RESUMEN
OBJECTIVE: Traumatic brain injury (TBI) and hemorrhage are responsible for the largest proportion of all trauma-related deaths. In polytrauma patients at risk of hemorrhage and TBI, the diagnosis, prognosis, and management of TBI remain poorly characterized. The authors sought to characterize the predictive capabilities of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) measurements in patients with hemorrhagic shock with and without concomitant TBI. METHODS: The authors performed a secondary analysis on serial blood samples derived from a prospective observational cohort study that focused on comparing early whole-blood and component resuscitation. A convenience sample of patients was used in which samples were collected at three time points and the presence of TBI or no TBI via CT imaging was documented. GFAP and UCH-L1 measurements were performed on plasma samples using the i-STAT Alinity point-of-care platform. Using classification tree recursive partitioning, the authors determined the measurement cut points for each biomarker to maximize the abilities for predicting the diagnosis of TBI, Rotterdam CT imaging scores, and 6-month Glasgow Outcome Scale-Extended (GOSE) scores. RESULTS: Biomarker comparisons demonstrated that GFAP and UCH-L1 measurements were associated with the presence of TBI at all time points. Classification tree analyses demonstrated that a GFAP level > 286 pg/ml for the sample taken upon the patient's arrival had an area under the receiver operating characteristic curve of 0.77 for predicting the presence of TBI. The classification tree results demonstrated that a cut point of 3094 pg/ml for the arrival GFAP measurement was the most predictive for an elevated Rotterdam score on the initial and second CT scans and for TBI progression between scans. No significant associations between any of the most predictive cut points for UCH-L1 and Rotterdam CT scores or TBI progression were found. The predictive capabilities of UCH-L1 were limited by the range allowed by the point-of-care platform. Arrival GFAP cut points remained strong independent predictors after controlling for all potential polytrauma confounders, including injury characteristics, shock severity, and resuscitation. CONCLUSIONS: Early measurements of GFAP and UCH-L1 on a point-of-care device are significantly associated with CT-diagnosed TBI in patients with polytrauma and shock. Early elevated GFAP measurements are associated with worse head CT scan Rotterdam scores, TBI progression, and worse GOSE scores, and these associations are independent of other injury attributes, shock severity, and early resuscitation characteristics.
RESUMEN
Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. Level of evidence: IV. Trial registration number: NCT02119182.
RESUMEN
Management of severe traumatic brain injury (sTBI) typically involves the use of sedation, which inherently results in benefits and risks. The cytochrome P450 enzyme CYP2B6 is involved in the biotransformation of particular drug classes, including many intravenous sedatives. Variants of the CYP2B6 gene can lead to decreased systemic clearance of some sedatives, including propofol. This study aimed to investigate the relationship of CYP2B6 gene variation and patient outcomes after TBI while also considering propofol administration. Patients who sustained a non-penetrating sTBI and admitted to a single-center Level 1 trauma hospital were included in this study (n = 440). The *6 functional allele of CYP2B6 that leads to reduced enzyme expression and activity required genotyping two single nucleotide polymorphisms, rs3745274 and rs2279343. Patient outcomes were evaluated using the Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) at 3 and 6 months post-injury. Data on sedative administration were abstracted from medical records. Individuals homozygous for the alleles coding for the reduced enzyme expression and activity were more likely to have worse outcomes. A relationship between propofol administration and 3-month GOS and 6-month DRS was noted when controlling for CYP2B6 genotype. These findings suggest that genetic variation in CYP2B6 may influence the impact of intravenous sedation on patient outcomes after TBI and warrants further investigation.
