Experimental investigation of brain contusion characteristics and dynamic response in low-age children using an animal model.

INTRODUCTION: Brain contusion is a prevalent traumatic brain injury (TBI) in low-age children, bearing the potential for coma and fatality. Hence, it is imperative to undertake comprehensive research in this field. METHODS: This study employed 4-week-old piglets as surrogates for children and introduced self-designed devices for both free-fall drop impact tests and drop-hammer impact tests. The study explored the characteristics of brain contusion and dynamic responses of brain under these distinct testing conditions. RESULTS: Brain contusions induced by free-fall and drop-hammer conditions both were categorized as the coup injury, except that slight difference in the contusion location was observed, with contusion occurring mainly in the surrounding regions beneath the impact location under free-fall condition and the region just right beneath the impact location under drop-hammer condition. Analysis of impact force and intracranial pressure (ICP) curves indicated similar trends in impact forces under both conditions, yet different trends in ICPs. Further examination of the peak impact forces and ICPs elucidated that, with increasing impact energy, the former followed a combined power and first-order polynomial function, while the latter adhered to a power function. The brain contusion was induced at the height (energy) of 2 m (17.2 J), but not at the heights of 0.4, 0.7, 1, 1.35 and 1.7 m, when the vertex of the piglet head collided with a rigid plate. In the case of a cylindrical rigid hammer (cross-sectional area constituting 40 % of the parietal bone) striking the head, the brain contusion was observed under the energy of 21.9 J, but not under energies of 8.1 J, 12.7 J and 20.3 J. Notably, the incidence of brain contusion was more pronounced under the free-fall condition. CONCLUSIONS: These findings not only facilitate a comprehensive understanding of brain contusion dynamics in pediatric TBIs, but also contribute to the validation of theories and finite element models for piglet heads, which are commonly employed as surrogates for children.

An analysis of neutrophil-to-lymphocyte ratios and monocyte-to-lymphocyte ratios with six-month prognosis after cerebral contusions.

Background and purpose: Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) have been identified as potential prognostic markers in various conditions, including cancer, cardiovascular disease, and stroke. This study aims to investigate the dynamic changes of NLR and MLR following cerebral contusion and their associations with six-month outcomes. Methods: Retrospective data were collected from January 2016 to April 2020, including patients diagnosed with cerebral contusion and discharged from two teaching-oriented tertiary hospitals in Southern China. Patient demographics, clinical manifestations, laboratory test results (neutrophil, monocyte, and lymphocyte counts) obtained at admission, 24 hours, and one week after cerebral contusion, as well as outcomes, were analyzed. An unfavorable outcome was defined as a Glasgow Outcome Score (GOS) of 0-3 at six months. Logistic regression analysis was performed to identify independent predictors of prognosis, while receiver characteristic curve analysis was used to determine the optimal cutoff values for NLR and MLR. Results: A total of 552 patients (mean age 47.40, SD 17.09) were included, with 73.19% being male. Higher NLR at one-week post-cerebral contusion (adjusted OR = 4.19, 95%CI, 1.16 - 15.16, P = 0.029) and higher MLR at admission and at 24 h (5.80, 1.40 - 24.02, P = 0.015; 9.06, 1.45 - 56.54, P = 0.018, respectively) were significantly associated with a 6-month unfavorable prognosis after adjustment for other risk factors by multiple logistic regression. The NLR at admission and 24 hours, as well as the MLR at one week, were not significant predictors for a 6-month unfavorable prognosis. Based on receiver operating characteristic curve analysis, the optimal thresholds of NLR at 1 week and MLR at admission after cerebral contusion that best discriminated a unfavorable outcome at 6-month were 6.39 (81.60% sensitivity and 70.73% specificity) and 0.76 (55.47% sensitivity and 78.26% specificity), respectively. Conclusion: NLR measured one week after cerebral contusion and MLR measured at admission may serve as predictive markers for a 6-month unfavorable prognosis. These ratios hold potential as parameters for risk stratification in patients with cerebral contusion, complementing established biomarkers in diagnosis and treatment. However, further prospective studies with larger cohorts are needed to validate these findings.

[Traumatic brain injury before the multiple sclerosis onset: a relationship with the progression of neurological disorders and pathobiochemical markers of the cerebrospinal fluid]. / Cherepno-mozgovaya travma do debyuta rasseyannogo skleroza: svyaz' s progressirovaniem nevrologicheskikh rasstroistv i patobiokhimicheskimi pokazatelyami tserebrospinal'noi zhidkosti.

