The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study.

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

Treatments and rehabilitation in the acute and chronic state of traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of acquired disability globally, and effective treatment methods are scarce. Lately, there has been increasing recognition of the devastating impact of TBI resulting from sports and other recreational activities, ranging from primarily sport-related concussions (SRC) but also more severe brain injuries requiring hospitalization. There are currently no established treatments for the underlying pathophysiology in TBI and while neuro-rehabilitation efforts are promising, there are currently is a lack of consensus regarding rehabilitation following TBI of any severity. In this narrative review, we highlight short- and long-term consequences of SRCs, and how the sideline management of these patients should be performed. We also cover the basic concepts of neuro-critical care management for more severely brain-injured patients with a focus on brain oedema and the necessity of improving intracranial conditions in terms of substrate delivery in order to facilitate recovery and improve outcome. Further, following the acute phase, promising new approaches to rehabilitation are covered for both patients with severe TBI and athletes suffering from SRC. These highlight the need for co-ordinated interdisciplinary rehabilitation, with a special focus on cognition, in order to promote recovery after TBI.

Ten-year outcome of early childhood traumatic brain injury: Diffusion tensor imaging of the ventral striatum in relation to executive functioning.

PRIMARY OBJECTIVE: The long-term effects of TBI on verbal fluency and related structures, as well as the relation between cognition and structural integrity, were evaluated. It was hypothesized that the group with TBI would evidence poorer performance on cognitive measures and a decrease in structural integrity. RESEARCH DESIGN: Between a paediatric group with TBI and a group of typically-developing children, the long-term effects of traumatic brain injury were investigated in relation to both structural integrity and cognition. Common metrics for diffusion tensor imaging (DTI) were used as indicators of white matter integrity. METHODS AND PROCEDURES: Using DTI, this study examined ventral striatum (VS) integrity in 21 patients aged 10-18 years sustaining moderate-to-severe traumatic brain injury (TBI) 5-15 years earlier and 16 demographically comparable subjects. All participants completed Delis-Kaplan Executive Functioning System (D-KEFS) sub-tests. MAIN OUTCOMES AND RESULTS: The group with TBI exhibited lower fractional anisotropy (FA) and executive functioning performance and higher apparent diffusion coefficient (ADC). DTI metrics correlated with D-KEFS performance (right VS FA with Inhibition errors, right VS ADC with Letter Fluency, left VS FA and ADC with Category Switching). CONCLUSIONS: TBI affects VS integrity, even in a chronic phase, and may contribute to executive functioning deficits.

The effect of maternal haematocrit on offspring IQ at 4 and 7 years of age: a secondary analysis.

OBJECTIVE: To determine whether maternal haematocrit during pregnancy is associated with offspring IQ. DESIGN/SETTING/POPULATION: A secondary analysis of the Collaborative Perinatal Project, which enrolled women between 1959 and 1966 at 12 university hospitals in the United States. METHODS: We evaluated the relation between maternal haematocrit and IQ at 4 and 7 years of age. Linear and log-linear regression models were used to adjust for possible confounders. Marginal structural models with stabilised weights were used to account for selection bias due to children lost to follow up. MAIN OUTCOME MEASURES: Offspring IQ at 4 and 7 years of age. RESULTS: Of 35 959 patients, 1521 (4.2%) had moderate anaemia, 13 769 (38.3%) had mild anaemia, 18 227 (50.7%) had a normal haematocrit, and 2442 (6.8%) had a high haematocrit. The mean IQ at 4 and 7 years was significantly lower in the moderate and mild anaemia groups than in the normal haematocrit group (92.3 and 94.7 versus 100.6, respectively, P < 0.01, at 4 years; and 90.2 and 93.4 versus 99.1 at 7 years, P < 0.01). The high haematocrit group had a significantly higher mean IQ (104.5 at 4 years; 103.2 at 7 years) when compared with the normal haematocrit group (P < 0.01). Women with moderate anaemia were more likely to have children with IQ of 70-84 at 4 years (RR 1.22, 95% CI 1.08-1.38) and <70 at 7 years (RR 1.59, 95% CI 1.14-2.23). Women with a high haematocrit were more likely to have children with an IQ ≥120 at 7 years (RR 1.22, 95% CI 1.08-1.39). CONCLUSIONS: Maternal haematocrit is associated with offspring IQ at 4 and 7 years of age. TWEETABLE ABSTRACT: There is a nonlinear relation between maternal haematocrit and offspring IQ at 4 and 7 years of age.

