Neurotrauma reports最新文献

Pain is prevalent and a major source of disability after a traumatic brain injury (TBI) and a spinal cord injury (SCI). With a view of reducing the pain burden in neurotrauma, this study aimed to describe the use of pain management strategies and the adverse effects of opioids in patients with TBI and SCI. We collected data at hospital discharge (T1) and at 3 months post-injury (T2). A total of 70 patients, including 49 with TBI and 21 with SCI, with a mean age of 56 years (±21.1, ±17.9) were included. Almost a third of participants with TBI (33%) and SCI (29%) had a moderate average pain intensity at T1, and most experienced mild average pain intensity at T2. At T1, 80% of participants used opioids, whereas at T2, 26% of participants with TBI and 53% of those with SCI did. The main co-analgesic used was acetaminophen, with 78% and 17% for participants with TBI and 81% and 40% for participants with SCI at T1 and T2. The most common non-pharmacological strategy in participants with TBI was rest at T1 (45%) and T2 (32%), and comfortable positioning in participants with SCI at both timepoints (81% and 53%). The two most frequent adverse effects of opioids in both populations at T1 and T2 were drowsiness (35% vs. 43%; 10% vs. 13%) and constipation (27% vs. 38%; 7% vs. 20%). Opioids remain the most widely used pain management strategy in neurotrauma. Promoting a judicious use of opioids, combined with other strategies, could help patients with neurotrauma achieve adequate and safe pain relief.

Research on mild traumatic brain injury (mTBI) and its impact on young adults is limited, despite this being an important time in their lives to work toward independence and career development. We analyzed data on 663 persons aged 17-29 years old with mTBI (i.e., TBI with Glasgow Coma Scale scores 13-15) and 170 controls who did not experience an injury from the multicenter, Transforming Research and Clinical Knowledge in TBI study. We assessed participants with mTBI, subdivided into those with computed tomography (CT) evidence of TBI (CT+) and those without (CT-), at 12 months post-injury with measures to examine symptom persistence, work and school status, and functional outcomes. Results indicated differences between mTBI and control participants related to return-to-work, return-to-school, and persistent symptoms. Those in the mTBI group were more likely to experience adverse symptoms and detrimental functional effects compared with controls at 12-months post-injury. However, other factors that may not have been measured could have contributed to these outcomes. Young adults are in a transition period where they are working to achieve independence and to establish careers; however, if they sustain a TBI, they, their families, and their medical providers may not understand how the injury contributes to their outcomes, and they may also have limited experience in seeking resources for care. Outcomes for mTBI could also disrupt their career and life trajectories, making this an important area for further investigation and intervention.

This study aimed to explore the experience and complications of cranioplasty (CP) with polyether ether ketone (PEEK) in pediatric and adolescent patients after decompressive craniectomy (DC). A total of 62 children (aged <18 years) with cranial bone defects due to DC underwent CP with a custom-made PEEK at our department between January 2018 and April 2023. The clinical characteristics, radiological features, surgical conditions, postoperative complications, and follow-up results of these patients were analyzed retrospectively. Kaplan-Meier survival analysis and Cox regression were used to analyze data. The age of the patients ranged from 2 to 17 years. The follow-up periods ranged from 12 to 70 months. Six patients experienced subcutaneous fluid accumulation (9.7%), five experienced epidural fluid accumulation (8.1%), and two experienced scalp inflammation (3.2%), which all were cured before discharge. Seven patients experienced bone gap expansion at the interface between the cranial bone and PEEK during follow-up (11.3%). Univariate analysis showed that DC-CP time interval (<3 months) and age were two influencing factors. Multivariate analysis revealed that age was the most important factor (p < 0.005, hazard ratio = 0.250, 95% confidence interval: 0.096-0.652). No reoperation was performed. Medical follow-ups were carried out further. For pediatric patients with cranial defects after DC who receive CP with a custom-made PEEK, two variables including younger age and too short DC-CP time interval may be unfavorable factors, to make patients experience bone gap expansion at the interface between the cranial bone and the PEEK. Additional data should be collected to validate our conclusions.

Repetitive head impacts from contact sports are associated with an increased risk of neurodegenerative conditions. While studies have examined acute and chronic outcomes in young and deceased athletes, research on middle-aged former athletes remains limited. We employed multiplex biomarker approaches to examine whether brain injury and systemic inflammatory blood biomarkers are reflective of ≥10 years of participation in contact sports in retired, middle-aged amateur athletes. This cross-sectional study included a cohort of 41 former contact athletes (32 male, 9 female) and 22 age- and sex-matched noncontact athletes (14 male, 8 female). Blood biomarkers of brain injury, including glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 (UCH-L1), tau, and neurofilament light (NfL), alongside 18 systemic inflammatory markers, were examined via linear regression models with age and concussion history as covariates. Our analyses revealed no significant differences in brain injury blood biomarkers between groups. However, increasing age was associated with increased NfL levels in contact athletes, while greater concussion history correlated with elevated UCH-L1 and tau in contact athletes only. Contact athletes exhibited significantly increased levels of systemic inflammatory markers, including IL-8, CCL-2, CCL-3, IL-2, VCAM-1, and S100B. While brain injury blood biomarkers did not differ between groups, the association between age, concussion history, and increased NfL, UCH-L1, and tau levels in the contact group suggests potential long-term neural consequences of repetitive head impacts. Elevated systemic inflammatory markers potentially highlight a chronic inflammatory response in former contact athletes, underscoring the need for continued monitoring and interventions to mitigate neurodegenerative risk.

