Brain Injury Research Articles

Microstructural brain changes following prospective memory rehabilitation in traumatic brain injury: An observational study

ABSTRACT Prospective memory (PM) impairment is a common consequence of moderate-severe traumatic brain injury (TBI). Compensatory strategy training and rehabilitation (COMP) is the usual treatment of PM deficits through environmental modification and the use of assistive methods such as diaries and routines. The study intends to examine the changes in white matter integrity, as measured by advanced diffusion magnetic resonance imaging (dMRI) following COMP intervention in moderate-severe TBI patients. Nine COMP intervention and twelve routine care comparison cohort moderate-severe TBI patients were recruited from level 1 trauma centres in the Brisbane metropolitan area. Both groups were imaged at least one-month post-TBI for a baseline scan. COMP group was imaged again after a 6-week COMP intervention program and the comparison group was imaged again at least 6 weeks after the baseline scan. MRI scan included structural imaging and dMRI, which the latter fitted for the Neurite Orientation Dispersion and Density Imaging (NODDI) model. Only the comparison group had decreased Neurite Density Index in the major white matter tracts and increased isotropic diffusion in the fluid space between the cortical folds. Our results indicated that COMP intervention slowed down the neural degeneration in moderate-severe TBI patients as compared to routine medical care/rehabilitation.

Brain injury in premature infants may be related to abnormal colonization of early gut microbiome.

Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother's body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16S rRNA technology. Fecal samples from typical premature infants (non-brain injury group, n = 17) and those with brain injuries (brain injury group, n = 21) were collected on days 1, 3, and 7 after birth for 16S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms' characteristics and differentiate the microorganisms between the two groups. At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group. Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota.

Minor Head Trauma in Children Younger Than 3 Months and Clinical Predictors of Clinically Important Traumatic Brain Injuries.

Major studies have defined clinical rules to regulate the use of computed tomography in children after head trauma. Infants younger than 3 months are considered at higher risk of brain injuries than older children and at the same time at higher risk of radiation-induced damage. Hence, it would be desirable to have clinical decision rules more adapted to this subset of patients. The objectives of this study are to compare the rate of brain injuries in children younger than 3 months or 3 to 24 months and to assess predictors of clinically important traumatic brain injuries (ciTBIs) (the ones causing death, neurosurgical intervention, long intubation, or hospitalization for 2 days or more) in the former group. Records of children younger than 24 months evaluated in a single emergency department for minor head trauma during a 3 years period were retrospectively reviewed. The rates of brain injuries were compared in children younger or older than 3 months. Variables associated with severe lesions were assessed in younger children. The study included 744 patients, 86 (11.6%) aged 0 to 90 days and 658 (88.4%) aged 91 to 730 days. Within the young group, we found higher rates of traumatic brain injuries (14.0% vs 4.1%, P = 0.0008) and ciTBI (8.1% vs 1.5%, P = 0.002) compared with the old group. A significant correlation with ciTBI in the young group was observed for heart rate (odds ratio [OR], 12.3; 95% confidence interval [CI], 2.4-62.4), nonfrontal scalp hematoma (OR, 9.2; 95% CI, 1.8-46.1), severe mechanism (OR, 5.6; 95% CI, 1.1-27.6), presence of hematoma (OR, 6.1; 95% CI, 1.2-30.0), hematoma size >3 cm (OR, 23.8; 95% CI, 4.2-135.6), and hematoma location (OR, 9.2; 95% CI, 1.8-46.1). Children younger than 3 months presenting after minor head trauma constitute a relevant population. Available clinical predictors well correlate with ciTBIs in this age group.

Long-Term Outcomes After Severe Acute Brain Injury Requiring Mechanical Ventilation: Recovery Trajectories Among Patients and Mental Health Symptoms of Their Surrogate Decision Makers.

