Traumatic Intracranial Lesions Research Articles

Diagnostic Performance of GFAP, UCH-L1, and MAP-2 Within 30 and 60 Minutes of Traumatic Brain Injury.

Data on the performance of traumatic brain injury (TBI) biomarkers within minutes of injury are lacking. To examine the performance of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein 2 (MAP-2) within 30 and 60 minutes of TBI in identifying intracranial lesions on computed tomography (CT) scan, need for neurosurgical intervention (NSI), and clinically important early outcomes (CIEO). This cohort study is a biomarker analysis of a multicenter prehospital TBI cohort from the Prehospital Tranexamic Acid Use for TBI clinical trial conducted across 20 centers and 39 emergency medical systems in North America from May 2015 to March 2017. Prehospital hemodynamically stable adult patients with traumatic injury and suspected moderate to severe TBI were included. Blood samples were measured for GFAP, UCH-L1, and MAP-2. Data were analyzed from December 1, 2023, to March 15, 2024. The presence of CT lesions, diffuse injury severity on CT, NSI within 24 hours of injury, and CIEO (composite outcome including early death, neurosurgery, or prolonged mechanical ventilation ≥7 days) within 7 days of injury. Of 966 patients enrolled, 804 patients (mean [SD] age, 41 [19] years; 418 [74.2%] male) had blood samples, including 563 within 60 minutes and 375 within 30 minutes of injury. Among patients with blood drawn within 30 minutes of injury, 212 patients (56.5%) had CT lesions, 61 patients (16.3%) had NSI, and 112 patients (30.0%) had CIEO. Among those with blood drawn within 60 minutes, 316 patients (56.1%) had CT lesions, 95 patients (16.9%) had NSI, and 172 patients (30.6%) had CIEO. All biomarkers showed significant elevations with worsening diffuse injury on CT within 30 and 60 minutes of injury. Among blood samples taken within 30 minutes, GFAP had the highest area under the receiver operating characteristic curve (AUC) to detect CT lesions, at 0.88 (95% CI, 0.85-0.92), followed by MAP-2 (AUC, 0.78; 95% CI, 0.73-0.83) and UCH-L1 (AUC, 0.75; 95% CI, 0.70-0.80). Among blood samples taken within 60 minutes, AUCs for CT lesions were 0.89 (95% CI, 0.86-0.92) for GFAP, 0.76 (95% CI, 0.72-0.80) for MAP-2, and 0.73 (95% CI, 0.69-0.77) for UCH-L1. Among blood samples taken within 30 minutes, AUCs for NSI were 0.78 (95% CI, 0.72-0.84) for GFAP, 0.75 (95% CI, 0.68-0.81) for MAP-2, and 0.69 (95% CI, 0.63-0.75) for UCH-L1; and for CIEO, AUCs were 0.89 (95% CI, 0.85-0.93) for GFAP, 0.83 (95% CI, 0.78-0.87) for MAP-2, and 0.77 (95% CI, 0.72-0.82) for UCH-L1. Combining the biomarkers was no better than GFAP alone for all outcomes. At GFAP of 30 pg/mL within 30 minutes, sensitivity for CT lesions was 98.1% (95% CI, 94.9%-99.4%) and specificity was 34.4% (95% CI, 27.2%-42.2%). GFAP levels greater than 6200 pg/mL were associated with high risk of NSI and CIEO. In this cohort study of prehospital patients with TBI, GFAP, UCH-L1, and MAP-2 measured within 30 and 60 minutes of injury were significantly associated with traumatic intracranial lesions and diffuse injury severity on CT scan, 24-hour NSI, and 7-day CIEO. GFAP was the strongest independent marker associated with all outcomes. This study sets a precedent for the early utility of GFAP in the first 30 minutes from injury in future clinical and research endeavors.

