Objective The study investigates experimental brain trauma in rabbits, assessing levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and interleukin 6 (IL-6) in serum and cerebrospinal fluid (CSF) and compares these biomarkers among trauma groups.
Methods Thirty rabbits were randomized to a control group (n=6) or to mild-, moderate-, and severe-trauma groups (n=8 each) created by dropping 200, 350, or 500 g weights, respectively, onto their skulls using a modified Marmarou impact acceleration model. CSF and venous blood samples were collected at 0, 12, and 24 hours after injury; UCH-1 L, GFAP, and IL-6 concentrations in CSF and serum were quantified by enzyme-linked immunosorbent assays, and group differences were analyzed with a Friedman test followed by Dunn-Bonferroni correction.
Results Neither CSF nor serum concentration of GFAP, IL-6, or UCH-L1 differed from those of controls after mild trauma. Severe head trauma produced markedly higher GFAP and IL-6 concentrations in CSF compared with the control group (P<0.05), with both biomarkers peaking at 12 hours after injury. Serum UCH-L1 increased significantly in both moderate-trauma (peak at 12 hours) and severe-trauma groups (peak at 24 hours) compared with the control group (P<0.05), whereas no intergroup difference in CSF UCH-L1 levels was evident.
Conclusion Serum UCH-L1 differentiated moderate and severe trauma from controls in a rabbit model, whereas CSF GFAP and IL-6 levels reflected severe injury. Validation in larger preclinical and clinical studies is warranted.
Objective To identify relationships between skull fracture (SF) and hyperfibrinolysis (HF) among patients with isolated traumatic brain injury (TBI). Methods This was a retrospective cohort study based on a nationwide neurotrauma database in Japan. Adult patients with isolated TBI (head Abbreviated Injury Scale [AIS] >2, any other AIS <3) and who were registered in the multicenter neurotrauma registry from 2015 to 2017 were included. To examine the relationship between SF and HF, we conducted multivariable logistic regression analyses to calculate the adjusted odds ratios (aORs) with their 95% confidence intervals (CIs) for HF. HF was defined as a D-dimer level ≥38 mg/L on arrival based on a previous study. Results A total of 335 patients were enrolled and the median age of the cohort was 64 years (interquartile range, 44–76 years). HF was observed in 161 patients (48.1%). The association of SF with HF yielded an aOR of 4.78 (95% CI, 2.71–8.42) compared to non-SF in multivariable logistic regression analysis. In addition, the associations of skull base fracture, skull vault fracture, and combination of skull base and vault fracture with HF yielded the corresponding aORs of 3.60 (95% CI, 1.20–10.81), 4.99 (95% CI, 2.63–9.44), and 4.84 (95% CI, 2.41–9.72), respectively, relative to non-SF. Conclusion This multicenter observational study demonstrated the association of SF with HF in patients with isolated TBI.
Kyung Won Park, Sung Wook Song, Woo Jeong Kim, Jeong Ho Kang, Ji Hwan Bu, Sung Kgun Lee, Seo Young Ko, Soo Hoon Lee, Chang Bae Park, Jin Gu Lee, Jong Yeon Kang, Jaeyoon Ha, Jiwon Kim
Clin Exp Emerg Med 2025;12(4):358-368. Published online January 15, 2025
Objective Traumatic brain injury (TBI) often occurs alongside injuries to other body regions, worsening patient outcomes. This study evaluates the impact of concomitant injuries on clinical outcomes in patients with isolated versus non-isolated TBI.
Methods This retrospective cross-sectional analysis was conducted using data from the Emergency Department-based Injury In-depth Surveillance (EDIIS) for 180,058 TBI patients admitted to 23 tertiary hospitals from January 1, 2020, to December 31, 2022. Patients were categorized into isolated TBI group (iTBI; n=127,673) and non-isolated TBI group (niTBI; n=52,385) based on injury diagnostic codes. Clinical outcomes—24-hour and 30-day mortality, hospital admission, and interhospital transfer—were compared. Multivariate logistic regression analyses adjusted for potential confounders were performed.
