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PubMed2006

Neuroprotection targets after traumatic brain injury.

PURPOSE OF REVIEW: The scarcity of pharmacological neuroprotective treatments for traumatic brain injury is a concern being targeted on various fronts. This review examines the latest treatments under investigation. RECENT FINDINGS: In the last 12-18 months, no drug has completed phase III clinical trials as a clearly proven method to treat traumatic brain injury. While the drugs work in rodents, when they make it to clinical trial they have failed primarily due to negative side-effects. Those still in trial show promise, and even those rejected have undergone modifications and now show potential, e.g. second-generation N-methyl-D-aspartic acid and alpha-amino-3-hydroxy-methyl-4-isoxazolyl-propionic acid receptor antagonists, calpain inhibitors, and cyclosporine A analogues. Also, several drugs not previously given much attention, such as the antibiotic minocycline, estrogen and progesterone, and a drug already approved for other diseases, erythropoietin, are being examined. Finally, a treatment generating some controversy, but showing potential, is the application of hypothermia to the patients. SUMMARY: Clearly, finding treatments for traumatic brain injury is not going to be easy and is evidently going to require numerous trials. The good news is that we are closer to finding one or more methods for treating traumatic brain injury patients.

Animals↗

PubMed2003

Hyperglycemia and outcomes from pediatric traumatic brain injury.

BACKGROUND: The clinical significance of hyperglycemia after pediatric traumatic brain injury is controversial. This study addresses the relationship between hyperglycemia and outcomes after traumatic brain injury in pediatric patients. METHODS: We identified trauma patients admitted during a single year to our regional pediatric referral center with head regional Abbreviated Injury Scale scores > or = 3. We studied identified patients for admission characteristics potentially influencing their outcomes. The primary outcome measure was Glasgow Outcome Scale score. RESULTS: Patients who died had significantly higher admission serum glucose values than those patients who survived (267 mg/dL vs. 135 mg/dL; p = 0.000). Admission serum glucose > or = 300 mg/dL was uniformly associated with death. Admission Glasgow Coma Scale score (odds ratio, 0.560; 95% confidence interval, 0.358-0.877) and serum glucose (odds ratio, 1.013; 95% confidence interval, 1.003-1.023) are independent predictors of mortality in children with traumatic head injuries. CONCLUSION Hyperglycemia and poor neurologic outcome in head-injured children are associated. The pathophysiology of hyperglycemia in neurologic injury after head trauma remains unclear.

Abbreviated Injury Scale↗

PubMed1995

Post-injury administration of BIBN 99, a selective muscarinic M2 receptor antagonist, improves cognitive performance following traumatic brain injury in rats.

Mild to moderate traumatic brain injury (TBI) is associated with enduring impairments of cognitive function in both humans and animals. However, few experiments have investigated the role of post-injury pharmacologic strategies for attenuating the observed cognitive impairment after TBI. This investigation examined the effects of selective blockade of the presynaptic muscarinic M2 autoreceptor with BIBN 99 on cognitive recovery following rodent TBI. Experiment 1 investigated the effects of delayed post-injury administration of BIBN 99 on cognitive performance following moderate central fluid percussion TBI (2.1 +/- 0.05 atm). On days 11-15 after injury-cognitive performance was assessed with a Morris water maze (MWM) task. One hour before MWM testing injured rats were injected (s.c.) with either vehicle (n = 9), 0.5 (n = 8), or 1.0 (n = 8) mg/kg of BIBN 99. Results indicated that injured rats receiving the delayed post-injury treatment with BIBN 99 performed no better than injured-vehicle treated rats. In experiment 2, injured rats were injected (s.c.) once daily with either vehicle (n = 9), 0.5 (n = 9), or 1.0 (n = 9) mg/kg of BIBN 99 throughout the duration of the experiment beginning 24 h after TBI. Sham-injured animals injected (s.c.) with vehicle (n = 9) or 1.0 (n = 8) mg/kg of BIBN 99 were included for comparison. On days 11-15 after injury, cognitive performance was assessed with the MWM procedure. Results of the second experiment indicated that both doses of BIBN 99 were effective in attenuating cognitive deficits in the MWM as compared to the injured-vehicle treated animals (P < 0.05 for both comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed2000

Personality change disorder in children and adolescents following traumatic brain injury.

