Increased hippocampal shape asymmetry and volumetric ventricular asymmetry in autism spectrum disorder

Autism spectrum disorder (ASD) is a prevalent and fast-growing pervasive neurodevelopmental disorder worldwide. Despite the increasing prevalence of ASD and the breadth of research conducted on the disorder, a conclusive etiology has yet to be established and controversy still exists surrounding the anatomical abnormalities in ASD. In particular, structural asymmetries have seldom been investigated in ASD, especially in subcortical regions. Additionally, the majority of studies for identifying structural biomarkers associated with ASD have focused on small sample sizes. Therefore, the present study utilizes a large-scale, multi-site database to investigate asymmetries in the amygdala, hippocampus, and lateral ventricles, given the potential involvement of these regions in ASD. Contrary to prior work, we are not only computing volumetric asymmetries, but also shape asymmetries, using a new measure of asymmetry based on spectral shape descriptors. This measure represents the magnitude of the asymmetry and therefore captures both directional and undirectional asymmetry. The asymmetry analysis is conducted on 437 individuals with ASD and 511 healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE) database. Results reveal significant asymmetries in the hippocampus and the ventricles, but not in the amygdala, in individuals with ASD. We observe a significant increase in shape asymmetry in the hippocampus, as well as increased volumetric asymmetry in the lateral ventricles in individuals with ASD. Asymmetries in these regions have not previously been reported, likely due to the different characterization of neuroanatomical asymmetry and smaller sample sizes used in previous studies. Given that these results were demonstrated in a large cohort, such asymmetries may be worthy of consideration in the development of neurodiagnostic classification tools for ASD

A prospective study of physician-observed concussion during a varsity university hockey season: White matter integrity in ice hockey players. Part 3 of 4

Object: The aim of this study was to investigate the effect of repetitive head impacts on white matter integrity that were sustained during 1 Canadian Interuniversity Sports (CIS) ice hockey season, using advanced diffusion tensor imaging (DTI). Methods: Twenty-five male ice hockey players between 20 and 26 years of age (mean age 22.24 ± 1.59 years) participated in this study. Participants underwent pre- and postseason 3-T MRI, including DTI. Group analyses were performed using paired-group tract-based spatial statistics to test for differences between preseason and postseason changes. Results: Tract-based spatial statistics revealed an increase in trace, radial diffusivity (RD), and axial diffusivity (AD) over the course of 1 season. Compared with preseason data, postseason images showed higher trace, AD, and RD values in the right precentral region, the right corona radiata, and the anterior and posterior limb of the internal capsule. These regions involve parts of the corticospinal tract, the corpus callosum, and the superior longitudinal fasciculus. No significant differences were observed between preseason and postseason for fractional anisotropy. Conclusions: Diffusion tensor imaging revealed changes in white matter diffusivity in male ice hockey players over the course of 1 season. The origin of these findings needs to be elucidated

Neuroimaging in repetitive brain trauma

Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report

REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer

Repetitive head impacts (RHI) are common in youth athletes participating in contact sports. RHI differ from concussions; they are considered hits to the head that usually do not result in acute symptoms and are therefore also referred to as \textquotedblsubconcussive\textquotedbl head impacts. RHI occur e.g., when heading the ball or during contact with another player. Evidence suggests that exposure to RHI may have cumulative effects on brain structure and function. However, little is known about brain alterations associated with RHI, or about the risk factors that may lead to clinical or behavioral sequelae. REPIMPACT is a prospective longitudinal study of competitive youth soccer players and non-contact sport controls aged 14 to 16~years. The study aims to characterize consequences of exposure to RHI with regard to behavior (i.e., cognition, and motor function), clinical sequelae (i.e., psychiatric and neurological symptoms), brain structure, function, diffusion and biochemistry, as well as blood- and saliva-derived measures of molecular processes associated with exposure to RHI (e.g., circulating microRNAs, neuroproteins and cytokines). Here we present the structure of the REPIMPACT Consortium which consists of six teams of clinicians and scientists in six countries. We further provide detailed information on the specific aims and the design of the REPIMPACT study. The manuscript also describes the progress made in the study thus far. Finally, we discuss important challenges and approaches taken to overcome these challenges

