Sensory Sensitivity in TBI: Implications for Chronic Disability.

PURPOSE OF REVIEW: This review investigates the relationship between sensory sensitivity and traumatic brain injury (TBI), and the role sensory sensitivity plays in chronic disability. RECENT FINDINGS: TBI is a significant cause of disability with a range of physical, cognitive, and mental health consequences. Sensory sensitivities (e.g., noise and light) are among the most frequently reported, yet least outwardly recognizable symptoms following TBI. Clinicians and scientists alike have yet to identify consistent nomenclature for defining noise and light sensitivity, making it difficult to accurately and reliably assess their influence. Noise and light sensitivity can profoundly affect critical aspects of independent function including communication, productivity, socialization, cognition, sleep, and mental health. Research examining the prevalence of sensory sensitivity and evidence for the association of sensory sensitivity with TBI is inconclusive. Evidence-based interventions for sensory sensitivity, particularly following TBI, are lacking.

Pain and chronic mild traumatic brain injury in the US military population: a Chronic Effects of Neurotrauma Consortium study.

PRIMARY OBJECTIVES: To describe the association between mild traumatic brain injury (mTBI) and pain intensity and pain interference outcomes while accounting for potential confounders and mediators including environmental factors and comorbidities in a cohort of US Veterans of the Iraq and Afghanistan wars. RESEARCH DESIGN: Cross-sectional snapshot of baseline data from a prospective, longitudinal study. METHODS: Effects of mTBI on pain intensity and pain interference were compared between participants with or without mTBI exposure. Data were analysed using covariate-adjusted regression analyses as well as structural equation modelling (SEM) methods to assess the robustness of findings across different modelling assumptions. As results of the two approaches were consistent with respect to the overall association between mTBI exposure and pain, the results focus primarily on the SEM findings. RESULTS: The mTBI exposed group reported significantly greater indices of post-traumatic stress disorder (PTSD), depression, anxiety and sleep disturbance. After accounting for other factors, mTBI exposure was significantly, but indirectly associated with the pain interference and pain intensity outcomes. CONCLUSIONS: mTBI is strongly associated with pain intensity and pain interference in this sample. However, the effect appears to be mediated by other common mTBI comorbidities: PTSD, depression, anxiety and sleep disturbance.

Suicide and Chronic Traumatic Encephalopathy.

For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships.

Beta-amyloid deposition in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid ß peptide (Aß) levels, the extent of Aß deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Aß deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Aß deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Aß deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p < 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Aß plaques and those without. Aß deposition was significantly associated with the presence of the APOE ε4 allele (p = 0.035), older age at symptom onset (p < 0.001), and older age at death (p < 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (ß = 2.43, p = 0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR = 4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE and AD, and in these subjects both Aß plaques and total levels of Aß1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that Aß deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that Aß is associated with both pathological and clinical progression of CTE independent of age.

Chronic traumatic encephalopathy in professional sports: retrospective and prospective views.

PRIMARY OBJECTIVE: The purposes of this paper are to review: (1) the history of chronic traumatic encephalopathy (CTE) in sports, (2) the similarities and differences between historic and current definitions of CTE, (3) recent epidemiology and cohort studies of CTE and (4) controversies regarding the current CTE positions. RESEARCH DESIGN: Not applicable. METHODS AND PROCEDURES: Selective review of published articles relevant to CTE. MAIN OUTCOME AND RESULTS: The current definitions of CTE have evolved from its original definition and now rely heavily on the post-mortem detection of hyperphosphorylated tau for diagnosis. As of 2013, there is a blended cohort of 110 professional athletes diagnosed with CTE. It is being assumed that concussions and/or sub-concussive impacts in contact sports are the sole cause of CTE. CONCLUSIONS: There are multiple causes of abnormal tau protein deposition in the human brain and the pathogenesis of CTE may not be related solely to concussion and/or sub-concussive injury. In all likelihood, the causes of CTE are a multivariate, as opposed to a univariate, phenomenon.

Military traumatic brain injury: a review.

Military mild traumatic brain injury (mTBI) differs from civilian injury in important ways. Although mTBI sustained in both military and civilian settings are likely to be underreported, the combat theater presents additional obstacles to reporting and accessing care. The impact of blast forces on the nervous system may differ from nonblast mechanisms, mTBI although studies comparing the neurologic and cognitive sequelae in mTBI survivors have not provided such evidence. However, emotional distress appears to figure prominently in symptoms following military mTBI. This review evaluates the extant literature with an eye towards future research directions.

Chronic traumatic encephalopathy and the availability cascade.

