Cerebrolysin as an adjuvant therapy after mechanical thrombectomy in large vessel occlusion cardioembolic stroke: a propensity score matching analysis

 

Your competent? doctor has been using Cerebrolysin for years now, correct?

Cerebrolysin (14 posts to June 2014)

Cerebrolysin as an adjuvant therapy after mechanical thrombectomy in large vessel occlusion cardioembolic stroke: a propensity score matching analysis

Ahmed ElBassiouny¹Mohamed S. A. Shehata^2,3*Amr S. Zaki¹Rady Y. Bedros¹Ayman Hassan El-Sudany¹Azza Abdel Nasser¹

• ¹Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
• ²Faculty of Medicine, Zagazig University, Zagazig, Egypt
• ³Egyptian Fellowship of Neurology, Ministry of Health, Cairo, Egypt

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.

Speech Therapy Combined With Cerebrolysin in Enhancing Nonfluent Aphasia Recovery After Acute Ischemic Stroke: ESCAS Randomized Pilot Study

 Your competent? doctor has been using Cerebrolysin for years now, correct?

Cerebrolysin (13 posts to June 2014)

Speech Therapy Combined With Cerebrolysin in Enhancing Nonfluent Aphasia Recovery After Acute Ischemic Stroke: ESCAS Randomized Pilot Study

Volker Homberg, MD, PhD https://orcid.org/0009-0008-8449-8681, Dragoș Cătălin Jianu, MD, PhD https://orcid.org/0000-0002-7827-818X, Adina Stan, MD, PhD https://orcid.org/0000-0001-8856-4078, Ștefan Strilciuc, MPH, PhD https://orcid.org/0000-0001-6112-0223, Vlad-Florin Chelaru, MD https://orcid.org/0000-0003-2954-3263, Michał Karliński, MD, PhD https://orcid.org/0000-0001-6728-2020, Michael Brainin, MD, PhD https://orcid.org/0000-0001-8363-4962, Wolf Dieter Heiss, MD, PhD, Dafin F. Muresanu, MD, PhD https://orcid.org/0000-0002-9536-1153 office@ssnn.ro, and Pamela M. Enderby, PhD https://orcid.org/0000-0002-4371-9053Author Info & Affiliations

Stroke

New online

https://doi.org/10.1161/STROKEAHA.124.049834

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Abstract

BACKGROUND:

Stroke-induced aphasia significantly impacts communication and quality of life. Despite the standard treatment being speech and language therapy, outcomes vary, highlighting the need for additional therapies. Cerebrolysin, a neuroprotective and neurotrophic agent, has shown potential in stroke management. This study addresses the notable gap in research about the combined use of Cerebrolysin and speech therapy, evaluating their synergistic potential in the treatment of aphasia.

METHODS:

The ESCAS trial (The Efficacy and Safety of Cerebrolysin in the Treatment of Aphasia After Acute Ischemic Stroke), a prospective, randomized-controlled, double-blinded study was conducted in 2 Romanian stroke centers. Participants included those with left middle cerebral artery territory ischemic stroke and nonfluent aphasia, enrolled 3 to 5 days poststroke. Inclusion criteria were right-handedness and Romanian as the mother tongue. Participants received Cerebrolysin or a placebo combined with speech and language therapy in 10-day cycles over 3 intervals, and evaluations were done at baseline, 30, 60, and 90 days respectively. The main outcome measure was Western Aphasia Battery for language function. Changes at days 30, 60, and 90 compared with baseline were quantified, and the effect estimand used was the difference in means between groups. Secondary outcome measurements were the National Institutes of Health Stroke Scale for neurological deficit, the modified Rankin Scale for global disability, and the Barthel Index for activities of daily living.

RESULTS:

Out of 132 enrolled patients, 123 were included in the intention-to-treat analysis, and 120 in the per-protocol analysis. Overall, both groups showed improvement at subsequent visits compared with the baseline for Western Aphasia Battery and the National Institutes of Health Stroke Scale. The Cerebrolysin group showed greater improvements in Western Aphasia Battery (visit 4 mean increase of 35.579±16.316 [95% CI, 31.289–39.869] points; P<0.001) compared with the placebo group (20.774±12.486 [95% CI, 17.603–23.945] points; P<0.001), a difference in means of 14.805 (95% CI, 9.521–20.089) points (P<0.001). The Cerebrolysin group also showed significant improvements (higher decreases) in National Institutes of Health Stroke Scale scores compared with the placebo group (2.085 [95% CI, 1.076–3.094] points; P<0.001). Safety analysis raised no concerns (number of patients with adverse events P=0.105, number of adverse events per patient P=0.134). Additionally, the Cerebrolysin group showed greater improvements in functional independence (Barthel Index) and a trend toward reduced disability (modified Rankin Scale) compared with the placebo group.

