Efficacy and safety of urgent carotid endarterectomy in patients with acute ischemic stroke.

INTRODUCTION: Acute symptomatic occlusion of the internal carotid artery (ICA) is associated with unfavorable prognosis. However, no clear definition of its optimal treatment exists. The aim of this study was to evaluate the efficacy and risks of urgent carotid endarterectomy (CEA) in patients with ischemic stroke due to acute extracranial ICA occlusion. METHODS: A retrospective analysis was performed of all consecutive patients undergoing urgent CEA for acute extracranial ICA occlusion during the period from July 2014 to June 2021. The primary outcome was functional independence at three months defined as modified Rankin Scale (mRS) score 2. Secondary outcomes included the severity of the neurological deficit at the time of discharge and its comparison with the preoperative condition as assessed using the National Institutes of Health Stroke Scale (NIHSS), the incidence of symptomatic intracerebral hemorrhage (ICH), and 30-day periprocedural mortality. RESULTS: During the study period, a total of 42 urgent CEAs were performed for acute extracranial ICA occlusions. The median preoperative NIHSS score was 7 (interquartile range [IQR] 5-13). The median time interval between the onset of symptoms and surgery was 290 minutes (IQR 235-340). Technical success rate of urgent CEA was 97.6% (41 patients). The median NIHSS at the time of hospital discharge was 2 (IQR 3-7; p.

Sex differences and brain development during puberty and adolescence.

Sex differences in behavior, and whether these behavioral differences are related to sex differences in brain development, has been a longstanding topic of debate. Presumably, sex differences can provide critically important leads for explaining the etiology of various illnesses that show (i) large sex differences in prevalence and (ii) have an origin before or during adolescence. The general aim of this chapter is to provide an overview of scientific studies on sex differences in normative brain and behavioral development across puberty and adolescence, including the (sex) hormone-driven transition phase of puberty. Moreover, we describe the literature on brain and behavioral development in gender dysphoria, a severe and persistent incongruence between the self-identified gender and the assigned sex at birth. From the literature it becomes clear there is evidence for a specific link between pubertal maturation and developmental changes in arousal, motivation, and emotion. However, this link is rather similar between boys and girls. Moreover, although there is substantial evidence for sex differences in mean brain structure, these have not always been linked to sex differences in behavior, cognition, or psychopathology. Furthermore, there is little evidence for sex differences in brain development and thus, studies so far have been unable to explain sex differences in cognition. Suggestions for future research and methodologic considerations are provided.

Combined endovascular and surgical treatment of symptomatic tandem occlusion of common carotid artery and middle cerebral artery - case repor.

INTRODUCTION: Cerebrovascular events are among the most common causes of invalidity or death. The aim of treatment in acute cerebral ischemia is to restore the blood flow before irreversible necrosis of brain tissue and persistent neurologic deficit occur. Pharmacological, endovascular and surgical methods are employed in the treatment of these patients. CASE REPORT: The authors present a case report of a 56-year-old woman with acute cerebral ischemia caused by tandem occlusion of the left common carotid artery and the M1 segment of middle cerebral artery. In the initial phase the patient was treated by intravenous thrombolysis with minimal success. Common carotid artery was occluded and mechanical extraction of embolus was successfully performed through direct carotid bifurcation puncture. Almost complete regression of neurologic deficit occurred after the endovascular recanalization. Occluded common carotid stump and bifurcation was considered as a source of embolization and therefore, to prevent further cerebrovascular event, a subclavian-carotid bypass was performed on the 15th day after the stroke. CONCLUSION: In the reported patient with symptomatic tandem occlusion of common carotid artery and the M1 part of middle cerebral artery, recanalization of cerebral artery was attained by the combination of pharmacological and endovascular method. Consequent subclavian-to-carotid bypass was performed in tertiary prevention of further cerebrovascular event.

Understanding the Role of Puberty in Structural and Functional Development of the Adolescent Brain.

