Cognitive rehabilitation using immersive virtual reality at young age: A case report on traumatic brain injury

Objective Traumatic brain injury (TBI) proves to be an obstacle for Bangladeshi patients due to the lack of facilities and specialist doctors in regional sections of the country. This study aimed to record different attributes of Bangladeshi TBI patients over a year i.e., their injury characteristics, treatments received and understand their impacts on the severity of TBI. Method This cross-sectional study was carried out among 280 TBI patients treated in a tertiary care hospital in Dhaka. The physicians determined TBI's severity and prognosis as per the Glasgow Coma Scale (GCS) and Glasgow Outcome Score (GOS) respectively. Results Most TBI patients were male (76.1%) and aged between 18 and 50 years (52.2%), as in previous studies in South Asian countries. However, the prevalence of TBI due to road traffic accidents (RTAs) was much higher (67.9%) than in the earlier studies in South Asia. Additionally, more patients suffered from severe TBI (29.3%) and moderate TBI (35.7%), and a higher percentage of patients went through surgery (56.8%) compared to previous studies. A significant association of demographic (residence) and clinical characteristics (consciousness after injury, CT scan findings and treatment type) with the severity of TBI was found in bivariate analysis. It also revealed the significant dependence of clinical characteristics (TBI etiology, post-injury consciousness, treatment type and TBI severity) on TBI prognosis. Multivariate analysis showed that patients who were unconscious after TBI and with evident brain injury observed in CT scans have a substantially higher risk of having moderate or severe TBI than mild TBI. Moreover, patients with TBI due to RTAs or falls, evident brain injury in CT scans, post-surgical seizure, and moderate or severe TBI have a significantly higher risk of getting a more unfavorable TBI prognosis than moderate disability. Conclusions In this study, RTAs were found to be the major cause of TBI. Additionally, some variables were identified as possible determinants of TBI severity and prognosis among Bangladeshi patients. The correlation of these variables with TBI should be further studied with the hopes that steps will be taken to reduce TBI incidents and improve its management to reduce the overall burden.

Traumatic Brain Injury (TBI) is a major problem in military and civilian medicine. Yet, there are no simple non-invasive diagnostics for TBI. Our goal is to develop and clinically validate blood-based biomarker assays for the diagnosis, prognosis and management of mild, moderate and severe TBI patients. These assays will ultimately be suitable for deployment to far-forward combat environments. Using a proteomic and systems biology approach, we identified over 20 candidate biomarkers for TBI and developed robust ELISAs for at least 6 candidate biomarkers, including Ubiquitin C-terminal hydrolase- L1 (UCH-L1), Glial Fibrillary Acidic Protein (GFAP) and a 145 kDa breakdown products of αII-spectrin (SBDP 145) generated by calpain proteolysis. In a multi-center feasibility study (Biomarker Assessment For Neurotrauma Diagnosis And Improved Triage System (BANDITS), we analyzed CSF and blood samples from 101 adult patients with severe TBI [Glasgow Coma Scale (GCS) ≤ 8] at 6 sites and analyzed 27 mild TBI patients and 5 moderate TBI patients [GCS 9-15] from 2 sites in a pilot study. We identified that serum levels of UCH-L1, GFAP and SBDP145 have strong diagnostic and prognostic properties for severe TBI over controls. Similarly initial post-TBI serum levels (< 6 h) of UCH-L1 and GFAP have diagnostic characteristics for moderate and mild TBI. We are now furthering assay production, refining assay platforms (both benchtop and point-ofcare/ handheld) and planning a pivotal clinical study to seek FDA approval of these TBI diagnostic assays.

Repeat head computed tomography (RHCT) is common and routine for pediatric traumatic brain injury (TBI) patients. In mild (Glasgow Coma Scale; GCS 13–15) to moderate (GCS 9–12) TBI, recent studies have shown that RHCT without clinical deterioration does not alter management. However, the effectiveness of routine RHCT for pediatric TBI patients under 2 years has not been investigated. This study aims to investigate whether routine RHCT changes management in mild-to-moderate TBI patients under 2 years. We performed a retrospective review at the emergency department of the National Center for Child Health and Development between January 2015 and December 2019. Mild-to-moderate TBI patients under 2 years with an acute intracranial injury on initial head CT scan and receiving follow-up CT scans were included. Mechanism, severity of TBI, indication for RHCT, and their findings were listed. Study outcome was intervention based on the findings of RHCT. Intervention was defined as intubation, ICP monitor placement, or neurosurgery. We identified 50 patients who met inclusion criteria and most patients (48/50) had mild TBI. The most common mechanism was ‘fall’ (68%). Almost all RHCT was routine and the overall incidence of radiographic progression on RHCT was 12%. RHCT without clinical deterioration did not lead to intervention, although one patient with moderate TBI required intervention due to radiographic progression with clinical symptoms. Our study showed that routine RHCT without clinical deterioration for mild TBI patients under 2 years may not alter clinical management. We suggest that RHCT be considered when there is clinical deterioration such as decrease in GCS.