CONCLUSIONS:

Cerebrolysin combined with speech and language therapy offers promising potential for enhancing recovery in poststroke nonfluent aphasia. Significant improvements were observed in language and neurological deficits, underscoring the importance of adjunctive therapies in nonfluent aphasia rehabilitation. Further research with larger cohorts is needed to fully establish the efficacy of this combination therapy.

REGISTRATION:

URL: https://www.isrctn.com; Unique identifier: ISRCTN54581790.

Graphical Abstract

Comparative Efficacy of Neuroprotective Agents for Improving Neurological Function and Prognosis in Acute Ischemic Stroke: A Network Meta-Analysis

 First of all, stop using the term, neuroprotection! Neuronal cascade of death is the correct term! It gives absolutely NO SENSE OF URGENCY! If you tell your patients, you know nothing about stopping  the 5 causes of the neuronal cascade of death in the first week thus letting die hundreds of millions to billions of neurons.  They might just get angry with your incompetence!

Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? I would like to know why you aren't solving stroke to 100% recovery, because this doesn't solve stroke recovery at all!

You'll have to ask your competent? doctor why the hell edaravone is approved in Japan since 2001 but not the US.

Has your stroke hospital done anything with any of these in the last decade? OR ARE THEY COMPLETELY FUCKING INCOMPENT AT EVERYTHING IN STROKE? 

 You can easily see how much research is out there to be implemented and your hospital is totally incompetent if not done. 

• Cerebrolysin (12 posts to June 2014)
• citicoline (15 posts to October 2011)

• minocycline (17 posts to May 2012)

• dl-NBP (1 post to April 2017)
• 
  
• NA-1 (5 posts to October 2012) 

• edaravone (12 posts to November 2011)

• Role of vinpocetine in ischemic stroke and poststroke outcomes: A critical review 2020

• Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature 2014

• A systematic review of vinpocetine therapy in acute ischaemic stroke 1999

• Vinpocetine inhibits NF-κB-dependent inflammation in acute ischemic stroke patients 2018

The latest here:

Comparative Efficacy of Neuroprotective Agents for Improving Neurological Function and Prognosis in Acute Ischemic Stroke: A Network Meta-Analysis

Yuchen Wang ^1,2 Mengqi Li ^1,2 Yuye Jiang ^1,2 Qiuhong JI ^1*

• ¹ Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
• ² School of Medicine, Nantong University, Nantong, Jiangsu Province, China

The final, formatted version of the article will be published soon.

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cause of combined disability and mortality globally. While reperfusion therapies play a critical role in the management of acute ischemic stroke (AIS), their applicability is limited, leaving many patients with significant neurological deficits and poor prognoses.Neuroprotective agents have garnered attention for their potential as adjunct therapies; however, their relative efficacy remains unclear. This study utilized a network metaanalysis (NMA) to systematically compare the efficacy of neuroprotective agents in improving neurological function and prognosis in stroke patients. Methods: This study adhered to PRISMA guidelines and the Cochrane Handbook for systematic reviews. Randomized controlled trials (RCTs) were identified through comprehensive searches of the PubMed, Embase, and Cochrane Library databases. Two independent reviewers conducted the selection process, data extraction, and quality assessment. Outcomes included 90-day modified Rankin Scale(90d-mRS)、change of National Institutes of Health Stroke Scale score from baseline to 90-day/14-day/7-day (90day/14d/7d-NIHSS) and 90-day/14-day Barthel Index (90d/14d-BI).Data analyses were performed using RevMan 5.4 and Stata 14.0. Results: A total of 42 RCTs involving 12,210 participants were included in this analysis. The interventions assessed included Cerebrolysin, Citicoline, Edaravone, Edaravone Dextranol, HUK, Minocycline, NA-1, NBP, Vinpocetine, and Control. The NMA results demonstrated that NBP ranked highest for the 90d-mRS, 90d-NIHSS, 14d-NIHSS, and 14d-BI outcomes. Edaravone was found to be the most effective intervention for the 7d-NIHSS and 90d-BI outcomes.The findings of this study indicate that different neuroprotective agents exhibit distinct advantages at specific stages of recovery. NBP showed outstanding performance in improving 90d-mRS and 90d-NIHSS, underscoring its potential in long-term rehabilitation. Edaravone demonstrated significant superiority in 7d-NIHSS scores, highlighting its role in early neuroprotection. These results provide valuable insights for individualized clinical treatment. To further validate the efficacy and safety of neuroprotective agents, future studies should involve larger sample sizes and conduct multicenter, large-scale randomized controlled trials.

Keywords: Neuroprotective Agents, Network meta-analysis, n-Butylphthalide, Edaravone, Neurological function, stroke rehabilitation

Received: 19 Nov 2024; Accepted: 13 Dec 2024.

Copyright: © 2024 Wang, Li, Jiang and JI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.   

Old Drug a New Option for Stroke-Related Aphasia?

 You can check if your doctor is already conversant in cerebrolysin. Never mind, not approved in the US.

Cerebrolysin (11 posts to June 2014)

Old Drug a New Option for Stroke-Related Aphasia?

Abu Dhabi, UAE — Cerebrolysin, a porcine-derived collection of growth factors already employed for a broad array of neurodegenerative disorders in Asia and Eastern Europe, was effective for stroke-related aphasia, the results of a double-blind, randomized controlled trial showed.

The study demonstrated that the drug, when used alongside speech therapy, led to greater improvements in stroke-related aphasia than speech therapy alone.

“If confirmed in larger studies, the combination of cerebrolysin and speech therapy could set a new standard in poststroke aphasia management,” said study investigator Dafin F. Muresanu, MD, PhD, Chairman, Department of Clinical Neurosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania.

He presented the study findings on October 24 at the 16th World Stroke Congress (WSC) 2024.

Studied for More Than 25 Years

Extracted from pig brain, one of the main constituents of cerebrolysin is brain-derived neurotrophic factor. Other peptides, such as glial cell line–derived neurotrophic factor, nerve growth factor, and ciliary neurotrophic factor, may also contribute to the neuroprotective and neuroregenerative effects observed in experimental work.

Clinical studies date back to at least 1998 and include clinical benefits observed in stroke, dementia, traumatic brain injury, and spinal cord injury. Although the degree of benefits has been mixed, including some trials that failed to show any significant benefit, many of the positive studies have been randomized and double-blind.

The European Cooperative Acute Stroke Study (ECASS) included 132 patients with non-fluent (Broca) aphasia who were enrolled within 3-5 days of the causative stroke. In this placebo-controlled, double-blind study, patients were randomly assigned in a 1:1 ratio.

In the experimental arm, patients received 30 mL/d cerebrolysin administered by intravenous (IV) infusion with a 0.9% saline solution. The placebo was an indistinguishable IV 250 mL 0.9% saline solution. The assigned therapies were administered at intervals for a total of 30 days over the 3-month period of the study. During this period, all patients in both groups received 1 hour of speech therapy per day.

The primary outcome was an improvement in language function as assessed by the Western Aphasia Battery (WAB). This was performed at days 0, 30, 60, and 90. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) scores were secondary outcomes assessed at the same intervals.

Prior stroke, preexisting neurodegenerative or psychiatric diseases, and severe liver or renal failure were among the exclusion criteria.

Primary Endpoint Met at 30 Days

For the primary outcome, the advantage of cerebrolysin over speech therapy alone was already significant at 30 days (P < .001), and this relative advantage increased incrementally at 60 and 90 days. At the 90-day visit, the increase from baseline in WAB exceeded 35 points in the experimental arm but climbed only about 20 points (P < .001) in the control arm.

Muresanu characterized the treatment effect as “medium” at the 30-day follow-up but “large” at both the 60- and 90-day timepoints. The follow-up from ECASS, which was called a pilot study, does not yet extend past 90 days.

For the secondary endpoints, cerebrolysin had an insignificant advantage over speech therapy alone at 30 days for the NIHSS score, but the relative advantage increased over time, reaching significance at both day 60 (P < .01) and day 90 (P < .001).

Cerebrolysin had no advantage over speech therapy alone for either mRS or BI at 30 days. At 60 days, cerebrolysin had a slight, non-significant advantage for the mRS endpoint, but there was no signal of benefit for the BI. However, cerebrolysin had a statistically significant, albeit modest, advantage for both of these secondary endpoints at 90 days (both P < .001).

Cerebrolysin was well tolerated in this study. This is consistent with the results of numerous other published studies of cerebrolysin, but anaphylaxis is a risk, according to several case reports. The most recent was published this year.

