Recovery of executive skills following paediatric traumatic brain injury (TBI): a 2 year follow-up

Primary objective: Disruptions to executive function (EF) may occur as a result of traumatic brain injury (TBI), in the context of direct damage to frontal regions or in association with disruption of connections between these areas and other brain regions. Little investigation of EF has occurred following TBI during childhood and there is little evidence of possible recovery trajectories in the years post-injury. The present study aimed to (i) examine whether a dose-response relationship exists between injury severity and EF; (ii) document recovery of EF in the 2 years post-injury and (iii) determine any additional predictors of outcome in the domain of EF. Research design: The study employed a prospective, longitudinal design, with participants recruited at time of injury and followed over a 2-year period. Methods and procedures: The study examined EF in a group of 69 children who had sustained a mild, moderate or severe TBI. Four components of EF were assessed: (i) attentional control; (ii) planning, goal setting and problem solving; (iii) cognitive flexibility; and (iv) abstract reasoning. Outcomes and results: Results showed that, while children with severe TBI performed most poorly during the acute stage post-injury, they exhibited greatest recovery of EF over a 24-month period. Regardless, functional deficits remained most severe for this group 2 years post-injury. Results demonstrated the multi-dimensional nature of EF and the differential recovery of skills, following childhood TBI. Pre-injury ability and age at injury were identified as significant predictors of EF and functional skills. Conclusions: Children sustaining severe TBI at a young age are particularly vulnerable to impairments in EF. While these difficulties do show some recovery with time since injury, long-term deficits remain and may impact on ongoing development.     

Intellectual ability 10 years after traumatic brain injury in infancy and childhood: what predicts outcome?

The long-term consequences of child traumatic brain injury (TBI) are poorly understood, but there are indications of ongoing deterioration in skills with time since injury. This study investigated outcomes up to 10 years post-injury, to determine the influences of injury severity, injury age, and environment. The study design was prospective and longitudinal. Participants included consecutive admissions to the Royal Children's Hospital, Melbourne, Australia. Children sustaining TBI between 2 and 12 years of age (n=76) were recruited on admission and divided according to injury severity (mild, moderate, and severe) and injury age (2-7 years and 8-12 years). Cognitive abilities were evaluated using standard measures of intellectual function (IQ) acutely and at 12 months, 30 months, and 10 years post-injury. At 10 years, mean IQs for survivors fell within the low average to average range. There were no significant effects of injury severity, injury age, or time since injury. In contrast, elevated rates of impairment were identified in association with severe TBI (global deficits), and early injury (non-verbal deficits). Impairments in processing speed were related to injury severity and age at injury. Predictors of 10-year outcome included pre-injury and social factors, injury age, and family function. Child survivors of serious TBI are at elevated risk of cognitive impairment, with recovery continuing into the third year post-injury. However, between 30 months and 10 years post-insult, children appear to make appropriate developmental gains, contrary to the speculation that these children "grow into their deficits."     

Recovery of function following severe traumatic brain injury: A retrospective 10-year follow-up

It has been widely assumed that most of the recovery following severe traumatic brain injury (TBI) occurs within the first 6 months, and that virtually all of the recovery occurs within the first 1-2 years post-injury. In an effort to evaluate the long-term recovery of patients who had sustained severe TBI, we interviewed the relatives and significant others of 20 patients who had sustained TBI at least 5 years earlier, using a modified version of the Portland Adaptability Inventory. Retrospective ratings were collected to evaluate the patients' psychosocial, cognitive, physical, and emotional status prior to their injury, and at 1, 2, 5, and an average of 10-3 years post-injury. The results indicated that TBI patients exhibit significant improvements in their social, cognitive, physical, and emotional functioning after 2 years post-injury regardless of the severity of their initial brain trauma. These data suggest that patients who sustain severe TBI continue to make gradual improvements in their functioning for at least 10 years post-injury. Our findings contradict the widely held assumption that the recovery process ends after 1 or 2 years post-injury.     

Children's brain injury: a postal follow-up of 525 children from one health region in the UK

Primary objectives : To follow-up a population of children admitted to one Hospital Trust with traumatic brain injury (TBI), and compare outcomes following mild TBI with outcomes following moderate or severe TBI.