Long-term outcomes of patients with severe acute brain injury (SABI) and their surrogate decision makers (SDMs) are insufficiently explored. We conducted a prospective, single-center, observational study of patients with SABI who required mechanical ventilation between September and November 2021. Two telephonic interviews were conducted at 6-12months and 18-24months post SABI. Patients' functional outcomes at both time points were measured on the Glasgow Outcome Scale-Extended and categorized as dead (1), dependent (2-4), or independent (5-8). SDMs were interviewed at 18-24months using validated screening tools for depression, anxiety, and posttraumatic stress disorder and qualitative questions about the hardest challenges during their recovery journey. We included 103 patients (median age 58years, 28% female, 77% White, 51% with stroke, 49% with traumatic brain injury); in-hospital mortality was 46%. At 6-12months and 18-24months, 34% and 36% were independent, respectively; the Glasgow Outcome Scale-Extended score improved ≥ 1 point for 32% between time points. Quality of life was perceived as acceptable for 47% of all survivors and 58% of independent patients by their SDMs. At 18-24months, we reached 56 SDMs (median age 58years, 71% female, 72% White). Symptoms of depression, anxiety, and posttraumatic stress disorder were reported in 18%, 30%, and 7%, respectively (23%, 34%, and 9% in the 35 SDMs of survivors and 10%, 24%, and 5% in the 21 SDMs to deceased patients). Main themes about challenges for patients and SDMs included extrinsic factors related to the health care system, and intrinsic factors related to the brain injury: difficulties in adapting to a new state, mental health symptoms, and social isolation. Mental health symptoms among SDMs of patients with SABI were frequent at 18-24months, and the patients' quality of life was deemed unacceptable for 42% of SDMs to independent survivors. Our findings underscore the need for psychosocial support to SDMs, the importance of addressing modifiable barriers to patient and SDM well-being, and the need for more patient/family-centric outcome measures.

Unsupervised Clustering in Neurocritical Care: A Systematic Review.

Managing patients with acute brain injury in the neurocritical care (NCC) unit has become increasingly complex because of technological advances and increasing information derived from multiple data sources. Diverse data streams necessitate innovative approaches for clinicians to understand interactions between recorded variables. Unsupervised clustering integrates different data streams and could be supportive. Here, we provide a systematic review on the use of unsupervised clustering using NCC data. The primary objective was to provide an overview of clustering applications in NCC studies. As a secondary objective, we discuss considerations for future NCC studies. Databases (Medline, Scopus, Web of Science) were searched for unsupervised clustering in acute brain injury studies including traumatic brain injury (TBI), subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, and hypoxic-ischemic brain injury published until March 13th 2024. We performed the systematic review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We identified 18 studies that used unsupervised clustering in NCC. Predominantly, studies focused on patients with TBI (12 of 18 studies). Multiple research questions used a variety of resource data, including demographics, clinical- and monitoring data, of which intracranial pressure was most oftenincluded (8 of 18 studies). Studies also covered various clustering methods, both traditional methods (e.g., k-means) and advanced methods, which are able to retain the temporal aspect. Finally, unsupervised clustering identified novel phenotypes for clinical outcomes in 9 of 12 studies. Unsupervised clustering can be used to phenotype NCC patients, especially patients with TBI, in diverse disease stages and identify clusters that may be used for prognostication. Despite the need for validation studies, this methodology could help to improve outcome prediction models, diagnostics, and understanding of pathophysiology.Registration number: PROSPERO: CRD4202347097676.

The Role of Cardiolipin in Brain Bioenergetics, Neuroinflammation, and Neurodegeneration.

Cardiolipin (CL) is an essential phospholipid that supports the functions of mitochondrial membrane transporters and oxidative phosphorylation complexes. Due to the high level of fatty acyl chain unsaturation, CL is prone to peroxidation during aging, neurodegenerative disease, stroke, and traumatic brain or spinal cord injury. Therefore, effective therapies that stabilize and preserve CL levels or enhance healthy CL fatty acyl chain remodeling are needed. In the last few years, great strides have been made in determining the mechanisms through which precursors for CL biosynthesis, such as phosphatidic acid (PA), are transferred from the ER to the outer mitochondrial membrane (OMM) and then to the inner mitochondrial membrane (IMM) where CL biosynthesis takes place. Many neurodegenerative disorders show dysfunctional mitochondrial ER contact sites that may perturb PA transport and CL biosynthesis. However, little is currently known on how neuronal mitochondria regulate the synthesis, remodeling, and degradation of CL. This review will focus on recent developments on the role of CL in neurological disorders. Importantly, due to CL species in the brain being more unsaturated and diverse than in other tissues, this review will also identify areas where more research is needed to determine a complete picture of brain and spinal cord CL function so that effective therapeutics can be developed to restore the rates of CL synthesis and remodeling in neurological disorders.

Prediction of Post Traumatic Epilepsy Using MR-Based Imaging Markers.