Limited Availability

The European Medicines Agency has characterized cerebrolysin as safe, but of the approximately 50 countries in which this medicine is now approved, only a handful are in Europe. Besides Romania, these include Austria, Germany, and Poland. But there are scattered approvals elsewhere, including South Korea, Mexico, Vietnam, and Ukraine. Most commonly, cerebrolysin is indicated as an adjunct for the acute treatment of stroke.

Given the mixed findings with this agent despite several decades of experimental and clinical studies, one of the moderators of the late-breaking study in which the ECASS results were presented indicated that multinational controlled studies are needed. According to Ana C. de Souza, MD, PhD, these studies are needed not only for the treatment of stroke aphasia but also for the treatment of other conditions and diseases associated with neurodegeneration.

Without high-quality trials of sufficient size to confirm clinical utility, the promise of both the experimental results remains difficult to interpret, according to de Souza, a clinician and researcher associated with Hospital Moinhos de Vento, Porto Alegre, Brazil.

The study received funding from EVER Neuro Pharma GmbH. Muresanu and de Souza reported no potential financial conflicts of interest.

Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials

 First of all, stop using the term, neuroprotection! Neuronal cascade of death is the correct term! It gives absolutely NO SENSE OF URGENCY! If you tell your patients, you know nothing about stopping  the 5 causes of the neuronal cascade of death in the first week thus letting die hundreds of millions to billions of neurons.  They might just get angry with your incompetence!

Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? I would like to know why you aren't solving stroke to 100% recovery, because this doesn't solve stroke recovery at all!

Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials 

Published: October 12, 2024

DOI: 10.7759/cureus.71343 

 Peer-Reviewed

Cite this article as: Hassan B, Dabas M M, Kanemitsu K, et al. (October 12, 2024) Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials. Cureus 16(10): e71343. doi:10.7759/cureus.71343

Abstract

This systematic review evaluates the effectiveness of various neuroprotective strategies in enhancing recovery following acute ischemic stroke, focusing on interventions such as normobaric oxygen (NBO), lithium, selective serotonin reuptake inhibitors (SSRIs), and Cerebrolysin. Drawing upon data from six primary studies, including randomized controlled trials (RCTs) and meta-analyses, we assessed these therapies' impact on functional outcomes, motor recovery, and neurological improvement. Normobaric oxygen, across 12 RCTs, demonstrated limited efficacy in improving recovery outcomes or reducing mortality. Lithium, supported by animal models but with inconclusive human data, showed potential in reducing stroke volume but did not significantly enhance functional recovery in clinical trials. SSRIs, particularly fluoxetine, showed moderate success in improving motor recovery, as evidenced by the FLAME (Fluoxetine for Motor Recovery after Acute Ischaemic Stroke) trial and meta-analyses. Cerebrolysin demonstrated consistent improvement in early neurological function and motor recovery, with a number-needed-to-treat (NNT) of 7.1 for early NIHSS (National Institutes of Health Stroke Scale) score improvements. Our Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search covered PubMed, Medline, Embase, and the Cochrane Library up to September 2024. These findings emphasize the mixed efficacy of these neuroprotective interventions and underscore the necessity for personalized treatment protocols and further large-scale, controlled trials to clarify their roles in clinical practice. This review contributes to the ongoing dialogue on optimizing post-stroke recovery and highlights the critical need for evidence-based neuroprotective strategies.

Introduction & Background

Stroke remains one of the leading causes of death and disability worldwide, with ischemic stroke accounting for the majority of cases. The pathophysiology of stroke involves a cascade of events, including excitotoxicity, oxidative stress, inflammation, and apoptosis, all contributing to brain injury and long-term neurological deficits [1]. Early intervention with neuroprotective therapies has the potential to limit such damage and enhance functional recovery [2]. Despite significant advancements in acute stroke care, such as thrombolysis and thrombectomy, there is still an unmet need for effective neuroprotective strategies that can be implemented during the subacute phase of stroke recovery [3].

