Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive ...neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE)--which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression--has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE.
...it might also be possible to specifically target individuals to address their patterns of risk-taking behaviour.183 Irrespective of the target population, information campaigns should employ a ...range of measures to raise awareness of key issues in prevention and care for TBI. Since awareness of child abuse has increased and family risk factors have been elucidated, local programmes have been developed in the USA and other countries to educate parents about the dangers and long-term effects of brain injury, and to provide caregiver relief and advice on coping skills for stress. The GCS42 is the most commonly used approach to quantify the clinical severity of TBI358 (figure 2), but this is relatively crude and does not reflect different pathoanatomical subsets of TBI. ...the increasing use of prehospital sedation and tracheal intubation often confounds assessment with the GCS and has reduced its usefulness as a metric of injury severity.359 Existing International Classification of Diseases codes360 also do not adequately capture severity of TBI.361 Alternative TBI coding taxonomies-including the Abbreviated Injury Scale (AIS), which categorises severity of intracranial and extracranial injury,362 and the Marshall classification system, which is based on head CT findings363-are anatomically oriented and summarise the type, location, and severity of injuries. ...current management strategies are based on guidelines that favour a one-size-fits-all approach, and the care of patients with TBI is therefore poorly individualised (section 5). ...despite investment of many billions of dollars by pharmaceutical companies, no effective drugs exist for treatment in the acute setting-a failing due, in part, to insufficient targeting of therapies to patients in whom the relevant mechanism is active.
Purpose of Review
Over the last years, the focus of clinical and animal research in subarachnoid hemorrhage (SAH) shifted towards the early phase after the bleeding based on the association of the ...early injury pattern (first 72 h) with secondary complications and poor outcome. This phase is commonly referenced as early brain injury (EBI). In this clinical review, we intended to overview commonly used definitions of EBI, underlying mechanisms, and potential treatment implications.
Recent Findings
We found a large heterogeneity in the definition used for EBI comprising clinical symptoms, neuroimaging parameters, and advanced neuromonitoring techniques. Although specific treatments are currently not available, therapeutic interventions are aimed at ameliorating EBI by improving the energy/supply mismatch in the early phase after SAH.
Summary
Future research integrating brain-derived biomarkers is warranted to improve our pathophysiologic understanding of EBI in order to ameliorate early injury patterns and improve patients’ outcomes.
When describing clinical or experimental traumatic brain injury (TBI), the adjectives 'mild,' 'moderate' and 'severe' are misleading. 'Mild' clinical TBI frequently results in long-term disability. ...'Severe' rodent TBI actually resembles mild or complicated mild clinical TBI.
Many mild TBI patients appear to have recovered completely but have postconcussive symptoms, deficits in cognitive and executive function and reduced cerebral blood flow. After moderate TBI, 31.8% of patients died or were discharged to skilled nursing or hospice. Among survivors of moderate and severe TBI, 44% were unable to return to work. On MRI, 88% of mild TBI patients have evidence of white matter damage, based on measurements of fractional anisotropy and mean diffusivity/apparent diffusion coefficient. After sports concussion, clinically recovered patients have abnormalities in functional connectivity on functional MRI. Methylphenidate improved fatigue and cognitive impairment and, combined with cognitive rehabilitation, improved memory and executive functioning. In comparison to clinical TB, because the entire spectrum of experimental rodent TBI, although defined as moderate or severe, more closely resembles mild or complicated mild clinical TBI.
Many patients after mild or moderate TBI suffer long-term sequelae and should be considered a major target for translational research. Treatments that improve outcome in rodent TBI, even when the experimental injuries are defined as severe, might be most applicable to mild or moderate TBI.
Traumatic brain injury (TBI) is a critical public health and socio-economic problem throughout the world. Reliable quantification of the burden caused by TBI is difficult owing to inadequate ...standardization and incomplete capture of data on the incidence and outcome of brain injury, with variability in the definition of TBI being partly to blame. Reports show changes in epidemiological patterns of TBI: the median age of individuals who experience TBI is increasing, and falls have now surpassed road traffic incidents as the leading cause of this injury. Despite claims to the contrary, no clear decrease in TBI-related mortality or improvement of overall outcome has been observed over the past two decades. In this Perspectives article, we discuss the strengths and limitations of epidemiological studies, address the variability in its definition, and highlight changing epidemiological patterns. Taken together, these analyses identify a great need for standardized epidemiological monitoring in TBI.
In this randomized trial involving patients with traumatic brain injury and elevated intracranial pressure, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result ...in outcomes better than those with standard care alone.
In Europe, traumatic brain injury is the most common cause of permanent disability in people younger than 40 years of age, with the annual cost exceeding €33 billion (approximately $37.5 billion in U.S. dollars).
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Recent statistics show a 21% increase in the incidence of traumatic brain injury during the past 5 years — three times greater than the increase in population. Despite this, management of traumatic brain injury has been underrepresented in medical research as compared with other health problems.
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Consequently, there are few data to support the commonly used stage 2 interventions (Figure 1) for the management of . . .
Traumatic brain injury (TBI) causes acute and subacute tissue damage, but is also associated with chronic inflammation and progressive loss of brain tissue months and years after the initial event. ...The trigger and the subsequent molecular mechanisms causing chronic brain injury after TBI are not well understood. The aim of the current study was therefore to investigate the hypothesis that necroptosis, a form a programmed cell death mediated by the interaction of Receptor Interacting Protein Kinases (RIPK) 1 and 3, is involved in this process. Neuron-specific RIPK1- or RIPK3-deficient mice and their wild-type littermates were subjected to experimental TBI by controlled cortical impact. Posttraumatic brain damage and functional outcome were assessed longitudinally by repetitive magnetic resonance imaging (MRI) and behavioral tests (beam walk, Barnes maze, and tail suspension), respectively, for up to three months after injury. Thereafter, brains were investigated by immunohistochemistry for the necroptotic marker phosphorylated mixed lineage kinase like protein(pMLKL) and activation of astrocytes and microglia. WT mice showed progressive chronic brain damage in cortex and hippocampus and increased levels of pMLKL after TBI. Chronic brain damage occurred almost exclusively in areas with iron deposits and was significantly reduced in RIPK1- or RIPK3-deficient mice by up to 80%. Neuroprotection was accompanied by a reduction of astrocyte and microglia activation and improved memory function. The data of the current study suggest that progressive chronic brain damage and cognitive decline after TBI depend on the expression of RIPK1/3 in neurons. Hence, inhibition of necroptosis signaling may represent a novel therapeutic target for the prevention of chronic post-traumatic brain damage.
Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after ...SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms "early brain injury" and "delayed brain injury" are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications.
Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of ...'chronic traumatic encephalopathy' (CTE) in athletes exposed to repetitive head injury. Originally termed 'dementia pugilistica' and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI.
Abstract Growing evidence indicates that multiple types of brain injury, including traumatic brain injury, are dynamic conditions that continue to change years after onset. For a subset of ...individuals who incur these injuries, decline occurs over time and is likely due to progressive neurodegenerative processes, comorbid conditions, aging, behavioral choices, and/or psychosocial factors. Deterioration, whether directly or indirectly associated with the original brain injury, necessitates a clinical approach as a chronic health condition, including identification of risk and protective factors, protocols for early identification, evidence-based preventive and ameliorative treatment, and training in self-management. We propose that the acknowledgment of chronic brain injury will facilitate the research necessary to provide a disease management approach.
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