Results The niTBI patients exhibited significantly higher 24-hour mortality (1.5% vs. 0.4%), 30-day mortality (2.6% vs. 1.0%), hospital admissions (24.5% vs. 8.4%), and interhospital transfers (3.6% vs. 1.1%) than iTBI patients (all P<0.001). Concomitant injuries increased the adjusted odds of 24-hour mortality (adjusted odds ratio [aOR], 1.456; 95% confidence interval [CI], 1.286–1.648) and 30-day mortality (aOR, 1.111; 95% CI, 1.022–1.208). Thoracic injuries were the most significant predictor of adverse outcomes in niTBI patients, increasing the odds of 24-hour mortality by nearly sixfold (aOR, 5.958; 95% CI 5.057–7.019).
Conclusions Concomitant injuries significantly worsen clinical outcomes in TBI patients, with thoracic injuries being the most critical predictor of mortality. These findings highlight the importance of comprehensive trauma assessments and targeted prevention strategies to improve survival rates and optimize resource allocation for patients with multiple injuries.
Patrick J. Coppler, David J. Gagnon, Katharyn L. Flickinger, Jonathan Elmer, Clifton W. Callaway, Francis X. Guyette, Ankur Doshi, Alexis Steinberg, Cameron Dezfulian, Ari L. Moskowitz, Michael Donnino, Teresa L May, David B Seder, Jon C. Rittenberger
Clin Exp Emerg Med 2024;11(2):205-212. Published online January 29, 2024
Objective We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. Methods We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. Results After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group.
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Objective This study was conducted to evaluate the association between changes in repeated brain computed tomography (CT) findings and the optic nerve sheath diameter (ONSD) determined by ocular ultrasonography in patients with moderate blunt traumatic brain injury (TBI).
Methods This cross-sectional study was performed on patients with moderate blunt TBI (Glasgow Coma Scale, 9–12) who were referred to the emergency department during a 1-year period. Initially, all patients underwent a brain CT scan and primary ocular ultrasonography. Patients who were candidates for a second brain CT scan under observation in the emergency department also underwent a second ocular ultrasound. The primary outcome was the progression of brain lesions on repeated brain CT scans. Logistic regression and the area under receiver operating characteristic curve (AUC) were used.
Results Overall, 204 patients with a mean age of 43±13.4 years were enrolled in the study. The study detected expanding changes in brain CT scans from 29 patients (14.2%). The progression of lesion on CT scan were significantly associated with changes in the Glasgow Coma Scale. In the second brain CT scan, there were significant associations between the progression of lesion on CT scan and the increased size of the ONSD measured on both axial and coronal sections (odds ratio, 17.3–47.5; AUC, 0.88–0.93).
Conclusion Among patients with moderate TBI, an increase in ONSD on ocular ultrasound seems to be an appropriate criterion for repeating a brain CT scan to select a suitable therapeutic intervention.
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Highly malignant electroencephalogram (EEG) patterns (including suppressed background and burst suppression) refer to a poor neurological outcome in cardiac arrest patients, but some of those patients may show a good neurological outcome. This is the first report that details the reason for their uncommon survival despite highly malignant EEG patterns after cardiac arrest. The brain cortical activities in very elderly patients (who are vulnerable to the usual sedative doses) showed a suppressed background and burst suppression but resulting in a good neurological outcome. The mean suppression rates from their EEGs were 100% and 68.4%, respectively, and a normal pattern was completely restored after the sedatives had affected their brain waves for 12 hours. It was speculated that sedatives given at an ordinary dose may negatively affect the brain’s cortical activity in elderly patients who demonstrate a good neurological outcome. When appropriate doses of sedatives are used, highly malignant EEG patterns in very elderly patients should be carefully interpreted for early neuroprognostication.
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Objective In the present study, intracranial pressure (ICP) changes were investigated in out-ofhospital cardiac arrest (OHCA) patients with and without malignant blood-brain barrier (BBB) disruption who underwent target temperature management.
Methods This prospective, single-center, observational study was conducted from June 2019 to December 2021. ICP and albumin quotient values were measured on days 1, 2, 3, and 4 of hospitalization. Malignant BBB disruption was defined as the sum of scores for the degree of BBB disruption ≥9 on days 1 to 4.