We selected normobaric oxygen (NBO), lithium, selective serotonin reuptake inhibitors (SSRIs), and Cerebrolysin for review due to their unique mechanisms of action and their emerging roles in neuroprotection and post-stroke recovery. These therapies have shown varying degrees of promise in both preclinical studies and early-phase clinical trials. NBO has been explored for its ability to increase oxygen delivery to ischemic brain tissue, though meta-analyses suggest that it may not significantly improve functional outcomes [4,5]. Lithium, widely known for its mood-stabilizing effects, has demonstrated potential in reducing stroke volume and improving post-stroke function in animal models, but human data remain inconclusive. SSRIs, particularly fluoxetine, have garnered attention for their ability to enhance motor recovery post-stroke, independent of their antidepressant effects, as supported by the FLAME (Fluoxetine for Motor Recovery After Acute Ischemic Stroke) trial and subsequent meta-analyses [6]. Cerebrolysin, a neuropeptide preparation, has been the subject of multiple randomized controlled trials (RCTs) and meta-analyses, with studies suggesting its potential for early neurological improvement, though evidence of long-term benefits remains limited [7].

These four interventions were selected based on their clinical relevance, availability of substantial data from RCTs and meta-analyses, and their distinct neuroprotective mechanisms. Compared to other emerging interventions, such as hypothermia, neurotrophic factors, and stem cell therapies, NBO, lithium, SSRIs, and Cerebrolysin have garnered the most clinical attention and research, making them well-suited for a focused systematic review. The objective of this review is to evaluate the efficacy of these neuroprotective strategies in improving post-stroke recovery, particularly in terms of functional outcomes, motor recovery, and neurological improvement. By synthesizing data from clinical trials and meta-analyses, this review aims to provide a clearer understanding of the benefits and limitations of these therapies in stroke rehabilitation.

More at link.

European Academy of Neurology and European Federation of Neurorehabilitation Societies guideline on pharmacological support in early motor rehabilitation after acute ischaemic stroke

What you really needed to do was write a strategy to solve this problem and create leadership that will drive the strategy to completion. But NO, 'hopefully' is all we get. USELESS.  Do you really think your stroke hospital will have these guidelines in place in the next year?

European Academy of Neurology and European Federation of Neurorehabilitation Societies guideline on pharmacological support in early motor rehabilitation after acute ischaemic stroke

Ettore Beghi, Heinrich Binder, Codruta Birle, Natan Bornstein, Karin Diserens, Stanislav Groppa, Volker Homberg, Vitalie Lisnic, Maura Pugliatti, Gary Randall, Leopold Saltuari … See all authors

First published: 21 June 2021

https://doi.org/10.1111/ene.14936

Approved by the EAN Scientific Committee and Guideline Production Group on 28 January 2021

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Abstract

Background and purpose

Early pharmacological support for post-stroke neurorehabilitation has seen an abundance of mixed results from clinical trials, leaving practitioners at a loss regarding the best options to improve patient outcomes. The objective of this evidence-based guideline is to support clinical decision-making of healthcare professionals involved in the recovery of stroke survivors.

Methods

This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. PubMed, Cochrane Library and Embase were searched (from database inception to June 2018, inclusive) to identify studies on pharmacological interventions for stroke rehabilitation initiated in the first 7 days (inclusive) after stroke, which were delivered together with neurorehabilitation. A sensitivity analysis was conducted on identified interventions to address results from breaking studies (from end of search to February 2020).

Results

Upon manually screening 17,969 unique database entries (of 57,001 original query results), interventions underwent meta-analysis. Cerebrolysin (30 ml/day, intravenous, minimum 10 days) and citalopram (20 mg/day, oral) are recommended for clinical use for early neurorehabilitation after acute ischaemic stroke. The remaining interventions identified by our systematic search are not recommended for clinical use: amphetamine (5, 10 mg/day, oral), citalopram (10 mg/day, oral), dextroamphetamine (10 mg/day, oral), Di-Huang-Yi-Zhi (2 × 18 g/day, oral), fluoxetine (20 mg/day, oral), lithium (2 × 300 mg/day, oral), MLC601(3 × 400 mg/day, oral), phosphodiesterase-5 inhibitor PF-03049423 (6 mg/day, oral). No recommendation ‘for’ or ‘against’ is provided for selegiline (5 mg/day, oral). Issues with safety and tolerability were identified for amphetamine, dextroamphetamine, fluoxetine and lithium.

Conclusions

This guideline provides information for clinicians regarding existing pharmacological support in interventions for neurorecovery after acute ischaemic stroke. Updates to this material will potentially elucidate existing conundrums, improve current recommendations, and hopefully expand therapeutic options for stroke survivors.

 

Enhanced Spontaneous Motor Recovery After Stroke in Mice Treated With Cerebrolysin

 Never mind, not approved in the US.