OBJECTIVE: To evaluate the association of traumatic brain injury (TBI) before the multiple sclerosis (MS) onset with the rate of progression of neurological disorders and cerebrospinal fluid markers of blood-brain barrier permeability, inflammation, demyelination, and gliosis. MATERIAL AND METHODS: Patients with relapsing-remitting MS in the Altai region of Russia with/without TBI before the MS onset (n=44; 19 men, 25 women in each group) participated in a prospective, controlled, randomized study. Disability rate was assessed retrospectively. Pleocytosis, levels of protein, albumin, C-reactive protein, TNF-alpha, myelin basic protein, S100 protein were measured in the cerebrospinal fluid in subgroups of patients (n=14 in each group) in MS remission and exacerbation. RESULTS: Concussion and mild brain contusion were documented in the group of patients with TBI before the MS onset in 35 (79.5%) and 9 (20.5%) patients, respectively. Traumatic brain injury was over the age of 15 in 72.5% of patients. The rate of MS progression was higher in the group with TBI compared to the group without TBI (0.76±1.28 and 0.40±0.43 EDSS points per year, respectively; p=0.014). TBI before the MS onset increases the risk of disability by more than 0.25 EDSS points per year (OR 2.74; 95 CI 1.10-6.85; p=0.029). Intergroup differences in cerebrospinal fluid parameters were not found either during MS exacerbation or remission. CONCLUSION: Concussion or mild brain contusion before the MS onset may be factors influencing the progression of neurological deficit in MS. It seems relevant to study the mechanisms of adverse effects of TBI on the MS progression.

Glibenclamide for Brain Contusions: Contextualizing a Promising Clinical Trial Design that Leverages an Imaging-Based TBI Endotype.

TBI heterogeneity is recognized as a major impediment to successful translation of therapies that could improve morbidity and mortality after injury. This heterogeneity exists on multiple levels including primary injury, secondary injury/host-response, and recovery. One widely accepted type of primary-injury related heterogeneity is pathoanatomic-the intracranial compartment that is predominantly affected, which can include any combination of subdural, subarachnoid, intraparenchymal, diffuse axonal, intraventricular and epidural hemorrhages. Intraparenchymal contusions carry the highest risk for progression. Contusion expansion is one of the most important drivers of death and disability after TBI. Over the past decade, there has been increasing evidence of the role of the sulfonylurea-receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel in secondary injury after TBI, including progression of both cerebral edema and intraparenchymal hemorrhage. Inhibition of SUR1-TRPM4 with glibenclamide has shown promising results in preclinical models of contusional TBI with benefits against cerebral edema, secondary hemorrhage progression of the contusion, and improved functional outcome. Early-stage human research supports the key role of this pathway in contusion expansion and suggests a benefit with glibenclamide inhibition. ASTRAL is an ongoing international multi-center double blind multidose placebo-controlled phase-II clinical trial evaluating the safety and efficacy of an intravenous formulation of glibenclamide (BIIB093). ASTRAL is a unique and innovative study that addresses TBI heterogeneity by limiting enrollment to patients with the TBI pathoanatomic endotype of brain contusion and using contusion-expansion (a mechanistically linked secondary injury) as its primary outcome. Both criteria are consistent with the strong supporting preclinical and molecular data. In this narrative review, we contextualize the development and design of ASTRAL, including the need to address TBI heterogeneity, the scientific rationale underlying the focus on brain contusions and contusion-expansion, and the preclinical and clinical data supporting benefit of SUR1-TRPM4 inhibition in this specific endotype. Within this framework, we summarize the current study design of ASTRAL which is sponsored by Biogen and actively enrolling with a goal of 160 participants.

Rapid absorption of frontal lobe contusion and laceration with hematoma: A case report and review of literature.

