Adult Traumatic Brain Injury Research Articles

Embedded validity indicators in Conners’ CPT-II: Do adult cutoffs work the same way in children?

ABSTRACTIn previous research, several subscales of Conners’ CPT-II were found to be useful as performance validity tests (PVTs) when administered to adults with traumatic brain injury (TBI). Furthermore, invalid response sets were associated with inflated scores on several CPT-II scales. The present study proposed to investigate whether these findings would replicate in a pediatric sample. The analyses were based on archival data from 15 children with TBI. The Omissions, Hit RT, Perseverations, and Hit RT BC scales proved effective at differentiating valid and invalid response sets. However, Commission errors were unrelated to scores on PVTs. A composite measure based on these four scores was a superior and more stable validity indicator than individual scales. Two or more T-scores >65 on any of these scales resulted in acceptable overall specificity (.86–1.00) and variable sensitivity (.00–1.00). Scores on CPT-II scales were generally higher among those who failed the reference PVTs. Results suggest that embedded CPT-II validity indices developed in adult TBI samples function similarly in children with TBI, with some notable exceptions. Although the use of adult PVT cutoffs in pediatric assessment is a common practice, and broadly supported by the present findings, there remains a clear need for the independent empirical validation of adult PVTs in children.

Abstracts from The 34(th) Annual National Neurotrauma Symposium June 26-29, 2016 Lexington, Kentucky.

Abstracts from The 34(th) Annual National Neurotrauma Symposium June 26-29, 2016 Lexington, Kentucky.

Resilience and Other Possible Outcomes After Mild Traumatic Brain Injury: a Systematic Review.

The relation between resilience and mild traumatic brain injury (TBI) outcome has been theorized but empirical studies have been scarce. This systematic review aimed to describe the research in this area. Electronic databases (Medline, CINAHL, PsychINFO, SPORTdiscus, and PILOTS) were searched from inception to August 2015 for studies in which resilience was measured following TBI. The search terms included 'TBI' 'concussion' 'postconcussion' 'resilience' and 'hardiness'. Inclusion criteria were peer reviewed original research reports published in English, human participants aged 18years and over with brain injury, and an accepted definition of mild TBI. Hand searching of identified articles was also undertaken. Of the 71 studies identified, five studies were accepted for review. These studies were formally assessed for risk of bias by two independent reviewers. Each study carried a risk of bias, most commonly a detection bias, but none were excluded on this basis. A narrative interpretation of the findings was used because the studies reflected fundamental differences in the conceptualization of resilience. No studies employed a trajectory based approach to measure a resilient outcome. In most cases, the eligible studies assessed trait resilience with a scale and used it as a predictor of outcome (postconcussion symptoms). Three of these studies showed that greater trait resilience was associated with better mild TBI outcomes (fewer symptoms). Future research of the adult mild TBI response that predicts a resilient outcome is encouraged. These studies could yield empirical evidence for a resilient, and other possible mild TBI outcomes.