Chronic traumatic encephalopathy (CTE) in sports has been known for > 85 years, and has experienced a resurgence of interest over the past decade, both in the media and in the scientific community. However, there appears to be a disconnection between the public's perception of CTE and the currently available scientific data. The cognitive bias known as the "availability cascade" has been suggested as a reason to explain this rift in knowledge. This review summarizes and updates the history of CTE in sports, discusses recent epidemiological and autopsy studies, summarizes the evidence base related to CTE in sports, and offers recommendations for future directions.

Modern chronic traumatic encephalopathy in retired athletes: what is the evidence?

It has been theorized that a career in contact sports may be associated with long-term neurodegenerative changes. This idea dates as far back as the 1920s, was initially reported in boxers, colloquially termed 'punch drunk,' later more formally termed dementia pugilistica (DP), and now coined chronic traumatic encephalopathy (CTE). Despite considerable ongoing interest on this topic, there is so far only limited evidence showing an association between sport-related concussion (SRC) and increased risk for late-life cognitive and neuropsychiatric impairment, with no causality or risk factors yet determined. The modern CTE description is nevertheless proposed as a unique tauopathy with characteristic pathological stages occurring in retired athletes who have experienced previous repetitive brain trauma. This review highlights the principal issues that so far preclude firm conclusions about the association of athletic head trauma and neurodegenerative diseases of any type. We consider alternative interpretations that may contribute to the clinical progressive neurological findings in some athletes and recommend carefully-controlled epidemiological work to overcome current limitations in this area of research and stimulate future research.

Chronic traumatic encephalopathy: where are we and where are we going?

Chronic traumatic encephalopathy (CTE, previously called punch drunk and dementia pugilistica) has a rich history in the medical literature in association with boxing, but has only recently been recognized with other contact sports, such as football and ice hockey, as well as with military blast injuries. CTE is thought to be a neurodegenerative disease associated with repeated concussive and subconcussive blows to the head. There is characteristic gross and microscopic pathology found in the brain, including frontal and temporal atrophy, axonal degeneration, and hyperphosphorylated tau and TAR DNA-binding protein 43 pathology. Clinically, there are characteristic progressive deficits in cognition (memory, executive dysfunction), behavior (explosivity, aggression), mood (depression, suicidality), and motor function (parkinsonism), which correlate with the anatomic distribution of brain pathology. While CTE shares clinical and neuropathological traits with other neurodegenerative diseases, the clinical syndrome and the neuropathology as a whole are distinct from other neurodegenerative diseases. Here we review the CTE literature to date. We also draw on the literature from mild traumatic brain injury and other neurodegenerative dementias, particularly when these studies provide guidance for future CTE research. We conclude by suggesting seven essential areas for future CTE research.

Heart rate variability biofeedback, executive functioning and chronic brain injury.

PRIMARY OBJECTIVE: To determine if individuals with brain injury can modify heart rate variability (HRV) through biofeedback and, if so, enhance its pattern to improve emotional regulation and problem-solving ability. DESIGN: A quasi-experimental design with repeated measures was employed. Thirteen individuals aged 23-63 years with severe brain injury (13-40 years post-onset) participating in a community-based programme were enrolled. MAIN OUTCOMES: Response-to-treatment was measured with HRV indices, Behavior Rating Inventory of Executive Function (BRIEF-A-Informant) and attention/problem-solving tests. RESULTS: At post-treatment, HRV indices (Low Frequency/High Frequency [LF/HF] and coherence ratio) increased significantly. Increased LF/HF values during the second-half of a 10-minute session were associated with higher attention scores. Participants who scored better (by scoring lower) in informant ratings at pre-treatment had highest HRV scores at post-treatment. Accordingly, at post-treatment, families' ratings of participants' emotional control correlated with HRV indices; staffs' ratings of participants' working memory correlated with participants' HRV indices. Self-ratings of the BRIEF-A Task Monitoring scale at post-treatment correlated with family ratings at pre-treatment and post-treatment. CONCLUSIONS: Results demonstrate an association between regulation of emotions/cognition and HRV training. Individuals with severe, chronic brain injury can modify HRV through biofeedback. Future research should evaluate the efficacy of this approach for modifying behavioural problems.

Increased risk of schizophrenia following traumatic brain injury: a 5-year follow-up study in Taiwan.