Research design : Population-based postal questionnaire survey.

Methods and procedures : Questionnaires were mailed to parents of all 974 surviving children on a register of paediatric TBI admissions, 525 completed questionnaires were returned (56.2%). Most children (419) had suffered mild TBI, 57 moderate, and 49 severe.

Main outcomes and results : Thirty per cent of parents received no information on post-injury symptoms, and clinical follow-up was limited. Statistically significant differences were observed between mild and moderate/severe groups for cognitive, social, emotional, and mobility problems. Nevertheless, ~20% of the mild group suffered from poor concentration, personality change and educational problems post-injury. Few schools (20%) made special provision for children returning after injury.

Conclusions : Children can have long-lasting and wide-ranging sequelae following TBI. Information should be routinely given to parents and schools after brain injury.     

Ultra-rapid cycling bipolar affective disorder following a closed-head injury

A young adult with no prior history of affective disease suffered the onset of a rapid cycling bipolar illness, marginally responsive to psychotropic medications, following a mild closed-head injury, and persisting after the cognitive effects of the injury had resolved. A concurrence of findings on the neurological examination, neurobehavioural examination, SPECT scan, EEG and neuropsychological test battery suggested the presence of a diffuse cerebral injury with a predominance of left frontotemporal findings. This case demonstrates that a severe and disabling mood disorder may follow a mild head injury, and that its course may be independent of cognitive impairment and recovery.     

Protein S-100 and neuropsychological functioning following severe traumatic brain injury

PRIMARY OBJECTIVE: To examine the relationship between serum concentrations of protein S-100beta and neuropsychological functioning following severe traumatic brain injury. DESIGN: Matched control group. METHODS: Blood samples were taken within 12 hours of injury and then daily up to 7 days post-injury (n=23). Within 2 weeks of emerging from post-traumatic amnesia (PTA), participants completed a battery of neuropsychological measures. These results were compared with a matched sample of healthy controls. RESULTS: Early measurement of S-100 not only reflected overall brain injury severity, but also related to neuropsychological deficits, with higher serum concentrations associated with poorer performance across most cognitive domains. PTA duration, measured by the Westmead PTA Scale, was found to be the strongest predictor of S-100 concentration (R2=0.59, p<0.001). CONCLUSIONS: These findings show that measurement of serum protein S-100 may further aid in the identification of individuals with severe TBI who are likely to experience cognitive difficulties.     

Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function

Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function.     

Monitoring emergence from coma following severe brain injury in an octogenarian using behavioural indicators, electrophysiological measures and metabolic studies: a demonstration of the potential for good recovery in older adults

This case study describes a multi-disciplinary investigation of the emergence from coma of an 80-year old female (KE) following severe traumatic brain injury. The relationship between cognitive/behavioural ability and the integrity of cerebral function was assessed using neuropsychological measures, positron emission tomography, electroencephalography, somatosensory evoked potentials and trans-cranial magnetic stimulation. These investigations were performed as KE was beginning to emerge from coma (4 weeks) and, again, ∼1 year following brain injury, when she was judged to have achieved her maximum level of recovery. Neuropsychological measures revealed improvement during the first year post-injury in KE's speed of information processing, memory and executive abilities. Electrophysiological and metabolic studies indicated a restoration of functional integrity that was consistent with the gradual recovery in higher brain function documented using behavioural procedures. This case study demonstrates the rehabilitation potential of pre-morbidly healthy older adults following severe traumatic brain injury.     

Neuropsychological functioning during the year following severe traumatic brain injury

The neuropsychological functioning of a group of 65 adults with severe traumatic brain injury was assessed at 6 months and 1 year post-injury. The cognitive domains assessed were pre-morbid intellectual level, current level of general intellectual functioning, simple and complex attention, verbal memory, executive functioning, and perceptual functioning. At least 40%, and up to 74%, of the TBI patients displayed some degree of impairment on tests administered at 6 months. Improvement was found to occur in all areas of cognitive functioning over the first year following injury. Despite this improvement at least 31%, and up to 63%, of TBI patients displayed some degree of impairment on tests administered at 1 year post-injury. The various types of neuropsychological functioning were affected to different degrees, indicating that different aspects of cognition are more susceptible to injury, and that recovery takes place at a differential rate across functions. The implications of these findings for the appropriate planning and allocation of treatment and rehabilitation resources, and the development of effective rehabilitation interventions are outlined.     