Post-traumatic epilepsy (PTE) is a debilitating neurological disorder that develops after traumatic brain injury (TBI). Despite the high prevalence of PTE, current methods for predicting its occurrence remain limited. In this study, we aimed to identify imaging-based markers for the prediction of PTE using machine learning. Specifically, we examined three imaging features: Lesion volumes, resting-state fMRI-based measures of functional connectivity, and amplitude of low-frequency fluctuation (ALFF). We employed three machine-learning methods, namely, kernel support vector machine (KSVM), random forest, and an artificial neural network (NN), to develop predictive models. Our results showed that the KSVM classifier, with all three feature types as input, achieved the best prediction accuracy of 0.78 AUC (area under the receiver operating characteristic (ROC) curve) using nested cross-validation. Furthermore, we performed voxel-wise and lobe-wise group difference analyses to investigate the specific brain regions and features that the model found to be most helpful in distinguishing PTE from non-PTE populations. Our statistical analysis uncovered significant differences in bilateral temporal lobes and cerebellum between PTE and non-PTE groups. Overall, our findings demonstrate the complementary prognostic value of MR-based markers in PTE prediction and provide new insights into the underlying structural and functional alterations associated with PTE.

Dexmedetomidine for Craniotomy in Traumatic Brain Injury.

Dexmedetomidine for Craniotomy in Traumatic Brain Injury.

Associations Between Instrumented Mouthguard-Measured Head Acceleration Events and Post-Match Biomarkers of Astroglial and Axonal Injury in MaleAmateur Australian Football Players.

Advances in instrumented mouthguards (iMGs) allow for accurate quantification of single high-acceleration head impacts and cumulative head acceleration exposure in collision sports. However, relationships between these measures and risk of brain cell injury remain unclear. The purpose of this study was to quantify measures of non-concussive head impact exposure and assess their association with blood glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and phosphorylated-tau-181 (p-tau-181) levels in male Australian football players. A total of 31 athletes underwent in-season (24h post-match) and post-season (> 5weeks) blood collections and/or wore HITIQ Nexus A9 iMGs measuring peak linear (PLA) and rotational (PRA) acceleration. Match footage was used to verify and code impacts. Blood GFAP, NfL, and p-tau-181 were quantified using Simoa and natural log transformed for analysis. Associations between post-match biomarkers and within match maximum single impact and cumulative PLA/PRA were assessed with linear mixed models. In-season versus post-season elevations were found for GFAP (mean difference 0.14, 95% CI 0.01-0.26, p = 0.033), NfL (mean difference = 0.21, 95% CI 0.09-0.32, p = 0.001) and p-tau-181 (mean difference = 0.49, 95% CI 0.33-0.65, p < 0.001). Post-match GFAP was associated with maximum single impact PLA (B = 0.003, 95% CI 0.0002-0.005, p = 0.036), cumulative PLA (B = 0.001, 95% CI 0.0002-0.002, p = 0.017), cumulativePRA (B = 0.01, 95% CI 0.002-0.02, p = 0.014), and impact number (B = 0.03, 95% CI 0.003-0.05, p = 0.029) within a single match. Change in NfL levels between two-matches correlated with cumulative PLA (r = 0.80, 95% CI 0.38-0.95, p = 0.005), PRA (r = 0.71, 95% CI 0.19-0.92, p = 0.019) and impact number (r = 0.63, 95% CI 0.05-0.89, p = 0.038). Maximum and cumulative head accelerations in Australian football, measured by iMGs, were associated with elevated blood biomarkers of brain injury, highlighting the potential of both technologies for head impact management in collision sports.

Quantity of Caloric Support After Pediatric Severe Traumatic Brain Injury: Description of Associated Outcomes in a Single Retrospective Center Cohort, 2010–2022

