Expression of Hsp70 and Caspase-3 in rabbits after severe traumatic brain injury

ObjectiveTo investigate the expression of Caspase-3 and Hsp70 in rabbits after severe traumatic brain injury (TBI) and to explore the feasibility of its application in estimation of injury time in forensic medicine.MethodsA rabbit model of heavy TBI was developed by high velocity impact on the parietal bone with an iron stick. Totally 8 healthy adult New Zealand white rabbits were randomly divided into control group (n=2) and injury group (n=6). Four hours after injury, tissue specimens from the parietal lobe, temporal lobe, occipital lobe, cerebellum and brainstem were harvested to detect the expression of Hsp70 and Caspase-3 by immunohistochemistry. Besides, the gray values of cells positive for Hsp70 and Caspase-3 were analyzed with an image analyzer.ResultsImmunohistochemistry staining demonstrated a low level of Caspase-3 and Hsp70 expression in normal control group. While in injury group, both the Caspase-3 and Hsp70 expression was significantly elevated (P<0.05). Positive cells gathered around the lesion focus. Occipital lobe and cerebellum had fewer positive cells while temporal and brainstem had the fewest.ConclusionThe expression of Caspase-3 and Hsp70 at an early stage following severe TBI is characteristic and can be applied to estimate the time of injury.     

Serum and cerebrospinal fluid magnesium in severe traumatic brain injury outcome

Serum magnesium concentration has a neuroprotective effect in experimental models of traumatic brain injury (TBI). This study was designed to assess the relationship between initial serum magnesium, cerebrospinal fluid (CSF) magnesium, neurological outcome and the efficacy of magnesium replacement therapy (MgSO4). A retrospective analysis was performed on a prospectively collected dataset from 216 patients admitted during 1996-2006 to the University of Pittsburgh Medical Center with severe TBI. Admission serum and CSF magnesium were dichotomized into low and normal magnesium concentration groups for serum and normal and high concentration groups for CSF. A logistic-regression analysis was performed with 6-month Glasgow Outcome Scale (GOS) scores as outcome variable. The outcome of a subset of 31 patients who presented with low serum magnesium and who were rapidly corrected within 24 h of admission was also analyzed. Low initial serum magnesium was measured in 56.67% of all patients. Patients with an initial serum magnesium of <1.3 mEq/L were 2.37 times more likely to have a poor outcome (CI: 1.18-4.78, p = 0.016). The prognostic significance of depressed serum magnesium remained, even in patients whose serum magnesium levels were corrected within 24 h (OR = 11.03, CI: 1.87-68.14, p = 0.008). Patients with an initial high CSF magnesium were 7.63 more likely to have a poor outcome (p = 0.05). Elevated CSF magnesium correlated with depressed serum magnesium only in patients with poor outcome (p = 0.013). Patients with low serum magnesium and high CSF magnesium are most likely to have poor outcome after severe TBI. Rapid correction of serum magnesium levels does not reverse the prognostic value of these markers.     

Isolated traumatic brain injury: age is an independent predictor of mortality and early outcome

BACKGROUND: Geriatric trauma patients have a worse outcome than the young with comparable injuries. The contribution of traumatic brain injury (TBI) to this increased mortality is unknown and has been confounded by the presence of other injuries. The purpose of this study was to investigate the role of age in the mortality and early outcome from isolated TBI. METHODS: This was a retrospective analysis of all adult patients with isolated TBI (Abbreviated Injury Scale score > or = 3) admitted during a 5-year period to two Level I trauma centers. Mortality, Glasgow Outcome Scale score at discharge, therapy, and complications were compared for elderly (age > or = 65 years) and younger patients. RESULTS: Of 694 patients, 22% were defined as elderly. The mortality for the elderly group was twice that of their younger counterparts (30% vs. 14%, p < 0.001), even for those with mild to moderate TBI (Glasgow Coma Scale score of 9-15). Thirteen percent of elderly survivors had a poor functional outcome (Glasgow Outcome Scale score of 2 or 3) at hospital discharge versus 5% in the young group (p < 0.01). Independent factors associated with a high mortality were age and Glasgow Coma Scale score. CONCLUSION: The mortality from TBI is higher in the geriatric population at all levels of head injury. In addition, functional outcome at hospital discharge is worse. Although some of this increased mortality may be explained by complications or type of head injury, age itself is an independent predictor for mortality in TBI.     

