compared to 56.7% for placebo, but this was statistically insignificant. Two patients developed headache and one patient complained of dizziness in the cerebrolysin group, but these resolved without any intervention. CONCLUSION: Use of cerebrolysin in postoperative cases of DCM is safe and results in improved hand function.Level of Evidence: 1.

INTRODUCTION: Endovascular recanalization therapy has demonstrated considerable efficacy in the treatment of acute ischemic stroke (AIS). However, not all patients appear to benefit on the long term from this therapy. No studies have assessed the role of Cerebrolysin following mechanical thrombectomy (MT). The present study was conducted to evaluate the safety and efficacy of Cerebrolysin as add-on treatment to MT in patients with cardioembolic AIS. METHODS: This study evaluated 150 patients admitted to the stroke unit. Data were prospectively collected from 75 patients with cardioembolic AIS and National Institutes of Health Stroke Scale (NIHSS) ≥10, who underwent successful MT ± recombinant tissue plasminogen activator (rt-PA). Patients fulfilling inclusion criteria were consecutively enrolled and treated with Cerebrolysin at a daily dose of 30 ml for 14 days, with treatment initiated within 8 h following MT. Patients were compared with a historical control group of 75 well-matched patients who underwent MT ± rt-PA but did not receive Cerebrolysin. The primary outcome measure was a favorable modified Rankin Scale (mRS = 0-2) at day 90. Secondary parameters included the NIHSS, the Montreal Cognitive Assessment (MoCA), the rate of hemorrhagic transformation, mortality, and adverse events. Propensity score matching was performed to match the variables between the compared groups. RESULTS AND DISCUSSION: The overall results demonstrated that patients treated with Cerebrolysin exhibited a significantly higher proportion of mRS scores of 0-2 at day 90 (64% vs. 34.7%) in comparison to the control group. This finding was consistent with lower NIHSS and mRS scores at all study visits, and a lower any hemorrhagic transformation rate (20% vs. 57.3%). Furthermore, the logistic regression analysis revealed that patients with favorable mRS scores were less likely to undergo hemorrhagic transformation (odds ratio = 2.75, 95% confidence interval = 1.17, 6.45; p = 0.002). The administration of Cerebrolysin as an add-on treatment resulted in a significant benefit for AIS patients following MT, characterized by an improvement in mRS and NIHSS scores, along with a reduced rate of hemorrhagic transformation. The administration of Cerebrolysin was safe and well tolerated. Further studies are required to confirm these results.