RATIONALE: It is rare for a traumatic intracranial hematoma to self-absorb rapidly after conservative treatment. To the best of our knowledge, there has been no report in the relevant literature of rapid absorption of hematoma formation following cerebral contusion and laceration. PATIENT CONCERNS: A 54-year-old male was admitted to our hospital with head trauma at 3 hours prior to admission. He was alert and oriented, glasgow coma scale score of 15. Head computed tomography (CT) showed left frontal brain contusion with hematoma, however, a reexamination of CT about 29 hours following the trauma revealed that the hematoma had been absorbed. DIAGNOSES: A diagnosis of contusion and laceration of left frontal lobe with hematoma formation was made based on the CT images. INTERVENTIONS: The patient underwent conservative treatment. OUTCOMES: After treatment, dizziness and headache subsided for the patient, and no special discomfort was reported. LESSONS: It is likely that the reason for rapid absorption in this case is that the hematoma is prone to liquefaction because of abnormal platelet values and coagulation dysfunction. As the liquefaction hematoma breaks into the lateral ventricle, it is redistributed and absorbed in the lateral ventricle and subarachnoid space. Further evidence is required to support this hypothesis.

Reducing morbidity associated with subdural drain placement after burr-hole drainage of unilateral chronic subdural hematomas: a retrospective series comparing conventional and modified Nelaton catheter techniques.

PURPOSE: Placement of a subdural drain after burr-hole drainage of chronic subdural hematoma (cSDH) significantly reduces risk of its recurrence and lowers mortality at 6 months. Nonetheless, measures to reduce morbidity related to drain placement are rarely addressed in the literature. Toward reducing drain-related morbidity, we compare outcomes achieved by conventional insertion and our proposed modification. METHODS: In this retrospective series from two institutions, 362 patients underwent burr-hole drainage of unilateral cSDH with subsequent subdural drain insertion by conventional technique or modified Nelaton catheter (NC) technique. Primary endpoints were iatrogenic brain contusion or new neurological deficit. Secondary endpoints were drain misplacement, indication for computed tomography (CT) scan, re-operation for hematoma recurrence, and favorable Glasgow Outcome Scale (GOS) score (≥ 4) at final follow-up. RESULTS: The 362 patients (63.8% male) in our final analysis included drains inserted in 56 patients by NC and 306 patients by conventional technique. Brain contusions or new neurological deficits occurred significantly less often in the NC (1.8%) than conventional group (10.5%) (P = .041). Compared with the conventional group, the NC group had no drain misplacement (3.6% versus 0%; P = .23) and significantly fewer non-routine CT imaging related to symptoms (36.5% versus 5.4%; P < .001). Re-operation rates and favorable GOS scores were comparable between groups. CONCLUSION: We propose the NC technique as an easy-to-use measure for accurate drain positioning within the subdural space that may yield meaningful benefits for patients undergoing treatment for cSDH and vulnerable to complication risks.

A novel rat model for longitudinal electrophysiological evaluation after cold-induced brain injury.

OBJECTIVE: Cerebral contusion models of cold-induced injury are widely used in animal studies. However, owing to the difficulty of longitudinal recording of electrical stimulation transcranial motor evoked potential (tcMEP) in brain injury models of incomplete paralysis, to the authors' knowledge there have been no multimodal evaluations of cold-induced brain injury models that have included motor function and electrophysiological and histological evaluations. Therefore, in this study the authors aimed to perform a multimodal evaluation of a rat model of brain injury. METHODS: A brain injury model in female rats and a tcMEP recording technique based on the authors' previous study were established to enable multifaceted analysis, including longitudinal electrophysiological evaluation. RESULTS: The model showed incomplete paralysis of the right forelimb. Motor function showed recovery over time, and histological evaluation showed tissue changes associated with cerebral contusion. In addition, stable tcMEP waveforms were recorded before and after surgery and up to 4 weeks after injury. The tcMEP amplitude decreased significantly after injury and recovered over time. Furthermore, the amplitudes at 1, 7, and 14 days after injury were significantly lower than those at preinjury (p < 0.0006, p < 0.0007, and p < 0.0067, respectively). CONCLUSIONS: In the present study, the authors established a novel cold-induced brain injury rat model and technique that allowed for the evaluation of longitudinal tcMEP recording and demonstrated that multimodal evaluation for brain injury can be performed. This model can potentially be applied in future investigations of various therapies for brain injury.

Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury.

OBJECTIVES: Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion. DESIGN: Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult). SETTING: Preclinical laboratory. SUBJECTS: Adult male C57BL/6J mice (n = 54). INTERVENTIONS: Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 µg/kg)/high-dose glibenclamide (10 µg/mouse). Seven-day subcutaneous infusions (0.4 µg/hr) were continued. MEASUREMENTS AND MAIN RESULTS: Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial. CONCLUSIONS: High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.

Establishment and validation of PTE prediction model in patients with cerebral contusion.