Over the past two decades, there has been a tremendous increase in our understanding of structural and functional brain development in adolescence. However, understanding the role of puberty in this process has received much less attention. This review examines this relationship by summarizing recent research studies where the role of puberty was investigated in relation to brain structure, connectivity, and task-related functional magnetic resonance imaging (fMRI). The studies together suggest that puberty may contribute to adolescent neural reorganization and maturational advancement, and sex differences also emerge in puberty. The current body of work shows some mixed results regarding impact and exact direction of pubertal influence. We discuss several limitations of current studies and propose future directions on how to move the field forward.

Pregnancy and adolescence entail similar neuroanatomical adaptations: A comparative analysis of cerebral morphometric changes.

Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long-lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface-based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first-time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first-time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.

Development of Multifaceted Risk Taking and the Relations to Sex Steroid Hormones: A Longitudinal Study.

Risk taking is a multidimensional construct. It is currently unclear which aspects of risk-taking change most during adolescence and if/how sex hormones contribute to risk-taking tendencies. This study applied a longitudinal design with three time-points, separated by 2 years, in participants aged 8-29 years (670 observations). The Balloon Analogue Risk Task, a delay discounting task, and various self-report questionnaires were administered, to measure aspects of risk taking. Longitudinal analyses demonstrated mostly nonlinear age-related patterns in risk-taking behavior and approach-related personality characteristics (peaking in late adolescence). Increased testosterone and estradiol were found to increase risk-taking behavior and impulsive personality, but decrease avoidance-like personality. This study demonstrates that risk taking is most pronounced in mid-to-late adolescence and suggests that sex hormones accelerate this maturational process.

Contributions of Reward Sensitivity to Ventral Striatum Activity Across Adolescence and Early Adulthood.

It was examined how ventral striatum responses to rewards develop across adolescence and early adulthood and how individual differences in state- and trait-level reward sensitivity are related to these changes. Participants (aged 8-29 years) were tested across three waves separated by 2 years (693 functional MRI scans) in an accelerated longitudinal design. The results confirmed an adolescent peak in reward-related ventral striatum, specifically nucleus accumbens, activity. In early to mid-adolescence, increases in reward activation were related to trait-level reward drive. In mid-adolescence to early adulthood decreases in reward activation were related to decreases in state-level hedonic reward pleasure. This study demonstrates that state- and trait-level reward sensitivity account for reward-related ventral striatum activity in different phases of adolescence and early adulthood.

Unraveling age, puberty and testosterone effects on subcortical brain development across adolescence.

The onset of adolescence in humans is marked by hormonal changes that give rise to secondary sexual characteristics, noted as puberty. It has, however, proven challenging to unravel to what extent pubertal changes may have organizing effects on the brain beyond chronological age, as reported in animal studies. The present longitudinal study aimed to characterize the unique effects of age and puberty on subcortical brain volumes and included three waves of data collection at two-year intervals and 680 T1-weighted MRI scans of 271 participants (54% females) aged between 8 and 29 years old. Generalized additive mixed model procedures were used to assess the effects of age, self-report pubertal status and testosterone level on basal ganglia, thalamus, hippocampus, amygdala and cerebellum gray matter volumes. We observed age-related increases in putamen and pallidum volumes, and decreases in accumbens and thalamus volumes, all show larger volumes in boys than girls. Only the cerebellum showed an interaction effect of age by sex, such that males showed prolonged increases in cerebellar volume than females. Next, we showed that changes in self-report puberty status better described developmental change than chronological age for most structures in males, and for caudate, pallidum and hippocampal volumes in females. Furthermore, changes in testosterone level were related to development of pallidum, accumbens, hippocampus and amygdala volumes in males and caudate and hippocampal volumes in females. The modeling approach of the present study allowed us to characterize the complex interactions between chronological age and pubertal maturational changes, and the findings indicate puberty unique changes in brain structure that are sex specific.

A multisample study of longitudinal changes in brain network architecture in 4-13-year-old children.

