Modifications neurométaboliques et microstructurales à la suite d'une commotion cérébrale chez les athlètes féminines

L’utilisation de méthodes d’investigation cérébrale avancées a permis de mettre en évidence la présence d’altérations à court et à long terme à la suite d’une commotion cérébrale. Plus spécifiquement, des altérations affectant l’intégrité de la matière blanche et le métabolisme cellulaire ont récemment été révélées par l’utilisation de l’imagerie du tenseur de diffusion (DTI) et la spectroscopie par résonance magnétique (SRM), respectivement. Ces atteintes cérébrales ont été observées chez des athlètes masculins quelques jours après la blessure à la tête et demeuraient détectables lorsque les athlètes étaient à nouveau évalués six mois post-commotion. En revanche, aucune étude n’a évalué les effets neurométaboliques et microstructuraux dans la phase aigüe et chronique d’une commotion cérébrale chez les athlètes féminines, malgré le fait qu’elles présentent une susceptibilité accrue de subir ce type de blessure, ainsi qu’un nombre plus élevé de symptômes post-commotionnels et un temps de réhabilitation plus long. Ainsi, les études composant le présent ouvrage visent globalement à établir le profil d’atteintes microstructurales et neurométaboliques chez des athlètes féminines par l’utilisation du DTI et de la SRM. La première étude visait à évaluer les changements neurométaboliques au sein du corps calleux chez des joueurs et joueuses de hockey au cours d’une saison universitaire. Les athlètes ayant subi une commotion cérébrale pendant la saison ont été évalués 72 heures, 2 semaines et 2 mois après la blessure à la tête en plus des évaluations pré et post-saison. Les résultats démontrent une absence de différences entre les athlètes ayant subi une commotion cérébrale et les athlètes qui n’en ont pas subie. De plus, aucune différence entre les données pré et post-saison a été observée chez les athlètes masculins alors qu’une diminution du taux de N-acetyl aspartate (NAA) n’a été mise en évidence chez les athlètes féminines, suggérant ainsi un impact des coups d’intensité sous-clinique à la tête. La deuxième étude, qui utilisait le DTI et la SRM, a révélé des atteintes chez des athlètes féminines commotionnées asymptomatiques en moyenne 18 mois post-commotion. Plus spécifiquement, la SRM a révélé une diminution du taux de myo-inositol (mI) au sein de l’hippocampe et du cortex moteur primaire (M1) alors que le DTI a mis en évidence une augmentation de la diffusivité moyenne (DM) dans plusieurs faisceaux de matière blanche. De iii plus, une approche par région d’intérêt a mis en évidence une diminution de la fraction d’anisotropie (FA) dans la partie du corps calleux projetant vers l’aire motrice primaire. Le troisième article évaluait des athlètes ayant subi une commotion cérébrale dans les jours suivant la blessure à la tête (7-10 jours) ainsi que six mois post-commotion avec la SRM. Dans la phase aigüe, des altérations neuropsychologiques combinées à un nombre significativement plus élevé de symptômes post-commotionnels et dépressifs ont été trouvés chez les athlètes féminines commotionnées, qui se résorbaient en phase chronique. En revanche, aucune différence sur le plan neurométabolique n’a été mise en évidence entre les deux groupes dans la phase aigüe. Dans la phase chronique, les athlètes commotionnées démontraient des altérations neurométaboliques au sein du cortex préfrontal dorsolatéral (CPDL) et M1, marquées par une augmentation du taux de glutamate/glutamine (Glx). De plus, une diminution du taux de NAA entre les deux temps de mesure était présente chez les athlètes contrôles. Finalement, le quatrième article documentait les atteintes microstructurales au sein de la voie corticospinale et du corps calleux six mois suivant une commotion cérébrale. Les analyses n’ont démontré aucune différence au sein de la voie corticospinale alors que des différences ont été relevées par segmentation du corps calleux selon les projections des fibres calleuses. En effet, les athlètes commotionnées présentaient une diminution de la DM et de la diffusivité radiale (DR) au sein de la région projetant vers le cortex préfrontal, un volume moindre des fibres de matière blanche dans la région projetant vers l’aire prémotrice et l’aire motrice supplémentaire, ainsi qu’une diminution de la diffusivité axiale (DA) dans la région projetant vers l’aire pariétale et temporale. En somme, les études incluses dans le présent ouvrage ont permis d’approfondir les connaissances sur les effets métaboliques et microstructuraux des commotions cérébrales et démontrent des effets délétères persistants chez des athlètes féminines. Ces données vont de pair avec la littérature scientifique qui suggère que les commotions cérébrales n’entraînent pas seulement des symptômes temporaires.The presence of short and long-term alterations following a sports-related concussion has been detected using advanced neuroimaging methods. Using Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy (MRS), alterations of white matter integrity and cellular metabolism have been revealed, respectively. These brain anomalies were detectable in male athletes a few days after a head injury and persisted when athletes were re-evaluated six months post-concussion. However, no study has evaluated the neurometabolic and microstructural effects in the acute and chronic phases of a concussion in female athletes, despite increased susceptibility in women to suffer this type of injury, and a higher number of post-concussion symptoms and rehabilitation time when this injury occurs. Thus, the studies comprising the present thesis aim to document the neurometabolic and microstructural profiles of female concussed athletes using DTI and MRS. The first study evaluated neurometabolic changes in the corpus callosum of male and female hockey players during a university season. Athletes who suffered a concussion were also assessed 72 hours, 2 weeks and 2 months after the head injury in addition to pre- and post-season evaluations. Results showed no difference between athletes who suffered a concussion and control athletes. Furthermore, no difference between pre- and post-season was observed in male athletes, while a decrease in NAA was found in female athletes, suggesting an impact of subconcussive hits to the head. The second study, which used DTI and MRS, revealed alterations in asymptomatic female concussed athletes evaluated an average of 18 months post-concussion. More specifically, MRS revealed a decrease in myo-inositol (mI) levels in the hippocampus and the primary motor cortices (M1) while DTI showed an increase in mean diffusivity (MD) in several white matter tracts. In addition, a region of interest approach of the corpus callosum showed decreased fractional anisotropy (FA) in the segment containing fibers projecting to M1. The third article evaluated athletes who suffered a concussion in the days following head injury (7-10 days) and six months post-concussion using MRS. In the acute phase, neuropsychological alterations and a higher severity of post-concussion and depressive v symptoms were found in concussed athletes relative to controls, but showed recovery in the chronic phase. In contrast, no neurometabolic differences were found between the two groups in the acute phase. In the chronic phase, concussed athletes showed neurometabolic impairments in prefrontal and motor cortices, characterized by a pathological increase of glutamate/glutamine (Glx). Also, a significant decrease in NAA was observed in control athletes at the second time point. Finally, the fourth study aimed to document microstructural alterations within the corticospinal tract and the corpus callosum (CC) of athletes suffering a sport-related concussion six months prior to testing. The analysis showed no difference in the corticospinal tract while several differences were found when segmenting the corpus callosum based on the projections of the callosal fibers. The concussed group had lower MD and lower radial diffusivity (RD) in the region of the CC projecting to the prefrontal cortex, a lower volume of white matter fibers was found in the region projecting to the premotor and supplementary motor areas and a decrease in axial diffusivity (AD) in the region projecting to the parietal and temporal areas was detected. In conclusion, the studies included in this thesis have helped increase knowledge about the neurometabolic and microstructural alterations following a sport-related concussion and showed persistent effects in female athletes. These data are consistent with the literature that suggests concussions are not only causing temporary symptoms

A prospective study of physician-observed concussion during a varsity university hockey season: Metabolic changes in ice hockey players. Part 4 of 4

Object: Despite negative neuroimaging findings using traditional neuroimaging methods such as MRI and CT, sports-related concussions have been shown to cause neurometabolic changes in both the acute and subacute phases of head injury. However, no prospective clinical study has used an independent physician-observer design in the monitoring of these changes. The objective of this study was to evaluate the effects of repetitive concussive and subconcussive head impacts on neurometabolic concentrations in a prospective study of two Canadian Interuniversity Sports (CIS) ice hockey teams using MR spectroscopy (MRS). Methods: Forty-five ice hockey players (25 men and 20 women) participated in this study. All participants underwent pre- and postseason MRI, including spectroscopy imaging, using a 3-T MRI machine. The linear combination model was used to quantify the following ratios: glutamate/creatine-phosphocreatine (Cr), myoinositol/Cr, and N-acetylaspartate (NAA)/Cr. Individuals sustaining a medically diagnosed concussion were sent for MRI at 72 hours, 2 weeks, and 2 months after injury. Results: No statistically significant differences were observed between athletes who were diagnosed with a concussion and athletes who were not clinically diagnosed as sustaining a concussion. Although no statistically significant longitudinal metabolic changes were observed among athletes who were diagnosed with a concussion, the results demonstrated a predictable pattern of initial impairment, followed by a gradual return to ratios that were similar to, but lower than, baseline ratios. No significant pre- to postseason changes were demonstrated among men who were not observed to sustain a concussion. However, a substantively significant decrease in the NAA/Cr ratio was noted among the female hockey players (t(13) = 2.58, p = 0.02, ζ2 = 0.34). Conclusions: A key finding in this study, from the standpoint of future research design, is the demonstration of substantively significant metabolic changes among the players who were not diagnosed with a concussion. In addition, it may explain why there are few statistically significant differences demonstrated between players who were diagnosed with a concussion and players who were not diagnosed with a concussion (that is, the potency of the independent variable was diminished by the fact that the group of players not diagnosed with a concussion might be better described as a subgroup of the players who may have sustained a concussion but were not observed and diagnosed with a concussion). This result suggests that definitions of concussion may need to be revisited within sports with high levels of repetitive subconcussive head impacts. Future analysis of these data will examine the relationships between the modes of MRI (diffusion tensor imaging, MRS, and susceptibility-weighted MR imaging) used in this study, along with other more sensitive evaluative techniques. This type of intermodal comparison may improve the identification of concussions that were previously dependent on the unreliable self-reporting of recognized concussion symptomatology by the athlete or on poorly validated neuropsychological tests

A prospective study of physician-observed concussion during a varsity university hockey season: metabolic changes in ice hockey players.

Object. Despite negative neuroimaging findings using traditional neuroimaging methods such as MRI and CT, sports-related concussions have been shown to cause neurometabolic changes in both the acute and subacute phases of head injury. However, no prospective clinical study has used an independent physician-observer design in the monitoring of these changes. The objective of this study was to evaluate the effects of repetitive concussive and subconcussive head impacts on neurometabolic concentrations in a prospective study of two Canadian Interuniversity Sports (CIS) ice hockey teams using MR spectroscopy (MRS). Methods. Forty-five ice hockey players (25 men and 20 women) participated in this study. All participants underwent pre- and postseason MRI, including spectroscopy imaging, using a 3-T MRI machine. The linear combination model was used to quantify the following ratios: glutamate/creatine-phosphocreatine (Cr), myoinositol/Cr, and N-acetylaspartate (NAA)/Cr. Individuals sustaining a medically diagnosed concussion were sent for MRI at 72 hours, 2 weeks, and 2 months after injury. Results. No statistically significant differences were observed between athletes who were diagnosed with a concussion and athletes who were not clinically diagnosed as sustaining a concussion. Although no statistically significant longitudinal metabolic changes were observed among athletes who were diagnosed with a concussion, the results demonstrated a predictable pattern of initial impairment, followed by a gradual return to ratios that were similar to, but lower than, baseline ratios. No significant pre- to postseason changes were demonstrated among men who were not observed to sustain a concussion. However, a substantively significant decrease in the NAA/Cr ratio was noted among the female hockey players (t(13) = 2.58, p = 0.02, h2 = 0.34). Conclusions. A key finding in this study, from the standpoint of future research design, is the demonstration of substantively significant metabolic changes among the players who were not diagnosed with a concussion. In addition, it may explain why there are few statistically significant differences demonstrated between players who were diagnosed with a concussion and players who were not diagnosed with a concussion (that is, the potency of the independent variable was diminished by the fact that the group of players not diagnosed with a concussion might be better described as a subgroup of the players who may have sustained a concussion but were not observed and diagnosed with a concussion). This result suggests that definitions of concussion may need to be revisited within sports with high levels of repetitive subconcussive head impacts. Future analysis of these data will examine the relationships between the modes of MRI (diffusion tensor imaging, MRS, and susceptibility-weighted MR imaging) used in this study, along with other more sensitive evaluative techniques. This type of intermodal comparison may improve the identification of concussions that were previously dependent on the unreliable self-reporting of recognized concussion symptomatology by the athlete or on poorly validated neuropsychological tests

Adipocyte hypertrophy associates with in vivo postprandial fatty acid metabolism and adipose single-cell transcriptional dynamics

Summary: Adipocyte hypertrophy is associated with metabolic complications independent of obesity. We aimed to determine: 1) the association between adipocyte size and postprandial fatty acid metabolism; 2) the potential mechanisms driving the obesity-independent, hypertrophy-associated dysmetabolism in vivo and at a single-cell resolution. Tracers with positron emission tomography were used to measure fatty acid metabolism in 40 men and women with normal or impaired glucose tolerance (NCT02808182), and single nuclei RNA-sequencing (snRNA-seq) to determine transcriptional dynamics of subcutaneous adipose tissue (AT) between individuals with AT hypertrophy vs. hyperplasia matched for sex, ethnicity, glucose-tolerance status, BMI, total and percent body fat, and waist circumference. Adipocyte size was associated with high postprandial total cardiac fatty acid uptake and higher visceral AT dietary fatty acid uptake, but lower lean tissue dietary fatty acid uptake. We found major shifts in cell transcriptomal dynamics with AT hypertrophy that were consistent with in vivo metabolic changes

Added value of 18F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study

International audienceIntroductionAlthough some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting.MethodsThis multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172).ResultsTwo hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases.DiscussionHigh-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases