Journal of neurotrauma最新文献

Athletes in collision sports frequently sustain repetitive head impacts (RHI), which, while not individually severe enough for a clinical mild traumatic brain injury (mTBI) diagnosis, can compromise neuronal organization by transferring mechanical energy to the brain. Although numerous studies target athletes with mTBI, there is a lack of longitudinal research on young collision sport participants, highlighting an unaddressed concern regarding cumulative RHI effects on brain microstructures. Therefore, this study aimed to investigate the microstructural changes in the brains' of high school rugby players due to repeated head impacts and to establish a correlation between clinical symptoms, cumulative effects of RHI exposure, and changes in the brain's microstructure. We conducted a longitudinal magnetic resonance imaging (MRI) study on 36 male high school rugby players across a season using 3D T1-weighted and multi-shell diffusion MRI sequences, comparing them with 20 matched controls. Players with concussions were separately tracked up to 6 weeks post-injury with three-times scans within this period. The Sport Concussion Assessment Tool (SCAT5) symptom scale assessed mTBI symptoms, and mouthguard-embedded kinematic sensors recorded head impacts. No significant volumetric changes in subcortical structures were found post-rugby season. However, there were substantial differences in mean diffusivity (MD) and axial diffusivity (AD) between the rugby players and controls across widespread brain regions. Diffusion metrics, especially AD, MD, and radial diffusivity of certain brain tracts, displayed strong correlations with SCAT5 symptom severity. Repeated head impacts during a rugby season may adversely affect the structural organization of the brain's white matter. The observed diffusion changes, closely tied to SCAT5 symptom burden, stress the profound effects of seasonal head impacts and highlight individual variability in response to repetitive head impact exposure. To better manage sports-related mTBI and guide return-to-play decisions, comprehensive studies on brain injury mechanisms and recovery post-mTBI/RHI exposure are required.

Vestibular/ocular motor provocation and state anxiety are both independently linked to poor recovery outcomes following concussion. However, the relationship between these two clinical presentations and their co-occurring effects on concussion recovery outcomes is understudied. The purpose was to examine the co-occurring effects of vestibular/ocular motor provocation and state anxiety following concussion. There were 532 participants (15-25 years) with concussions who completed the vestibular/ocular motor screening (VOMS), State-Trait Anxiety Inventory, and the Post-Concussion Symptom Scale within 30 days of injury. Participants were classified into provocation (PROV) and no provocation (NO PROV) groups based on exceeding/not exceeding VOMS cutoffs. An analysis of covariance was used to examine between-group comparisons on state anxiety scores; and logistic regressions, with adjusted odds ratios (Adj OR), were used to evaluate predictors of clinical levels of state anxiety and protracted recovery. A total of 418 participants (78.6%; age = 17.2 ± 2.6; 65% female) exceeding VOMS cutoffs were in the PROV, and 114 (21.4%; age = 16.6 ± 2.2; 53% female) participants were in the NO PROV group. The PROV group (mean [M] = 39.50, standard deviation [SD] = 12.05) exhibited significantly higher state anxiety scores than the NO PROV group (M = 32.45, SD = 10.43) (F[1, 532] = 15.36, p < 0.001, η²= 0.03). Vestibular/ocular motor provocation (Adj OR =3.35, p < 0.001, 95% confidence interval [CI]: 1.42-3.88) was the most robust predictor of clinical state anxiety following concussion (χ² [4, 532] = 86.78, p < 0.001). Participants exhibiting vestibular/ocular motor provocation with clinical levels of state anxiety were at 2.47 times (p < 0.001, 95% CI: 1.53-3.99) greater odds of experiencing a protracted concussion recovery than participants with vestibular/ocular motor provocation without clinical state anxiety. Vestibular/ocular motor provocation is associated with increased state anxiety following concussion, and the addition of clinical state anxiety to vestibular/ocular motor provocation increases the odds for protracted recovery. Clinicians should assess vestibular/ocular motor function and anxiety following concussion.