RESUMEN
INTRODUCTION: Severe traumatic brain injury (TBI) presentation and late clinical outcomes are usually evaluated by the Glasgow Outcome Scale-Extended (GOS-E), which lacks strong prognostic predictability. Several blood biomarkers have been linked to TBI, such as Tau, GFAP, UCH-L1, S-100B, and NSE. Clinical values of TBI biomarkers have yet to be evaluated in a focused multi-study meta-analysis. We reviewed relevant articles evaluating potential relationships between TBI biomarkers and both early and 6-month outcomes. METHODS: All PubMed article publications from January 2000 to November 2023 with the search criteria "Protein Biomarker" AND "Traumatic Brain Injury" were included. Amongst all comparative studies, the sensitivity means and range values of biomarkers in predicting CT Rotterdam scores, ICU admission in the early period, or predicting GOS-E < 4 at the 6-month period were calculated from confusion matrices. Sensitivity values were modeled for each biomarker across studies and compared statistically for heterogeneity and differences. RESULTS: From the 65 articles that met the criteria, 13 were included in this study. Six articles involved early-period TBI outcomes and seven involved 6-month outcomes. In the early period TBI outcomes, GFAP had a superior sensitivity to UCH-L1 and S-100B, and similar sensitivity to the CT Rotterdam score. In the 6-month period TBI outcomes, total Tau and NSE both had significant interstudy heterogeneity, making them inferior to GFAP, phosphorylated Tau, UCH-L1, and S-100B, all four of which had similar sensitivities at 75â¯%. This sensitivity range at 6-month outcomes was still relatively inferior to the CT Rotterdam score. Total Tau did not show any prognostic advantage at six months with GOS-E < 4, and phosphorylated Tau was similar in its sensitivity to other biomarkers such as GFAP and UCH-L1 and still inferior to the CT Rotterdam score. CONCLUSION: This data suggests that TBI protein biomarkers do not possess better prognostic value with regards to outcomes.
Asunto(s)
Biomarcadores , Lesiones Traumáticas del Encéfalo , Lesiones Traumáticas del Encéfalo/sangre , Humanos , Biomarcadores/sangre , Pronóstico , Escala de Consecuencias de Glasgow , Proteínas Sanguíneas/análisis , Proteínas tau/sangre , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Traumatic brain injury (TBI) with skull fractures parallel to or crossing venous sinuses is a recognized risk factor for traumatic cerebral venous sinus thrombosis (tCVST). Despite the recognition of this traumatic pathology in the literature, no consensus regarding management has been achieved. This study aimed to evaluate the impact of tCVST on TBI outcomes and related complications. METHODS: Patients within a prospective registry at a level I trauma center from 2014 to 2023 were reviewed to identify tCVST cases. The impact of tCVST presence on Glasgow Outcome Scale scores at 6 months, 30-day mortality, and hospital length of stay were evaluated in multivariable-adjusted analyses. RESULTS: Among 607 patients with TBI, 61 patients were identified with skull fractures extending to the vicinity of venous sinuses with dedicated venography. Twenty-eight of these 61 patients (44.3%) had tCVST. The majority (96.4%) of tCVST were located in a unilateral transverse or sigmoid sinus. Complete recanalization was observed in 28% of patients on follow-up imaging (7/25 with follow-up imaging). None of the 28 patients suffered attributable venous infarcts or thrombus propagation. In the adjusted analysis, there was no difference in the 30-day mortality or Glasgow Outcome Scale at 6 months between patients with and without tCVST. CONCLUSIONS: Unilateral tCVST follows a benign clinical course without associated increased mortality or morbidity. The management of tCVST should be distinct as compared to spontaneous CVST, likely without the need for anticoagulation.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Trombosis de los Senos Intracraneales , Humanos , Trombosis de los Senos Intracraneales/etiología , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Masculino , Femenino , Adulto , Persona de Mediana Edad , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/terapia , Resultado del Tratamiento , Escala de Consecuencias de Glasgow , Adulto Joven , Anciano , Fracturas Craneales/complicaciones , Fracturas Craneales/diagnóstico por imagen , Estudios Prospectivos , Sistema de Registros , Estudios RetrospectivosRESUMEN
The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3 inflammasome is also strongly associated with other pro-inflammatory conditions, such as obesity. Little is known about the potential effect of mild TBI (mTBI) on the NLRP3 inflammasome and the extent to which modifying factors, such as obesity, may augment the inflammatory response to mTBI. The purpose of this study was to evaluate the association of NLRP3 inflammasome proteins with obese body mass index (BMI ≥ 30) within 24 h of mTBI after presenting to a level 1 trauma center emergency department. This is a secondary analysis of prospectively enrolled patients with mTBI who presented to the emergency department of one U.S. Level 1 trauma center from 2013 to 2018 (n = 243). A series of regression models were built to evaluate the association of NLRP3 proteins obtained from blood plasma within 24 h of injury and BMI as well as the potential interaction effect of higher BMI with NLRP3 proteins (n = 243). A logistic regression model revealed a significant association between IL-18 (p < 0.001) in mTBI patients with obese BMI compared to mTBI patients with non-obese BMI (< 30). Moderation analyses revealed statistically significant interaction effects between apoptotic speck-like protein (ASC), caspase-1, IL-18, IL-1ß and obese BMI which worsened symptom burden, quality of life, and physical function at 2 weeks and 6 months post-injury. Higher acute concentrations of IL-1ß in the overall cohort predicted higher symptoms at 6-months and worse physical function at 2-weeks and 6-months. Higher acute concentrations of IL-18 in the overall cohort predicted worse physical function at 6-months. In this single center mTBI cohort, obese BMI interacted with higher acute concentrations of NLRP3 inflammasome proteins and worsened short- and long-term clinical outcomes.