The occurrence of personality change due to traumatic brain injury (PC), and its clinical and neuroimaging correlates were investigated. Ninety-four children, ages 5 through 14 at the time of hospitalization following traumatic brain injury (TBI; severe TBI N = 37; mild-moderate TBI N = 57), were assessed. Standardized psychiatric, adaptive functioning, cognitive functioning, family functioning, family psychiatric history, severity of injury, and neuroimaging assessments were conducted. The Neuropsychiatric Rating Schedule (NPRS) was used to establish a diagnosis of PC. Approximately 40% of consecutively hospitalized severe TBI participants had ongoing persistent PC an average of 2 years postinjury. An additional approximately 20% had a history of a remitted and more transient PC. PC occurred in 5% of mild-moderate TBI but was always transient. Interrater reliability for the diagnosis of PC was good (Kappa = .70). In severe TBI participants, persistent PC was significantly associated with severity of injury, particularly impaired consciousness over 100 hr, adaptive and intellectual functioning decrements, and concurrent diagnosis of secondary attention deficit hyperactivity disorder, but was not significantly related to any psychosocial adversity variables. These findings suggest that PC is a frequent diagnosis following severe TBI in children and adolescents, but is much less common following mild-moderate TBI.

Brain Injury, Chronic↗

PubMed1997

Urban and rural traumatic brain injuries in Colorado.

PURPOSE: The purpose of this study was to compare and contrast the epidemiology of traumatic brain injury among urban and rural residents of Colorado. METHODS: Cases of traumatic brain injury (ICD 800, 801, 803, 804, 850-854) for 1991 and 1992 from the Colorado surveillance system of hospitalized and fatal traumatic brain injuries were used. Urban cases resided in counties designated by the U.S. Census Bureau as metropolitan statistical areas (MSA). Rural cases were divided into two groups: "rural, nonremote," if the country of residence was adjacent to an MSA county or if it had a population of 2500, and "rural, remote," if not. RESULTS: Average annual age-adjusted rates of hospitalized and fatal traumatic brain injury varied significantly from 97.8 per 100,000 population for the most urban group to 172.1 per 100,000 population for the residents of rural, remote counties. Similarly, total mortality ranged from 18.1 per 100,000 population among residents of the most urban counties to 33.8 among residents of rural, remote counties. Prehospital mortality ranged from 10.0 to 27.7 traumatic brain injuries per 100,000 population. CONCLUSIONS: These results provide justification for expanding efforts to prevent traumatic brain injury to include the small, but high-risk group of residents in rural areas.

Adolescent↗

PubMed2005

Dynamic change of serum protein S100b and its clinical significance in patients with traumatic brain injury.

OBJECTIVE: To analyze the dynamic change of serum protein S100b in patients with traumatic brain injury and its clinical value in assessing brain damage. METHODS: According to Glasgow coma scale (GCS), 102 cases of traumatic brain injury were divided into mild brain injury group (GCS > or = 13, n = 31, Group A), moderate brain injury group (8 < GCS < 13, n = 37, Group B) and severe brain injury group (GCS < or = 8, n = 34, Group C). Serial S100b concentrations were analyzed by enzyme-linked immunosorbent assay (ELISA) in blood samples taken on admission, 12 h, 24 h, 48 h, 72 h and 7 days after traumatic brain injury. RESULTS: The severe brain injury group showed significantly higher concentration of serum S100b, with earlier increase and longer duration, than the mild and moderate brain injury groups. The patients with higher S100b exhibited lower GCS scores and poor clinical prognosis. The increase in S100b could emerge before clinical image evidence indicated so. CONCLUSIONS: Serum S100b can be used as a sensitive index for assessment and prediction of traumatic brain injury severity and prognosis.

Adolescent↗

PubMed2004

Gender and age effects on outcome after pediatric traumatic brain injury.

OBJECTIVE: To evaluate whether girls have better outcomes after traumatic brain injury than boys. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: A 16,586 patient subset of the National Pediatric Trauma Registry with nonpenetrating traumatic brain injury. INTERVENTIONS: Retrospective review. MEASUREMENTS AND MAIN RESULTS: The patients were subdivided by age into prepubertal (0-7 yrs), indeterminate pubertal (8-12 yrs), and probable pubertal (13-19 yrs). All analyses were adjusted for injury severity using the Injury Severity Score. Outcome variables were in-hospital death rate, intensive care unit length of stay, total length of stay, discharge to home vs. rehabilitation, and functional status at discharge. Overall, 6.1% of girls and 5.3% of boys died. A higher proportion of girls were injured in motor vehicle crashes. Gender did not have a significant effect on in-hospital mortality rate after adjustment for age, Injury Severity Score, and motor vehicle crashes. Boys had a shorter intensive care unit length of stay (p =.027). There were no statistically significant differences between boys and girls in total hospital length of stay, functional outcome, and discharge location, although for every outcome there was a trend toward girls doing worse. CONCLUSIONS: There is evidence from this large study that girls do not have a better outcome after pediatric traumatic brain injury than boys, with a suggestion that girls may do worse.

