Severe Traumatic Brain Injury Group Research Articles

Factors Associated with Difficulty in Returning to School in Students After Traumatic Brain Injury.

Traumatic brain injury (TBI) often causes behavioral problems and difficulties with school work, but the specific factors associated with difficulty in returning to school after TBI still remain unclear. The purpose of this study was to investigate factors associated with difficulty in returning to school within 1 year of injury in students with traumatic brain injury. This study is a secondary analysis of existing data sets. We recruited patients aged 16 years in the United States with a primary rehabilitation diagnosis of TBI registered in the Traumatic Brain Injury Model Systems National Database. We compared variables between the students who returned to school and those who did not return to school. In addition, subgroup analyses were performed focused on traumatic brain injury severity. We excluded those were received <10 years of schooling, and 309 eligible students were identified for the analysis. Of these, 246 (80%) did not return to school within 1 year of injury. There were fewer cases of severe TBI in the group of students who returned to school than in the group who did not return to school (29% vs 44%, P = 0.03). The duration of rehabilitation was significantly longer in the group who returned to school than in the group who did not return to school (mean days 40 vs 29, P = 0.001), and a subgroup analysis showed in the severe traumatic brain injury group (mean days 46 vs 29; P = 0.02) and the non-severe traumatic brain injury group (mean days 37 vs 26; P = 0.02) similar results. Insufficient amount of rehabilitation was associated with difficulty in returning to school in students after TBI, regardless of the severity of the injury.

Comparative Study of Derangement of Coagulation Profile between Adult and Pediatric Population in Moderate to Severe Traumatic Brain Injury: A Prospective Study in a Tertiary Care Trauma Center.

Object:Coagulopathy is a common occurrence following traumatic brain injury (TBI). There are various studies showing incidence and risk factors of coagulopathy and their correlation with poor outcome in adult as well as paediatric age groups. Exact incidence, associated risk factors, treatment guideline for coagulopathy and its impact on outcome are still lacking. In our study we compared the adults and paediatric age groups TBI patients for incidence and risk factors of coagulopathy and its impact on outcome.Methods:Prospective study of 200 patients including 152 adult patients (age > 18 years) and 48 paediatric (Age < 18 years) patients of TBI admitted in intensive care unit of trauma centre of a tertiary care centre was performed from august 2015 to march 2016. Both population were further subdivided into moderate TBI and severe TBI as per Glasgow coma score (GCS). Patient with long bone injury, chest injury and abdominal injuries, coagulation disorder, liver disease, medical disease like diabetes mellitus and hypertension were excluded from study. Coagulation profile were compared in the both groups (Adult and paediatric) and correlated with the outcome. Chi- Square test, student t test and Odds ratios were used for statistical analysis.Results:Mean age among the adult and paediatric population were 37.89 ± 11.88 years and 11.41 ± 5.90, respectively. Among the patient with moderate TBI, coagulopathy was seen in 30% patients of adult TBI whereas it was 12.5% among the paediatric TBI (P = 0.185). Among the severe TBI group coagulopathy was observed in 68.03% and 37.5% of adult and paediatric age group respectively (P = 0.0016). There was significant correlation found between midline shift and coagulopathy in the paediatric age group (P = 0.022; OR - 4.58). E. There was significant association of coagulopathy and contusion on CT scan among the adult population (P = 0.007; OR - 3.487) found whereas no such correlation were observed in paediatric population.Conclusion:Coagulopathy was significantly higher among the adult patient with severe TBI as compare to paediatric patient with severe TBI. There was no statistically significant difference in mortality among patients of both the age groups with coagulopathy.

Notch inhibitor can attenuate apparent diffusion coefficient and improve neurological function through downregulating NOX2-ROS in severe traumatic brain injury.