Sex‐Related Differences in the Effects of Sports‐Related Concussion: A Review

Sports‐related concussion is a serious health challenge, and females are at higher risk of sustaining a sports‐related concussion compared to males. Although there are many studies that investigate outcomes following concussion, females remain an understudied population, despite representing a large proportion of the organized sports community. In this review, we provide a summary of studies that investigate sex‐related differences in outcome following sports‐related concussion. Moreover, we provide an introduction to the methods used to study sex‐related differences after sports‐related concussion, including common clinical and cognitive measures, neuroimaging techniques, as well as biomarkers. A literature search inclusive of articles published to March 2020 was performed using PubMed. The studies were reviewed and discussed with regard to the methods used. Findings from these studies remain mixed with regard to the effect of sex on clinical symptoms, concussion‐related alterations in brain structure and function, and recovery trajectories. Nonetheless, there is initial evidence to suggest that sex‐related differences following concussion are important to consider in efforts to develop objective biomarkers for the diagnosis and prognosis of concussion. Additional studies on this topic are, however, clearly needed to improve our understanding of sex‐related differences following concussion, as well as to understand their neurobiological underpinnings. Such studies will help pave the way toward more personalized clinical management and treatment of sports‐related concussion

Neuroimaging in repetitive brain trauma

Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report

Hockey Concussion Education Project, Part 1. Susceptibility-weighted imaging study in male and female ice hockey players over a single season: Clinical article

Object. Concussion, or mild traumatic brain injury (mTBI), is a commonly occurring sports-related injury, especially in contact sports such as hockey. Cerebral microbleeds (CMBs), which appear as small, hypointense lesions on T2*-weighted images, can result from TBI. The authors use susceptibility-weighted imaging (SWI) to automatically detect small hypointensities that may be subtle signs of chronic and acute damage due to both subconcussive and concussive injury. The goal was to investigate how the burden of these hypointensities changes over time, over a playing season, and postconcussion, in comparison with subjects who did not suffer a medically observed and diagnosed concussion. Methods. Images were obtained in 45 university-level adult male and female ice hockey players before and after a single Canadian Interuniversity Sports season. In addition, 11 subjects (5 men and 6 women) underwent imaging at 72 hours, 2 weeks, and 2 months after concussion. To identify subtle changes in brain tissue and potential CMBs, nonvessel clusters of hypointensities on SWI were automatically identified, and a hypointensity burden index was calculated for all subjects at the beginning of the season (BOS), the end of the season (EOS), and at postconcussion time points (where applicable). Results. A statistically significant increase in the hypointensity burden, relative to the BOS, was observed for male subjects with concussions at the 2-week postconcussion time point. A smaller, nonsignificant rise in the burden for female subjects with concussions was also observed within the same time period. There were no significant changes in burden for nonconcussed subjects of either sex between the BOS and EOS time points. However, there was a statistically significant difference in the burden between male and female subjects in the nonconcussed group at both the BOS and EOS time points, with males having a higher burden. Conclusions. This method extends the utility of SWI from the enhancement and detection of larger (\u3e 5 mm) CMBs, which are often observed in more severe cases of TBI, to cases involving smaller lesions in which visual detection of injury is difficult. The hypointensity burden metric proposed here shows statistically significant changes over time in the male subjects. A smaller, nonsignificant increase in the burden metric was observed in the female subjects. ©AANS, 2014

Neuro-Metabolite Changes in a Single Season of University Ice Hockey Using Magnetic Resonance Spectroscopy

Background: Previous research has shown evidence for transient neuronal loss after repetitive head impacts (RHI) as demonstrated by a decrease in N-acetylaspartate (NAA). However, few studies have investigated other neuro-metabolites that may be altered in the presence of RHI; furthermore, the relationship of neuro-metabolite changes to neurocognitive outcome and potential sex differences remain largely unknown.Objective: The aim of this study was to identify alterations in brain metabolites and their potential association with neurocognitive performance over time as well as to characterize sex-specific differences in response to RHI.Methods: 33 collegiate ice hockey players (17 males and 16 females) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012. The MRS voxel was placed in the corpus callosum. Pre- and postseason neurocognitive performances were assessed using the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Absolute neuro-metabolite concentrations were then compared between pre- and postseason MRS were (level of statistical significance after correction for multiple comparisons: p < 0.007) and correlated to ImPACT scores for both sexes.Results: A significant decrease in NAA was observed from preseason to postseason (p = 0.001). Furthermore, a trend toward a decrease in total choline (Cho) was observed (p = 0.044). Although no overall effect was observed for glutamate (Glu) over the season, a difference was observed with females showing a decrease in Glu and males showing an increase in Glu, though this was not statistically significant (p = 0.039). In both males and females, a negative correlation was observed between changes in Glu and changes in verbal memory (p = 0.008).Conclusion: The results of this study demonstrate changes in absolute concentrations of neuro-metabolites following exposure to RHI. Results suggest that changes in Glu are correlated with changes in verbal memory. Future studies need to investigate further the association between brain metabolites and clinical outcome as well as sex-specific differences in the brain's response to RHI

Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe

Aims/hypothesis: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. Methods: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. Results: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24–28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35–37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. Conclusions/interpretation: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies