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Concept: Concussion

239

Head injuries have been associated with subsequent suicide among military personnel, but outcomes after a concussion in the community are uncertain. We assessed the long-term risk of suicide after concussions occurring on weekends or weekdays in the community.

Concepts: Concussion

203

In their Perspective, Donald A. Redelmeier and Sheharyar Raza discuss the significance of Seena Fazel and colleagues' longitudinal study of traumatic brain injury (TBI)-associated outcomes.

Concepts: Longitudinal study, Traumatic brain injury, Sociology, Repeated measures design, Concussion

174

BACKGROUND: Mild traumatic brain injury (mTBI) secondary to blast exposure is the most common battlefield injury in Southwest Asia. There has been little prospective work in the combat setting to test the efficacy of new countermeasures. The goal of this study was to compare the efficacy of N-acetyl cysteine (NAC) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting. METHODS: This study was a randomized double blind, placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq. All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate. Individuals underwent a baseline evaluation and then were randomly assigned to receive either N-acetyl cysteine (NAC) or placebo for seven days. Each subject was re-evaluated at 3 and 7 days. Outcome measures were the presence of the following sequelae of mTBI: dizziness, hearing loss, headache, memory loss, sleep disturbances, and neurocognitive dysfunction. The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study. Logistic regression on the outcome of ‘no day 7 symptoms’ indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo. CONCLUSION: This study, conducted in an active theatre of war, demonstrates that NAC, a safe pharmaceutical countermeasure, has beneficial effects on the severity and resolution of sequelae of blast induced mTBI. This is the first demonstration of an effective short term countermeasure for mTBI. Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00822263.

Concepts: Brain, Medical terms, Traumatic brain injury, Effectiveness, Term, Post-concussion syndrome, Concussion, BLAST

169

Over the past decade, there has been a considerable increase in research on, and media attention to, sports-related concussion. However, despite accurate diagnosis, effective treatment and management of sports-related concussion have remained a challenge. There are approximately 1.8 million traumatic brain injuries in the United States annually (Faul et al., 2010) and emergency department pediatric visits for suspected concussion have doubled in the past decade (Bakhos et al., 2010). However, health care providers and medical researchers have yet to offer an effective, reliable evidence-based treatment for concussive brain injury. The Zurich 2008 Consensus Statement on Concussion in Sport codified the prescription for cognitive and physical rest immediately following a concussion based on clinical acumen and common sense (McCrory et al., 2009). Currently, rest is the considered the best immediate treatment for concussion. Other supportive and anecdotal treatments are often applied throughout the post-concussive recovery process to address persistent symptoms. The need for empirical research to translate current guidelines for rest into evidence-based treatment protocols is essential. A recent study evaluated the efficacy of comprehensive rest and concluded that such rest may be helpful whether applied soon after a concussion or weeks to months later (Moser et al., 2012). Here, we present a case illustrating the effectiveness of rest in a youth athlete, commenced after experiencing 13 months of post-concussion symptoms. There appears to be value in applying a specific period of cognitive and physical rest following concussion, whether immediately or later in the recovery phase.

Concepts: Traumatic brain injury, Effectiveness, Research, Efficacy, Post-concussion syndrome, Focal and diffuse brain injury, Concussion, Dementia pugilistica

116

Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries.

Concepts: Central nervous system, Brain, Traumatic brain injury, Neurology, Acoustics, Sound, Concussion, Audio signal processing

107

It is time to stop using the term concussion as it has no clear definition and no pathological meaning. This confusion is increasingly problematic as the management of ‘concussed’ individuals is a pressing concern. Historically, it has been used to describe patients briefly disabled following a head injury, with the assumption that this was due to a transient disorder of brain function without long-term sequelae. However, the symptoms of concussion are highly variable in duration, and can persist for many years with no reliable early predictors of outcome. Using vague terminology for post-traumatic problems leads to misconceptions and biases in the diagnostic process, producing uninterpretable science, poor clinical guidelines and confused policy. We propose that the term concussion should be avoided. Instead neurologists and other healthcare professionals should classify the severity of traumatic brain injury and then attempt to precisely diagnose the underlying cause of post-traumatic symptoms.

Concepts: Time, Medical terms, Traumatic brain injury, Illness, Neurology, Psychiatry, Post-concussion syndrome, Concussion

88

The high prevalence of traumatic brain injuries (TBI) among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI.

Concepts: Traumatic brain injury, Concussion

60

The complexity of the traumatic brain injury (TBI) pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing), and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.

Concepts: DNA, Gene, Genetics, Gene expression, Brain, Traumatic brain injury, Neurology, Concussion

57

The acknowledgement of risks for traumatic brain injury in American football players has prompted studies for sideline concussion diagnosis and testing for neurological deficits. While concussions are recognized etiological factors for a spectrum of neurological sequelae, the consequences of sub-concussive events are unclear. We tested the hypothesis that blood-brain barrier disruption (BBBD) and the accompanying surge of the astrocytic protein S100B in blood may cause an immune response associated with production of auto-antibodies. We also wished to determine whether these events result in disrupted white matter on diffusion tensor imaging (DT) scans. Players from three college football teams were enrolled (total of 67 volunteers). None of the players experienced a concussion. Blood samples were collected before and after games (n = 57); the number of head hits in all players was monitored by movie review and post-game interviews. S100B serum levels and auto-antibodies against S100B were measured and correlated by direct and reverse immunoassays (n = 15 players; 5 games). A subset of players underwent DTI scans pre- and post-season and after a 6-month interval (n = 10). Cognitive and functional assessments were also performed. After a game, transient BBB damage measured by serum S100B was detected only in players experiencing the greatest number of sub-concussive head hits. Elevated levels of auto-antibodies against S100B were elevated only after repeated sub-concussive events characterized by BBBD. Serum levels of S100B auto-antibodies also predicted persistence of MRI-DTI abnormalities which in turn correlated with cognitive changes. Even in the absence of concussion, football players may experience repeated BBBD and serum surges of the potential auto-antigen S100B. The correlation of serum S100B, auto-antibodies and DTI changes support a link between repeated BBBD and future risk for cognitive changes.

Concepts: Immune system, Brain, Traumatic brain injury, College football, Blood-brain barrier, American football, Concussion, Football

56

Previous epidemiological studies suggest that working-aged persons with a history of moderate-to-severe traumatic brain injury (TBI) may have an increased risk for developing neurodegenerative disease (NDD) while persons with a history of mild TBI do not. In this comprehensive nationwide study in Finland, we assessed the risk of NDD and history of moderate-to-severe TBI in the working-age population.

Concepts: Cohort study, Medicine, Epidemiology, Demography, Traumatic brain injury, Actuarial science, Neurology, Concussion