Adolescent↗

PubMed2000

Attenuation of brain edema, blood-brain barrier breakdown, and injury volume by ifenprodil, a polyamine-site N-methyl-D-aspartate receptor antagonist, after experimental traumatic brain injury in rats.

OBJECTIVE: Traumatic brain injury (TBI) has been shown to induce a significant change in polyamine metabolism. Polyamines and polyamine-dependent calcium influx play an important role in mediating the effects of excitotoxic amino acids at the N-methyl-D-aspartate (NMDA) receptor site. We studied the effects of ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, on brain edema formation, blood-brain barrier breakdown, and volume of injury after TBI. METHODS: Experimental TBI was induced in Sprague-Dawley rats by a controlled cortical impact device, functioning at a velocity of 3 m/s to produce a 2-mm deformation. Ifenprodil or saline (10 mg/kg) was injected intraperitoneally immediately after the cortical impact injury and then every 90 minutes until 6 hours after TBI. Blood-brain barrier breakdown was evaluated quantitatively 6 hours after injury by fluorometric assay of Evans blue extravasation. Brain water content, an indicator of brain edema, was measured with the wet-dry method 24 hours after TBI. Injury volume was quantitated from the brain slices stained with 2% cresyl violet solution 7 days after TBI. RESULTS: Blood-brain barrier breakdown was significantly lower in the traumatic cortex of the ifenprodil-treated group than in the saline-treated group (84.4 +/- 26.8 microg/g versus 161.8 +/- 27 microg/g, respectively, P < 0.05). Brain edema was significantly reduced in the cortex of the ifenprodil-treated group relative to that in the saline-treated group (80.9 +/- 0.5% versus 82.4 +/- 0.6% respectively, P < 0.05). Ifenprodil treatment reduced injury volume significantly (14.9 +/- 8.1 mm3 versus 24.4 +/- 6.7 mm3, P < 0.05). CONCLUSION: The polyamine-site NMDA receptor antagonist ifenprodil affords significant neuroprotection in a controlled cortical impact brain injury model and may hold promise for the discovery and treatment of the mechanism of delayed neurological deficits after TBI.

Animals↗

PubMedDate not supplied

Traumatic brain injury registries in the United States: an overview.

In the United States, injuries account for more death and disability in the one to 44 year age group than all communicable diseases and other conditions combined. Concerns about this, about the cost of acute and rehabilitation care after injury, and about quality of life for survivors are mounting, as epitomized by Federal Government initiatives. Public health surveillance of injuries such as traumatic brain injury has recently begun to evolve, following decades of experience with similar methods for infectious and chronic disease conditions. In 1985, the Centers for Disease Control began to promote the development of surveillance systems for 'sentinel injuries' at both the state and national level. Many states have developed, or are in the process of developing, statewide registries for traumatic brain injury. The rationale behind the establishment of these registries is fourfold: 1) to identify injured persons in order to facilitate and coordinate their rehabilitation and other needed services; 2) to gather data for injury prevention and control; 3) to gather data for health care planning; and 4) to evaluate services provided to injured persons. Purpose, content, and scope of these registries are presented in detail.

Brain Injuries↗

PubMed1991

Fluid percussion barotrauma chamber: a new in vitro model for traumatic brain injury.

Advances in the understanding of the pathophysiology of traumatic brain injury have implicated a number of cellular events as fundamental to the evolution of neurologic dysfunction in this process. Following the primary biomechanical insult, a highly complex series of biochemical changes occur, some of which are reversible. The development of fluid percussion injury as an in vivo model for traumatic brain injury has greatly improved our ability to study this disease. However, a comparable in vitro model of biomechanical injury which would enable investigators to study the response to injury in isolated cell types has not been described. We have developed a model of transient barotrauma in cell culture to examine the effects of this form of injury on cell metabolism. This model employs the same fluid percussion device commonly used in in vivo brain injury studies. The effect of this injury was evaluated in monolayers of human glial cells. Cell viability by trypan blue exclusion and the production of leukotrienes following increasing barotrauma was investigated. This model provided a reproducible method of subjecting cells in culture to forces similar to those currently used in animal experimental head injury.

Barotrauma↗

PubMed2002

Indomethacin--a review of its role in the management of traumatic brain injury.