Asunto(s)
Índice de Masa Corporal , Conmoción Encefálica , Inflamasomas , Interleucina-18 , Proteína con Dominio Pirina 3 de la Familia NLR , Obesidad , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Femenino , Obesidad/complicaciones , Inflamasomas/metabolismo , Adulto , Persona de Mediana Edad , Conmoción Encefálica/complicaciones , Conmoción Encefálica/sangre , Interleucina-18/sangre , Interleucina-18/metabolismo , Estudios Prospectivos , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Caspasa 1/metabolismoRESUMEN
Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) scan is often regarded as a "mild" injury, with reduced need for additional workup. However, tSAH is also a predictor of incomplete recovery and unfavorable outcome. This study aimed to evaluate the characteristics of CT-occult intracranial injuries on brain magnetic resonance imaging (MRI) scan in TBI patients with emergency department (ED) arrival Glasgow Coma Scale (GCS) score 13-15 and isolated tSAH on CT. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI; enrollment years 2014-2019) enrolled participants who presented to the ED and received a clinically-indicated head CT within 24 h of TBI. A subset of TRACK-TBI participants underwent venipuncture within 24 h for plasma glial fibrillary acidic protein (GFAP) analysis, and research MRI at 2-weeks post-injury. In the current study, TRACK-TBI participants age ≥17 years with ED arrival GCS 13-15, isolated tSAH on initial head CT, plasma GFAP level, and 2-week MRI data were analyzed. In 57 participants, median age was 46.0 years [quartile 1 to 3 (Q1-Q3): 34-57] and 52.6% were male. At ED disposition, 12.3% were discharged home, 61.4% were admitted to hospital ward, and 26.3% to intensive care unit. MRI identified CT-occult traumatic intracranial lesions in 45.6% (26 of 57 participants; one additional lesion type: 31.6%; 2 additional lesion types: 14.0%); of these 26 participants with CT-occult intracranial lesions, 65.4% had axonal injury, 42.3% had subdural hematoma, and 23.1% had intracerebral contusion. GFAP levels were higher in participants with CT-occult MRI lesions compared with without (median: 630.6 pg/mL, Q1-Q3: [172.4-941.2] vs. 226.4 [105.8-436.1], p = 0.049), and were associated with axonal injury (no: median 226.7 pg/mL [109.6-435.1], yes: 828.6 pg/mL [204.0-1194.3], p = 0.009). Our results indicate that isolated tSAH on head CT is often not the sole intracranial traumatic injury in GCS 13-15 TBI. Forty-six percent of patients in our cohort (26 of 57 participants) had additional CT-occult traumatic lesions on MRI. Plasma GFAP may be an important biomarker for the identification of additional CT-occult injuries, including axonal injury. These findings should be interpreted cautiously given our small sample size and await validation from larger studies.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Imagen por Resonancia Magnética , Hemorragia Subaracnoidea Traumática , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemorragia Subaracnoidea Traumática/diagnóstico por imagen , Adulto , Tomografía Computarizada por Rayos X/métodos , Estudios Prospectivos , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Anciano , Escala de Coma de GlasgowRESUMEN
OBJECTIVE: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. METHODS: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). RESULTS: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome. CONCLUSIONS: The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Escala de Coma de Glasgow , Escala de Consecuencias de Glasgow , Humanos , Lesiones Traumáticas del Encéfalo/mortalidad , Lesiones Traumáticas del Encéfalo/terapia , Persona de Mediana Edad , Femenino , Pronóstico , Masculino , Adulto , Estudios Prospectivos , Anciano , Estudios de Cohortes , Adulto Joven , AdolescenteRESUMEN
Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) within 12h of suspected traumatic brain injury (TBI) have been approved by the Food and Drug administration to aid in determining the need for a brain computed tomography (CT) scan. The current study aimed to determine whether this context of use can be expanded beyond 12h post-TBI in patients presenting with Glasgow Coma Scale (GCS) 13-15. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled TBI participants aged ≥17 years who presented to a United States Level 1 trauma center and received a clinically indicated brain CT scan within 24h post-injury, a blood draw within 24h and at 14 days for biomarker analysis. Data from participants with emergency department arrival GCS 13-15 and biomarker values at days 1 and 14 were extracted for the primary analysis. A subgroup of hospitalized participants with serial biomarkers at days 1, 3, 5, and 14 were analyzed, including plasma GFAP and UCH-L1, and serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B). The primary analysis compared biomarker values dichotomized by head CT results (CT+/CT-). Area under receiver-operating characteristic curve (AUC) was used to determine diagnostic accuracy. The overall cohort included 1142 participants with initial GCS 13-15, with mean age 39.8 years, 65% male, and 73% Caucasian. The GFAP provided good discrimination in the overall cohort at days 1 (AUC = 0.82) and 14 (AUC = 0.72), and in the hospitalized subgroup at days 1 (AUC = 0.84), 3 (AUC = 0.88), 5 (AUC = 0.82), and 14 (AUC = 0.74). The UCH-L1, NSE, and S100B did not perform well (AUC = 0.51-0.57 across time points). This study demonstrates the utility of GFAP to aid in decision-making for diagnostic brain CT imaging beyond the 12h time frame in patients with TBI who have a GCS 13-15.
Asunto(s)
Biomarcadores , Lesiones Traumáticas del Encéfalo , Proteína Ácida Fibrilar de la Glía , Ubiquitina Tiolesterasa , Humanos , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/diagnóstico , Proteína Ácida Fibrilar de la Glía/sangre , Masculino , Femenino , Adulto , Persona de Mediana Edad , Biomarcadores/sangre , Ubiquitina Tiolesterasa/sangre , Estudios Prospectivos , Anciano , Tomografía Computarizada por Rayos X , Escala de Coma de Glasgow , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: Early recognition of traumatic brain injury (TBI) is important to facilitate time-sensitive care. Electroencephalography (EEG) can identify TBI, but feasibility of EEG has not been evaluated in prehospital settings. We tested the feasibility of obtaining single-channel EEG during air medical transport after trauma. We measured association between quantitative EEG features, early blood biomarkers, and abnormalities on head computerized tomography (CT). METHODS: We performed a pilot prospective, observational study enrolling consecutive patients transported by critical care air ambulance from the scene of trauma to a Level I trauma center. During transport, prehospital clinicians placed a sensor on the patient's forehead to record EEG. We reviewed EEG waveforms and selected 90 seconds of recording for quantitative analysis. EEG data processing included fast Fourier transform to summarize component frequency power in the delta (0-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) ranges. We collected blood samples on day 1 and day 3 post-injury and measured plasma levels of two brain injury biomarkers (ubiquitin C-terminal hydrolase L1 [UCH-L1] and glial fibrillary acidic protein [GFAP]). We compared predictors between individuals with and without CT-positive TBI findings. RESULTS: Forty subjects were enrolled, with EEG recordings successfully obtained in 34 (85%). Reasons for failure included uncharged battery (n = 5) and user error (n = 1). Data were lost in three cases. Of 31 subjects with data, interpretable EEG signal was recorded in 26 (84%). Mean age was 48 (SD 16) years, 79% were male, and 50% suffered motor vehicle crashes. Eight subjects (24%) had CT-positive TBI. Subjects with and without CT-positive TBI had similar median delta power, alpha power, and theta power. UCH-L1 and GFAP plasma levels did not differ across groups. Delta power inversely correlated with UCH-L1 day 1 plasma concentration (r = -0.60, p = 0.03). CONCLUSIONS: Prehospital EEG acquisition is feasible during air transport after trauma.