Post-traumatic epilepsy (PTE) is an important cause of poor prognosis in patients with cerebral contusions. The primary purpose of this study is to evaluate the high-risk factors of PTE by summarizing and analyzing the baseline data, laboratory examination, and imaging features of patients with a cerebral contusion, and then developing a Nomogram prediction model and validating it. This study included 457 patients diagnosed with cerebral contusion who met the inclusion criteria from November 2016 to November 2019 at the Qinghai Provincial People's Hospital. All patients were assessed for seizure activity seven days after injury. Univariate analysis was used to determine the risk factors for PTE. Significant risk factors in univariate analysis were selected for binary logistic regression analysis. P < 0.05 was statistically significant. Based on the binary logistic regression analysis results, the prediction scoring system of PTE is established by Nomogram, and the line chart model is drawn. Finally, external validation was performed on 457 participants to assess its performance. Univariate and binary logistic regression analyses were performed using SPSS software, and the independent predictors significantly associated with PTE were screened as Contusion site, Chronic alcohol use, Contusion volume, Skull fracture, Subdural hematoma (SDH), Glasgow coma scale (GCS) score, and Non late post-traumatic seizure (Non-LPTS). Based on this, a Nomogram model was developed. The prediction accuracy of our scoring system was C-index = 98.29%. The confidence interval of the C-index was 97.28% ~ 99.30%. Internal validation showed that the calibration plot of this model was close to the ideal line. This study developed and verified a highly accurate Nomogram model, which can be used to individualize PTE prediction in patients with a cerebral contusion. It can identify individuals at high risk of PTE and help us pay attention to prevention in advance. The model has a low cost and is easy to be popularized in the clinic. This model still has some limitations and deficiencies, which need to be verified and improved by future large-sample and multicenter prospective studies.

Risk Factors for Postoperative Brain Contusion and Early Outcomes in Patients with Anterior Skull Base Meningiomas Undergoing Unifrontal Surgery: Single Center Experience with 110 Patients.

Background: Though frontal lobe contusion is a major cause for morbidity and prolonged hospitalization following excision of anterior skull base meningiomas, there is only limited literature on this complication. This study aimed to find out the incidence of postoperative frontal lobe contusion, identify the risk factors for its development and its impact on early postoperative outcome. Methods: Data from 110 patients who underwent excision of anterior skull base meningiomas through a unilateral supraorbital craniotomy from 2001 to 2018 were retrospectively analyzed. The risk factors analyzed for development of postoperative contusion were tumor location, size, volume, peritumoral edema, tumor consistency, extent of resection, tumor grade and type of retraction used. Results: Simpson grade II excision was achieved in ninety-two patients (83.6%). There was no frontal lobe contusion in eighty-two patients (74.5%). Frontal lobe contusion was noted in twenty-eight patients (25.5%), but was severe in only four patients (3.6%). On multivariate analysis, fixed retractor use (OR 11.56 [1.21-110.03]; P =0.03) and WHO grade II tumor (OR 3.29 [1.11-9.77]; P =0.03) were independently associated with postoperative frontal lobe contusion. Patients with higher contusion grade had significantly longer postoperative hospitalization (P =.02) and lower KPS score at discharge (P =.01). Conclusions: Unilateral supraorbital craniotomy and lateral subfrontal approach is an excellent procedure for excision of anterior skull base meningiomas with minimal postoperative complications related to frontal lobe retraction. Frontal lobe contusion should be avoided with the use of dynamic retraction, since postoperative contusion prolongs hospitalization and worsens the functional outcome at discharge.

Logistic Regression Analysis of the Mechanism of Blunt Brain Injury Inference Based on CT Images.

