Hippocampus, amygdala and global brain changes 10 years after childhood traumatic brain injury

Traumatic brain injury (TBI) in children results in damage to the developing brain, particularly in severely injured individuals. Little is known, however, of the long-term structural aspects of the brain following childhood TBI. This study investigated the integrity of the brain 10 years post-TBI using magnetic resonance imaging volumetrics in a sample of 49 participants with mild, moderate and severe TBI, evaluated against a normative sample of 20 individuals from a pediatric database with comparable age and gender distribution. Structural integrity was investigated in gray and white matter, and by manually segmenting two regions of interest (hippocampus, amygdala), potentially vulnerable to the effects of childhood TBI. The results indicate that more severe injuries caused a reduction in gray and white brain matter, while all TBI severity levels resulted in increased volumes of cerebrospinal fluid and smaller hippocampal volumes. In addition, enlarged amygdala volumes were detected in severely injured patients compared to their mild and moderate counterparts, suggesting that childhood TBI may disrupt the development of certain brain regions through diffuse pathological changes. The findings highlight the lasting impact of childhood TBI on the brain and the importance of monitoring brain structure in the long-term after early injury.     

Working memory after traumatic brain injury in children

To investigate the effects of traumatic brain injury on working memory in children, we administered semantic (letter identity) and phonological (letter rhyme) N-back tasks to children who were on average 5 years post-mild (n = 54) or -severe (n = 26) traumatic brain injury and 44 typically developing children who were comparable in age. The correct detection of targets and false alarms were measured for each task. Memory load (which varied from 0 to 3 letters back) and age significantly affected the detection of targets and false alarms in both tasks. The severity of traumatic brain injury affected the correct detection of letters on the identity task and false alarms on the rhyme task. Traumatic brain injury severity also interacted with memory load in its effect on false alarms on the rhyme task. Traumatic brain injury results in impaired working memory and diminished inhibition in children. The N-back working memory task is feasible for administration to brain-injured children and potentially could be useful for studying brain activation associated with working memory and effects of drug therapy in this group of patients.     

Inhibitory control after traumatic brain injury in children

Inhibitory control describes a number of distinct processes. Effortless inhibition refers to acts of control that are automatic and reflexive. Effortful inhibition refers to voluntary, goal-directed acts of control such as response flexibility, interference control, cancellation inhibition, and restraint inhibition. Disruptions to a number of inhibitory control processes occur as a consequence of childhood traumatic brain injury (TBI). This paper reviews the current knowledge of inhibition deficits following childhood TBI, and includes an overview of the inhibition construct and a discussion of the specific deficits shown by children and adolescents with TBI and the factors that mediate the expression of these deficits, including injury-related variables and the expression of pre- and post-injury attention-deficit/hyperactivity disorder. The review illustrates that inhibitory control processes differ in terms of measurement, assessment, and neurological underpinnings, and also that childhood TBI may selectively disrupt particular forms of inhibition.     

Executive functions after traumatic brain injury in children

There is growing recognition that executive function, the superordinate, managerial capacity for directing more modular abilities, is frequently impaired by traumatic brain injury in children and mediates the neurobehavioral sequelae exhibited by these patients. This review encompasses the definition of specific executive functions, age-related changes in executive functions in typically developing children, and the effects of traumatic brain injury on executive functions. The neural substrate for executive functions is described, including relevant functional brain imaging studies that have implicated mediation by prefrontal and parietal cortex and their circuitry. The vulnerability of the neural substrate for executive function to the pathophysiology of traumatic brain injury is discussed, including focal lesions and diffuse axonal injury. Domains of executive functions covered in this review include the basic processes of working memory and inhibition and more complex processes such as decision making. Other domains of executive function, including motivation, self-regulation, and social cognition are discussed in terms of research methodology, clinical assessment, and findings in children with traumatic brain injury. Proposed approaches to the rehabilitation of executive functions are presented.     

Functional outcome and health-related quality of life 10 years after moderate-to-severe traumatic brain injury

Objectives – To describe the functional outcome and health‐related quality of life (HRQL) 10 years after moderate‐to‐severe traumatic brain injury (TBI). Material and methods – A retrospective, population‐based study of 62 survivors of working‐age with moderate‐to‐severe TBI injured in 1995/1996, and hospitalized at the Trauma Referral Center in Eastern Norway. Functional status was measured by the Glasgow Outcome Scale‐Extended (GOS‐E). HRQL was assessed by the SF‐36 questionnaire. Results – The mean current‐age was 40.8 years. The frequency of epilepsy was 19% and the depression rate 31%. A majority had good recovery (48%) or moderate disability (44%). Employment rate was 58%. Functional and employment status were associated with initial injury severity in contrast to HRQL. Study patients had significantly lower scores in all SF‐36 dimensions when compared with the general Norwegian population. Conclusion – At 10‐years follow‐up, our study population is still in their most productive years and affected domains should be considered in long‐term follow‐up and intervention programs.     

Predicting neuropsychologic outcome after traumatic brain injury in children

The ability to predict long-term neurologic and neuropsychologic outcomes in 22 children, ages 1 week to 14 years at the time of traumatic brain injury, was investigated using proton magnetic resonance spectroscopy acquired post injury and compared with standardized neurologic, intellectual, and neuropsychologic testing done 1-7 years later. Clinical indicators of acute injury severity including age at injury, electroencephalography, spectroscopy metabolite ratio variables (N-acetyl aspartate/choline, choline/creatine) and lactate presence accurately classified children as functioning above or below the average range for most intellectual and neuropsychologic outcome measures. Combined clinical and spectroscopy variables accounted for approximately 50% of the variance in cognitive and neuropsychologic outcome confirming the validity of their predictive use. Of the injury severity indictors, presence of lactate is a particularly important prognostic marker of poor long-term intellectual and neuropsychologic functioning. Our findings indicate the potential for providing accurate estimates of long-term intellectual and neuropsychologic function after traumatic brain injury in infants and children using proton magnetic resonance spectroscopy in combination with clinical variables.     

Verbal selective learning after traumatic brain injury in children

Selective learning (SL), the ability to select items to learn from among other items, engages cognitive control, which is purportedly mediated by the frontal cortex and its circuitry. Using incentive-based auditory word recall and expository discourse tasks, we studied the efficiency of SL in children ages 6 to 16 years who had sustained severe traumatic brain injury (TBI) at least 1 year earlier. We hypothesized that SL would be compromised by severe TBI. Results indicated that children with severe TBI performed significantly worse than age-matched typically developing children on word- and discourse-level measures of SL efficiency with no significant group differences in number of items recalled from auditory word lists or declarative facts. We conclude that severe TBI disrupts incentive-based cognitive control processes, possibly due to involvement of frontal neural networks.     

儿童重型颅脑损伤

目的探讨儿童重型颅脑损伤的发病机理、临床特点及治疗方法。方法回顾性分析儿童重型颅脑损伤131例。结果临床结果根据GOS标准判断：Ⅴ级(良好)91例，Ⅳ级(中残)10例，Ⅲ级(重残)6例，Ⅱ级(植物生存)0例，Ⅰ级(死亡)24例。结论儿童在颅脑解剖、中枢神经系统生理及病理生理方面有其固有的特性，颅脑损伤后耐受性差，病情常突变，而小儿巾枢神经系统修复能力相对较强，如及时解除脑受压，神经功能恢复快，疗效好。早期诊断、正确选择治疗方法及手术方式能明显改善患儿的预后．     

Alterations in cerebral oxygen metabolism after traumatic brain injury in children

Traumatic brain injury (TBI) is the most common cause of acquired disability in children. Metabolic defects, and in particular mitochondrial dysfunction, are important contributors to brain injury after TBI. Studies of metabolic dysfunction are limited, but magnetic resonance methods suitable for use in children are overcoming this limitation. We performed noninvasive measurements of cerebral blood flow and oxygen metabolic index (OMI) to assess metabolic dysfunction in children with severe TBI. Cerebral blood flow is variable after TBI but hypoperfusion and low OMI are predominant, supporting metabolic dysfunction. This finding is consistent with preclinical and adult clinical studies of brain metabolism and mitochondrial dysfunction after TBI.     