Consequences of mild traumatic brain injury on information processing assessed with attention and short-term memory tasks

In this investigation, we explored the impact of mild traumatic brain injury (mTBI) upon short term or working memory and attention. The performance of 37 individuals with mTBI was compared with that of 53 age, sex and education-matched controls. All participants were staff members or individuals seeking medical care at a University hospital serving a large metropolitan area. A battery of computerized tests measured sustained visual attention, short-term memory (STM), simple reaction time, and decision time. Individuals with mTBI showed a performance deficit at sustained visual attention, STM scanning and a trend towards slowing in choice decision making. These observed changes in the cognitive performance of mTBI individuals are hypothesized to be a consequence of impaired central information processing. Our results suggest that mTBI can elicit meaningful cognitive deficits for several months post-injury. Additionally, we believe that the tasks employed in the current investigation demonstrate their utility for understanding cognitive deficits in mTBI individuals.     

Mood disorders following traumatic brain injury: identifying the extent of the problem and the people at risk

The extent of mood disorders following traumatic brain injury (TBI), and the possible risk factors, are investigated. New data are presented from a prospective study of consecutive hospital admissions. Six months post-TBI, 99 adults completed a standardized assessment of emotional state, the Wimbledon Self-Report Scale. Cognitive performance and the impact of the injury on everyday functioning were also assessed. The rate of clinically significant mood disorders (caseness) was 38%. Of the demographic or injury characteristics, only pre-injury occupational status predicted post-injury caseness. Those unoccupied pre-injury were more likely to report mood disturbances post-injury. In contrast, post injury occupational status was not related to caseness either for the whole group or the subgroup of those previously occupied, despite the adverse effects on occupational functioning for a significant proportion of subjects. Associations were found between emotional state and cognitive and everyday functioning 6 months post-injury. Psychosocial disabilities appeared more strongly associated to mood disorders than did physical disabilities. A significant level of unmet need has been highlighted, and possible risk factors identified, which may inform the purchase and provision of TBI rehabilitation services. Follow-up data on these subjects are available and will be reported separately.     

Comparison of behavioral deficits and acute neuronal degeneration in rat lateral fluid percussion and weight-drop brain injury models

The behavioral and histological effects of the lateral fluid percussion (LFP) brain injury model were compared with the weight drop impact-acceleration model with 10 min of secondary hypoxia (WDIA + H). LFP injury resulted in significant motor deficits on the beam walk and inclined plane, and memory deficits on the radial arm maze and Morris water maze. Motor deficits following LFP remained throughout 6 weeks of behavioral testing. WDIA + H injury produced significant motor deficits on the beam walk and inclined plane immediately following injury, but these effects were transient and recovered by 14 days post-injury. In contrast to the LFP injury, the WDIA + H injured animals showed no memory deficits on the radial arm maze and Morris water maze. In order to determine if the differences in behavioral outcome between models were due to differences in injury mechanism or injury severity, 10 LFP-injured animals were matched with 10 WDIA-injured animals based on injury severity (i.e., time to regain righting reflex after brain injury). The LFP-matched injury group showed greater impairment than the WDIA + H matched injury group on the radial arm maze and Morris water maze. Histological examination of LFP-injured brains with Fluoro-Jade staining 24 h, 48 h, and 7 days post-injury revealed degenerating neurons in the cortex, thalamus, hippocampus, caudate-putamen, brainstem, and cerebellum, with degenerating fibers tracts in the corpus callosum and other major tracts throughout the brain. Fluoro-Jade staining following WDIA+H injury revealed damage to fibers in the optic tract, lateral olfactory tract, corpus callosum, anterior commissure, caudate-putamen, brain stem, and cerebellum. While both models produce reliable and characteristic behavioral and neuronal pathologies, their differences are important to consider when choosing a brain injury model.     

Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide

Blast injuries, that is injuries caused by the complex pressure wave generated by some explosions, show increasing frequency throughout the world. However, whether blast injury is capable of inducing memory dysfunction has not been previously investigated. The present study examines the effects of blast injury-induced neurotrauma on memory deficit in rats. Furthermore, it is hypothesized that blast injury, stimulating nitric oxide production in the medial mesodiencephalic reticular formation and the dorsal hippocampus, both structures being involved in memory processing, may induce memory deficits. Prior to blast injury, Wistar rats were trained for an active avoidance task for 6 days. On day 6, rats that had acquired the avoidance response were subjected to whole-body blast injury, using a BT-I shock tube. Neurotrauma was confirmed by electron microscopical examination. At the completion of cognitive testing, rats were sacrificed at 3, 24 hours and 5 days after injury. The nitric oxide production in the brain structures was determined by the total nitrite/nitrate concentration, and by the expression of inducible nitric oxide synthase mRNA. The rats with blast injury revealed significant deficits in performance of the active avoidance task that persisted up to 5 days post-injury. Electron microscopical findings in both brain structures showed swellings of neurons, glial reaction, myelin debris, and increased pinocytotic activity on the fifth day following trauma. In blast injured rats, there was a significant elevation in total nitrite/nitrate levels 3 and 24 hours following injury which was comparable with the changes in the expression of inducible nitric oxide synthase mRNA. The results indicate that blast injury-induced neurotrauma is able to cause cognitive deficits.     

Mild traumatic brain injury induces persistent cognitive deficits and behavioral disturbances in mice

Victims of mild traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer from long-lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study, we investigated the effects of experimental mTBI in mice on cognition, spatial and non-spatial tasks, and depressive-like behavior in mice. Experimental brain injury was induced using a concussive head trauma, which creates the TBI by a weight-drop device. Different groups of mice were tested at 7, 30, 60, and 90 days post-injury for cognitive function (the swim T-maze and the passive avoidance test) and for depression-like behavior (the forced swimming test). These tests have been used infrequently in the past in mTBI research. Significant differences were observed between the injured mice compared to the controls in both the swim T-maze (day 30: p < 0.001) and passive avoidance (day 30: p < 0.05) tests. In addition, a significant difference was detected in the forced swimming test between the injured mice and the controls (day 7: p < 0.05; day 90: p < 0.01), which showed a depressive- like state in the injured animals beginning 7 days post-injury. These results demonstrate that persistent deficits in these tests of cognitive learning abilities and emergence of depressive-like behavior in injured mice are similar to those reported in human post-concussion syndrome.     

Clinical and cerebral blood flow studies in patients with intracranial hemorrhage and amyloid angiopathy typical of Alzheimer's disease

Spontaneous intracerebral hemorrhages can occur in patients with severe amyloid angiopathy and other morphological signs of Alzheimer's disease (AD). We observed 15 patients in whom histological examination of brain tissue specimens obtained at surgery revealed characteristic congophilic amyloid deposits in subcortical arteries and/or nerve cells. Clinical follow-up examinations were carried out up to 9 years after diagnosis. In addition, three survivors from the operated group were investigated by neuropsychological testing and single photon emission computer tomography (SPECT) using Tc-99m-HMPAO for determination of regional cerebral blood flow (rCBF).SPECT could not differentiate between the typical Alzheimer disease pattern of bilateral temporo-parietal rCBF reduction and flow deficits resulting from previous hemorrhage. Intellectual functioning was found to be impaired to various degrees ranging from normal function to severe dementia (MMS test scores varied between 15 and 26 points); again, it was difficult to differentiate clinically between the nosologic entities mentioned above.On the basis of our present experience we cannot distinguish between brain dysfunction due to Alzheimer's disease and intracranial hemorrhage from amyloid angiopathy. This supports the idea that intracranial hemorrhage may only be one clinical manifestation of amyloid deposits, another one being Alzheimer's disease with varying preponderance.     

Cognitive functioning of adult survivors of cerebral hypoxia

What should clinical neuropsychologists look out for when asked to assess someone with hypoxic brain damage? To determine whether there are typical cognitive profiles of hypoxic patients, all referrals for a neuropsychological assessment made to the author over a period of 16 years were scanned to identify those with a primary diagnosis of cerebral hypoxia as recorded in the hospital notes. From a total sample of 567 patients, 18 (3·17%) had sustained primary cerebral hypoxia from a variety of causes including carbon monoxide poisoning, cardiac arrest, anaesthetic accident, respiratory failure following a pulmonary embolus, hanging and drowning. Not surprisingly, in view of the different degrees of brain damage, the cognitive functioning of the 18 patients was variable, with the greatest number showing deficits of memory and executive functioning (n = 6). Three presented with an amnesic syndrome; two with memory, executive and visuospatial deficits; and three with visuospatial or visuoperceptual problems without severe memory impairments. The remaining four patients were very severely impaired intellectually (VSI), with widespread cognitive deficits precluding the use of neuropsychological assessment procedures designed for adults.     

Severity profile of penetrating ballistic-like brain injury on neurofunctional outcome, blood-brain barrier permeability, and brain edema formation

This study evaluated the injury severity profile of unilateral, frontal penetrating ballistic-like brain injury (PBBI) on neurofunctional outcome, blood-brain barrier (BBB) permeability, and brain edema formation. The degree of injury severity was determined by the delivery of a water-pressure pulse designed to produce a temporary cavity by rapid (<40?ms) expansion of the probe's elastic balloon calibrated to equal 5%, 10%, 12.5%, or 15% of total rat brain volume (control groups consisted of sham surgery or insertion of the probe only). Neurofunctional assessments revealed motor and cognitive deficits related to the degree of injury severity, with the most clear-cut profile of PBBI injury severity depicted by the Morris water maze (MWM) results. A biphasic pattern of BBB leakage was detected in the injured hemisphere at all injury severity levels at 4?h post-injury, and again at 48-72?h post-injury, which remained evident out to 7 days post-PBBI in the 10% and 12.5% PBBI groups. Likewise, significant brain edema was detected in the injured hemisphere by 4?h post-injury and remained elevated out to 7 days post-injury in the 10% and 12.5% PBBI groups. However, following 5% PBBI, significant levels of edema were only detected from 24?h to 48h post-injury. These results identify an injury severity profile of BBB permeability, brain edema, and neurofunctional impairment that provides sensitive and clinically relevant outcome metrics for studying potential therapeutics.     

Prediction of long-term cognitive outcome of brain injury with neuropsychological, severity of injury, and demographic data

A comparison was made of the relative power of a brief post-injury neuropsychological assessment and a brain-injury severity measure (PTA) to predict long-term cognitive outcome after severe brain injury. Subjects were 78 patients with severe brain injury. Regression analysis revealed that neuropsychological variables were as predictive of outcome as PTA. A combination of neuropsychological, brain-injury severity, and demographic variables predicted a substantial proportion of variance in both general cognitive ability and memory functioning at outcome. Removal of PTA from the set of predictors had only modest impact on predictive power, suggesting that, in the absence of accurate injury severity data, meaningful prediction about long-term cognitive outcome can still be made.     

Predicting family functioning after TBI: impact of neurobehavioral factors

OBJECTIVE: To identify risk factors for poor family functioning and neurobehavioral problems after traumatic brain injury (TBI) or orthopedic injuries (OI). DESIGN: Longitudinal analyses of data from an inception cohort. PARTICIPANTS: Seventy-five patients with moderate/severe TBI, 47 patients with mild TBI, and 44 patients with OI at discharge; and 49 patients with moderate/severe TBI, 24 patients with mild TBI, and 33 patients with OI at 1-year follow-up. OUTCOME MEASURES: Measures of family functioning (Family Assessment Device) and Neurobehavioral Functioning Index at hospital discharge and 1-year follow-up. RESULTS: At discharge, patients with moderate/severe TBI had more symptoms of depression, memory/attention problems, and motor impairments than patients with OI and greater communication difficulties than patients with OI or mild TBI. At follow-up, patients with moderate/severe TBI continued to have more problems in memory/attention, depression, and communication. Approximately one third of each group had unhealthy family functioning at each assessment period. Few patients reported both impaired family functioning and clinical depression. Distressed family functioning correlated strongly with increased rates of neurobehavioral symptoms. Family dysfunction at follow-up was best predicted by family dysfunction at discharge and depression or memory/attention deficits at follow-up. CONCLUSIONS: After TBI, patients at the greatest risk for distress at follow-up were those with family dysfunction at discharge and continued neurobehavioral problems. High-risk families need to be identified so that necessary referrals and/or treatment can be offered.