The Lancet Neurology Commission

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

To investigate whether the number of years of schooling are causally associated traumatic brain injury (TBI). We aimed to investigate whether the number of years of schooling are causally associated TBI.

We investigate the prospective causal effect of years of schooling on TBI using summary statistical data. The statistical dataset comprising years of schooling (n = 293,723) from genome-wide association studies (GWASs) deposited in the UK Biobank was used for exposure. We used the following GWAS available in the FinnGen dataset: individuals with TBI (total = 13,165; control = 136,576; number of single nucleotide polymorphisms [SNPs] = 16,380,088).

Seventy significant genome-wide SNPs from GWAS datasets with annotated years of schooling were selected as instrumental variables. The inverse variance weighted method results supported a causal relationship between years of schooling and TBI (odds ratio (OR), 0.78; 95 % confidence interval (CI), 0.62–0.98; P = 0.029). MR-Egger regression showed that polydirectionality was unlikely to bias the results (intercept = 0.007, SE = 0.01, P = 0.484) and demonstrated no causal relationship between years of schooling and TBI (OR, 0.52; 95%CI, 0.17–1.64; P = 0.270). The weighted median method revealed a causal relationship with TBI (OR, 0.73; 95%CI, 0.55–0.98; P = 0.047). A Cochran's Q test and funnel plot did not show heterogeneity nor asymmetry, indicating no directional pleiotropy.

The current investigation yields substantiation of a causal association between years of schooling and TBI development. More years of schooling may be causally associated with a reduced risk of TBI, which has implications for clinical and public health practices and policies.

Tranexamic acid (TXA) holds a pivotal role in the therapeutic approach to traumatic conditions. Nevertheless, its precise influence on diminishing mortality and limiting the progression of intracranial hemorrhage (ICH) during the treatment of traumatic brain injury (TBI) remains indeterminate.

PubMed, EMBASE, Cochrane Library, and Web of Science were searched for randomized controlled trials that compared TXA and a placebo in adults with TBI up to September 31, 2023. Two authors independently abstracted the data and assessed the quality of evidence. Additionally, subgroup analyses were performed to assess outcomes with low heterogenety.

Our search strategy yielded 11,299 patients from 11 studies. The result showed that TXA had no effect on mortality (RR 0.93 [0.86, 1.00], p = 0.06; I²: 0%, p = 0.79), poor clinical outcomes (RR 0.92 [0.78, 1.09], p = 0.34; I²: 0%, p = 0.40), adverse events (RR 0.94 [0.83, 1.07], p = 0.34; I²: 48%, p = 0.10), vascular occlusive events (RR 0.85 [0.68, 1.06], p = 0.16; I²: 32%, p = 0.22), pulmonary embolism (RR 0.76 [0.47, 1.22], p = 0.26; I²: 0%, p = 0.83), seizure (RR 1.11 [0.92, 1.35], p = 0.27; I²: 0%, p = 0.49) and hemorrhagic complications (RR 0.78 [0.55, 1.09], p = 0.14; I²: 0%, p = 0.42). TXA might reduce the rate of hemorrhagic expansion (RR 0.83 [0.70, 0.99], p = 0.03; I²: 18%, p = 0.29) and mean hemorrhage volume (SMD −0.39 [−0.60, −0.18], p <0.001; I²: 44%, p = 0.13).When the time interval from symptom onset to treatment was <3 h, TXA reduced mean hemorrhage volume (SMD −0.51 [−0.81, −0.20], p = 0.001; I²: 0%, p = 0.94).

TXA did not elevate the risk of adverse event, however, the lack of reduction in mortality and the poor clinical outcomes constrain the value of clinical application. Early administration of TXA (within 3 h) may significantly decrease the likelihood of ICH growth in patients with TBI.

