The conflicts in Iraq and Afghanistan have placed an increased awareness on traumatic brain injury (TBI). Various publications have estimated the incidence of TBI for our deployed servicemen, however all have been based on extrapolations of data sets or subjective evaluations due to our current method of diagnosing a TBI. Therefore it has been difficult to get an accurate rate and severity of deployment related TBIs, or the incidence of multiple TBIs our service members are experiencing. As such, there is a critical need to develop a rapid objective method to diagnose TBI on the battlefield. Because of the austere environment of the combat theater the ideal diagnostic platform faces numerous logistical constraints not encountered in civilian trauma centers. Consequently, a simple blood test to diagnosis TBI represents a viable option for the military. This perspective will provide information on some of the current options for TBI biomarkers, detail concerning battlefield constraints, and a possible acquisition strategy for the military. The end result is a non-invasive TBI diagnostic platform capable of providing much needed advances in objective triage capabilities and improved clinical management of in-Theater TBI.
TBI; military; biomarkers; diagnosis; concussion
Return to work may be easily monitored as a surrogate of long-term functional outcome for benchmarking and performance improvement of trauma systems. We hypothesized that employment rates among survivors of traumatic brain injury (TBI) decrease following injury and remain depressed for an extended period of time. Data were obtained from a statewide surveillance system of 3522 TBI patients (aged >15 years) who were discharged alive from acute care hospitals and followed yearly using telephone interviews (1996–1999). The study population consisted of patients with severe TBI (head abbreviated injury score 3, 4, or 5) and complete follow-up for 3 years postinjury (n = 572). Patients were mostly young males (43 ± 19 years, 65% male) with blunt TBI (92%). The preinjury employment rate was 67%, which declined to 52% (P < 0.001) in the first year and slowly rose in subsequent years but never reached the preinjury level (54% in year 2, P < 0.001; 57% in year 3, P = 0.001). Increasing severity of TBI was associated with a lower employment rate. Patients who remained employed worked the same number of hours as they did before the injury (47.8 ± 10.5 hours). Female employment rates rose similar to rates for males. However, women who were employed full-time before TBI were more likely to work part-time after TBI than men (50% vs 24%, P < 0.001). In conclusion, survivors of severe injury do not attain preinjury employment levels for several years. Once validated in other studies, postinjury employment may be used as an indicator to monitor functional outcomes in trauma registries.
Intracranial bleeding (IB) is a common and serious consequence of traumatic brain injury (TBI). IB can be classified according to the location into: epidural haemorrhage (EDH) subdural haemorrhage (SDH) intraparenchymal haemorrhage (IPH) and subarachnoid haemorrhage (SAH). Studies involving repeated CT scanning of TBI patients have found that IB can develop or expand in the 48 hours after injury. If IB enlarges after hospital admission and larger bleeds have a worse prognosis, this would provide a therapeutic rationale for treatments to prevent increase in the extent of bleeding. We analysed data from the Trauma Audit & Research Network (TARN), a large European trauma registry, to evaluate the association between the size of IB and mortality in patients with TBI.
We analysed 13,962 patients presenting to TARN participating hospitals between 2001 and 2008 with a Glasgow Coma Score (GCS) less than 15 at presentation or any head injury with Abbreviated Injury Scale (AIS) severity code 3 and above. The extent of intracranial bleeding was determined by the AIS code. Potential confounders were age, presenting Glasgow Coma Score, mechanism of injury, presence and nature of other brain injuries, and presence of extra-cranial injuries. The outcomes were in-hospital mortality and haematoma evacuation. We conducted a multivariable logistic regression analysis to evaluate the independent effect of large and small size of IB, in comparison with no bleeding, on patient outcomes. We also conducted a multivariable logistic regression analysis to assess the independent effect on mortality of large IB in comparison with small IB.
Almost 46% of patients had at some type of IB. Subdural haemorrhages were present in 30% of the patients, with epidural and intraparenchymal present in approximately 22% each. After adjusting for potential confounders, we found that large IB, wherever located, was associated with increased mortality in comparison with no bleeding. We also found that large IB was associated with an increased risk of mortality in comparison with small IB. The odds ratio for mortality for large SDH, IPH and EDH, in comparison with small bleeds, were: 3.41 (95% CI: 2.68-4.33), 3.47 (95% CI: 2.26-5.33) and 2.86 (95% CI: 1.86-4.38) respectively.
Large EDH, SDH and IPH are associated with a substantially higher probability of hospital mortality in comparison with small IB. However, the limitations of our data, such as the large proportion of missing data and lack of data on other confounding factors, such as localization of the bleeding, make the results of this report only explanatory. Future studies should also evaluate the effect of IB size on functional outcomes.
Uncertainties exist about the rates, predictors and outcomes of major depressive disorder (MDD) among people with traumatic brain injury (TBI).
