Comparación de la efectividad entre distintas intervenciones en los síntomas posconmoción en adolescentes y jóvenes: una revisión bibliográfica / Comparison of effectiveness between different interventions in postconcussive symptoms in adolescents and young people: A literature review

Introducción: Actualmente la conmoción cerebral se considera un problema de gran magnitud, siendo los adolescentes y jóvenes la población de riesgo, ya que se encuentran en proceso de maduración. Nuestro objetivo ha sido comparar la eficacia de diferentes intervenciones (ejercicio físico terapéutico, terapia vestibular y descanso) en adolescentes y jóvenes con conmoción cerebral.Desarrollo: Se realizó una búsqueda bibliográfica en las principales bases de datos. Una vez aplicados los criterios de inclusión/exclusión y la escala metodológica Physiotherapy Evidence Database PEDro, fueron revisados seis artículos. Los resultados apoyan la utilización del ejercicio y la terapia vestibular en las etapas iniciales para disminuir los síntomas posconmoción. Según la mayoría de los autores, el ejercicio físico terapéutico y la terapia vestibular reportan mayores beneficios, aunque se necesitaría un protocolo que unificara escalas de valoración, variables de estudio y parámetros de análisis para poder realizar la inferencia en la población diana.Conclusión: Desde el momento del alta hospitalaria del paciente, la aplicación combinada de ejercicio físico y terapia vestibular, podría considerarse como la mejor opción para disminuir los síntomas posconmoción.(AU)

Introduction: Currently, concussion considers a problem of great magnitude, adolescents and young people being the population at risk, since it is in the process of maturation. Our goal has been to compare the effectiveness of different interventions (exercise therapy, vestibular rehabilitation and rest) in adolescents and young people with concussion. Development: A bibliographic search was carried out in the main databases. Once the inclusion / exclusion criteria and the PEDro methodological scale were applied, 6 articles were reviewed. The results support the use of exercise and vestibular rehabilitation in the initial stages to reduce post-concussion symptoms. According to most authors, therapeutic physical exercise and vestibular rehabilitation report greater benefits, although a protocol that unifies assessment scales, study variables and analysis parameters would be needed to be able to make the inference in the target population. Conclusión: From the moment of hospital discharge, the combined application of exercise and vestibular rehabilitation could be the best option to reduce post-concussion symptoms.(AU)

Cerebral Vasospasm After Burr Hole Evacuation of Chronic Subdural Hematoma.

Cerebral vasospasm is a frequent complication of subarachnoid hemorrhage. We report a case of chronic subdural hematoma complicated by cerebral vasospasm after burr hole evacuation. A 74-year-old woman underwent burr hole evacuation of a chronic subdural hematoma. She developed left hemiparesis and disturbance of consciousness on postoperative day 3. Magnetic resonance imaging showed a right parietal infarct and decreased cerebral blood flow signal in the right middle cerebral artery territory. Digital subtraction angiography showed multiple segmental narrowings of the right middle cerebral artery. Her neurological symptoms recovered with conservative treatment. Follow-up angiography showed improvement in the arterial narrowing, which finally led to a diagnosis of cerebral vasospasm. Cerebral vasospasm can occur after burr hole evacuation of chronic subdural hematoma. Magnetic resonance angiography is useful for determining the cause of postoperative neurological worsening in chronic subdural hematoma patients.

Edema progression in proximity to traumatic microbleeds: evolution of cytotoxic and vasogenic edema on serial MRI.