BACKGROUND: Whether traumatic brain injury (TBI) is an independent risk factor for the subsequent development of schizophrenia has evoked considerable controversy. No evidence has been previously reported from Asia. This study estimated the risk of schizophrenia during a 5-year period following hospital admission for TBI relative to a comparison group of non-TBI patients during the same period in Taiwan. METHOD: Two datasets were linked: the Traumatic Brain Injury Registry and the Taiwan National Health Insurance Research Dataset. A total of 3495 patients hospitalized with a diagnosis of TBI from 2001 to 2002 were included, together with 17 475 non-TBI patients as the comparison group, matched on sex, age, and year of TBI hospitalization. Each individual was followed for 5 years to identify any later diagnosis of schizophrenia. Cox proportional hazard regressions were performed for analysis. RESULTS: During the 5-year follow-up period, patients who had suffered TBI were independently associated with a 1.99-fold (95% confidence interval 1.28-3.08) increased risk of subsequent schizophrenia, after adjusting for monthly income and residential geographical location. The severity and type of TBI was not associated with the subsequent development of schizophrenia. CONCLUSIONS: Our findings add important evidence from Asia and suggest a potential link between TBI and schizophrenia. Our study suggests that clinicians and family members should be alert to possible neuropsychiatric conditions following TBI.

Sleep-wake disturbances 3 years after traumatic brain injury.

BACKGROUND: 6 months after traumatic brain injury (TBI), almost three out of four patients suffer from sleep-wake disturbances (SWD) such as post-traumatic hypersomnia (increased sleep need of ≥2 h compared with before injury), excessive daytime sleepiness (EDS), fatigue and insomnia. The long-term course of post-traumatic SWD, however, is unknown. OBJECTIVES: To assess the prevalence and characteristics of post-traumatic SWD 3 years after trauma. DESIGN: Prospective longitudinal clinical study in 51 consecutive TBI patients (43 males, eight females, mean age 40±16 years). MAIN OUTCOME MEASURES: EDS (as assessed by the Epworth sleepiness scale), fatigue (fatigue severity scale), post-traumatic hypersomnia (sleep length per 24 h), insomnia, depression and anxiety. RESULTS: Post-traumatic SWD were found in 34 patients (67%): post-traumatic hypersomnia in 14 (27%), EDS in six (12%), fatigue in 18 patients (35%) and insomnia in five patients (10%). SWD were not associated with severity or localisation of, or time interval since, TBI. Insomnia was linked to depressive symptoms. CONCLUSIONS: This prospective study shows that 3 years after TBI, two out of three patients suffer from residual SWD, particularly fatigue and post-traumatic hypersomnia. In 45% of TBI patients, SWD appear directly related to the trauma itself.

Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic.

BACKGROUND: Traumatic brain injury (TBI) is a significant public health concern. According to the Centers for Disease Control and Prevention, about 1.4 million people in the United States sustain a TBI annually. OBJECTIVE: This review places particular emphasis on the current knowledge of effective treatment of TBI symptoms, and proposes directions for future research. RESULTS: Neuropsychiatric problems are more prevalent and longer-lasting in TBI patients than in the general population. About 40% of TBI victims suffer from two or more psychiatric disorders, and a similar percentage experience at least one unmet need for cognitive, emotional, or job assistance 1 year after injury. The entire spectrum of TBI severity, from mild to severe, is associated with an increase in psychiatric conditions. CONCLUSION: Despite the high incidence of severe consequences of TBI, there are scarce empirical data to guide psychiatric treatment. Some approaches that have been helpful include cognitive and behavioral therapy and pharmacologic treatment. The authors list specific research recommendations that could further identify useful therapeutic interventions.

Psychiatric disorders following traumatic brain injury: their nature and frequency.

OBJECTIVES: To retrospectively establish the nature and frequency of Axis I psychiatric disorders pre- and post-TBI. PARTICIPANTS: One hundred participants who were 0.5 to 5.5 years post mild to severe TBI and 87 informants, each evaluated at a single time point. MAIN MEASURE: The Structured Clinical Interview for DSM-IV Disorders (SCID-I). RESULTS: Preinjury, 52% received a psychiatric diagnosis, most commonly substance use disorder (41%), followed by major depressive disorder (17%) and anxiety (13%). Postinjury, 65% received a diagnosis, of which major depression became the most common (45%), followed by anxiety (38%) and substance use disorder (21%). Frequency of depression, generalized anxiety disorder, posttraumatic stress disorder, panic disorder, and phobias rose from preinjury to postinjury. More than two-thirds of postinjury depression and anxiety cases were novel and showed poor resolution rates. Few novel cases of substance use disorder were noted. Psychotic disorders, somatoform disorders, and eating disorders occurred at frequencies similar to those in the general population. CONCLUSIONS: A high frequency of postinjury psychiatric disorders was evident up to 5.5 years postinjury, with many novel cases of depression and anxiety. Individuals with TBI should be screened for psychiatric disorders at various time points post-injury without reliance on history of psychiatric problems to predict who is at risk, so that appropriate intervention can be offered.

Major depression following traumatic brain injury.

BACKGROUND: Major depression is a frequent psychiatric complication among patients with traumatic brain injury (TBI). To our knowledge, however, the clinical correlates of major depression have not been extensively studied. OBJECTIVE: To determine the clinical, neuropsychological, and structural neuroimaging correlates of major depression occurring after TBI. DESIGN: Prospective, case-controlled, surveillance study conducted during the first year after the traumatic episode occurred. Settings University hospital level I trauma center and a specialized rehabilitation unit. METHODS: The study group consisted of 91 patients with TBI. In addition, 27 patients with multiple traumas but without evidence of central nervous system injury constituted the control group. The patients' conditions were evaluated at baseline and at 3, 6, and 12 months after the traumatic episode. Psychiatric diagnosis was made using a structured clinical interview and DSM-IV criteria. Neuropsychological testing and quantitative magnetic resonance imaging were performed at the 3-month follow-up visit. RESULTS: Major depressive disorder was observed in 30 (33%) of 91 patients during the first year after sustaining a TBI. Major depressive disorder was significantly more frequent among patients with TBI than among the controls. Patients with TBI who had major depression were more likely to have a personal history of mood and anxiety disorders than patients who did not have major depression. Patients with major depression exhibited comorbid anxiety (76.7%) and aggressive behavior (56.7%). Patients with major depression had significantly greater impairment in executive functions than their nondepressed counterparts. Major depression was also associated with poorer social functioning at the 6-and 12-month follow-up, as well as significantly reduced left prefrontal gray matter volumes, particularly in the ventrolateral and dorsolateral regions. CONCLUSIONS: Major depression is a frequent complication of TBI that hinders a patient's recovery. It is associated with executive dysfunction, negative affect, and prominent anxiety symptoms. The neuropathological changes produced by TBI may lead to deactivation of lateral and dorsal prefrontal cortices and increased activation of ventral limbic and paralimbic structures including the amygdala.

Psychiatric illness following traumatic brain injury in an adult health maintenance organization population.

BACKGROUND: Psychiatric illness after traumatic brain injury (TBI) has been shown to be prevalent in hospitalized and tertiary care patient populations. OBJECTIVE: To determine the risk of psychiatric illness after TBI in an adult health maintenance organization population. DESIGN: Prospective cohort study. SETTING: Large staff-model health maintenance organization. PARTICIPANTS: Nine hundred thirty-nine health plan members diagnosed as having TBI in 1993 and enrolled in the prior year, during which no TBI was ascertained. Three health plan members per TBI-exposed subject were randomly selected as unexposed comparisons, matched for age, sex, and reference date. MAIN OUTCOME MEASURE: Psychiatric illness in the 3 years after the TBI reference date, determined using computerized records of psychiatric diagnoses according to the International Classification of Diseases, Ninth Revision, Clinical Modification, prescriptions, and service utilization. RESULTS: Prevalence of any psychiatric illness in the first year was 49% following moderate to severe TBI, 34% following mild TBI, and 18% in the comparison group. Among subjects without psychiatric illness in the prior year, the adjusted relative risk for any psychiatric illness in the 6 months following moderate to severe TBI was 4.0 (95% confidence interval [CI], 2.4-6.8) and following mild TBI was 2.8 (95% CI, 2.1-3.7; P<.001) compared with those without TBI. Among subjects with prior psychiatric illness, the adjusted relative risk for any psychiatric illness in the 6 months following moderate to severe TBI was 2.1 (95% CI, 1.3-3.3) and following mild TBI was 1.6 (95% CI, 1.2-2.0; P =.005). Prior psychiatric illness significantly modified the relationship between TBI and subsequent psychiatric illness (P =.04) and was a significant predictor (P<.001). Persons with mild TBI and prior psychiatric illness had evidence of persisting psychiatric illness. CONCLUSIONS: Both moderate to severe and mild TBI are associated with an increased risk of subsequent psychiatric illness. Whereas moderate to severe TBI is associated with a higher initial risk, mild TBI may be associated with persistent psychiatric illness.

The risk of chronic traumatic brain injury in professional boxing: change in exposure variables over the past century.

OBJECTIVES: To determine if boxing exposure has changed over time and hence if current professional boxers are at the same risk of developing chronic traumatic brain injury (CTBI) as historical controls. DESIGN: Literature review of published studies and analysis of data of active professional boxers. SUBJECTS: Professional boxers in the United Kingdom and Australia. MAIN OUTCOME MEASURES: Boxing history and participation in sparring and professional bouts. RESULTS: Since the 1930s, the average duration of a professional boxer's career has dropped from 19 years to five years, and the mean number of career bouts has reduced from 336 to 13. This is despite no significant decline in participation rates from 1931 until 2002. CONCLUSIONS: The incidence of boxing related CTBI will diminish in the current era of professional boxing because of the reduction in exposure to repetitive head trauma and increasing medical monitoring of boxers, with preparticipation medical and neuroimaging assessments resulting in the detection of early and potentially pre-symptomatic cases of CTBI.