To compare the incremental prognostic value of pupillary reactivity captured as part of the Glasgow Coma Scale-Pupils (GCS-P) score or added as separate variable to the GCS+P, in traumatic brain injury (TBI). We analyzed patients enrolled between 2014 and 2018 in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI, n = 3521) and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI, n = 1439) cohorts. Logistic regression was utilized to quantify the prognostic performances of GCS-P (GCS minus number of unreactive pupils) and GCS+P versus GCS alone according to Nagelkerke's R². End-points were mortality and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-4) at 6 month post-injury. We estimated 95% confidence intervals (CIs) with bootstrap resampling to summarize the improvement in prognostic capability. In a meta-analysis of CENTER-TBI and TRACK-TBI, GCS as a linear score had a R² of 25% (95% CI 19-31%) for mortality and 33% (4-41%) for unfavorable outcome. Pupillary reactivity as a separate variable improved the R² by an absolute value of 6% (4.0-7.7%) and 2% (1.2-3.0%) for mortality and unfavorable outcome, respectively, while comparatively half of this improvement was captured by the GCS-P score (3% [2.1-3.3%], 1% [1-1.7%], respectively). GCS-P showed a stronger association with 6-month outcome after TBI than GCS alone and provides a single integrated score. However, this comes at a loss of clinical and prognostic information compared with GCS+P. For prognostic models, inclusion of GCS and pupillary reactivity as separate factors may be preferable to using a GCS-P summary score.

Following spinal cord injury (SCI), there is a short-lived recovery phase that ultimately plateaus. Understanding changes within the spinal cord over time may facilitate targeted approaches to prevent and/or reverse this plateau and allow for continued recovery. Untargeted metabolomics revealed distinct metabolic profiles within the injured cord during recovery (7 days postinjury [DPI]) and plateau (21 DPI) periods in a mouse model of severe contusion SCI. Alterations in lipid metabolites, particularly those involved in phospholipid (PL) metabolism, largely contributed to overall differences. PLs are hydrolyzed by phospholipases A2 (PLA2s), yielding lysophospholipids (LPLs) and fatty acids (FAs). PL metabolites decreased between 7 and 21 DPI, whereas LPLs increased at 21 DPI, suggesting amplified PL metabolism during the plateau phase. Expression of various PLA2s also differed between the two time points, further supporting dysregulation of PL metabolism during the two phases of injury. FAs, which can promote inflammation, mitochondrial dysfunction, and neuronal damage, were increased regardless of time point. Carnitine can bind with FAs to form acylcarnitines, lessening FA-induced toxicity. In contrast to FAs, carnitine and acylcarnitines were increased at 7 DPI, but decreased at 21 DPI, suggesting a loss of carnitine-mediated mitigation of FA toxicity at the later time point, which may contribute to the cessation of recovery post-SCI. Alterations in oxidative phosphorylation and tricarboxylic acid cycle metabolites were also observed, indicating persistent although dissimilar disruptions in mitochondrial function. These data aid in increasing our understanding of lipid metabolism following SCI and have the potential to lead to new biomarkers and/or therapeutic strategies.