 

Enhanced Spontaneous Motor Recovery After Stroke in Mice Treated With Cerebrolysin

Show all authors

Scott R. DeBoer, MD, PhD, Robert Hubbard, Mahlet Mersha, PhD, ...

First Published May 6, 2021 Research Article Find in PubMed 

https://doi.org/10.1177/15459683211000734

Article information

Abstract

Background

Motor recovery after stroke in humans and in rodent models is time sensitive. Recovery in patients is a result of biological spontaneous recovery via endogenous repair mechanisms and is likely improved by enhancing the synaptic plasticity required for endogenous repair. Cerebrolysin is a polypeptide preparation known to enhance neuroplasticity and may improve recovery in patients. In mice, we tested the hypothesis that Cerebrolysin can act poststroke to enhance both spontaneous and training-associated motor recovery.

Methods

Mice were trained to perform a skilled prehension task. We then induced a photothrombotic stroke in the caudal forelimb area, after which we retrained animals on the prehension task in the presence or absence of Cerebrolysin after a 2-day or 8-day delay. Mice received daily intraperitoneal Cerebrolysin or saline injections starting poststroke day 1 or poststroke day 7.

Results

Prior studies showed that poststroke recovery of prehension can occur if animals receive rehabilitative training during an early sensitive period but is incomplete if rehabilitative training is delayed. In contrast, we show complete recovery of prehension, despite a delay in rehabilitative training, when mice receive daily Cerebrolysin administration starting on poststroke day 1 or on poststroke day 8. When Cerebrolysin is given on poststroke day 1, recovery occurred even in the absence of training. Stroke volumes were similar across groups.

Conclusions

Poststroke Cerebrolysin administration leads to recovery of motor function independent of rehabilitative training without a protective effect on stroke volume. This is one of the first demonstrations of training-independent motor recovery in rodent stroke models.

Keywords stroke, rehabilitation, spontaneous recovery, prehension, mouse model, Cerebrolysin

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Cerebrolysin for stroke, neurodegeneration, and traumatic brain injury: review of the literature and outcomes

 Never mind, not approved in the US.

Cerebrolysin for stroke, neurodegeneration, and traumatic brain injury: review of the literature and outcomes

• Brian Fiani,
• Claudia Covarrubias,
• Amelia Wong,
• Thao Doan,
• Taylor Reardon,
• Daniel Nikolaidis &
• Erika Sarno 

Neurological Sciences (2021)Cite this article

Abstract

Cerebrolysin therapy has the potential to significantly aid in the treatment of a wide variety of debilitating neurological diseases including ischemic strokes, neurodegenerative disorders, and traumatic brain injuries. Although Cerebrolysin is not approved for use in the USA, it is used clinically in over 50 countries worldwide. In this review, we focus on outlining the role that Cerebrolysin has in stimulating the molecular signaling pathways that are critical for neurological regeneration and support. An extensive evaluation of these signaling pathways reveals that Cerebrolysin has the potential to intervene in a diverse array of pathophysiological causes of neurological diseases. In the clinical setting, Cerebrolysin is generally safe for human use and has provided functional improvement when used as an adjunct treatment. However, our literature review revealed inconsistent results, as several clinical studies suggested that Cerebrolysin treatment has minor clinical relevance and did not have significant advantages over a placebo. In conclusion, we found that Cerebrolysin therapy can potentially play a major role in the treatment of many neurological diseases. Nevertheless, there remains much to be elucidated about the efficacy of this treatment for specific neurological conditions, and more robust clinical data is needed to reach a consensus and properly define the therapeutic role of Cerebrolysin.

 

• Cerebrolysin (7)
  

Effect of cerebrolysin on motor function restoration during medical rehabilitation

Since it was successful in restoring motor function, HOW FUCKING LONG BEFORE IT GETS TO YOUR HOSPITAL? I'M GUESSING NEVER. 

No one in your hospital is responsible for translating research into interventions.  The board of directors and president need to be fired for such incompetence. 

Earlier research here which I'm sure they did nothing on. 

• Cerebrolysin (5 post to November 2015)
• Cerebrolysin® (1  post to June 2014)

Effect of cerebrolysin on motor function restoration during medical rehabilitation

 Влияние церебролизина на восстановление двигательной функции в процессе медицинской реабилитации.  Neurology, Neuropsychiatry, Psychosomatics , Volume 8(2) , Pgs. 80-86.

NARIC Accession Number: I245736.  What's this?
Author(s): Kustova M.A.; Tolmachev A.P; Shamalov N.A.
Publication Year: 2016.
Abstract: This paper presents the January 2016 results of the randomized placebo-controlled multicenter study Cerebrolysin and Recovery After Stroke (CARS), which demonstrates the positive effect of cerebrolysin versus placebo according to the primary efficiency criterion, the Action Research Arm Test (ARAT) scale, and total outcome 90 days after disease onset. Ischemic stroke (IS) is characterized by high prevalence, mortality, and disability rates. Therapy aimed to correct one biochemical or molecular stage of ischemic cell injury fails to treat stroke, suggesting that it is necessary to study multimodality therapy affecting several related pathophysiological components. The CARS investigation enrolled mainly patients with moderate or severe IS (the mean National Institutes of Health Stroke Scale score was 9 at baseline). The specific features of the CARS study versus those of other clinical trials of neuroprotectors were the initial planning of narrower end criteria of efficiency (arm motor function recovery, whereas the major goal of many investigations was to reduce mortality rates), as well as a standardized rehabilitation program in both treatment groups. Such investigations did not previously consider the nature and volume of rehabilitation measures, although the latter may have a substantial impact on the outcome of stroke. The CARS study is the first among the previously conducted clinical trials of neuroprotectors that has attained the primary objective (to restore motor function), which presents fresh opportunities for the medical support of rehabilitation measures in patients with IS.
Descriptor Terms: Drugs, Rehabilitation, Stroke.
Language: Russian
Geographic Location(s): Europe, Russia.

Can this document be ordered through NARIC's document delivery service*?: Request Information.
Get this Document: https://nnp.ima-press.net/nnp/article/view/613/563.

Citation: Kustova M.A., Tolmachev A.P, Shamalov N.A. (2016). Effect of cerebrolysin on motor function restoration during medical rehabilitation.  Влияние церебролизина на восстановление двигательной функции в процессе медицинской реабилитации.  Neurology, Neuropsychiatry, Psychosomatics , 8(2), Pgs. 80-86. Retrieved 11/22/2019, from REHABDATA database.

Hope Dies Last—Evidence Again Fails to Support a Neuroprotectant Cerebrolysin for Acute Ischemic Stroke

Then whom is going to analyze and explain why these neuroprotectant trials failed so the stroke strategy can be updated for this failure? Using the Barthel Index, Rankin Scale and National Institutes of Health Stroke Scale means they were using subjective endpoints rather than objective ones like scans showing 3d size and location of dead and damaged areas. Don't these people know how to run research at all?  With a thousand failures someone should be able to identify the commonality so a new direction in strategy can be undertaken. Does no one in the stroke medical world have two functioning neurons to rub together to create a spark of intelligence?
http://stroke.ahajournals.org/content/48/9/2343?etoc=

Daniel Bereczki

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https://doi.org/10.1161/STROKEAHA.117.018202

Stroke. 2017;48:2343-2344

Originally published July 26, 2017

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• Editorials
• effectiveness
• neuroprotectant
• outcome
• stroke
• systematic review

See related article, p e245

It has been a long-lasting hope in basic and clinical research to identify neuroprotectant agents that improve clinical outcome after an ischemic stroke. Over a thousand compounds have been tested in the western world¹ without identifying a single compound supported by firm evidence for use in acute stroke. Although 21 traditional Chinese medicines evaluated in clinical trials claimed to improve clinical outcome after stroke and 7 of them also allegedly decreased case fatality,² because of methodological flaws in these trials, no recommendations can be made on these treatments until properly designed trials are completed.³ None of the Cochrane reviews recommends the use of any neuroprotectants for the treatment of acute stroke,⁴ and current guidelines are also against the use of such agents.⁵

Cerebrolysin is an extract of porcine brain containing a mixture of free amino acids and oligopeptides.⁶ Randomized clinical trials addressed its safety and efficacy in several conditions like Alzheimer’s disease⁷ and traumatic brain injury.⁸ One recent Cochrane review based on 6 trials evaluates the effects of cerebrolysin in acute ischemic stroke and concludes that the use of cerebrolysin has no effect on fatality.^9,10 Five of the included trials were small, and in the largest trial, the comparison groups were not balanced for prognostic factors. The loss to follow-up was considerable in the trials. None of the 6 trials, including overall 1501 participants, had low risk of bias.