OBJECTIVE: To review the use of indomethacin in the management of traumatic brain injury. DATA SOURCES: Articles reported from 1966 to 2001 and identified through a MEDLINE search of the English language literature on the use of indomethacin in traumatic brain injury. SUMMARY OF REVIEW: Traumatic brain injury (TBI) is a frequent cause of mortality and morbidity in patients with head injury. The use of indomethacin in treating raised intracranial pressure (ICP) secondary to TBI is controversial. Clinical studies suggest that it may be useful in the management of intracranial hypertension, when used in combination with standard techniques, by decreasing cerebral blood flow and reducing ICP during the restoration of the blood brain barrier. Its unique mechanism of action may be due to precapillary vasoconstriction, which reduces the transcapillary transfer of fluid into the cerebral extracellular space. However, large, prospective, randomised and controlled studies have not yet been performed to confirm its benefit in patients with TBI. CONCLUSIONS: Indomethacin should only be considered as an experimental therapy for refractory intracranial hypertension in TBI patients, as current evidence is not available to support its routine use in the management of an elevated ICP. Its use in patients with cerebral vasospasm, renal failure, bleeding disorders, peptic ulceration and coagulopathies is contraindicated.

Journal Article↗

PubMed2006

Vulnerability of the anterior commissure in moderate to severe pediatric traumatic brain injury.

In relation to the adult brain, the immature brain might be more vulnerable to damage during and following traumatic brain injury, particularly in white-matter tracts. Given well-established evidence of corpus callosum atrophy, we hypothesized that anterior commissure volume (using quantitative magnetic resonance imaging [MRI]) in this structure would be decreased in children with moderate to severe traumatic brain injury relative to typically developing children. Second, given the purported role of the anterior commissure in interhemispheric axon conveyance between temporal lobes, we hypothesized that temporal lobe white matter, temporal lesion volume, and injury severity (Glasgow Coma Scale score) would be predictive of decreased anterior commissure cross-sectional volume in patients with traumatic brain injury. Finally, we wished to establish the relationship between the anterior commissure and the temporal stem, a major white-matter tract into the temporal lobes, using diffusion tensor imaging fiber-tracking maps for each patient. We also hypothesized that children with traumatic brain injury would exhibit decreased fractional anisotropy in relation to typically developing children in a fiber system including the anterior commissure and the temporal lobes. Decreased anterior commissure cross-sectional volume was observed in patients with traumatic brain injury, and, as predicted, anterior commissure and temporal white-matter volumes were positively related to each other and to higher Glasgow Coma Scale scores. Lesion volume was not independently predictive of anterior commissure volume in the overall model. Diffusion tensor imaging fractional anisotropy values differed between the groups for the temporal stem-anterior commissure system, with the traumatic brain injury group exhibiting decreased fractional anisotropy. The anterior commissure, like the corpus callosum, appears to be highly vulnerable to white-matter degenerative changes resulting from mechanisms such as the direct impact of trauma, progressive axonal injury as tissue in other brain regions atrophies, or myelin degeneration. This is the first systematic examination of anterior commissure atrophy following traumatic brain injury using in vivo quantitative MRI and diffusion tensor imaging fiber tracking in pediatric subjects.

Adolescent↗

PubMed1999

Induction of tolerance against traumatic brain injury by ischemic preconditioning.

We tested the hypothesis that a transient non-lethal ischemic insult lasting 2 min would protect against subsequent moderate traumatic brain injury. Sprague-Dawley rats were randomized into three experimental groups, including sham ischemia procedures and ischemic preconditioning (IPC) followed 48 h later by moderate traumatic brain injury (TBI) provoked by parasagittal fluid percussion injury (1.8-2.1 atm) and IPC followed by 48 h sham TBI. Seven days after the secondary insult, animals were perfusion-fixed for quantitative histopathological analysis. The CA3 necrotic cell count was decreased by 63% in TBI animals that had undergone IPC as compared to TBI animals that underwent sham IPC. TBI animals that had undergone IPC demonstrated significantly smaller contusion volumes than the TBI alone group (6.44 +/- 1.51 vs 1.37 +/- 0.63 mm3, mean +/- s.e.m.) These data indicate that IPC applied 2 days before moderate fluid percussion brain injury increases the brain resistance to traumatic brain damage.

Animals↗

PubMed2001

The best practice for gaining and maintaining employment for individuals with traumatic brain injury.

There are currently 5.3 million Americans with traumatic brain injury, the majority were young at onset and have a lengthy life expectancy. Return to work is a key to quality of life for many of these individuals. This article provides a literature review of current traumatic brain injury vocational rehabilitation programs including: holistic cognitive rehabilitation, school to work transition, and supportive employment followed by a proposal for the best practice.

Journal Article↗

PubMed2004

Sex differences in injury severity and outcome measures after traumatic brain injury.

OBJECTIVE: To investigate the effect of a patient's sex on various measures of injury severity and outcome after rehabilitation in a matched sample of patients with traumatic brain injury (TBI). DESIGN: Retrospective data were retrieved from a database that contains information routinely collected on all patients admitted for inpatient rehabilitation. SETTING: Inpatient rehabilitation unit of major teaching hospital in Australia. PARTICIPANTS: Fifty-four women with TBI after a motor vehicle crash (MVC) were identified from the Brain Injury Rehabilitation Database. An equal number of men were then matched for age and years of education. All subjects met the study admission criteria of having being involved in a high-speed MVC. Exclusion criteria included history of a previous head injury, chronic amnesia, psychiatric disturbance, and significant alcohol and/or substance abuse. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Differences, by sex, in patient scores on measures of injury severity and outcome after TBI. RESULTS: Men had significantly greater levels of injury severity as indicated by the Glasgow Coma Scale scores (U=994.0, P=.002) and length of posttraumatic amnesia (U=880.0, P=.016) when compared with women. No significant sex differences existed in the outcome measures or in injuries not associated with the central nervous system. CONCLUSIONS: Few investigations exist on the effect of patient sex on measures of injury severity and outcome after a TBI. In the present study, men's levels of injury severity were greater than women's despite the same admission criteria (high-speed MVC) being applied to both sexes.

Adult↗

PubMed2006

California verbal learning test indicators of Malingered Neurocognitive Dysfunction: sensitivity and specificity in traumatic brain injury.

The present study used well-defined traumatic brain injury (TBI) and mixed neurological (other than TBI) and psychiatric samples to examine the specificity and sensitivity to Malingered Neurocognitive Dysfunction (MND) of four individual California Verbal Learning Test (CVLT) variables and eight composite CVLT malingering indicators. Participants were 275 traumatic brain injury and 352 general clinical patients seen for neuropsychological evaluation. The TBI patients were assigned to one of five groups using the Slick, Sherman, and Iverson (1999) criteria: no incentive, incentive only, suspect, and malingering (both Probable MND and Definite MND). Within TBI, persons with the strongest evidence for malingering (Probable and Definite) had the most extreme scores. Good sensitivity (approximately 50%) in the context of excellent specificity (> 95%) was found in the TBI samples. Issues related to the appropriate clinical application of these data are discussed.

Brain Injuries↗

PubMed2001

Diagnostic criteria and differential diagnosis of mild traumatic brain injury.

Brain injury is classified clinically as severe, moderate or mild brain injury characteristics, including admission Glasgow coma score, duration of unconsciousness and post-traumatic amnesia and any focal neurological findings. Most traumatic brain injuries are classified as mild traumatic brain injury (MTBI). Headache, nausea and dizziness are frequent symptoms after MTBI and may continue for weeks to months after the trauma. MTBI may also be complicated by intracranial injuries. Experimental animal models and post-mortem studies have shown axonal damage and dysfunction in MTBI. This damage is mostly localized in the frontal lobes. Serum S-100 and NSE have been reported to be markers for the seventy of brain damage. In the literature, indications for radiodiagnostic evaluation following MTBI have been the subject of debate. Radiographs of the skull are used to exclude skull fractures, but are not useful for an evaluation of brain injury. Computed tomography of the brain seems to be the best way to exclude the development of relevant intracranial lesions. MTBI has a good clinical outcome, although a substantial group of patients develop post-concussional complaints (PCC). There is little information on the effectiveness of various methods suggested for reducing the frequency of PCC.

Brain Injuries↗

PubMed1996

An attempt towards differentiating attentional deficits in traumatic brain injury.

Attentional deficits in patients suffering traumatic brain injury (TBI) can occur with minor to severe impact to the brain. Based on reviews of both the cognitive and neurobehavioral literature, the following three concepts of attention are addressed: (a) arousal/alertness, (b) selective attention, and (c) energetic aspects of attention, which include such components as effort, resource allocation, and speed of processing. Within each concept, definitions are proposed, the underlying brain mechanisms are identified, and the specific deficits associated with TBI are explored. This review combines theoretical perspectives and clinical findings with the objective of leading toward a diagnostic differentiation that in turn will benefit treatment planning.

Arousal↗