Brain activation during working memory after traumatic brain injury in children

Eight children with moderate to severe traumatic brain injury (TBI) and eight matched, uninjured control children underwent fMRI during an N-back task to test effects of TBI on working memory performance and brain activation. Two patterns in the TBI group were observed. Patients whose criterion performance was reached at lower memory loads than control children demonstrated less extensive frontal and extrafrontal brain activation than controls. Patients who performed the same, highest (3-back) memory load as controls demonstrated more frontal and extrafrontal activation than controls. Our findings of performance and brain activation changes in children after TBI await longitudinal investigation.     

Early recovery of walking in children and youths after traumatic brain injury

A consecutive series of 106 children and adolescents (mean age 10 years, 6 months; SD 4 years, 8 months) with recent traumatic brain injury admitted to a regional hospital-based rehabilitation program was assessed to determine the rate of walking recovery, and characteristics that distinguish between independent walkers, non-walkers, and device-assisted walkers at hospital discharge. Data were collected through a retrospective medical record review of patients admitted between 1994 and 2001. Mean hospital stays were 66.7 days (SD 88.5, range 7 to 140 days). All children (72 male, 34 female) had recent injuries (from 1 to 8 weeks after onset of traumatic brain injury) and were independent walkers before injury. Sixty-four children (60.4%) were discharged as independent walkers, 13 (12.3%) walked with the assistance of a device, and 29 (27.3%) were non-walkers. Non-walkers had a higher proportion of prolonged loss of consciousness, lower-extremity injury, impaired responsiveness, and lower-extremity spasticity than independent walkers. In addition, non-walkers had poorer discharge mobility and social function scores, longer average hospital stays, and a greater proportion of non-community discharges. Device-only walkers were older, more likely to be male, and had a higher proportion of lower-extremity injuries than independent walkers. Results highlight several demographic, clinical, and outcome variables that distinguish independent walkers from device-assisted walkers and non-walkers. These variables might help to determine the prognosis for ambulation, resource needs, and discharge plans for children and adolescents with traumatic brain injury after episodes of inpatient rehabilitation.     

Self-esteem in children after traumatic brain injury: an exploratory study

Children with a traumatic brain injury (TBI) often have difficulties in adjusting to their injury and altered abilities, and may be at risk of low self-esteem and loss of confidence. However, few studies have examined self-esteem in this client group. The current study measured the self-esteem of a group of children who were, on average, two years post-TBI and compared this to their performance on other psychometric measures. Participants were 96 children with TBI and 31 peer controls, their parents and teachers. Self-esteem was measured using the Coopersmith Self-esteem Inventory (CSEI). CSEI scores were compared with performance on Wechsler Intelligence Scales (WISC-III), Hospital Anxiety and Depression Scale (HADS); Children's Memory Scale (CMS), Vineland Adaptive Behaviour Scales (VABS) and Parental Stress Index (PSI). Self-esteem was highly correlated with IQ; HADS anxiety and depression; and parental stress (p< 0.001). Children with TBI had significantly lower self-esteem than controls and population norms (p=0.015). Many children with TBI demonstrate low self-esteem and this is closely linked with anxiety and depression. This may hamper academic performance and could lead to further psychosocial problems. It is recommended that self-esteem is routinely assessed after brain injury and rehabilitation strategies implemented to promote a sense of self-worth.     

Validity of the WCST-64 after traumatic brain injury in children

The Wisconsin Card Sorting Test-64 (WCST-64) is a recently normed modification of the Wisconsin Card Sorting Test (WCST) that utilizes only one deck of cards. The present study investigated the validity of the WCST-64 in a sample of fifty-six 10- to 16-year-old children with traumatic brain injury (TBI). Standard scores for perseverative responses from the WCST-64 and from the full-length WCST shared 83% of common variance. Less than 10% of this sample had a discrepancy between the respective indexes that was greater than one standard deviation. Correlations with external criteria such as length of coma and Full Scale IQ were not significantly different between the two versions of the instrument. The findings suggest that the WCST-64 may be used interchangeably with the original WCST in older children with TBI.     

