Journal of neurotrauma最新文献

The existing research on the microstructural alterations associated with sport-related concussions (SRCs) has primarily focused on deep white matter (DWM) fibers, while the impact of SRCs on the superficial white matter (SWM) and gray matter (GM) remains unknown. This study aimed to characterize the altered metrics obtained from neurite orientation dispersion and density imaging (NODDI) in boxers with SRCs, and thereby determine whether distinct regional patterns of microstructural alterations can offer valuable insights for accurate diagnosis and prognosis. Concussed boxers (n = 56) and healthy controls (HCs) with typically developing (n = 72) underwent comprehensive neuropsychological assessment and magnetic resonance imaging (MRI) examinations. The tract-based spatial statistics approach was used to investigate alterations in the DWM and SWM, while the gray matter-based spatial statistics approach was used to examine changes in the GM. The median time from the last SRC to MRI in the SRC group was 33.5 days (interquartile range, 45.25). In comparison with HCs, the SRC group exhibited lower fractional anisotropy (FA), neurite density index (NDI), and isotropic volume fraction (ISOVF), as well as higher mean diffusivity, axial diffusivity (AD), and radial diffusivity in both the DWM and SWM. Moreover, the SRC group exhibited lower FA, NDI, orientation dispersion index, and ISOVF in the GM, as well as higher AD. The altered microstructure of both gray and white matter was found to be associated with deficits in working memory and vocabulary memory among boxers. In addition to characterizing the DWM impairment, NODDI further elucidated the effects of SRCs on the microstructure of GM and SWM, offering a reliable imaging biomarker for SRC diagnosis and shedding light on the pathophysiological changes underlying SRCs.

Mental health conditions and concussion history reported by a collegiate athlete may contribute to prolonged recovery and symptom severity after concussion. This work examined the potential associations among concussion history, preexisting conditions, and sex relative to initial symptom severity and recovery duration following sport-related concussion (SRC) in a cohort of Division 1 National Collegiate Athletic Association athletes. This prospective cohort study analyzed symptom severity, recovery, and return-to-play (RTP) times reported post-SRC using data collected as part of the Pac-12 Concussion Assessment, Research and Education Affiliated Program and Health Analytics Program. Health history questionnaires that included self-reported history of preexisting conditions were completed at baseline. When consented athletes were diagnosed with a concussion, daily postconcussion symptom scores were evaluated until an athlete was clinically determined to be asymptomatic. Generalized linear and Cox proportional hazards models were used to determine associations between preexisting conditions and recovery and RTP times. Ninety-two concussions met inclusion criteria. Notable differences in initial symptom severity existed between females and males who had mood disorders (effect size [d] = 0.51) and attention-deficit hyperactivity disorder (ADHD; d = 0.93). The number of previous concussions was a strong predictor of athletes reporting preexisting mood disorders, depression, anxiety, and ADHD (p = 0.008-0.04). Females with ≥2 previous concussions required more days to RTP than males (d = 0.31-0.72). Weekly recovery and RTP probabilities substantially differed between athletes who did or did not have learning disorders (LDs; hazard ratio [HR]_Recovery = 0.32, HR_RTP = 0.22, d = 1.96-2.30) and ADHD (HR_Recovery = 3.38, HR_RTP = 2.74, d = 1.71-4.14). Although no association existed between concussion history and acute symptom severity, collegiate athletes with a history of concussion had higher probabilities of reporting depression, mood disorders, anxiety, and ADHD. Having ADHD or LDs likely strongly affects time to recovery and RTP for collegiate athletes.

Control over symptoms postconcussion is central to an active self-directed recovery process. Therefore, assessing a patient's confidence in controlling their symptoms and facilitating their concussion recovery is an important component of treatment. Previously, no measures existed to assess symptom-specific self-efficacy (SE) in pediatric concussion recovery. SE is an individual's belief or confidence in their capabilities to execute action plans necessary to perform certain behaviors. Based on this definition, we developed the Progressive Activities of Controlled Exertion-Self-Efficacy (PACE-SE) scale to measure a patient's SE related to pediatric concussion recovery-specific activities. The aim of this article is to present the psychometric characteristics (evidence of reliability, validity) of the PACE-SE scale. The 17-item PACE-SE was administered to children and adolescents, 10-18 years of age, recovering from a diagnosed concussion as part of a standard clinical evaluation. Results revealed a four-factor structure producing the following scales: Managing My Stress, Managing My Activity, Seeking Adult Assistance, and Maintaining Positive Outlook. The PACE-SE scores indicated excellent internal consistency reliability with reasonable test-retest reliability over time. Evidence for the association between recovery status and greater confidence and control over recovery-related activities as measured by the PACE-SE was supported by: (1) an inverse association with symptom status reflecting lower confidence for managing recovery with higher symptom load, (2) greater reported problems with school performance associated with lower SE, (3) positive change in SE ratings across two clinic visits associated with symptom improvement, and (4) a significant difference in SE ratings evident between recovered and nonrecovered patients. The psychometric evidence supporting the PACE-SE scale provides the clinician with a measure to understand the child/adolescent patient's self-confidence in facilitating their concussion recovery.

Chronic post-traumatic headache (CPTH) after a mild traumatic brain injury (mTBI) has been reported in up to 60% of patients and can be extremely debilitating. While pharmacological treatments are typically used for CPTH, they frequently cause side effects and have limited effectiveness, leading individuals with CPTH to be unsatisfied with current treatment options and to seek nonpharmacological options. Acupuncture has been identified as a potential treatment option; however, the evidence in this population remains limited. The overall goal of this study was to examine the effect of a once weekly (e.g., low dose) versus twice weekly (e.g., high dose) of acupuncture treatment on CPTH in individuals with mTBI. Thirty-eight individuals were randomized to receive either 5 or 10 acupuncture treatments using a standard protocol over 5 weeks. The protocol consisted of 14 points using traditional acupuncture and 4 points using electroacupuncture. Headache outcomes, safety, treatment adherence, sleep quality, and quality of life (QOL) were assessed. The results showed that while there were no differences between dose groups for any of the outcomes assessed, acupuncture significantly reduced the number of headache days and headache pain intensity in individuals with CPTH. There were no significant changes in acute medication use or sleep quality. While there were some QOL improvements identified, these results should be interpreted with caution. Overall, acupuncture was shown to be safe and well-tolerated in people with CPTH after mTBI, and five acupuncture treatments using a standardized protocol shows promise in providing headache relief for this population.

Deep vein thrombosis and pulmonary embolism prophylaxis is an important part of trauma care. Despite an increased risk of thrombotic complications, the use of venous thrombosis chemoprophylaxis in penetrating traumatic brain injury (pTBI) patients is met with reluctance from neurosurgeons because of concern for the exacerbation of intracerebral hemorrhage. The objective of this study was to provide initial pre-clinical evidence of the effects of Lovenox (LVX) administration following pTBI with significant intracerebral hemorrhage. Sprague-Dawley rats received a penetrating ballistic-like brain injury. Animals were randomly divided into two groups following injury: LVX (25 mg/kg) or vehicle (VEH, saline). LVX or vehicle was administered subcutaneously beginning 24 h after the injury and continued daily for 7 days post-injury. A neurological assessment was performed daily and magnetic resonance imaging (MRI) was performed at baseline, 1, 2, 3, and 7 days post-injury. Following the final MRI, brains were isolated and prepared for histological analysis. Thromboelastography demonstrated dramatic anticoagulation effects which were confirmed by significant increases in partial thromboplastin time (p < 0.001). Daily neurological assessment revealed no worsening of functional deficits following LVX treatment. MRI analysis demonstrated no differences in cerebral edema or intracranial hemorrhage volumes between treatment groups at any tested post-injury time points. However, LVX elicited a significant reduction in fibrin deposition in the ipsilateral striatum and lesion site at 7 days post-injury (p < 0.05). Serum levels of beta-amyloid were decreased at 7 days following LVX treatment (p < 0.05) which may indicate neuroprotective effects but was not correlated to brain levels. The results presented indicate that administration of LVX at a dose capable of inducing anticoagulation is safe in a rodent model of pTBI without exacerbation of intracerebral hemorrhage within the first 7 days of injury.

Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI (mTBI). Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion magnetic resonance imaging in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in 19 U.S. military veterans with chronic mTBI, compared with a matched control group of 14 veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata (ACR) in the GOALS group compared with the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right ACR pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the ACR in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract.

Traumatic brain injury (TBI), a risk factor for later-life dementia, leads to salient brain atrophy, particularly in the white matter. It is not clear how white matter atrophy progresses or why some brain regions are damaged while others are spared. We hypothesized that spatial variations of cell-specific gene expression contributed to the selective white matter loss vulnerability following mild TBI (mTBI). Gene expression data were sourced from the publicly available Allen Human Brain Atlas, which comprises microarray data spanning nearly the entire brain, derived from six neurologically normal adult donors. A total of 100 patients with acute stage (within 7 days post-injury) mTBI were enrolled. Of these, 60 patients were followed up at 3 months post-injury and 37 were followed up at 6-12 months post-injury. In addition, 59 healthy controls (HCs), matched for age, gender, and education, were included for comparative analysis. White matter volume changes were analyzed at both the acute stage, 3 months, and 6-12 months follow-up in mTBI patients compared with HCs. Patients with mTBI exhibited significant white matter atrophy in the frontal, parietal, and temporal cortices at 3 months post-injury, which even persisted at 6-12 months follow-up. In addition, mTBI patients with cognitive deficits showed more severe brain atrophy compared with those without cognitive deficits. Crucially, the gene expression marking endothelial cells and S1 pyramidal neurons were associated with increased brain atrophy, whereas the gene expression marking microglia and CA1 pyramidal neurons were associated with decreased brain atrophy in mTBI patients at 3 months post-injury. Microglia and endothelial cells can explain 23.6% of regional variations in the white matter atrophy. These findings suggested that modulating cellular activation, especially by promoting microglial activation at 3 months post-injury, might be a promising approach to prevent white matter atrophy, enhance cognitive outcomes, and reduce the risk of later-life dementia.

Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals with either stable or critical vital signs were euthanized within 4 h after injury for neuropathological assessment, with emphasis on axonal and vascular pathologies in the brainstem. The majority of cases were characterized by fractures of the cranium at or about the impact site, extensive subarachnoid hemorrhages, coup and contrecoup contusions, and primarily diffuse axonal and vascular lesions throughout the cerebrum, particularly in the brainstem. Absence of spontaneous respiration that was encountered frequently was associated with both severity of impact and the severity of brainstem axonal and vascular lesions. A focused regional examination of brainstem pathology indicated a link between adverse outcomes and diffuse axonal lesions within the medial medulla or vascular lesions within the anteroventral brainstem, a pattern suggesting that injury to brainstem respiratory centers may play a role in apnea following BHBT. In addition, while the overall burden of diffuse axonal and vascular pathologies correlated with each other, we found minimal overlap in their regional distribution. Our findings indicate that high-energy, blunt-force impact TBI causes diffuse lesions in axons and blood vessels associated with poor outcomes. They also suggest that axons and vessels may have distinct responses to tissue deformation and that commonly used markers of vascular pathology, for example, in diagnostic radiology, cannot be used as direct surrogates of diffuse axonal injury. In concert, our study underscores the role of regional axonal and vascular injuries in the brainstem in acute respiratory decompensation after high-rate blunt TBI, even in the presence of head protection; it also emphasizes the importance of detailed clinicopathological work in complex brains in the field of TBI.

This study compared the roles of extraparenchymal autonomic nervous system (ANS) control of cerebral blood flow (CBF) versus intraparenchymal cerebrovascular autoregulation in 487 patients with aneurysmal subarachnoid hemorrhage (SAH) and 413 patients with traumatic brain injury (TBI). Vasomotion intensity of extraparenchymal and intraparenchymal vessels were quantified as the amplitude of oscillations of arterial blood pressure (ABP) and intracranial pressure (ICP) in the very low frequency range of 0.02-0.07 Hz, or periods of 55-15 sec, computed with a bandpass filter. A version of the pressure reactivity index (PRx-55-15) was computed as the correlation of the filtered waveforms, ABP-55-15 and ICP-55-15. Since ABP-55-15 is measured in the radial artery, any influence of cerebral factors must be mediated by the ANS. ICP-55-15 is measured in the brain and is influenced by intraparenchymal chemical and metabolic factors in addition to the ANS. Patient outcome was assessed using the Extended Glasgow Outcome Score (GOSe). Ten-day mean cerebral perfusion pressure (CPP) was negatively correlated with GOSe in the TBI cohort (R = -0.13, p = 0.01) but positively correlated with GOSe in the SAH cohort, (R = 0.32, p < 0.00001), indicating a much greater dependence on ANS support in the form of elevated CPP in SAH. The optimal CPP range for TBI was 60-70 mmHg, but for SAH it was 110-120 mmHg. The percentage of monitoring time with PRx-55-15 < 0.8, indicating very pressure-active cerebral vessels that resist ANS influence via systemic ABP, is positively correlated with GOSe in the TBI cohort (R = 0.14, p = 0.003), but negatively correlated with GOSe in the SAH cohort (R = -0.10, p = 0.004). The TBI cohort optimal PRx-55-15 for patient outcome was -1.0, while the SAH optimum was 0.3. For the TBI cohort, the correlation of ABP-55-15 amplitude with 10-day mean ICP-55-15 amplitude was 0.29. For the SAH cohort the correlation was 0.51, which is stronger (p = 0.0001). The TBI cohort had a median GOSe of 5 (interquartile range [IQR] 3-7), while SAH had a median of 3 (IQR 3-5), which is worse (p < 0.00001). The higher optimal CPP in patients with SAH, more passive optimal pressure reactivity, and greater dependence of cerebral on systemic vasomotion indicate that they require more active support by the ANS and systemic circulation for CBF than patients with TBI. CBF in patients with TBI is more reliant on cerebrovascular autoregulation based on metabolic demand. This appears to be deficient following SAH, making the heightened ANS support necessary. Although this support is beneficial, it does not fully compensate for the loss of cerebrovascular autoregulation, as reflected in the problems in the SAH cohort with delayed cerebral ischemia and poor outcome.