The mechanisms underpinning concussion, traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE) are poorly understood. Using neuropathological analyses of brains from teenage ...athletes, a new mouse model of concussive impact injury, and computational simulations, Tagge et al. show that head injuries can induce TBI and early CTE pathologies independent of concussion.
Abstract
The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.
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OBJECTIVE Decompressive craniectomy is an established therapy for refractory intracranial hypertension. Cranioplasty following decompressive craniectomy not only provides protection to the brain ...along with cosmetic benefits, but also enhances rehabilitation with meaningful functional recovery of potentially reversible cortical and subcortical damaged areas of the affected as well as the contralateral hemisphere. The aim of the study was to assess neurological and cognitive outcome as well as cerebral blood flow after cranioplasty. METHODS Thirty-four patients admitted for replacement cranioplasty after decompressive craniectomy for head injury were studied prospectively. Clinical, neurological, and cognitive outcomes were assessed by the Glasgow Outcome Scale (GOS), the Glasgow Coma Scale, and a battery of cognitive tests, respectively. Simultaneously, cerebral blood perfusion was assessed by technetium-99m ethyl cysteinate dimer (
Tc-ECD) brain SPECT imaging 7 days prior to and 3 months after cranioplasty. RESULTS Prior to cranioplasty 9 patients (26.5%) had GOS scores of 5 and 25 patients (73.5%) had GOS scores of 4, whereas postcranioplasty all 34 patients (100%) improved to GOS scores of 5. Approximately 35.3%-90.9% patients showed cognitive improvement postcranioplasty in various tests. Also, on comparison with brain SPECT, 94% of patients showed improvement in cerebral perfusion in different lobes. CONCLUSIONS Cranioplasty remarkably improves neurological and cognitive outcomes supported by improvement in cerebral blood perfusion.
All families live in areas with a higher than average Index of Multiple Deprivation (national mean 15 200; cohort mean 19 867), and 70% of parents had significant underlying vulnerabilities: two had ...previous criminal histories, three had mental health disorders, and four had financial concerns. The spectrum of socioeconomic and psychosocial challenges associated with such measures can increase parental stress, reflected as increased substance misuse among caregivers—a potential risk in itself.2 Our cohort is aligned to the literature in its portrayal of socioeconomic deprivation and parental vulnerability as significant risk factors for abuse, both of which may be exacerbated as a result of the stresses imposed by quarantine measures. The child’s increased exposure to their parents and decreased interaction with reporting bodies further heightens this risk.2 4 The complex links between abuse, mental health, substance misuse, and socioeconomic circumstances are often interdependent and cannot be effectively addressed in isolation.5 Hence, in the background of the intensely public SARS-CoV-2 pandemic, a more silent pandemic is occurring, of which the medical community must remain astutely aware.
To characterize racial and ethnic disparities in the evaluation and reporting of suspected abusive head trauma (AHT) across the 18 participating sites of the Pediatric Brain Injury Research Network ...(PediBIRN). We hypothesized that such disparities would be confirmed at multiple sites and occur more frequently in patients with a lower risk for AHT.
Aggregate and site-specific analysis of the cross-sectional PediBIRN dataset, comparing AHT evaluation and reporting frequencies in subpopulations of white/non-Hispanic and minority race/ethnicity patients with lower vs higher risk for AHT.
In the PediBIRN study sample of 500 young, acutely head-injured patients hospitalized for intensive care, minority race/ethnicity patients (n = 229) were more frequently evaluated (P < .001; aOR, 2.2) and reported (P = .001; aOR, 1.9) for suspected AHT than white/non-Hispanic patients (n = 271). These disparities occurred almost exclusively in lower risk patients, including those ultimately categorized as non-AHT (P = .001 aOR, 2.4 and P = .003 aOR, 2.1) or with an estimated AHT probability of ≤25% (P < .001 aOR, 4.1 and P < .001 aOR, 2.8). Similar site-specific analyses revealed that these results reflected more extreme disparities at only 2 of 18 sites, and were not explained by local confounders.