Guiding lights in the early postoperative computed tomography following cranial surgery for traumatic brain injury patients

BackgroundComputed tomography (CT) can be a substantial source of guiding lights during the early postoperative hours in traumatic brain injury (TBI) patients. However, controversy still exists regarding: What is the appropriate time for the first postoperative CT? And what are the guiding lights that can be gained from an early follow-up CT? Therefore, our objective was to reach more clear answers for these questions and to design a simple algorithm for the follow-up of TBI patients during the first 24 h after cranial surgery.MethodsThis is a retrospective study included 164 TBI patients who were surgically treated for various traumatic cranial and/or intracranial lesions in our neurosurgery department from January 2022 to April 2023. Pre- and postoperative clinical and radiological data of these patients were collected and analyzed.ResultsThe mean age was (23.46 ± 15.126) years. The mean glasgow coma scale (GCS) on presentation was (11.62 ± 3.004). 51.2% of patients had their first follow-up CT done within the first postoperative hour (0–1 h). Postoperative remarkable CT findings were detected in 39 patients (23.8%), with 13 cases (33.3%) of them required re-surgery. 69.2% of the postoperative remarkable findings were recognized in the first hour CT (P = 0.025). Acute subdural hematoma was the only significant primary lesion associated with the need for re-surgery (P = 0.015). Postoperative development of remarkable CT findings was significantly (P < 0.001) associated with increased possibility of re-surgery, high mortality rate, prolonged hospital stay and poor outcome.ConclusionsImmediate (0–1 h) follow-up CT brain can be more lucrative in the early postoperative assessment for TBI patients. The first hour CT can provide distinct guiding lights of significant value for the subsequent postoperative management and prediction of patients' clinical course and discharge outcome.

Isolated Traumatic Subarachnoid Hemorrhage on Head Computed Tomography Scan May Not Be Isolated: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI) Study.

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.

248 Isolated Traumatic Subarachnoid Hemorrhage on Head Computed Tomography Scan May Not Be Isolated

INTRODUCTION: Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) is often regarded as a “mild” injury, with reduced need for additional workup. However, tSAH is also a predictor of unfavorable outcomes. Magnetic resonance imaging (MRI) and blood-based biomarkers may improve the diagnosis of concurrent intracranial injury. METHODS: The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury study enrolled patients presenting to ED within 24 hours (h) of TBI who received a clinically-indicated head CT. A subset underwent venipuncture within 24h for plasma glial fibrillary acidic protein (GFAP) analysis, and 2-week research MRI. Participants aged = 17-years with GCS 13-15, isolated tSAH on initial CT, GFAP, and MRI data were analyzed. RESULTS: In 57 patients, median age was 46.0-years [quartile 1 to 3 (Q1-Q3): 34-57] and 53% were male. At ED disposition, 12.3% were discharged home, 61.4% admitted to hospital ward, and 26.3% to intensive care.MRI identified additional traumatic intracranial lesions in 45.6% of patients (1 type: 31.6%; 2 types: 14.0%); of these, 65.4% had axonal injury, 42.3% subdural hematoma, and 23.1% contusion. GFAP levels were higher in patients with additional MRI lesions (median: 630.6-pg/ml, Q1-Q3: [172.4-941.2] vs. 226.4 [105.8-436.1], p = 0.049), and correlated with axonal injury severity (none: median 226.7 [109.6-435.1], traumatic axonal injury: 716.3 [304.0-892.3], diffuse axonal injury: 873.2 [407.2-1321.4], p = 0.034). CONCLUSIONS: Isolated tSAH on head CT is insufficient to rule out additional traumatic injuries in GCS 13-15 TBI. Forty-six percent of patients had additional traumatic lesions on MRI. Plasma GFAP may be an important biomarker for the identification of additional injuries, including axonal injury. Patients with isolated tSAH on CT may require close clinical surveillance and follow-up.

Noninvasive postmortem investigation of cases refusing autopsy using computed tomography

Background: CT is a well-known tool to assess several conditions in living patients. The post-mortem CT (PMCT) has been introduced to determine the cause of death in dead subjects. CT is also the imaging modality of choice for the analysis of autopsy findings including fracture, hematoma, gas collection and gross tumor injury. The rate of standard autopsy is continuing to decline and there are several reasons for refusing autopsy. Objective: The current research endeavor is investigate the usefulness of computed tomography (CT) in cases refusing autopsy. Materials and Methods: In this study, the PMCT were evaluated in 150 subjects in different contexts of death. The causes of death were classified into four categories which include a definite cause of death, a possible cause of death, a minor pathological finding and no fatal findings. For the definite cause of death and the possible cause of death, the specific lesions are described in detail. Results: The definite cause of death was detected in 48 (32%) of the subjects. The possible cause of death was detected in 18 (12%) of the subjects. The remaining 84 subjects were classified into minor pathological findings and no fatal findings in 46 (30.7%) and 38 (25.3%) of the patients, respectively. The fatal lesions of PMCT were found in 93 lesions(48 subjects) that were demonstrated by anatomical locations into the traumatic bone, intracranial, spine, thoracic, heart leak and abdominal lesions. We found definite causes of death in 6 subjects, which had no history of trauma and malignancy and were mentioned about a cardiopulmonary failure as a cause of death at first. Conclusion: The PMCT is a useful tool for identifying the cause of death in many cases that have limitations for conventional autopsy. The morphological change such as intracranial hemorrhage is easily diagnosed with PMCT. The PMCT appears to be an alternative tool to assess the cause of death in any reason of objections.