Prolonged latency of preterm prelabour rupture of membranes and neurodevelopmental outcomes: a secondary analysis.

OBJECTIVE: To determine whether prolonged latency after preterm prelabour rupture of membranes (PPROM) is associated with an increased risk for adverse neurodevelopmental outcomes. DESIGN: This is a secondary analysis of the randomised controlled trial of magnesium sulphate for the prevention of cerebral palsy. SETTING: Multicentre trial. POPULATION: A total of 1305 women with PPROM were analysed, 1056 of whom had an interval of <3 weeks between diagnosis and delivery and 249 of whom had an interval of ≥3 weeks between diagnosis and delivery. METHODS: We evaluated whether the time interval between diagnosis of PPROM and delivery was associated with an increased risk for adverse neurodevelopmental outcomes. Latency was analysed as a continuous variable and categorised by weeks of latency. MAIN OUTCOME MEASURES: The primary outcome was motor and mental Bayley scores of <70 at 2 years of age. Secondary outcomes included motor and mental Bayley scores <85 and mean Bayley scores. Logistic regression was used to control for confounding factors. RESULTS: In the univariate analysis, motor and mental Bayley scores of <70 were similar in the <3 weeks (16.8 and 14.4%) and ≥3 weeks (15.3 and 14.1%) groups. In the regression analysis adjusting for confounding factors, PPROM for ≥3 weeks was an independent risk factor for motor (adjusted odds ratio (aOR) 2.12; 95% confidence interval, 95% CI 1.29-3.49) and mental (aOR 1.83, 95% CI 1.13-3.00) Bayley scores of <70. Neonatal sepsis, gestational age at delivery, maternal education, and race were significantly associated with neurodevelopmental outcomes. CONCLUSIONS: Whereas delivery at later gestational age is associated with improved prognosis for many outcomes, prolonged exposure to an intrauterine environment of PPROM is an independent risk factor for adverse neurodevelopmental outcomes. TWEETABLE ABSTRACT: Prolonged PPROM was associated with motor and mental Bayley scores of <70.

Clinical indication and timing of antenatal corticosteroid administration at a single centre.

OBJECTIVE: To determine how well antenatal corticosteroids (ACS) were timed, based on the indication for administration for women delivering preterm. DESIGN: Retrospective cohort study. SETTING: Tertiary medical centre. POPULATION: Six hundred and thirty women who had singleton preterm births between 24 and 34 weeks' gestational age. METHODS: Charts from 2006 to 2011 were reviewed for indications for ACS administration, which included premature rupture of membranes, threatened preterm labour, risk factors for spontaneous preterm birth such as short ultrasound cervical length, positive fetal fibronectin, and hypertensive disorders of pregnancy. Charts were reviewed for timing of ACS administration in relation to delivery. MAIN OUTCOME MEASURES: The primary outcome was optimal timing, defined as administration of ACS ≥ 24 hours to ≤ 7 days prior to delivery. RESULTS: Of 630 women who delivered preterm, 589 (93%) received ACS prior to delivery. ACS timing was optimal in 40% (238 of 589) of cases. Women with hypertensive disorders were most likely to have steroids optimally timed (62%). Asymptomatic women at increased risk for preterm delivery were less likely to receive optimally timed ACS (12%). The majority of women who received steroids >2 weeks prior to delivery (57%) received a second course. CONCLUSION: A majority of women who delivered preterm did not receive optimally timed ACS. Diagnostic tools that identified women at risk for preterm birth were not able to identify patients for appropriate steroid timing. Given the range of clinical scenarios in which patients are at increased risk for preterm delivery, further research is needed to assist clinicians in optimising steroid administration. TWEETABLE ABSTRACT: Optimal timing of antenatal steroids prior to delivery does not occur in most cases.