Significant race/ethnicity-based disparities in AHT evaluation and reporting were observed at only 2 of 18 sites and occurred almost exclusively in lower risk patients. In the absence of local confounders, these disparities likely represent the impact of local physicians' implicit bias.
Hypothermia for traumatic brain injury Lewis, Sharon R; Evans, David JW; Butler, Andrew R ...
Cochrane database of systematic reviews,
09/2017, Letnik:
2017, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Background
Hypothermia has been used in the treatment of brain injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger ...trials.
Objectives
To determine the effect of mild hypothermia for traumatic brain injury (TBI) on mortality, long‐term functional outcomes and complications.
Search methods
We ran and incorporated studies from database searches to 21 March 2016. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), PubMed, ISI Web of science (SCI‐EXPANDED, SSCI, CPCI‐S & CPSI‐SSH), clinical trials registers, and screened reference lists. We also re‐ran these searches pre‐publication in June 2017; the result from this search is presented in 'Studies awaiting classification'.
Selection criteria
We included randomised controlled trials of participants with closed TBI requiring hospitalisation who were treated with hypothermia to a maximum of 35 ºC for at least 12 consecutive hours. Treatment with hypothermia was compared to maintenance with normothermia (36.5 to 38 ºC).
Data collection and analysis
Two review authors assessed data on mortality, unfavourable outcomes according to the Glasgow Outcome Scale, and pneumonia.
Main results
We included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re‐assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification.
Studies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty‐three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability), and 14 studies reported pneumonia. Visual inspection of the results for these outcomes showed inconsistencies among studies, with differences in the direction of effect, and we did not pool these data for meta‐analysis. We considered duration of hypothermia therapy and the length of follow‐up in collected data for these subgroups; differences in study data remained such that we did not perform meta‐analysis.
Studies were generally poorly reported and we were unable to assess risk of bias adequately. Heterogeneity was evident both in the trial designs and participant inclusion. Inconsistencies in results may be explained by heterogeneity among study participants or bias introduced by individual study methodology but we did not explore this in detail in subgroup or sensitivity analyses. We used the GRADE approach to judge the quality of the evidence for each outcome and downgraded the evidence for mortality and unfavourable outcome to very low. We downgraded the evidence for the pneumonia outcome to low.
Authors' conclusions
Despite a large number studies, there remains no high‐quality evidence that hypothermia is beneficial in the treatment of people with TBI. Further research, which is methodologically robust, is required in this field to establish the effect of hypothermia for people with TBI.
Head injury and 25‐year risk of dementia Schneider, Andrea L. C.; Selvin, Elizabeth; Latour, Lawrence ...
Alzheimer's & dementia,
September 2021, Letnik:
17, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Introduction
Head injury is associated with significant morbidity and mortality. Long‐term associations of head injury with dementia in community‐based populations are less clear.
Methods
Prospective ...cohort study of 14,376 participants (mean age 54 years at baseline, 56% female, 27% Black, 24% with head injury) enrolled in the Atherosclerosis Risk in Communities (ARIC) Study. Head injury was defined using self‐report and International Classification of Diseases, Ninth/Tenth Revision (ICD‐9/10) codes. Dementia was defined using cognitive assessments, informant interviews, and ICD‐9/10 and death certificate codes.
Results
Head injury was associated with risk of dementia (hazard ratio HR = 1.44, 95% confidence interval CI = 1.3‐1.57), with evidence of dose‐response (1 head injury: HR = 1.25, 95% CI = 1.13‐1.39, 2+ head injuries: HR = 2.14, 95% CI = 1.86‐2.46). There was evidence for stronger associations among female participants (HR = 1.69, 95% CI = 1.51‐1.90) versus male participants (HR = 1.15, 95% CI = 1.00‐1.32), P‐for‐interaction < .001, and among White participants (HR = 1.55, 95% CI = 1.40‐1.72) versus Black participants (HR = 1.22, 95% CI = 1.02‐1.45), P‐for‐interaction = .008.
Discussion
In this community‐based cohort with 25‐year follow‐up, head injury was associated with increased dementia risk in a dose‐dependent manner, with stronger associations among female participants and White participants.
