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Recovery of memory and learning functions following traumatic brain injury.

Twenty-four traumatically brain-injured males, of whom eight had sustained right-sided, eight left-sided, and eight bilateral or diffuse closed head injuries, took a battery of neuropsychological tests within the first six months, the second six months, the second year and the third year post injury. Performances on WAIS Digits Forward and Backward and Rey's Auditory-Verbal Learning Test were classified as within or below normal range. Comparisons were made (1) between time periods and tests and (2) between subgroups formed by severity, site of lesion, and age. The findings give an overall picture of wide performance variability with consistent improvement in immediate memory span and learning. Recovery varied with the specific nature of the tested function, task complexity, and severity of injury. Neither age, site of injury, not recency were associated with improvement.

Adult

Personalized Repetitive Transcranial Magnetic Stimulation (PrTMS®) Coupled with Transcranial Photobiomodulation (tPBM) For Co-Occurring Traumatic Brain Injury (TBI) and Post-Traumatic Stress Disorder (PTSD).

This study provides further evidence demonstrating the beneficial effects of PrTMS® treatment in co-occurring disorders. Furthermore, this study illustrates the benefit of augmenting PrTMS® with tPBM for superior outcomes. The positive results of this novel case study can be attributed to brain wave neuromodulation and increased neuronal ATP production, resulting in synergistic enhanced neuroplasticity and brain optimization. Further, large-scale, randomized and blinded studies are recommended to validate our promising preliminary observations utilizing multifaceted interventions for co-occurring disorders.

Co-Occurring Disorders

Factors underlying neuropsychological test performance in chronic severe traumatic brain injury.

The neuropsychological test performance of subjects with traumatic brain injury (TBI) of the closed head type was investigated using a test battery consisting of traditional clinical instruments with expanded language measures. TBI subjects were specifically selected to include only those with a pattern of predominantly diffuse cerebral injury to allow conclusions regarding language performance in the absence of focal aphasia-producing lesions. Factor analysis of the test scores resulted in the extraction of three interpretable factors associated with performance on this battery: perceptual, general language, and mental efficiency. The results were compared to those obtained in previous factor-analytic studies of brain-damaged subjects, revealing patterns for the language/verbal subtests that diverged from those observed formerly. Two explanations are considered for these findings, the first interpretation centering on the notion of select impairments to specific cognitive processes and the second relating to impairments in the capacity to allocate resources effectively.

Brain

Neurotransmitter-mediated mechanisms of traumatic brain injury: acetylcholine and excitatory amino acids.

Research into traumatic brain injury (TBI), focusing on changes in energy metabolism, cerebrovascular dysfunction, and brain parenchymal morphology, has not produced complete descriptions of mechanisms mediating the pathophysiology of TBI. New studies indicate that neurochemical alterations mediate important components of brain physiology associated with TBI, and these alterations may be responsive to pharmacologic therapy. We discuss rodent models of TBI, review current experimental evidence of muscarinic cholinergic and excitatory amino acid (EAA) receptor involvement in its pathophysiology, and address issues relevant to the interpretation of these data.

Acetylcholine

Analysis of the Relationship between Early Clinical Factors and Glasgow Outcome Scale in Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to evaluate the association between early clinical factors and the Glasgow outcome scale (GOS) in patients with traumatic brain injury (TBI). METHODS: We conducted a retrospective analysis of 98 TBI patients who underwent emergency surgery between January 2021 and January 2024. Based on GOS scores at 6 months post-surgery, patients were classified into a favorable outcome group (GOS&#xa0;&#x2265;&#xa0;4, defined as moderate disability or good recovery,&#xa0;n = 58) and an unfavorable outcome group (GOS < 4, i.e., death, persistent vegetative state, or severe disability,&#xa0;n = 40). Baseline and early clinical parameters were compared between groups. Statistically significant variables from univariate analysis were entered into a multivariate logistic regression model to identify independent prognostic factors. RESULTS: Significant intergroup differences were observed in age, time from injury to surgery, bleeding site, midline shift, Glasgow coma scale (GCS) score at admission, blood glucose level, and D-dimer level (all p < 0.05). Multivariate analysis confirmed that age, time from injury to surgery, GCS score, blood glucose, and D-dimer level were independent predictors of GOS (all p < 0.05). CONCLUSION: Early clinical factors, including age, time to surgery, GCS score, blood glucose, and D-dimer level, independently influence GOS in TBI patients. Time from injury to surgery&#xa0;emerged as a potentially modifiable factor in this cohort, suggesting that minimizing delays may improve outcomes.

Humans

Symptoms of Allodynia and Pain Thresholds Amongst Those with Acute Post-Traumatic Headache Attributed to Mild Traumatic Brain Injury: A Prospective, Longitudinal Study.

BACKGROUND: Post-traumatic headache (PTH) is a common acute and persistent symptom following mild traumatic brain injury (mTBI). Symptoms of cutaneous allodynia and presence of nociceptive sensitization might be associated with acute PTH and its persistence. The objectives of this study were to compare allodynia symptoms and cutaneous heat pain thresholds amongst males and females with acute PTH to healthy controls (HC) and determine if pain thresholds and allodynia symptoms are associated with PTH outcomes. METHODS: This prospective longitudinal study enrolled 139 adults with acute PTH attributed to mTBI as defined by the International Classification of Headache Disorders and 95 HC. All PTH participants completed a baseline research visit near PTH onset and a follow-up visit three to four months later. All PTH participants and a subset of HC completed the Allodynia Symptom Checklist (ASC-12) at each research visit. A different subset of the participants underwent quantitative sensory testing (QST) during baseline, 4-week, and 16-week research visits to quantify cutaneous heat pain thresholds at the forehead and forearms. Data from daily headache diaries were used to determine longitudinal PTH improvement versus non-improvement at three months. ASC-12 score and pain threshold comparisons were made between PTH and HC groups, PTH improved versus non-improved cohorts, and between PTH males and females. RESULTS: Participants with PTH had an average age of 42.6 years and 64.0% were female. HC had an average age of 40.0 years and 65.3% were female. At the first visit, PTH participant ASC-12 scores averaged 3.6 versus 0.1 amongst HC, p < 0.001. 44.8% of PTH participants had headache improvement at 3 months. ASC-12 scores were higher in the PTH non-improved versus improved group at baseline (4.0 versus 2.4, p = 0.038) and 3-month follow-up (3.4 versus 1.9, p = 0.012). ASC-12 scores were higher in females than males at baseline (4.7 versus 1.6, p < 0.001) and 3-months (3.9 versus 1.2, p < 0.001). Cutaneous heat pain thresholds at the forehead and forearm did not differ between any group. CONCLUSIONS: PTH attributed to mTBI is associated with symptoms of cutaneous allodynia. Greater allodynia symptoms are present in females with PTH compared to males and may be associated with PTH non-improvement.

allodynia

The role of oxygen radicals in the pathobiology of traumatic brain injury.

This manuscript considers some of the most prominent consequences of traumatic brain injury (TBI), namely vascular and axonal change, and evaluates the role of damaging oxygen radicals in their pathogenesis. To this end, existing as well as new data derived from traumatically injured experimental animals and humans was employed. Experimental animals were subjected to fluid-percussion brain injury. Some animals were equipped with cranial windows to allow for the functional assessment of the pial vasculature, while others received various exogenous tracers to assess blood-brain barrier status. In order to identify traumatically induced axonal change, some animals were also processed for the light and electron microscopic visualization of antibodies targeted to the neurofilament subunits. Similar immunocytochemical strategies were employed in the postmortem study of humans who had sustained severe TBI. Through these approaches, TBI was recognized to result in vascular abnormalities ranging from impaired vascular responsiveness to altered blood-brain barrier status. Typically, these vascular abnormalities continued for several hours postinjury and showed evolution which correlated with the production of damaging oxygen radicals. Importantly, the use of radical scavengers reversed these vascular abnormalities and provided protection. Traumatically induced axonal damage was also associated with evolving posttraumatic change. This involved the continued posttraumatic disassembly and misalignment of the intra-axonal neurofilament subunits which caused impaired axoplasmic transport leading to axonal swelling and detachment. Although these intra-axonal changes did not appear to be directly caused by oxygen radicals, it is suggested that the presence of oxygen radicals may exacerbate the progression of these reactive events.

