Subset Of Traumatic Brain Injury Patients Research Articles

A Criteria to Reduce Interhospital Transfer of Traumatic Brain Injuries in Greater East Texas.

Traumatic brain injury (TBI) due to single-level falls (SLF) are frequent and often require interhospital transfer. This retrospective cohort study aimed to assess the safety of a criteria for non-transfer among a subset of TBI patients who could be observed at their local hospital, vs mandatory transfer to a level 1 trauma center (L1TC). We conducted a 7-year review of patients with TBI due to SLF at a rural L1TC. Patients were classified as transfer/non-transfer according to the Brain Injuries in Greater East Texas (BIGTEX) criteria. The primary outcome measure was the occurrence of a critical event defined as deteriorating repeat head computed tomography (CT) scan or neurological status, neurosurgical intervention, or death. Of the 689 included patients, 63 (9.1%) were classified as non-transfer. Although there were 4 cases with a neurological change and one with a head CT change among the non-transfer group, there were no neurosurgical procedures or deaths. The Cox Proportional Hazard model showed a near 3-fold increased risk of experiencing a critical event if classified as a non-transfer. The multivariable regression model showed patients with an Abbreviated Injury Scale (AIS) of 3 was twice as likely to experience a critical event, with an AIS of 4, three times, and 3 times more likely to be classified to transfer. The BIGTEX criteria identify a subset of patients who can safely be observed at their local hospital. To confirm the safety and efficacy of this transfer criteria recommendation, a prospective study is warranted.

PRMT7 can prevent neurovascular uncoupling, blood-brain barrier permeability, and mitochondrial dysfunction in repetitive and mild traumatic brain injury

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of fission and fusion. Overall, these pathophysiological findings correlated with decreased protein arginine methyltransferase 7 (PRMT7) protein levels and activity post-rmTBI. Here, we increased PRMT7 levels in vivo to assess the role of the neurovasculature and mitochondria post-rmTBI. In vivo overexpression of PRMT7 using a neuronal specific AAV vector led to restoration of neurovascular coupling, prevented BBB leakage, and promoted mitochondrial respiration, altogether to suggest a protective and functional role of PRMT7 in rmTBI.

327 Identification of Clinically Relevant Patient Endotypes in Traumatic Brain Injury (TBI) Using Latent Class Analysis

INTRODUCTION: Despite advances in medical knowledge, TBI still has a significant burden of disease. Better prognostic factors would allow for earlier identification of patients at risk for poor outcomes and enable targeted interventions to improve outcomes and reduce costs. METHODS: We obtained clinical information from a subset of TBI patients from the MIMIC-III dataset and codified each patient's comorbidities based on the Elixhauser comorbidity groups. Latent class analysis was performed on the patients based on their codified comorbidities to identify distinct patient endotypes. The characteristics (comorbidity distribution, mortality rate) of these patient endotypes were then visualized using Matplotlib. A Chi-squared test of homogeneity was performed to determine if mortality rates differed across patient endotypes. Relationships between the codified comorbidities were visualized using a network graph across all TBI patients and within each patient endotype. RESULTS: 2981 patients qualified under our TBI query. Average age was 58 ± 21. The network graph shows that there is only one major connected component composed of the most common comorbidities. An elbow plot was constructed to help identify 8 as the optimal number of classes to model patient endotypes. The distribution of comorbidities differs between patient endotypes. Furthermore, there was a significant difference in survival rates between the patient endotypes (p < 0.0001) with Endotype 1 having the lowest survival and Endotype 6 having the highest. Intra-endotype network analysis and comorbidity distributions suggest that Endotype 1 is a cancer-related endotype whereas Endotype 6 is a relatively "healthy" endotype with some degree of alcohol and drug abuse. CONCLUSIONS: In this study, we use LCA to demonstrate the existence of patient endotypes in a TBI population that differ in their comorbidity profiles and clinical outcomes.

Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury

Background and PurposeDysfunction of the blood–brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI. Materials and MethodsDCE MRI was performed in 40 adult patients a median of 23 days after hospitalized TBI and in 21 healthy controls. DCE data was analyzed using Patlak and linear models, and derived metrics of BBB leakage including the volume transfer constant (Ktrans) and the normalized permeability index (NPI) were compared between groups. BBB metrics were compared with focal lesion distribution as well as with contemporaneous measures of symptomatology and cognitive function in TBI patients. Finally, BBB metrics were examined longitudinally among 18 TBI patients who returned for a second MRI a median of 204 days postinjury. ResultsTBI patients exhibited higher mean Ktrans (p = 0.0028) and proportion of suprathreshold NPI voxels (p = 0.001) relative to controls. Tissue-based analysis confirmed greatest TBI-related BBB disruption in association with focal lesions, however elevated Ktrans was also observed in perilesional (p = 0.011) and nonlesional (p = 0.044) regions. BBB disruption showed inverse correlation with quality of life (rho = −0.51, corrected p = 0.016). Among the subset of TBI patients who underwent a second MRI several months after the initial evaluation, metrics of BBB disruption did not differ significantly at the group level, though variable longitudinal changes were observed at the individual subject level. ConclusionsThis pilot investigation suggests that TBI-related BBB disruption is detectable in the early post-injury period in association with focal and diffuse brain injury.

Alterations of the GH/IGF-I Axis and Gut Microbiome after Traumatic Brain Injury: A New Clinical Syndrome?

Pituitary dysfunction with abnormal growth hormone (GH) secretion and neurocognitive deficits are common consequences of traumatic brain injury (TBI). Recognizing the comorbidity of these symptoms is of clinical importance; however, efficacious treatment is currently lacking. A review of studies in PubMed published between January 1980 to March 2020 and ongoing clinical trials was conducted using the search terms "growth hormone," "traumatic brain injury," and "gut microbiome." Increasing evidence has implicated the effects of TBI in promoting an interplay of ischemia, cytotoxicity, and inflammation that renders a subset of patients to develop postinjury hypopituitarism, severe fatigue, and impaired cognition and behavioral processes. Recent data have suggested an association between abnormal GH secretion and altered gut microbiome in TBI patients, thus prompting the description of a hypothesized new clinical syndrome called "brain injury associated fatigue and altered cognition." Notably, these patients demonstrate distinct characteristics from those with GH deficiency from other non-TBI causes in that their symptom complex improves significantly with recombinant human GH treatment, but does not reverse the underlying mechanistic cause as symptoms typically recur upon treatment cessation. The reviewed data describe the importance of alterations of the GH/insulin-like growth factor I axis and gut microbiome after brain injury and its influence in promoting neurocognitive and behavioral deficits in a bidirectional relationship, and highlight a new clinical syndrome that may exist in a subset of TBI patients in whom recombinant human GH therapy could significantly improve symptomatology. More studies are needed to further characterize this clinical syndrome.

Relationship of Cerebral Blood Flow to Cognitive Function and Recovery in Early Chronic Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, for which biomarkers are needed to better understand the underlying pathophysiology. Microvascular injury represents a subset of pathological mechanisms contributing to cognitive dysfunction after TBI, which may also impair subsequent neural repair thereby inhibiting cognitive recovery. Magnetic resonance imaging (MRI)-based measurement of cerebral blood flow (CBF) by arterial spin labeling (ASL) provides an appealing means of assessing microvascular disruption in TBI; however, the relationship between CBF alterations in the early chronic post-TBI setting and cognitive dysfunction as well as subsequent cognitive recovery remain poorly understood. Structural MRI and ASL were performed in 42 TBI subjects 3 months post-injury and 35 matched healthy controls. Neuropsychological testing was performed in each subject, as well as in a subset of TBI patients (n = 33) at 6 and/or 12 months post-injury. TBI and control subject CBF data were compared between groups in a voxel-wise fashion while controlling for the effects of structural atrophy. A region-of-interest approach was then used to compare CBF to clinical and neuropsychological measures within the TBI group in a cross-sectional fashion, as well as to the degree of subsequent cognitive recovery among subjects with follow-up testing. At 3 months post-injury, the TBI group demonstrated lower performance in each cognitive domain (p < 0.05), as well as widespread reductions in gray matter CBF independent of structural atrophy (p < 0.05). Within the TBI group, CBF was moderately correlated with injury severity (r = -0.43; p = 0.009) and executive function (r = 0.43; p = 0.01). In the longitudinal analysis, there was a positive correlation between initial CBF and processing speed recovery (r = 0.43; p = 0.015) independent of age, education level, and initial test score. Early chronic TBI is associated with widespread gray matter CBF deficits, which are correlated with injury severity and cognitive dysfunction. CBF may predict subsequent recovery in some cognitive domains.