The neuro-ophthalmology of head trauma Ventura, Rachel E, MD; Balcer, Laura J, Prof; Galetta, Steven L, Dr
Lancet neurology,
10/2014, Letnik:
13, Številka:
10
Journal Article
Recenzirano
Summary Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Concussion, a form of mild TBI, might be associated with long-term neurological symptoms. The effects of TBI and ...concussion are not restricted to cognition and balance. TBI can also affect multiple aspects of vision; mild TBI frequently leads to disruptions in visual functioning, while moderate or severe TBI often causes structural lesions. In patients with mild TBI, there might be abnormalities in saccades, pursuit, convergence, accommodation, and vestibulo-ocular reflex. Moderate and severe TBI might additionally lead to ocular motor palsies, optic neuropathies, and orbital pathologies. Vision-based testing is vital in the management of all forms of TBI and provides a sensitive approach for sideline or post-injury concussion screening. One sideline test, the King-Devick test, uses rapid number naming and has been tested in multiple athlete cohorts.
We aimed to investigate the incidence, prevalence, and etiology of sixth cranial nerve (CN6) palsy in the general Korean population. The nationally representative dataset of the Korea National Health ...Insurance Service-National Sample Cohort from 2006 through 2015 was analyzed. The incidence and prevalence of CN6 palsy were estimated in the cohort population, confirming that incident cases of CN6 palsy involved a preceding disease-free period of ≥4 years. The etiologies of CN6 palsy were presumed using comorbidity conditions. Among the 1,108,256 cohort subjects, CN6 palsy developed in 486 patients during the 10-year follow-up. The overall incidence of CN6 palsy was estimated to be 4.66 per 100,000 person-years (95% confidence interval CI, 4.26-5.08) in the general population. This incidence increased with age, accelerating after 60 years of age and peaking at 70-74 years of age. The mean male-to-female incidence ratio was estimated as 1.41 in the whole population, and the incidence and prevalence of CN6 palsy showed an increasing trend over time in the study period. Surgical incidence for CN6 palsy was only 0.19 per 100,000 person-years (95% CI, 0.12-0.29). The etiologies were presumed to be vascular (56.6%), idiopathic (27.2%), neoplastic (5.6%), and traumatic (4.9%). In conclusion, the incidence of CN6 palsy increases with age, peaking at around 70 years, and shows a mild male predominance in Koreans.
•The finite element model of E-scooter fall was developed and validated.•E-scooter falls always cause oblique head-ground impacts, mostly on the forehead.•High risks of severe head injuries can ...result from E-scooter falls.•The helmet greatly reduced head linear acceleration but not angular acceleration.•Yet, even with the helmet, the computed risk of severe head injuries remained high.
Head injuries are common injuries in E-scooter accidents which have dramatically increased in recent years. The head impact conditions and helmet performance during E-scooter accidents are barely investigated. This study aims to characterize the head-ground impact biomechanics and evaluate bicycle helmet protection in typical E-scooter falls.
The finite element (FE) model of a hybrid III dummy riding an E-scooter was developed and validated. The FE model with and without a bicycle helmet was used to reproduce twenty-seven E-scooter falls caused by the collision with a curb, in which different riding speeds (10, 20, and 30 km/h), curb orientations (30, 60, and 90°), and E-scooter orientations (−15, 0, and 15°) were simulated. Head-ground impact velocities and locations were evaluated for the unhelmeted configurations while the helmet performance was evaluated with the reduction of head injury metrics.
E-scooter falls always resulted in an oblique head-ground impact, with 78 % on the forehead. The mean vertical and tangential head-ground impact velocities were respectively 5.7 ± 1.5 m/s and 3.7 ± 2.0 m/s. The helmet significantly (p < 0.1) reduced the head linear acceleration, angular velocity, HIC_36, and BrIC, but not the angular acceleration. However, even with the helmet, the head injury metrics were mostly above the thresholds of severe head injuries.
Typical E-scooter falls might cause severe head injuries. The bicycle helmet was efficient to reduce head injury metrics but not to prevent severe head injuries. Future helmet standard evaluations should involve higher impact energy and the angular acceleration assessment in oblique impacts.
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