Introduction: Although cerebral edema is common following traumatic brain injury (TBI), its formation and progression are poorly understood. This is especially true for the mild TBI population, who rarely undergo magnetic resonance imaging (MRI) studies, which can pick up subtle structural details not visualized on computed tomography, in the first few days after injury. This study aimed to visually classify and quantitatively measure edema progression in relation to traumatic microbleeds (TMBs) in a cohort of primarily mild TBI patients up to 30 days after injury. Researchers hypothesized that hypointense lesions on Apparent Diffusion Coefficient (ADC) detected acutely after injury would evolve into hyperintense Fluid Attenuated Inversion Recover (FLAIR) lesions. Methods: This study analyzed the progression of cerebral edema after acute injury using multimodal MRI to classify TMBs as potential edema-related biomarkers. ADC and FLAIR MRI were utilized for edema classification at three different timepoints: ≤48 hours, ~1 week, and 30 days after injury. Hypointense lesions on ADC (ADC+) suggested the presence of cytotoxic edema while hyperintense lesions on FLAIR (FLAIR+) suggested vasogenic edema. Signal intensity Ratio (SIR) calculations were made using ADC and FLAIR to quantitatively confirm edema progression. Results: Our results indicated the presence of ADC+ lesions ≤48 hours and ~1 week were associated with FLAIR+ lesions at ~1 week and 30 days, respectively, suggesting some progression of cytotoxic edema to vasogenic edema over time. Ten out of 15 FLAIR+ lesions at 30 days (67%) were ADC+ ≤48 hours. However, ADC+ lesions ≤48 hours were not associated with FLAIR+ lesions at 30 days; 10 out of 25 (40%) ADC+ lesions ≤48 hours were FLAIR+ at 30 days, which could indicate that some lesions resolved or were not visualized due to associated atrophy or tissue necrosis. Quantitative analysis confirmed the visual progression of some TMB lesions from ADC+ to FLAIR+. FLAIR SIRs at ~1 week were significantly higher when lesions were ADC+ ≤48 hours (1.22 [1.08-1.32] vs 1.03 [0.97-1.11], p=0.002). Conclusion: Awareness of how cerebral edema can evolve in proximity to TMBs acutely after injury may facilitate identification and monitoring of patients with traumatic cerebrovascular injury and assist in development of novel therapeutic strategies.

Superficial Siderosis After Traumatic Brain Injury: A Case Report.

Superficial siderosis (SS) is a rare condition in which chronic accumulation of the blood in the subarachnoid space over time leads to the buildup of hemosiderin deposits, which in turn cause neurological dysfunction in those affected. While reversibility of the damage done by this condition is nearly impossible, early detection can allow for immediate surgical intervention and thus prevent further progression of ataxia, hearing loss, and other neurological deficits caused by SS. We present a case of a 53-year-old male who was successfully diagnosed with SS secondary to a chronic post-traumatic pseudomeningocele and underwent surgical repair with the resolution of his symptoms. We aim to encourage more extensive workups for common neurological dysfunctions such as tinnitus or vertigo in patients who have a history of traumatic brain injury or any significant motor vehicle accidents.

The Effect of Dexamethasone on Neuroinflammation and Cerebral Edema in Rats With Traumatic Brain Injury Combined With Seawater Drowning.

OBJECTIVE: To investigate the effect and mechanism of dexamethasone (DX) on axonal injury after traumatic brain injury (TBI) combined with seawater drowning (SWD) in rats. METHODS: To gain an in-depth understanding of TBI + SWD in rats, we established the compound injury model of rats by the Marmarou method and intratracheal pumping of seawater to simulate the pathological conditions. Rats in the DX group received intraperitoneal injections of DX (1 mg/kg) immediately after injury, and rats in the sham group and TBI + SWD group received intraperitoneal injections of the same amount of normal saline. RESULTS: Hematoxylin-eosin (HE) showed that DX improved matrix looseness, cell swelling, and nuclear condensation 168 hours after injury. Immunohistochemistry (IHC) staining showed that the protein expression of AQP4 was decreased in the DX group compared with the TBI + SWD group from 12 hours to 168 hours after injury. DX decreased the modified neurological severity score (mNSS) significantly at 24 hours and 168 hours after injury (P < 0.05). At 72 h and 168 h after injury, DX significantly lowered the expressions of IL-8 and TNF-α (P < 0.05). CONCLUSION: DX may play a neuroprotective role by reducing cerebral edema and inflammatory response after TBI + SWD injury in rats.