To describe MDD related rates, predictors, outcomes and treatment during the first year after TBI
Cohort from 6/2001–3/2005 followed by structured telephone interviews at months 1–6, 8, 10, and 12 (data collection ending 2/2006).
Harborview Medical Center, a Level I trauma center in Seattle, WA
559 consecutively hospitalized adults with complicated mild to severe TBI
Main Outcome Measures
The Patient Health Questionnaire (PHQ) depression and anxiety modules were administered at each assessment and the European Quality of Life measure (EQ-5D) was given at 12 months.
53% met criteria for MDD at least once in the follow-up period. Point prevalences ranged between 31% at one month and 21% at six months. In a multivariate model, increased risk of MDD after TBI was associated with MDD at the time of injury (risk ratio [RR], 1.62; 95% confidence interval [CI], 1.37–1.91), history of MDD prior to injury (but not at the time of injury) (RR, 1.54; 95% CI, 1.31–1.82), age (RR, 0.61; 95% CI, 0.44–0.83 for 60+ years vs. 18–29 years) and lifetime alcohol dependence (RR, 1.34; 95% CI, 1.14–1.57). Those with MDD were more likely to report co-morbid anxiety disorders after TBI than those without MDD (60% versus 7%; RR, 8.77; 95% CI, 5.56–13.83). Only 44% of those with MDD received antidepressants or counseling. After adjusting for predictors of MDD, persons with MDD reported lower quality of life at one year, compared to the nondepressed group.
Among a cohort of patients hospitalized for TBI, 53% met criteria for MDD during the first year after TBI. MDD was associated with prior history of MDD and was an independent predictor of poorer health-related quality of life.
Traumatic brain injury (TBI) is a significant problem in older adults. In persons aged 65 and older, TBI is responsible for more than 80,000 emergency department visits each year; three-quarters of these visits result in hospitalization as a result of the injury. Adults aged 75 and older have the highest rates of TBI-related hospitalization and death. Falls are the leading cause of TBI for older adults (51%), and motor vehicle traffic crashes are second (9%). Older age is known to negatively influence outcome after TBI. Although geriatric and neurotrauma investigators have identified the prognostic significance of preadmission functional ability, comorbidities, sex, and other factors such as cerebral perfusion pressure on recovery after illness or injury, these variables remain understudied in older adults with TBI. In the absence of good clinical data, predicting outcomes and providing care in the older adult population with TBI remains problematic. To address this significant public health issue, a refocusing of research efforts on this population is justified to prevent TBI in the older adult and to discern unique care requirements to facilitate best patient outcomes.
traumatic brain injury; head injury; geriatric; trauma; injury; epidemiology; outcomes; functional status
We examined the financial and social costs resulting from traumatic brain injury (TBI) in Missouri.
We computed mortality rates from death certificates, the direct cost of TBI from hospital and emergency department (ED) visit charges, the social cost in terms of years of potential life lost (YPLL) using an abridged Missouri life table, and the indirect financial cost in terms of lost productivity due to premature death for all TBI and four major causes of TBI in Missouri.
During 2001–2005, a mean of 1,358 lives were lost due to TBI in Missouri. Four major causes—unintentional falls, motor vehicle traffic crashes, motorcycle crashes, and firearms—accounted for 88% of all TBI deaths. We estimated the annual direct medical cost of TBI at $95 million, or about $1.67 million per 100,000 Missourians. This cost increased by about 60% between 2001 and 2005. The four major causes of TBI accounted for 68% of all direct medical costs of TBI. We estimated the cost per hospitalization and ED visit at $6,948 and the indirect social cost at 48,501 YPLL. During this period, the mean age of TBI fatality was 44 years. We determined the lost productivity due to TBI mortality—$1.1 billion, or about $18.8 million per 100,000 Missourians—to be three times as high for males as for females.
The types of costs covered in this study underestimated the total cost of TBI in Missouri, as we did not include outpatient care, rehabilitation, and drug costs. Nevertheless, we found the health and economic burden from medical care and mortality related to TBI to be substantial in Missouri.
Acquired Brain Injury (ABI) from traumatic and non traumatic causes is a leading cause of disability worldwide yet there is limited research summarizing the health system economic burden associated with ABI. The objective of this study was to determine the direct cost of publicly funded health care services from the initial hospitalization to three years post-injury for individuals with traumatic (TBI) and non-traumatic brain injury (nTBI) in Ontario Canada.
A population-based cohort of patients discharged from acute hospital with an ABI code in any diagnosis position in 2004 through 2007 in Ontario was identified from administrative data. Publicly funded health care utilization was obtained from several Ontario administrative healthcare databases. Patients were stratified according to traumatic and non-traumatic causes of brain injury and whether or not they were discharged to an inpatient rehabilitation center. Health system costs were calculated across a continuum of institutional and community settings for up to three years after initial discharge. The continuum of settings included acute care emergency departments inpatient rehabilitation (IR) complex continuing care home care services and physician visits. All costs were calculated retrospectively assuming the government payer’s perspective.
