Pediatric traumatic brain injury: quo vadis?

In this review, five questions serve as the framework to discuss the importance of age-related differences in the pathophysiology and therapy of traumatic brain injury (TBI). The following questions are included: (1) Is diffuse cerebral swelling an important feature of pediatric TBI and what is its etiology? (2) Is the developing brain more vulnerable than the adult brain to apoptotic neuronal death after TBI and, if so, what are the clinical implications? (3) If the developing brain has enhanced plasticity versus the adult brain, why are outcomes so poor in infants and young children with severe TBI? (4) What contributes to the poor outcomes in the special case of inflicted childhood neurotrauma and how do we limit it? (5) Should both therapeutic targets and treatments of pediatric TBI be unique? Strong support is presented for the existence of unique biochemical, molecular, cellular and physiological facets of TBI in infants and children versus adults. Unique therapeutic targets and enhanced therapeutic opportunities, both in the acute phase after injury and in rehabilitation and regeneration, are suggested.     

Compensation and malingering in traumatic brain injury: a dose-response relationship?

The purpose of this study was to determine if there is a dose-response relationship between potential monetary compensation and failure on psychological indicators of malingering in traumatic brain injury. 332 traumatic brain injury patients were divided into three groups based on incentive to perform poorly on neuropsychological testing: no incentive; limited incentive as provided by State law; high incentive as provided by Federal law. The rate of failure on five well-validated malingering indicators across these groups was examined. Cases handled under Federal workers compensation laws showed considerably higher rates of failure and diagnosable malingering than cases handled under State law. The findings indicate that monetary compensation associated with workers compensation claims is a major motive for exaggeration and malingering of problems attributed to work-related brain injuries. The clinician's index of suspicion regarding exaggeration and malingering of symptoms and deficits should be much higher in the context of Federal workers compensation claims, particularly in patients who have suffered only mild traumatic brain injury.     

The predictive brain state: timing deficiency in traumatic brain injury?

Attention and memory deficits observed in traumatic brain injury (TBI) are postulated to result from the shearing of white matter connections between the prefrontal cortex, parietal lobe, and cerebellum that are critical in the generation, maintenance, and precise timing of anticipatory neural activity. These fiber tracts are part of a neural network that generates predictions of future states and events, processes that are required for optimal performance on attention and working memory tasks. The authors discuss the role of this anticipatory neural system for understanding the varied symptoms and potential rehabilitation interventions for TBI. Preparatory neural activity normally allows the efficient integration of sensory information with goal-based representations. It is postulated that an impairment in the generation of this activity in traumatic brain injury (TBI) leads to performance variability as the brain shifts from a predictive to reactive mode. This dysfunction may constitute a fundamental defect in TBI as well as other attention disorders, causing working memory deficits, distractibility, a loss of goal-oriented behavior, and decreased awareness.     

Reversible dysfunction of receptors in traumatic brain injury?

In many brain disorders reduced binding of central benzodiazepine receptor ligands indicates irreversible neuronal damage. The data presented by Koizumi et al (2010) demonstrate that this is not the case in traumatic brain injury suggesting different pathogenetic mechanisms leading to tissue damage. The proof for this hypothesis requires further studies that should also consider thresholds of ligand binding as indicators of irreversible damage.     

Sleep disturbance after mild traumatic brain injury: indicator of injury?

Mild traumatic brain injury (mTBI) is a complex entity with no known objective diagnostic markers. To test the hypothesis that sleep disturbances in the acute mTBI period can serve as an indicator of brain injury, the authors compared sleep polysomnograms (PSG) and sleep EEG power spectra (PS) data in seven mTBI subjects with seven age- and race-matched healthy-control subjects. The two groups differed significantly on PS measures, suggesting that mTBI can result in a disruption of sleep microarchitecture and, in theory, could be of use as a marker for brain injury. These pilot findings need to be replicated on larger samples.     

Executive function in traumatic brain injury and obsessive–compulsive disorder: An overlap?

Thirteen individuals with traumatic brain injury, 13 individuals with obsessive-compulsive disorder (OCD) and 10 normal controls were compared on neuropsychological measures of executive function. Individuals with a traumatic brain injury performed significantly poorer than the other two groups on a test measuring visuo-spatial strategy. Although the traumatic brain injury group made more errors on a test of maze learning and the OCD group less than the control group, this did not reach statistical significance. No support for an overlap in executive dysfunction in traumatic brain injury and OCD was found. It may be that the 'error prevention system' in the brain was influenced in a contrasting way by executive dysfunction in these disorders. This difference may reveal itself clinically in impulsivity/perseveration and slowness, respectively. Further studies were needed to test this hypothesis.     