Recent investments in large-scale mortem tissue collection have accelerated opportunities to understand the neuropathology of traumatic brain injury (TBI) and post-traumatic neurodegeneration (PTND). Clinicopathological correlation requires ante-mortem clinical information. Post-mortem family interviews (PFIs) are an established method to capture comprehensive ante-mortem clinical information. The aim of this report was to summarize our experience of using the PFI in the Late Effects of TBI (LETBI) brain donor program to facilitate replication, expansion, and refinement of PFI methods in TBI brain donor programs. We describe the content development and structure of the LETBI PFI; interviewer training and qualifications; and considerations regarding interview duration, informant selection, and interview timing, as well as PFI inter-rater reliability. We also compare the information captured in the PFI with data abstracted from the medical records for 34 decedents in the LETBI brain donor program to illustrate the complementarity of these approaches and highlight the unique contributions of the PFI. The PFI can provide granular details about a decedent's clinical history and symptom trajectories over time, potential contributing factors to PTND including social determinants of health (e.g., race and years of education), family history of medical and psychiatric conditions, and contextual information regarding cause(s) of death. The PFI is an important component of a multi-modal autopsy that provides unique insights essential for clinical-pathological correlation investigations of chronic TBI and PTND neuropathology.

The objective of this retrospective cohort study was to evaluate mortality risk over five years among 6,432 female patients with a health care encounter diagnosis of TBI from hospitals and outpatient clinics within a university health system. We used TBI severity, defined by the Centers for Disease Control and Department of Defense/Veterans Affairs: mild, moderate/severe/penetrating, indeterminate severity. To determine patient death, we used death in a Penn Medicine facility and linkage to the Social Security Death Index. We used Cox proportional hazards models adjusted for age at the time of TBI diagnosis, race, and encounter type to estimate associations of TBI severity with mortality risk. We evaluated interactions with encounter type and age, and stratified results by inpatient/outpatient and age group (≥65 years). Median age was 47 years (25th-75th percentiles: 29-63). Patients were most commonly self-reported White race (n = 4,126, 64.0%), and diagnosed at an outpatient encounter (n = 5,099, 79.3%; among them, 1-2% urgent/emergent). Median follow-up time was 4.22 years (IQR, 2.3-4.9 years). Overall, 2.9% (n = 185) of patients died within five years of injury. Compared with mild TBI, mortality risk over five years was 2.06 times higher (95% CI = 1.27-3.33) for moderate/severe/penetrating TBI, and 1.54 times higher (95% CI = 0.98-2.42) for indeterminate TBI. Associations were attenuated among females with inpatient encounter type and those aged 65 years or older. Our results demonstrate that TBI severity affects survival among females, and this differs by encounter type and age. Findings motivate future, more focused research into the dynamics of TBI among females.

Most individuals with moderate-to-severe diffuse axonal injury (DAI) have impaired verbal fluency (VF) capacity. Still, the relationship between brain and VF recovery post-DAI has remained mostly unknown. The aim was to assess brain changes in 13 cortical thickness regions of interest (ROIs), fractional anisotropy (FA), and free water (FW) in three language-related tracts; the VF performance at 6 and 12 months after the DAI; and whether brain changes from 3 to 6 months predict VF performance from 6- to 12-month post-DAI. Twenty-one adults with moderate and severe DAI were analyzed. Structural and diffusion data were acquired on a 3T system 3 and 6 months after the injury. The differences in cortical thickness, FA, and FW values over time were analyzed as factors for the phonemic and semantic VF scores between the 6th and 12th months following the DAI. All analyses were corrected for multiple comparisons. Cortical thickness increased over time in 7 of the 13 ROIs in the right hemisphere and 5 of the 13 ROIs in the left hemisphere. There was an increase in FA in the right arcuate fasciculus and the inferior longitudinal fasciculus over time. An increase in phonemic VF scores was detected between 6 and 12 months post-traumatic brain injury, but not in semantic VF scores over time. Cortical thickness changes in the left posterior inferior frontal pars opercularis and left anterior superior temporal sulcus from 3 to 6 months were associated with improved phonemic VF scores over time. There was no association between diffusion magnetic resonance imaging metrics and VF scores. Our findings suggest that brain plasticity plays a significant role in the initial year following traumatic brain injury, as evidenced by increased cortical thickness and white matter integrity. Improved VF is associated with increased thickness in cortical motor regions responsible for speech performance. However, a larger sample size is needed to confirm these findings.