Direct medical costs in an ABI population are substantial with mean cost in the first year post-injury per TBI and nTBI patient being $32132 and $38018 respectively. Among both TBI and nTBI patients those discharged to IR had significantly higher treatment costs than those not discharged to IR across all institutional and community settings. This tendency remained during the entire three-year follow-up period. Annual medical costs of patients hospitalized with a brain injury in Ontario in the first follow-up year were approximately $120.7 million for TBI and $368.7 million for nTBI. Acute care cost accounted for 46-65% of the total treatment cost in the first year overwhelming all other cost components.
The main finding of this study is that direct medical costs in ABI population are substantial and vary considerably by the injury cause. Although most expenses occur in the first follow-up year ABI patients continue to use variety of medical services in the second and third year with emphasis shifting over time from acute care and inpatient rehabilitation towards homecare physician services and long-term institutional care. More research is needed to capture economic costs for ABI patients not admitted to acute care.
Fever, in the presence of traumatic brain injury (TBI), is associated with worsened neurologic outcomes. Studies prior to the publication of management guidelines revealed an undertreatment of fever in patients with neurologic insults. Presently the adult TBI guidelines state that maintenance of normothermia should be a standard of care therefore improvement in management of fever in these patients would be expected. The specific aims of the study were to: 1) determine the incidence of fever (T> 38.5° C) in a population of critically ill patients with TBI. 2) describe what interventions were recorded by intensive care unit (ICU) nurses in managing fever. 3) ascertain the rate of adherence with published normothermia guidelines. Medical record review of available hospital records was conducted on patients admitted to a level I trauma center following severe TBI (N=108) from the parent study. Temperature data was abstracted and contemporaneous nursing documentation was examined for evidence of intervention for fever and adherence with published standards. Data analyses were performed that included descriptive statistics. Seventy-nine percent of TBI patients (85/108) had at least one recorded fever event while in the ICU. However in only 31% of events did the patient receive any documented intervention by nursing staff for the elevated temperature. The most frequently documented intervention was pharmacologic (358/1166 elevations). Other nursing actions (e.g. use of fan) accounted for a minority (<1%) of nursing interventions documented. Patients were more likely to have a high temperature that exceeded 40°C (13%) than a temperature that was normothermic (5%). There continues to be an under treatment of fever in patients with TBI by critical care nurses despite our knowledge of its negative effects on outcomes. There remains a gap in translation between patient outcomes research and bedside practice that needs to be overcome, thus research efforts need to now focus on understanding nurses’ decision-making processes and the best methods of fever reduction in patients with TBI.
head injury; hyperthermia; normothermia; clinical decision making; evidence-based practice
The study aims were to examine the association between age, comorbidity, and cause of injury in older adults with traumatic brain injury (TBI); and to determine which comorbidities relate to mortality, length of stay, and functional outcome at hospital discharge, controlling for initial injury severity, age, and sex. A retrospective cohort study design was used; clinical and outcome trauma registry data were obtained for 196 adults 55 and older with TBI. The majority had at least one comorbid condition (e.g., hypertension, alcohol abuse). In-hospital mortality was 31%. Among the oldest-old, motor vehicle collisions and falls were significantly associated with specific chronic diseases. Prior myocardial infarction was significantly associated with an increased risk of in-hospital death. Injury Severity Score and Glasgow Coma Scale score were predictive of discharge function, but comorbidity did not add significantly to the model. Primary TBI prevention efforts in older adults must consider the impact of comorbidity and cause of injury, particularly in the oldest-old. Alcohol abuse is common in older adults with TBI; screening should be conducted and interventions developed to prevent future injury. Future study is warranted to understand the interplay between pathophysiology of comorbid disease and injury and how to best manage rehabilitation within the context of aging.
Traumatic brain injury (TBI) remains a leading cause of death and disability.
The National Institute for Health and Clinical Excellence (NICE) guidelines
recommend transfer of severe TBI cases to neurosurgical centres,
irrespective of the need for neurosurgery. This observational study
investigated the risk-adjusted mortality of isolated TBI admissions in
England/Wales, and Victoria, Australia, and the impact of neurosurgical
centre management on outcomes.
Isolated TBI admissions (>15 years, July 2005–June 2006) were
extracted from the hospital discharge datasets for both jurisdictions.
