Haptoglobin phenotype and apolipoprotein E polymorphism: relationship to posttraumatic seizures and neuropsychological functioning after traumatic brain injury.

The relationship of genetic predisposition to reduced iron capacity and apolipoprotein E (APOE) to posttraumatic seizures (PTSs) and neuropsychological outcomes was investigated in patients with traumatic brain injuries from a prior valproate clinical study. Haptoglobin concentration/phenotype and APOE genotype were determined in 25 patients with PTSs and 26 control (no PTSs) subjects approximately 10 years after traumatic brain injury. Haptoglobin phenotype was also determined in previously collected frozen samples for 25 additional patients with PTSs and 32 no-PTS subjects. There was no relationship between haptoglobin phenotype or APOE genotype and occurrence of PTSs. APOE genotype was not related to neuropsychological outcome; however, when adjustments were made for differences in educational levels, APOE epsilon4 subjects did worse, especially on tests of verbal intellectual and verbal memory skills. In contrast to our hypothesis, those with haptoglobin 1-1 (high-affinity binder of hemoglobin) scored somewhat worse on Verbal IQ and Tapping D at 1 and 12 months after injury.

The Temporal Relationship of Mental Health Problems and Functional Limitations following mTBI: A TRACK-TBI and TED Study.

Mental health problems, such as depression and anxiety, are often associated with functional limitations after traumatic brain injury (TBI), prompting researchers to explore which of these TBI-related sequelae tends to precede the other. Past studies among patients with injuries ranging in severity have predominantly reported that functional impairments predict subsequent psychological concerns, rather than the other way around; however, it remains unclear whether this directionality holds for individuals with mild TBI (mTBI). The present study utilized a cross-lagged panel design within a structural equation modeling analytical framework to explore the longitudinal relationships of symptoms of depression and anxiety to functional status among 717 adult mTBI patients, with assessments occurring at 2 weeks and 3 months post-injury. Symptoms of both depression and anxiety significantly predicted subsequent functional limitations (λs = -0.21 and -0.25), whereas the reverse effects were nonsignificant (λs = -0.05 and -0.03); thus, psychological concerns appeared to function as a precursor to functional impairment. This pattern was particularly pronounced among patients with normal head computed tomography (CT) results; however, results were less clear cut among those subjects whose injuries were accompanied by intracranial abnormalities detected on CT imaging, suggesting the possibility of a more reciprocal relationship in the case of CT-positive mTBI. These results may serve to partially explain the incidence of persistent functional limitations observed among subsets of mTBI patients in past studies. Findings likewise highlight the importance of assessment and treatment for mental health problems after mTBI as an important factor to promote psychological well-being and functional recovery.

Functional limitations and depression after traumatic brain injury: examination of the temporal relationship.

OBJECTIVE: To examine the temporal relationship between self-reported injury-related functional limitations and depressive symptomatology after traumatic brain injury (TBI). DESIGN: A longitudinal cohort study with 3 evaluation points. SETTING: A level I trauma center. PARTICIPANTS: Adolescents and adults (N=135) with complicated mild to severe TBI (72% had complicated mild injuries) who were recruited within 24 hours of injury and then completed the measure at all 3 time points. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sickness Impact Profile and Center for Epidemiological Studies-Depression Scale. RESULTS: Individuals who reported more depressive symptomatology consistently endorsed more injury-related difficulties, showing the strong relationship between depression and perceived psychosocial functioning. Examination of these relationships over time revealed that increased depressive symptomatology follows higher levels of perceived injury-related changes but that reports of injury-related changes are not associated with earlier depression. These findings suggest a unidirectional temporal relationship between these variables. CONCLUSIONS: Perceived changes in daily functioning appear to influence emotional well-being over time after TBI. However, depressive symptoms do not appear to negatively impact individuals' perception of later functioning. These results further our understanding of the complicated relationship between these variables and may have important implications for treatment of depression after TBI.

Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial.

BACKGROUND: Traumatic brain injuries represent an important and costly health problem. Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models. We aimed to test whether treatment with magnesium favourably affects outcome in head-injured patients. METHODS: In a double-blind trial, 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August, 1998, and October, 2004, with moderate or severe traumatic brain injury were randomly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days. Magnesium doses were targeted to achieve serum magnesium ranges of 1.0-1.85 mmol/L or 1.25-2.5 mmol/L. The primary outcome was a composite of mortality, seizures, functional measures, and neuropsychological tests assessed up to 6 months after injury. Analyses were done according to the intention-to-treat principle. This trial is registered with , number . FINDINGS: Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose (mean=55 average percentile ranking on magnesium vs 52 on placebo, 95% CI for difference -7 to 14; p=0.70). Those randomly assigned magnesium at the lower dose did significantly worse than those assigned placebo (48 vs 54, 95% CI -10.5 to -2; p=0.007). Furthermore, there was higher mortality with the higher magnesium dose than with placebo. Other major medical complications were similar between groups, except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group. No subgroups were identified in which magnesium had a significantly positive effect. INTERPRETATION: Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury.

Gaining insight into patients' perspectives on participation in home management activities after traumatic brain injury.

OBJECTIVE: This study investigated performance of home management activities 1 year after traumatic brain injury (TBI), as reported on the Functional Status Examination. METHOD: Home management performance of 164 rehabilitation inpatients (mean age 35.4 years, 77% men, 75% white) with moderate to severe TBI was examined in relation to demographics, injury severity, neuropsychological functioning, and living situation. RESULTS: Fifty-nine percent reported more difficulty or more assistance with home management at 1 year. Nonperformance of individual activities before injury ranged from 16% to 76%. Age (p= .001), living situation after injury (p = .002), and neuropsychological function at 1 year (p = .001) were associated with more limited home management performance after injury as compared to premorbid function. CONCLUSIONS: Home management is challenging 1 year after TBI, especially for older adults and those with greater cognitive impairments. Accurate preinjury information is needed to determine the nature and extent of subsequent losses, guide treatment planning and interventions, and characterize recovery of function.

Patterns of Alcohol Use after Traumatic Brain Injury.

Alcohol misuse and traumatic brain injury (TBI) frequently co-occur. The negative consequences of this interaction are well documented, but the patterns of long-term post-injury alcohol consumption are less clear. This study examined patterns of alcohol use among 170 adults with a history of complicated mild to severe TBI. Participants were recruited from a Level 1 Trauma Center at the time of their injury and completed evaluations at 1 month, 6 months, 12 months, and 3-5 years post-injury. Pre-injury alcohol use was also assessed at the time of the 1-month assessment. A modified Quantity-Frequency Index of alcohol consumption was then calculated for each time point. The results revealed high levels of pre-injury alcohol consumption, followed by a reduction in consumption at 1-month post-injury. A significant increase in consumption was noted by 6 months post-injury, followed by more gradual increases in alcohol consumption at 1 year. Post-injury alcohol consumption was comparable to the general public at 6 months, 12 months, and 3-5 years post-injury. These results suggest that the first 6 months post-injury may be the critical window of opportunity for alcohol intervention.

Correlates of functional status 3-5 years after traumatic brain injury with CT abnormalities.

The Functional Status Examination (FSE) is a relatively new measure of functional outcome after traumatic brain injury (TBI). This study examines functional status limitations and what contributes to them to further enhance interpretability of the FSE and to continue its development as an outcome measure. The measure was given to 209 adults sustaining TBI with CT abnormalities who were followed prospectively until three to five years after injury. Relationships between functional status change as assessed by the FSE and characteristics of the injury and pre-injury characteristics of the person injured were evaluated as were relationships with concurrent measures of neuropsychological, emotional, and psychosocial functioning, health status, quality of life, and other functional status measures. Groups based on degree of functional status limitations due to the injury differ significantly on injury severity, especially length of impaired consciousness. They do not differ on most pre-injury characteristics of the person injured, although pre-existing conditions, primarily alcohol abuse, are more common in those with more negative functional changes after injury. All concurrent measures examined differ significantly among FSE groups with strongest relationships with measures of quality of life, psychosocial functioning, and other measures of health status and functional status (each p < 0.001). The Functional Status Examination shows promise as a measure reflecting a broad range of functional limitations. The FSE is an excellent tool combining clinical relevance, face validity, strong relationships to other measures of relevant constructs (criterion-related validity), and reasonable sensitivity to TBI severity even long after the injury and in a mostly moderately injured group.

The measurement and magnitude of awareness difficulties after traumatic brain injury: a longitudinal study.

Previous research suggests that reduced self-awareness is common following traumatic brain injury (TBI). However, few studies have examined the magnitude of this problem in a sample representative of hospitalized individuals. In this longitudinal study, individuals with complicated mild to severe TBIs and their significant others (SO) were evaluated at 1 and 12 months postinjury on the Sickness Impact Profile. Awareness was measured by comparing the level of injury-related problems reported by a person with TBI and their SO. Overall, individuals with TBI did not report fewer difficulties than their SO. In contrast, they frequently reported more injury-related difficulties than their SO. As there is no commonly or universally accepted definition for differential awareness, the magnitude of underreporting and over-reporting problems is presented using four different cutoff scores. A minimum discrepancy is proposed for defining awareness difficulties that is based on the standard error of measurement of the test-retest difference of the measure. Reduced self-awareness was inconsistent across both time and functional domains. These results suggest that reduced self-awareness is not the norm at 1 or 12 months postinjury and highlight the need for a more standardized approach to the measurement and classification of self-awareness.

Neurobehavioral outcome in persons with violent or nonviolent traumatic brain injury.

OBJECTIVE: To broaden the investigation of those injured violently by examining neuropsychological and psychosocial outcomes in relation to circumstances of traumatic brain injury and preinjury factors. DESIGN: A prospective, longitudinal study. PARTICIPANTS: A total of 752 adults with traumatic brain injury was grouped into those injured by violent or nonviolent circumstances and followed to 1-year post injury. MAIN OUTCOME MEASURES: Circumstance groups were compared on demographics, preexisting conditions, brain injury severity, and neuropsychological and psychosocial outcomes. RESULTS: The results indicate significant differences between the groups on demographics, preexisting conditions, and head injury severity. Neuropsychological and psychosocial outcome did not differ between the circumstance groups when all other factors were taken into account. CONCLUSIONS: Injury severity and characteristics of the person that predate the injury were important to outcome rather than the circumstances of the injury itself.

Outcome 3 to 5 years after moderate to severe traumatic brain injury.

OBJECTIVE: To investigate neuropsychologic, emotional, and functional status and quality of life (QOL) 3 to 5 years after moderate to severe traumatic brain injury (TBI). DESIGN: Observational cohort. SETTING: Level I trauma center. PARTICIPANTS: Consecutive adult admissions with TBI involving intracranial abnormalities, prospectively followed up for 3 to 5 years, with 80% follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neuropsychologic functioning (Paced Auditory Serial Addition Test, California Verbal Learning Test), emotional status (Center for Epidemiologic Studies Depression Scale, Brief Symptom Inventory), functional status (Functional Status Examination, Glasgow Outcome Scale, Medical Outcomes Study 36-Item Short-Form Health Survey, employment), and perceived QOL. RESULTS: Significant functional limitations were observed in all areas. Recovery to preinjury levels ranged from 65% of cases in personal care to approximately 40% in cognitive competency, major activity, and leisure and recreation. Brain injury severity, measured by the modified Abbreviated Injury Scale, related to functional status and neuropsychologic functioning, but not to emotional or QOL measures. Length of impaired consciousness appeared to contribute to outcome more than did anatomic lesions. CONCLUSIONS: The results provide representative estimates of long-term morbidity in patients with TBI involving intracranial lesions. The magnitude of morbidity was high. Although direct costs of TBI have received the most attention, the long-term consequences and their cost implications are much larger, unfold over time, and are borne by the survivors, their families, and the public subsidy system.

Nonrandomized studies of rehabilitation for traumatic brain injury: can they determine effectiveness?

OBJECTIVE: To examine the feasibility of investigating rehabilitation effectiveness for traumatic brain injury (TBI) with a nonrandomized design. DESIGN: Observational cohort with confounder control by regression methodology. SETTING: Level I trauma center. PARTICIPANTS: Consecutive series of 365 individuals with TBI discharged to inpatient rehabilitation or home (78% follow-up). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Glasgow Outcome Scale (GOS), Sickness Impact Profile (SIP), Burden Inventory, and Perceived Quality of Life (PQOL). The predictors of interest: discharge to comprehensive inpatient rehabilitation or home and inpatient rehabilitation length of stay (LOS). RESULTS: Discharge to rehabilitation was associated with poorer functioning on the GOS (P=.03) and SIP (P=.57), an increase on the Burden Inventory (P=.14), and improved PQOL (P=.20). Similar results were found for longer lengths of inpatient rehabilitation. CONCLUSIONS: The results appear to be because of a confounding effect rather than rehabilitation. The study design could not control for confounding that resulted from unmeasured or difficult to measure aspects of the clinical decisions for discharge placement and rehabilitation LOS. Furthermore, typical severity indices were inadequate to control for injury severity and recovery. Matching designs that investigate TBI rehabilitation are also at risk for inadequate confounder control.

Natural history of depression in traumatic brain injury.

OBJECTIVE: To examine prospectively the rates, risk factors, and phenomenology of depression over 3 to 5 years after traumatic brain injury (TBI). DESIGN: Inception cohort longitudinal study. SETTING: Level I trauma center. PARTICIPANTS: Consecutive admissions of 283 adults with moderate to severe TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: The rates of moderate to severe depression ranged from 31% at 1 month to 17% at 3 to 5 years. With 1 exception, the relation between brain injury severity and depression was negligible. Less than high school education, preinjury unstable work history, and alcohol abuse predicted depression after injury. Examination of CES-D factors indicate that, in addition to somatic symptoms, both depressed affect and lack of positive affect contribute to elevated CES-D scores. CONCLUSIONS: High rates of depressive symptoms cannot be dismissed on grounds that somatic symptoms related to brain injury are mistaken for depression. Depressed affect and lack of positive affect are also elevated in persons with TBI. Preinjury psychosocial factors are predictive of depression and knowing them should facilitate efforts to detect, prevent, and treat depression after TBI.