Working Memory Brain Activation Following Severe Traumatic Brain Injury

Objectives:In most of the emergency trauma intensive care units (ICUs) of India, neurosurgical opinion is sought for patients presenting with head trauma after earliest possible resuscitation to determine the further line of management. This study aimed to identify common risk factors, leading to neurological deterioration in conservatively managed patients of traumatic brain injury (TBI).Materials and Methods:This retrospective study analyzed patients admitted with acute TBI and traumatic intracranial hematoma under emergency trauma care ICU who did not require neurosurgical operation within 48 h of trauma. The recorded data were analyzed to determine the predictors of neurological deterioration using univariate and binary logistic regression analysis in SPSS-16 software.Results:Medical records of consecutive 275 patients of acute TBI presenting to the emergency department were studied. One hundred and ninety-three patients were afflicted with mild TBI (70.18%), 49 patients had moderate TBI (17.81%), and 33 had severe TBI (12%). In the outcome, 74.54% of patients were discharged, and operative decision was made on 6.18% of patients and 19.27% died. Severe TBI is the independent predictor of neurological deterioration during their stay in ICU. Progressive hemorrhagic injury (PHI) showed neurological deterioration in 86.5% of patients. Systemic inflammatory response syndrome (SIRS) was present in 93.5% of patients who had deteriorated neurologically. Dyselectrolytemia was the biochemical derangements seen in 24.36% of cases.Conclusion:This study revealed severe TBI, PHI, and SIRS to be strong and independent risk factors of neurological deterioration.

Persistent hiccups in neurocritical care patients can lead to negative outcomes, including exhaustion, sleep deprivation, malnutrition, depression, and even death. This study aims to evaluate demographic and clinical characteristics, risk factors, and management in trauma intensive care unit patients. This study investigates persistent hiccups in traumatic brain injury (TBI) patients admitted to the Trauma ICU at Banaras Hindu University, Varanasi, from July 2020 to January 2024. The study involved monitoring and recording hiccups during patients' ICU stays. Exclusion criteria included not participating, having GERD, advanced cancer, spinal cord injury, other CNS pathologies, deranged liver and renal profile, or on drugs causing hiccups, on sedative and neuro-muscular blocking agents. The study involved 59.8% of patients aged <40 years, with a mean age of 41.75±17.16 years. Most patients were male, with a male-to-female ratio of 1.88:1. Road traffic accidents (RTAs) were present in 60.3% of patients, followed by falls from height (17.5%). 75.7% of patients had severe type TBI, while the remaining had moderate type TBI. Out of 189 patients, 86 (45.5%) died and 103 (54.5%) survived. Age was a significant factor in TBI-related persistent hiccups, with severe TBI significantly associated with female gender and ventilator-associated pneumonia and the need for mechanical ventilation. The type of TBI (moderate or severe) and length of ICU stay were also associated with TBI-related persistent hiccups. A strong relationship was observed between severe TBI patients who fall from height and were not responsive to drugs for hiccups compared to moderate TBI. The length of ICU stay was also associated with TBI-related persistent hiccups, with patients with a length of ICU stay of >14 days having a higher risk of hiccups.Severe TBI is linked to female gender, ventilator-associated pneumonia, and mechanical ventilation. The type of TBI and length of ICU stay are also linked to persistent hiccups. Patients with severe TBI who fell from height are less responsive to hiccup drugs. Patients with over 14 days of ICU stay have a higher risk of developing persistent hiccups.

MEDLINE, PubMed Central, Embase, and CENTRAL. Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021. Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison. Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; p = 0.030). Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.

