Dementia after traumatic brain injury

Early retrospective studies suggested that individuals with a history of a traumatic brain injury (TBI) had a higher risk for dementia than those without a history of TBI. Two meta-analyses demonstrated that the risk for dementia is higher among men, but not women, with a history of TBI. More recent prospective studies, however, are providing discrepant findings, probably due to important methodological differences. TBI is usually associated with significant neuropsychological deficits, primarily in the domains of attention, executive functioning and memory. These deficits may not improve with time. TBI may also lower the threshold for the clinical expression of dementia among predisposed individuals, and the onset of Alzheimer's disease (AD)-like neuropathological and biochemical changes immediately after severe TBI may play an important role in this mechanism.     

Dose-dependent neuronal injury after traumatic brain injury

The Fluoro-Jade (FJ) stain reliably identifies degenerating neurons after multiple mechanisms of brain injury. We modified the FJ staining protocol to quickly stain frozen hippocampal rat brain sections and to permit systematic counts of stained, injured neurons at 4 and 24 h after mild, moderate or severe fluid percussion traumatic brain injury (TBI). In adjacent sections, laser capture microdissection was used to collect uninjured (FJ negative) CA3 hippocampal neurons to assess the effect of injury severity on mRNA levels of selected genes. Rats were anesthetized, intubated, mechanically ventilated and randomized to sham, mild (1.2 atm), moderate (2.0 atm) or severe (2.3 atm) TBI. Four or 24 h post-TBI, ten frozen sections (10 microm thick, every 15th section) were collected from the hippocampus of each rat, stained with FJ and counterstained with cresyl violet. Fluoro-Jade-positive neurons were counted in hippocampal subfields CA1, CA3 and the dentate gyrus/dentate hilus. At both 4 and 24 h post-TBI, numbers of FJ-positive neurons in all hippocampal regions increased dose-dependently in mildly and moderately injured rats but were not significantly more numerous after severe injury. Although analysis of variance demonstrated no overall difference in expression of mRNA levels for heat shock protein 70, bcl-2, caspase 3, caspase 9 and interleukin-1beta in uninjured CA3 neurons at all injury levels, post hoc analysis suggested that TBI induces increases in neuroprotective gene expression that offset concomitant increases in deleterious gene expression.     

A forensic peer group approach to bullying after traumatic brain injury

A forensic peer group programme adapted for bullying behaviour and antisocial attitudes in three young men with traumatic brain injury (TBI) is presented. Three TBI clients who had previously been resistant to an intensive neurobehavioural rehabilitation residential programme were enrolled into the EQUIP programme. EQUIP focused on teaching pro-social skills as they related to aggression, increasing moral development, and altering pro-aggressive attitudes. The group ran four days per week over six weeks, with each session lasting 30 minutes. Post-group assessment indicated that two of the three participants altered their beliefs regarding antisocial behaviour. At three-month follow up, of the two who demonstrated change one had returned to baseline while the other had maintained his progress. Aggression and bullying behaviour reduced in all three clients during the EQUIP programme and these improvements were maintained at three-month follow up. Self-esteem measures did not alter across the assessment period. Antisocial beliefs and their potential for change in clients with severe TBI are discussed.     

A forensic peer group approach to bullying after traumatic brain injury

A forensic peer group programme adapted for bullying behaviour and antisocial attitudes in three young men with traumatic brain injury (TBI) is presented. Three TBI clients who had previously been resistant to an intensive neurobehavioural rehabilitation residential programme were enrolled into the EQUIP programme. EQUIP focused on teaching pro-social skills as they related to aggression, increasing moral development, and altering pro-aggressive attitudes. The group ran four days per week over six weeks, with each session lasting 30 minutes. Post-group assessment indicated that two of the three participants altered their beliefs regarding antisocial behaviour. At three-month follow up, of the two who demonstrated change one had returned to baseline while the other had maintained his progress. Aggression and bullying behaviour reduced in all three clients during the EQUIP programme and these improvements were maintained at three-month follow up. Self-esteem measures did not alter across the assessment period. Antisocial beliefs and their potential for change in clients with severe TBI are discussed.     

Microglia/macrophage polarization dynamics in white matter after traumatic brain injury

Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT–PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation–induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment.     