Recent advances in human neuroimaging research have revealed that white-matter connectivity can be described in terms of an integrated network, which is the basis of the human connectome. However, the developmental changes of this connectome in childhood are not well understood. This study made use of two independent longitudinal diffusion-weighted imaging data sets to characterize developmental changes in the connectome by estimating age-related changes in fractional anisotropy (FA) for reconstructed fibers (edges) between 68 cortical regions. The first sample included 237 diffusion-weighted scans of 146 typically developing children (4-13 years old, 74 females) derived from the Pediatric Longitudinal Imaging, Neurocognition, and Genetics (PLING) study. The second sample included 141 scans of 97 individuals (8-13 years old, 62 females) derived from the BrainTime project. In both data sets, we compared edges that had the most substantial age-related change in FA to edges that showed little change in FA. This allowed us to investigate if developmental changes in white matter reorganize network topology. We observed substantial increases in edges connecting peripheral and a set of highly connected hub regions, referred to as the rich club. Together with the observed topological differences between regions connecting to edges showing the smallest and largest changes in FA, this indicates that changes in white matter affect network organization, such that highly connected regions become even more strongly imbedded in the network. These findings suggest that an important process in brain development involves organizing patterns of inter-regional interactions. Hum Brain Mapp 39:157-170, 2018. © 2017 Wiley Periodicals, Inc.

Neural Mechanisms Underlying Risk and Ambiguity Attitudes.

Individual differences in attitudes to risk (a taste for risk, known probabilities) and ambiguity (a tolerance for uncertainty, unknown probabilities) differentially influence risky decision-making. However, it is not well understood whether risk and ambiguity are coded differently within individuals. Here, we tested whether individual differences in risk and ambiguity attitudes were reflected in distinct neural correlates during choice and outcome processing of risky and ambiguous gambles. To these ends, we developed a neuroimaging task in which participants ( n = 50) chose between a sure gain and a gamble, which was either risky or ambiguous, and presented decision outcomes (gains, no gains). From a separate task in which the amount, probability, and ambiguity level were varied, we estimated individuals' risk and ambiguity attitudes. Although there was pronounced neural overlap between risky and ambiguous gambling in a network typically related to decision-making under uncertainty, relatively more risk-seeking attitudes were associated with increased activation in valuation regions of the brain (medial and lateral OFC), whereas relatively more ambiguity-seeking attitudes were related to temporal cortex activation. In addition, although striatum activation was observed during reward processing irrespective of a prior risky or ambiguous gamble, reward processing after an ambiguous gamble resulted in enhanced dorsomedial PFC activation, possibly functioning as a general signal of uncertainty coding. These findings suggest that different neural mechanisms reflect individual differences in risk and ambiguity attitudes and that risk and ambiguity may impact overt risk-taking behavior in different ways.

Exploring the role of testosterone in the cerebellum link to neuroticism: From adolescence to early adulthood.

Previous research has found an association between a smaller cerebellar volume and higher levels of neuroticism. The steroid hormone testosterone reduces stress responses and the susceptibility to negative mood. Together with in vitro studies showing a positive effect of testosterone on cerebellar gray matter volumes, we set out to explore the role of testosterone in the relation between cerebellar gray matter and neuroticism. Structural magnetic resonance imaging scans were acquired, and indices of neurotic personality traits were assessed by administering the depression and anxiety scale of the revised NEO personality inventory and Gray's behavioural avoidance in one hundred and forty-nine healthy volunteers between 12 and 27 years of age. Results demonstrated an inverse relation between total brain corrected cerebellar volumes and neurotic personality traits in adolescents and young adults. In males, higher endogenous testosterone levels were associated with lower scores on neurotic personality traits and larger cerebellar gray matter volumes. No such relations were observed in the female participants. Analyses showed that testosterone significantly mediated the relation between male cerebellar gray matter and measures of neuroticism. Our findings on the interrelations between endogenous testosterone, neuroticism and cerebellar morphology provide a cerebellum-oriented framework for the susceptibility to experience negative emotions and mood in adolescence and early adulthood.

Amygdala-orbitofrontal connectivity predicts alcohol use two years later: a longitudinal neuroimaging study on alcohol use in adolescence.

This study tested the relation between cortical-subcortical functional connectivity and alcohol consumption in adolescents using an accelerated longitudinal design, as well as normative developmental patterns for these measures. Participants between ages 8 and 27 completed resting-state neuroimaging scans at two time points separated by two years (N = 274 at T1, N = 231 at T2). In addition, participants between ages 12 and 27 reported on recent and lifetime alcohol use (N = 193 at T1, N = 244 at T2). Resting-state connectivity analyses focused on amygdala-orbitofrontal connectivity given prior research linking reduced coupling between these regions to alcohol use. Mixed model analyses revealed that age had a cubic relationship with alcohol use, with little to no use in childhood, steep increases in adolescence and leveling off in adulthood. No age effects were found for amygdala-OFC connectivity. Prediction analyses showed that left amygdala-orbitofrontal connectivity at the first time point predicted recent and lifetime alcohol use two years later. There was no evidence for the reversed relation, suggesting that brain connectivity measures precede explorative risk-taking behavior in adolescence, possibly because decreased subcortical-frontal connectivity biases towards more explorative or risky behavior.

Reference values for salivary testosterone in adolescent boys and girls determined using Isotope-Dilution Liquid-Chromatography Tandem Mass Spectrometry (ID-LC-MS/MS).

The measurement of testosterone in saliva is an attractive alternative to serum analysis due to the simple and non-invasive sample collection. In children and adolescents salivary testosterone is mainly measured to investigate whether puberty has started or not. This study aimed to establish reference values for salivary testosterone during puberty in boys and girls. We measured salivary testosterone using ID-LC-MS/MS in a cohort of 131 girls and 123 boys of whom each had salivary testosterone measured at two time points during puberty. Salivary testosterone concentrations start to increase with the start of puberty around eight years and continuously increase up to adult concentrations in the following ten years. Reference values were calculated using the Lambda-Mu-Sigma (LMS)-curve fitting method and provided per year from 8 to 26 years of age in boys and girls. These reference ranges may help clinicians and researchers to interpret salivary testosterone results in both individual patients and study subjects.

Frontostriatal White Matter Integrity Predicts Development of Delay of Gratification: A Longitudinal Study.

The ability to delay gratification increases considerably across development. Here, we test the hypothesis that this impulse control capacity is driven by increased maturation of frontostriatal circuitry using a fiber-tracking approach combined with longitudinal imaging. In total, 192 healthy volunteers between 8 and 26 years underwent diffusion tensor imaging scanning and completed a delay-discounting task twice, separated by a 2-year interval. We investigated dynamic associations between frontostriatal white matter (WM) integrity and delay of gratification skills. Moreover, we examined the predictive value of frontostriatal WM integrity for future delay of gratification skills. Results showed that delay discounting increases with age in a quadratic fashion, with greatest patience during late adolescence. Data also indicated nonlinear development of frontostriatal WM, with relative fast development during childhood and early adulthood and--on average--little change during mid-adolescence. Furthermore, the positive association between age and delay discounting was further increased in individuals with higher WM integrity of the frontostriatal tracts. Predictive analysis showed that frontostriatal WM development explained unique variance in current and future delay of gratification skills. This study adds to a descriptive relation between WM integrity and delay of gratification by showing that maturation of frontostriatal connectivity predicts changes in delay of gratification skills. These findings have implications for studies examining deviances in impulse control by showing that the developmental path between striatum and prefrontal cortex may be an important predictor for when development goes astray. SIGNIFICANCE STATEMENT: During the transition from childhood to adulthood, individuals generally show increased patience and become better in delaying gratification. The exact neural correlates of delay of gratification, however, remain poorly understood. By measuring both frontostriatal white matter (WM) integrity and delay of gratification skills at two time points, we were able to provide links for our understanding of the neural mechanisms underlying this type of impulse regulation capacity. We demonstrate that the ability to delay gratification improves between childhood and young adulthood and this improvement is predicted by the integrity of frontostriatal WM connections. This study adds to a descriptive relation between WM quality and delay of gratification by showing that maturation of frontostriatal connectivity predicts improvements in delay of gratification skills.