Severe isolated TBI (AIS severity >3) admissions were provided by the
Trauma Audit and Research Network (TARN) and Victorian State Trauma Registry
(VSTR) for England/Wales, and Victoria, respectively. Multivariable logistic
regression was used to compare risk-adjusted mortality between
Mortality was 12% (749/6256) in England/Wales and 9% (91/1048)
in Victoria for isolated TBI admissions. Adjusted odds of death in
England/Wales were higher compared to Victoria overall (OR 2.0, 95%
CI: 1.6, 2.5), and for cases <65 years (OR 2.36, 95% CI: 1.51,
3.69). For severe TBI, mortality was 23% (133/575) for TARN and
20% (68/346) for VSTR, with 72% of TARN and 86% of VSTR
cases managed at a neurosurgical centre. The adjusted mortality odds for
severe TBI cases in TARN were higher compared to the VSTR (OR 1.45,
95% CI: 0.96, 2.19), but particularly for cases <65 years (OR
2.04, 95% CI: 1.07, 3.90). Neurosurgical centre management modified
the effect overall (OR 1.12, 95% CI: 0.73, 1.74) and for cases <65
years (OR 1.53, 95% CI: 0.77, 3.03).
The risk-adjusted odds of mortality for all isolated TBI admissions, and
severe TBI cases, were higher in England/Wales when compared to Victoria.
The lower percentage of cases managed at neurosurgical centres in England
and Wales was an explanatory factor, supporting the changes made to the NICE
BACKGROUND: Although regional variations in the use of many health care services have been reported, little attention has been devoted to home care practices. Given the dramatic shift in care settings from hospitals to private homes, it is important to determine the extent to which home care practices vary by geographic region. METHODS: Data from the Canadian Institute for Health Information and the Ontario Home Care Administration System database were used to assess regional variations in rates of home care use following inpatient care and same-day surgery for the fiscal years 1993, 1994 and 1995. Various measures of regional variation were employed. RESULTS: Of the 2,870,695 inpatient separations and 1,803,307 same-day surgery separations during the study period, 359,972 and 64,541, respectively, were followed by home care. The rate of home care use per 100 separations was 12.5 for inpatients and 3.6 for same-day surgery patients. There was a a 3.5-fold regional variation in the rates of home care use following inpatient care and a 7-fold variation in rates of use following same-day surgery. Additional home care funding to attain calculated target rates was estimated to be $48.9 million (30% of expenditures for patients recently discharged from hospital over the study period). For a 20% increase in service provision it was estimated that an additional injection of $42.2 million is required. INTERPRETATION: The wide regional variations in rates of home care use highlight the importance of modifying home care funding to ensure that all residents of Ontario have equal access to services. To achieve this our estimates suggest that a substantial increase in home care funding is warranted.
Available approaches to the investigation of traumatic brain injury (TBI) are frequently hampered, to some extent, by the unsatisfactory abilities of existing methodologies to efficiently define and represent affected structural connectivity and functional mechanisms underlying TBI-related pathology. In this paper, we describe a patient-tailored framework which allows mapping and characterization of TBI-related structural damage to the brain via multimodal neuroimaging and personalized connectomics. Specifically, we introduce a graphically driven approach for the assessment of trauma-related atrophy of white matter connections between cortical structures, with relevance to the quantification of TBI chronic case evolution. This approach allows one to inform the formulation of graphical neurophysiological and neuropsychological TBI profiles based on the particular structural deficits of the affected patient. In addition, it allows one to relate the findings supplied by our workflow to the existing body of research that focuses on the functional roles of the cortical structures being targeted. A graphical means for representing patient TBI status is relevant to the emerging field of personalized medicine and to the investigation of neural atrophy.
connectomics; traumatic brain injury; atrophy; rehabilitation; DTI
The aim of this paper is to examine factors associated with discharge destination after acquired brain injury in a publicly insured population using the Anderson Behavioral Model as a framework.
We utilized a retrospective cohort design. Inpatient data from provincial acute care records from fiscal years 2003/4 to 2006/7 with a diagnostic code of traumatic brain injury (TBI) and non-traumatic brain injury (nTBI) in Ontario, Canada were obtained for the study. Using multinomial logistic regression models, we examined predisposing, need and enabling factors from inpatient records in relation to major discharge outcomes such as discharge to home, inpatient rehabilitation and other institutionalized care.
Multinomial logistic regression revealed that need factors were strongly correlated with discharge destinations overall. Higher scores on the Charlson Comorbidity Index were associated with discharge to other institutionalized care in the nTBI population. Length of stay and special care days were identified as markers for severity and were both strongly positively correlated with discharge to other institutionalized care and inpatient rehabilitation, compared to discharge home, in both nTBI and TBI populations. Injury by motor vehicle collisions was found to be positively correlated with discharge to inpatient rehabilitation and other institutionalized care for patients with TBI. Controlling for need factors, rural location was associated with discharge to home versus inpatient rehabilitation.
These findings show that need factors (Charlson Comorbidity Index, length of stay, and number of special care days) are most significant in terms of discharge destination. However, there is evidence that other factors such as rural location and access to supplemental insurance (e.g., through motor vehicle insurance) may influence discharge destination outcomes as well. These findings should be considered in creating more equitable access to healthcare services across the continuum of care.