Objectives: To examine the relationship between adequacy of caloric nutritional support during the first week after severe traumatic brain injury (TBI) and outcome. Design: Single-center retrospective cohort, 2010–2022. Setting: Tertiary care children’s hospital with a level 1 trauma center. Patients: Children younger than 18 years with PICU stay greater than 7 days for management of TBI, who had severe TBI, defined as Glasgow Coma Scale (GCS) score less than or equal to 8 at initial presentation and/or placement of an intracranial pressure monitor or external ventricular drain, and/or decompressive hemicraniectomy. Interventions: None. Measurements and Main Results: A total of 93 patients were identified (median age 46 mo; 53% male; median GCS 5; hospital mortality 4%). Caloric goal was assigned by a dietician and the proportion of prescribed calories delivered to each patient over the first 7 days of PICU admission were analyzed. At the end of the first 7 days post-injury, overall median (interquartile range [IQR]) caloric and protein adequacies were 42% (IQR, 28–62%) and 48% (IQR, 29–61%), respectively. We failed to identify an association between adequacy of caloric support and greater odds of higher Functional Status Scale (FSS) score or higher Glasgow Outcome Scale Extended for Pediatrics score at discharge. However, at outpatient follow-up, prior adequacy of PICU caloric support was associated with greater odds of worse FSS (multiplicative increase per 10% increase in calories [MI], 1.10; 95% CI, 1.03–1.18; p = 0.002) and worse GOS E-Peds (MI, 1.16; 95% CI, 1.08–1.27; p &lt; 0.001) at outpatient follow-up. Conclusions: In pediatric patients with severe TBI, there is an association between delivery of a greater proportion of their goal calories during the first 7 days after injury and greater odds of worse outcome at outpatient follow-up.

Factors Influencing Poststroke Cognitive Dysfunction: Cross-Sectional Analysis.

Poststroke cognitive impairment (PSCI) is a common and debilitating complication that affects stroke survivors, impacting memory, attention, and executive function. Despite its prevalence, the factors contributing to PSCI remain unclear, with limited insights into how demographic and clinical variables influence cognitive outcomes. This study investigates the incidence of cognitive impairment in patients with stroke and examines key demographic and clinical factors, such as age, gender, and education level, which contribute to cognitive decline. The aim is to provide a deeper understanding of PSCI to inform early intervention strategies for improving patient outcomes. A cross-sectional study was conducted on 305 patients with ischemic stroke admitted to Zhongda Hospital, Southeast University, from January 2019 to September 2022. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) within 72 hours of hospital admission. Demographic information, including age, gender, and education level, were collected. Statistical analyses were performed using chi-square tests, independent t tests, and multivariate regression to assess the relationship between cognitive function and key variables. Pearson correlation analysis explored associations among age, education, and MMSE scores. Among the 305 patients with stroke, 16.7% (n=51) were diagnosed with cognitive impairment based on MMSE scores. The prevalence of cognitive impairment was slightly higher in males (17.6%, n=159) than females (15.8%, n=146), but this difference was not statistically significant. A strong negative correlation was found between MMSE scores and age (r=-0.32; P<.01), indicating that older patients had lower cognitive function. Education level showed a positive correlation with MMSE scores (r=0.41; P<.01), with patients with higher educational attainment demonstrating better cognitive outcomes. Cognitive function showed a marked decline in patients older than 60 years, particularly in domains such as memory, attention, and language skills. This study confirms that age and education are significant factors in determining cognitive outcomes after stroke. The results align with existing literature showing that cognitive function declines with age, while higher educational attainment serves as a protective factor. The findings suggest that individuals with greater cognitive reserve, often linked to higher education, are better equipped to cope with the impact of brain injury. However, the study's reliance on MMSE may have limited its ability to detect domain-specific impairments. Future studies should consider using more sensitive cognitive tools, such as the Montreal Cognitive Assessment (MoCA), to provide a more comprehensive evaluation of PSCI. Cognitive impairment is prevalent among stroke survivors, with age and education level being key factors influencing outcomes. These findings underscore the importance of early detection and targeted interventions to mitigate cognitive decline. Further research with larger samples and more sensitive cognitive assessments is needed to fully understand PSCI and improve rehabilitation strategies for patients with stroke.

Traumatic brain injury, posttraumatic stress disorder, and vascular risk are independently associated with white matter aging in Vietnam-Era veterans.

Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions-TBI history, PTSD, and vascular risk-and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition. We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance. Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p's >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p's <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052). Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.

Traumatic Brain Injury and Risk of Incident Dementia: Forensic Applications of Current Research.