Dysautonomia after traumatic brain injury: a forgotten syndrome?

OBJECTIVES: To better establish the clinical features, natural history, clinical management, and rehabilitation implications of dysautonomia after traumatic brain injury, and to highlight difficulties with previous nomenclature. METHODS: Retrospective file review on 35 patients with dysautonomia and 35 sex and Glasgow coma scale score matched controls. Groups were compared on injury details, CT findings, physiological indices, and evidence of infections over the first 28 days after injury, clinical progress, and rehabilitation outcome. RESULTS: the dysautonomia group were significantly worse than the control group on all variables studied except duration of stay in intensive care, the rate of clinically significant infections found, and changes in functional independence measure (FIM) scores. CONCLUSIONS: Dysautonomia is a distinct clinical syndrome, associated with severe diffuse axonal injury and preadmission hypoxia. It is associated with a poorer functional outcome; however, both the controls and patients with dysautonomia show a similar magnitude of improvement as measured by changes in FIM scores. It is argued that delayed recognition and treatment of dysautonomia results in a preventable increase in morbidity.     

Is therapeutic hypothermia beneficial for pediatric patients with traumatic brain injury? A meta-analysis

Purpose

Hypothermia therapy shows its unique potential for reducing mortality in animal study and improving neurologic outcome in patients with traumatic brain injury. However, therapeutic hypothermia for pediatric traumatic brain injury remains a controversial issue. To determine the effectiveness and safety of hypothermia treatment for pediatric traumatic brain injury patients, we conducted this meta-analysis.

Patients and methods

We analyzed the data from MEDLINE, Pubmed, EMBASE, and Cochrane Library by electronic searching. No limitation of language was selected for analysis. We extracted the mortality and adverse events from the published trials.

Results

Six clinical trials and 366 pediatric patients met our inclusion criteria. Pediatric patients with traumatic brain injury treated with hypothermia had more unfavorable outcome than those in the normothermia group (RR 1.73, 95 % CI 1.06 to 2.84), and this increased risk is statistically significant. Patients with therapeutic hypothermia are slightly likely to be induced by cardiac arrhythmia, and the likelihood is also significant (RR 2.57, 95 % CI 1.01 to 6.54). Risk of pneumonia has no statistical difference between normothermia and hypothermia arms (RR 0.90, 95 % CI 0.73 to 1.12). Two of the included trials have reported their detail randomization assignment.

Conclusions

Hypothermia may slightly increase the risk of mortality in children with traumatic brain injury and the ratio of cardiac arrhythmia after this hypothermia therapy is slightly higher than that in normothermia groups. In the future, more randomized controlled trials and multicenter studies on the mechanism of therapeutic hypothermia are required.     

Can traumatic brain injury cause psychiatric disorders?

Traumatic brain injury (TBI) may cause psychiatric illness. This article reviews the evidence on the basis of an established set of causation criteria. The evidence is convincing for a strong association between TBI and mood and anxiety disorders. Substance abuse and schizophrenia are not strongly associated with TBI, and there is little research into the rates of personality disorders after TBI. Evidence for a biologic gradient is lacking, but such a gradient may not be relevant to TBI. Evidence for the correct temporal sequence is present. Preliminary evidence suggests a biologic rationale for TBI causing psychiatric illness. Further and methodologically improved research is supported and required.     

How useful is magnetic resonance imaging in predicting severity and outcome in traumatic brain injury?

Major advances have been made in the ever-expanding field of magnetic resonance imaging and related technologies, such as magnetic resonance spectroscopy, haemodynamic and functional imaging. Although these magnetic resonance modalities are of great research interest, it is still questionable as to how useful these investigations are in the clinical setting. All of these modalities strive to define a few variables that might dominate the heterogeneous but common aetiopathology of traumatic brain injury. Recent studies have found that the use of various magnetic resonance imaging techniques at early and delayed time points can provide useful information with regard to the severity and clinical outcome of patients following traumatic brain injury. These new observations offer opportunities for improved clinical management in such patients.     