Results ICP in OHCA patients without malignant BBB disruption on days 1, 2, 3, and 4 of hospitalization was 9.58±0.53, 12.32±0.65, 14.39±0.76, and 13.88±0.87 mmHg, respectively, and in OHCA patients with malignant BBB disruption 13.65±0.74, 15.72±0.67, 16.10±0.92, and 15.22±0.87 mmHg, respectively (P<0.001, P<0.001, P=0.150, and P=0.280, respectively). The P-values of changes in ICP between days 1 and 2, days 2 and 3, and days 3 and 4 of hospitalization in OHCA patients without malignant BBB disruption were P<0.001, P=0.001, and P=0.540, respectively, and in OHCA patients with malignant BBB disruption were P=0.002, P=0.550, and P=0.100, respectively.
Conclusion Among OHCA patients treated with target temperature management, ICP was higher on days 1 and 2 of hospitalization and an increase in ICP occurred earlier with malignant BBB disruption than without malignant BBB disruption.
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Objective Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model.
Methods Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured.
Results Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals.
Conclusion Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI.
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Objective Among the pediatric population with minor head trauma, it is difficult to determine an indication for the usage of brain computerized tomography (CT). Our study aims to compare the efficiency of the most commonly used clinical decision rules: the Pediatric Emergency Care Applied Research Network (PECARN) and Canadian Assessment of Tomography for Childhood Head Injury 2 (CATCH2).
Methods This retrospective study investigated whether the PECARN and CATCH2 rules were applicable to Korean children with minor head trauma for reducing the use of brain CT imaging, while detecting intracranial pathology.
Results Overall, 251 patients (0–5 years old) admitted to emergency rooms within 24 hours of injury were included between August 2015 to August 2018. The performance results are as follows: the PECARN and CATCH2 rules had a sensitivity of 80.00% (51.91%–95.67%) and 100% (78.20%–100.00%) with a specificity of 28.39% (22.73%–34.60%) and 15.25% (10.92%–20.49%), respectively; the negative predictive values were 98.58% and 100%, respectively. Overall, the CATCH2 rule was more successful than the PECARN rule in detecting intracranial pathology; however, there was no significant difference between them. Furthermore, the PECARN and CATCH2 rules lowered the rate of head CT imaging in our study group.
Conclusion Both the rules significantly lowered the rate of indicated brain CT. However, since the CATCH2 rule had higher sensitivity and negative predictive value than the PECARN rule, it is more appropriate to be used in emergency rooms for detecting intracranial pathology in children with minor head trauma.
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Methods We obtained comprehensive data (demographics, injury characteristics, injury severities, and outcomes) of geriatric and super-geriatric TBI patients from an emergency department-based injury surveillance system database from 2011 to 2016. Multivariate logistic regression analysis was performed to compare the mortality and nonroutine discharge (NRDC) status between both groups.
Results Among 442,533 TBI patients, 48,624 were older than 65 years. A total of 48,446 patients (37,140 geriatric and 11,306 super-geriatric) without exclusion criteria were included in the final analysis. Both overall in-hospital mortality (adjusted odds ratio, 1.88; 95% confidence interval [CI], 1.28 to 2.74; P=0.001) and NRDC (adjusted odds ratio, 1.35; 95% CI, 1.07 to 1.71; P=0.011) were significantly higher in the super-geriatric group. In the stratified analysis, there were no significant differences in NRDC rate for all stratifications of treatment timing (emergency department vs. ward admission), but mortality remained to be significant for all stratifications.
Conclusion Super-geriatric TBI patients showed a significantly higher risk-adjusted overall mortality and more inadequate medical resource utilization than did geriatric TBI patients. However, super-geriatric patients were more likely to undergo NRDC after admission; thus, further research about age-related health inequalities is needed in the treatment of super-geriatric patients.
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Objective Traumatic brain injury (TBI) is an important public health concern due to its high prevalence and mortality rate among young people. We investigated the clinical and social characteristics of patients who visited the emergency department due to TBI in whom brain computed tomography, was performed by age.