Background: Concussion is a type of traumatic brain injury (TBI) that can be sustained through sport-related and non-sport-related (e.g., motor vehicle accidents, falls, assaults) mechanisms of injury (MOI). Variations in concussion incidence and MOI may be present throughout the four geographic regions (Midwest, Northeast, South, West) of the United States. However, there is limited evidence exploring concussion cause and diagnosis patterns based on geographic region and MOI. These factors have implications for better understanding the burden of concussion and necessary efforts that can translate to the mitigation of safety concerns. Purpose: The purpose of this study was to identify patterns of sport-related concussion (SRC) and non-sport-related concussion (NSRC) across the four geographic regions of the United States. Methods: A descriptive epidemiology study of patient visits to the emergency department (ED) for concussion between 2010 and 2018, using publicly available data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) was conducted. The exposure of interest was geographic region while the main outcome measures were concussion diagnosis and MOI. Descriptive statistics were calculated using population-weighted frequencies and percentages. The association between geographic region and MOI (SRC vs. NSRC) was analyzed using logistic regression models. Odds ratios (OR) presented with 95% confidence intervals (CI) were included. Univariate analyses were conducted followed by multivariable analyses adjusting for sex, age, race/ethnicity, and primary source of payment. Statistical significance was set a priori at p < 0.05 for all analyses. Results: From 2010 to 2018, 1,161 visits resulted in a concussion diagnosis, representing an estimated 7,111,856 visits nationwide. A greater proportion of concussion diagnoses occurred within EDs in the South (38.2%) followed by the West (25.8%), Midwest (21.4%), and Northeast (14.6%). Compared to the West region, patients visiting the ED in the Midwest (OR = 0.75, 95% CI = 0.57–0.98) and Northeast (OR = 0.71, 95% CI = 0.51–0.98) had a lower odds of being diagnosed with a concussion. More patients sustained a NSRC MOI (94.3%) compared to SRC MOI (5.7%). For both mechanisms, the South region had the highest population-weighted frequency of SRC (n = 219,994) and NSRC diagnoses (n = 2,495,753). Univariate and multivariable logistic regression analyses did not reveal statistically significant associations for geographic region and MOI (p > 0.05). Conclusion: Our findings showed that the Midwest and Northeast regions had a lower odds of concussion diagnoses in EDs. Overall, the vast majority of concussions were not sport-related, which has public health implications. These findings improve our understanding of how concussion injuries are being sustained geographically nationwide and help to explain care-seeking patterns for concussion in the ED setting.

Armcx1 is a member of the ARMadillo repeat-Containing protein on the X chromosome (ARMCX) family, which is recognized to have evolutionary conserved roles in regulating mitochondrial transport and dynamics. Previous research has shown that Armcx1 is expressed at higher levels in mice after axotomy and in adult retinal ganglion cells after crush injury, and this protein increases neuronal survival and axonal regeneration. However, its role in traumatic brain injury (TBI) is unclear. Therefore, the aim of this study was to assess the expression of Armcx1 after TBI and to explore possible related mechanisms by which Armcx1 is involved in TBI. We used C57BL/6 male mice to model TBI and evaluated the role of Armcx1 in TBI by transfecting mice with Armcx1 small interfering RNA (siRNA) to inhibit Armcx1 expression 24 h before TBI modeling. Western blotting, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Nissl staining, transmission electron microscopy, adenosine triphosphate (ATP) level measurement, neuronal apoptosis analysis, neurological function scoring and the Morris water maze were performed. The results demonstrated that Armcx1 protein expression was elevated after TBI and that the Armcx1 protein was localized in neurons and astroglial cells in cortical tissue surrounding the injury site. In addition, inhibition of Armcx1 expression further led to impaired mitochondrial transport, abnormal morphology, reduced ATP levels, aggravation of neuronal apoptosis and neurological dysfunction, and decrease Miro1 expression. In conclusion, our findings indicate that Armcx1 may exert neuroprotective effects by ameliorating neurological injury after TBI through a mitochondrial transport pathway involving Miro1.

Traumatic brain injury (TBI) results in 2.5 million emergency department (ED) visits per year in the US, with mild traumatic brain injury (mTBI) accounting for 90% of cases. There is considerable evidence that many experience chronic symptoms months to years later. This population is rarely represented in interventional studies. Management of adult mTBI in the ED has remained unchanged, without consensus of therapeutic options. The aim of this review was to synthesize existing literature of patient-centered ED treatments for adults who sustain an mTBI, and to identify practices that may offer promise.