The microbiome may be affected by trauma and critical illness. Many studies of the microbiome in critical illness are restricted to a single body site or time point and confounded by preexisting conditions. We report temporal and spatial alterations in the microbiome of previously healthy children with severe traumatic brain injury (TBI). We collected oral, rectal, and skin swabs within 72 hours of admission and then twice weekly until ICU discharge. Samples were analyzed by 16S rRNA gene amplicon sequencing. Children undergoing elective outpatient surgery served as controls. Alpha and beta diversity comparisons were performed with Phyloseq, and differentially abundant taxa were predicted using Analysis of Composition of Microbiomes. Five quaternary-care PICUs. Patients less than 18 years with severe TBI requiring placement of an intracranial pressure monitor. None. Three hundred twenty-seven samples were analyzed from 23 children with severe TBI and 35 controls. The community composition of initial oral (F = 3.2756, R2 = 0.0535, p = 0.012) and rectal (F = 3.0702, R2 = 0.0649, p = 0.007) samples differed between TBI and control patients. Rectal samples were depleted of commensal bacteria from Ruminococcaceae, Bacteroidaceae, and Lachnospiraceae families and enriched in Staphylococcaceae after TBI (p < 0.05). In exploratory analyses, antibiotic exposure, presence of an endotracheal tube, and occurrence of an infection were associated with greater differences of the rectal and oral microbiomes between TBI patients and healthy controls, whereas enteral nutrition was associated with smaller differences (p < 0.05). The microbiome of children with severe TBI is characterized by early depletion of commensal bacteria, loss of site specificity, and an enrichment of potential pathogens. Additional studies are needed to determine the impact of these changes on clinical outcomes.

To investigate hippocampal volume changes in moderate to severe traumatic brain injury (TBI) patients compared to healthy controls and assess their association with post-traumatic epilepsy (PTE), focusing on age-related effects. Imaging and demographic data for TBI patients were obtained from the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) database; healthy controls matched by age and sex were sourced from Alzheimer's Disease Neuroimaging Initiative (ADNI), the National Institute of Mental Health (NIMH) Intramural Healthy Volunteer Dataset, the Parkinson's Progression Markers Initiative (PPMI), and the Autism Brain Imaging Data Exchange (ABIDE). MRI images for TBI subjects were obtained within 14-32 days post-injury. MRI data were preprocessed and segmented using FreeSurfer's recon-all pipeline and the hippocampal subfield segmentation module. TBI patients showed significantly smaller average hippocampal volumes than controls (β = -191.0, p = 8.33e-04, FDR p = 1.47e-03, Cohen's d = -0.36), notably in the right and left CA1 head regions. No significant hippocampal volume differences were found between TBI+ and TBI- patients overall. In patients aged 60+, TBI+ patients had significantly larger volumes in the right CA1 head than TBI- patients (β = 57.43, p = 0.0300, FDR p = 0.040; Cohen's d = 1.06). Hippocampal atrophy is evident in TBI patients but not directly linked to PTE development in most age groups. In patients over 60, hypertrophy in the right CA1 head may be associated with PTE, suggesting age and regional hippocampal changes influence epilepsy risk post-TBI. These findings highlight the complexity of hippocampal involvement in PTE and suggest potential shared mechanisms with neurodegenerative disorders such as Alzheimer's disease.

Introduction: Levetiracetam is a common therapy for seizure prophylaxis in patients presenting with a severe traumatic brain injury (TBI). National guidelines recommend seizure prophylaxis (PPX) for 7 days for severe TBIs. Institutional protocol is to give 20 mg/kg of a loading dose (LD) followed by scheduled dose pending renal function for 7 days. Due to variability in practice, the purpose of this study was to assess institutional use of levetiracetam for seizure prophylaxis in patients with suspected TBI and to assess institutional guideline adherence. Methods: This was a retrospective analysis of patients treated with levetiracetam for seizure prophylaxis at a level 1, academic health system. Patients were identified via the electronic medical record and an institutional TBI database. Patients were included if they received a levetiracetam LD and/or PPX dosing for seizure prophylaxis in TBI. Patients were excluded if the levetiracetam was for active seizing or if the PPX dose was given for an aneurysmal subarachnoid hemorrhage. The admission reason, head bleed location (if applicable), and incidence of seizure within one week of admit were collected as well. Results: A total of 69 patients were included. There were 11 (16%) patients with severe TBI correctly given a LD. There were 15 (22%) patients with severe TBI correctly treated with 7 days of PPX. However, only 5 (7%) of those patients correctly received both the LD and PPX dose per institutional protocol for severe TBI. Of the patients who got a LD, there were 5 (7%) that received status epilepticus dosing (60 mg/kg, max 4500mg) instead of TBI LD. There were 7 (10%) other patients with a severe TBI that had the LD inappropriately withheld. A fixed dose strategy of 1 or 2 grams for a loading dose was used in 4 (6%) patients. A total of 31 (45%) patients with mild/moderate TBIs had levetiracetam correctly withheld. There were 9 (13%) patients with a mild/moderate TBI that inappropriately received a LD. There were 20 (29%) patients with mild/moderate TBIs that inappropriately received 7 days of PPX dosing. Conclusions: Levetiracetam dosing varied widely and there was low protocol adherence. Given these results institution guidelines were updated to only recommend 7 days of levetiracetam prophylaxis and remove the loading dose recommendation.