Concussion and Psychiatric Outcome in Adults and Children

I accepted the invitation to write this editorial on the traumatic brain injury (TBI) manuscripts in this edition of the Journal because of my career focus on psychiatric aspects of TBI. I disclose that I am also privileged to be a contributing author on both of the TBI articles. The 2 articles that focus on TBI in this edition are review articles of conditions of high public health concern. Public awareness of adult sports-related TBI has risen in the past few years, especially in the arena of football. Therefore, a review of adult sports-related TBI is timely. Similarly, there has been a marked increase in concern regarding mild TBI (mTBI) in children and adolescents, especially in sports (e.g., Institute of Medicine report). Sports capture the imagination of a large segment of society. Adult sports stars tend to become role models for people of all ages, and professional sports are associated with substantial financial implications for players, franchise owners, media, fans, city coffers, and vendors. Thus, when our stars appear to be stricken with psychiatric disorders allegedly from multiple concussions, the sport itself has to respond to investigate the extent and nature of the problem for the safety of participants and the perpetuation of the sport. Concussion in youth has similarly become more prominent in societal discourse. Although pediatric TBI encompasses a much broader problem than sports-related concussion, such is the ubiquity and passion for youth sports in our society that sports have become the driver for public attention to youth TBI. The role of youth sports in society is a positive force for socialization and physical health of our children. Youth sports also involve parents encouraging their children and potentially enhancing parent-child relationships. In addition, parents find that their social networks are extended by socializing with fellow parents of youth team members. The timely question asked is that if adult sport is associated with psychiatric complications from concussion, ‘‘how likely is it that our children who participate in sports face similar risks?’’ The review of psychiatric sequelae of concussion related to adult sports suggested that there is a developing body of evidence supporting the existence of long-term psychiatric and psychological complications. Specifically, in most studies, depressive symptoms were linked to concussion. The studies with regard to anxiety and also substance abuse were few, and findings were mixed with regard to a connection with concussion. Studies that focused on behavioural changes typically identified behaviour and/or cognitive changes after sports concussion, and a link was suggested in 2 studies. Chronic traumatic encephalopathy, a degenerative neurological disease that occurs years after concussion or repetitive head trauma, was included in this review. This broad syndrome is associated with mood, behavior, cognitive, and substance use problems. Clear subtypes and aetiologies have not yet emerged, but there is some evidence of symptom patterns of initial onset of cognitive problems followed by psychiatric complications or early psychiatric problems followed by cognitive decline. The systematic review of psychiatric, psychological, and behavioural outcomes after mTBI in children and adolescents found that problems were more prevalent earlier in the recovery period, when the injury was of sufficient severity to result in hospitalization, where there was preinjury psychiatric disorder, when assessment relied on retrospective recall, and when the comparison group consisted of noninjured healthy children rather than an injured child (e.g., orthopedic fracture) comparison group. There is a clear common characteristic that both these reviews expose. There is a surprising paucity of data on topics that have such a high public health cost and that have generated such public interest and concern. The goldstandard psychiatric assessment, which uses a structured or semistructured psychiatric interview complemented by

Adult sports-related traumatic brain injury in United States trauma centers.

OBJECTIVE Sports-related traumatic brain injury (TBI) is an important public health concern estimated to affect 300,000 to 3.8 million people annually in the United States. Although injuries to professional athletes dominate the media, this group represents only a small proportion of the overall population. Here, the authors characterize the demographics of sports-related TBI in adults from a community-based trauma population and identify predictors of prolonged hospitalization and increased morbidity and mortality rates. METHODS Utilizing the National Sample Program of the National Trauma Data Bank (NTDB), the authors retrospectively analyzed sports-related TBI data from adults (age ≥ 18 years) across 5 sporting categories-fall or interpersonal contact (FIC), roller sports, skiing/snowboarding, equestrian sports, and aquatic sports. Multivariable regression analysis was used to identify predictors of prolonged hospital length of stay (LOS), medical complications, inpatient mortality rates, and hospital discharge disposition. Statistical significance was assessed at α < 0.05, and the Bonferroni correction for multiple comparisons was applied for each outcome analysis. RESULTS From 2003 to 2012, in total, 4788 adult sports-related TBIs were documented in the NTDB, which represented 18,310 incidents nationally. Equestrian sports were the greatest contributors to sports-related TBI (45.2%). Mild TBI represented nearly 86% of injuries overall. Mean (± SEM) LOSs in the hospital or intensive care unit (ICU) were 4.25 ± 0.09 days and 1.60 ± 0.06 days, respectively. The mortality rate was 3.0% across all patients, but was statistically higher in TBI from roller sports (4.1%) and aquatic sports (7.7%). Age, hypotension on admission to the emergency department (ED), and the severity of head and extracranial injuries were statistically significant predictors of prolonged hospital and ICU LOSs, medical complications, failure to discharge to home, and death. Traumatic brain injury during aquatic sports was similarly associated with prolonged ICU and hospital LOSs, medical complications, and failure to be discharged to home. CONCLUSIONS Age, hypotension on ED admission, severity of head and extracranial injuries, and sports mechanism of injury are important prognostic variables in adult sports-related TBI. Increasing TBI awareness and helmet use-particularly in equestrian and roller sports-are critical elements for decreasing sports-related TBI events in adults.

Guideline adherence and outcomes in severe adult traumatic brain injury for the CHIRAG (Collaborative Head InjuRy and Guidelines) study

Guideline adherence and outcomes in severe adult traumatic brain injury for the CHIRAG (Collaborative Head InjuRy and Guidelines) study

Continuous Multimodality Monitoring in Children after Traumatic Brain Injury-Preliminary Experience.