Default mode network connectivity predicts sustained attention deficits after traumatic brain injury

Traumatic brain injury (TBI) frequently produces impairments of attention in humans. These can result in a failure to maintain consistent goal-directed behavior. A predominantly right-lateralized frontoparietal network is often engaged during attentionally demanding tasks. However, lapses of attention have also been associated with increases in activation within the default mode network (DMN). Here, we study TBI patients with sustained attention impairment, defined on the basis of the consistency of their behavioral performance over time. We show that sustained attention impairments in patients are associated with an increase in DMN activation, particularly within the precuneus and posterior cingulate cortex. Furthermore, the interaction of the precuneus with the rest of the DMN at the start of the task, i.e., its functional connectivity, predicts which patients go on to show impairments of attention. Importantly, this predictive information is present before any behavioral evidence of sustained attention impairment, and the relationship is also found in a subgroup of patients without focal brain damage. TBI often results in diffuse axonal injury, which produces cognitive impairment by disconnecting nodes in distributed brain networks. Using diffusion tensor imaging, we demonstrate that structural disconnection within the DMN also correlates with the level of sustained attention. These results show that abnormalities in DMN function are a sensitive marker of impairments of attention and suggest that changes in connectivity within the DMN are central to the development of attentional impairment after TBI.     

Neuroendocrine disorders after traumatic brain injury

Traumatic brain injury (TBI) is the most common cause of death and disability in young adults living in industrialised countries, in which 180-250 persons per 100 000 per year die or are hospitalised as a result. Neuroendocrine derangements after TBI have received increasing recognition in recent years because of their potential contribution to morbidity, and possibly mortality, after trauma. Marked changes of the hypothalamo-pituitary axis have been documented in the acute phase of TBI, with as many as 80% of patients showing evidence of gonadotropin deficiency, 18% of growth hormone deficiency, 16% of corticotrophin deficiency and 40% of patients demonstrating vasopressin abnormalities leading to diabetes insipidus or the syndrome of inappropriate anti-diuresis. Longitudinal prospective studies have shown that some of the early abnormalities are transient, whereas new endocrine dysfunctions become apparent in the post-acute phase. There remains a high frequency of hypothalamic-pituitary hormone deficiencies among long-term survivors of TBI, with approximately 25% patients showing one or more pituitary hormone deficiencies. This is a higher frequency than previously thought and suggests that most cases of post-traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. PTHP has been associated with adverse outcome both in the acute and chronic phases after injury. These data underscore the need for the identification and appropriate timely management of hormone deficiencies, in order to optimise patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated hypopituitarism.     

Bipolar disorder after traumatic brain injury

Objective. We report the case of a 47-year-old man with no psychiatric antecedents who developed manic and depressive symptoms after traumatic brain injury (TBI). Methods and results. Findings on neurobehavioral examination, neuropsychological test battery, electrophysiological and imaging exams suggested the presence of a diffuse cerebral injury with a predominance of left fronto-temporal findings. Conclusions. This case demonstrates that TBI may cause vulnerability to psychiatric disorders, with long latency periods, and that its course may be independent of cognitive impairment and recovery.     

Obsessive-compulsive disorder after traumatic brain injury

Traumatic brain injury (?TBI) neuropsychiatric sequelae are a significant cause of morbidity in TBI victims. Among the recognized sequelae are anxiety, obsessions, compulsions and obsessive-compulsive disorder (OCD). This review addresses the emergence of OCD and OCD symptoms after TBI with an emphasis on neural circuits that underlie OCD symptom expression that may be affected by the injury. Current studies suggest that post-TBI emergent psychopathology, including OCD, is influenced by underlying sub-clinical diathesis, brain injury lesions sites, environmental stressors and the rehabilitation process. Pre-morbid status can be obtained by structured psychiatric interviews, and TBI brain lesions can be defined with advanced neuroimaging techniques. This information along with the management of family and environmental stressors and the enhanced clinical identification of symptoms of anxiety and OCD can be used in the rehabilitation process to improve prognosis after TBI.     