IntroductionSecondary brain injury is a major factor that affects the prognosis and outcome of traumatic brain injury (TBI) patients. Secondary brain edema is considered to be an initiating factor in secondary brain injury after TBI. A previous study has indicated that Notch signaling activation contributes to neuron death in mice affected by stroke; however, its role in neuronal oxidation stress for brain edema after TBI is not well established. Apparent diffusion coefficient (ADC) values can represent the brain edema after TBI.MethodsWe established a rat model of acute craniocerebral injury, using functional MRI to evaluate the ADC and cerebral blood flow values. The present study was designed to determine the effect of Notch inhibitor DAPT upon oxidation stress for brain edema after TBI. Rats were randomly distributed into five groups, control group, severe TBI group, severe TBI + vehicle group, severe TBI + DAPT group, and severe TBI + DPI group. All rats were sacrificed at 24 hours after TBI.ResultsOur data indicated that Notch signaling inhibitor DAPT significantly reduced the ADC values and improved the neurological function after TBI. In addition, DAPT decreased NOX2 levels and the ROS levels. Furthermore, DPI can decrease NOX2 levels and ROS levels.ConclusionThis study indicated that DAPT Notch signal inhibitors can inhibit NOX2-ROS generation, reduce the ADC values, relieve cerebral edema, and improve nerve function.

Expression profile of plasma microRNAs and their roles in diagnosis of mild to severe traumatic brain injury.

Traumatic brain injury (TBI) is associated with trauma-related death. In this study, we evaluated differences in the expression of plasma microRNAs (miRNAs) in patients with different degrees of TBI, and explored the potential of miRNAs for use as diagnostic TBI biomarkers. The miRNA microarray results showed upregulation of 65, 33, and 16 miRNAs and downregulation of 29, 27, and 6 miRNAs in patients with mild, moderate, and severe TBI, respectively, compared with healthy controls. Thirteen miRNAs (seven upregulated and six downregulated) were found to be present in all TBI groups. Seven upregulated miRNAs were selected for validation in an enlarged cohort of samples and showed good diagnostic accuracy. The expression levels of miR-3195 and miR-328-5p were higher in the severe TBI group than in the mild and moderate TBI groups. In summary, our study demonstrates different expression profiles in plasma miRNAs among patients with mild to severe TBI. A subset of seven miRNAs can be used for diagnosis of TBI. Moreover, miR-3195 and miR-328-5p may be utilized during diagnosis to distinguish mild and moderate TBI from severe TBI.

Enteral Nutrition Initiation in Children Admitted to Pediatric Intensive Care Units After Traumatic Brain Injury.

Traumatic brain injury (TBI) is the leading cause of death and long-term disability among injured children. Early feeding has been shown to improve outcomes in adults, with some similar evidence in children with severe TBI. We aimed to examine the current practice of initiation of enteral nutrition in children with TBI and to evaluate the risk factors associated with delayed initiation of enteral nutrition. This retrospective, multicenter study used the Pediatric Trauma Assessment and Management Database including all children with head trauma discharged from five pediatric intensive care units (PICU) at pediatric trauma centers between January 1, 2013 and December 31, 2013. We compared demographics, injury and procedure data, time to initiation of nutrition, and injury and illness severity scores between patients who received enteral nutrition early (≤ 48h) and late (> 48h). Fisher's exact and Mann-Whitney U tests compared discrete and continuous variables. Univariate and multivariable analyses evaluated variables associated with delayed initiation of feeding. Outcomes of interest included mortality, complications, ventilator days, hospital and ICU length of stay, and functional status at ICU discharge. In the 416 patients in the study, the overall mortality was 2.6%. The majority of patients (83%; range 69-88% between five sites, p = 0.0008) received enteral nutrition within 48h of PICU admission. Lower Glasgow Coma Scale scores and higher Injury Severity Score (ISS) were independently associated with delayed initiation of enteral nutrition. Delayed enteral nutrition was independently associated with worse functional status at PICU discharge (p = 0.02) but was not associated with mortality or increased length of stay. Children with severe TBI and higher ISS were more likely to have delayed initiation of enteral nutrition. Delayed enteral nutrition was an independent risk factor for worse functional status at ICU discharge for the entire cohort, but not for the severe TBI group.

A Prospective Analysis of Derangement of Coagulation Profile in Adult and Pediatric Age Group in Moderate-to-Severe Traumatic Brain Injury

Abstract Background and Aim of Study Coagulopathy is a common occurrence following traumatic brain injury (TBI). Various studies have reported the incidence and risk factors of coagulopathy and their correlation with poor outcome in adult as well as pediatric age group. In our study, we aim to analyze trauma-induced coagulopathy in adult and pediatric patients. Methods Adult (&gt; 18 years) and pediatric (&lt; 18 years) patients of TBI admitted in the intensive care unit of a trauma center of a tertiary care center had been studied from August 2015 to March 2018. Patients were further subdivided into moderate and severe TBI based on Glasgow Coma Scale (GCS) of 9 to 12 and &lt; 9, respectively. Coagulation profile (prothrombin time [PT], activated partial thromboplastin time [APTT], thrombin time, fibrinogen, and D-dimer) and arterial blood gas (ABG) analysis were done on day of admission and on days 3 and 7. Coagulation profiles were analyzed in both the age groups, and risk factors were studied and correlated with the mortality and morbidity based on the Glasgow outcome score. Results Two hundred patients including 143 adults and 57 pediatric patients were included. Mean age among the adult and pediatric population was 31.51 ± 16.83 and 11.5 ± 5.90 years, respectively. In adults, 96 (83.62%) out of 116 in severe TBI group and 20 (74.07%) out of 27 in moderate TBI group developed coagulopathy, and in pediatric age group, 14 (70%) out of 20 in moderate TBI and 30 (81.08%) out of 37 in severe TBI developed coagulopathy. Midline shift was significantly associated with coagulopathy in both the age groups (p value &lt; 0.039). Mortality was not significantly different in patients with coagulopathy between the age groups, but improved status as per the Glasgow outcome score was more in pediatric age group. Conclusion The development of coagulopathy is a frequent complication in patients with moderate to severe TBI in both age groups. Even though it is not closely associated with death in this study, it may be regarded as a marker of injury severity.

The Association of Cognitive Reserve in Chronic-Phase Functional and Neuropsychological Outcomes Following Traumatic Brain Injury.

Examine the association of cognitive reserve (CR) factors (estimated premorbid intelligence quotient [IQ], years of education, and occupational attainment) and traumatic brain injury (TBI) severity with functional and neuropsychological outcomes 1 to 5 years following TBI. Patients with mild (N = 58), moderate (N = 25), or severe (N = 17) TBI. Cognitive reserve factors (estimated premorbid IQ, years of education, and occupational attainment); neuropsychological test battery; Glasgow Outcome Scale-Extended; Short Form-36 Health Survey. Spearman-Brown correlations, linear regression models, and analyses of covariance were used to analyze the relation between CR factors and outcome measures. Analyses revealed significant relations between estimated premorbid IQ and neuropsychological outcomes (P < .004): California Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition working memory, Booklet Category Test, Trail Making Test B, and Grooved Pegboard Test. There was also a significant correlation between estimated premorbid IQ and Wechsler Adult Intelligence Scale-Fourth Edition processing speed. Years of education had significant relations with California Verbal Learning Test and Wechsler Adult Intelligence Scale-Fourth Edition working memory and processing speed scores. There were significant differences between TBI severity groups and performance on the Trail Making Test A, Grooved Pegboard Test, and Finger Tapping Test. Cognitive reserve factors may be associated with outcomes following TBI. Additional alternatives to TBI severity are needed to help guide rehabilitative planning postinjury.

Relationship of calcitonin gene-related peptide with disease progression and prognosis of patients with severe traumatic brain injury.

Calcitonin gene-related peptide (CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury (TBI) remains poorly understood. In this study, 96 adult patients with TBI (enrolled from September 2015 to December 2016) were divided into a mild/moderate TBI group (36 males and 25 females, aged 38 ± 13 years) and severe TBI group (22 males and 13 females, aged 38 ± 11 years) according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls (15 males and 10 females, aged 39 ± 13 years). Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI.

Predicting Fatigue 12 Months after Child Traumatic Brain Injury: Child Factors and Postinjury Symptoms.

Fatigue is a common and persisting symptom after childhood brain injury. This study examined whether child characteristics and symptomatology preinjury or 6 months postinjury (pain, sleep, and mood, inattention) predicted fatigue at 12months postinjury. Parents of 79 children (0-18 years) rated fatigue at 12 months after injury on a multidimensional scale (general, sleep/rest, and cognitive). Demographic and clinical data were collected at injury. Parents rated child sleep, pain, physical/motor function, mood, and inattention at injury (preinjury description), and 6 months postinjury. Children were divided into two traumatic brain injury severity groups: mild TBI (n=57) and moderate/severe TBI (n=27). Hierarchical regression models were used to examine (i) preinjury factors and (ii) symptoms 6 months postinjury predictive of fatigue (general, sleep/rest, and cognitive) at 12 months postinjury. Sleep/rest fatigue was predicted by preinjury fatigue (7% of variance) and psychological symptoms preinjury (10% of variance). General fatigue was predicted by physical/motor symptoms (27%), sleep (10%) and mood symptoms (9%) 6 months postinjury. Sleep/rest fatigue was predicted by physical/motor symptoms (10%), sleep symptoms (13%) and mood symptoms (9%) 6 months postinjury. Cognitive fatigue was predicted by physical/motor symptoms (17%) 6 months postinjury. Preinjury fatigue and psychological functioning identified those at greatest risk of fatigue 12 months post-TBI. Predictors of specific fatigue domains at 12 months differed across each of the domains, although consistently included physical/motor function as well as sleep and mood symptoms postinjury. (JINS, 2018, 24, 224-236).

Comparison of the Buschke Selective Reminding Test and the California Verbal Learning Test – Second Edition in a heterogeneous sample of people with traumatic brain injury

ABSTRACTThis study examined score and classification differences between the Buschke Selective Reminding Test (SRT) and the California Verbal Learning Test - Second Edition (CVLT-II) in a TBI sample. Seventy-nine participants with traumatic brain injury (TBI) were included and were comprised of 49 mild TBI, 11 moderate TBI, and 14 severe TBI. The majority of participants with mild TBI were involved in litigation. Scores were compared between the CVLT-II and SRT on the total sample and after segregating TBI severity. Correlations between the SRT and CVLT-II were variable (r = .23 to .72). Total List score was lower on the SRT across all levels of TBI severity (p < .006). Learning score was lower on the SRT in mild and severe TBI groups (p < .006). Long delay free recall score was lower on the SRT in mild TBI group only (p < .006). Across TBI severity, lower scores were found on the CVLT-II between severe and mild TBI (p = .04). Scores on the SRT did not differ between TBI severities. The two tests appear to provide different clinical interpretations in a TBI sample. Results may be due to features of the normative data, test procedures, and/or word lists. Clinical implications and limitations are discussed.

Dynamic changes and their clinical significance of serum insulin-like growth factor-1 in patients with acute traumatic brain injury

Objective To investigate the dynamic changes of serum insulin-like growth factor-1 (IGF-1) in acute traumatic brain injury (TBI) as well as their correlations with the initial severity of TBI and prognosis. Methods A total of 229 patients with acute TBI admitted from September 2014 to June 2016 were retrospectively studied. Patients were further classified as mild TBI group (GCS 13-15 points), moderate TBI group (GCS 9-12 points) and severe TBI group (GCS 3-8 points) according to Glasgow coma score (GCS). The control group consisted of 30 healthy subjects. The prognosis was evaluated by using Glasgow outcome scale (GOS) at 6 months after TBI. The IGF-1 levels were further tested at days 1, 3, 5, 7 and 14 and their correlations with the initial GCS and GOS at 6 months after injury were evaluated. Results (1) The serum IGF-1 levels of mild, moderate and severe TBI group at all time points were significantly lower than those of the control group (P<0.05); the serum IGF-1 levels of severe and moderate TBI groups at all time points after injury were significantly lower than those of the mild TBI group (P<0.05); the serum IGF-1 levels of the severe group at days 1, 3, 5 and 7 d after injury were lower than those of the moderate TBI group (P<0.05). (2) IGF-1 levels were significantly different between the two groups (P<0.05) at different time points during the follow-up of 6 months. (3)IGF-1 levels were positively correlated with both GCS and GOS at the acute stage of TBI and sub-acute stage following TBI (P<0.05). Conclusion The dynamic changes of serum IGF-1 levels in patients with acute TBI are related to both initial severity of TBI and the neurological outcomes and can be used as a reliable biomarker for early severity assessment and prognostic prediction of TBI. Key words: Craniocerebral trauma; Insulin-like growth factor Ⅰ; Injury severity score; Prognosis

Home Environment as a Predictor of Long-Term Executive Functioning following Early Childhood Traumatic Brain Injury.

This study examined the relationship of the home environment to long-term executive functioning (EF) following early childhood traumatic brain injury (TBI). Participants (N=134) were drawn from a larger parent study of 3- to 6-year-old children hospitalized for severe TBI (n=16), complicated mild/moderate TBI (n=44), or orthopedic injury (OI; n=74), recruited prospectively at four tertiary care hospitals in the United States and followed for an average of 6.8 years post-injury. Quality of the home environment, caregiver psychological distress, and general family functioning were assessed shortly after injury (i.e., early home) and again at follow-up (i.e., late home). Participants completed several performance-based measures of EF at follow-up. Hierarchical regression analyses examined the early and late home environment measures as predictors of EF, both as main effects and as moderators of group differences. The early and late home environment were inconsistent predictors of long-term EF across groups. Group differences in EF were significant for only the TEA-Ch Walk/Don't Walk subtest, with poorer performance in the severe TBI group. However, several significant interactions suggested that the home environment moderated group differences in EF, particularly after complicated mild/moderate TBI. The home environment is not a consistent predictor of long-term EF in children with early TBI and OI, but may moderate the effects of TBI on EF. The findings suggest that interventions designed to improve the quality of stimulation in children's home environments might reduce the long-term effects of early childhood TBI on EF. (JINS, 2018, 24, 11-21).

The family environment predicts long-term academic achievement and classroom behavior following traumatic brain injury in early childhood.

This study examined how the family environment predicts long-term academic and behavioral functioning in school following traumatic brain injury (TBI) in early childhood. Using a concurrent cohort, prospective design, 15 children with severe TBI, 39 with moderate TBI, and 70 with orthopedic injury (OI) who were injured when they were 3-7 years of age were compared on tests of academic achievement and parent and teacher ratings of school performance and behavior on average 6.83 years postinjury. Soon after injury and at the longer term follow-up, families completed measures of parental psychological distress, family functioning, and quality of the home environment. Hierarchical linear regression analyses examined group differences in academic outcomes and their associations with measures of the early and later family environment. The severe TBI group, but not the moderate TBI group, performed worse than did the OI group on all achievement tests, parent ratings of academic performance, and teacher ratings of internalizing problems. Higher quality early and late home environments predicted stronger academic skills and better classroom behavior for children with both TBI and OI. The early family environment more consistently predicted academic achievement, whereas the later family environment more consistently predicted classroom functioning. The quality of the home environment predicted academic outcomes more strongly than did parental psychological distress or family functioning. TBI in early childhood has long-term consequences for academic achievement and school performance and behavior. Higher quality early and later home environments predict better school outcomes for both children with TBI and children with OI. (PsycINFO Database Record

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Frontal Traumatic Brain Injury Increases Impulsive Decision Making in Rats: A Potential Role for the Inflammatory Cytokine Interleukin-12.

Traumatic brain injury (TBI) is associated with the development of numerous psychiatric diseases. Of particular concern for TBI patients is the impact of chronic impulsivity on daily functioning. Despite the scope of the human problem, little has been done to address impulsivity in animal models of brain injury. In the current study, we examined the effects of either a severe or a milder bilateral frontal controlled cortical impact injury on impulsivity using the Delay Discounting Task (DDT), in which preference for smaller-sooner over larger-later rewards is indicative of greater impulsive choice. Both milder and severe TBI caused a significant, chronic increase in impulsive decision making. Despite these pronounced changes in performance of the DDT, memory function, as assessed by the Morris Water Maze, was not impaired in more mildly injured rats and only transiently impacted in the severe TBI group. Whereas a significant lesion was only evident in severely injured rats, analysis of cytokine levels within the frontal cortex revealed a selective increase in interleukin (IL)-12 that was associated with the magnitude of the change in impulsive choice caused by both milder and severe TBI. These findings suggest that tissue loss alone cannot explain the increased impulsivity observed, and that inflammatory pathways mediated by IL-12 may be a contributing factor. The findings from this study highlight the sensitivity of sophisticated behavioral measures designed to assess neuropsychiatric dysfunction in the detection of TBI-induced cognitive impairments and their utility in identifying potential mechanistic pathways and therapeutic targets.