Serum biomarker concentrations and outcome after pediatric traumatic brain injury

Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. The study objective was to assess whether biomarkers concentrations obtained at the time of injury are associated with outcome. Serial serum concentrations of neuron-specific enolase (NSE), S100B and myelin basic protein (MBP) were measured in 152 children with acute TBI. Outcome was assessed with the Glasgow Outcome Scale (GOS) score and/or GOS-Extended Pediatric (GOS-E Peds). Spearman's rank correlation and binary logistic regression assessed the relationship between biomarker concentrations and outcome. For all biomarkers and time points, higher biomarker concentrations were associated with worse outcome. Initial and peak NSE concentrations and initial MBP concentrations were more strongly correlated with outcome in children < or =4 years compared with those >4 years of age. Using binary logistic regression to evaluate the simultaneous affect of all biomarkers on outcome, there was significant overall model fit predicting a dichotomous GOS from biomarker concentrations with a 77% correct classification rate and a negative and positive predictive value of 97% and 75%, respectively. We conclude that NSE, S100B, and MBP concentrations obtained at the time of TBI may be useful in predicting outcome. Future studies should focus on assessing the differential benefit of biomarkers compared with clinical variables and in assessing a continuous rather than categorical outcome variable.     

Blood pressure and outcome after severe pediatric traumatic brain injury

BACKGROUND: The relationship between systolic blood pressure and outcome in children after severe traumatic brain injury (TBI) is unclear. We examined the relationship between age-appropriate systolic blood pressure (AASBP) percentile and outcome after severe pediatric TBI. METHODS: We examined the association between AASBP percentiles and outcome in 172 children younger than 14 years of age with a Glasgow Coma Scale score < 9. Outcome was evaluated using discharge Glasgow Outcome Scale score. Poor outcome was defined as a Glasgow Outcome Scale score < 4. RESULTS: Poor outcome was associated with AASBP < 75th percentile (odds ratio, 4.2; 95% confidence interval, 2.1-8.3). Patients with systolic blood pressure (SBP) > or = 90 mm Hg and AASBP < 75th percentile had a higher odds for poor outcome compared with patients with SBP > or = 90 mm Hg and AASBP > or = 75th percentile (odds ratio, 3.5; 95% confidence interval, 1.7-7.3). CONCLUSION AASBP < 75th percentile was associated with poor outcome after severe pediatric TBI, even when SBP was > or = 90 mm Hg.     

Acute hyperglycemia is a reliable outcome predictor in children with severe traumatic brain injury

Purpose  

Hyperglycemia in the acute phase after trauma could adversely affect outcome in children with severe traumatic brain injury (TBI). The goal of this study was to identify the relationship between acute spontaneous hyperglycemia and outcome in children with severe TBI at hospital discharge and 6 months later.     

Transcranial doppler ultrasonography as an early outcome forecaster following severe brain injury

Knowledge of post-traumatic cerebral haemodynamic disturbances might be beneficial for predicting the management outcome when measuring the basal cerebral arteries blood flow velocity by ultrasonic transcranial Doppler device immediately after severe head injury. Thirty patients who sustained severe brain injury underwent an early blood velocity measuring by transcranial Doppler ultrasonography during a 1-year period of study. The standard technique of measuring the mean blood flow velocity in the middle cerebral artery was applied. The outcome was assessed at 6-month follow-up by the Glasgow Outcome Score. The middle cerebral artery low blood flow velocity, and the increased values of the pulsatility index significantly correlated to an unfavourable outcome. Transcranial Doppler ultrasonography for measuring the middle cerebral artery blood flow velocity has been proved worthy as a possible predictor of severe head injury management outcome. This non-invasive and simple procedure could be engaged in the daily management of severely brain-injured patients.     

One-year outcome and course of recovery after severe traumatic brain injury

Goal  

To describe the outcome of patients with severe traumatic brain injury (TBI) 3, 6 and 12 months after trauma.     

Participation as an outcome of traumatic brain injury rehabilitation

OBJECTIVES: Participation in meaningful life situations is an important aspect of functioning after traumatic brain injury (TBI). However, to date, few studies have included measures of social participation or community integration as outcome measures after TBI rehabilitation. This paper is a selective review of the literature that examines the effects of TBI rehabilitation on measures of participation or community integration. It also addresses the related questions of clinically significant improvements in community integration, variability in patterns of community functioning, and the relationship of participation and quality of life after TBI. DESIGN: Literature review. CONCLUSIONS: A small number of studies suggest that postacute TBI rehabilitation can produce improvements in participation and community integration. However, a considerable amount of variability in rehabilitation outcomes may be apparent. Analysis of clinically significant changes in individual's functioning suggests that rehabilitation may exert its benefits not only by facilitating improvements, but also by preventing declines in community functioning. Subjective well-being and quality of life have generally been ignored as TBI rehabilitation outcomes. There is considerable evidence that participation and subjective well-being represent distinct and dissociable outcomes after TBI, which may reflect the importance of patients' preferences and values in evaluating the effectiveness of rehabilitation.     