Sex differences in time course and diagnostic accuracy of GFAP and UCH-L1 in trauma patients with mild traumatic brain injury

Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers’ diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4 h of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7 days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24 h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.

Short-term outcome of treatment of elderly patients with epidural hematomas.

There is substantial literature data dedicated to intracranial epidural hematomas affecting young and middle-aged individuals, but studies focusing on their characteristics in elderly patients are scarce, assuming that old age is a poor prognostic factor.

Evaluation of Clinical Characteristics and CT Decision Rules in Elderly Patients with Minor Head Injury: A Prospective Multicenter Cohort Study.

Age is variably described as a minor or major risk factor for traumatic intracranial lesions after head injury. However, at present, no specific CT decision rule is available for elderly patients with minor head injury (MHI). The aims of this prospective multicenter cohort study were to assess the performance of existing CT decision rules for elderly MHI patients and to compare the clinical and CT characteristics of elderly patients with the younger MHI population. Thirty-day mortality between two age groups (cutoff ≥ 60 years), along with clinical and CT characteristics, was evaluated with four CT decision rules: the National Institute for Health and Care Excellence (NICE) guideline, the Canadian CT Head Rule (CCHR), the New Orleans Criteria (NOC), and the CT Head Injury Patients (CHIP) rule. Of the 5517 MHI patients included, 2310 were aged ≥ 60 years. Elderly patients experienced loss of consciousness (17% vs. 32%) and posttraumatic amnesia (23% vs. 31%) less often, but intracranial lesions (13% vs. 10%), neurological deterioration (1.8% vs. 0.2%), and 30-day mortality (2.0% vs. 0.1%) were more frequent than in younger patients (all p < 0.001). Elderly patients with age as their only risk factor showed intracranial lesions in 5% (NOC and CHIP) to 8% (CCHR and NICE) of cases. The sensitivity of decision rules in the elderly patients was 60% (CCHR) to 97% (NOC) when age was excluded as a risk factor. Current risk factors considered when evaluating elderly patients show lower sensitivity to identify intracranial abnormalities, despite more frequent intracranial lesions. Until age-specific CT decision rules are developed, it is advisable to scan every elderly patient with an MHI.

Clinical outcomes and prognostic factors of traumatic basal ganglia hematomas: A 4-year single-center study.

Traumatic basal ganglia hematomas (TBGH) are rare entities. They are situated in the deep cerebral parenchyma and have also been termed as intermediate coup contusions. Available literature is sparse with regards to the characteristics and prognosis of TBGH. We aim to share our experience in the management, outcomes, and prognostic factors of TBGH. A 4-year retrospective study which included all cases of TBGH, except dot contusions (<2 mL) and those with coagulopathies. Admission variables were correlated with Glasgow Outcome Scale score at discharge and 12 months. Thirty-two patients were analyzed. The mean age was 39.2 years. Two-thirds were due to road traffic accidents. Around 60% were severe head injuries. The mean Glasgow coma scale (GCS) score at presentation was 8.5. Twenty patients had moderate-to-severe hemiparesis. The mean hematoma volume was 18.1 mL. Associated traumatic intracranial lesions were seen in 28 cases. Only 7 patients (22%) underwent surgery. The mean follow-up was 17.4 months (range 14-34 months). The mortality rate was 12.5% (n = 4). Among the survivors, only 39% (n = 11) had good outcomes at discharge which showed modest improvement to 54% (n = 15) at 12 months. Our study noted that poor admission GCS scores, poor motor response, presence of significant hemiparesis, and larger hematoma volumes (>20 mL) correlated with poor outcomes at 12 months. The overall outcomes have been mostly unfavorable as observed in majority of studies due to deeper location of these hematomas, high proportion of severe head injuries, and high proportion of residual weakness in survivors.

Risk for intracranial hemorrhage in individuals after mild traumatic brain injury who are taking serotonergic antidepressants.

Serotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding. This was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication. The study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50-83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use. Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI.

Biomarker S100B in plasma a screening tool for mild traumatic brain injury in an emergency department

ABSTRACT Introduction A computerized tomography (CT) scan is an effective test for detecting traumatic intracranial findings after mild traumatic brain injury (mTBI). However, a head CT is costly, and can only be performed in a hospital. Objective To determine if the addition of plasma S100B to clinical guidelines could lead to a more selective scanning strategy without compromising safety. Methods We conducted a single center prospective cohort study at the emergency department. Patients (≥16 years) who received head CT and had a blood draw were included. The primary outcome was the accuracy of plasma S100B to predict the presence of any traumatic intracranial lesion on head CT. Results We included 495 patients, out of the 74 patients who had traumatic intracranial lesions, 5 patients had a plasma S100B level below the cutoff value of 0.105 ug/L. For the detection of traumatic intracranial injury, S100B had a sensitivity of 0.932 , a specificity of 0.157, a negative predictive value of 0.930, and a positive predictive value of 0.163. Conclusions Among patients undergoing guideline-based CT scan for mTBI, the use of S100B, would results in a further decrease (14.8%) of CT scans but at a cost of missed injury, without clinical consequence, on CT.

Revised indications for head CT in elderly patients with minor traumatic injuries: A retrospective analysis

PurposeThe purpose of this study was to assess the performance of a decision-tree for head-CT indication in elderly patients presenting minor traumatic injuries Materials and MethodsA single-centre retrospective study was performed and analyses were based on emergency CT scans of all patients aged 65 and over who experienced minor head trauma due to falls. The primary judgement criteria was the diagnosis of a traumatic intracranial haemorrhagic lesion (tICH) depicted on the CT scan. Focal neurological deficit and history of tICH on a previous CT scan were used to create the decision-tree. ResultsA total of 1001 patients were included. Ninety-five (9.5%) had tICH on the CT scan. Of these patients, 42 (46.1%) had an abnormal Glasgow Coma Scale, 30 (31.6%) a focal neurological deficit and 13 (13.7%) a history of tICH on a previous CT scan. The presence of at least one of these 3 risk factors was associated with the occurrence of tICH (p <0.001). The decision-tree developed from these risk factors allowed the appropriate classification of 63 of 95 patients (66.3%) with tICH. Undetected haemorrhagic lesions in patients with no clinical severity criteria evolved favourably. The decision-tree correctly identified 97% of patients without any tICH on the CT. ConclusionSystematic head CT for elderly patients presenting minor head trauma could be irrelevant. A decision-tree based on objective clinical severity criteria for the indication of head CT could detect the majority of tICH requiring surgical intervention. Prospective randomized studies are mandatory to confirm these hypotheses.

Evaluating the optimal number of burr-holes for treating chronic subdural haematomas: good results from a single burr-hole?

Chronic subdural haematomas (cSDH) are one of the most common types of traumatic intracranial lesion. Burr-hole craniostomy followed by closed-system drainage has become the treatment of choice. However, there is no definitive indication as to the number of burr-holes needed. Our aim was to to assess clinical and radiological outcomes taking into account the number of burr-holes made. A retrospective single-centre-study was performed including patients treated for cSDH by performing burr-hole craniostomy from 2012 to 2018. After collecting data regarding demographics, comorbidities, and clinical and radiological records, haematomas were grouped depending on the number of burr-holes made (Group 1: single burr-hole; Group 2: double burr-holes). Clinical and radiological outcomes were statistically compared between groups, as well as the main complications. After collecting 171 patients, 205 cSDHs were analysed. 173 were treated with a single burr-hole (we called these Group 1) and 32 with double burr-holes (Group 2). No differences in preoperative characteristics were found between the groups, except for diabetes mellitus and previous antiplatelet/anticoagulation treatment. No radiological differences were found regarding haematoma volume (p = 0.7) or thickness (p = 0.3). Surgical site infection (p = 0.13), recurrence (p = 0.6), acute rebleeding (p = 0.25) and mortality (p = 0.94) were assessed without evidencing statistically significant differences. At the time of hospital discharge, most patients showed a remarkable clinical improvement, regardless of the number of burr-holes made (p = 0.7). This study suggests that cSDH can be efficiently evacuated by a single burr-hole craniostomy, a less invasive and shorter surgical procedure with quite good clinical outcomes and a low rate of complications.