Dysautonomia after severe traumatic brain injury

Background: Dysautonomia after traumatic brain injury (TBI) is characterized by episodes of increased heart rate, respiratory rate, temperature, blood pressure, muscle tone, decorticate or decerebrate posturing, and profuse sweating. This study addresses the incidence of dysautonomia after severe TBI, the clinical variables that are associated with dysautonomia, and the functional outcome of patients with dysautonomia. Methods: A historic cohort study in patients with severe TBI [Glasgow Coma Scale (GCS) ≤ 8 on admission]. Results: Seventy‐six of 119 patients survived and were eligible for follow‐up. The incidence of dysautonomia was 11.8%. Episodes of dysautonomia were prevalent during a mean period of 20.1 days (range 3–68) and were often initiated by discomfort. Patients with dysautonomia showed significant longer periods of coma (24.78 vs. 7.99 days) and mechanical ventilation (22.67 vs. 7.21 days). Dysautonomia was associated with diffuse axonal injury (DAI) [relative risk (RR) 20.83, CI 4.92–83.33] and the development of spasticity (RR 16.94, CI 3.96–71.42). Patients with dysautonomia experienced more secondary complications. They tended to have poorer outcome. Conclusions: Dysautonomia occurs in approximately 10% of patients surviving severe TBI and is associated with DAI and the development of spasticity at follow‐up. The initiation of dysautonomia by discomfort supports the Excitatory: Inhibitory Ratio model as pathophysiological mechanism.     

Obsessive-compulsive disorder after traumatic brain injury

Traumatic brain injury ( TBI) neuropsychiatric sequelae are a significant cause of morbidity in TBI victims. Among the recognized sequelae are anxiety, obsessions, compulsions and obsessive-compulsive disorder (OCD). This review addresses the emergence of OCD and OCD symptoms after TBI with an emphasis on neural circuits that underlie OCD symptom expression that may be affected by the injury. Current studies suggest that post-TBI emergent psychopathology, including OCD, is influenced by underlying sub-clinical diathesis, brain injury lesions sites, environmental stressors and the rehabilitation process. Pre-morbid status can be obtained by structured psychiatric interviews, and TBI brain lesions can be defined with advanced neuroimaging techniques. This information along with the management of family and environmental stressors and the enhanced clinical identification of symptoms of anxiety and OCD can be used in the rehabilitation process to improve prognosis after TBI.     

Rehabilitation outcome after traumatic brain injury

Rehabilitation goals after traumatic brain injury are improving function, increasing the level of independence as high as possible, preventing complications and providing an acceptable environment to the patient. Several complications can be encountered during the rehabilitation period which lead to physical, cognitive and neurobehavioral impairments that cause major delay in functional improvement. This prospective study was designed in order to investigate the complications and their relations with functional recovery in patients that were included in the acute phase of a rehabilitation program. Thirty traumatic brain injured patients admitted to the Intensive Care Units of Uludag University School of Medicine were included in the study. Rehabilitation program consisted in appropriate positioning, range of motion exercises, postural drainage and respiratory exercises. Complications that were encountered during intensive care rehabilitation program were recorded. All patients were evaluated by Functional Independence Measure, Disability Rating Scale and Ranchos Los Amigos Levels of Cognitive Function Scale at admission and discharge. Improvement was observed in patients in terms of functional outcome and disability levels. Pneumonia, athelectasis, anemia and meningitis were the most frequent complications. Deterioration in functional outcome and disability levels was noted as the number of these complications increased. In conclusion, rehabilitation has an important role in the management of traumatic brain injured patients. Reduction of frequency of complications and improvement in functional outcome and disability levels can be achieved through rehabilitation programs. Long-term controlled studies with large number of patients are needed in order to obtain accurate data on factors associated with rehabilitation outcomes.     

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.     

Pituitary insufficiency after traumatic brain injury

After traumatic brain injury (TBI), patients present with psychological disorders that may be explained by post-traumatic pituitary insufficiency (PI). The goal of this study was to determine the relationship between hypopituitarism, neuropsychological changes and findings on CT scans after TBI. Hospital charts of 55 TBI patients were screened for age, Glasgow Coma Scale (GSC) score, hypoxia or hypotension. The first two CT scans were analyzed for hemorrhagic lesions. Basal levels of the following hormones were recorded: cortisol, prolactin, estradiol, testosterone, insulin-like growth factor 1 and free thyroxine. Hormonal stimulation tests were performed either if the basal hormone screening revealed an abnormality or if the patient answered “yes” to at least one question in the non-evaluated neuropsychological questionnaire. Overall, 14 out of 55 patients (25.4%) presented with PI; one of them with two hormonal deficits. Growth hormone deficit, hypothyroidism and hypocortisolism were found in one, one and two patients, respectively. Neuropsychological complaints were present in 67% of the patients and were associated with intracerebral hemorrhagic lesions and not PI. Neuropsychological complaints after TBI are more frequent than PI. Brain tissue damage is most important than PI in the development of psychological changes after TBI.