Case Report: An MRI Traumatic Brain Injury Longitudinal Case Study at 7 Tesla: Pre- and Post-injury Structural Network and Volumetric Reorganization and Recovery.

Importance: A significant limitation of many neuroimaging studies examining mild traumatic brain injury (mTBI) is the unavailability of pre-injury data. Objective: We therefore aimed to utilize pre-injury ultra-high field brain MRI and compare a collection of neuroimaging metrics pre- and post-injury to determine mTBI related changes and evaluate the enhanced sensitivity of high-resolution MRI. Design: In the present case study, we leveraged multi-modal 7 Tesla MRI data acquired at two timepoints prior to mTBI (23 and 12 months prior to injury), and at two timepoints post-injury (2 weeks and 8 months after injury) to examine how a right parietal bone impact affects gross brain structure, subcortical volumetrics, microstructural order, and connectivity. Setting: This research was carried out as a case investigation at a single primary care site. Participants: The case participant was a 38-year-old female selected for inclusion based on a mTBI where a right parietal impact was sustained. Main outcomes: The main outcome measurements of this investigation were high spatial resolution structural brain metrics including volumetric assessment and connection density of the white matter connectome. Results: At the first scan timepoint post-injury, the cortical gray matter and cerebral white matter in both hemispheres appeared to be volumetrically reduced compared to the pre-injury and subsequent post-injury scans. Connectomes produced from whole-brain diffusion-weighted probabilistic tractography showed a widespread decrease in connectivity after trauma when comparing mean post-injury and mean pre-injury connection densities. Findings of reduced fractional anisotropy in the cerebral white matter of both hemispheres at post-injury time point 1 supports reduced connection density at a microstructural level. Trauma-related alterations to whole-brain connection density were markedly reduced at the final scan timepoint, consistent with symptom resolution. Conclusions and Relevance: This case study investigates the structural effects of traumatic brain injury for the first time using pre-injury and post-injury 7 Tesla MRI longitudinal data. We report findings of initial volumetric changes, decreased structural connectivity and reduced microstructural order that appear to return to baseline 8 months post-injury, demonstrating in-depth metrics of physiological recovery. Default mode, salience, occipital, and executive function network alterations reflect patient-reported hypersomnolence, reduced cognitive processing speed and dizziness

The chronic and evolving neurological consequences of traumatic brain injury.

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population

Prior history of traumatic brain injury among persons in the Traumatic Brain Injury Model Systems National Database

OBJECTIVE: To determine the association between demographic, psychosocial, and injury-related characteristics and traumatic brain injury (TBI) occurring prior to a moderate or severe TBI requiring rehabilitation. DESIGN: Secondary data analysis. SETTING: TBI Model System inpatient rehabilitation facilities. PARTICIPANTS: Persons (N=4464) 1, 2, 5, 10, 15, or 20 years after TBI resulting in participation in the TBI Model System National Database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: History of TBI prior to the TBI Model System Index injury, pre-Index injury demographic and behavioral characteristics, Index injury characteristics, post-Index injury behavioral health and global outcome. RESULTS: Twenty percent of the cohort experienced TBIs preceding the TBI Model System Index injury-80% of these were mild and 40% occurred before age 16. Pre- and post-Index injury behavioral issues, especially substance abuse, were highly associated with having had a prior TBI. Greater severity of the pre-Index injury as well as occurrence before age 6 often showed stronger associations. Unexpectedly, pre-Index TBI was associated with less severe Index injuries and better functioning on admission and discharge from rehabilitation. CONCLUSIONS: Findings suggest that earlier life TBI may have important implications for rehabilitation after subsequent TBI, especially for anticipating behavioral health issues in the chronic stage of recovery. Results provide additional evidence for the potential consequences of early life TBI, even if mild

The Longitudinal Effects of Comorbid Health Burden on Functional Outcomes for Adults With Moderate to Severe Traumatic Brain Injury

Objective: To evaluate the impact of physical, mental, and total health condition burden on functional outcome and life satisfaction up to 10 years after moderate to severe traumatic brain injury (TBI). Setting: Six TBI Model Systems centers. Participants: Three hundred ninety-three participants in the TBI Model Systems National Database. Design: Retrospective cohort study. Main measures: Self-reported physical and mental health conditions at 10 years postinjury. Functional Independence Measure Motor and Cognitive subscales and the Satisfaction With Life Scale measured at 1, 2, 5, and 10 years. Results: In 10-year longitudinal individual growth curve models adjusted for covariates and inverse probability weighted to account for selection bias, greater physical and mental health comorbidity burden was negatively associated with functional cognition and life satisfaction trajectories. Physical, but not mental, comorbidity burden was negatively associated with functional motor trajectories. Higher total health burden was associated with poorer functional motor and cognitive trajectories and lower life satisfaction. Conclusions: This study offers evidence that comorbidity burden negatively impacts longitudinal functional and life satisfaction outcomes after TBI. The findings suggest that better identification and treatment of comorbidities may benefit life satisfaction, functional outcome, reduce healthcare costs, and decrease reinjury. Specific guidelines are needed for the management of comorbidities in TBI populations

