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Journal of Neurology Nov 2019Traumatic brain injury (TBI) is the most common cause of death and disability in those aged under 40 years in the UK. Higher rates of morbidity and mortality are seen... (Review)
Review
Traumatic brain injury (TBI) is the most common cause of death and disability in those aged under 40 years in the UK. Higher rates of morbidity and mortality are seen in low-income and middle-income countries making it a global health challenge. There has been a secular trend towards reduced incidence of severe TBI in the first world, driven by public health interventions such as seatbelt legislation, helmet use, and workplace health and safety regulations. This has paralleled improved outcomes following TBI delivered in a large part by the widespread establishment of specialised neurointensive care. This update will focus on three key areas of advances in TBI management and research in moderate and severe TBI: refining neurointensive care protocolized therapies, the recent evidence base for decompressive craniectomy and novel pharmacological therapies. In each section, we review the developing evidence base as well as exploring future trajectories of TBI research.
Topics: Brain Injuries, Traumatic; Decompressive Craniectomy; Drug Therapy; Humans; Hypothermia, Induced; Neurophysiological Monitoring
PubMed: 31563989
DOI: 10.1007/s00415-019-09541-4 -
The Lancet. Neurology Sep 2017A substantial minority of patients who survive an acquired brain injury develop a state of sympathetic hyperactivity that can persist for weeks or months, consisting of... (Review)
Review
A substantial minority of patients who survive an acquired brain injury develop a state of sympathetic hyperactivity that can persist for weeks or months, consisting of periodic episodes of increased heart rate and blood pressure, sweating, hyperthermia, and motor posturing, often in response to external stimuli. The unifying term for the syndrome-paroxysmal sympathetic hyperactivity (PSH)-and clear diagnostic criteria defined by expert consensus were only recently established. PSH has predominantly been described after traumatic brain injury (TBI), in which it is associated with worse outcomes. The pathophysiology of the condition is not completely understood, although most researchers consider it to be a disconnection syndrome with paroxysms driven by a loss of inhibitory control over excitatory autonomic centres. Although therapeutic strategies to alleviate sympathetic outbursts have been proposed, their effects on PSH are inconsistent between patients and their influence on outcome is unknown. Combinations of drugs are frequently used and are chosen on the basis of local custom, rather than on objective evidence. New rigorous tools for diagnosis could allow better characterisation of PSH to enable stratification of patients for future therapeutic trials.
Topics: Autonomic Nervous System Diseases; Brain Injuries; Humans; Sympathetic Nervous System
PubMed: 28816118
DOI: 10.1016/S1474-4422(17)30259-4 -
Cell Transplantation Jul 2017Traumatic brain injury (TBI) presents in various forms ranging from mild alterations of consciousness to an unrelenting comatose state and death. In the most severe form... (Review)
Review
Traumatic brain injury (TBI) presents in various forms ranging from mild alterations of consciousness to an unrelenting comatose state and death. In the most severe form of TBI, the entirety of the brain is affected by a diffuse type of injury and swelling. Treatment modalities vary extensively based on the severity of the injury and range from daily cognitive therapy sessions to radical surgery such as bilateral decompressive craniectomies. Guidelines have been set forth regarding the optimal management of TBI, but they must be taken in context of the situation and cannot be used in every individual circumstance. In this review article, we have summarized the current status of treatment for TBI in both clinical practice and basic research. We have put forth a brief overview of the various subtypes of traumatic injuries, optimal medical management, and both the noninvasive and invasive monitoring modalities, in addition to the surgical interventions necessary in particular instances. We have overviewed the main achievements in searching for therapeutic strategies of TBI in basic science. We have also discussed the future direction for developing TBI treatment from an experimental perspective.
Topics: Animals; Brain Injuries, Traumatic; Disease Models, Animal; Humans; Nerve Regeneration
PubMed: 28933211
DOI: 10.1177/0963689717714102 -
The Lancet. Neurology Jun 2017Severe traumatic brain injury (TBI) is currently managed in the intensive care unit with a combined medical-surgical approach. Treatment aims to prevent additional brain... (Review)
Review
Severe traumatic brain injury (TBI) is currently managed in the intensive care unit with a combined medical-surgical approach. Treatment aims to prevent additional brain damage and to optimise conditions for brain recovery. TBI is typically considered and treated as one pathological entity, although in fact it is a syndrome comprising a range of lesions that can require different therapies and physiological goals. Owing to advances in monitoring and imaging, there is now the potential to identify specific mechanisms of brain damage and to better target treatment to individuals or subsets of patients. Targeted treatment is especially relevant for elderly people-who now represent an increasing proportion of patients with TBI-as preinjury comorbidities and their therapies demand tailored management strategies. Progress in monitoring and in understanding pathophysiological mechanisms of TBI could change current management in the intensive care unit, enabling targeted interventions that could ultimately improve outcomes.
Topics: Brain Injuries, Traumatic; Critical Care; Humans
PubMed: 28504109
DOI: 10.1016/S1474-4422(17)30118-7 -
Expert Review of Molecular Diagnostics Feb 2018Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of... (Review)
Review
Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome prognosis and possible identification of post-TBI neurodegernative diseases (e.g. chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic tools in pre-clinical and clinical settings. Expert commentary: A spectrum of biomarkers is now at or near the stage of formal clinical validation of their diagnostic and prognostic utilities in the management of TBI of varied severities including concussions. TBI biomarkers could serve as a theranostic tool in facilitating drug development and treatment monitoring.
Topics: Biomarkers; Brain Injuries, Traumatic; Humans; Liquid Biopsy; Neuroimaging; Prognosis; Severity of Illness Index
PubMed: 29338452
DOI: 10.1080/14737159.2018.1428089 -
Journal of Internal Medicine Jun 2019Traumatic brain injury (TBI) is a major cause of acquired disability globally, and effective treatment methods are scarce. Lately, there has been increasing recognition... (Review)
Review
Traumatic brain injury (TBI) is a major cause of acquired disability globally, and effective treatment methods are scarce. Lately, there has been increasing recognition of the devastating impact of TBI resulting from sports and other recreational activities, ranging from primarily sport-related concussions (SRC) but also more severe brain injuries requiring hospitalization. There are currently no established treatments for the underlying pathophysiology in TBI and while neuro-rehabilitation efforts are promising, there are currently is a lack of consensus regarding rehabilitation following TBI of any severity. In this narrative review, we highlight short- and long-term consequences of SRCs, and how the sideline management of these patients should be performed. We also cover the basic concepts of neuro-critical care management for more severely brain-injured patients with a focus on brain oedema and the necessity of improving intracranial conditions in terms of substrate delivery in order to facilitate recovery and improve outcome. Further, following the acute phase, promising new approaches to rehabilitation are covered for both patients with severe TBI and athletes suffering from SRC. These highlight the need for co-ordinated interdisciplinary rehabilitation, with a special focus on cognition, in order to promote recovery after TBI.
Topics: Brain Injuries; Brain Injuries, Traumatic; Brain Injury, Chronic; Humans; Injury Severity Score; Patient Care Team
PubMed: 30883980
DOI: 10.1111/joim.12900 -
Handbook of Clinical Neurology 2015Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma... (Review)
Review
Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects.
Topics: Animals; Brain; Brain Injuries; Encephalitis; Glasgow Coma Scale; Humans
PubMed: 25702209
DOI: 10.1016/B978-0-444-52892-6.00004-0 -
Journal of Neurology Oct 2020Traumatic brain injury (TBI) is one of the commonest presentations to emergency departments and is associated with seizures carrying different significance at different... (Review)
Review
Traumatic brain injury (TBI) is one of the commonest presentations to emergency departments and is associated with seizures carrying different significance at different stages following injury. We describe the epidemiology of early and late seizures following TBI, the significance of intracranial haemorrhage of different types in the risk of later epilepsy and the gaps in current understanding of risk factors contributing to the risk of post-traumatic epilepsy (PTE). The delay from injury to epilepsy presents an opportunity to understand the mechanisms underlying changes in the brain and how they may reveal potential targets for anti-epileptogenic therapy. We review existing treatments, both medical and surgical and conclude that current research is not tailored to differentiate between PTE and other forms of focal epilepsy. Finally, we review the increasing understanding of the frequency and significance of dissociative seizures following mild TBI.
Topics: Brain Concussion; Brain Injuries, Traumatic; Epilepsy; Epilepsy, Post-Traumatic; Humans; Seizures
PubMed: 32444981
DOI: 10.1007/s00415-020-09926-w -
Neurologia Medico-chirurgica Feb 2017Traumatic brain injury (TBI) is the leading cause of death and disability in children. Pediatric TBI is associated with several distinctive characteristics that differ... (Review)
Review
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Pediatric TBI is associated with several distinctive characteristics that differ from adults and are attributable to age-related anatomical and physiological differences, pattern of injuries based on the physical ability of the child, and difficulty in neurological evaluation in children. Evidence suggests that children exhibit a specific pathological response to TBI with distinct accompanying neurological symptoms, and considerable efforts have been made to elucidate their pathophysiology. In addition, recent technical advances in diagnostic imaging of pediatric TBI has facilitated accurate diagnosis, appropriate treatment, prevention of complications, and helped predict long-term outcomes. Here a review of recent studies relevant to important issues in pediatric TBI is presented, and recent specific topics are also discussed. This review provides important updates on the pathophysiology, diagnosis, and age-appropriate acute management of pediatric TBI.
Topics: Adolescent; Age Factors; Brain Injuries, Traumatic; Child; Child, Preschool; Humans; Infant; Infant, Newborn
PubMed: 28111406
DOI: 10.2176/nmc.ra.2016-0191 -
JAMA Neurology Mar 2015Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public... (Review)
Review
IMPORTANCE
Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI.
OBJECTIVES
To review known inflammatory mechanisms in TBI and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of TBI.
EVIDENCE REVIEW
We searched articles in PubMed published between 1960 and August 1, 2014, using the following keywords: traumatic brain injury, sterile injury, inflammation, astrocytes, microglia, monocytes, macrophages, neutrophils, T cells, reactive oxygen species, alarmins, danger-associated molecular patterns, purinergic receptors, neuroprotection, and clinical trials. Previous clinical trials or therapeutic studies that involved manipulation of the discussed mechanisms were considered for inclusion. The final list of selected studies was assembled based on novelty and direct relevance to the primary focus of this review.
FINDINGS
Traumatic brain injury is a diverse group of sterile injuries induced by primary and secondary mechanisms that give rise to cell death, inflammation, and neurologic dysfunction in patients of all demographics. Pathogenesis is driven by complex, interacting mechanisms that include reactive oxygen species, ion channel and gap junction signaling, purinergic receptor signaling, excitotoxic neurotransmitter signaling, perturbations in calcium homeostasis, and damage-associated molecular pattern molecules, among others. Central nervous system resident and peripherally derived inflammatory cells respond to TBI and can provide neuroprotection or participate in maladaptive secondary injury reactions. The exact contribution of inflammatory cells to a TBI lesion is dictated by their anatomical positioning as well as the local cues to which they are exposed.
CONCLUSIONS AND RELEVANCE
The mechanisms that drive TBI lesion development as well as those that promote repair are exceedingly complex and often superimposed. Because pathogenic mechanisms can diversify over time or even differ based on the injury type, it is important that neuroprotective therapeutics be developed and administered with these variables in mind. Due to its complexity, TBI has proven particularly challenging to treat; however, a number of promising therapeutic approaches are now under pre-clinical development, and recent clinical trials have even yielded a few successes. Given the worldwide impact of TBI on the human population, it is imperative that research remains active in this area and that we continue to develop therapeutics to improve outcome in afflicted patients.
Topics: Animals; Brain Injuries; Clinical Trials as Topic; Humans; Inflammation; Neuroprotective Agents; Reactive Oxygen Species
PubMed: 25599342
DOI: 10.1001/jamaneurol.2014.3558