The predefined primary outcome is one of the most important issues in clinical trials. Death is certainly an important outcome, but dependency on others is also a bad outcome after stroke. Death or dependency, the preferred composite primary outcome after stroke, was not a primary outcome in any of the 6 trials. Although subgroup and post hoc analyses suggested potential benefit, the largest study with over 1000 patients¹¹ had neutral results regarding the predefined primary outcome: a combined test of the modified Rankin Scale, the Barthel Index, and the National Institutes of Health Stroke Scale at the end of follow-up. No significant effect on neurological signs or disability was reported in 2 smaller trials with over 100 participants.^12,13 The rest 3 trials included <50 patients each.

Despite the lack of evidence from systematic reviews for efficacy regarding both fatality⁹ and functional outcome,¹⁴ cerebrolysin has been used in several countries, with limited healthcare resources in Asia and Eastern Europe. Although subgroup- and post hoc analyses suggested potential benefit of cerebrolysin, these claims should be currently considered only hypotheses. The routine use of cerebrolysin in acute stroke is not justified until randomized well-designed trials indeed prove efficacy in these patient groups. In these trials, patient-centered predefined outcomes will have to be used.¹⁵

Cerebrolysin for acute ischaemic stroke

Interesting that these other pieces of research looked good. Ask your doctor what the fuck is going on.

Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke  March 2016 

Cerebrolysin and Recovery After Stroke (CARS)  Jan. 2016

Cerebrolysin for acute ischaemic stroke

Ziganshina L, Abakumova T, Vernay L; The Cochrane Database of Systematic Reviews 4 CD007026 (Apr 2017)

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• cerebrolysin
• Stroke

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BACKGROUND Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries.
OBJECTIVES To assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke.
SEARCH METHODS In May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma).
SELECTION CRITERIA Randomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke.
DATA COLLECTION AND ANALYSIS Two review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data.
MAIN RESULTS We identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events (SAEs): there was no significant difference in the total number of SAEs with cerebrolysin (RR 1.16, 95% CI 0.81 to 1.67). This comprised no difference in fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38) and an increase in the number of people with non-fatal SAEs (20/667 with cerebrolysin and 8/668 with placebo: RR 2.47, 95% CI 1.09 to 5.58, P = 0.03) (3 trials, 1335 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence).
AUTHORS' CONCLUSIONS The findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence of an increase in non-fatal SAEs with cerebrolysin use but not in total SAEs.

Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke

No clue on what the mechanism of action is that would deliver these better results. Just saying it is neuroprotective is worthless puffery if you have no clue why it works. 

Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke

• Won Hyuk Chang†,
• Chang-hyun Park†,
• Deog Young Kim,
• Yong-Il Shin,
• Myoung-Hwan Ko,
• Ahee Lee,
• Shin Yi Jang and
• Yun-Hee KimEmail author

†Contributed equally

BMC NeurologyBMC series – open, inclusive and trusted201616:31

DOI: 10.1186/s12883-016-0553-z

©  Chang et al. 2016

Received: 23 June 2015

Accepted: 25 February 2016

Published: 2 March 2016

Open Peer Review reports

Abstracts

Background

Cerebrolysin is a neuropeptide preparation with neuroprotective and neurorestorative effects. Combining Cerebrolysin treatment with a standardized rehabilitation program may have a potential synergistic effect in the subacute stage of stroke. This study aims to evaluate whether Cerebrolysin provides additional motor recovery on top of rehabilitation therapy in the subacute stroke patients with moderate to severe motor impairment.

Methods

This phase IV trial was designed as a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A total of 70 patients (Cerebrolysin n = 35, placebo n  = 35) with moderate to severe motor function impairment were included within 7 days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo, given in addition to standardized rehabilitation therapy. Assessments were performed at baseline, immediately after treatment as well as 2 and 3 months after stroke onset. The plasticity of motor system was assessed by diffusion tensor imaging and with resting state functional magnetic resonance imaging.

Results

Both groups demonstrated significant improvement in motor function (p  < 0.05); however, no significant difference was found between the two groups. In the stroke patients with severe motor impairment, the Cerebrolysin group exhibited significantly more improvement in motor function compared with the placebo group (p  < 0.05). Effects of Cerebrolysin were demonstrated as restricted increments of corticospinal diffusivity and as recovery of the sensorimotor connectivity.

Conclusion

The combination of standard rehabilitation therapy with Cerebrolysin treatment in the subacute stroke has shown additional benefit on motor recovery and plastic changes of the corticospinal tract in patients with severe motor impairment.

Trial registration

NCT01996761 (November 5, 2013)