Alzheimer's Disease-Related Dementias Summit 2022: National Research Priorities for the Investigation of Post-Traumatic Brain Injury Alzheimer's Disease and Related Dementias

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and to assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including common data elements (CDEs) for ante-mortem and post-mortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression, and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure, to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways

Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome

Background and Purpose—Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. Methods—A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Results—Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, −16.8 to −9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3–2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1–23.4; P<0.001). Conclusions—Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events

The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies

Intimate partner violence, substance use, and health comorbidities among women: A narrative review

Exposure to intimate partner violence (IPV), including physical, sexual, and psychological violence, aggression, and/or stalking, impacts overall health and can have lasting mental and physical health consequences. Substance misuse is common among individuals exposed to IPV, and IPV-exposed women (IPV-EW) are at-risk for transitioning from substance misuse to substance use disorder (SUD) and demonstrate greater SUD symptom severity; this too can have lasting mental and physical health consequences. Moreover, brain injury is highly prevalent in IPV-EW and is also associated with risk of substance misuse and SUD. Substance misuse, mental health diagnoses, and brain injury, which are highly comorbid, can increase risk of revictimization. Determining the interaction between these factors on the health outcomes and quality of life of IPV-EW remains a critical need. This narrative review uses a multidisciplinary perspective to foster further discussion and research in this area by examining how substance use patterns can cloud identification of and treatment for brain injury and IPV. We draw on past research and the knowledge of our multidisciplinary team of researchers to provide recommendations to facilitate access to resources and treatment strategies and highlight intervention strategies capable of addressing the varied and complex needs of IPV-EW

Longitudinal Effects of Medical Comorbidities on Functional Outcome and Life Satisfaction After Traumatic Brain Injury: An Individual Growth Curve Analysis of NIDILRR Traumatic Brain Injury Model System Data

Objective: To explore associations of specific physical and neuropsychiatric medical conditions to motor and cognitive functioning and life satisfaction over the first 10 years following traumatic brain injury (TBI). Setting: Telephone follow-up through six TBI Model System centers. Participants: 404 individuals or proxies with TBI enrolled in the TBI Model System longitudinal study participating in 10 year follow-up. Design: Individual growth curve analysis. Main Measures: FIM™ Motor and Cognitive subscales, Life Satisfaction Scales, Medical and Mental Health Co-Morbidities Interview. Results: Hypertension, diabetes, cancers, rheumatoid arthritis, and anxiety negatively affected the trajectory of motor functioning over time. Diabetes, cancers, chronic bronchitis, anxiety, and depression negatively impacted cognitive functioning. Numerous neuropsychiatric conditions (sleep disorder, alcoholism, drug addiction, anxiety, panic attacks, PTSD, depression, bipolar disorder), as well as hypertension, liver disease, and cancers diminished life satisfaction. Other medical conditions had a negative effect on functioning and satisfaction at specific follow-up periods. Conclusion: Natural recovery after TBI may include delayed onset of functional decline or early recovery followed by progressive deterioration and is negatively affected by medical comorbidities. Results contribute to the growing evidence that TBI is most appropriately treated as a chronic medical condition complicated by a variety of comorbid conditions

Prevalence of Medical and Psychiatric Comorbidities Following Traumatic Brain Injury

Objective: To examine the prevalence of selected medical and psychiatric comorbidities that existed prior to, or up to 10 years following, traumatic brain injury (TBI) requiring acute rehabilitation. Design: Retrospective cohort. Setting: Six TBI Model Systems centers. Participants: 404 participants in the TBI Model System National Database who experienced TBI 10 years prior. Interventions: Not applicable. Main Outcome Measure: Self-reported medical and psychiatric comorbidities and the onset time of each endorsed comorbidity. Results: At 10 years post-injury, the most common comorbidities developing post-injury, in order, were: back pain, depression, hypertension, anxiety, fractures, high blood cholesterol, sleep disorders, panic attacks, osteoarthritis, and diabetes. Comparing those 50 years and older to those less than 50 years, diabetes (OR = 3.54; p = 0.0016), high blood cholesterol (OR = 2.04; p = 0.0092), osteoarthritis (OR = 2.02; p = 0.0454), and hypertension (OR = 1.84; p = 0.0175) were significantly more prevalent in the older cohort while panic attacks (OR = 0.33; p = 0.0022) were significantly more prevalent in the younger cohort. No significant differences in prevalence rates between the older and younger cohorts were found for back pain, depression, anxiety, fractures, or sleep disorders. Conclusions: People with moderate-severe TBI experience other medical and mental health comorbidities during the long-term course of recovery and life after injury. The findings can inform further investigation into comorbidities associated with TBI and the role of medical care, surveillance, prevention, lifestyle, and healthy behaviors in potentially modifying their presence and/or prevalence over the life span