Concomitant chest trauma and traumatic brain injury, biomarkers correlate with worse outcomes.

Clinical data are lacking on the influence of chest trauma on the secondary injury process after traumatic brain injury (TBI), with some data suggesting that multiple trauma may worsens brain injury. Blunt chest trauma and TBI represent the two major single injury entities with the highest risk of complications and are potential biomarker targets. Trauma patients with severe TBI were enrolled. Serum biomarker levels were obtained every 6 hours for 72 hours. Baseline, 6 hours and 24 hours CT head scans were evaluated. Neurologic worsening was defined as increased contusions, ischemia, compression of basal cisterns, and/or midline shift. The TBI patients with chest injury (Abbreviated Injury Scale chest score ≥1) and those without chest injury were compared. Wilcoxon rank sum test, univariate logistic regression and receiver operating characteristic were reported. Fifty-seven patients. Mean age of 40.5 years. Median motor Glasgow Coma Scale score at admission and 24 hours was 3 (interquartile range, 1-5) and 5 (interquartile range, 3-5). Of the patients enrolled, 12.2% patients underwent craniotomy within 6 hours from the time of admission and 22.8% within 12 hours. Patients with chest trauma, 24.5% had a chest Abbreviated Injury Scale score of 3 or greater, and 73.6% sustained blunt chest trauma. Stratifying TBI patients with and without chest injury revealed higher mean levels of IL-4, IL-5, IL-8, and IL-10 and lower mean IFN-γ and IL-7 levels in patient with chest injury. IL-7 levels adjusted for chest injury predicted neurological worsening with area under the receiver operating characteristic of 0.59 (p value = 0.011). The TBI and chest trauma patients' IL-4 and neuron-specific enolase levels were predictive of mortality (area under the receiver operating characteristic of 0.67 and 0.63, p = 0.0001, 0.003), respectively. Utilizing biomarkers for early identification of patients with TBI and chest trauma has the capability of modifying adverse factors affecting morbidity and mortality in this subset of TBI patients. Level III.

Autoimmunity and Traumatic Brain Injury

Traumatic brain injury (TBI) causes injured brain cells to release brain-specific proteins, which may trigger an autoantibody response. In this review, we will discuss how autoimmunity is triggered after TBI and summarize the identified brain antigens to which an autoimmune response has been observed as well as their clinical implications. TBI leads injured brain cells to release brain proteins, in their intact or proteolytic fragment form, into extracellular fluids and eventually into circulating blood. These brain proteins treated by the immune system as foreign antigens can evoke the systemic production of both IgM and IgG isoforms. Increasing evidence shows that in a subset of TBI patients, there are circulating autoantibodies recognizing a range of brain proteins, including glial proteins like S100B, glial fibrillary acidic protein, and peroxirerdoxin; neuroreceptors such as glutamate receipt subunits NR1; and oligodendrocyte-originated myelin basic protein. Autoimmunity is triggered in TBI, targeting a range of brain-specific antigens in a subset of TBI patients. Such autoantibodies might be useful for biofluid-based diagnosis in order to identify patients who might benefit from immunotherapy.

Does Isolated Traumatic Subarachnoid Hemorrhage Merit a Lower Intensity Level of Observation Than Other Traumatic Brain Injury?