Ventilation rates and health: multidisciplinary review of the scientific literature.

UNLABELLED: The scientific literature through 2005 on the effects of ventilation rates on health in indoor environments has been reviewed by a multidisciplinary group. The group judged 27 papers published in peer-reviewed scientific journals as providing sufficient information on both ventilation rates and health effects to inform the relationship. Consistency was found across multiple investigations and different epidemiologic designs for different populations. Multiple health endpoints show similar relationships with ventilation rate. There is biological plausibility for an association of health outcomes with ventilation rates, although the literature does not provide clear evidence on particular agent(s) for the effects. Higher ventilation rates in offices, up to about 25 l/s per person, are associated with reduced prevalence of sick building syndrome (SBS) symptoms. The limited available data suggest that inflammation, respiratory infections, asthma symptoms and short-term sick leave increase with lower ventilation rates. Home ventilation rates above 0.5 air changes per hour (h(-1)) have been associated with a reduced risk of allergic manifestations among children in a Nordic climate. The need remains for more studies of the relationship between ventilation rates and health, especially in diverse climates, in locations with polluted outdoor air and in buildings other than offices. PRACTICAL IMPLICATIONS: Ventilation with outdoor air plays an important role influencing human exposures to indoor pollutants. This review and assessment indicates that increasing ventilation rates above currently adopted standards and guidelines should result in reduced prevalence of negative health outcomes. Building operators and designers should avoid low ventilation rates unless alternative effective measures, such as source control or air cleaning, are employed to limit indoor pollutant levels.

Voxel-based analysis of diffusion tensor imaging in mild traumatic brain injury in adolescents.

BACKGROUND AND PURPOSE: DTI of normal-appearing WM as evaluated by conventional MR imaging in mTBI has the potential to identify important regional abnormalities that relate to PCS. VBA was used to examine WM changes in acute mTBI. MATERIALS AND METHODS: WM was assessed between 1 and 6 days postinjury with voxel-based DTI analyses in 10 adolescent patients with mTBI and 10 age-matched control participants. In addition to the voxel-based group, analysis used to identify brain pathology across all patients with mTBI, 2 voxel-based linear regressions were performed. These analyses investigated the relation between 1) the ADC and PCS severity scores, and 2) ADC and scores on the BSI of emotional symptoms associated with mTBI. We hypothesized that frontotemporal WM changes would relate to symptoms associated with PCS and endorsed on the BSI. RESULTS: Patients with mTBI demonstrated significant reductions in ADC in several WM regions and in the left thalamus. As expected, no increases in ADC were found in any region of interest. All injury-affected regions showed decreased radial diffusivity, unchanged AD, and increased FA, which is consistent with axonal cytotoxic edema, reflective of acute injury. CONCLUSIONS: Whole-brain WM DTI measures can detect abnormalities in acute mTBI associated with PCS symptoms in adolescents.

Predictors of individual visual memory decline after unilateral anterior temporal lobe resection.

BACKGROUND: Different types of neuropsychological visual memory tasks have been created to quantify deficits associated with right hemisphere dysfunction. There are reports of visual memory impairment after right anterior temporal lobe resection (ATR) compared to left ATR for the processing of faces, abstract designs, and spatial locations, but there are also studies showing no between-group differences. One potential reason for the conflicting results is the use of group mean changes, which mask individual differences. METHODS: Proportions of individual subjects with decline, no change, or improvement in memory for spatial locations, abstract designs, and unfamiliar faces were evaluated in 83 individuals who underwent a standard ATR (47 right, 36 left) and were left hemisphere language dominant. RESULTS: Type of visual memory ability was an important factor as there were differential individual declines found for memory for spatial locations after right ATR compared to left ATR (27.3% vs 5.9%), but not memory for abstract designs or face memory. Logistic regression indicated that the odds of a spatial memory decline were six times higher for patients who underwent right ATR than left ATR. CONCLUSIONS: Memory for spatial locations appears to be particularly vulnerable to decline when a patient undergoes right-anterior temporal lobe resection (ATR) and when the patient has better spatial memory before surgery. Results provide proportions of subjects with significant change to help clinicians and patients make better informed decisions about risks associated with undergoing right ATR.