Proton Magnetic Resonance Spectroscopy (¹H-MRS) Study of Early Traumatic Brain Injury in Rabbits.

BackgroundThe aim of this study was to investigate the relationship between dynamic changes of cerebral metabolism and degree of trauma in rabbit models of traumatic brain injury (TBI) by using proton magnetic resonance spectroscopy (1H-MRS).Material/MethodsThirty-five Chinese rabbits were randomly divided into control, mild, moderate, and severe TBI groups. 1H-MRS was performed 1, 6, and 24 h after trauma. The concentrations of NAA, Cr, Cho, and Lac, and NAA/Cr and Cho/Cr ratios in each group, were estimated.ResultsCompared with the control group, NAA, Cr, and Cho peaks were decreased. NAA/Cr ratio in the ipsilateral cortex was reduced in the mild, moderate, and severe TBI groups by 12.79%, 28.90%, and 45.02% at 1 h, and decreased by 25.11%, 39.81%, and 51.18% at 24 h after trauma, respectively. There were significant negative correlations between NAA/Cr ratio and severity of attack. Cho/Cr ratio in the ipsilateral cortex in the mild, moderate, and severe TBI groups was decreased by 10.86%, 15.94%, and 34.78% at 1 h, and reduced by 24.63%, 29.71%, and 42.02% at 6 h, respectively, and increased slightly at 24 h after trauma. The Lac/Cr ratio in the injured side was increased, most obviously in the severe TBI group. NAA/Cr ratio and Cho/Cr ratio showed significant changes between each group at the same time point.Conclusions1H-MRS can noninvasively and dynamically detect metabolic changes in early TBI. The NAA/Cr ratio is most sensitive, and has positive significance for early diagnosis and prognosis assessment of TBI.

A prospective pilot study on serum cleaved tau protein as a neurological marker in severe traumatic brain injury

Objective: Neurotrauma has been labelled as a “silent epidemic” affecting both the developed and the developing nations. To date, no single brain-specific biomarker has been unanimously accepted for routine clinical use in TBI. Our study aims to determine the correlation of “cleaved-tau protein” in severe traumatic brain injury (TBI) with Glasgow Coma Scale (GCS) at the time of admission, mode of injury, CT findings and outcome at discharge.Methods: The study has been approved by the institutional ethical committee. 40 cases with severe TBI and 40 randomly selected healthy controls were included in this prospective study. Venous blood samples were collected and serum cleaved tau protein levels were measured and correlated with gender, mode of injury, CT findings GCS score and GOS score at discharge.Results: In the severe TBI group, the mean serum cleaved tau protein levels in males were 91.65 ± 41.34 pg/ml (mean ± S.D.), and females were 104.43 ± 53.08 pg/ml (mean ± S.D.), (p = 0.27). Mean serum C-tau level in study group was 95.48 ± 44.87 pg/ml (range 36.44-192.34), 95% C.I. (81.13–109.83) and in controls was 33.82 ± 13.65 pg/ml (range 2.48–66.54), 95% C.I. (29.46–38.19) (p < 0.001). The distribution of serum C-tau was in severe TBI group varied in all categories of GCS at 0th day (p < 0.001). Serum cleaved tau protein levels in the good outcome group were 74.26 ± 25.43 pg/ml (mean ± S.D.), range 36.44–144.54, 95% C.I. (63.52-85.00) and the poor-outcome group were 127.32 ± 49.40 pg/ml, range 66.65–192.34, 95% C.I. (100.99-153.64) (p = 0.001).Conclusion: In severe TBI, serum cleaved tau protein levels were significantly higher as compared to the controls in this prospective study. However, results of this study are preliminary in nature and there is a need to undertake larger prospective studies to reach a definitive conclusion.

Social and Behavioral Outcomes following Childhood Traumatic Brain Injury: What Predicts Outcome at 12 Months Post-Insult?