Evidence is emerging that isolated traumatic subarachnoid hemorrhage (ITSAH) may be a milder form of traumatic brain injury (TBI). If true, ITSAH may not benefit from intensive care unit (ICU) admission, which would, in turn, decrease resource utilization. We conducted a retrospective review of all TBI admissions to our institution between February 2010 and November 2012 to compare the presentation and clinical course of subjects with ITSAH to all other TBI. We then performed descriptive statistics on the subset of ITSAH subjects presenting with a Glasgow Coma Score (GCS) of 13-15. Of 698 subjects, 102 had ITSAH and 596 had any other intracranial hemorrhage pattern. Compared to all other TBI, ITSAH had significantly lower injury severity scores (p<0.0001), lower head abbreviated injury scores (p<0.0001), higher emergency department GCS (p<0.0001), shorter ICU stays (p=0.007), higher discharge GCS (p=0.005), lower mortality (p=0.003), and significantly fewer head computed tomography scans (p<0.0001). Of those ITSAH subjects presenting with a GCS of 13-15 (n=77), none underwent placement of an intracranial monitor or craniotomy. One subject (1.3%) demonstrated a change in exam (worsened headache and dizziness) concomitant with a progression of his intracranial injury. His symptoms resolved with readmission to the ICU and continued observation. Our results suggest that ITSAH are less-severe brain injuries than other TBI. ITSAH patients with GCS scores of 13-15 demonstrate low rates of clinical progression, and when progression occurs, it resolves without further intervention. This subset of TBI patients does not appear to benefit from ICU admission.

Mismatch negativity abnormality in traumatic brain injury without macroscopic lesions on conventional MRI

Traumatic brain injury (TBI) causes damage through complex pathophysiological mechanisms. Deficits related to traumatic axonal injury persist in a subset of patients with no macroscopic lesions on conventional MRI. We examined two event-related brain potentials, mismatch negativity (MMN) and P3a, to identify possible electrophysiological anomalies in this subset of TBI patients in comparison with TBI patients with focal abnormalities on MRI/computed tomography and healthy controls. Each group consisted of 10 individuals. A passive oddball paradigm, in which the individuals were instructed to ignore auditory stimuli while watching a silent movie, consisted of non-native speech sounds presented in a random order. Patients with no discernible lesions on conventional MRI showed a significantly augmented amplitude of the brain's involuntary change-detection response MMN, relative to that of the two other groups. In patients with focal neuroradiological abnormalities, this MMN anomaly was not found, whereas the subsequent orientation-related P3a response was significantly enlarged when compared with that of the controls. The present findings demonstrate that MMN is indicative of a functional abnormality in the mechanisms of involuntary attention in chronic TBI patients with normal conventional MRI findings, indexing their increased distractibility associated with the traumatically-induced loss of neural integrity.

An Update on Substance Use and Treatment following Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among young adults. Substance abusers constitute a disproportionate percentage of these patients. A history of substance abuse predicts increased disability, poorer prognosis, and delayed recovery. While consensus in the literature indicates that substance-abuse rates decline following injury, conflicting literature shows a significant history of brain injury in addicts. We reviewed the literature on substance abuse after TBI to explore the state of knowledge on TBI as a risk factor for substance abuse. While recent reviews regarding substance abuse in TBI patients concur that substance-abuse rates decline even after mild TBI, an emerging literature suggests mild TBI may cause subtle impairments in cognitive, executive, and decision-making functions that are often poorly recognized in early diagnosis and treatment. When combined with difficulties in psychosocial adjustment and coping skills, these impairments may increase the risk for chronic substance abuse in a subset of TBI patients. Preliminary results from veterans indicate these patterns hold in a combat-related post-traumatic stress disorder population with TBI. This increasingly prevalent combination presents a specific challenge in rehabilitation. While this comorbidity presents a challenge for the successful treatment and rehabilitation of both disorders, there is sparse evidence to recommend any specific treatment strategy for these individuals. Mild TBI and substance abuse are bidirectionally related both for risks and treatment. Further understanding the neuropsychiatric pathology and different effects of different types of injuries will likely improve the implementation of effective treatments for each of these two conditions.