Incidence of surgically treated post-traumatic hydrocephalus 6 months following head injury in patients undergoing acute head computed tomography

BackgroundPost-traumatic hydrocephalus (PTH) is a well-known complication of head injury. The percentage of patients experiencing PTH in trauma cohorts (0.7–51.4%) varies greatly in the prior literature depending on the study population and applied diagnostic criteria. The objective was to determine the incidence of surgically treated PTH in a consecutive series of patients undergoing acute head computed tomography (CT) following injury.MethodsAll patients (N = 2908) with head injuries who underwent head CT and were treated at the Tampere University Hospital’s Emergency Department (August 2010–July 2012) were retrospectively evaluated from patient medical records. This study focused on adults (18 years or older) who were residents of the Pirkanmaa region at the time of injury and were clinically evaluated and scanned with head CT at the Tampere University Hospital’s emergency department within 48 h after injury (n = 1941). A thorough review of records for neurological signs and symptoms of hydrocephalus was conducted for all patients having a radiological suspicion of hydrocephalus. The diagnosis of PTH was based on clinical and radiological signs of the condition within 6 months following injury. The main outcome was surgical treatment for PTH. Clinical evidence of shunt responsiveness was required to confirm the diagnosis of PTH.ResultsThe incidence of surgically treated PTH was 0.15% (n = 3). Incidence was 0.08% among patients with mild traumatic brain injury (TBI) and 1.1% among those with moderate to severe TBI. All the patients who developed PTH underwent neurosurgery during the initial hospitalization due to the head injury. The incidence of PTH among patients who underwent neurosurgery for acute traumatic intracranial lesions was 2.7%.ConclusionThe overall incidence of surgically treated PTH was extremely low (0.15%) in our cohort. Analyses of risk factors and the evaluation of temporal profiles could not be undertaken due to the extremely small number of cases.

Concussion severity and functional outcome using biomarkers in children and youth involved in organized sports, recreational activities and non-sport related incidents

ABSTRACT This prospective multicenter study evaluated differences in concussion severity and functional outcome using glial and neuronal biomarkers glial Fibrillary Acidic (GFAP) and Ubiquitin C-terminal Hydrolase (UCH-L1) in children and youth involved in non-sport related trauma, organized sports, and recreational activities. Children and youth presenting to three Level 1 trauma centersfollowing blunt head trauma with a GCS 15 with a verified diagnosis of a concussion were enrolled within 6 hours of injury. Traumatic intracranial lesions on CT scan and functional outcome within 3 months of injury were evaluated. 131 children and youth with concussion were enrolled, 81 in the no sports group, 22 in the organized sports group and 28 in the recreational activities group. Median GFAP levels were 0.18, 0.07, and 0.39 ng/mL in the respective groups (p = 0.014). Median UCH-L1 levels were 0.18, 0.27, and 0.32 ng/mL respectively (p = 0.025). A CT scan of the head was performed in 110 (84%) patients. CT was positive in 5 (7%), 4 (27%), and 5 (20%) patients, respectively. The AUC for GFAP for detecting +CT was 0.84 (95%CI 0.75–0.93) and for UCH-L1 was 0.82 (95%CI 0.71–0.94). In those without CT lesions, elevations in UCH-L1 were significantly associated with unfavorable 3-month outcome. Concussions in the 3 groups were of similar severity and functional outcome. GFAP and UCH-L1 were both associated with severity of concussion and intracranial lesions, with the most elevated concentrations in recreational activities .

Return to work after mild traumatic brain injury: association with positive CT and MRI findings

BackgroundReturn to work (RTW) might be delayed in patients with complicated mild traumatic brain injury (MTBI), i.e., MTBI patients with associated traumatic intracranial lesions. However, the effect of different types of lesions on RTW has not studied before. We investigated whether traumatic intracranial lesions detected by CT and MRI are associated with return to work and post-concussion symptoms in patients with MTBI.MethodsWe prospectively followed up 113 adult patients with MTBI that underwent a brain MRI within 3–17 days after injury. Return to work was assessed with one-day accuracy up to one year after injury. Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Glasgow Outcome Scale Extended (GOS-E) were conducted one month after injury. A Kaplan–Meier log-rank analysis was performed to analyze the differences in RTW.ResultsFull RTW-% one year after injury was 98%. There were 38 patients with complicated MTBI, who had delayed median RTW compared to uncomplicated MTBI group (17 vs. 6 days), and more post-concussion symptoms (median RPQ 12.0 vs. 6.5). Further, RTW was more delayed in patients with multiple types of traumatic intracranial lesions visible in MRI (31 days, n = 19) and when lesions were detected in the primary CT (31 days, n = 24). There were no significant differences in GOS-E.ConclusionsThe imaging results that were most clearly associated with delayed RTW were positive primary CT and multiple types of lesions in MRI. RTW-% of patients with MTBI was excellent and a single intracranial lesion does not seem to be a predictive factor of disability to work.