To examine the influence of definition and location (field, emergency department [ED] or Pediatric Intensive Care Unit [PICU]) of hypotension on outcome following severe pediatric Traumatic Brain Injury (TBI).
Retrospective Cohort study.
Harborview Medical Center (level I pediatric trauma center), Seattle, WA over a 5 year period between 1998–2003.
93 children < 14 years of age with TBI following injury, head abbreviated injury score (AIS) ≥ 3, and PICU admission Glasgow Coma Sale (GCS) score < 9 formed the analytic sample. Data sources included the Harborview Trauma Registry and Hospital Records.
The relationship between hypotension and outcome was examined comparing two definitions of hypotension: 1) systolic blood pressure (SBP) < 5th percentile for age and 2) SBP < 90 mmHg. Hospital discharge Glasgow Outcome score (GOS) < 4, or disposition of either death or discharge to a skilled nursing facility were considered poor outcomes. PICU and hospital length of stay (LOS) were also examined.
SBP < 5th percentile for age was more highly associated with poor hospital discharge GOS (p = 0.001), poor disposition (p = 0.02), PICU LOS (RR 9.5; 95% CI 6.7–12.3) and hospital LOS (RR 18.8; 95% CI 14.0–23.5) than SBP < 90mmHg. Hypotension occurring in either the field or ED, but not in the PICU, was associated with poor GOS (p = 0.008), poor disposition (p= 0.03) and hospital LOS (RR 18.7; 95% CI 13.1–24.2).
Early hypotension, defined as SBP < 5th percentile for age in the field and/or ED, was a better predictor of poor outcome than delayed hypotension or the use of SBP < 90 mmHg.
blood pressure; brain injury; pediatric trauma; children; head trauma; hemodynamics
Traumatic Brain Injury (TBI) is a “signature” injury of the current wars in Iraq and Afghanistan. Structured electronic data regarding TBI findings is important for research, population health and other secondary uses but requires appropriate underlying standard terminologies to ensure interoperability and reuse. Currently the U.S. Department of Veterans Affairs (VA) uses the terminology SNOMED CT and the Department of Defense (DOD) uses Medcin.
We developed a comprehensive case definition of mild TBI composed of 68 clinical terms. Using automated and manual techniques, we evaluated how well the mild TBI case definition terms could be represented by SNOMED CT and Medcin, and compared the results. We performed additional analysis stratified by whether the concepts were rated by a TBI expert panel as having High, Medium, or Low importance to the definition of mild TBI.
SNOMED CT sensitivity (recall) was 90% overall for coverage of mild TBI concepts, and Medcin sensitivity was 49%, p < 0.001 (using McNemar’s chi square). Positive predictive value (precision) for each was 100%. SNOMED CT outperformed Medcin for concept coverage independent of import rating by our TBI experts.
SNOMED CT was significantly better able to represent mild TBI concepts than Medcin. This finding may inform data gathering, management and sharing, and data exchange strategies between the VA and DOD for active duty soldiers and veterans with mild TBI. Since mild TBI is an important condition in the civilian population as well, the current study results may be useful also for the general medical setting.
The aims of this study were to describe the occurrence of substance use at the time of injury and pre-injury substance abuse in patients with moderate-to-severe traumatic brain injury (TBI). Effects of acute substance use and pre-injury substance abuse on TBI severity were also investigated.
A prospective study of 111 patients, aged 16-55 years, injured from May 2005 to May 2007 and hospitalised at the Trauma Referral Centre in Eastern Norway with acute TBI (Glasgow Coma Scale 3-12). Based on structural brain damages shown on a computed tomography (CT) scan, TBI severity was defined by modified Marshall classification as less severe (score <3) and more severe (score ≥3). Clinical definition of substance use (alcohol and/or other psychoactive substances) was applied when hospital admission records reflected blood alcohol levels or a positive drug screen, or when a physician verified influence by examining the patient. Pre-injury substance abuse (alcohol and drug problems) was screened by using the CAGE questionnaire.
Forty-seven percent of patients were positive for substance use on admission to hospital. Significant pre-injury substance abuse was reported by 26% of patients. Substance use at the time of injury was more frequent in the less severe group (p = 0.01). The frequency of pre-injury substance abuse was higher in the more severe group (30% vs. 23%). In a logistic regression model, acute substance use at time of injury tended to decrease the probability of more severe intracranial injury, but the effect was not statistically significant after adjusting for age, gender, education, cause of injury and substance abuse, OR = 0.39; 95% CI 0.11-1.35, p = 0.14. Patients with positive screens for pre-injury substance abuse (CAGE ≥2) were more likely to have more severe TBI in the adjusted regression analyses, OR = 4.05; 95% CI 1.10-15.64, p = 0.04.
Acute substance use was more frequent in patients with less severe TBI caused by low-energy events such as falls, violence and sport accidents. Pre-injury substance abuse increased the probability of more severe TBI caused by high-energy trauma such as motor vehicle accidents and falls from higher levels. Preventive efforts to reduce substance consumption and abuse in at-risk populations are needed.