Computed tomography findings and early cognitive outcome after traumatic brain injury

Primary objective: To examine the relationship between CT abnormalities and early neuropsychological outcome following traumatic brain injury (TBI) using quantitative CT analyses, data reduction methods for neuropsychological results and specific hypotheses based on literature review.

Research design: Observational, prospective cohort study using acute (emergency) CT data and neuropsychological test data from 89 participants with TBI who were hospitalized for rehabilitation.

Methods and procedures: Principal components analysis with varimax rotation was used to reduce data from a standard battery of eight neuropsychological tests administered after clearance of post-traumatic amnesia (1 month post-TBI on average). Bivariate correlations were used to examine relationships of three factors (verbal memory, cognitive processing speed and verbal working memory) to quantitative volumetric analysis of CT scan abnormalities (size, number and location). Specific hypotheses as to CT predictors of poor performance on each factor were tested using multivariable linear regression that included injury severity and demographic variables.

Main results: Eighty-nine per cent of participants had some pathology on initial CT. Age, education and time to follow commands (TFC), an index of overall injury severity, were significantly associated with the neuropsychological factors. However, none of the specific hypotheses about CT scan variables and cognitive outcome were strongly supported by the data. There was a trend for any CT abnormality to predict slower speed of processing and for higher number of brain lesions to predict worse memory performance.

Conclusions: Despite the precision added by quantitative CT analysis, CT findings did not improve on demographic factors and TFC in predicting early cognitive outcome of TBI. Imaging methods that are more sensitive to white matter integrity may be needed to develop pathophysiologic predictors of TBI outcome.     

Serum neuron-specific enolase as a predictor of short-term outcome and its correlation with Glasgow Coma Scale in traumatic brain injury

Elevated serum neuron-specific enolase levels are correlated with brain cell damage. Low scores according to Glasgow Coma Scale are also considered as serious poor prognostic factor. The aims of the study were to investigate whether there is a correlation between the two measurements in patients with traumatic brain injury and whether serum neuron-specific enolase levels have potential as a screening test to predict outcome. A total of 169 consecutive patients with traumatic brain injury admitted to our clinic between 2002 and 2005 are included in this study. Those patients, who had any major health problem before trauma, were excluded from the study. However, patients with isolated head injury were included in the study. Serial serum neuron-specific enolase concentrations taken at the first 2, 24, and 48 h after traumatic brain injury were analyzed. A computed tomography was performed on each patient on admission. Their Glasgow Coma Scale scores were recorded serially. The relationship between Glasgow Coma Scale scores and the serum neuron-specific enolase levels were assessed by statistical methods. There was a significant negative correlation between the serum neuron-specific enolase levels and Glasgow Coma Scale scores. The levels of neuron-specific enolase were significantly higher in the patients who died in 30 days after trauma and whose scores were lower than or equal to 8 points in Glasgow Coma Scale. Although there are several serious limitations of the use of neuron-specific enolase as a biomarker in traumatic brain injury (i.e., hypoperfusion, extracranial trauma, bleeding, liver, or kidney damage also increase the level of neuron-specific enolase), its concentrations may be useful as a practical and helpful screening test to identify neurotrauma patients who are at increased risk and may provide supplementary estimation with radiological and clinical findings.     

Role of plasma DNA as a predictive marker of fatal outcome following severe head injury in males

The prediction of outcome is one of the major problems associated with traumatic brain injury. Recently, investigations have been performed on the potential use of circulating cell-free DNA in plasma for clinical diagnosis and prognosis of a variety of conditions. In this study, we investigated DNA plasma concentrations after severe traumatic brain injury (TBI) and its correlation with primary outcome. We studied 41 male victims of TBI, with isolated severe TBI or severe TBI with associated exracranial injuries. Control samples were obtained from 13 healthy male volunteers. Plasma DNA was measured by a real-time PCR assay for the beta-globin gene. The mean time for first sampling (study entry) was 11.7 +/- 5.2 h after injury; subsequent DNA determinations were performed 24 h after study entry. Mean plasma DNA concentrations were significantly increased in TBI patients (366,485 and 131,708 kilogenomes-equivalents/L, at study entry and 24 h later, respectively) compared with the control group (3031 kilogenomes-equivalents/L). Additionally, a significant correlation between higher plasma DNA concentrations, determined 24 h after study entry, and fatal outcome was observed. However, at second sampling, there was no significant correlation between plasma DNA concentrations and the presence of associated extracranial injuries. High plasma DNA concentrations at second sampling time predicted fatal outcome with a sensitivity of 67% and specificity of 76%, considering a cut-off value of 77,883 kilogenomes-equivalents/L. Thus, this study showed that severe TBI is associated with elevated DNA plasma levels and suggests that persistent DNA elevations correlate with mortality.     