The diagnostic and prognostic value of glial fibrillary acidic protein in traumatic brain injury: a systematic review and meta-analysis.

Over the years, blood biomarkers have been extensively applied for diagnostic and prognostic assessment of traumatic brain injury (TBI). Herein, we conducted a meta-analysis to evaluate the diagnostic and prognostic value of glial fibrillary acidic protein (GFAP) for TBI patients. The online databases, including PubMed, Embase, Cochrane Library, CNKI, and WFSD, were systematically retrieved from inception until May 2021. The RevMan 5.3 software and Stata 15 were used to conduct data analysis. A total of 22 eligible studies comprising 3709 patients were included in this meta-analysis. The pooled results indicated that serum GFAP had a diagnostic value in detecting traumatic intracranial lesions (AUC 0.81; 95% CI 0.77-0.84; p < 0.00001). The pooled sensitivity and specificity were 0.93 (95% CI 0.81-0.98), and 0.66 (95% 0.53-0.77; p < 0.00001), respectively. For assessment of unfavorable outcome, the pooled sensitivity, specificity and AUC value were 0.66 (95% CI 0.54-0.76; p < 0.00001), 0.82(95% CI 0.72-0.90; p < 0.00001), and 0.82 (95% CI 0.76-0.88; p < 0.00001), respectively. Besides, GFAP exhibited a significant value in predicting mortality (AUC 0.81; 95% CI 0.77-0.84; p < 0.00001), with high sensitivity and specificity (0.86, 95% CI 0.79-0.92, p < 0.00001, and 0.66, 95% CI 0.52-0.77, p < 0.00001). The subgroup analysis indicated that the type of TBI and cut-off value were potential sources of heterogeneity, which influenced the pooled AUC values for mortality prediction. Our meta-analysis indicated that GFAP had diagnostic and prognostic value for TBI patients, especially during the early TBI.

Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury

In 2018, the combination of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels became the first US Food and Drug Administration-approved blood test to detect intracranial lesions after mild to moderate traumatic brain injury (MTBI). How this blood test compares with validated clinical decision rules remains unknown. To compare the performance of GFAP and UCH-L1 levels vs 3 validated clinical decision rules for detecting traumatic intracranial lesions on computed tomography (CT) in patients with MTBI and to evaluate combining biomarkers with clinical decision rules. This prospective cohort study from a level I trauma center enrolled adults with suspected MTBI presenting within 4 hours of injury. The clinical decision rules included the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), and National Emergency X-Radiography Utilization Study II (NEXUS II) criteria. Emergency physicians prospectively completed data forms for each clinical decision rule before the patients' CT scans. Blood samples for measuring GFAP and UCH-L1 levels were drawn, but laboratory personnel were blinded to clinical results. Of 2274 potential patients screened, 697 met eligibility criteria, 320 declined to participate, and 377 were enrolled. Data were collected from March 16, 2010, to March 5, 2014, and analyzed on August 11, 2021. The presence of acute traumatic intracranial lesions on head CT scan (positive CT finding). Among enrolled patients, 349 (93%) had a CT scan performed and were included in the analysis. The mean (SD) age was 40 (16) years; 230 patients (66%) were men, 314 (90%) had a Glasgow Coma Scale score of 15, and 23 (7%) had positive CT findings. For the CCHR, sensitivity was 100% (95% CI, 82%-100%), specificity was 33% (95% CI, 28%-39%), and negative predictive value (NPV) was 100% (95% CI, 96%-100%). For the NOC, sensitivity was 100% (95% CI, 82%-100%), specificity was 16% (95% CI, 12%-20%), and NPV was 100% (95% CI, 91%-100%). For NEXUS II, sensitivity was 83% (95% CI, 60%-94%), specificity was 52% (95% CI, 47%-58%), and NPV was 98% (95% CI, 94%-99%). For GFAP and UCH-L1 levels combined with cutoffs at 67 and 189 pg/mL, respectively, sensitivity was 100% (95% CI, 82%-100%), specificity was 25% (95% CI, 20%-30%), and NPV was 100%; with cutoffs at 30 and 327 pg/mL, respectively, sensitivity was 91% (95% CI, 70%-98%), specificity was 20% (95% CI, 16%-24%), and NPV was 97%. The area under the receiver operating characteristic curve (AUROC) for GFAP alone was 0.83; for GFAP plus NEXUS II, 0.83; for GFAP plus NOC, 0.85; and for GFAP plus CCHR, 0.88. The AUROC for UCH-L1 alone was 0.72; for UCH-L1 plus NEXUS II, 0.77; for UCH-L1 plus NOC, 0.77; and for UCH-L1 plus CCHR, 0.79. The GFAP biomarker alone (without UCH-L1) contributed the most improvement to the clinical decision rules. In this cohort study, the CCHR, the NOC, and GFAP plus UCH-L1 biomarkers had equally high sensitivities, and the CCHR had the highest specificity. However, using different cutoff values reduced both sensitivity and specificity of GFAP plus UCH-L1. Use of GFAP significantly improved the performance of the clinical decision rules, independently of UCH-L1. Together, the CCHR and GFAP had the highest diagnostic performance.

Personalized Connectome-Based Modeling in Patients with Semi-Acute Phase TBI: Relationship to Acute Neuroimaging and 6 Month Follow-Up.

Following traumatic brain injury (TBI), cognitive impairments manifest through interactions between microscopic and macroscopic changes. On the microscale, a neurometabolic cascade alters neurotransmission, while on the macroscale diffuse axonal injury impacts the integrity of long-range connections. Large-scale brain network modeling allows us to make predictions across these spatial scales by integrating neuroimaging data with biophysically based models to investigate how microscale changes invisible to conventional neuroimaging influence large-scale brain dynamics. To this end, we analyzed structural and functional neuroimaging data from a well characterized sample of 44 adult TBI patients recruited from a regional trauma center, scanned at 1–2 weeks postinjury, and with follow-up behavioral outcome assessed 6 months later. Thirty-six age-matched healthy adults served as comparison participants. Using The Virtual Brain, we fit simulations of whole-brain resting-state functional MRI to the empirical static and dynamic functional connectivity of each participant. Multivariate partial least squares (PLS) analysis showed that patients with acute traumatic intracranial lesions had lower cortical regional inhibitory connection strengths than comparison participants, while patients without acute lesions did not differ from the comparison group. Further multivariate PLS analyses found correlations between lower semiacute regional inhibitory connection strengths and more symptoms and lower cognitive performance at a 6 month follow-up. Critically, patients without acute lesions drove this relationship, suggesting clinical relevance of regional inhibitory connection strengths even when traumatic intracranial lesions were not present. Our results suggest that large-scale connectome-based models may be sensitive to pathophysiological changes in semi-acute phase TBI patients and predictive of their chronic outcomes.

Blood Biomarkers and Structural Imaging Correlations Post-Traumatic Brain Injury: A Systematic Review.

Blood biomarkers are of increasing importance in the diagnosis and assessment of traumatic brain injury (TBI). However, the relationship between them and lesions seen on imaging remains unclear. To perform a systematic review of the relationship between blood biomarkers and intracranial lesion types, intracranial lesion injury patterns, volume/number of intracranial lesions, and imaging classification systems. We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, and Cumulative Index to Nursing and Allied Health Literature from inception to May 2021, and the references of included studies were also screened. Heterogeneity in study design, biomarker types, imaging modalities, and analyses inhibited quantitative analysis, with a qualitative synthesis presented. Fifty-nine papers were included assessing one or more biomarker to imaging comparisons per paper: 30 assessed imaging classifications or injury patterns, 28 assessed lesion type, and 11 assessed lesion volume or number. Biomarker concentrations were associated with the burden of brain injury, as assessed by increasing intracranial lesion volume, increasing numbers of traumatic intracranial lesions, and positive correlations with imaging classification scores. There were inconsistent findings associating different biomarkers with specific imaging phenotypes including diffuse axonal injury, cerebral edema, and intracranial hemorrhage. Blood-based biomarker concentrations after TBI are consistently demonstrated to correlate burden of intracranial disease. The relation with specific injury types is unclear suggesting a lack of diagnostic specificity and/or is the result of the complex and heterogeneous nature of TBI.