IntroductionMultimodality monitoring is regularly employed in adult traumatic brain injury (TBI) patients where it provides physiologic and therapeutic insight into this heterogeneous condition. Pediatric studies are less frequent.MethodsAn analysis of data collected prospectively from 12 pediatric TBI patients admitted to Addenbrooke’s Hospital, Pediatric Intensive Care Unit (PICU) between August 2012 and December 2014 was performed. Patients’ intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were monitored continuously using brain monitoring software ICM+®,) Pressure reactivity index (PRx) and ‘Optimal CPP’ (CPPopt) were calculated. Patient outcome was dichotomized into survivors and non-survivors.ResultsAt 6 months 8/12 (66%) of the cohort survived the TBI. The median (±IQR) ICP was significantly lower in survivors 13.1±3.2 mm Hg compared to non-survivors 21.6±42.9 mm Hg (p = 0.003). The median time spent with ICP over 20 mm Hg was lower in survivors (9.7+9.8% vs 60.5+67.4% in non-survivors; p = 0.003). Although there was no evidence that CPP was different between survival groups, the time spent with a CPP close (within 10 mm Hg) to the optimal CPP was significantly longer in survivors (90.7±12.6%) compared with non-survivors (70.6±21.8%; p = 0.02). PRx provided significant outcome separation with median PRx in survivors being 0.02±0.19 compared to 0.39±0.62 in non-survivors (p = 0.02).ConclusionOur observations provide evidence that multi-modality monitoring may be useful in pediatric TBI with ICP, deviation of CPP from CPPopt, and PRx correlating with patient outcome.

Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury

Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague-Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14days. Our results showed that 14days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option.

The prognostic value of magnetic resonance imaging in moderate and severe traumatic brain injury: a systematic review and meta-analysis protocol.

BackgroundTraumatic brain injury (TBI) is a devastating condition with significant long-term mortality and morbidity. Despite current need for objective indicators to guide initial decision-making, few reliable acute phase prognostic factors have been identified. Early magnetic resonance imaging (MRI) has been investigated as a prognostic tool, but uncertainty remains in both its discriminative predictive value and which acute phase lesion patterns correlate with long-term outcome.MethodsWe will conduct a systematic review of observational cohort studies and randomized controlled trials of adult moderate or severe TBI patients who underwent MRI in the acute phase after trauma. A high sensitivity search strategy will be employed in MEDLINE, EMBASE, BIOSIS, and Cochrane CENTRAL to identify citations. Two reviewers will independently screen all identified references for eligibility and extract data into a standardized form. Data will be collected on study design, baseline demographics, trauma characteristics, magnetic resonance (MR) technical specifications, lesion patterns, and outcomes as related to acute MRI imaging. If meta-analysis is possible, quantitative data for each outcome will be pooled per type of lesion pattern using random effects models and expressed as Mantel-Haenszel relative risks in order to determine the prognostic value of lesions detected on acute MRI and their strength as discriminatory predictors of long-term outcome. Statistical heterogeneity will be evaluated with the I2 statistics, and risk of bias and reporting quality will be assessed with standardized scales. Subgroup analyses are planned as a function of TBI severity, MRI-timing post-TBI, MRI field strength, MRI sequence, timing of outcome assessment, and risk of bias.DiscussionWe expect significant clinical heterogeneity, as eligible studies will likely encompass different periods in evolving MRI technology in addition to significant variability of image sequence protocols and timing of acquisition between centers. Based on existing studies in TBI, we expect lesions detected in the brainstem to be of significant predictive value as MRI is particularly sensitive for imaging the brain’s posterior fossa. Our systematic review will allow clinicians to more accurately interpret MRI in the context of determining prognosis for moderate and severe TBI patients and inform researchers in this domain to improve the methodology of future studies.Systematic review registrationProspero CRD42015017074Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0184-x) contains supplementary material, which is available to authorized users.