Methods We retrospectively analyzed 15,567 TBI patients who received a brain computed tomography evaluation at the emergency department of Korea University Hospital from March 2013 to February 2016. We divided patients into age groups by decade and analyzed factors such as sex, trauma mechanism, need for operation, hospitalization, and results of treatment.
Results The mean age was 42.0±22.8 years; the most common age group was the 50s (16.5%). Except for the age group over 70 years, males predominated. Under 9 years of age, public ambulance usage rate was lower than in other age groups. Regarding severity based on the Glasgow Coma Scale score, the proportion of mild cases was higher in those under 9 years of age (99.3%) and the proportion of severe cases was higher in those in their 20s (4.6%). The most common injury mechanism was blunt trauma, followed by car accidents. For those under 9 years of age, falls were more common than in other age groups. Only 20.5% of TBI patients were hospitalized and 11.9% were treated surgically, while 70.6% of patients were discharged home after treatment.
Conclusion TBI may present with different characteristics depending on the age of the patients, thus prevention policies and clinical practice should be tailored to age.
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Objective Traumatic brain injury (TBI) is characterized by damage to the blood-brain barrier, inflammation, and edema formation. In this pilot study, we aimed to investigate the effects of a complement inhibitor, C1-esterase inhibitor (C1 INH), on brain edema and inflammation in a rat model of mild TBI.
Methods Thirty-six male Sprague Dawley rats were randomly assigned to control, TBI, or TBI plus C1 INH groups. TBI and TBI plus C1 INH rats received an injection of saline or 25 IU/kg C1 INH, respectively, with TBI using a weight drop model. Control rats received saline only. Rats were subsequently euthanized and their brain tissue harvested for analysis. The primary outcome was the extent of edema as assessed by the brain’s water content. Secondary outcomes included enzyme-linked immunosorbent assays to determine levels of pro-inflammatory mediators.
Results Tumor necrosis factor-α levels were significantly greater in TBI rats than control rats, indicating that inflammation was generated by the weight drop impact. Brain water content following TBI was significantly different between TBI rats treated with C1-INH (78.7%±0.12), untreated TBI rats (79.3%±0.12), and control rats (78.6%±0.15, P=0.001). There was a significant decrease in C3a and interleukin 2 levels among C1 INH–treated rats compared with untreated TBI rats, but no change in levels of tumor necrosis factor-α and S100β.
Conclusion C1-INH inhibited the complement pathway, suggesting that C1-INH may have a therapeutic benefit in TBI. Further studies are needed to investigate the effect of C1-INH on clinical outcomes.
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Objective To evaluate the predictive performance of optic nerve sheath thickness (ONST) on the outcomes of traumatic brain injury (TBI) and to compare the inter-observer agreement To evaluate the predictive performance of optic nerve sheath thickness (ONST) for traumatic brain injury (TBI) and to compare the predictive performance and inter-observer agreement between ONST and optic nerve sheath diameter (ONSD) on facial computed tomography (CT).
Methods We retrospectively enrolled patients with a history of facial trauma and who underwent both facial CT and brain CT. Two reviewers independently measured ONST and ONSD of each patient using facial CT images. Final brain CT with clinical outcome was used as the reference standard for TBI. Multivariate logistic regression analyses, receiver operating characteristic (ROC) curves, and intraclass correlation coefficients were used for statistical analyses.
Results Both ONST (P=0.002) and ONSD (P=0.001) on facial CT were significantly independent factors to distinguish between TBI and healthy brains; an increase in ONST and ONSD values corresponded with an increase in the risk of TBI by 8.9- and 7.6-fold, respectively. The predictive performances of the ONST (sensitivity, 96.2%; specificity, 94.3%; area under the ROC curve, 0.968) and ONSD (sensitivity, 92.6%; specificity, 90.2%; area under the ROC curve, 0.955) were excellent and exhibited similar sensitivity, specificity, and area under the curve (P=0.18–0.99). Interobserver and intraobserver intraclass correlation coefficients for ONST were significantly higher than those for ONSD (all P<0.001).
Conclusion ONST on facial CT is a feasible predictor of TBI and demonstrates similar performance and superior observer agreement than ONSD. We recommend using ONST measurements to assess the need for additional brain CT scans in TBI-suspected cases.
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