Post-traumatic headache (PTH) is among the most prevalent of the secondary headache disorders. As currently classified by the International Classification of Headache Disorders, 2nd edition (ICHD-2), PTH must start within 7 days of a mild, moderate, or severe traumatic brain injury (TBI). PTH transitions from an acute subtype to a chronic subtype 3 months after the injury (1). No other defining clinical characteristics set PTH apart from other primary or secondary headache disorders. In fact, most PTHs appear to have a phenotype indistinguishable from primary headache disorders and may respond to the same treatments as primary headache disorders (2,3). It seems altogether intuitive that headaches would occur acutely in the majority of individuals after a mild TBI (or concussion). More vexing, and controversial, is the link between head trauma and the subsequent development of chronic headaches (4,5). PTHs persist beyond the acute period in a significant proportion of patients. Up to 60% of TBI patients have chronic headaches persisting for up to 12 months (4,6). That chronic PTHs develop more often in mild versus moderate to severe TBI, in cases with impending litigation or in the setting of analgesic medication overuse, suggests a role for factors independent of trauma in the process of headache chronification (4,7,8). While each (or all) of these factors may be important in the genesis of chronic headaches in individual cases, there is a lack of evidence supporting them as unifying hypotheses to explain the spectrum of chronic PTHs in civilian and military patient populations. A better understanding of the processes leading to headache chronification after brain trauma is needed. Over the past 3 years, large epidemiological studies of headaches in military, civilian, and veteran populations with head trauma have been completed (9–11), providing a valuable opportunity to better understand and classify PTHs. In this issue, Lucas et al. (10) report the findings of a multi-center, longitudinal study of headaches in a population of 378 patients with moderate to severe TBI. The subjects underwent a baseline headache evaluation shortly after TBI and were then followed by telephone interview at 3, 6, and 12 months after injury to longitudinally assess headache incidence and headache characteristics. To our knowledge, this is one of the largest longitudinal studies of headaches in TBI patients. Many interesting findings emerge from this study, parts of which have been published previously (10, 11). The cumulative headache incidence in the study cohort was 71% over 12 months. Forty-three percent of patients had headaches at the baseline assessment shortly after TBI and this proportion was stable over the next 12 months. There were no differences in headache incidence between mild, moderate, and severe TBI patients. Eighteen percent of all patients had a history of headaches prior to TBI with 57% of these being migraine or probable migraine. Similar to previous studies, pre-traumatic headache and female sex were risk factors for reporting headaches after TBI. Migraine and probable migraine were the most common headache types after trauma, accounting for 52% of headaches at baseline and 60% of headaches 6 months after injury. Migrainous headaches were 2–3fold more common than tension-type headaches (TTHs; 7–21%) at all time points. The high prevalence of migraine observed by Lucas et al. (10) sharply contrasts with older studies which suggested a higher prevalence of TTH after TBI, but are similar to the findings of recent studies in military and veteran populations which found migraine in 60 to over 90% of cases (2,3,9,12). Comparing PTH studies and study populations can be difficult, but the accumulation of

Establishing neurological prognoses in traumatic brain injury (TBI) patients remains challenging. To help physicians in the early management of severe TBI, we have designed a visual score (ICEBERG score) including multimodal monitoring and treatment-related criteria. We evaluated the ICEBERG scores among patients with severe TBI to predict the 28-day mortality and long-term disability (Extended Glasgow Outcome Scale score at 3 years). In addition, we made a preliminary assessment of the nurses and doctors on the uptake and reception to the use of the ICEBERG visual tool. This study was part of a larger prospective cohort study of 207 patients with severe TBI in the Parisian region (PariS-TBI study). The ICEBERG score included six variables from multimodal monitoring and treatment-related criteria: cerebral perfusion pressure, intracranial pressure, body temperature, sedation depth, arterial partial pressure of CO 2 , and blood osmolarity. The primary outcome measures included the ICEBERG score and its relationship with hospital mortality and Extended Glasgow Outcome Score. The hospital mortality was 21% (45/207). The ICEBERG score baseline value and changes during the 72nd first hours were more strongly associated with TBI prognosis than the ICEBERG parameters measured individually. Interestingly, when the clinical and computed tomography parameters at admission were combined with the ICEBERG score at 48 hours using a multimodal approach, the predictive value was significantly increased (area under the curve = 0.92). Furthermore, comparing the ICEBERG visual representation with the traditional numerical readout revealed that changes in patient vitals were more promptly detected using ICEBERG representation ( p < 0.05). The ICEBERG score could represent a simple and effective method to describe severity in TBI patients, where a high score is associated with increased mortality and disability. In addition, ICEBERG representation could enhance the recognition of unmet therapeutic goals and dynamic evolution of the patient's condition. These preliminary results must be confirmed in a prospective manner. Diagnostic Tests or Criteria; Level III.