Diffusion tensor imaging of acute mild traumatic brain injury in adolescents.

BACKGROUND: Despite normal CT imaging and neurologic functioning, many individuals report postconcussion symptoms following mild traumatic brain injury (MTBI). This dissociation has been enigmatic for clinicians and investigators. METHODS: Diffusion tensor imaging tractography of the corpus callosum was performed in 10 adolescents (14 to 19 years of age) with MTBI 1 to 6 days postinjury with Glasgow Coma Scale score of 15 and negative CT, and 10 age- and gender-equivalent uninjured controls. Subjects were administered the Rivermead Post Concussion Symptoms Questionnaire and the Brief Symptom Inventory to assess self-reported cognitive, affective, and somatic symptoms. RESULTS: The MTBI group demonstrated increased fractional anisotropy and decreased apparent diffusion coefficient and radial diffusivity, and more intense postconcussion symptoms and emotional distress compared to the control group. Increased fractional anisotropy and decreased radial diffusivity were correlated with severity of postconcussion symptoms in the MTBI group, but not in the control group. CONCLUSIONS: In adolescents with mild traumatic brain injury (MTBI) with Glasgow Coma Scale score of 15 and negative CT, diffusion tensor imaging (DTI) performed within 6 days postinjury showed increased fractional anisotropy and decreased diffusivity suggestive of cytotoxic edema. Advanced MRI-based DTI methods may enhance our understanding of the neuropathology of TBI, including MTBI. Additionally, DTI may prove more sensitive than conventional imaging methods in detecting subtle, but clinically meaningful, changes following MTBI and may be critical in refining MTBI diagnosis, prognosis, and management.

Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson's disease.

BACKGROUND: We investigated the cognitive and psychiatric outcome 6 months after bilateral subthalamic nucleus deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) using a disease control group. METHODS: 23 patients who underwent DBS were compared with 28 medically treated patients with PD at baseline and at 6 months for neuropsychological measures. In addition to the group outcomes, we report reliable change indices (RCI) and a dementia caseness analysis. RESULTS: Patients who underwent DBS demonstrated a significant decline in verbal memory compared with the control group (p<0.003), and trends for decline on oral information processing, including verbal fluency, timed transcription and word naming. Patients who underwent DBS demonstrated declines in attention, set shifting and semantic fluency but these changes were similar to the rate of decline in the PD group. RCI indicated that patients who underwent DBS demonstrated clinically significant declines in verbal fluency (p<0.01) and inhibition of a dominant response (p<0.003), with trends for declines in set shifting (p<0.02) and verbal long term recall (p<0.08), indicative of frontostriatal dysfunction. Patients who underwent DBS did not demonstrate significant changes in depression, anxiety or psychological distress scores. The caseness analysis revealed that one of the patients who underwent DBS (4%) converted to dementia over 6 months compared with none of the PD controls. CONCLUSIONS: Our findings demonstrated that patients who underwent DBS experienced declines in verbal recall and trends for declines in oral information processing 6 months following surgery, even when good motor outcome was achieved. Potential candidates should be counselled about the risk of mild frontostriatal cognitive declines following DBS to weigh the risks and benefits of surgery.

Short and long-term motor and cognitive outcome of staged bilateral pallidotomy: a retrospective analysis.