Asunto(s)
Ambulancias Aéreas , Lesiones Traumáticas del Encéfalo , Servicios Médicos de Urgencia , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Ubiquitina Tiolesterasa , Lesiones Traumáticas del Encéfalo/diagnóstico , Estudios de Cohortes , Biomarcadores , Estudios Observacionales como AsuntoRESUMEN
BACKGROUND: Anisocoria (unequal pupil size) has been defined using cut points ranging from greater than 0.3 mm to greater than 2.0 mm for absolute difference in pupil size. This study explored different pupil diameter cut points for assessing anisocoria as measured by quantitative pupillometry before and after light stimulus. METHODS: An exploratory descriptive study of international registry data was performed. The first observations in patients with paired left and right quantitative pupillometry measurements were included. Measurements of pupil size before and after stimulus with a fixed light source were used to calculate anisocoria. RESULTS: The sample included 5769 patients (mean [SD] age, 57.5 [17.6] years; female sex, 2558 patients [51.5%]; White race, 3669 patients [75.5%]). Anisocoria defined as pupil size difference of greater than 0.5 mm was present in 1624 patients (28.2%) before light stimulus; 645 of these patients (39.7%) also had anisocoria after light stimulus (P < .001). Anisocoria defined as pupil size difference of greater than 2.0 mm was present in 79 patients (1.4%) before light stimulus; 42 of these patients (53.2%) also had anisocoria after light stimulus (P < .001). DISCUSSION: The finding of anisocoria significantly differed before and after light stimulus and according to the cut point used. At most cut points, fewer than half of the patients who had anisocoria before light stimulus also had anisocoria after light stimulus. CONCLUSION: The profound difference in the number of patients adjudicated as having anisocoria using different cut points reinforces the need to develop a universal definition for anisocoria.
Asunto(s)
Anisocoria , Luz , Humanos , Femenino , Persona de Mediana Edad , PupilaRESUMEN
Importance: One traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited. Objective: To investigate associations between sustaining 1 or more TBIs (ie, postindex TBIs) after study enrollment (ie, index TBIs) and multidimensional outcomes at 1 year and 3 to 7 years. Design, Setting, and Participants: This cohort study included participants presenting to emergency departments enrolled within 24 hours of TBI in the prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years, February 2014 to July 2020). Participants who completed outcome assessments at 1 year and 3 to 7 years were included. Data were analyzed from September 2022 to August 2023. Exposures: Postindex TBI(s). Main Outcomes and Measures: Demographic and clinical factors, prior TBI (ie, preindex TBI), and functional (Glasgow Outcome Scale-Extended [GOSE]), postconcussive (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]), psychological distress (Brief Symptom Inventory-18 [BSI-18]), depressive (Patient Health Questionnaire-9 [PHQ-9]), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5 [PCL-5]), and health-related quality-of-life (Quality of Life After Brain Injury-Overall Scale [QOLIBRI-OS]) outcomes were assessed. Adjusted mean differences (aMDs) and adjusted relative risks are reported with 95% CIs. Results: Of 2417 TRACK-TBI participants, 1572 completed the outcomes assessment at 1 year (1049 [66.7%] male; mean [SD] age, 41.6 [17.5] years) and 1084 completed the outcomes assessment at 3 to 7 years (714 [65.9%] male; mean [SD] age, 40.6 [17.0] years). At 1 year, a total of 60 participants (4%) were Asian, 255 (16%) were Black, 1213 (77%) were White, 39 (2%) were another race, and 5 (0.3%) had unknown race. At 3 to 7 years, 39 (4%) were Asian, 149 (14%) were Black, 868 (80%) were White, 26 (2%) had another race, and 2 (0.2%) had unknown race. A total of 50 (3.2%) and 132 (12.2%) reported 1 or more postindex TBIs at 1 year and 3 to 7 years, respectively. Risk factors for postindex TBI were psychiatric history, preindex TBI, and extracranial injury severity. At 1 year, compared with those without postindex TBI, participants with postindex TBI had worse functional recovery (GOSE score of 8: adjusted relative risk, 0.57; 95% CI, 0.34-0.96) and health-related quality of life (QOLIBRI-OS: aMD, -15.9; 95% CI, -22.6 to -9.1), and greater postconcussive symptoms (RPQ: aMD, 8.1; 95% CI, 4.2-11.9), psychological distress symptoms (BSI-18: aMD, 5.3; 95% CI, 2.1-8.6), depression symptoms (PHQ-9: aMD, 3.0; 95% CI, 1.5-4.4), and PTSD symptoms (PCL-5: aMD, 7.8; 95% CI, 3.2-12.4). At 3 to 7 years, these associations remained statistically significant. Multiple (2 or more) postindex TBIs were associated with poorer outcomes across all domains. Conclusions and Relevance: In this cohort study of patients with acute TBI, postindex TBI was associated with worse symptomatology across outcome domains at 1 year and 3 to 7 years postinjury, and there was a dose-dependent response with multiple postindex TBIs. These results underscore the critical need to provide TBI prevention, education, counseling, and follow-up care to at-risk patients.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Humanos , Masculino , Adulto , Femenino , Estudios de Cohortes , Estudios Prospectivos , Calidad de Vida , Lesiones Traumáticas del Encéfalo/epidemiologíaRESUMEN