Traumatic Brain Injury (TBI) has been identified as a risk factor for later developing neurodegenerative disorders, and there has been significant attention on this association in forensic settings. As a result, forensic neuropsychologists are frequently asked to comment on risk for dementia after an alleged TBI in litigation and criminal cases. This article provides an evidence-based foundation to aid forensic practice by synthesizing comprehensive information pertaining to: (i) the role of the neuropsychologist in TBI-related litigation, (ii) the complexities associated with identifying TBIs in forensic cases, (iii) the science of TBI in relation to incident dementia, and (iv) current scientific evidence for chronic traumatic encephalopathy. Developing a neurodegenerative disorder after TBI is the exception rather than the rule. Prevalence rates suggest that only a small subset (< 5%) of individuals with moderate-to-severe TBI, and even fewer (< 1%) with mild TBI (mTBI), appear to develop certain neurodegenerative diseases, and the characteristics that place some at risk remain unclear. The literature is mixed in terms of identifying a relationship between mTBI and later-in-life dementia risk. Also, the quality of positive evidence for risk of dementia after mTBI is weak and mostly consists of observational studies characterized by methodological limitations. Methods used to establish the likely occurrence of a TBI in a forensic context are typically more extensive than those used in a routine clinical evaluation. Research methodology to define TBI is often even more rudimentary and inconsistent. Applying clinical research results of TBI and dementia outcomes to forensic cases at an individual level carries significant limitations. Estimating the contribution of remote head hits or concussion in a causal manner to dementia is a challenge forensic experts sometimes face, yet at present, the task is impossible beyond correlations and speculation.

Formoterol dynamically alters endocannabinoid tone in the periaqueductal gray inducing headache

BackgroundHeadache is a pain disorder present in populations world-wide with a higher incidence in females. Specifically, the incidences of medication overuse headache (MOH) have increased worldwide. Comorbidities of MOH include photosensitivity, anxiety, “brain fog”, and decreased physical activity. The FDA-approved long-lasting selective β2-adrenergic receptor agonist, formoterol, is currently approved for use in severe asthma and chronic obstructive pulmonary disease. Recently, interest in repurposing formoterol for use in other disorders including Alzheimer’s disease, and neuropathic pain after spinal cord injury and traumatic brain injury has gained traction. Thus, revisiting known side-effects of formoterol, like headache and anxiety, could inform treatment paradigms. The endocannabinoid (eCB) system is implicated in the etiology of preclinical headache, with observed decreases in the circulating levels of endogenous cannabinoids, referred to as Clinical Endocannabinoid Deficiency. As cross-talk between the eCB system and adrenergic receptors has been reported, this study investigated the role of the eCB system and ability of formoterol to induce headache-like periorbital allodynic behavior.MethodsFemale 8-week-old C57Bl/6J mice were treated daily with formoterol (0.3 mg/kg, i.p.) for up to 42-days, during which they were assessed for periorbital allodynia, open field/novel object recognition, and photosensitivity. At the end of the study, the periaqueductal grey (PAG), a brain region known to contribute to both headache induction and maintenance, was collected and subjected to LC-MS to quantify endocannabinoid levels.ResultsMice exhibited periorbital allodynia at nearly all time points tested and photosensitivity from 28-days onward. Levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), along with cannabinoid receptor 1 (CB1R) expression were altered by both age and upon treatment with formoterol. Administration of FAAH/MAGL inhibitors, to target the eCB system, and a non-selective cannabinoid receptor agonist, WIN 55,212 reversed the formoterol-induced periorbital allodynia.ConclusionsThese results suggest that formoterol is dysregulates eCB tone to drive headache-like periorbital allodynic behaviors. These results could help inform preventative treatment options for individuals receiving formoterol, as well as provide information on the interaction between the eCB and adrenergic system.Graphical

NaHS alters synaptic plasticity proteins and enhances dendritic arborization to improve cognitive and motor deficits after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a complex medical condition affecting people globally. Hydrogen sulfide (H2S) is a recently discovered gaseous mediator and is dysregulated in the brain after TBI. Sodium hydrogen sulfide (NaHS), a known donor of H2S, is beneficial in various biological processes involving aging and diseases, including injury. It is neuroprotective against oxidative stress, neuroinflammation, and other secondary injury processes. However, the NaHS-H2S system has not been investigated as a regulator of injury-mediated synaptic plasticity proteins and the underlying mechanisms after TBI. We developed a model of TBI in Swiss albino mice to study the effects of exogenous H2S, administered as NaHS. We assessed cognitive function (Barnes maze and novel object recognition) and motor function (rotarod). Brain tissue was analysed with ELISA, qRT-PCR, immunoblotting, Golgi-cox staining, and immunofluorescence. NaHS administration restored the injury-caused decline in H2S levels. Injury-mediated oxidative stress parameters were improved following NaHS. It down-regulated TBI biomarkers, ameliorated the synaptic marker proteins, and improved cognitive and motor deficits. These changes were accompanied by enhanced dendritic arborization and spine number. Restoration of N-methyl D-aspartate receptor subunits and diminished glutamate and calcium levels, along with marked changes in microtubule-associated protein 2 A and calcium/calmodulin-dependent protein kinase II, formed the basis of the underlying mechanism(s). Our findings suggest that NaHS could have therapeutic activity against TBI, as it ameliorated cognitive and motor deficits caused by changes in synaptic plasticity proteins and dendritic arborisation, in our model.