Brain pathology and symptoms linked to concussion history: beyond chronic traumatic encephalopathy.

Repeated head trauma acquired through sports injuries has been associated with the development of long-term disabling symptoms that negatively impact the quality of life. In this retrospective case series, 52 male former professional athletes involved in contact sports and with a history of multiple concussions were evaluated for chronic clinical symptoms and post-mortem neuropathological diagnoses. The clinical symptoms of 19 cases were examined in greater detail for symptom type, severity and duration. Information on neurological, psychiatric and physical symptoms, substance use profiles and concussion histories was obtained from the athletes' next of kin and assessed in relation to post-mortem neuropathological diagnoses. Cases were categorized into three different neuropathological groups: no major neuropathological findings, the presence of only chronic traumatic encephalopathy (CTE) and the diagnosis(es) of other neurodegenerative diseases. Age at death and the presence of DNA damage in the post-mortem brains were analysed for correlation with the clinical symptoms. In this case series, 14/52 (26.9%) cases (mean age 48.2 ± 11.4) had neuropathological evidence of low-stage/low-burden CTE. A total of 11/52 (21.2%) cases (mean age 38.7 ± 12.7) presented a similar profile and severity of behavioural symptoms to those with CTE, despite the lack of significant post-mortem neuropathological findings. A total of 27/52 (51.9%) cases (mean age 75.5 ± 8.7) presented with complex post-mortem neurodegenerative diagnoses, including Alzheimer's disease and other mixed pathologies, and clinical symptoms associated with language, memory and sensory dysfunction. The presence of DNA damage in the brain was found in all neuropathological groups, predominantly in the ependymal lining of ventricles, and phosphorylated histone H2AX staining was correlated with higher age at death (r = 0.59) and symptoms of language dysfunction (r = 0.56). Findings from our case series suggest that post-concussive symptoms are not driven by CTE. Our findings show that proteinopathies alone may not account for the complexity of the clinical manifestations and suggest the possibility of other drivers, such as DNA damage, as potentially useful markers of brain trauma. Broadening the search for biological markers that reflect the effects of brain injury, even when proteinopathy is not observed, and taking a symptom-driven approach are therefore advised.

The evolution of whole-brain turbulent dynamics during recovery from traumatic brain injury.

It has been previously shown that traumatic brain injury (TBI) is associated with reductions in metastability in large-scale networks in resting-state fMRI (rsfMRI). However, little is known about how TBI affects the local level of synchronization and how this evolves during the recovery trajectory. Here, we applied a novel turbulent dynamics framework to investigate whole-brain dynamics using an rsfMRI dataset from a cohort of moderate to severe TBI patients and healthy controls (HCs). We first examined how several measures related to turbulent dynamics differ between HCs and TBI patients at 3, 6, and 12 months post-injury. We found a significant reduction in these empirical measures after TBI, with the largest change at 6 months post-injury. Next, we built a Hopf whole-brain model with coupled oscillators and conducted in silico perturbations to investigate the mechanistic principles underlying the reduced turbulent dynamics found in the empirical data. A simulated attack was used to account for the effect of focal lesions. This revealed a shift to lower coupling parameters in the TBI dataset and, critically, decreased susceptibility and information-encoding capability. These findings confirm the potential of the turbulent framework to characterize longitudinal changes in whole-brain dynamics and in the reactivity to external perturbations after TBI.

Effectiveness of biomedical interventions on the chronic stage of traumatic brain injury: a systematic review of randomized controlled trials.

Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.

Relationship between sodium level and in-hospital mortality in traumatic brain injury patients of MIMIC IV database.