Annual Research Review: Neural contributions to risk-taking in adolescence--developmental changes and individual differences.

BACKGROUND: Risk-taking, which involves voluntary choices for behaviors where outcomes remain uncertain, undergoes considerable developmental changes during childhood, adolescence, and early adulthood. In addition, risk-taking is thought to be a key element of many externalizing disorders, such as ADHD, delinquency, conduct disorder, and substance abuse. In this review, we will discuss the potential adaptive and nonadaptive properties of risk-taking in childhood and adolescence. FINDINGS: We propose that the changes in brain architecture and function are a crucial element underlying these developmental trajectories. We first identify how subcortical and cortical interactions are important for understanding risk-taking behavior in adults. Next, we show how developmental changes in this network underlie changes in risk-taking behavior. Finally, we explore how these differences can be important for understanding externalizing behavioral disorders in childhood and adolescence. CONCLUSIONS: We conclude that longitudinal studies are of crucial importance for understanding these developmental trajectories, and many of these studies are currently underway.

Nucleus accumbens response to rewards and testosterone levels are related to alcohol use in adolescents and young adults.

During adolescence there is a normative increase in risk-taking behavior, which is reflected in, for example, increases in alcohol consumption. Prior research has demonstrated a link between testosterone and alcohol consumption, and between testosterone and neural responses to rewards. Yet, no study to date tested how testosterone levels and neural responses to rewards relate to and predict individual differences in alcohol use. The current study aimed to investigate this by assessing alcohol use, testosterone levels and neural responses to rewards in adolescents (12-17 years old) and young adults (18-26 years old). Participants were measured twice with a two-year interval between testing sessions. Cross-sectional analysis showed that at the second time point higher neural activity to rewards, but not testosterone levels, explained significant variance above age in reported alcohol use. Predictive analyses showed that, higher testosterone level at the first time point, but not neural activity to rewards at the first time point, was predictive of more alcohol use at the second time point. These results suggest that neural responses to rewards are correlated with current alcohol consumption, and that testosterone level is predictive of future alcohol consumption. These results are interpreted in the context of trajectory models of adolescent development.

Longitudinal changes in adolescent risk-taking: a comprehensive study of neural responses to rewards, pubertal development, and risk-taking behavior.

Prior studies have highlighted adolescence as a period of increased risk-taking, which is postulated to result from an overactive reward system in the brain. Longitudinal studies are pivotal for testing these brain-behavior relations because individual slopes are more sensitive for detecting change. The aim of the current study was twofold: (1) to test patterns of age-related change (i.e., linear, quadratic, and cubic) in activity in the nucleus accumbens, a key reward region in the brain, in relation to change in puberty (self-report and testosterone levels), laboratory risk-taking and self-reported risk-taking tendency; and (2) to test whether individual differences in pubertal development and risk-taking behavior were contributors to longitudinal change in nucleus accumbens activity. We included 299 human participants at the first time point and 254 participants at the second time point, ranging between ages 8-27 years, time points were separated by a 2 year interval. Neural responses to rewards, pubertal development (self-report and testosterone levels), laboratory risk-taking (balloon analog risk task; BART), and self-reported risk-taking tendency (Behavior Inhibition System/Behavior Activation System questionnaire) were collected at both time points. The longitudinal analyses confirmed the quadratic age pattern for nucleus accumbens activity to rewards (peaking in adolescence), and the same quadratic pattern was found for laboratory risk-taking (BART). Nucleus accumbens activity change was further related to change in testosterone and self-reported reward-sensitivity (BAS Drive). Thus, this longitudinal analysis provides new insight in risk-taking and reward sensitivity in adolescence: (1) confirming an adolescent peak in nucleus accumbens activity, and (2) underlining a critical role for pubertal hormones and individual differences in risk-taking tendency.

[Optimizing the treatment procedure in crural ulcers - a pilot study of the surgical method]. / Optimalizace lécebného postupu u kozního trofického defektu bérce pilotní studie chirurgické metody.