Decision-making after traumatic brain injury in children: a preliminary study

Decision-making under conditions of uncertainty was studied in 11 children with moderate to severe post-acute traumatic brain injury (TBI) using a modification of the Iowa Gambling Task (Bechara et al., 1994). We hypothesized that decision-making would be compromised in children with TBI. The results revealed that when divided into subgroups by lesion location, children with lesions in the amygdala (AM) were impaired on modified gambling task performance, but children with ventromedial (VM) lesions did not appear to be impaired on the task. These results are in contrast to studies of decision-making in adults with focal lesions of vascular etiology.     

Dementia after traumatic brain injury

Early retrospective studies suggested that individuals with a history of a traumatic brain injury (TBI) had a higher risk for dementia than those without a history of TBI. Two meta-analyses demonstrated that the risk for dementia is higher among men, but not women, with a history of TBI. More recent prospective studies, however, are providing discrepant findings, probably due to important methodological differences. TBI is usually associated with significant neuropsychological deficits, primarily in the domains of attention, executive functioning and memory. These deficits may not improve with time. TBI may also lower the threshold for the clinical expression of dementia among predisposed individuals, and the onset of Alzheimer's disease (AD)-like neuropathological and biochemical changes immediately after severe TBI may play an important role in this mechanism.     

Dose-dependent neuronal injury after traumatic brain injury

The Fluoro-Jade (FJ) stain reliably identifies degenerating neurons after multiple mechanisms of brain injury. We modified the FJ staining protocol to quickly stain frozen hippocampal rat brain sections and to permit systematic counts of stained, injured neurons at 4 and 24 h after mild, moderate or severe fluid percussion traumatic brain injury (TBI). In adjacent sections, laser capture microdissection was used to collect uninjured (FJ negative) CA3 hippocampal neurons to assess the effect of injury severity on mRNA levels of selected genes. Rats were anesthetized, intubated, mechanically ventilated and randomized to sham, mild (1.2 atm), moderate (2.0 atm) or severe (2.3 atm) TBI. Four or 24 h post-TBI, ten frozen sections (10 microm thick, every 15th section) were collected from the hippocampus of each rat, stained with FJ and counterstained with cresyl violet. Fluoro-Jade-positive neurons were counted in hippocampal subfields CA1, CA3 and the dentate gyrus/dentate hilus. At both 4 and 24 h post-TBI, numbers of FJ-positive neurons in all hippocampal regions increased dose-dependently in mildly and moderately injured rats but were not significantly more numerous after severe injury. Although analysis of variance demonstrated no overall difference in expression of mRNA levels for heat shock protein 70, bcl-2, caspase 3, caspase 9 and interleukin-1beta in uninjured CA3 neurons at all injury levels, post hoc analysis suggested that TBI induces increases in neuroprotective gene expression that offset concomitant increases in deleterious gene expression.     

Identity, grief and self-awareness after traumatic brain injury

The objective of this study was to investigate perceived identity change in adults with traumatic brain injury (TBI) and explore associations between identity change, grief, depression, self-esteem and self-awareness. The participants were 29 adults with TBI who were being followed up by a community brain injury rehabilitation service. Participants were longer post-injury than those more commonly studied. Time since injury ranged from 2.25 to 40 years (mean = 11.17 years, SD = 11.4 years). Participants completed a battery of questionnaires. Significant others and clinicians completed a parallel version of one of these measures. Questionnaires included the Head Injury Semantic Differential Scale (HISDS-III), Brain Injury Grief Inventory (BIGI), Hospital Anxiety and Depression Scale - Depression, Rosenberg Self-Esteem Scale (RSES) and the Awareness Questionnaire (Self/Significant other/Clinician versions). The main findings were that participants reported significant changes in self-concept with current self being viewed negatively in comparison to pre-injury self. Perceived identity change was positively associated with depression and grief and negatively associated with self-esteem and awareness. Awareness was negatively associated with self-esteem and positively associated with depression. These findings were consistent with previous research, revealing changes in identity following TBI. Further research is needed to increase our understanding of the psychological factors involved in emotional adjustment after TBI and to inform brain injury rehabilitation interventions, including psychotherapy approaches.