Guideline Adherence and Outcomes in Severe Adult Traumatic Brain Injury for the CHIRAG (Collaborative Head Injury and Guidelines) Study

We examined the effect of early intensive care unit (ICU) adherence to 2007 Brain Trauma Foundation Guideline indicators after traumatic brain injury (TBI) on inpatient mortality at a level 1 trauma center in India (Jay Prakash Narayan Apex Trauma Center [JPNATC]) and Harborview Medical Center (HMC) in U.S. among adults older than 18 years with severe TBI. At each site, ICU Guideline adherence in first 72 hours for 17 indicators was determined and expressed as a percentage. Outcomes were in-hospital mortality and Glasgow Outcome Scale (GOS) scores at 3, 6, and 12 months after discharge. JPNATC and HMC Guideline adherence rates were 74.9% [11.0] and 71.6 % (SD ±10.4), and overall in-hospital mortality was 24% and 27%, respectively. At JPNATC, less than 65% ICU Guideline adherence was associated with higher inpatient mortality (adjusted relative risk [aRR], 1.92; 95% confidence interval [CI], 1.11-3.33) and an increase in ICU Guideline adherence rate by 1% was associated with a 3% lower in-hospital mortality (aRR, 0.97; 95% CI, 0.95-0.99). Among patients discharged with a GOS score of 2-4 at JPNATC, 67% improved at 12 months (R(2)= 0.991; P < 0.01; 99% follow-up rate) compared with discharge, but 35%, 25%, and 14% of patients discharged with a GOS score of 3-5 deteriorated at 3, 6, and 12 months to a lower GOS at home. Achieving early ICU adherence to guideline indicators was feasible and associated with significantly lower in-hospital mortality at JPNATC. Although the intracranial pressure (ICP) monitoring rates varied, in-hospitals deaths were similar between the two institutions. Although long-term outcomes generally improved, patients discharged with favorable GOS score often deteriorated at home.

Guidelines for the diagnosis and treatment of severe traumatic brain injury. Part 2. Intensive care and neuromonitoring

Traumatic brain injury (TBI) is one of the major causes of death and disability in young and middle-aged people. The most problematic group is comprised of patients with severe TBI who are in a coma. The adequate diagnosis of primary brain injuries and timely prevention and treatment of the secondary injury mechanisms largely define the possibility of reducing mortality and severe disabling consequences. When developing these guidelines, we used our experience in the development of international and national recommendations for the diagnosis and treatment of mild traumatic brain injury, penetrating gunshot wounds to the skull and brain, severe traumatic brain injury, and severe consequences of brain injuries, including a vegetative state. In addition, we used international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe traumatic brain injury, which had been published in recent years. The proposed guidelines concern intensive care of severe TBI in adults and are particularly intended for neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in the treatment of these patients.

Guidelines for the management of severe traumatic brain injury. Part 3. Surgical management of severe traumatic brain injury (Options)

Traumatic brain injury (TBI) is one of the main causes of mortality and severe disability in young and middle age patients. Patients with severe TBI, who are in coma, are of particular concern. Adequate diagnosis of primary brain injuries and timely prevention and treatment of secondary injury mechanisms markedly affect the possibility of reducing mortality and severe disability. The present guidelines are based on the authors' experience in developing international and national recommendations for the diagnosis and treatment of mild TBI, penetrating gunshot wounds of the skull and brain, severe TBI, and severe consequences of brain injury, including a vegetative state. In addition, we used the materials of international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe TBI, which were published in recent years. The proposed recommendations for surgical treatment of severe TBI in adults are addressed primarily to neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in treating these patients.

Hypothermia for severe traumatic brain injury in adults: Recent lessons from randomized controlled trials.

Background:Traumatic brain injury (TBI) is a worldwide health concern associated with significant morbidity and mortality. In the United States, severe TBI is managed according to recommendations set forth in 2007 by the Brain Trauma Foundation (BTF), which were based on relatively low quality clinical trials. These guidelines prescribed the use of hypothermia for the management of TBI. Several randomized controlled trials (RCTs) of hypothermia for TBI have since been conducted. Despite this new literature, there is ongoing controversy surrounding the use of hypothermia for the management of severe TBI.Methods:We searched the PubMed database for all RCTs of hypothermia for TBI since 2007 with the intent to review the methodology outcomes of these trials. Furthermore, we aimed to develop evidence-based, expert opinions based on these recent studies.Results:We identified 8 RCTs of therapeutic hypothermia published since 2007 that focused on changes in neurologic outcomes or mortality in patients with severe TBI. The majority of these trials did not identify improvement with the use of hypothermia, though there were subgroups of patients that may have benefited from hypothermia. Differences in methodology prevented direct comparison between studies.Conclusions:A growing body of literature disfavors the use of hypothermia for the management of severe TBI. In general, empiric hypothermia for severe TBI should be avoided. However, based on the results of recent trials, there may be some patients, such as those in Asian centers or with focal neurologic injury, who may benefit from hypothermia.

Prevalence of anxiety following adult traumatic brain injury: A meta-analysis comparing measures, samples and postinjury intervals.

Anxiety following a traumatic brain injury (TBI) is a common problem; however, disparate prevalence estimates limit the clinical utility of research. The purpose of the current study was to examine how differences in methodological variables and sample characteristics impact on the prevalence of anxiety. Data from 41 studies that examined either the prevalence of generalized anxiety disorder (GAD) diagnoses or clinically significant "cases" of self-reported anxiety following adult, nonpenetrating TBI were analyzed, and the impact of diagnostic criteria, measure, postinjury interval and injury severity was evaluated. Overall, 11% of people were diagnosed with GAD and 37% reported clinically significant levels of anxiety following TBI. Prevalence estimates varied for different diagnostic criteria (range: 2%-19%), interview schedules (range: 2%-28%), and self-report measures (range: 36%-50%). GAD and "cases" of anxiety were most prevalent 2 to 5 years postinjury. The rates of GAD increased with injury severity (mild: 11%, severe 15%), but "cases" decreased (mild: 53%, severe: 38%), although neither difference was significant. Anxiety is common after a TBI and ongoing monitoring and treatment should be provided. Methodological and sample characteristics should be clear and well-defined, as differences across studies (e.g., how anxiety is conceptualized, which measure is used, time since injury, injury severity) impact prevalence rates.

Management of Adult Traumatic Brain Injury: A Review

Traumatic brain injury (TBI) is a significant source of morbidity and mortality in the adult population. The management of traumatic brain injury depends on its severity. It must be recognized that almost all forms of treatment for TBI are geared towards the minimization of secondary injury, as it is assumed that primary injury is irreversible. The discussion here represents much of what is known up-to-date concerning TBI management, but its treatment continues to evolve once new mechanisms of injury are discovered and those that we know of now are refined. The treating staffs are encouraged to keep up with the current state of the literature to stay informed.

The Effect of Hemoglobin Levels on Mortality in Pediatric Patients with Severe Traumatic Brain Injury.

Objective. There is increasing evidence of adverse outcomes associated with blood transfusions for adult traumatic brain injury patients. However, current evidence suggests that pediatric traumatic brain injury patients may respond to blood transfusions differently on a vascular level. This study examined the influence of blood transfusions and anemia on the outcome of pediatric traumatic brain injury patients. Design. A retrospective cohort analysis of severe pediatric traumatic brain injury (TBI) patients was undertaken to investigate the association between blood transfusions and anemia on patient outcomes. Measurements and Main Results. One hundred and twenty patients with severe traumatic brain injury were identified and included in the analysis. The median Glasgow Coma Scale (GCS) was 6 and the mean hemoglobin (Hgb) on admission was 115.8 g/L. Forty-three percent of patients (43%) received at least one blood transfusion and the mean hemoglobin before transfusion was 80.1 g/L. Multivariable regression analysis revealed that anemia and the administration of packed red blood cells were not associated with adverse outcomes. Factors that were significantly associated with mortality were presence of abusive head trauma, increasing PRISM score, and low GCS after admission. Conclusion. In this single centre retrospective cohort study, there was no association found between anemia, blood transfusions, and hospital mortality in a pediatric traumatic brain injury patient population.