Traumatic brain injury (TBI) is frequently associated with hypopituitarism. The hypothalamic-pituitary axis appears to be susceptible to the same forces that cause injury to the parenchyma of the brain. Following even a mild TBI (mTBI), patients may suffer transient or permanent decreases in anterior pituitary hormones, including somatotropin (growth hormone [GH]), gonadotropins (luteinizing hormone and follicle-stimulating hormone), thyrotropin, and adrenocorticotropic hormone, with the most frequent long-term deficiency being GH deficiency (GHD). GHD is common after mTBI and is often the cause of persistent post-concussive symptoms a year or more post-injury. GHD is known to cause physical and cognitive fatigue, cognitive inefficiency, metabolic changes, and a range of psychological symptoms. Confusing the picture is that some symptoms of GHD are also common to brain injury itself. To facilitate the detection of GHD when comorbid with TBI, we utilized a new symptom inventory, the Quality-of-Life Scale-99 (QoLS-99), and administered it to a cohort of chronic TBI subjects with and without GHD, distinguished using the insulin tolerance test (ITT). Between 2018 and 2023, 371 patients completed the QoLS-99, of which 263 underwent GH testing with the ITT. Of these 263 patients, 136 (52%) were diagnosed with GHD. A retrospective comparison of QoLS-99 scores found that loss of libido (p < 0.006), a reliance on sleep aids (p < 0.011), and feeling overweight (p < 0.015) were the strongest univariate predictors of GHD. Most survey items did not elicit a significant difference in response between the GHD groups, and for those that did, effect sizes were mild to moderate. Still, initial findings demonstrate strong predictive value in a subset of survey items (i.e., GHD symptoms) that are most discriminating in the sample of patients with TBI. A multivariate prediction model using this subset of questions was able to differentiate GHD status in patients with TBI, correctly identifying 88% of GHD cases with a 37% false positive rate. Based on these findings, we recommend that clinicians inquire about libido, insomnia, and body image as potential markers for GHD. Furthermore, given the amenability of patients with GHD to growth hormone replacement therapy, we strongly encourage clinicians and basic scientists to develop interventions for the large and underserved population of patients with TBI with comorbid GHD.

Cervical spinal cord injury usually leads to cardiorespiratory dysfunction due to interruptions of the supraspinal pathways innervating the phrenic motoneurons and thoracic sympathetic preganglionic neurons. Although clinical guidelines recommend maintaining the mean arterial pressure within 85-90 mmHg during the first week of injury, there is no pre-clinical evidence from animal models to prove the therapeutic efficacy of hemodynamic management. Accordingly, the present study was designed to investigate the therapeutic efficacy of hemodynamic management in rats with cervical spinal cord contusion. Adult male rats underwent cervical spinal cord contusion and the implantation of osmotic pumps filled with saline or norepinephrine (NE) (125 μg/(kg·h) for 1 week). The cardiorespiratory function of unanesthetized rats was examined using a non-invasive blood pressure analyzer and double-chamber plethysmography. Cervical spinal cord contusion caused a long-term reduction in the mean arterial pressure and tidal volume. This hypotensive response was significantly reversed in contused rats receiving NE (1 day: 88 ± 19 mmHg; 2 weeks: 96 ± 13 mmHg) compared with contused rats receiving saline (1 day: 72 ± 15 mmHg; 2 weeks: 82 ± 10 mmHg). NE also significantly improved the tidal volume 1 day post-injury (contused + NE: 0.7 ± 0.2 mL; contused + saline: 0.5 ± 0.1 mL). Immunofluorescence staining results revealed that injury-induced reductions of noradrenergic and glutamatergic fibers within the thoracic spinal cord were significantly improved by NE. These results provided the evidence demonstrating that hemodynamic management using NE significantly improves cardiorespiratory function by alleviating neural pathway damage after cervical spinal cord contusion.

Resting-state electroencephalography (rsEEG) has developed as a method to explore functional network alterations related to sport-related concussion (SRC). Although exercise is an integral part of an athlete's return to sport (RTS) protocol, our understanding of the effects of exercise on (impaired) brain network activity in elite adult athletes is limited. However, this information may be beneficial to inform recovery and RTS progressions. Recording (128-channel) rsEEG datasets before and after a standardized moderate aerobic bike exercise test, this study aimed to explore functional connectivity patterns in whole brain and relevant functional networks in a group of elite adult athletes post-injury compared with healthy matched controls. The following networks were selected a priori: whole brain (68 regions of interest [ROIs]), default mode network (14 ROIs), central autonomic network (CAN, 24 ROIs), and visual network (8 ROIs). Twenty-one SRC athletes and 21 age-, sex-, sport type-, and skill level-matched healthy controls participated in this study. The SRC athletes were recruited during their RTS protocol (days since injury: 2-140 days). All athletes were able to achieve the exercise goal of reaching a moderate intensity (70% of their age-calculated maximum heart rate) while staying sub-symptomatic. Before and after exercise, functional connectivity was calculated by the phase locking value, in the alpha band (7-13 Hz). Mann-Whitney U and Wilcoxon signed rank tests were used to explore neurophysiological differences between and within groups, respectively. Whole-brain connectivity increased significantly from pre- to post-exercise within both groups (SRC: 0.264-0.284; p = 0.011 vs. controls: 0.253-0.257; p = 0.011). While CAN connectivity significantly increased only within the SRC group from pre-(0.298) to post-exercise (0.317; p = 0.003). Although all athletes reached their exercise goal without exacerbation of symptoms, the impact of exercise on the CAN appears to be greater for the SRC athletes, than matched healthy controls. The potential clinical significance of this finding is that it may have revealed an underlying mechanism for the cardiac autonomic alterations post-injury. This study merits further investigation into the CAN, as a network of interest more closely aligned with the clinical features (e.g., autonomic dysfunction) during athletes' RTS.

Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with AD risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to find such associations. This review covers literature that uses positron emission tomography (PET) of β-amyloid (Aβ) and/or tau to examine individuals with a history of TBI who are at increased risk for AD due to age. A comprehensive literature search was conducted on January 9, 2023, and 26 resulting citations met inclusion criteria. Common methodological concerns included small samples, limited clinical detail about participants' TBI, recall bias due to reliance on self-reported TBI, and an inability to establish causation. For both Aβ and tau, results were widespread but inconsistent. The regions that showed the most compelling evidence for increased Aβ deposition were the cingulate gyrus and cuneus/precuneus. Evidence for elevated tau was strongest in the medial temporal lobe, entorhinal cortex, precuneus, and frontal, temporal, parietal, and occipital lobes. However, conflicting findings across most regions in both Aβ- and tau-PET studies indicate the critical need for future work in expanded samples and with greater clinical detail to offer a clearer picture of the relationship between TBI and protein deposition in older individuals at risk for AD.

Mild traumatic brain injury (mTBI) is a growing health concern in the context of an aging population. Older adults comprise a distinct population, with an increased vulnerability for mTBI due to comorbid diseases and age-associated frailty compared with the adult population. The aim of this study was to assess the recovery course and determinants of outcome in a large cohort of older patients with mTBI. For this study, 154 patients aged ≥60 years with mTBI admitted to the Emergency Department were investigated in a prospective observational cohort (ReCONNECT study). Demographics and injury characteristics (computed tomography scan, Glasgow Coma Scale) were determined on admission. Early determinants of outcome were assessed at 2 weeks post-injury (e.g., early post-traumatic complaints and emotional distress) with validated questionnaires. Quality of life (QoL) was determined at 3 months with the World Health Organization Quality of Life Scale-Shortened Version. Functional outcome was determined at 3 (early) and 6 months (long term) post-injury with the Glasgow Outcome Scale Extended (GOSE). Logistic regression analyses identified predictors of outcome with dichotomized GOSE scores as dependent variable (incomplete recovery was defined by GOSE ≤ 7 and complete recovery by GOSE 8). Complete recovery was observed in 42% of patients at 3 months post-injury without significant sex differences. More early post-traumatic complaints were present in patients with incomplete recovery, compared with patients with complete recovery (p < 0.001). Scores on overall QoL, general health-related QoL and all subdomains were lower for patients with incomplete recovery compared with patients with complete recovery (p < 0.05). Incomplete recovery at 3 months post-injury was predicted by increased physical frailty and early post-traumatic complaints (Nagelkerke R² = 0.25). At 6 months post-injury, 53% of patients had complete recovery with higher frequency in males (60%) compared with females (42%) (p = 0.025). None of the investigated variables significantly predicted long-term outcome at 6 months post-injury (Nagelkerke R² = 0.14), which might be explained by the changing cohort characteristics over time due to age-related morbidity. Our results demonstrate that almost half of older patients with mTBI show complete recovery with complaints and physical frailty as predictors of outcome at 3 months post-injury. Recovery still improves after 3 months and further follow-up is necessary to identify other factors that are associated with long-term outcomes in this specific category of patients with mTBI. The recovery course in older patients with mTBI is dynamic and further research on factors associated with long-term outcomes in this specific patient population is imperative to enhance treatment strategies.