The objective was to assess functional outcome of rehabilitation in chronic severe traumatic brain injury (TBI) in-patients.
The study was performed at university tertiary research hospital.
A prospective cross-sectional study
Materials and Methods:
Forty patients (34 men) with mean age of 30.1 years (range 6--60, SD 10.8), severe TBI (Glasgow coma scale 3--8, duration of coma > 6 hours, post-traumatic amnesia> 1 day postinjury) were admitted in rehabilitation unit minimum 3 months (mean 7.7±4.6 months, range 3--22 months) following injury falling in Glasgow outcome scale (GOS) of 3. Functional recovery was assessed using the Barthel Index (BI) score and disability rating scores (DRS).
Paired Student's t-test was used for the assessment of functional recovery using mean BI scores at admission and discharge. The Wilcoxon nonparametric test was used for the assessment of functional recovery by comparing admission and discharge DRS scores.
Mean duration of stay was 30.8 days (range 18--91, SD15.6). Significant functional recovery observed in patients comparing BI and DRS scores at admission and discharge (mean BI admission 50.5±25.4, range 0--85 vs. mean discharge BI score 61.1±25.3, range 0--95, P<0.001, mean DRS admission score 7.57±4.1, range 2.5--21.0 vs. mean discharge DRS score 6.36±4.3, range 1.0-21.0, P<0.001).
Patients with severe TBI continue to show functional recovery even in chronic phase with rehabilitation. They are left with significant residual physical and cognitive deficits and would require long-term care and assistance from care givers for the daily activities, as suggested by the mean DRS score at discharge.
Functional outcome; inpatient rehabilitation; severe traumatic brain injury
Environmental enrichment (EE) is a complex living milieu that has been shown to enhance functional recovery vs. standard (STD) housing after experimental traumatic brain injury (TBI) and therefore may be considered a rodent correlate of rehabilitation. However, the typical EE paradigm consists of continuous exposure to enrichment after TBI, which is inconsistent with the limited time frame in clinical rehabilitation.
To determine whether abbreviated EE (i.e., rehabilitation-relevant dose response) confers benefits similar to typical EE after TBI.
Adult male rats received either a controlled cortical impact (2.8 mm depth at 4 m/sec) or sham injury and were then randomly assigned to TBI + EE, TBI + EE (2hr), TBI + EE (4hr), TBI + EE (6hr), TBI + STD, and respective sham controls. Motor (beam-balance/beam-walk; BB/BW) and cognitive (Morris water maze; MWM) performance was assessed on post-operative days 1-5 and 14-19, respectively.
The TBI + EE (2hr) and TBI + EE (4hr) groups were not statistically different from the TBI + STD group in any behavioral assessment. In contrast, the TBI + EE (6hr) group exhibited significant enhancement of motor and cognitive performance vs. the TBI + STD group, as well as the TBI + EE (2hr) and TBI + EE (4hr) groups (p < 0.003), and did not differ from the TBI + EE (typical) group.
These data demonstrate that abbreviated EE (6hr) produces motor and cognitive benefits similar to continuous EE after TBI and thus may be considered a dose-relevant rehabilitation paradigm.
controlled cortical impact; environmental enrichment; functional recovery; galantamine, learning and memory; Morris water maze
Vasopressors are commonly used to increase mean arterial blood pressure (MAP) and cerebral perfusion pressure (CPP) after traumatic brain injury (TBI), but there are few data comparing vasopressor effectiveness after pediatric TBI. Objective: To determine which vasopressor is most effective at increasing MAP and CPP in children with moderate-to-severe TBI.
After institutional review board approval, we performed a retrospective cohort study of children 0–17 years old admitted to a level 1 trauma center (Harborview Medical Center, Seattle, Wash., USA) between 2002 and 2007 with moderate-to-severe TBI who received a vasopressor to increase blood pressure. Baseline demographic and physiologic characteristics and hourly physiologic monitoring for 3 h after having started a vasopressor were abstracted. We evaluated differences in MAP and CPP at 3 h after initiation of therapy between phenylephrine, dopamine and norepinephrine among patients who did not require a second vasopressor during this time. Multivariate linear regression was used to adjust for age, gender, injury severity score and baseline MAP or CPP and to cluster by subject.