Background: An association between prognosis and high sodium levels in Traumatic Brain Injury (TBI) patients in Intensive Care Units (ICUs) has been noted, but limited research exists on the ideal sodium level in these patients or the impact on early mortality, using the MIMIC-IV database. Methods: A retrospective survey was conducted on TBI patients from the MIMIC-IV database. Patients were divided into two categories based on their highest serum sodium level within 24 h of admission exceeding 145 mmol/L: those with hypernatremia, and those with moderate-to-low sodium levels. Collected covariates encompasses demographic, clinical, laboratory, and intervention variables. A multivariate logistic regression model was implemented to forecast in-hospital mortality. Results: The study included 1749 TBI patients, with 209 (11.5%) experiencing in-hospital deaths. A non-linear test exposed an L-shaped correlation between sodium level and in-hospital mortality, with mortality rates increasing after a turning point at 144.1 mmol/L. Compared to the moderate-to-low group's 9.3% mortality rate, the hypernatremia group had a significantly higher mortality rate of 25.3% (crude odds ratio = 3.32, 95% confidence interval: 2.37 ~ 4.64, p < 0.001). After adjusting for all covariates, the hypernatremia group continued to show a significant correlation with higher mortality risk (adjusted odds ratio = 2.19, 95% confidence interval: 1.38 ~ 3.47, p = 0.001). This trend remained consistent regardless of the analyses stratification. Conclusion: The study reveals an L-shaped relationship between sodium levels and in-hospital deaths, with a pivotal point at 144.1 mmol/L. TBI patients displaying hypernatremia were independently linked to higher in-hospital mortality, underlining the need for further studies into targeted management of sodium levels in these patients.

Xuefu Zhuyu decoction promotes synaptic plasticity by targeting miR-191a-5p/BDNF-TrkB axis in severe traumatic brain injury.

BACKGROUND: Xuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal formula known for its ability to eliminate blood stasis and improve blood circulation, providing neuroprotection against severe traumatic brain injury (sTBI). However, the underlying mechanism is still unclear. PURPOSE: We aim to investigate the neuroprotective effects of XFZYD in sTBI from a novel mechanistic perspective of miRNA-mRNA. Additionally, we sought to elucidate a potential specific mechanism by integrating transcriptomics, bioinformatics, and conducting both in vitro and in vivo experiments. METHODS: The sTBI rat model was established, and the rats were treated with XFZYD for 14 days. The neuroprotective effects of XFZYD were evaluated using a modified neurological severity score, hematoxylin and eosin staining, as well as Nissl staining. The anti-inflammatory effects of XFZYD were explored using quantitative real-time PCR (qRT-PCR), Western blot analysis, and immunofluorescence. Next, miRNA sequencing of the hippocampus was performed to determine which miRNAs were differentially expressed. Subsequently, qRT-PCR was used to validate the differentially expressed miRNAs. Target core mRNAs were determined using various methods, including miRNA prediction targets, mRNA sequencing, miRNA-mRNA network, and protein-protein interaction (PPI) analysis. The miRNA/mRNA regulatory axis were verified through qRT-PCR or Western blot analysis. Finally, morphological changes in the neural synapses were observed using transmission electron microscopy and immunofluorescence. RESULTS: XFZYD exhibited significant neuroprotective and anti-inflammatory effects on subacute sTBI rats' hippocampus. The analyses of miRNA/mRNA sequences combined with the PPI network revealed that the therapeutic effects of XFZYD on sTBI were associated with the regulation of the rno-miR-191a-5p/BDNF axis. Subsequently, qRT-PCR and Western blot analysis confirmed XFZYD reversed the decrease of BDNF and TrkB in the hippocampus caused by sTBI. Additionally, XFZYD treatment potentially increased the number of synaptic connections, and the expression of the synapse-related protein PSD95, axon-related protein GAP43 and neuron-specific protein TUBB3. CONCLUSIONS: XFZYD exerts neuroprotective effects by promoting hippocampal synaptic remodeling and improving cognition during the subacute phase of sTBI through downregulating of rno-miR-191a-5p/BDNF axis, further activating BDNF-TrkB signaling.

