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.

Cognitive function: holarchy or holacracy?

Cognition is the most complex function of the brain. When exploring the inner workings of cognitive processes, it is crucial to understand the complexity of the brain's dynamics. This paper aims to describe the integrated framework of the cognitive function, seen as the result of organization and interactions between several systems and subsystems. We briefly describe several organizational concepts, spanning from the reductionist hierarchical approach, up to the more dynamic theory of open complex systems. The homeostatic regulation of the mechanisms responsible for cognitive processes is showcased as a dynamic interplay between several anticorrelated mechanisms, which can be found at every level of the brain's organization, from molecular and cellular level to large-scale networks (e.g., excitation-inhibition, long-term plasticity-long-term depression, synchronization-desynchronization, segregation-integration, order-chaos). We support the hypothesis that cognitive function is the consequence of multiple network interactions, integrating intricate relationships between several systems, in addition to neural circuits.

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.

The Effect of Cerebrolysin on the Predictive Value of Baseline Prognostic Risk Score in Moderate and Severe Traumatic Brain Injury.

Cognitive dysfunction is a significant complaint among patients after moderate to severe traumatic brain injury (TBI), with devastating consequences on functional recovery and quality of life. Prognostic models allow a better assessment and management of neurotrauma patients. The aim of the study was to demonstrate the predictive value of the Baseline Prognostic Risk Score (BPRS) in moderate to severe TBI, in a sample of patients treated with neurotrophic factors. Eighty patients with moderate-severe TBI from the CAPTAIN II study were included in secondary data analysis. Patients received active treatment with Cerebrolysin, 50 mL per day for ten days, followed by two treatment cycles with 10 mL per day for ten days. BPRS was determined on admission; the age was recorded, and patients were evaluated using the following neurocognitive tests: Mini-Mental State Essay (MMSE), Wechsler Adult Intelligence Scale-Third Edition Processing Speed Index (WAIS-III PSI) and Stroop Colour Word Test-Victoria Version at 10, 30 and 90 days. Hierarchical regression analysis was performed to investigate the unique predictive value of BPRS on cognitive evolution, independent of age. BPRS independently predicted scores on the WAIS-III PSI DSCales and the Word subscale of the Stroop Colour Word Test at 90 days. Age was a significant predictor for all the investigated scales at 10, 30, and 90 days. This study demonstrates the predictive value of a validated prognostic model (BPRS) for medium-term neurocognitive outcomes in a sample of moderate-severe traumatic brain injury treated with neurotrophic factors.

Prediction of Neurocognitive Outcome after Moderate-Severe Traumatic Brain Injury Using Serum Neuron-Specific Enolase and S100 biomarkers.

Seric biomarkers have been tested in a large number of studies on traumatic brain injuries (TBI) patients in order to predict severity, especially related to the short-term outcome. However, TBI patients have a high risk of developing long-term complications such as physical disability, cognitive impairment, psychiatric pathology, epilepsy, and others. The aim of this study was to assess the correlation between protein biomarkers S100 and neuron-specific enolase (NSE) and neurocognitive status at 10- and 90-days post-injury. Both biomarkers were tested in the first 4h and after 72h post-injury in 62 patients with moderate-severe TBI. The patients were evaluated by a series of neurocognitive tests: Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale-Extended (GOSE), The Mini-Mental State Examination (MMSE), Processing Speed Index (PSI), and Stroop Test, at 10 and 90 days post-injury and supplementary by the Hospital Anxiety and Depression Scale at 90 days. For evaluating the whole neurocognitive status instead of every scale separately, we used Structural Equation Modeling (SEM), while for anxiety and depressive symptoms, we used multiple regression analyses. SEM showed that NSE values at 4 hours were significant predictors of the cognitive status at 10 (p=0.034) and 90 days (p= 0.023). Also, there were found significant correlations between NSE at 4h and the anxiety level. This study demonstrated a significant correlation between NSE at 4h and short and medium-term neuropsychological outcomes, which recommends using this biomarker for selecting patients with a higher risk of cognitive dysfunction.

VaD - An Integrated Framework for Cognitive Rehabilitation.

BACKGROUND & OBJECTIVE: Vascular dementia is the second most common cause of dementia, with clinical features that depend on neural substrates affected by the vascular lesions. Like most neurological disorders, it involves alterations that range from the molecular level to neuronal networks. Such alterations begin as compensatory mechanisms that reshape every subsystem involved in the brain's homeostasis. Although there have been recent huge advances in understanding the pathophysiology of cognitive dysfunction, a suitable therapeutic approach to vascular dementia remains elusive. Pharmacological interventions have failed to sustainably improve cognitive function, and it is a well-known fact that there is a need to change the current view for providing neuroprotection and enhancing neurorecovery after stroke. Studies regarding cognitive training are also faced with the difficulty of drawing up protocols that can embrace a holistic approach in cognitively impaired patients. CONCLUSION: This review will present a brief synthesis of current results from basic research data and clinical studies regarding pharmacological and non-pharmacological interventions in vascular dementia and will offer an integrated view from the perspective of systems biology.

A hypertensive patient with multiple intracerebral hemorrhages due to brain metastases.

We report the case of a 55-year-old man, hypertensive, who presented to the Emergency Room with intense occipital cephaleea, nausea, vomiting and disturbance of balance. The peculiarity of this case was given by the simultaneous presence of two brain hemorrhagic lesions and an unusual hypodensity with digitiform borders at cerebral CT scan, which suggested a different etiology than hypertension and leaded us to further investigations, which confirmed the diagnosis of lung cancer with multiple brain metastases.