Pharmacotherapy for chronic cognitive impairment in traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of chronic disability. Worldwide, it is the leading cause of disability in the under 40s, resulting in severe disability in some 150 to 200 million people per annum. In addition to mood and behavioural problems, cognition-particularly memory, attention and executive function-are commonly impaired by TBI. Cognitive problems following TBI are one of the most important factors in determining people's subjective well-being and their quality of life. Drugs are widely used in an attempt to improve cognitive functions. Whilst cholinergic agents in TBI have been reviewed, there has not yet been a systematic review or meta-analysis of the effect on chronic cognitive problems of all centrally acting pharmacological agents. To assess the effects of centrally acting pharmacological agents for treatment of chronic cognitive impairment subsequent to traumatic brain injury in adults. We searched ALOIS-the Cochrane Dementia and Cognitive Improvement Group's Specialised Register-on 16 November 2013, 23 February 2013, 20 January 2014, and 30 December 2014 using the terms: traumatic OR TBI OR "brain injury" OR "brain injuries" OR TBIs OR "axonal injury" OR "axonal injuries". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. Supplementary searches were also performed in MEDLINE, EMBASE, PsycINFO, The Cochrane Library, CINAHL, LILACs, ClinicalTrials.gov, the World Health Organization (WHO) Portal (ICTRP) and Web of Science with conference proceedings. We included randomised controlled trials (RCTs) assessing the effectiveness of any one centrally acting pharmacological agent that affects one or more of the main neurotransmitter systems in people with chronic traumatic brain injury; and there had to be a minimum of 12 months between the injury and entry into the trial. Two review authors examined titles and abstracts of citations obtained from the search. Relevant articles were retrieved for further assessment. A bibliographic search of relevant papers was conducted. We extracted data using a standardised tool, which included data on the incidence of adverse effects. Where necessary we requested additional unpublished data from study authors. Risk of bias was assessed by a single author. Only four studies met the criteria for inclusion, with a total of 274 participants. Four pharmacological agents were investigated: modafinil (51 participants); (-)-OSU6162, a monoamine stabiliser (12 participants of which six had a TBI); atomoxetine (60 participants); and rivastigmine (157 participants). A meta-analysis could not be performed due to the small number and heterogeneity of the studies.All studies examined cognitive performance, with the majority of the psychometric sub-tests showing no difference between treatment and placebo (n = 274, very low quality evidence). For (-)-OSU6162 modest superiority over placebo was demonstrated on three measures, but markedly inferior performance on another. Rivastigmine was better than placebo on one primary measure, and a single cognitive outcome in a secondary analysis of a subgroup with more severe memory impairment at baseline. The study of modafinil assessed clinical global improvement (n = 51, low quality evidence), and did not find any difference between treatment and placebo. Safety, as measured by adverse events, was reported by all studies (n = 274, very low quality evidence), with significantly more nausea reported by participants who received rivastigmine compared to placebo. There were no other differences in safety between treatment and placebo. No studies reported any deaths. There is insufficient evidence to determine whether pharmacological treatment is effective in chronic cognitive impairment in TBI. Whilst there is a positive finding for rivastigmine on one primary measure, all other primary measures were not better than placebo. The positive findings for (-)-OSU6162 are interpreted cautiously as the study was small (n = 6). For modafinil and atomoxetine no positive effects were found. All four drugs appear to be relatively well tolerated, although evidence is sparse.

Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults.

BackgroundAcute management of traumatic brain injury (TBI), in particular mild TBI, focuses on the detection of the 5–7 % who may be harboring potentially life-threatening intracranial hemorrhage (IH) using CT scanning. Guidelines intending to reduce unnecessary head CT scans using available clinical variables to detect those at high IH risk have shown varying results. Recently, the Scandinavian Neurotrauma Committee (SNC) derived a new set of high-IH risk variables for adults with TBI using an evidence-based literature review. Unlike previous guidelines, the SNC guideline incorporates serum values of the brain protein S100B with clinical variables.MethodsWe performed a nested cohort study of adults with mild TBI presenting to six emergency departments in New York and Pennsylvania within 6 h of injury. Patients were managed according to existing guidelines for CT selection. All patients underwent head CT scanning and serum S100B measurement, as well as prospective collection of clinical variables, as a requirement of the parent study. Using the SNC guidelines, S100B values and clinical variables were applied to these subjects, classifying each into one of five pre-defined severity categories, as well as predicting the need for head CT scanning to identify IH. This classification was then compared to actual head CT results to determine guideline sensitivity and specificity.ResultsIn total, 662 adults (mean age 42 years, range 18–96; 258 females, 549 Caucasians) were available for analysis; 36 (5 %) had IH on head CT scan. The SNC guidelines had a sensitivity of 97 % (95 % CI, 84–100 %) and a specificity of 34 % (95 % CI, 30–37 %) for the detection of IH on head CT. Application of the SNC guidelines would have resulted in a CT reduction of 32 % (211/662 patients). One patient with low-risk mild TBI and a S100B level under 0.10 μg/L had a traumatic CT abnormality and would have been discharged with strict adherence to the guidelines. However, this patient did not need any intervention for the injury and had a good outcome.ConclusionUsing the SNC guideline could save approximately one third of CT scans in a pre-selected cohort of mild TBI patients with little or no impact on patient outcome.