INTRODUCTION: Current medical knowledge has provided us with a wide range of possibilities of treating chronic wounds. Over the recent decades, in particular, significant progress has been made in this field. The authors present an overview of current knowledge of chronic wound healing, pointing out the surgeons role in the process of chronic wound management. Using surgical therapy, we are able to heal a chronic wound in a shorter period of time, particularly if the treatment is accelerated by the application of platelet-rich plasma (PRP) as a source of growth factors. METHODS: The pilot randomized prospective study included four patients with chronic wounds of the lower leg after previous failure of conservative therapy who were indicated for skin transplantation. Following previous vacuum-assisted closure therapy, the patients undergoing skin transplantation were prospectively randomized into two groups. Autologous PRP was used in one of the groups and standard skin transplantation without PRP was performed in the other one. RESULTS: In the PRP group, 99% of the wound areas were healed on the 15th day after the operation. In the other group, 90% of the areas were healed on the 15th day following the operation. In the PRP group, complete healing of the defect occurred in both patients at 15 and 20 days post-surgery. In the second group, one patient completely healed within 28 days; the other one was not fully healed even at 3 months post-surgery. CONCLUSIONS: Most patient groups at great risk may benefit from the method using PRP, as well as patients with chronic wounds who have failed conventional methods available for both general and local therapy. This fact has been confirmed by the authors initial experience presented.Key words: platelet-rich plasma (PRP) - platelets wound healing chronic wound.

The link between testosterone and amygdala-orbitofrontal cortex connectivity in adolescent alcohol use.

Alcohol consumption is one of the most problematic and widespread forms of risk taking in adolescence. It has been hypothesized that sex hormones such as testosterone play an important role in risk taking by influencing the development of brain networks involved in emotion and motivation, particularly the amygdala and its functional connections. Connectivity between the amygdala and the orbitofrontal cortex (OFC) may be specifically related to alcohol use, given the association of this tract with top-down control over behavioral approach tendencies. In line with this, prior studies in adults indicate a link between alcohol use and functional connectivity between the amygdala and the orbitofrontal cortex (OFC), as well as between testosterone and amygdala-OFC connectivity. We consolidated these research lines by investigating the association between alcohol use, testosterone and resting state functional brain connectivity within one large-scale adolescent sample (n=173, aged 12-25 years). Mediation analyses demonstrated an indirect effect of testosterone levels on alcohol use through amygdala-OFC intrinsic functional connectivity, but only in boys. That is, increased testosterone in boys was associated with reduced amygdala-OFC connectivity, which in turn was associated with increased alcohol intake. This study is the first to demonstrate the interplay between adolescent alcohol use, sex hormones and brain mechanisms, thus taking an important step to increase our understanding of the mechanisms behind this form of adolescent risk-taking.

Short fused? associations between white matter connections, sex steroids, and aggression across adolescence.

Functional neuroimaging studies in adults show that aggression involves reduced brain communication between subcortical and cortical areas dedicated to motivation and control, respectively. Prior research indicates that sex steroid hormone production during adolescence negatively influences the rapid development of white matter connectivity between subcortical and cortical areas during adolescence and may potentiate aggression. Here, we tested this hypothesis in 258 participants between 8 and 25 years of age by using Diffusion Weighted Imaging to examine the microstructure of white matter connections within the fronto-temporal-subcortical network. Trait aggression was measured using the Buss Perry Aggression Questionnaire and testosterone and estradiol levels were measured in saliva. Results indicated that higher levels of testosterone were associated with less white matter integrity within the fronto-temporal-subcortical network (i.e., higher mean diffusivity [MD] longitudinal [LD], and radial diffusivity [RD]). Furthermore, lower fractional anisotropy and higher MD, LD, and RD values within this network increased expressive forms of aggression and reduced inhibited forms of aggression (hostility). Our study indicates higher levels of testosterone relating to lower quality of structural cortical-subcortical connectivity, arguably resulting in a shift from inhibited towards expressive forms of aggression. Our data adds evidence to the idea that aggressive tendencies are subcortically driven, but individuals with relatively high testosterone might have lower structural connectivity within cortical control areas, resulting in a stronger tendency to act on these aggressive tendencies.