A systematic review was conducted using the PubMed and Cochrane databases, while following PRISMA guidelines. Studies describing pediatric patients, moderate to severe TBI, or interventions outside the ED were excluded. Two reviewers independently performed title and abstract screening. A third blinded reviewer resolved discrepancies. The Mixed Methods Appraisal Tool (MMAT) was employed to assess the methodological quality of the studies.

Our search strategy generated 1002 unique titles. 95 articles were selected for full-text screening. The 26 articles chosen for full analysis were grouped into one of the following intervention categories: (1) predictive models for Post-Concussion Syndrome (PCS), (2) discharge instructions, (3) pharmaceutical treatment, (4) clinical protocols, and (5) functional assessment. Studies that implemented a predictive PCS model successfully identified patients at highest risk for PCS. Trials implementing discharge related interventions found the use of video discharge instructions, encouragement of daily light exercise or bed rest, and text messaging did not significantly reduce mTBI symptoms. The use of electronic clinical practice guidelines (eCPG) and longer leaves of absence from work following injury reduced symptoms. Ondansetron was shown to reduce nausea in mTBI patients. Studies implementing ED Observation Units found significant declines in inpatient admissions and length of hospital stay. The use of tablet-based tasks was found to be superior to many standard cognitive assessments.

Validated instruments are available to aid clinicians in identifying patients at risk for PCS or serious cognitive impairment. EDOU management and evidence-based modifications to discharge instructions may improve mTBI outcomes. Additional research is needed to establish the therapeutic value of medications and lifestyle changes for the treatment of mTBI in the ED.

Traumatic brain injuries (TBI) resulting from head impacts are a major public health concern, which prompted our research to investigate the complex relationship between the material properties of brain tissue and the severity of TBI. The goal of this research is to investigate how variations in brain and skull density influence the vulnerability of brain tissue to traumatic injury, thereby enhancing our understanding of injury mechanism.

To achieve this goal, we employed a well-validated finite element head model (FEHM). The current investigation was divided into two phases: in the first one, three distinct brain viscoelastic materials that had been utilized in prior studies were analyzed. The review of the properties of these three materials has been meticulous, encompassing both the spectrum of mechanical properties and the behaviors that are relevant to the way in which brain tissue reacts to traumatic loading conditions. In the second phase, the material properties of both the brain and skull tissue, alongside the impact conditions, were held constant. After this step, the focus was directed towards the variation of density in the brain and skull, which was consistent with the results obtained from previous experimental investigations, in order to determine the precise impact of these variations in density. This approach allowed a more profound comprehension of the impacts that density had on the simulation results.

In the first phase, Material No. 2 exhibited the highest maximum first principal strain value in the frontal region (${\epsilon }_{\mathit{max}}=15.41\%$), indicating lower stiffness to instantaneous deformation. This characteristic suggests that Material No. 2 may deform more extensively upon impact, potentially increasing the risk of injury due to its viscoelastic behavior. In contrast, Material No. 1, with a lower maximum first principal strain in the frontal region (${\epsilon }_{\mathit{max}}=7.87\%$), displayed greater stiffness to instantaneous deformation, potentially reducing the risk of brain injury upon head impact. The second phase provided quantitative findings revealing a proportional relationship between brain tissue density and the pressures experienced by the brain. A 2 % increase in brain tissue density corresponded to approximately a 1 % increase in pressure on the brain tissue. Similarly, changes in skull density exhibited a similar quantitative relationship, with a 6 % increase in skull density leading to a 2.5 % increase in brain pressure. This preliminary approximate ratio of 2 to 1 between brain and skull density variations provides an initial quantitative framework for assessing the impact of density changes on brain vulnerability. These findings have several implications for the development of protective measures and injury prevention strategies, particularly in contexts where head trauma is a major issue.