Animals

Severe traumatic brain injury and risk for osteoporosis: a Mendelian randomization study.

BACKGROUND: The influence of nervous system activity on bone remodeling has been widely reported. Patients with traumatic brain injury (TBI) exhibit a high incidence of osteoporosis (OP). Nevertheless, the relationship between severe TBI (sTBI) and OP remains unclear. We performed Mendelian randomization (MR) analysis to assess the potential causal relationship between sTBI and OP. METHODS: Data on exposure and outcomes were acquired from genome-wide association studies (GWAS). Data on OP was obtained from UK Biobank (5,266 cases of OP and 331,893 controls). Data on sTBI was obtained from FinnGen Consortium (6,687 cases and 370,590 controls). Single nucleotide polymorphisms (SNPs) that underwent strict screening were regarded as instrumental variables. We used the inverse variance weighted (IVW), constrained maximum likelihood and model averaging (CML-MA), MR-Egger, and weighted median methods for causal effect estimation. To test the reliability of the results, sensitivity analysis was performed using Cochran's Q, leave-one-out, MR-Egger intercept, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) tests. RESULTS: The IVW analysis indicates that sTBI and OP have a suggestive association (odds ratio [OR]&#x2009;=&#x2009;1.004, 95% confidence interval [CI]&#x2009;=&#x2009;1.001,1.007; p&#x2009;=&#x2009;0.002), and no heterogeneity (Q&#x2009;=&#x2009;11.536, p&#x2009;=&#x2009;0.241) or directional pleiotropy was observed (egger_intercept&#x2009;=&#x2009;7.368&#x2009;&#xd7;&#x2009;10-&#x2009;5, p&#x2009;=&#x2009;0.870). The robustness of the results was validated using a leave-one-out sensitivity test. CONCLUSION: According to the MR analysis, sTBI and OP are likely suggestively related. This finding contributes to the prevention of OP in patients with sTBI and provides genetic evidence supporting the theory that the nervous system regulates bone remodeling.

Humans

The effect of age on motor and cognitive deficits after traumatic brain injury in rats.

Age is one of the most important predictors of outcome after human traumatic brain injury. This study used fluid percussion brain injury to investigate the effects of aging on outcome after brain injury in rats. Three-month-old (n = 8) and 20-month-old (n = 11) rats were injured at a low level (1.7-1.8 atm) of fluid percussion brain injury or received a sham injury (n = 6 for both age groups). Body weight and motor function (beam balance and beam walking) were assessed before injury and for the first 5 days after injury. Cognitive outcome was assessed with the Morris water maze on Days 11 to 15 after injury. Injury did not produce significant weight loss in either age group. At the low level of brain injury used in this study, the 3-month-old rats did not demonstrate any significant motor deficits on the beam-balance or beam-walking tasks. However, the 20-month-old rats displayed significant beam-balance deficits on each of the 5 postinjury test days and significant beam-walking deficits for the first 3 postinjury days. Although Morris water maze performance was impaired in both age groups, the magnitude of impairment was greater in the aged animals. These data demonstrate that traumatic brain injury in the aged animal is marked by increased motor and cognitive deficits, in the absence of pronounced compromise of the animal's general health.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Restrictive vs Liberal Transfusion Strategy in Traumatic Brain Injury: A Secondary Analysis of the TRAIN Trial.

IMPORTANCE: Anemia is a prevalent condition among patients with traumatic brain injury (TBI); however, the optimal hemoglobin (Hb) threshold to initiate red blood cell transfusion (RBCT) is not well defined. OBJECTIVE: To assess which of 2 different Hb thresholds for guiding RBCT in patients with anemia and TBI is associated with a more favorable neurological outcome. DESIGN, SETTING, AND PARTICIPANTS: This was a preplanned secondary analysis of the Transfusion Strategies in Acute Brain Injured Patients multicentric randomized clinical trial, conducted in 72 intensive care units across 22 countries between September 1, 2017, and December 31, 2022. Follow-up was completed June 30, 2023. Only patients with TBI were included in the present analysis, conducted from February to May 2025. INTERVENTIONS: Liberal (transfusion at Hb <9 g/dL [to convert to g/L, multiply by 10.0]) vs restrictive (transfusion at Hb <7 g/dL) RBCT strategy over a maximum of 28 days. MAIN OUTCOME AND MEASURES: The primary outcome was the occurrence of unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5 (overall range, 1-8, with higher scores indicating more favorable outcome) at 180 days. In addition, 14 prespecified serious adverse events, including infection and cerebral ischemia, were assessed. Data were analyzed using both the intention-to-treat and per-protocol principles. RESULTS: Of 486 patients who presented with TBI (mean [SD] age, 46.8 [17.6] years; 347 [71.4%] male), 475 were included in the primary outcome analysis: 236 were randomized to the liberal transfusion strategy group and 239 to the restrictive transfusion strategy group. Both groups had similar baseline characteristics. In total, 534 RBCTs were administered in the liberal transfusion strategy group, compared with 246 RBCTs in the restrictive group. At 180 days after randomization, 138 patients (58.5%) in the liberal group had unfavorable neurological outcome compared with 161 patients (67.4%) in the restrictive group (relative risk [RR], 0.86 [95% CI, 0.75-1.00]; P&#x2009;=&#x2009;.047; fragility index&#x2009;=&#x2009;1). There were no significant differences in the occurrence of secondary outcomes (eg, 28-day mortality: 42 of 240 [17.5%] vs 51 of 244 [20.9%]; RR, 0.84 [95% CI, 0.58-1.21]; P&#x2009;=&#x2009;.34) or serious adverse events (eg, RR, 1.13 [95% CI, 0.88-1.43]; P&#x2009;=&#x2009;.34 for infection and RR, 0.87 [95% CI, 0.40-1.90]; P&#x2009;=&#x2009;.72 for cerebral ischemia). After adjustment for several confounders, being randomized to the liberal group was associated with a lower observed probability of unfavorable neurological outcome (odds ratio, 0.60 [95% CI, 0.38-0.94]; P&#x2009;=&#x2009;.03). CONCLUSIONS AND RELEVANCE: In this secondary analysis of a multicenter randomized clinical trial, a liberal RBCT strategy was associated with a lower risk than a restrictive RBCT strategy of unfavorable neurological outcome at 180 days among patients with TBI. These findings should be interpreted with caution in light of the inherent uncertainty of the estimate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02968654.

Humans

Prediction of motor status 3 and 6 months post severe traumatic brain injury: a preliminary study.

The prediction of outcome following severe traumatic brain injury has received considerable attention in recent years. Previous prediction studies have focused on a long-term follow-up or prediction period. The reported outcome measures generally adopted a global approach (e.g. independent living) in terms of the prediction of physical function. The objective of the present study was to construct clinically useful predictive equations of motor system status, as represented by selected postural reactions (indicators of central nervous system function). Specifically, these equations would serve to predict the recovery of equilibrium and protective reactions both at 3 and 6 months post-injury, respectively. A stepwise multiple logistic regression analysis was performed, where nine predictive variables were considered using a multivariate approach. The results indicate that coma duration followed by age contribute significantly to the predictive capability of the models at both 3 and 6 months post-injury. Specifically, at 3 months, the predictive variables 'coma duration' and 'age' enabled an 84.62% correct prediction rate, whereas, at 6 months, 'coma duration' and 'age' enabled a 79.49% correct prediction rate. In addition, the exact probabilities (for given sample ages and coma durations) and associated 95% confidence intervals were calculated based on the predictive models obtained. The theoretical framework underlying these predictive models can form the basis for further studies. Furthermore, these preliminary predictive models have potential implications for early treatment planning and patient management.

Adult

Oro-esophageal feeding for tracheostomized patients with severe traumatic brain injury: a randomized controlled trial.

BACKGROUND: This study reports the clinical effects of intermittent oro-esophageal tube feeding (IOE) versus nasogastric tube feeding (NGT) on nutritional status, aspiration pneumonia, decannulation, and level of consciousness in tracheostomized patients with severe traumatic brain injury (sTBI). METHODS: A randomized controlled trial was conducted between March 2024 and October 2025 in China and included tracheostomized patients with sTBI. Participants were randomized 1:1 to the intervention and control groups for 28-day interventions. IOE or NGT was used for nutritional supports, respectively. The primary outcome was nutritional status, including hemoglobin, albumin, prealbumin and body mass index. The secondary outcomes included aspiration pneumonia, decannulation, and level of consciousness assessed using the Glasgow Coma Scale (GCS). Generalized linear mixed-effects models, generalized estimating equations, and Cox regression were used for data analyze. RESULTS: A total of 104 participants were included in the analysis. After intervention, significant interaction effects were observed in hemoglobin (&#x3b2;&#x2009;=&#x2009;5.272, 95% CI: 2.707, 7.837), albumin (&#x3b2;&#x2009;=&#x2009;3.675, 95% CI: 1.854, 5.496), prealbumin (&#x3b2;&#x2009;=&#x2009;11.835, 95% CI: 6.623, 17.047), body mass index (&#x3b2;&#x2009;=&#x2009;1.719, 95% CI: 0.868, 2.569), the GCS (&#x3b2;&#x2009;=&#x2009;0.981, 95% CI: 0.572, 1.390), and aspiration pneumonia (OR= 0.304, 95% CI: 0.133, 0.693). The Cox model revealed that group significantly influenced the decannulation outcomes [HR (95% CI) =5.556 (3.197, 9.657), p&#x2009;<&#x2009;0.001]. CONCLUSIONS: In tracheostomized patients with sTBI who received routine treatment, IOE is more conducive to decannulation and the improvement in nutritional status, aspiration pneumonia, and level of consciousness than NGT. CLINICAL TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT06328985, 03/18/2024, clinicaltrials.gov/study/NCT06328985).

Humans

Estimating energy expenditure in traumatic brain injury: comparison of indirect calorimetry with predictive formulas.

A high degree of variability in energy expenditure has characterized the metabolic response to traumatic brain injury. A goal of parenteral or enteral repletion in this population is the precise estimation of caloric requirement to avoid complications associated with overfeeding and underfeeding. The first aim of this study was to evaluate three predictive formulas for comparison to measured energy expenditure (MEE) derived from indirect calorimetry in patients with traumatic brain injury. A total of 385 measurements were obtained in 102 patients and were compared concurrently with these predictive formulas. The best predictive method in this phase (bivariate regression) yielded r = 0.39 and P less than 0.001 (231 repeated measures). This best prediction, when compared with MEE, however, was able to capture values within 75 to 125% of MEE in only 56% of measurements. The two remaining formulas yielded r = 0.38 (P less than 0.001) and r = 0.23 (P less than 0.001) in 386 and 267 repeated measures, respectively. The second aim of this study was to evaluate the ability of additional nutritional markers to improve predictive ability. Regression analyses were performed on nutritional markers including indices of severity of injury, concurrent drug therapy, vital signs, neurological status, gluconeogenesis, protein synthesis/excretion, and immune response. The statistical results of the analysis on these multiple nutritional markers showed only heart rate, temperature, and number of days elapsed after injury to be significant predictors of MEE by indirect calorimetry in multiple regression analyses (R = 0.32; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Differential treatment of focal traumatic brain injury].

On the basis of observation of 65 patients with focal traumatic injury to the brain (hematoma of mater encephali was noted in 24, intracerebral--in 27, a focus of type III brain contusion--in 24, type IV--in 11, multiple hematomas and foci on contusion-crush--in 21), the criteria for their non-surgical treatment have been substantiated. Choice of a method for the treatment depends on the sizes of a hematoma, focus of contusion-crush, location of an injury, degree of its influence on the brain structures (deformation, shift), value of intracerebral pressure, dynamics of the clinico-roentgenologic symptoms.

Adolescent

Regional cerebrovascular responses to progressive hypotension after traumatic brain injury in cats.

We investigated the effects of hypotension on cerebral blood flow (CBF) after traumatic brain injury (TBI) in cats. Isoflurane-anesthetized cats were prepared for TBI and for microsphere measurements of total (T) and regional (r) CBF. Four groups were studied: sham injury (group I, n = 6); TBI (group II, n = 6); isoflurane anesthesia, no TBI or hypotension (group III, n = 4); and isoflurane and TBI, no hypotension (group IV, n = 8). After TBI or sham trauma, mean arterial pressure (MAP) was reduced to 80, 60, and 40 mmHg by hemorrhage. Group I TCBF did not change significantly from baseline until MAP reached 40 mmHg, but rCBF was more dependent on MAP in anterior hemispheric than in brain stem regions. Group II TCBF was significantly lower than baseline, and group I TCBF at all levels of hypotension and autoregulation was impaired at higher MAP levels in anterior than in posterior brain regions. Groups III and IV indicated that decreases in TCBF were not due to duration of the preparation or to TBI in the absence of hemorrhagic hypotension. We conclude that global and regional autoregulation are absent in response to hemorrhagic hypotension after TBI.

Anesthesia

The differential diagnosis of perceptual deficits in traumatic brain injury patients.

This article describes a perceptual testing battery useful in the evaluation of the traumatic-brain-injury patient. Areas of visual perceptual deficits significant in this population are discussed. Key tests, familiar to optometrists, are indicated for the evaluation of these areas. A differential diagnosis based on the results of these tests can be made. This allows for an effective visual rehabilitation program to be developed for these patients.

Brain Injuries

Traumatic brain injury crisis intervention and family therapy--management and outcome. Brain Injury Treatment and Research Group.

This article presents a model for crisis intervention and family therapy after traumatic brain injury. Our program, firmly rooted in object-relations theory and transactional analysis, included patients and family members (significant others) living within 100 miles from the University Hospital of Umeå. The effects of the interventions were gauged at one and two years after the trauma are presented in terms of agreement/disagreement between the patient and the significant other concerning inter- and intrapersonal relationships as well as through a short case presentation. As a conclusion of our study a point is made to expand the scope of intervention to include also other segments of the social network of the patient.

Adult

Microtubule-associated protein 2 levels decrease in hippocampus following traumatic brain injury.

We examined microtubule-associated protein 2 (MAP2) levels in hippocampal and cortical tissue 3 h following moderate traumatic brain injury (TBI) in the rat. MAP2 levels were assayed by quantitative immunoreactivity in tissue fractions obtained from naive, sham-injured, or fluid percussion-injured animals. Tissues were homogenized in the presence of protease inhibitors (0.3 mM phenylmethylsulfonyl fluoride, PMSF), a specific calpain inhibitors (0.1 mM leupeptin), and chelators (2 mM ethylene glycol-bis-tetraacetic acid, EGTA; 1 mM ethylenedinitrilo-tetraacetic acid, EDTA) to eliminate in vitro MAP2 proteolysis during tissue processing. Compared to naive rats, sham injury had no effect on soluble MAP2 levels in either cortex (105.0 +/- 4.4% of naive value) or hippocampus (106.6 +/- 5.2% of naive value). However, TBI caused a significant (p < 0.005) decrease in hippocampal MAP2 levels (55.7 +/- 5.9% of sham-injured controls). The effect appeared to be regionally selective, since the MAP2 decrease did not occur in cortex (89.1 +/- 1.4%). The degree of MAP2 decrease in hippocampus was similar in both membrane (57.8%) and cytosolic (55.7%) fractions, ruling out the possibility of partitioning artifacts. The data suggest that sublethal alterations of neuronal structure and function caused by MAP2 degradation may play an important role in the development of TBI-induced functional deficits. Since MAP2 is exclusively associated with the cytoskeleton in somal and dendritic compartments of neurons, the pathophysiology of sublethal magnitudes of TBI may also involve dendritic and somal dysfunction.

Animals