Are geriatric transfer patients with traumatic brain injury at risk for worse outcomes compared to non-geriatric? Propensity-matched study.

OBJECTIVE: To compare outcomes between geriatric and non-geriatric patients with traumatic brain injury (TBI) transferred to trauma center and effects of anticoagulants/antiplatelets (AC/AP) and reversal therapy. METHODS: A retrospective review of 1,118 patients with TBI transferred from acute care facilities to level 1 trauma center compared in groups: geriatric versus non-geriatric, geriatric with AC/AP therapy versus without, and geriatric AC/AP with AC/AP reversal therapy versus without. RESULTS: Patients with TBI constituted 54.4% of trauma transfers. Mean transfer time was 3.9 h. Propensity matched by Injury Severity Score and Abbreviated Injury Score (AIS) head geriatric compared to non-geriatric patients had more AC/AP use (53.9% vs 8.8%), repeat head computed tomography (93.7% vs 86.1%), intensive care unit (ICU) admissions (57.4% vs 45.7%) and mortality (9.8% vs 3.2%), all p < 0.004. Patients on AC/AP versus without had more ICU admissions (69.1% vs 51.8%, p < 0.001). Patients with AC/AP reversals compared to without reversals had more AIS head 5 (32.0% vs 13.1%), brain surgeries (17.8% vs 3.5%) and ICU admissions (84.8% vs 57.1%), all p < 0.001. CONCLUSION: TBI constituted half of trauma transfers and 10% required surgery. Based on higher ICU admissions, mortality, and prevalence of AC/AP therapy requiring reversal, geriatric patients with TBI on anticoagulants/antiplatelets should be considered for direct trauma center admission.

Recall and recognition of similarities items in neuropsychological assessment: Memory, validity, and meaning.

The current study examined whether the Memory Similarities Extended Test (M-SET), a memory test based on the Similarities subtest of the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II), has value in neuropsychological testing. The relationship of M-SET measures of cued recall (CR) and recognition memory (REC) to brain injury severity and memory scores from the Wechsler Memory Scale, Fourth Edition (WMS-IV) was analyzed in examinees with traumatic brain injuries ranging from mild to severe. Examinees who passed standard validity tests were divided into groups with intracranial injury (CT + ve, n = 18) and without intracranial injury (CT-ve, n = 50). In CT + ve only, CR was significantly correlated with Logical Memory I (LMI: rs = .62) and Logical Memory II (LMII: rs = .65). In both groups, there were smaller correlations with delayed visual memory (VRII: rs = .38; rs = .44) and psychomotor speed (Coding: rs = .29; rs = .29). The REC score was neither an indicator of memory ability nor an internal indicator of performance validity. There were no differences in M-SET or WMS-IV scores for CT-ve and CT + ve, and reasons for this are discussed. It is concluded that M-SET has utility as an incidental cued recall measure.

FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Evaluating GCS and FOUR Score in Predicting Mortality of Traumatic Brain Injury Patients (TBI): A Prospective Study in a Tertiary Hospital of South Malabar.

Objective: This study evaluated the full outline of Unresponsiveness (FOUR) score and Glasgow Coma Scale (GCS) to predict traumatic brain injury (TBI) outcomes. Methods: Among 107 patients, FOUR and GCS grading systems analyzed emergency department patients within 24 hours. FOUR and GCS were assessed simultaneously. Patients were followed for 15 days/discharge/death to evaluate the results. Modified Rankin scores measured in-hospital mortality, morbidity, and stay. Results: 65.42% of patients were 25-65. 10% were under 25, and 25% were over 65. Patients were 81% male. Road traffic accidents (RTAs) (90%), falls (7.48%), and assaults (1.47%) caused TBI. 19.62% died. 85.7% of 21 non-survivors had GCS <5 and FOUR <4. GCS mortality sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.71%, 93.02%, 75, and 96.4 (P < 0.0001). FOUR score mortality sensitivity, specificity, PPV, and NPV were 85.71%, 96.51%, 85.7, and 96.5 (P < 0.0001). GCS and FOUR AUCs matched (P = 0.52). The unadjusted model reduced in-hospital mortality by 14% for every one point increase in GCS. Every 1-point FOUR score increase reduced in-hospital mortality by 40% in the unadjusted model. GCS and FOUR scored 0.9 Spearman. Conclusion: The FOUR score was comparable in the prediction of mortality in these patients.

Assessment of GCS and FOUR Score as Prognostic Indicators for Hospital Stay and Morbidity in Traumatic Brain Injury Patients: An Observational Study.

Aim: The objective of the present research was to evaluate variations in hospital stay as well as morbidity based on the Glasgow Coma Scale (GCS) and Full Outline of Un-Responsive (FOUR) scores for patients who had traumatic brain injury (TBI). Materials and Methods: A total of 107 patients with TBI patients who attended the emergency department of MES Medical College, Perinthalmanna, were enrolled into the study. FOUR and GCS scoring systems were used to assess the patients within 24 hours of the presentation to the emergency department. Both FOUR and GCS scoring systems were assessed at the same time. The outcome was measured in terms of length of hospital stay and morbidity, which was assessed using modified Rankin score. Chi-square test was used to calculate sensitivity, specificity, positive predictive value, and negative predictive value. The area under the curve (AUC) was calculated using receiver operating characteristic curve analysis. A P value <0.05 was considered significant. Results: We found a strong positive correlation between GCS and FOUR score with a Spearman coefficient of 0.9. Comparison of AUC between GCS score and FOUR score showed a statistically significant difference (P = 0.0044), predicting that FOUR score was a better predictor of hospital stay (>15 days) than GCS score. Comparison of AUC between GCS score and FOUR score showed a significant statistical difference (P = 0.0002), showing that FOUR score was a better predictor of morbidity than GCS. Conclusion: FOUR score was a better predictor of hospital stay and morbidity as compared to GCS score.

Applying the Consensus Criteria for Traumatic Encephalopathy Syndrome Retrospectively to Case Studies of Boxers from the 20th Century.

There are no validated diagnostic criteria for traumatic encephalopathy syndrome (TES). During the early and middle 20th century, TES was described as a clinical condition that was experienced by some high-exposure boxers-and it was believed to reflect chronic traumatic brain injury. Consensus criteria for the diagnosis of TES were published in 2021. We applied the consensus criteria for TES retrospectively to cases of chronic brain damage in boxers described in articles published in the 20th century that were obtained from narrative and systematic reviews. The sample included 157 boxers identified in 21 articles published between 1929 and 1999. Two authors reviewed each case description and coded the criteria for TES. For the core clinical features, cognitive impairment was noted in 63.1%, and in 28.7% of cases the person's cognitive functioning appeared to be broadly normal. Neurobehavioral dysregulation was present in 25.5%. One third (34.4%) were identified as progressive, 30.6% were not progressive, and the course could not be clearly determined in 35.0%. In total, 29.9% met the TES consensus criteria, 28.0% did not, and 42.0% had insufficient information to make a diagnostic determination. TES, in the 20th century, was described as a neurological condition, not a psychiatric disorder-and this supports the decision of the 2021 consensus group to remove primary and secondary psychiatric diagnoses from being a core diagnostic feature. Future research is needed to determine whether, or the extent to which, cognitive impairment or neurobehavioral dysregulation described as characterizing TES are associated with chronic traumatic encephalopathy neuropathological change.

Comparative Analysis of Clinical Severity and Outcomes in Penetrating Versus Blunt Traumatic Brain Injury Propensity Matched Cohorts.

Traumatic brain injury (TBI) is a global health challenge; however, penetrating brain injury (PBI) remains under-represented in evidence-based knowledge and research efforts. This study utilized data from the Trauma Quality Improvement Program (TQIP) of the National Trauma Data Bank (NTDB) to investigate outcomes of PBI as compared with clinical-severity-matched non-penetrating or blunt TBI. A total of 1765 patients with PBI were 1:1 propensity score-matched for clinical severity with blunt TBI patients. The intent of PBI was self-inflicted in 34.1% of the cases, and the mechanism was firearm-inflicted in 89.1%. Mortality was found to be significantly more common in PBI than in the severity- matched TBI cohort (33.9% vs. 14.3 %, p < 0.001) as was unfavorable outcome. Mortality was mediated by withdrawal of life-sustaining therapies (WOLST) 30% of the time, and WOLST occurred earlier (median 3 days vs. 6 days, p < 0.001) in PBI. Increased rate of mortality was observed with a Glasgow Coma Scale (GCS) of <11 in PBI as compared with <7 in blunt TBI. In conclusion, PBI patients exhibited higher mortality rates and unfavorable outcomes; one third of excess mortality was mediated by WOLST. The study also brings into question the applicability of the conventional TBI classification, based on GCS, in PBI. We emphasize the need to address the observed disparities and better understand the distinctive characteristics and mechanisms underlying PBI outcomes to improve patient care and reduce mortality.

Relationships between vestibular issues, noise sensitivity, anxiety and prolonged recovery from mild traumatic brain injury among adults: a scoping review.

BACKGROUND: We investigated the extent of literature and findings on relationships between vestibular issues, noise sensitivity (NS), and anxiety. We were interested in how relationships among these factors impacted adults' recovery three months or more after mild traumatic brain injury (mTBI). METHODS: We conducted a scoping review to evaluate the extent of evidence linking relationships between vestibular issues, NS and anxiety with recovery after mTBI. Data relating to study characteristics and key findings were extracted and used to inform a critical narrative synthesis of findings. RESULTS: After screening and full-text review, we included two studies. Both studies considered the combination of vestibular issues, NS and anxiety and mTBI recovery. Vestibular issues, NS and anxiety were all significantly associated with one another and their presence was the strongest indicator that symptoms would extend beyond three-months after mTBI. CONCLUSION: Few studies have focused on the relationships that vestibular issues, NS and anxiety have with one another and recovery after mTBI. Given the apparent strong relationships between these factors and prolonged recovery, we highlight this as an area warranting further investigation.

Vestibular issues, noise sensitivity and anxiety all appear to impact on recovery from mild traumatic brain injury.There appear to be quite strong relationships between vestibular, noise sensitivity and anxiety symptoms following mild traumatic brain injury.More work exploring these key symptoms and how they impact recovery from mild traumatic brain injury using a wide range of study methods and approaches are needed to advance the field.

DREADD-mediated activation of the periaqueductal gray restores nociceptive descending inhibition after traumatic brain injury in rats.

Traumatic Brain Injury (TBI) patients frequently experience chronic pain that can enhance their suffering and significantly impair rehabilitative efforts. Clinical studies suggest that damage to the periaqueductal grey matter (PAG) following TBI, a principal center involved in endogenous pain control, may underlie the development of chronic pain. We hypothesized that TBI would diminish the usual pain control functions of the PAG, but that directly stimulating this center using a chemogenetic approach would restore descending pain modulation. We used a well-characterized lateral fluid percussion model (1.3 ±0.1 atm) of TBI in male rats (n=271) and measured hindpaw mechanical nociceptive withdrawal thresholds using von Frey filaments. To investigate the role of the PAG in pain both before and after TBI we activated the neurons of the PAG using a Designer Receptor Exclusively Activated by Designer Drug (DREADD) viral construct. Immunohistochemical analysis of brain tissue was used to assess the location, and confirm the appropriate expression of the viral constructs in the PAG. Activation of the PAG DREADD using clozapine N-oxide (CNO) caused hindpaw analgesia that could be blocked using opioid receptor antagonist, naloxone, in uninjured but not TBI rats. Due to the importance of descending serotonergic signaling in modulating nociception, we ablated spinal serotonin signaling using 5,7-DHT. This treatment strongly reduced CNO-mediated anti-nociceptive effects in TBI but not uninjured rats. To define the serotonergic receptor(s) required for the CNO-stimulated effects in TBI rats we administered 5-HT7 (SB-269970) and 5-HT1A (WAY-100635) receptor antagonists but observed no effects. The selective 5-HT2A receptor antagonist ketanserin, however, blocked CNO's effects in the DREADD expressing TBI but not DREADD expressing sham TBI animals. Blockade of alpha-1 adrenergic receptors with prazosin also had no effect after TBI. Descending pain control originating in the PAG is mediated through opioid receptors in uninjured rats. TBI, however, fundamentally alters the descending nociceptive control circuitry such that serotonergic influences predominate, and those are mediated by the 5-HT2A receptor. These results provide further evidence that the PAG is a key target for anti-nociception after TBI.

Lesion Frequency Distribution Maps of Traumatic Axonal Injury on Early Magnetic Resonance Imaging after Moderate and Severe Traumatic Brain Injury and Associations to 12 Months Outcome.

Traumatic axonal injury (TAI) is a common finding on MRI in patients with moderate - severe traumatic brain injury (TBI), and the burden of TAI is associated with outcome in this patient group. Lesion mapping offers a way to combine imaging findings from numerous individual patients into common lesion maps where the findings from a whole patient cohort can be assessed. The aim of this study was to evaluate the spatial distribution of traumatic axonal injury (TAI) lesions on different MRI sequences and its associations to outcome with use of lesion mapping. 269 patients (8-70 years) with moderate or severe TBI traumatic brain injury and magnetic resonance imaging (MRI) within six weeks after injury were prospectively included. TAI lesions were evaluated and manually segmented on fluid-attenuated inversed recovery (FLAIR), diffusion weighted imaging (DWI) and either T2* gradient echo (T2*GRE) or susceptibility weighted imaging (SWI). The segmentations were registered to the Montreal Neurological Institute space and combined to lesion frequency distribution maps. Outcome was assessed with Glasgow Outcome Scale Extended (GOSE) score at 12 months. The frequency and distribution of TAI was assessed qualitatively by evaluated visually reading. Univariable associations to outcome was assessed qualitatively by visual reading evaluated visually and also quantitatively with use of voxel-based lesion-symptom mapping (VLSM). The highest frequency of TAI was found in the posterior half of corpus callosum. The frequency of TAI was higher in the frontal- and temporal lobes than in the parietal- and occipital lobes, and in the upper parts of the brainstem than in the lower. On At the group level, all the voxels in mesencephalon had TAI on FLAIR. The patients with poorest outcome (GOSE scores ≤ 4) had higher frequencies of TAI. On VLSM, poor outcome was associated with TAI lesions univariable associations to outcome was found bilaterally in the splenium, and in the right side of tectum, tegmental mesencephalon and pons. With this study, we present lesion frequency distribution maps of TAI in a large cohort of patients with moderate and severe TBI. In conclusion, we found the highest higher frequency of TAI in posterior corpus callosum, and TAI in splenium, mesencephalon and pons were associated to with poor outcome. In the future, integration into picture archiving systems would enable comparison of individual patient maps with If lesion frequency distribution maps containing outcome information based on imaging findings from numerous patients in the future can be compared to the imaging findings from individual patients, it would offer a new tool in the clinical work-up and outcome prediction of TBI patient. Key Words: Brain injuries, traumatic; Diffuse axonal injury; Neuroimaging; Brain mapping; Artificial intelligence.