Apolipoprotein E polymorphism and gender difference in outcome after severe traumatic brain injury

Background: Traumatic brain injury (TBI) is one of the most common causes of death and dismal outcome among children and young adults. The morbidity and mortality differ but more aggressive monitoring and more designated neuro intensive care units have improved the results. Studies have demonstrated a connection between apolipoprotein E (APOE) genotype and outcome after TBI, but few are prospective and none is from northern Europe. APOE has three alleles: ?2, ?3 and ?4. Methods: A total of 96 patients with Glasgow coma score (GCS) ≤8 were prospectively and consecutively included. APOE genotypes were all analyzed at the same laboratory from blood samples by polymerase chain reaction‐restriction fragment length polymorphism. Results: All patients were assessed at 1 year with Glasgow outcome scale extended (GOSE), National Institute of Health Stroke Scale (NIHSS) and the Barthel daily living index. The genotype was available in all patients. Twenty‐six patients expressed APOE ?4 while 70 patients did not. Outcome demonstrated that patients with APOE ?4 had worse outcome vs. those lacking this allele. When subdividing patients into gender, males with APOE ?4 did worse, a difference not detected among female patients. Conclusions: APOE ?4 correlated to worse outcome in TBI patients. We also found that males with APOE ?4 had poor outcome while females did not. Thus, the results indicate that genetic polymorphism may influence outcome after TBI.     

Hybrid outcome prediction model for severe traumatic brain injury

Numerous studies addressing different methods of head injury prognostication have been published. Unfortunately, these studies often incorporate different head injury prognostication models and study populations, thus making direct comparison difficult, if not impossible. Furthermore, newer artificial intelligence tools such as machine learning methods have evolved in the field of data analysis, alongside more traditional methods of analysis. This study targets the development of a set of integrated prognostication model combining different classes of outcome and prognostic factors. Methodologies such as discriminant analysis, logistic regression, decision tree, Bayesian network, and neural network were employed in the study. Several prognostication models were developed using prospectively collected data from 513 severe closed head-injured patients admitted to the Neurocritical Unit at National Neuroscience Institute of Singapore, from April 1999 to February 2003. The correlation between prognostic factors at admission and outcome at 6 months following injury was studied. Overfitting error, which may falsely distinguish different outcomes, was compared graphically. Tenfold cross-validation technique, which reduces overfitting error, was used to validate outcome prediction accuracy. The overall prediction accuracy achieved ranged from 49.79% to 81.49%. Consistently high outcome prediction accuracy was seen with logistic regression and decision tree. Combining both logistic regression and decision tree models, a hybrid prediction model was then developed. This hybrid model would more accurately predict the 6-month post-severe head injury outcome using baseline admission parameters.     

Apolipoprotein E4 allele presence and functional outcome after severe traumatic brain injury

Presence of the apolipoprotein E (APOE) 4 allele has been associated with increased incidence and faster progression of neurodegenerative diseases, poorer recovery from neurologic insult, and decreased cognitive function in the well-elderly. The specific association between APOE genotype and recovery from severe traumatic brain injury (TBI) is conflicting with many groups finding the APOE 4 allele to be associated with poorer outcome while others have found no association. The purpose of this study was to investigate the association between APOE 4 allele presence and recovery during the two years after injury from severe TBI in light of other potential covariates, such as age, race, gender, hypotension or hypoxia before hospital admission and severity of injury. APOE genotype was determined for 123 subjects with severe TBI. Glasgow outcome score (GOS) and mortality were collected at 3, 6, 12, and 24 months after injury. Results showed individuals improved over the two year period following injury and those with the 4 allele had a slower recovery rate than those without the APOE 4 allele over the two year period. We did not however find significant differences in GOS at individual time points when controlling for other covariates. Our findings suggest that APOE 4 allele presence influences recovery rate from severe TBI independent of other covariates. The findings of this study are unique in that they address not only the relationship between APOE 4 allele presence and outcome from severe TBI, but also describe differences in trajectory of recovery by APOE 4 allele presence.