Invasive neuromonitoring is a bedrock procedure in neurosurgery and neurocritical care. Intracranial hypertension is a recognized emergency that can potentially lead to herniation, ischemia, and neurological decline. Over 50,000 external ventricular drains (EVDs) are performed in the United States annually for traumatic brain injuries (TBI), tumors, cerebrovascular hemorrhaging, and other causes. The technical challenge of a bedside ventriculostomy and/or parenchymal monitor placement may be increased by complex craniofacial trauma or brain swelling, which will decrease the tolerance of brain parenchyma to applied procedural force during a craniostomy. Herein, we report on the implementation and safety of a disposable power drill for bedside neurosurgical practices compared with the manual twist drill that is the current gold standard. Mechanical testing of the drill's stop extension (n = 8) was conducted through a calibrated tensile tester, simulating an axial plunging of 22.68 kilogram (kg) or 50 pounds of force (lbf) and measuring the strength-responsive displacement. The mean displacement following compression was 0.18 ± 0.11 mm (range of 0.03 mm to 0.34 mm). An overall cost analysis was calculated based on the annual institutional pricing, with an estimated $64.90 per unit increase in the cost of the disposable electric drill. Power drill craniostomies were utilized in a total of 34 adult patients, with a median Glasgow Coma Scale (GCS) score of six. Twenty-seven patients were male, with a mean age of 50.7 years old. The two most common injury mechanisms were falls and motor vehicle/motorcycle accidents. EVDs were placed in all subjects, and additional quad-lumen neuromonitoring was applied to 23 patients, with no incidents of plunging events or malfunctions. One patient developed an intracranial infection and another had intraparenchymal tract hemorrhaging. Two illustrative TBI cases with concomitant craniofacial trauma were provided. The disposable power drill was successfully implemented as an option for bedside ventriculostomies and had an acceptable safety profile.
RESUMEN
Chronic consequences of mild traumatic brain injury (mTBI) are heterogeneous, but may be treatable with targeted medical and rehabilitation interventions. A biological signature for the likelihood of response to therapy (i.e., "predictive" biomarkers) would empower personalized medicine post-mTBI. The purpose of this study was to correlate pre-intervention blood biomarker levels and the likelihood of response to targeted interventions for patients with chronic issues attributable to mTBI. Patients with chronic symptoms and/or disorders secondary to mTBI >3 months previous (104 days to 15 years; n = 74) were enrolled. Participants completed pre-intervention assessments of symptom burden, comprehensive clinical evaluation, and blood-based biomarker measurements. Multi-domain targeted interventions for specific symptoms and impairments across a 6-month treatment period were prescribed. Participants completed a follow-up testing after the treatment period. An all-possible model's backward logistic regression was built to identify predictors of improvement in relation to blood biomarker levels before intervention. The minimum clinically important difference (MCID) of the change score (post-intervention subtracted from pre-intervention) for the Post-Concussion Symptom Scale (PCSS) to identify treatment responders from non-responders was the primary outcome. The MCID for total PCSS score was 10. The model to predict change in PCSS score over the 6-month intervention was significant (R2 = 0.09; p = 0.01) and identified ubiquitin C-terminal hydrolase L1 (odds ratio [OR] = 2.53; 95% confidence interval [CI], 1.18-5.46; p = 0.02) and hyperphosphorylated tau (p-tau; OR = 0.70; 95% CI, 0.51-0.96; p = 0.03) as significant predictors of symptom improvement beyond the PCSS MCID. In this cohort of chronic TBI subjects, blood biomarkers before rehabilitation intervention predicted the likelihood of response to targeted therapy for chronic disorders post-TBI.