Eighty-two patients contributed data to the entire dataset. The most common initial medication was phenylephrine for 47 (57%). Patients receiving phenylephrine and norepinephrine tended to be older than those receiving dopamine and epinephrine. Thirteen (16%) of the patients received a second vasopressor during the first 3 h of treatment and were thus not included in the regression analyses; these patients received more fluid resuscitation and exhibited higher in-hospital mortality (77 vs. 32%; p = 0.004) compared to patients receiving a single vasopressor. The norepinephrine group exhibited a 5 mm Hg higher MAP (95% CI: −4 to 13; p = 0.31) and a 12 mm Hg higher CPP (95% CI: −2 to 26; p = 0.10) than the phenylephrine group, and a 5 mm Hg higher MAP (95% CI: −4 to 15; p = 0.27) and a 10 mm Hg higher CPP (95% CI: −5 to 25; p = 0.18) than the dopamine group. However, in post hoc analysis, after adjusting for time to start of vasopressor, hypertonic saline and pentobarbital, the effect on MAP was lost, but the CPP was 8 mm Hg higher (95% CI: −10 to 25; p = 0.39) than in the phenylephrine group, and 5 mm Hg higher (95% CI: −14 to 24; p = 0.59) than in the dopamine group.
Vasopressor use varied by age. While there was no statistically significant difference in MAP or CPP between vasopressor groups, norepinephrine was associated with a clinically relevant higher CPP and lower intracranial pressure at 3 h after start of vasopressor therapy compared to the other vasopressors examined.
Hypotension; Head injury; Children; Vasopressor
Traumatic brain injury (TBI) causes elevation of matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier (BBB) disruption, hemorrhage and cell death. We hypothesized that patients with TBI have an increase in MMPs in the ventricular cerebrospinal fluid (CSF) and plasma.
Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement, and 24 and 72 hrs after admission. Seven TBI patients were entered into the study with six having complete data for analysis. Only patients that had a known time of insult that fell within a six hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus (NPH). Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblotting.
We found a significant elevation in the levels of the latent form of MMP-9 (92-kDa) in the CSF obtained at the time of arrival (TOA) (p<0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly elevated in the CSF, indicating endogenous MMP production. Western immunoblots showed increased levels of MMP-3 in CSF at all times measured, while MMP-3 was not detected in the CSF of NPH.
We show that MMPs are elevated in CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated elevations of MMP-3 and MMP-9 in ventricular CSF in TBI patients compared to controls. While these preliminary results will need to be replicated, we propose that MMPs may be important in BBB opening and hemorrhage secondary to brain injury in patients.
Traumatic brain injury; matrix metalloproteinases; cerebrospinal fluid; ventriculostomy
Aims: To describe the epidemiology of children with traumatic brain injury (TBI) admitted to paediatric intensive care units (PICUs) in the UK.
Methods: Prospective collection of clinical and demographic information from paediatric and adult intensive care units in the UK and Eire between February 2001 and August 2003.
Results: The UK prevalence rate for children (0–14 years) admitted to intensive care with TBI between February 2001 and August 2003 was 5.6 per 100 000 population per year (95% Poisson exact confidence intervals 5.17 to 6.05). Children admitted to PICUs with TBI were more deprived than the population as a whole (mean Townsend score for TBI admissions 1.19 v 0). The commonest mechanism of injury was a pedestrian accident (36%), most often occurring in children over 10. There was a significant summer peak in admissions in children under 10 years. Time of injury peaked in the late afternoon and early evening, a pattern that remained constant across the days of the week. Injuries involving motor vehicles have the highest mortality rates (23% of vehicle occupants, 12% of pedestrians) compared with cyclists (8%) and falls (3%). In two thirds of admissions (65%) TBI was an isolated injury.
Conclusions: TBI in children requiring intensive care is more common in those from poorer backgrounds who have been involved in accidents as pedestrians. The summer peak in injury occurrence for 0–10 year olds and late afternoon timing give clear targets for community based injury prevention.
Concerns have been raised about the enrollment of racial and ethnic minorities in research in the emergency setting when it is not possible to obtain informed consent. However, there is a paucity of data related to the validity of such claims.
Retrospective comparison of registry enrollment (4/1/06–3/31/07) and trial enrollment (4/1/07–3/31/08) from 3 sites in the Resuscitation Outcomes Consortium. Subjects compared met the following criteria: 1) Shock, defined by blunt or penetrating force to the body with either systolic blood pressure (SBP) ≤ 70 mmHg or SBP 71–90 mmHg and heart rate ≥ 108 beats/min; and/or 2) Traumatic Brain Injury (TBI), defined by blunt force to the head with out-of- hospital Glasgow Coma Score ≤ 8.
Overall, compared to a registry there were no differences in the percent of racial or ethnic groups enrolled in the clinical trial [Odds Ratio (OR) for Blacks versus Whites: 0.87, 95% Confidence Interval (CI) 0.65–1.16, p=.34; OR for Hispanics versus Whites 1.04; CI 0.72–1.49, p=.85]. However, Blacks were less likely than Whites to be enrolled in the TBI cohort [OR 0.58 (0.34–0.97); p=.04].
Despite some discordance in subgroups, there was no overall difference in the racial and ethnic distribution of subjects enrolled in a multi-center clinical trial of severe trauma compared to a registry accounting for study entry criteria. These findings help address justice concerns about enrollment of racial and ethnic minorities in trauma research performed using an exception from informed consent under emergency circumstances.
