Neurotrauma reports最新文献

Management of severe traumatic brain injury (sTBI) typically involves the use of sedation, which inherently results in benefits and risks. The cytochrome P450 enzyme CYP2B6 is involved in the biotransformation of particular drug classes, including many intravenous sedatives. Variants of the CYP2B6 gene can lead to decreased systemic clearance of some sedatives, including propofol. This study aimed to investigate the relationship of CYP2B6 gene variation and patient outcomes after TBI while also considering propofol administration. Patients who sustained a non-penetrating sTBI and admitted to a single-center Level 1 trauma hospital were included in this study (n = 440). The *6 functional allele of CYP2B6 that leads to reduced enzyme expression and activity required genotyping two single nucleotide polymorphisms, rs3745274 and rs2279343. Patient outcomes were evaluated using the Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) at 3 and 6 months post-injury. Data on sedative administration were abstracted from medical records. Individuals homozygous for the alleles coding for the reduced enzyme expression and activity were more likely to have worse outcomes. A relationship between propofol administration and 3-month GOS and 6-month DRS was noted when controlling for CYP2B6 genotype. These findings suggest that genetic variation in CYP2B6 may influence the impact of intravenous sedation on patient outcomes after TBI and warrants further investigation.

Translation of spinal cord injury (SCI) therapeutics from pre-clinical animal studies into human studies is challenged by effect size variability, irreproducibility, and misalignment of evidence used by pre-clinical versus clinical literature. Clinical literature values reproducibility, with the highest grade evidence (class 1) consisting of meta-analysis demonstrating large therapeutic efficacy replicating across multiple studies. Conversely, pre-clinical literature values novelty over replication and lacks rigorous meta-analyses to assess reproducibility of effect sizes across multiple articles. Here, we applied modified clinical meta-analysis methods to pre-clinical studies, comparing effect sizes extracted from published literature to raw data on individual animals from these same studies. Literature-extracted data (LED) from numerical and graphical outcomes reported in publications were compared with individual animal data (IAD) deposited in a federally supported repository of SCI data. The animal groups from the IAD were matched with the same cohorts in the LED for a direct comparison. We applied random-effects meta-analysis to evaluate predictors of neuroconversion in LED versus IAD. We included publications with common injury models (contusive injuries) and standardized end-points (open field assessments). The extraction of data from 25 published articles yielded n = 1841 subjects, whereas IAD from these same articles included n = 2441 subjects. We observed differences in the number of experimental groups and animals per group, insufficient reporting of dropout animals, and missing information on experimental details. Meta-analysis revealed differences in effect sizes across LED versus IAD stratifications, for instance, severe injuries had the largest effect size in LED (standardized mean difference [SMD = 4.92]), but mild injuries had the largest effect size in IAD (SMD = 6.06). Publications with smaller sample sizes yielded larger effect sizes, while studies with larger sample sizes had smaller effects. The results demonstrate the feasibility of combining IAD analysis with traditional LED meta-analysis to assess effect size reproducibility in SCI.

A sizable proportion of patients with mild traumatic brain injury (mTBI) have persistent symptoms and functional impairments months to years following injury. This phenomenon is continually observed despite an explosion of research and interest in improving mTBI clinical outcomes over the last two decades. All pharmacological clinical trials to date have failed to demonstrate improved outcomes for mTBI. One possible explanation for these continued failures is an overly myopic approach to treating mTBI (i.e., testing the effect of a single drug with a specific mechanism on a group of people with highly heterogenous injuries). Clinical presentation and prognosis of mTBI vary considerably between patients, and yet we continue to assess group-level effects of a homogenized treatment. We need to utilize an equally complex treatment approach to match the extraordinary complexity of the human brain. Dynamical systems theory has been used to describe systems composed of multiple subsystems who function somewhat independently but are ultimately interconnected. This theory was popularized in the motor control literature as an overarching framework for how the mind and body connect to interact and move through the environment. However, the human body can be viewed as a dynamical system composed of multiple subsystems (i.e., organ systems) who have isolated functions, which are also codependent on the health and performance of other interconnected organ systems. In this perspective piece, we will use the example of mTBI in the obese patient to demonstrate how broadening our approach to treatment of the individual (and not necessarily the injury) may ultimately yield improved outcomes. Furthermore, we will explore clinical and pre-clinical evidence demonstrating multiple system interactions in the context of obesity and TBI and discuss how expanding our understanding of the mechanistic interplay between multiple organ systems may ultimately provide a more personalized treatment approach for this mTBI patient subpopulation.

The aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) is to design a data dictionary to inform data collection and facilitate prediction of outcomes for moderate-severe traumatic brain injury (TBI) across Australia. The process has engaged diverse stakeholders across six areas: social, health, clinical, biological, acute interventions, and long-term outcomes. Here, we report the results of the clinical review. Standardized searches were implemented across databases to April 2022. English-language reports of studies evaluating an association between a clinical factor and any clinical outcome in at least 100 patients with moderate-severe TBI were included. Abstracts, and full-text records, were independently screened by at least two reviewers in Covidence. The findings were assessed through a consensus process to determine inclusion in the AUS-TBI data resource. The searches retrieved 22,441 records, of which 1137 were screened at full text and 313 papers were included. The clinical outcomes identified were predominantly measures of survival and disability. The clinical predictors most frequently associated with these outcomes were the Glasgow Coma Scale, pupil reactivity, and blood pressure measures. Following discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous studies evaluating associations between clinical factors and outcomes in patients with moderate-severe TBI. A small number of factors were reported consistently, however, how and when these factors were assessed varied. The findings of this review and the subsequent consensus process have informed the development of an evidence-informed data dictionary for moderate-severe TBI in Australia.

Mild traumatic brain injury (mTBI), or concussion, is a major public health problem, and ambiguity still exists regarding its diagnosis. While functional magnetic resonance imaging (fMRI) has been identified as a helpful screening tool for concussion, its limited accessibility in clinical or field settings necessitates a more efficient alternative. Oculomotor function deficit is an often-reported pathology in mTBI. Due to the neuroanatomical overlap between eye-movement circuitry and mTBI pathophysiology, visual deficits are expected. In this study, we investigate the possibility of using an oculomotor assessment tool for finding biomarkers in concussion. We used fMRI with tasks evaluating oculomotor functions: smooth pursuit (SP), saccades, anti-saccades, and optokinetic nystagmus (OKN). Before the scanning, the testing with a system of virtual reality goggles with integrated eye- and head-tracking was used where subjects performed the same tasks as those used in fMRI. Twenty-nine concussed symptomatic adults (CSA) within 1-month postconcussion and 29 age- and sex-matched healthy controls (HCS) were tested to examine blood oxygen level-dependent (BOLD) fMRI alterations associated with performances in oculomotor function after mTBI and evaluate the efficacy of the oculomotor assessment in detecting oculomotor and gaze deficits following mTBI. Comparing CSA with HCS, significant differences were observed in anti-saccades and OKN performance. CSA group exhibited elevated %BOLD signal change on each task compared with HCS: in the superior frontal gyrus during the smooth pursuit, inferior frontal gyrus during the saccades, putamen and dorsolateral prefrontal cortex (DLPFC) during the anti-saccades, and lingual gyrus and IFG during the OKN. Key findings include the following: (1) oculomotor deficits in concussed subjects compared with controls, (2) abnormal activation patterns in areas related to the regulation and control of oculomotor movements, suggesting concussion-induced disruptions, and (3) the potential of oculomotor assessment as a promising approach for mTBI biomarkers, with anti-saccades and OKN identified as the most sensitive tasks.

Traumatic brain injury (TBI), a significant global health issue, is affecting ∼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.

In interventional clinical trials for persons with spinal cord injury (SCI), the influence of experimental biological, pharmacological, or device-related interventions must be differentiated from that of physical and occupational therapy interventions, as rehabilitation influences motor-related outcomes. The International Spinal Cord Injury (ISCI) Physical Therapy-Occupational Therapy Basic Data Set (PT-OT BDS) was developed with the intent to track the content and time of rehabilitation interventions that are delivered concurrently with experimental interventions. We assessed the reliability of the PT-OT BDS based on agreement between users. Following an online training session, physical therapists (PTs) and occupational therapists (OTs) from 10 SCI clinical centers across 7 countries participated. At each center, pairs of therapists (a treating therapist and an observing therapist; PT/PT, OT/OT, or PT/OT) used the PT-OT BDS to record the content and time of therapy sessions for 20 patients. Data were analyzed to determine agreement between therapist pairs regarding the content of the therapy session. The influence of therapist characteristics (professional discipline [PT/OT], years of experience working with individuals with SCI), patient characteristics (level [tetraplegia/paraplegia] and severity [complete/incomplete] of injury), setting (inpatient/outpatient), and whether the center was U.S.- versus non-U.S.-based were also analyzed. There was high agreement for five of seven categories and medium agreement for the remaining two categories. For six of the seven intervention categories, there were no significant differences between the treating and the observing therapists in the percentage of instances that a specific category was selected. Characteristics of the therapists, characteristics of the patient, therapy setting, and global location of the center had no meaningful influence on level of agreement between therapist pairs. The BDS is reliable for use across settings, countries, and with patients of various impairment levels. The study also helped identify additional areas where refinement of the syllabus would be of value.

Low vitamin D (VD) has been associated with poor clinical course in several neurological diseases. Supplementation has been suggested to improve outcomes. Severe acquired brain injury (sABI) subjects have low VD levels and disabling conditions requiring rehabilitation. The aim of the present study was to evaluate if VD supplementation produced a better clinical course and a better functional outcome in sABI during rehabilitation. A randomized single-blind study was performed. sABI subjects were randomized to the VD supplementation group (VDsG) (initial dose of 50.000 UI and 1.000 daily) and usual care control group (CG). Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS), and Level of Cognitive Functioning (LCF) were used in assessing disability. A total of 73 subjects (42 M and 31 F; mean age 53.2 ± 15.7) were randomized: 36 (21 M and 15 F; mean age 57.52 ± 14.88) to VDsG and 37 (20 M and 17 F; mean age 48.28 ± 17.47) to CG. Both groups significantly improved after rehabilitation, and no between-group difference was observed. The mean score values for DRS, GOS, and LCF in VDsG were 18.83 ± 4.27 and 9.42 ± 5.83; 2.89 ± 0.32 and 3.78 ± 0.80; and 4.81 ± 1.70 and 7.53 ± 1.28, at admission and discharge, respectively. Likewise, mean values for DRS, GOS, and LCF in CG were 18.57 ± 4.80 and 9.84 ± 6.34; 2.84 ± 0.37 and 3.81 ± 0.94; and 4.97 ± 2.01 and 7.41 ± 1.32, respectively. VD supplementation did not improve functional outcomes in sABI during rehabilitation treatment.

The objective was to assess the severity of neurological injury in acute traumatic spinal cord injury (ATSCI) using the BASIC (Brain and Spinal Injury Center) score, to correlate with the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade at admission and at 3 months postinjury in patients managed for ATSCI at National Hospital, Abuja, and thereby validate the novel BASIC score. This was a prospective longitudinal hospital-based study involving consecutive patients diagnosed with ATSCI and managed at the National Hospital, Abuja. Sixty-five participants met the inclusion criteria. Each patient was resuscitated along the Advanced Trauma Life Support protocol, followed by history, neurological examination according to the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI), and AIS grades that were recorded. Magnetic resonance imaging scan of the injured spinal cord was done, and BASIC scores were assigned. Further management was as per the standard. Three months after injury, neurological examination was again carried out based on ISNCSCI and AIS grades assigned. Data were collected, analyzed, and correlated using Excel and SPSS version 23. Means, medians, correlation coefficients, and Fisher's exact t-tests were determined. p-Value <0.05 was considered statistically significant. Results show mean age was 39.1 ± 12.3 years. The majority (81.5%) were males, whereas 18.5% were females. The majority (67.7%) were skilled professionals, 13.8% were unskilled, and 18.5% were students. Most injuries (90.8%) were due to road traffic accidents, whereas 9.2% were due to falls. Majority (72.3%) of the patients had complete SCI (AIS grade A), whereas AIS grade E accounted for the least number (3.1%). Cervical spine injury affected 92.3% of patients, whereas 7.7% had thoracic spine injury. Most patients had BASIC 4 pattern on MRI (44.6%), whereas BASIC 1 pattern was the fewest (3.1%). Surgery was not done for 58.5% of patients, whereas 41.5% had surgical decompression and spine fusion. At 3 months postinjury, 15.4% of patients had AIS grade improvement, whereas 84.6% maintained their AIS grade. The largest AIS grade improvement was from grade B to C (6.2%), which was statistically significant (p = 0.04). BASIC score correlated moderately with admission AIS grade (p = 0.532). BASIC score also correlated moderately with AIS grade at 3 months postinjury (p = 0.546). BASIC score 4 was best at predicting poor outcome in ATSCI. In conclusion, BASIC score has a moderate correlation with AIS grade in ATSCI and can predict poor outcomes in ATSCI. BASIC score of 4 has the best discriminant value in prognosticating and represents severe SCI.

Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and proimmune properties; however, their use has not been rigorously studied in human TBI populations. A single-center, retrospective, descriptive observational study was conducted at the LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ≤ 8) who remained in the ICU for ≥2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared with those who received standard, polymeric EN with regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention.