A study on the predictive value of glial fibrillary acidic protein for prediction of traumatic brain injury severity

Inflicted Childhood Neurotrauma: New Insight into The Detection, Pathobiology, Prevention, and Treatment of Our Youngest Patients with Traumatic Brain Injury

To determine the predictors of traumatic head injury (TBI) severity in adult patients involved in motor vehicle collisions or accidents, and to report on the outcomes of hospital admission, in-hospital death, and return to the Ed within 72 hours of discharge. This is an observational cohort of adult patients (≥18 years) who sustained a TBI through involvement in motor vehicle collisions (MVC). Demographic, pre-hospital and clinical data were collected from medical records of patients. In our cohort, patients who had loss of consciousness, alteration of consciousness, or post-traumatic amnesia were individual predictors of more severe traumatic brain injury. TBI severity was categorized by using GCS scores on emergency department arrival. Similarly, male patients, those who did not wear seat belts, and those with alcohol consumption were more likely to have severe TBI. When controlling for sex, loss of consciousness, no seat belt use, and alcohol consumption prior to injury were still statistically significant predictors of having more serious traumatic brain injury. Lack of seat belt use, alcohol consumption before injury, and loss of consciousness because of injury are significant predictors of having more severe head injury. These data support a call for action to implement more widespread injury prevention, seat belt use education and advocacy.

Background: Traumatic brain injury is a serious physical injury that can cause brain function impairment. Evaluating the severity of traumatic brain injury is crucial for patient management. Glial Fibrillary Acidic Protein (GFAP) has been identified as a potential biomarker for brain injury. This study aims to evaluate the relationship between serum GFAP levels and the severity of traumatic brain injury measured using the Glasgow Coma Scale (GCS) and Rotterdam Computed Tomography (CT) score. Methods: This study was conducted using a cross-sectional design to analyse the relationship between GFAP, GCS, and Rotterdam CT score. Data were collected from traumatic brain injury patients in the Emergency Department, Dr. Soetomo Surabaya Regional Hospital during the period from July 1, 2023, to November 30, 2023. GFAP levels were measured using the enzyme-linked immunosorbent assay (ELISA) method from blood serum samples. Results: Patients with traumatic brain injury showed an average increase in GFAP levels of 1.65 µg/L and an increase in Rotterdam CT score with an average score of 4. GFAP levels increased with decreasing GCS score, indicating a relationship between GFAP and the severity of brain injury. There was a positive correlation between increased GFAP and increased Rotterdam CT score, indicating a pathological response to brain injury. Conclusion: This study demonstrates that serum GFAP levels correlate with the severity of traumatic brain injury measured using GCS and Rotterdam CT score.

XV. Steroids

Studies show that fibrinogen concentrations <2 g/L in patients with traumatic brain injury (TBI) is associated with increased mortality. However, little is known regarding fibrinogen levels and TBI severity as well as mortality in sub-Saharan Africa despite shouldering a high burden of TBI. We therefore set out to determine whether fibrinogen levels are associated with TBI severity and outcome. To determine the sensitivity and specificity of fibrinogen levels and the association with severity and mortality among TBI patients at Mulago Hospital. We prospectively enrolled 213 patients with TBI aged between 13 and 60 years of age and presenting within 24 hours of injury. Patients with preexisting coagulopathy, concurrent use of anticoagulant or antiplatelet agents, preexisting hepatic insufficiency, diabetes mellitus and who were pregnant were excluded. Fibrinogen levels were determined using the Clauss fibrinogen assay. Logistic regression analyses were conducted to identify the association between fibrinogen level and 7-day outcomes. Majority of the patients were male (88.7%) and nearly half were aged 30 or less (48.8%). Fibrinogen levels <2 g/L were observed in 35.1% of the study participants. The average time spent in the study was 3.7 ± 2.4 days. The sensitivity and specificity using fibrinogen <2 g/L was 56.5% and 72.9% respectively. Fibrinogen levels predict TBI severity with an AUC = 0.656 (95% CI 0.58–0.73: P = .000) Fibrinogen levels <2 g/L (hypofibrinogenemia) were independently associated with severe TBI. (Adjusted odds ratio 2.87 CI, 1.34–6.14: P = .007). Levels above 4.5 g/L were also independently associated with injury severity (adjusted odds ratio 2.89, CI 1.12–7.48: P < .05) Fibrinogen levels more than 4.5 g/L were independently associated with mortality (OR 4.5, CI; 1.47–13.61, P < .05). The fibrinogen level is a useful tool in predicting severity including mortality of TBI. Fibrinogen levels may be used as an additional tool to screen TBI patients for injury severity especially among patients with Glasgow coma scale scores of <14.

IntroductionFibrinogen levels drop quicker than any other factors in severe trauma such as Traumatic Brain Injury (TBI). Contemporaneous studies show that fibrinogen concentrations < 2 g/L are strongly related to mortality. However, little is known regarding fibrinogen levels and TBI severity as well as mortality in sub-Saharan Africa. We therefore set out to determine whether fibrinogen levels are associated with TBI severity and seven days outcomes.ObjectivesTo determine the sensitivity and specificity of fibrinogen levels and the association with severity and mortality among TBI patients at Mulago Hospital.MethodsWe prospectively enrolled 213 patients with TBI aged between 13 and 60 years of age and presenting within 24hrs of injury. Patients with pre-existing coagulopathy, concurrent use of anticoagulant or antiplatelet agents, pre-existing hepatic insufficiency, diabetes mellitus and who were pregnant were excluded. Fibrinogen levels were determined using the Clauss fibrinogen assay.ResultsMajority of the patients were male (88.7%) and nearly half were aged 30 or less (48.8%). Fibrinogen levels less than 2g/L were observed in 74 (35.1%) of the patients while levels above 4.5 g/L were observed in 30(14.2%) of the patients. The average time spent in the study was 3.7 ± 2.4 days. The sensitivity and specificity using fibrinogen < 2g/L was 56.5% and 72.9% respectively. Fibrinogen levels predict TBI severity with an AUC = 0.656 (95% CI 0.58–0.73: p = 0.000) Fibrinogen levels < 2g/L (hypofibrinogenemia) were independently associated with severe TBI. (AOR 2.87 CI,1.34–6.14: p = 0.007). Levels above 4.5g/L were also independently associated with injury severity (AOR 2.89, CI 1.12–7.48: p < 0.05) Fibrinogen levels more than 4.5g/L were independently associated with mortality (OR 4.5, CI;1.47–13.61, p < 0.05).ConclusionsThe fibrinogen level is a useful tool in predicting severity including mortality of TBI in our settings. We recommend the routine use of fibrinogen levels in TBI patient evaluations as levels below 2g/L and levels above 4.5g/L are associated with severe injuries and mortality

We examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury. A total of 143 patients with TBI and 43 controls were studied cross-sectionally and longitudinally up to 5 years with multiple assessments, which included brain magnetic resonance imaging, cognitive testing, and serum biomarkers. TBI patients showed progressive volume loss regardless of injury severity over several years, andTAI was independently associated with accelerated brain atrophy. Cognitive performance improved over time. Higher baseline serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were associated with greater rate of brain atrophy over 5 years. Spatial patterns of atrophy differ by injury severity and TAI is associated with the progression of brain atrophy. Serum NfL and GFAP show promise as non-invasive prognostic biomarkers of progressive neurodegeneration in TBI. In this longitudinal study of patient with mild, moderate, and severe traumatic brain injury (TBI) who were assessed with paired magnetic resonance imaging (MRI), blood biomarkers, and cognitive assessments, we found that brain atrophy after TBI is progressive and continues for many years even after a mild head trauma without signs of brain injury on conventional MRI. We found that spatial pattern of brain atrophy differs between mild, moderate, and severe TBI, where in patients with mild TBI , atrophy is mainly seen in the gray matter, while in those with moderate to severe brain injury atrophy is predominantly seen in the subcortical gray matter and whiter matter. Cognitive performance improves over time after a TBI. Serum measures of neurofilament light or glial fibrillary acidic protein are associated with progression of brain atrophy after TBI.

Introduction

The Evolution of Ketamine in Severe Pediatric Traumatic Brain Injury, From Contraband to Promising Neuroprotectant?

Hypothermia in patients with brain injury: the way forward?

In this study we assessed the clinical utility of quantitative assessments of alphaII-spectrin breakdown products (SBDP145 produced by calpain, and SBDP120 produced by caspase-3) in cerebrospinal fluid (CSF) as markers of brain damage and outcome after severe traumatic brain injury (TBI). We analyzed 40 adult patients with severe TBI (Glasgow Coma Scale [GCS] score <or=8) who underwent ventriculostomy. Patients requiring CSF drainage for other medical reasons served as controls. CSF samples were taken at admission and every 6 h thereafter for a maximum of 7 days and assessed using novel quantitative fragment-specific ELISAs for SBDPs. Outcome was assessed using the 3-month Glasgow Outcome Scale. Mean CSF levels of SBDPs were significantly higher in TBI patients than in controls at all time points examined. Different temporal release patterns of CSF SBDP145 and SBDP120 were observed. SBDP145 provided accurate diagnoses at all time points examined, while SBDP120 release was more accurate 24 h after injury. Within 24 h after injury, SBDP145 CSF concentrations significantly correlated with GCS scores, while SBDP120 levels correlated with age. SBDP levels were significantly higher in patients who died than in those who survived. SBDP145 levels (>6 ng/mL) and SBDP120 levels (>17.55 ng/mL) strongly predicted death (odds ratio 5.9 for SBDP145, and 18.34 for SBDP120). The time course of SBDPs in nonsurvivors also differed from that of survivors. These results suggest that CSF SBDP levels can predict injury severity and mortality after severe TBI, and can be useful complements to clinical assessment.

Background: Currently used clinical and radiological findings of particularly mild traumatic brain injury have limited diagnostic and prognostic value. Methods and results: We conducted a systematic review of selected primary clinical studies on biochemical markers of traumatic brain injury in the last 10 years, using an electronic search of the National Library of Medicine’s database MEDLINE. The most explored and clinically relevant biochemical markers of acute brain injury are protein S100B, neuron-specific enolase and glial fibrillary acidic protein. In addition, novel markers such as spectrin breakdown product, c-tau and amiloid-b are presented. Based on clinical trials, the rationale for their use in the context of severity of traumatic brain injury is outlined. Conclusions: Measurement of biochemical markers of brain injury should be introduced in the clinical management of mild traumatic brain injury. The predictive value of current clinical and radiological findings can be markedly improved by the determination of biochemical markers in mild and severe traumatic brain injury.

The management of severe traumatic brain injury (TBI) is complex and difficult as patients present with a vast heterogeneity of injuries and may deteriorate due to secondary injuries despite treatment. Cerebrally enriched proteins of brain tissue fate in serum have been introduced as biomarkers attempting to better evaluate damage extent and trajectories. In this narrative chapter, we review the most commonly studied protein biomarkers, S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L), and how they predict injury severity and functional outcome, monitor deterioration, and may be used to determine treatment efficacy in trials. Further, we highlight opportunities and pitfalls in combinations of biomarkers, extracranial trauma, pediatric use, and available assays with the focus on creating a working manual for implementing protein biomarkers in clinical use of severe TBI.

Chapter 8. Hyperosmolar therapy

Chapter 7. Neuroimaging