Effect of Time, Injury, Age and Ethanol on Interpatient Variability in Valproic Acid Pharmacokinetics after Traumatic Brain Injury

Traumatic brain injury (TBI) results in an increase in hepatic metabolism. The increased metabolism is in significant contrast to a large body of in vitro and in vivo data demonstrating that activation of the host-defence response downregulates hepatic metabolism. Theoretically, this occurs because of activation of the pro-inflammatory cytokines tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-1 and IL-6. As part of a large double-blind, placebo-controlled clinical trial evaluating the use of valproic acid for prophylaxis of post-traumatic seizures, we obtained extensive valproic acid concentration-time data. Valproic acid is a hepatically metabolised, low extraction-ratio drug. Therefore, unbound clearance (CL(u)) is equal to intrinsic or metabolic clearance. The objective of this study was to evaluate the time-dependent effects of TBI on the pharmacokinetics of total and unbound valproic acid with the goal of identifying patient factors that may predict changes in total clearance (CL) and CL(u). In addition, by determining the factors that influence the magnitude and time course of induction of hepatic metabolism and understanding their interaction with the host-defence mediators, we can further our insight into the mechanism(s) responsible for the changes in CL and CL(u). Valproic acid plasma concentration data were obtained from 158 TBI patients. Unbound valproic acid plasma concentrations were estimated using total valproic acid plasma and albumin concentrations following a Scatchard equation binding model previously developed in a subset of TBI patients. The effect of 13 patient factors on CL and CL(u) was evaluated initially in a univariate analysis. The significant factors were then included in a multiple linear regression analysis by use of step-wise selection and forward selection procedures. CL and CL(u) were significantly increased after TBI in a time-dependent manner. The average increase was >75% by weeks 2 and 3 post-injury. The magnitude of the induction of CL was increased with decreased albumin concentrations, in addition to the presence of ethanol on admission, increased severity of head injury, tube feeding and total parenteral nutrition (TPN). The magnitude of induction of CL(u) was increased by older age, presence of ethanol on admission, increased severity of head injury, tube feeding, TPN, and if the patient had a post-injury neurosurgical procedure. The time to normalisation of CL(u) was significantly longer in patients with head injury plus other injuries compared with those with head injury alone. As has been reported with other drugs, TBI results in a significant increase in the metabolism of valproic acid. The patient factors identified in this study that resulted in an increase in the magnitude and time course of the induction of CL(u) (ethanol, older age, presence of a neurosurgical procedure, severity of TBI and presence of multiple non-TBI injuries) have all been reported to cause a shift to the anti-inflammatory mediators IL-4 and IL-10. This suggests that the increase in hepatic metabolism after TBI may be due to the increased presence of anti-inflammatory mediators in contrast to the inhibition effect of the pro-inflammatory mediators in non-TBI inflammation and infection.

Eye care practitioners in blood pressure related health care: Jack E. Terry, Veterans Administration Hospital, Huntington, WV

To identify a form of binocular vision dysfunction (vertical heterophoria) in a traumatic brain injury (TBI) population and to assess the effect of individualized prismatic spectacle lenses on postconcussive symptoms.Retrospective study.Private physical medicine and rehabilitation practice and private optometric practice.A subset of TBI patients who were initially evaluated by a single physiatrist and who received standard treatments and medications yet had persistent postconcussive symptoms. These patients were then assessed by a single optometrist, and those found to have vertical heterophoria were treated with individualized prismatic spectacle lenses. A total of 83 patients were referred for testing; 77 were positive for vertical heterophoria on screening, of which 43 had complete data sets and were included for analysis.All patients were treated with individualized prismatic spectacle lenses to correct for vertical heterophoria.Outcomes were measured by the difference in score before and after intervention of an objective, self-administered vertical heterophoria symptom burden instrument (Vertical Heterophoria Symptom Questionnaire [VHS-Q], presently undergoing validation) and by subjective improvement in symptoms as expressed by the patient at the end of intervention.There was a 71.8% decrease in subjective symptom burden when compared with preintervention baseline. There was a mean 16.7 point absolute reduction in the VHS-Q score on a 75-point scale, which represents a relative reduction in VHS-Q score of 48.1%.Vertical heterophoria was identified in a group of TBI patients with postconcussive symptoms and treatment of the vertical heterophoria with individualized prismatic spectacle lenses resulted in a 71.8% decrease in subjective symptom burden and a relative reduction in VHS-Q score of 48.1%. It appears that vertical heterophoria can be acquired from TBI.