BACKGROUND: We investigated retrospectively the short and long-term motor and cognitive functioning of staged bilateral pallidotomy using motor testing and a comprehensive neuropsychological battery before and after each procedure. METHODS: Fifteen patients with idiopathic Parkinson's disease were assessed at baseline and at least 3 months after each of their two staged surgeries. Motor and neuropsychological results were compared to 15 non-surgical Parkinson's disease patients matched for disease stage and mental status. In addition, nine bilateral pallidotomy patients were evaluated for long-term cognitive changes (>2 years). FINDINGS: Bilateral pallidotomy patients demonstrated significant improvements in motor functioning in the "on" and "off" states and with dyskinesias after the first surgery, with an additional improvement reported for dyskinesias after the second procedure. On long-term follow-up, dyskinesia improvements were maintained. Bilateral pallidotomy patients did not show significant cognitive declines following both procedures on the short-term follow-up and when compared to the Parkinson's disease group. However, significant cognitive declines were found on the long-term follow-up evaluation. CONCLUSIONS: Parkinson's disease patients received significant short- and long-term motor benefits, particularly reduced dyskinesias, following staged bilateral pallidotomy without significant short-term cognitive consequences. Two years following the second procedure, bilateral pallidotomy patients tended to show an increase in both motor and non-motor symptoms of Parkinson's disease, particularly cognitive decline.

cerebellar atrophy after moderate-to-severe pediatric traumatic brain injury.

BACKGROUND AND PURPOSE: Although the cerebellum has not attracted the same degree of attention as cortical areas and the hippocampus in traumatic brain injury (TBI) literature, there is limited structural and functional imaging evidence that the cerebellum is also vulnerable to insult. The cerebellum is emerging as part of a frontocerebellar system that, when disrupted, results in significant cognitive and behavioral consequences. We hypothesized that cerebellar volume would be reduced in children following TBI and wished to examine the relation between the cerebellum and known sites of projection, including the prefrontal cortex, thalamus, and pons. MATERIALS AND METHODS: Quantitative MR imaging was used to measure cerebellar white and gray matter and lesion volumes 1-10 years following TBI in 16 children 9-16 years of age and 16 demographically matched typically developing children 9-16 years of age. Cerebellar volumes were also compared with volumetric data from other brain regions to which the cerebellum projects. RESULTS: A significant group difference was found in cerebellar white and gray matter volume, with children in the TBI group consistently exhibiting smaller volumes. Repeating the analysis after excluding children with focal cerebellar lesions revealed that significant group differences still remained for cerebellar white matter (WM). We also found a relation between the cerebellum and projection areas, including the dorsolateral prefrontal cortex, thalamus, and pons in 1 or both groups. CONCLUSION: Our finding of reduced cerebellar WM volume in children with TBI is consistent with evidence from experimental studies suggesting that the cerebellum and its related projection areas are highly vulnerable to fiber degeneration following traumatic insult.

Impairment and recovery in inhibitory control after traumatic brain injury in children: effect of age at injury, injury severity and lesion location.

We examined the effect of traumatic brain injury (TBI) on inhibitory control, trajectories of recovery of inhibitory control, and the effect of age at injury, severity, and lesion location on recovery. Participants were 127 children with TBI aged 5-16 years and 117 controls of similar age. Latency of response inhibition was measured with the stop signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. Performance of children with TBI was compared with that of controls. Growth curve analyses showed impairments in response inhibition postinjury. Compared with controls, TBI children improved over time in response inhibition. Younger TBI children recovered better on response inhibition than older TBI children. No significant effect of severity or right frontal lesion on recovery of response inhibition was found. TBI has an acute effect on inhibitory control but which recovers over time.

The evolution of transposons in Schizosaccharomyces pombe.

Recent studies of the LTR-retrotransposons of Schizosaccharomyces pombe have shed considerable light on their evolution and function. The sequencing of the S. pombe genome allowed analysis of its transposon content. This analysis provides information about the maintenance and loss of transposons in the genome. The results of transposition assays and biochemical analyses demonstrate that the N-terminal protein of Tf1 is functionally equivalent to the Gag proteins of retroviruses and retrotransposons. Despite this conservation of function, the N-terminal protein of Tf1 lacks any sequence similarity to other known Gag proteins. Sequence analysis and experimental data also indicate that the Tf1 transposons of S. pombe target their integration into specific sites in the host genome. Transposition events resulting from the expression of Tf1 reveal a strong preference for intergenic regions, specifically at pol II promoters in a window 100-400 bp upstream of open reading frames. The complete and partial copies of Tf transposons in the sequenced genome of S. pombe show the same association of integration with promoter regions. This body of work explores how the transposon interacts with the host, the balance between the transposons propagation and loss, and how different families of transposons evolve.