Chronic alterations in rat brain α-adrenoceptors following traumatic brain injury

Norepinephrine (NE) has been implicated in cerebral plasticity and recovery of function after brain injury. To examine the status of noradrenergic mechanisms in the brain following traumatic brain injury (TBI), male Sprague-Dawley rats underwent right sensorimotor cortex contusions and were observed for the next 30 days for recovery of motor function by measurement of the time taken to perform a modified beam walking task! At 30 days, their brains were assayed by receptor autoradiography for αr- and α2-adrenoceptor binding with 1 nM [3H]prazosin and 1 nM [3H]paraminoclonidine, respectively. One day after contusion, TBI rats took 60% longer to run the beam than sham-lesioned controls. Run times were directly proportional (r = 0.784; P = 0.012) to lesion volume determined at 30 days. The motor deficit persisted for 8 days, after which TBI and control rats had similar run times, largely due to increased run times in sham rats. At 30 days, TBI rats had a generalized, bilateral decrease in [3H]prazosin binding across all brain areas read (F[l,13] = 9.23; P = 0.009) with specific 12%-21% decreases in the cortex contralateral to the lesion and bilaterally in the dorsomedial hypothalamic and three thalamic nuclei. On the other hand, [3H]paraminoclonidine binding did not differ from sham lesion controls in any brain area of TBI rats. Thus, unilateral TBI is followed by widespread, bilateral changes in α1-adrenoceptor binding which would leave the animal vulnerable to any factors which reduced the access of NE to its postsynaptic adrenoceptors. This is compatible with the observation that α1-antagonists and α2-agonists can transiently reinstate the motor deficit after recovery has occurred.     

Diffusion tensor imaging in moderate-to-severe pediatric traumatic brain injury: changes within an 18 month post-injury interval

Traumatic brain injury (TBI) is a leading cause of death and disability in children, yet little is known regarding the pattern of TBI-related microstructural change and its impact on subsequent development. Diffusion tensor imaging (DTI) was used to examine between-group differences at two time points (planned intervals of 3 months and 18 months post-injury) and within-group longitudinal change in a group of children and adolescents aged 7–17 years with moderate-to-severe TBI (n?=?20) and a comparison group of children with orthopedic injury (OI) (n?=?21). In the 3- and 18-month cross-sectional analyses, tract-based spatial statistics (TBSS) generally revealed decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) in the TBI group in regions of frontal, temporal, parietal, and occipital white matter as well as several deep subcortical structures, though areas of FA decrease were more prominent at the 3-month assessment, and areas of ADC increase were more prominent at the 18 month assessment, particularly in the frontal regions. In terms of the within-group changes over time, the OI group demonstrated primarily diffuse increases in FA over time, consistent with previous findings of DTI-measured white matter developmental change. The TBI group demonstrated primarily regions of FA decrease and ADC increase over time, consistent with presumed continued degenerative change, though regions of ADC decrease were also appreciated. These results suggest that TBI-related microstructural changes are dynamic in children and continue until at least 18 months post-injury. Understanding the course of these changes in DTI metrics may be important in TBI for facilitating advances in management and intervention.     

Prospective investigation of anterior pituitary function in the acute phase and 12 months after pediatric traumatic brain injury

Purpose

Although head trauma is common in childhood, there is no enough prospective study investigating both acute phase and 12 months after injury. Therefore, a prospective clinical trial was planned to evaluate the pituitary function in childhood in the acute and chronic phase after traumatic brain injury (TBI).

Methods

Forty-one children (27 boys and 14 girls, mean age 7?±?4.3), who were admitted to neurosurgery intensive care unit due to head trauma, were included. Twenty-one (51.2 %) patients had mild, 10 (24.4 %) had moderate, and 10 (24.4 %) had severe TBI. Twenty-two of them were reevaluated 12 months after TBI. Basal pituitary hormone levels were measured during acute (first 24 h) and chronic phase of TBI. Additionally, in the chronic phase, GHRH–arginine test was used for the diagnosis of growth hormone (GH) deficiency.

Results

In the acute phase, 10 patients (24.4 %) had ACTH deficiency, and the overall 44.3 % of patients had at least one pituitary hormone dysfunction. All the pituitary hormone deficiencies during the acute phase were recovered after 12 months. Two patients (9.1 %) had new-onset GH deficiency in the chronic phase, and in one of them, ACTH deficiency was also present.

Conclusions

Present prospective data clearly demonstrated that most of the hormonal changes in the early acute phase were transient, suggesting an adaptive response, and these changes did not predict the hormone deficiencies after 1 year. In the chronic phase, although GH deficiency was present, the frequency of TBI-induced hypopituitarism was clearly lower than the adult patients.