Provider Identified Access Barriers to Delivering Acupuncture to Persons with Traumatic Brain Injury and Chronic Pain: A Cross-Sectional Self-Report Survey.

Objective: Traumatic brain injury (TBI) clinical practice guidelines for pain management and rehabilitation support the use of nonpharmacologic complementary and integrative health (CIH) modalities, such as acupuncture for remediating pain. Barriers to delivering CIH modalities, such as acupuncture warrant examination. The objective of this study is to explore provider perspectives on challenges to accessing acupuncture treatment for chronic pain in persons with TBI and describe differences across health care settings. Setting: Civilian, Veterans Affairs (VA), and Department of Defense health care systems. Participants: Health care providers (n = 145) were recruited from November 2022 to March 2023 via email through professional organizations and health care systems. Design: Descriptive cross-sectional self-report online survey. Main Measures: A survey assessed barriers using a 5-point Likert scale (always a barrier to never a barrier) using the Levesque Access to Care framework. Results: Of the 137 participants who provided information on setting, 86 (63%) worked in civilian health care; 47 (34%) worked in the Department of VA; and 4 (2.6%) in the Department of Defense (8 were missing data). Overall, providers endorsed all ten items as being barriers to accessing acupuncture treatment. However, these barriers were more statistically more frequently reported for civilian providers compared with VA providers for six of the 10 items, including lack of caregiver support (p < 0.0001); own knowledge and understanding of the treatment (p = 0.0025); health care setting culture discourages the treatment (p = 0.0181); lack of qualified providers (p = 0.0467); insurance does not cover (p < 0.0001), and patient cannot afford (p < 0.0001). VA provider respondents were more likely to answer all six items, as "Rarely/Never a Barrier," while providers in a civilian setting were more likely to respond "Always/Frequently" or "Sometimes" a barrier. Conclusion: Results reflect the cultural, organizational, and structural differences that make acupuncture more accessible within the VA. understanding barriers to delivering care is critical to inform implementation strategy mapping efforts, to tailor strategies that are aimed to increase access and engagement with acupuncture treatment in civilian health care settings.

Genetic Differences Modify Anesthetic Preconditioning of Traumatic Brain Injury in Drosophila.

Pre-clinical vertebrate models of traumatic brain injury (TBI) routinely use anesthetics for animal welfare; however, humans experience TBI without anesthetics. Therefore, translation of findings from vertebrate models to humans hinges on understanding how anesthetics influence cellular and molecular events that lead to secondary injuries following TBI. To investigate the effects of anesthetics on TBI outcomes, we used an invertebrate Drosophila melanogaster model to compare outcomes between animals exposed or not exposed to anesthetics prior to the same primary injury. Using a common laboratory fly line, w1118, we found that exposure to the volatile anesthetics isoflurane or sevoflurane, but not ether, prior to TBI produced a dose-dependent reduction in mortality within 24 h following TBI. Thus, isoflurane and sevoflurane precondition w1118 flies to deleterious effects of TBI. To examine the effects of genetic differences on anesthetic preconditioning of TBI, we repeated the experiment with the Drosophila Genetic Reference Panel (DGRP) collection of genetically diverse, inbred fly lines. Pre-exposure to either isoflurane or sevoflurane revealed a wide range of preconditioning levels among 171 and 144 DGRP lines, respectively, suggesting a genetic component for variation in anesthetic preconditioning of mortality following TBI. Finally, genome-wide association study analyses identified single-nucleotide polymorphisms in genes associated with isoflurane or sevoflurane preconditioning of TBI. Several of the genes, including the fly ortholog of mammalian Calcium Voltage-Gated Subunit Alpha1 D (CACNA1D), are highly expressed in neurons and are functionally linked to both anesthetics and TBI. These data indicate that anesthetic dose and genetic background should be considered when investigating effects of anesthetics in vertebrate TBI models, and they support use of the fly model for elucidating the mechanisms underlying anesthetic preconditioning of TBI.