[The neurobehavioral rating scale-revised: assessment of concurrent validity]. / Echelle neurocomportementale révisée: étude de la validité concourante.

UNLABELLED: Cognitive and behavioral impairment are a major source of disability in daily living of patients with traumatic brain injury (TBI). The Neurobehavioral Rating Scale-Revised (NRS-R) is a short, easy-to administer interview tool developed to improve assessment by clinicians. Data are available on its criterion validity and reliability, but the concurrent validity of the French NRS-R was not yet documented. OBJECTIVE: To assess the concurrent validity of the NRS-R with current psychometric tests. METHOD: One hundred and four patients with TBI enrolled in a community adjustment program underwent concurrent examination with the NRS-R, cognitive tests assessing memory, attention, and executive functions, and scales of anxiety (STAI) and depressive mood (CES-D). Intercorrelations were undertaken between these variables and the five factors of the NRS-R: F1, intentional behavior; F2, lowered emotional state; F3, survival-oriented behaviour/hightened emotional state; F4, arousal state; and F5, language. Patients were 82 men and 22 women, the mean age was 28.5 years, and 70% had severe TBI (Glasgow coma score [GCS] below 8 on admission). They were assessed 52 months on average after their injury. RESULTS: Factor F1 was correlated with results on the GCS (P<0.05), the Tower of London test (TL, P<0.01), the Trail Making Test (TMT, P<0.01), divided attention (DA) and inhibition (IN) subscales of the Zimmermann and Fimm's Attention battery (TEA) (P<0.01) and reverse digit span (DS, P<0.05). Factor F2 was positively related to age at injury, time since injury (TSI) (P<0.05) and CESD and STAI scores (P<0.001). Factor F3 was related to DA (P<0.01) TL scores and TSI (P<0.05). Factor F4 was related to TL, TMT, DA, flexibility, DS (P<0.05), TSI, duration of post-traumatic amnesia, CES-D score (P<0.05) and STAI scores (P<0.01). Factor F5 was related to GCS, DA (P<0.05), and reaction time on the subscales IN and Go/nogo (GO) of the TEA battery (P<0.01). The NRS-R total score was related to CESD, STAI scores, TMT score, DA (P<0.01) and TL score, IN and GO scores and TSI (P<0.05). DISCUSSION: As McCauley et al found with the English version of the NRS-R, significant relationships were found between NRS-R factor scores, cognitive tests and emotional scales. Relationships were also found between factor scores and indicators of injury severity and time since injury. These data suggest fair concurrent validity of the NRS-R.

An fMRI study of executive functioning after severe diffuse TBI.

PRIMARY OBJECTIVE: Preliminary study of whether severe diffuse traumatic brain injury (TBI) increases extent of frontal tissue recruited by cognitive control tasks. RESEARCH DESIGN: Functional magnetic resonance imaging (fMRI) on N-back working memory (WM)and arrows inhibition tasks in a 46 year old man who had severe diffuse TBI 1 year earlier, a 44 year old man (inhibition task) and three women (working memory task), age 20-26 years. Images were acquired by 1.5 T magnet with BOLD method and PRESTO pulse sequence and analysed using SPM. MAIN OUTCOMES AND RESULTS: Frontal activation increased under 2-back relative to 1-back condition of working memory in all participants with more extensive activation in the TBI patient relative to controls. Frontal activation increased with inhibition on the arrows task, but was greater in the TBI patient. CONCLUSION: Severe diffuse TBI results in recruitment of additional neural resources for cognitive control.

Intercenter variance in clinical trials of head trauma--experience of the National Acute Brain Injury Study: Hypothermia.

OBJECT: In a recently conducted trial of hypothermia in patients with severe brain injury, differences were found in the effects of hypothermia treatment among various centers. This analysis explores the reasons for such differences. METHODS: The authors reviewed data obtained in 392 patients treated for severe brain injury. Prerandomization variables, critical physiological variables, treatment variables, and accrual methodologies were investigated among various centers. Hypothermia was found to be detrimental in patients older than the age of 45 years, beneficial in patients younger than 45 years of age in whom hypothermia was present on admission, and without effect in those in whom normothermia was documented on admission. Marginally significant differences (p < 0.054) in the intercenter outcomes of hypothermia-treated patients were likely the result of wide differences in the percentage of patients older than 45 years of age and in the percentage of patients in whom hypothermia was present on admission among centers. The trial sensitivity was likely diminished by significant differences in the incidence of mean arterial blood pressure (MABP) less than 70 mm Hg (p < 0.001) and cerebral perfusion pressure (CPP) less than 50 mm Hg (p < 0.05) but not intracranial pressure (ICP) greater than 25 mm Hg (not significant) among patients in the various centers. Hours of vasopressor usage (p < 0.03) and morphine dose (p < 0.001) and the percentage of dehydrated patients varied significantly among centers (p < 0.001). The participation of small centers increased intercenter variance and diminished the quality of data. CONCLUSIONS: For Phase III clinical trials we recommend: 1) a detailed protocol specifying fluid and MABP, ICP, and CPP management: 2) continuous monitoring of protocol compliance; 3) a run-in period for new centers to test accrual and protocol adherence; and 4) inclusion of only centers in which patients are regularly randomized.

The neurobehavioural rating scale-revised: sensitivity and validity in closed head injury assessment.

OBJECTIVES: To investigate the factor structure and psychometric properties of the neurobehavioural rating scale-revised (NRS-R) and to determine its usefulness in clinical trials. METHODS: A consecutive series of patients sustaining severe closed head injury were evacuated to one of 11 large regional North American trauma centres and entered into a randomised, phase III, multicentre clinical trial investigating the therapeutic use of moderate hypothermia. Acute care personnel were blinded to outcome and outcome personnel were blinded to treatment condition. The Glasgow outcome scale (GOS) was the primary outcome measure. Secondary outcome measures included the disability rating scale (DRS) and the NRS-R. RESULTS: Exploratory factor analysis of NRS-R data collected at 6 months after injury (n=210) resulted in a five factor model including: (1) executive/cognition, (2) positive symptoms, (3) negative symptoms, (4) mood/affect, and (5) oral/motor. These factors showed acceptable internal consistency (0.62 to 0.88), low to moderate interfactor correlations (0.19 to 0.61), and discriminated well between GOS defined groups. Factor validity was demonstrated by significant correlations with specific neuropsychological domains. Significant change was measured from 3 to 6 months after injury for the total score (sum of all 29 item ratings) and all factor scores except mood/affect and positive symptoms. The total score and all factor scores correlated significantly with concurrent GOS and DRS scores. CONCLUSIONS: The NRS-R is well suited as a secondary outcome measure for clinical trials as its completion rate exceeds that of neuropsychological assessment and it provides important neurobehavioural information complementary to that provided by global outcome and neuropsychological measures.

Longitudinal outcome of verbal discourse in children with traumatic brain injury: three-year follow-up.

PURPOSE: This study compared changes in discourse ability between two groups of children age 5 to 10 years after brain injury: those with severe traumatic brain injury (TBI) and those with mild/moderate injury over 3-year follow-up testing. MATERIALS AND METHODS: Forty-three children with TBI were recruited from a larger research project examining cognitive and linguistic recovery after injury. Twenty-two of these patients had severe injuries and 21 sustained mild/moderate injuries. All children were presented an ordered sequence of pictures and asked to verbally produce a story/narrative discourse. Each child was then asked to produce a lesson relating to the story. RESULTS: The severe group performed significantly worse than the mild/moderate group when performance across all four discourse domains was considered. Both groups improved across time on selected discourse measures. Qualitative analysis suggested that the severe group showed differential rates of improvement across the individual discourse variables over the 3-year interval. CONCLUSIONS: Severe TBI can have a pernicious effect on discourse abilities in children years after injury compared with children with mild/moderate injuries. The major caveat is that the discourse measures must be sufficiently challenging when used to assess older children and children with milder forms of TBI.