RESUMEN
OBJECTIVES: Obesity is associated with chronic inflammation, which may impact recovery from mild traumatic brain injury (mTBI). The objective was to assess the role of obesity in recovery of symptoms, functional outcome and inflammatory blood biomarkers after mTBI. METHODS: TRACK-TBI is a prospective study of patients with acute mTBI (Glasgow Coma Scale=13-15) who were enrolled ≤24 hours of injury at an emergency department of level 1 trauma centres and followed for 12 months. A total of 770 hospitalised patients who were either obese (body mass index (BMI) >30.0) or healthy mass (BMI=18.5-24.9) were enrolled. Blood concentrations of high-sensitivity C reactive protein (hsCRP), interleukin (IL) 6, IL-10, tumour necrosis factor alpha; Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Quality of Life After Brain Injury and Glasgow Outcome Score-Extended reflecting injury-related functional limitations at 6 and 12 months were collected. RESULTS: After adjusting for age and gender, obese participants had higher concentrations of hsCRP 1 day after injury (mean difference (MD)=0.65; 95% CI: 0.44 to 0.87, p<0.001), at 2 weeks (MD=0.99; 95% CI: 0.74 to 1.25, p<0.001) and at 6 months (MD=1.08; 95% CI: 0.79 to 1.37, p<0.001) compared with healthy mass participants. Obese participants had higher concentrations of IL-6 at 2 weeks (MD=0.37; 95% CI: 0.11 to 0.64, p=0.006) and 6 months (MD=0.42; 95% CI: 0.12 to 0.72, p=0.006). Obese participants had higher RPQ total score at 6 months (MD=2.79; p=0.02) and 12 months (MD=2.37; p=0.049). CONCLUSIONS: Obesity is associated with higher symptomatology at 6 and 12 months and higher concentrations of blood inflammatory markers throughout recovery following mTBI.
Asunto(s)
Conmoción Encefálica , Lesiones Traumáticas del Encéfalo , Humanos , Conmoción Encefálica/complicaciones , Calidad de Vida , Estudios Prospectivos , Proteína C-Reactiva , Obesidad/complicaciones , Lesiones Traumáticas del Encéfalo/complicacionesRESUMEN
Sleep disturbances occur in up to 70% of patients with mild traumatic brain injury (mTBI). Modern mTBI management recommends targeted treatment for the patient's unique clinical manifestations (i.e., obstructive sleep apnea, insomnia). The purpose of this study was to evaluate the association of plasma biomarkers with symptom reports, overnight sleep evaluations, and response to treatment for sleep disturbances secondary to mTBI. This study is a secondary analysis of a prospective multiple interventional trial of patients with chronic issues related to mTBI. Pre- and post-intervention assessments were conducted, including overnight sleep apnea evaluation, the Pittsburgh Sleep Quality Index (PSQI), and blinded analysis of blood biomarkers. Bivariate Spearman correlations were conducted for pre-intervention plasma biomarker concentrations and 1) PSQI change scores and 2) pre-intervention sleep apnea outcomes (i.e., oxygen saturation measures). A backward logistic regression model was built to evaluate the association of pre-intervention plasma biomarkers with improvement in PSQI over the treatment period (p < 0.05). Participants were 36.3 ± 8.6 years old and 6.1 ± 3.8 years from their index mTBI. Participants reported subjective improvements (PSQI = -3.7 ± 3.8), whereas 39.3% (n = 11) had improved PSQI scores beyond the minimum clinically important difference (MCID). PSQI change scores correlated with von Willebrand factor (vWF; ρ = -0.50; p = 0.02) and tau (ρ = -0.53; p = 0.01). Hyperphosphorylated tau correlated with average saturation (ρ = -0.29; p = 0.03), lowest desaturation (ρ = -0.27; p = 0.048), and baseline saturation (ρ = -0.31; p = 0.02). The multi-variate model (R 2 = 0.33; p = 0.001) retained only pre-intervention vWF as a predictor (odds ratio = 3.41; 95% confidence interval, 1.44-8.08; p = 0.005) of improving PSQI scores beyond the MCID. vWF had good discrimination (area under the curve = 0.83; p = 0.01), with an overall accuracy of 77%, sensitivity of 46.2%, and specificity of 90.0%. Validation of vWF as a potential predictive biomarker of sleep improvement post-mTBI could optimize personalized management and healthcare utilization.
