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Background: N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative electroencephalography (QEEG) parameters in patients with subacute to chronic supratentorial ischemic lesions., Methods: We performed secondary data analysis on an exploratory clinical trial (ISRCTN10702895), assessing the efficacy and safety of 90 days of once-daily treatment with 90 mg N-Pep-12 on neurocognitive function and neurorecovery outcome in patients with post-stroke cognitive impairment against a control group. All participants performed two 32-channel QEEG in resting and active states at baseline (30-120 days after stroke) and 90 days later. Power spectral density on the alpha, beta, theta, delta frequency bands, delta/alpha power ratio (DAR), and (delta+theta)/(alpha+beta) ratio (DTABR) were computed and compared across study groups using means comparison and descriptive methods. Secondarily, associations between QEEG parameters and available neuropsychological tests were explored., Results: Our analysis showed a statistically significant main effect of EEG segments (p<0.001) in alpha, beta, delta, theta, DA, and DTAB power spectral density. An interaction effect between EEG segments and time was noticed in the alpha power. There was a significant difference in theta spectral power between patients with N-Pep-12 supplementation versus placebo at 0.05 alpha level (p=0.023), independent of time points., Conclusion: A 90-day, 90 mg daily administration of N-Pep-12 had significant impact on some QEEG indicators in patients after supratentorial ischemic stroke, confirming possible enhancement of post-stroke neurorecovery. Further research is needed to consolidate our findings., (© 2021. Fondazione Società Italiana di Neurologia.)

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., (© 2021 European Academy of Neurology.)

This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30-50 ml Cerebrolysin once daily for 10-21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P < 0.0001, N = 1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P = 0.0118, N = 314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.

This meta-analysis combines the results of two identical stroke studies (CARS-1 and CARS-2) assessing efficacy of Cerebrolysin on motor recovery during early rehabilitation. Cerebrolysin is a parenterally administered neuropeptide preparation approved for the treatment of stroke. Both studies had a prospective, randomized, double-blind, placebo-controlled design. Treatment with 30 ml Cerebrolysin once daily for 3 weeks was started 24-72 h after stroke onset. In addition, patients participated in a standardized rehabilitation program for 21 days that was initiated within 72 h after stroke onset. For both studies, the original analysis data were used for meta-analysis (individual patient data analysis). The combination of these two studies by meta-analytic procedures was pre-planned, and the methods were pre-defined under blinded conditions. The nonparametric Mann-Whitney (MW) effect size of the two studies on the ARAT score on day 90 indicated superiority of Cerebrolysin compared with placebo (MW 0.62, P < 0.0001, Wei-Lachin pooling procedure, day 90, last observation carried forward; N = 442). Also, analysis of early benefit at day 14 and day 21 by means of the National Institutes of Health Stroke Scale, which is regarded as most sensitive to early improvements, showed statistical significance (MW 0.59, P < 0.002). The corresponding number-needed-to-treat (NNT) for clinically relevant changes in early NIHSS was 7.1 (95% CI: 4 to 22). Cerebrolysin had a beneficial effect on motor function and neurological status in early rehabilitation patients after acute ischemic stroke. Safety aspects were comparable to placebo, showing a favourable benefit/risk ratio.

Background and Purpose : The aim of this study was to evaluate the efficacy, safety, and tolerability of cerebrolysin in the early recovery phase after acute ischemic stroke. Methods. This prospective, randomized, double-blinded, placebo-controlled, multicenter, parallel-group study enrolled a total of 100 patients within 18 h after the onset of stroke. The patients were treated with Cerebrolysin (30 mL over seven days followed by 10 mL until day 30) or placebo once daily over a period of four weeks. Efficacy was primarily assessed by the NIH Stroke Scale at day 30, and additional parameters included the modified Rankin Scale, the Clinical Global Impression, the Patient Global Satisfaction (PGS) and the Mini Mental State Examination (MMSE). Nonparametric statistical procedures employing the Wilcoxon-Mann-Whitney test were used for data analysis. Safety and tolerability were assessed by adverse events, vital signs, and laboratory parameters. Results. The estimated effect size on the change from baseline in the NIH Stroke Scale on day 30 indicated a medium to large superiority of cerebrolysin compared to placebo (Mann-Whitney [MW] 0.66; 95% confidence interval [CI] 0.55-0.78, P=0.005). Similar effect sizes were reported for the modified Ranking Scale (MW 0.65; 95% CI 0.54-0.76; P=0.010) and the Clinical Global Impression (MW 0.70; 95% CI 0.55-0.85; P=0.006). Effect sizes in the MMSE and PGS did not reach statistical significance. No significant group differences were seen in any of the safety parameters. Conclusions. Cerebrolysin was effective, safe, and well tolerated in the early recovery phase after acute ischemic stroke and significantly improved neurological and global function outcomes compared to placebo.

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.

Stroke is the third most common cause of death in the United States and it is the leading cause of disability. Early diagnosis and immediate therapeutic interventions are important factors to reduce the extent of brain tissue damage and the risk of stroke-related death. A rapid blood test that can confirm the clinical or imaging diagnosis or that can add to the stratification of the risk would be very useful. Such a test has to be validated in large studies and has to be based on a simple and low-cost technology. Many biological markers were tested for their ability to serve as 'would-be' stroke biological markers; some of them appear to have a place in the diagnostic work-up of stroke patients. These molecules include Glial Fibrillary Acidic Protein (GFAP), the N-methyl-D-aspartate receptor (NMDA), APO C-III, APO C-I, PARK7, nucleoside diphosphate kinase A (NDKA), S100B, B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. There are obvious limitations to this study, among them the fact that disability does not necessarily correlate with the amount of cerebral tissue lost (the site of stroke may be more important) and the role of the blood-brain barrier in delaying the release of the neuronal proteins in the blood stream. Further studies are awaited to confirm the role of these molecules in the management of acute stroke patients.

Unlabelled: The purpose of the study was to investigate the efficacy and safety of Cerebrolysin in patients with hemorrhagic stroke. The primary objective of this trial was to assess the clinical efficacy and safety of a 10-days course of therapy with a daily administration of Cerebrolysin (50 mL i.v. per day). The trial had to demonstrate that Cerebrolysin treatment is safe in hemorrhagic stroke., Methods: The study was performed as a prospective, randomized, double blind, placebo-controlled, parallel group study with 2 treatment groups. Efficacy measures were the Unified Neurological Stroke Scale, Barthel Index, and Syndrome Short Test. The duration of the trial was of 21 days for each patient. Out of 100 randomized patients, a total of 96 (96%) completed the study., Results: Overall, no statistically significant group effects were observed based on single average comparisons at the individual visits. It could be shown that the treatment of hemorrhagic stroke with Cerebrolysin is safe and well tolerated., Conclusion: In the changes of UNSS, BI and SST from baseline to day 21, the group differences are not statistically significant; however, the use of Cerebrolysin in hemorrhagic stroke is safe and well tolerated and studies with a larger sample size may provide statistical evidence of Cerebrolysin's efficacy in patients with hemorrhagic stroke.

The 2nd International Salzburg Conference on Neurorecovery was held on the 28th and 29th of November, 2013, in Salzburg, one of the most beautiful cities in Austria, which is well known for its rich cultural heritage, world-famous music and beautiful surrounding landscapes. The aim of the conference was to discuss the progress in the field of neurorecovery. The conference brought together internationally renowned scientists and clinicians, who described the clinical and therapeutic relevance of translational research and its applications in neurorehabilitation. [ABSTRACT FROM AUTHOR]