Effects of N-Pep-12 dietary supplementation on neurorecovery after ischemic stroke.

BACKGROUND: The aim of the study was to evaluate the effects of N-Pep-12 dietary supplementation on neurorecovery of middle-aged and older adults with cognitive impairment after ischemic stroke, using neuropsychological outcome scales. METHODS: This was a pilot randomized-controlled, phase IV, academic clinical trial that aimed to assess the effect and the safety of a single daily dose of oral 90 mg of N-Pep-12 for 90 days in supporting neurorecovery, as compared with a control group, performed on middle-aged and older adults after supratentorial ischemic stroke. RESULTS: Study group differences in baseline changes at day 90 for Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS) - Anxiety subscale, Color Trails 1 and Symbol Search (number incorrect) were statistically significant (Mann-Whitney U test). For MoCA at day 90, a borderline 'intermediate effect' in favour of N-PEP-12 was observed (dCohen = 0.491, η2 = 0.057, OR = 2.436, p = 0.010). HADS Anxiety and Color Trails 1 at day 90 registered a 'small-to-intermediate' effect in favour of N-PEP-12 (dCohen = 0.424, η2 = 0.043, OR = 2.157, p = 0.026; dCohen = 0.481, η2 = 0.055, OR = 2.3927, p = 0.013, respectively). For symbol search errors, an 'intermediate' effect in favour of the control group was observed (dCohen = 0.501, η2 = 0.059, OR = 2.4811, p = 0.007). CONCLUSION: This exploratory clinical trial indicates a signal for the benefit of dietary supplementation with N-Pep-12 for the enhancement of neurorecovery after supratentorial ischemic stroke.

Biomarkers in traumatic brain injury: new concepts.

Traumatic brain injury is a multifaceted condition that encompasses a spectrum of injuries: contusions, axonal injuries in specific brain regions, edema, and hemorrhage. Brain injury determines a broad clinical and disability spectrum due to the implication of various cellular pathways, genetic phenotypes, and environmental factors. It is challenging to predict patient outcomes, to appropriately evaluate the patients, to determine a suitable treatment strategy and rehabilitation program, and to communicate with patient relatives. Biomarkers detected from body fluids are potential evaluation tools for traumatic brain injury patients. These may serve as internal indicators of cerebral damage, delivering valuable information about the dynamic cellular, biochemical, and molecular environments. The diagnostic and prognostic value of biomarkers tested both in animal models of traumatic brain injury is still under question, despite a considerable scientific literature. Recent publications emphasize that a more realistic approach involves combining multiple types of biomarkers with other investigative tools (imaging, outcome scales, and genetic polymorphisms). Additionally, there is increasing interest in the use of biomarkers as tools for treatment monitoring and as surrogate outcome variables to facilitate the design of distinct randomized controlled trials. This review highlights the latest available evidence regarding biomarkers in adults after traumatic brain injury and discusses new approaches in the evaluation of this patient group.

Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial.

INTRODUCTION: The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. MATERIALS AND METHODS: The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. RESULTS: The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a "small-to-medium"-sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. CONCLUSION: Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.