RESUMEN
INTRODUCTION: Neuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization. METHODS: Adult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan <24 h post-injury. Neuroworsening was defined as a decline in motor GCS at ED disposition (vs. ED admission). Clinical and CT characteristics, neurosurgical intervention, in-hospital mortality, and 3- and 6-month Glasgow Outcome Scale-Extended (GOS-E) scores were compared by neuroworsening status. Multivariable regressions were performed for neurosurgical intervention and unfavorable outcome (GOS-E ≤ 3). Multivariable odds ratios (mOR) with [95% confidence intervals] were reported. RESULTS: In 481 subjects, 91.1% had ED admission GCS 13-15 and 3.3% had neuroworsening. All neuroworsening subjects were admitted to intensive care unit (vs. non-neuroworsening: 26.2%) and were CT-positive for structural injury (vs. 45.4%). Neuroworsening was associated with subdural (75.0%/22.2%), subarachnoid (81.3%/31.2%), and intraventricular hemorrhage (18.8%/2.2%), contusion (68.8%/20.4%), midline shift (50.0%/2.6%), cisternal compression (56.3%/5.6%), and cerebral edema (68.8%/12.3%; all p < 0.001). Neuroworsening subjects had higher likelihoods of cranial surgery (56.3%/3.5%), intracranial pressure (ICP) monitoring (62.5%/2.6%), in-hospital mortality (37.5%/0.6%), and unfavorable 3- and 6-month outcome (58.3%/4.9%; 53.8%/6.2%; all p < 0.001). On multivariable analysis, neuroworsening predicted surgery (mOR = 4.65 [1.02-21.19]), ICP monitoring (mOR = 15.48 [2.92-81.85], and unfavorable 3- and 6-month outcome (mOR = 5.36 [1.13-25.36]; mOR = 5.68 [1.18-27.35]). CONCLUSIONS: Neuroworsening in the ED is an early indicator of TBI severity, and a predictor of neurosurgical intervention and unfavorable outcome. Clinicians must be vigilant in detecting neuroworsening, as affected patients are at increased risk for poor outcomes and may benefit from immediate therapeutic interventions.
RESUMEN
The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24 h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1-4/5-8); and incomplete versus full recovery (GOSE <8/ = 8). One-hundred sixty TBI subjects, 28 OCs, and 18 HCs were included. Markers discriminating TBI/OC: HMGB-1 (AUC = 0.835), IL-1b (0.795), IL-16 (0.784), IL-7 (0.742), and TARC (0.731). Markers discriminating GCS 3-12/13-15: IL-6 (AUC = 0.747), CRP (0.726), IL-15 (0.720), and SAA (0.716). Markers discriminating CT positive/CT negative: SAA (AUC = 0.767), IL-6 (0.757), CRP (0.733), and IL-15 (0.724). At 3 months, IL-15 (AUC = 0.738) and IL-2 (0.705) discriminated GOSE 5-8/1-4. At 6 months, IL-15 discriminated GOSE 1-4/5-8 (AUC = 0.704) and GOSE <8/ = 8 (0.711); SAA discriminated GOSE 1-4/5-8 (0.704). We identified a profile of acute circulating inflammatory proteins with potential relevance for TBI diagnosis, severity differentiation, and prognosis. IL-15 and serum amyloid A are priority markers with acceptable discrimination across multiple diagnostic and outcome categories. Validation in larger prospective cohorts is needed. ClinicalTrials.gov Registration: NCT01565551.
RESUMEN
Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers-plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase-among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17-39 years, middle-aged: 40-64 years, older: 65-90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84-0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6â hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.
RESUMEN
BACKGROUND: The occurrence of traumatic brain injury with spinal cord injury (SCI) in polytrauma patients is associated with significant morbidity. Clinicians face challenges from a decision-making and rehabilitative perspective. Management is complex and understudied. Treatment should be systematic beginning at the scene, focusing on airway resuscitation and hemodynamic stabilization, immobilization, and timely transport. Early operative interventions should be provided, followed by minimizing secondary pathophysiology. The authors present a case to delineate decision-making in the treatment of combined cranial and spinal trauma. OBSERVATIONS: A 19-year-old man presented as a level I trauma patient after falling 30 feet as the result of scaffolding collapse. The patient was unresponsive and was intubated; he had an initial Glasgow Coma Scale score of 4. Computed tomography revealed multicompartmental bleeding and herniation, for which supra- and infratentorial decompressive craniectomies were performed. The patient also suffered from thoracic SCI that resulted in complete paraplegia. Multimodality monitoring was used. After stabilization and lengthy rehabilitation, the patient obtained significant functional improvement. LESSONS: The approach to initial management of concomitant head and spine trauma is to establish intracranial stability followed by intraspinal stability. Patients can make considerable recovery, particularly younger patients, who are more likely to benefit from early aggressive interventions and medical treatment.