This study sought to investigate social and behavioral outcomes 12 months following childhood traumatic brain injury (TBI) and to identify predictors of these outcomes. The study also compared rates of impairment in social and behavioral outcomes at 12 months post-injury between children with TBI and a typically developing (TD) control group. The study comprised 114 children ages 5.5 to 16.0 years, 79 with mild, moderate, or severe TBI and 35 TD children, group-matched for age, sex and socio-economic status. Children with TBI were recruited via consecutive hospital admissions and TD children from the community. Social and behavioral outcomes were measured via parent-rated questionnaires. Analysis of covariance models identified a significant mean difference between the mild and moderate groups for social problems only, but the moderate and severe TBI groups showed a higher rate of impairment, particularly in externalizing problems. Pre-injury function, injury severity, parent mental health, and child self-esteem all contributed significantly to predicting social and behavioral outcomes. Both injury and non-injury factors should be considered when identifying children at risk for long-term difficulties in social and behavioral domains.

Reconsidering the Word Memory Test as a Memory Measure in Traumatic Brain Injury.

This study examined relationships among traumatic brain injury (TBI) severity, the Word Memory Test (WMT), and California Verbal Learning Test-Second Edition (CVLT-II). Participants (N=104) passed WMT validity indices and were categorized by TBI severity on the basis of medical records. Outcome measures included norm-referenced scores on the CVLT-II and WMT. Participants grouped by TBI severity significantly differed on the CVLT-II but not WMT. Post-traumatic amnesia (PTA) significantly correlated with the CVLT-II but not WMT. In a non-medicolegal sample subset (N=61), TBI severity groups significantly differed on CVLT-II and WMT FR; PTA significantly correlated with the CVLT-II and WMT FR. CVLT-II impairment groups differed onall WMT variables. Participants grouped by neuroimaging findings differed on CVLT-II but not WMT. WMT FR predicted two-level TBI severity using logistic regression but did not contribute in a model including the CVLT-II. Overall, WMT memory subtests appeared less sensitive to TBI severity than the CVLT-II.

Early expression of serum neutrophil gelatinase-associated lipocalin (NGAL) is associated with neurological severity immediately after traumatic brain injury

PurposeIntracranial bleeding and inflammatory reactions are common consequences of traumatic brain injury (TBI). Neutrophil gelatinase-associated lipocalin (NGAL), an iron-handling and acute phase protein, may participate in the pathogenesis of TBI. Therefore, we hypothesize that NGAL may be of high diagnostic and therapeutic relevance in the prognosis of TBI. Methods74 subjects were recruited in this study. 30 TBI patients receiving emergent operation were designated as severe TBI group (sTBI), 24 TBI patients receiving conservative treatment as mild TBI group (mTBI), while 20 age-matched healthy volunteers as healthy controls (CNT). We detected the expression and localization of NGAL in brain tissue by Q-PCR, western blotting, and immunofluorescence. Serum NGAL was evaluated by ELISA. Clinical manifestations and outcomes were measured by Glasgow Score (GCS), Trauma score (TS), Revised Trauma score (RTS), APACHEII, Sequential Organ Failure Assessment (SOFA), and Abbreviated Injury Scale (AIS) 85 at admission. Glasgow outcome score (GOS) and Karnofsky Performance Score (KPS) were documented at discharge. ResultsNGAL mRNA and protein levels in brain tissue from sTBI group were profoundly higher than control tissue. Double labeled NGAL with GFAP, NeuN and Iba-1 by immunofluroscence demonstrated that increased NGAL was mainly located in neurons. Compared to CNT and mTBI groups, serum NGAL were significantly increased in sTBI group (sTBI: 532.6±71.77ng/ml vs. mTBI: 230.5±29.59ng/ml, p<0.01; sTBI: 532.6±71.77ng/ml vs. CNT 178.0±19.83ng/ml, p<0.01). Linear regression analysis indicated that there was a negative correlation between the NGAL levels and GCS (r=−0.427, p=0.033), TS (r=−0.429, p=0.032), RTS (r=−0.413, p=0.040) in sTBI group. However, NGAL levels did not correlated with GOS and KPS scores. The NAGL cut-off value of 244.13ng/ml yielded good sensitivity at 84% and specificity at 78.9%. ConclusionNGAL may be a novel biomarker reflecting TBI severity, which increased obviously and negatively correlated with GCS, TS, and RTS scores; additionally, this characteristic of NGAL may be helpful in guiding clinical TBI therapeutic strategies.