Traumatic brain injury (TBI) is one of the leading causes of morbidity, disability and mortality across all age groups globally. Currently, only palliative treatments exist, but these are suboptimal and do little to combat the progressive damage to the brain that occurs after a TBI. However, multiple experimental treatments are currently available that target the primary and secondary biochemical and cellular changes that occur after a TBI. Some of these drugs have progressed to clinical trials and are currently being evaluated for their therapeutic benefits in TBI patients. The aim of this study was to identify which drugs are currently being evaluated in clinical trials for TBI. A search of ClinicalTrials.gov was performed on 3 December 2021 and all clinical trials that mentioned “TBI” OR “traumatic brain injury” AND “drug” were searched, revealing 362 registered trials. Of the trials, 46 were excluded due to the drug not being mentioned, leaving 138 that were completed and 116 that were withdrawn. Although the studies included 267,298 TBI patients, the average number of patients per study was 865 with a range of 5–200,000. Of the completed studies, 125 different drugs were tested in TBI patients but only 7 drugs were used in more than three studies, including amantadine, botulinum toxin A and tranexamic acid (TXA). However, previous clinical studies using these seven drugs showed variable results. The current study concludes that clinical trials in TBI have to be carefully conducted so as to reduce variability across studies, since the severity of TBI and timing of therapeutic interventions were key aspects of trial success.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are the most common causes of severe acute brain injury in younger Intensive Care Unit (ICU) patients. Dysglycemia (abnormal peak glycemia, glycemic variability, mean glycemia, nadir glycemia) is common in these patients but its comparative outcome associations are unclear. In a retrospective, cross-sectional, study of adults admitted to Australian and New Zealand ICUs with TBI and SAH from 2005 to 2015, we studied the relationship between multiple aspects of early (first 24 hours) dysglycemia and mortality and compared TBI and SAH patients with the general ICU population and with each other. Among 670,301 patients, 11,812 had TBI and 6,098 had SAH. After adjustment for illness severity, we found that the mortality rate increased with each quintile of glycemia for each aspect of early dysglycemia (peak glycemia, glycemic variability, mean glycemia, nadir glycemia; P<0.0001 for all). This increased risk of death was greater in TBI and SAH patients than in the general ICU population. Moreover, it was stronger for mean glycemia (increase in mortality from 9.2% in the lowest quintile to 15.1% in general ICU patients compared with an increase in mortality from 4.4% to 49.0% for TBI and SAH patients; P<0.0001). Finally, in TBI patients, this relationship was significantly stronger than in SAH patients (P<0.0001). In TBI and SAH patients, greater dysglycemia is associated with greater mortality. This association is significantly stronger than in the general population and it is significantly stronger in patients with TBI compared with SAH.

Background: Post-Traumatic Epilepsy (PTE) affects one-third of severe traumatic brain injury (TBI) patients and is associated with poor functional outcomes. While TBI is characterized by continued recovery years after injury, the trajectory of functional recovery in PTE patients is not well understood. Using a novel sliding scale, we hypothesized that PTE acts as a ‘second hit’ after TBI, slowing recovery over time. Methods: We performed a retrospective analysis of severe TBI patients (Glasgow Coma Scale (GCS) ≤ 8) treated from 2002 to 2018 at a Level 1 trauma center. We used the International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) model to assign a sliding scale score. This score was based on the difference between the expected threshold for an unfavorable outcome (Glasgow Outcome Scale (GOS) = 1-3) and the actual score. Hence, a sliding score captures the magnitude of change between levels on the GOS according to each patient’s baseline prognosis. Scores ranged from -3 to +2, with positive scores denoting improvement compared to baseline prognosis, as expected in most TBI patients. Thus, a sliding scale score serves as a marker of a patient’s expected recovery over time. We used the Wilcoxon Rank-Sum test to compare the change in sliding scores over time for patients with and without PTE. Results: We had 392 patients with a median age of 33 (interquartile range (IQR)=23-47.5) Improvement for patients with PTE on the sliding scale was less (25.42% compared to 32.62% without PTE) over two years post-injury. PTE patients show a significant decline in functional outcomes compared to non-PTE patients during the 6 to 24-month follow-up period (p=0.04.) Conclusion: Post-traumatic epilepsy is associated with delayed recovery after severe TBI. Future PTE clinical trials should consider a sliding scale approach to explore if early, aggressive treatment improves functional outcomes.