Long-term persistence of inappropriate antidiuretic hormone secretion following minor head injury

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of euvolemic hyponatremia, resulting from non-osmotic release of antidiuretic hormone (ADH). SIADH is frequently associated with neurological conditions, including traumatic brain injury (TBI). TBI-associated SIADH usually develops within days to weeks and resolves within a few weeks. We present the case of a 74-year-old man who, after a fall resulting in TBI, initially had normal sodium levels. Fifteen days later, he developed moderate-to-severe hyponatremia (120 mmol/l) and significant neurological symptoms. Treatment with urea effectively normalized his sodium levels and resolved symptoms. However, recurrent hyponatremia persisted for over six months whenever urea treatment was discontinued. This unusual duration of TBI-associated SIADH underscores the importance of long-term follow-up in the management of post-traumatic hyponatremia.

Critical Review of Recently Published Studies Claiming Long-Term Neurocognitive Abnormalities in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most common claimed personal injury condition for which neuropsychologists are retained as forensic experts in litigation. Therefore, it is critical that experts have accurate information when testifying as to neurocognitive outcome from concussion. Systematic reviews and six meta-analyses from 1997 to 2011 regarding objective neurocognitive outcome from mTBI provide no evidence that concussed individuals do not return to baseline by weeks to months post-injury. In the current manuscript, a critical review was conducted of 21 research studies published since the last meta-analysis in 2011 that have claimed to demonstrate long-term (i.e., ≥12months post-injury) neurocognitive abnormalities in adults with mTBI. Using seven proposed methodological criteria for research investigating neurocognitive outcome from mTBI, no studies were found to be scientifically adequate. In particular, more than 50% of the 21 studies reporting cognitive dysfunction did not appropriately diagnose mTBI, employ prospective research designs, use standard neuropsychological tests, include appropriate control groups, provide information on motive to feign or use PVTs, or exclude, or adequately consider the impact of, comorbid conditions known to impact neurocognitive scores. We additionally analyzed 15 studies published during the same period that documented no longer term mTBI-related cognitive abnormalities, and demonstrate that they were generally more methodologically robust than the studies purporting to document cognitive dysfunction. The original meta-analytic conclusions remain the most empirically-sound evidence informing our current understanding of favorable outcomes following mTBI.

Correlation Between EtCO2 and PCO2 in Patients Undergoing Critical Care Transport

Objectives End-tidal carbon dioxide (EtCO2) monitoring is widely used as a surrogate for the partial pressure of carbon dioxide (PCO2) in critically ill patients receiving manual or mechanical ventilation in prehospital, emergency, and critical care settings. Specific targets for ETCO2 are a key component of Emergency Medical Services (EMS) protocols, especially for specific patient groups such as those with traumatic brain injury. However, the correlation between EtCO2 and venous or arterial PCO2 is uncertain. We aimed to assess the correlation between EtCO2 and PCO2 in intubated patients undergoing critical care transport (CCT), and in specific subgroups of patients. Methods We performed a retrospective review of patients undergoing emergency transport by a multi-state CCT agency. Patients were included if they had an advanced airway and both an EtCO2 and PCO2 reading within 5 min of each other. We obtained data on patient demographics, transport characteristics, medical categories, vital signs, lab values, and specific interventions. We performed univariable and multivariable binary logistic regression to assess the association between delta PCO2 and these characteristics. Results We included 6,459 patients (mean age 58.4 years [SD 18.5], 57.1% male), of which a subset of 551 patients had multiple EtCO2-PCO2 measurements within 5 min. The median (IQR) initial delta PCO2 was 12.9 mmHg (7.1, 21.9). 3,967 (61.4%) patients had a delta PCO2 >10 mmHg and 1,843 (28.5%) had a delta PCO2 >20 mmHg. We identified an independent association between delta PCO2 >10 mmHg and age, male sex, interfacility transport, venous sampling site, respiratory rate, hypotension, hypoxia, and thoracostomy. In patients with multiple blood gas measurements, 76% had delta PCO2 >10 mmHg over the duration of the transport. Conclusions We identified substantial differences between EtCO2 and PCO2 across patients with medical and traumatic conditions undergoing critical care transport. The PCO2 assessment should be strongly considered as part of ventilatory management in patients encountered in emergency and critical care settings.