Cerebrovascular Pressure Reactivity in Children With Traumatic Brain Injury*

Traumatic brain injury is a significant cause of morbidity and mortality in children. Cerebral autoregulation disturbance after traumatic brain injury is associated with worse outcome. Pressure reactivity is a fundamental component of cerebral autoregulation that can be estimated using the pressure-reactivity index, a correlation between slow arterial blood pressure, and intracranial pressure fluctuations. Pressure-reactivity index has shown prognostic value in adult traumatic brain injury, with one study confirming this in children. Pressure-reactivity index can identify a cerebral perfusion pressure range within which pressure reactivity is optimal. An increasing difference between optimal cerebral perfusion pressure and cerebral perfusion pressure is associated with worse outcome in adult traumatic brain injury; however, this has not been investigated in children. Our objective was to study pressure-reactivity index and optimal cerebral perfusion pressure in pediatric traumatic brain injury, including associations with outcome, age, and cerebral perfusion pressure. Prospective observational study. ICU, Royal Children's Hospital, Melbourne, Australia. Patients with traumatic brain injury who are 6 months to 16 years old, are admitted to the ICU, and require arterial blood pressure and intracranial pressure monitoring. None. Arterial blood pressure, intracranial pressure, and end-tidal CO2 were recorded electronically until ICU discharge or monitoring cessation. Pressure-reactivity index and optimal cerebral perfusion pressure were computed according to previously published methods. Clinical data were collected from electronic medical records. Outcome was assessed 6 months post discharge using the modified Glasgow Outcome Score. Thirty-six patients were monitored, with 30 available for follow-up. Pressure-reactivity index correlated with modified Glasgow Outcome Score (Spearman ρ = 0.42; p = 0.023) and was higher in patients with unfavorable outcome (0.23 vs -0.09; p = 0.0009). A plot of pressure-reactivity index averaged within 5 mm Hg cerebral perfusion pressure bins showed a U-shape, reaffirming the concept of cerebral perfusion pressure optimization in children. Optimal cerebral perfusion pressure increased with age (ρ = 0.40; p = 0.02). Both the duration and magnitude of negative deviations in the difference between cerebral perfusion pressure and optimal cerebral perfusion pressure were associated with unfavorable outcome. In pediatric patients with traumatic brain injury, pressure-reactivity index has prognostic value and can identify cerebral perfusion pressure targets that may differ from treatment protocols. Our results suggest but do not confirm that cerebral perfusion pressure targeting using pressure-reactivity index as a guide may positively impact on outcome. This question should be addressed by a prospective clinical study.

Magnetic Resonance Spectroscopy for Traumatic Brain Injury.

Magnetic resonance spectroscopy (MRS) provides a noninvasive tool to assess metabolic change in the brain following head injury. Observable metabolites reflect neuronal density and viability, glial density, membrane injury, and hypoxia or ischemia. MRS has been used in traumatic brain injury (TBI) research for nearly 20 years and this article reviews the MRS findings in the adult TBI population.Although MRS observations are heterogeneous, there are consistent patterns in TBI with the neuronal metabolite N-acetyl-aspartate (NAA) significantly reduced in the vast majority of studies, while the membrane related choline signal (Cho) is almost equally found to be elevated. The glial metabolites myo-inositol is often observed to be increased postinjury and this elevation persists into the chronic phase, which is interpreted as revealing gliosis. Observation of elevated lactate levels are sporadic and mainly in acute studies in severely injured subjects. In general, these spectral changes show a dependency on injury severity and acute changes relate to both neuropsychological deficits and to long-term outcome.