Heterogeneity associated with traumatic brain injury (TBI) outcomes necessitates validated controls to differentiate pathophysiological events from experimental methodology. While craniectomies are commonly used in TBI research, inadvertent dura disruption can result in structural deficits, impacting cellular function and neurobehavioral outcomes. Thus, there is a critical need to evaluate the effect of craniectomy on neurological outcomes to develop robust experimental controls and improve pre-clinical TBI research. In this study, craniectomy mice undergoing surgical and anesthetic intervention were assessed against naïve mice for neurological deficits and pathophysiological dysfunction. T2-weighted magnetic resonance imaging confirmed that no lesions or cavities were observed postcraniectomy. However, the cranial defect induced midline shifting over time, which might contribute to poorer behavioral outcomes in the novel object recognition assessment. Immunohistochemical analysis demonstrated an increase in GFAP and Iba1, indicating craniectomy elicited an inflammatory response. Indeed, neuroinflammation led to an increase in neuronal cell death, as measured by increases in α-II-spectrin breakdown products. However, craniectomy mice also presented with decreases in LC3BII and SQSTM1 expression, indicating an inhibition of autophagy. Last, craniectomy contributed to the altered expression of several tight junction proteins, including occludin and claudin-1/5, suggesting the blood-brain barrier was perturbed. Overall, the deficits associated with craniectomy preclude its use as an adequate sole control for TBI research, as craniectomy limits translational insights into the neurological changes observed in TBI. Additionally, these results support the need for the use of closed-head injury models where uninjured control mice do not show significant confounding minor injury patterns.

Retrospective evaluations of repeated head injury are needed to better understand associations between head injury exposure and later-life deleterious outcomes. However, there is limited assessment of whether head injury recall assessments produce consistent measures over time, and no assessment of whether the reporting is related to current health status. The concussion signs and symptoms scale (CSS; developed for the Football Players Health Study at Harvard University) was designed to measure cumulative head injury exposure history by asking about the frequency of 10 CSS during active football play. Responses are summed with a total CSS range of 0-130. Former professional American-style football players completed the CSS at two timepoints. A subset of participants also reported on current health (subjective cognitive symptoms [Quality of Life in Neurological Disorders], depression [Patient Health Questionnaire], anxiety [Generalized Anxiety Disorder], pain [Patient-Reported Outcome Measurement Information System (PROMIS) Global], and overall health [PROMIS Global]) at each timepoint. To examine reporting consistency and recall bias, we calculated the Spearman correlation between measures assessed an average of 74.5 (standard deviation [SD] = 41.2) months apart and estimated associations between change in demographic, football-related, and current health factors and change in CSS (ΔCSS) over time using multivariable linear regression. Across the 335 participants, the mean (SD) CSS score at times 1 and 2 were 30.2 (25.5) and 29.1 (25.2), respectively, with an average change in CSS (ΔCSS) of -1.1 (SD = 19.8). There was no significant association between ΔCSS and years since play, months between timepoints, or age at time 1 (0.49 < p < 0.84). Eighty-one (24.2%) participants completed identical questions on current health factors at times 1 and 2. In separate multivariable models, there was no association between changes in pain, cognitive symptoms, health, depression, and anxiety reporting and ΔCSS (0.17 < p < 0.92). On average, the CSS score as a measure of retrospective concussion exposure did not change meaningfully over an average of 75 months, and changes in current health status were not significantly associated with ΔCSS. Results suggest that the CSS scale is stable over time and appears robust against changes in health status. The CSS should be considered for other retrospective studies of brain-injured populations to measure prior cumulative concussion history.

Traumatic brain injury (TBI) impairs a patient's capacity for informed decision-making, necessitating surrogate decision-makers to decide whether to continue life-sustaining therapies. Patient sex and social determinants of health (SDH)-for example, economic stability, education, and health care access-possibly affect such decisions. We aimed to explore interactions between sex, SDH, and redirection of care in a cohort of patients with TBI from a high-income, high-resource country. Adult patients with consecutive TBI admitted to intensive care were included. Data on demographics, TBI characteristics, advance directives, and SDH (civil status, living situation, dependence for daily activities, income, employment, religion, nationality) were extracted. The primary end-point was redirection of care, followed by in-hospital mortality. Differences were analyzed univariably, after prognostic score matching, and through random forest models to assess the importance of each factor. Seven hundred and twelve patients (26.4% female, median age 56) were included. Women were older, more often widowed, and more frequently dependent on help, while men had higher income and education levels. Redirection of care and mortality were more common in women, even after prognostic score matching, though the difference disappeared after adjusting for redirection of care. Random forest models identified employment status and dependence on support as key factors associated with redirection of care, while sex did not improve model performance. Our results underline the importance of SDH for prognostication of patients with TBI and suggest that it is not sex per se, but the associated sex differences in SDH that affect the frequency of redirection of care and ultimately in-hospital mortality.