The relationship between isolated traumatic brain injury (TBI) associated coagulopathy and patient prognosis frequently lacks information regarding the time course of coagulation disorders throughout the post-traumatic period. This study was conducted to assess the prevalence and time course of post-traumatic coagulopathy in patients with isolated TBI and the relationship of these hemostatic disorders with outcome.
The local Human Subjects Committee approved the study. We retrospectively studied the medical records of computed tomography (CT)-confirmed isolated TBI patients with an extracranial abbreviated injury scale (AIS) <3 who were primarily referred to a Level 1 trauma centre in Amsterdam (n = 107). Hemostatic parameters including activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, hemoglobin, hematocrit, glucose, pH and lactate levels were recorded throughout a 72-hour period as part of a routine standardized follow-up of TBI. Coagulopathy was defined as a aPPT >40 seconds and/or a PTT in International Normalized Ratio (INR) >1.2 and/or a platelet count <120*109/l.
Patients were mostly male, aged 48 ± 20 years with a median injury severity score of 25 (range 20 to 25). Early coagulopathy as diagnosed in the emergency department (ED) occurred in 24% of all patients. The occurrence of TBI-related coagulopathy increased to 54% in the first 24 hours post-trauma. In addition to an increased age and disturbed pupillary reflex, both coagulopathy upon ED arrival and during the first 24 hours post-trauma provided an independent prognostic factor for unfavorable outcome (odds ratio (OR) 3.75 (95% CI 1.07 to 12.51; P = 0.04) and OR 11.61 (2.79 to 48.34); P = 0.003).
Our study confirms a high prevalence of early and delayed coagulopathy in patients with isolated TBI, which is strongly associated with an unfavorable outcome. These data support close monitoring of hemostasis after TBI and indicate that correction of coagulation disturbances might need to be considered.
Blast-related traumatic brain injury (bTBI) and post-traumatic stress disorder (PTSD) have been of particular relevance to the military and civilian health care sectors since the onset of the Global War on Terror, and TBI has been called the “signature injury” of this war. Currently there are many questions about the fundamental nature, diagnosis, and long-term consequences of bTBI and its relationship to PTSD. This workshop was organized to consider these questions and focus on how brain imaging techniques may be used to enhance current diagnosis, research, and treatment of bTBI. The general conclusion was that although the study of blast physics in non-biological systems is mature, few data are presently available on key topics such as blast exposure in combat scenarios, the pathological characteristics of human bTBI, and imaging signatures of bTBI. Addressing these gaps is critical to the success of bTBI research. Foremost among our recommendations is that human autopsy and pathoanatomical data from bTBI patients need to be obtained and disseminated to the military and civilian research communities, and advanced neuroimaging used in studies of acute, subacute, and chronic cases, to determine whether there is a distinct pathoanatomical signature that correlates with long-term functional impairment, including PTSD. These data are also critical for the development of animal models to illuminate fundamental mechanisms of bTBI and provide leads for new treatment approaches. Brain imaging will need to play an increasingly important role as gaps in the scientific knowledge of bTBI and PTSD are addressed through increased coordination, cooperation, and data sharing among the academic and military biomedical research communities.
animal models of blast-related injury; blast physics; blast-related traumatic brain injury; brain imaging; post-traumatic stress disorder
Diagnosing inflicted traumatic brain injury (TBI) in young children is difficult in practice. Comparisons of children with inflicted and non-inflicted TBI may help to identify markers of inflicted TBI. The objective of this study was to compare inflicted and noninflicted TBI in terms of presenting complaints, clinical features, and hospital outcomes.
The presenting complaint, clinical finding, hospital course, and outcome of all children who were aged 2 years or younger in North Carolina and were admitted to a pediatric intensive care unit or died with a TBI in 2000 and 2001 were reviewed. Clinical presentation and injury types were compared between children with inflicted and noninflicted TBI. Risk ratios were used to compare clinical and outcome characteristics between the 2 groups. Among survivors, multivariate binomial regression was used to examine the adjusted risk of a poor outcome dependent on injury type.
A total of 80 (52.6%) children had inflicted and 72 (47.3%) children had noninflicted TBI. Children with noninflicted TBI (not in a motor vehicle crash) were more likely to present to the emergency department asymptomatic (44.8% vs 8.3%) and to have a specific history of trauma than children with inflicted TBI. Retinal hemorrhage, metaphyseal fracture, rib fracture, and subdural hemorrhage were more commonly found in children with inflicted compared with noninflicted TBI. Skeletal survey and ophthalmologic examination combined would have missed 8 (10.0%) inflicted TBI cases.
Manner of presentation and injury types are helpful in distinguishing inflicted TBI. Clinicians should not rule out inflicted TBI on the basis of skeletal survey and ophthalmoscopy alone but should proceed to computed tomography and/or magnetic resonance imaging.