OBJECTIVES: To study the correlation between CT imaging features of acceleration and deceleration brain injury and injury degree. METHODS: A total of 299 cases with acceleration and deceleration brain injury were collected and divided into acceleration brain injury group and deceleration brain injury group according to the injury mechanism. Subarachnoid hemorrhage (SAH) and Glasgow coma scale (GCS), combined with skull fracture, epidural hematoma (EDH), subdural hematoma (SDH) and brain contusion on the same and opposite sides of the stress point were selected as the screening indexes. χ2 test was used for primary screening, and binary logistic regression analysis was used for secondary screening. The indexes with the strongest correlation in acceleration and deceleration injury mechanism were selected. RESULTS: χ2 test showed that skull fracture and EDH on the same side of the stress point; EDH, SDH and brain contusion on the opposite of the stress point; SAH, GCS were correlated with acceleration and deceleration injury (P<0.05). According to binary logistic regression analysis, the odds ratio (OR) of EDH on the same side of the stress point was 2.697, the OR of brain contusion on the opposite of the stress point was 0.043 and the OR of GCS was 0.238, suggesting there was statistically significant (P<0.05). CONCLUSIONS: EDH on the same side of the stress point, brain contusion on the opposite of the stress point and GCS can be used as key indicators to distinguish acceleration and deceleration injury mechanism. In addition, skull fracture on the same side of the stress point, EDH and SDH on the opposite of the stress point and SAH were relatively weak indicators in distinguishing acceleration and deceleration injury mechanism.

Construction and Evaluation of Prognosis Prediction Model for Patients with Brain Contusion and Laceration Based on Machine Learning.

Objective: Finding valuable risk factors for the prognosis of brain contusion and laceration can help patients understand the condition and improve the prognosis. This study is aimed at analyzing the risk factors of poor prognosis in patients with brain contusion after the operation. Methods: A total of 136 patients with cerebral contusion and laceration combined with cerebral hernia treated by neurosurgical craniotomy in our hospital were retrospectively selected and divided into a training set (n = 95) and a test set (n = 41) by the 10-fold crossover method. Logistic regression and back-propagation neural network prediction models were established to predict poor prognosis factors. The receiver operating characteristic curve (ROC) and the calibration curve were used to verify the differentiation and consistency of the prediction model. Results: Based on logistic regression and back-propagation neural network prediction models, GCS score ≤ 8 on admission, blood loss ≥ 30 ml, mannitol ≥ 2 weeks, anticoagulants before admission, and surgical treatment are the risk factors that affect the poor prognosis of patients with a cerebral contusion after the operation. The area under the ROC was 0.816 (95% CI 0.705~0.926) and 0.819 (95% CI 0.708~0.931), respectively. Conclusion: The prediction model based on the risk factors that affect the poor prognosis of patients with brain contusion and laceration has good discrimination and accuracy.

Characteristics, image findings and clinical outcome of moderate and severe traumatic brain injury among severely injured children: a population-based cohort study.

PURPOSE: The aim of this study was to explore patient and injury characteristics, image findings, short-term clinical outcome and time trends of moderate and severe traumatic brain injury in severely injured children. METHODS: This study is an observational cohort study based on prospectively collected data from an institutional trauma registry database covering all trauma patients in South West Norway. All paediatric patients registered in the database between 01.01.2004 and 31.12.2019 were included. RESULTS: During the 16 years-study periods, 82 paediatric patients with moderate (n = 42) and severe (n = 40) traumatic brain injury were identified. Median age was 13.0 years, 45% were female and median Glasgow Coma Scale score at admission was 9.0. Cranial fractures were common image findings in both groups. Cerebral contusions (32%) and epidural hematomas (29%) were more commonly found in moderate traumatic brain injury; cerebral contusions (49%), diffuse axonal injury (31%) and cerebral oedema (46%) were more prominent in severe traumatic brain injury. All children with moderate traumatic brain injury survived and favourable outcome was registered in 98%. Overall mortality in the severe traumatic brain injury cohort was 38% (thereof 25% due to TBI) and only 38% had a favourable short-term outcome. CONCLUSIONS: In this population-based study on paediatric trauma patients over a period of 16 years severe traumatic brain injury in children still had a considerably high mortality and a higher proportion of patients experienced an unfavourable clinical short-term outcome. Moderate traumatic brain injury resulted in favourable clinical outcome.

Combined Radiomics Model for Prediction of Hematoma Progression and Clinical Outcome of Cerebral Contusions in Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury is a common and devastating injury that is the leading cause of neurological disability and death worldwide. Patients with cerebral lobe contusion received conservative treatment because of their mild manifestations, but delayed intracranial hematoma may increase and even become life-threatening. We explored the noninvasive method to predict the prognosis of progression and Glasgow Outcome Scale (GOS) by using a quantitative radiomics approach and statistical analysis. METHODS: Eighty-eight patients who were pathologically diagnosed were retrospectively studied. The radiomics method developed in this work included image segmentation, feature extraction, and feature selection. The nomograms were established based on statistical analysis and a radiomics method. We conducted a comparative study of hematoma progression and GOS between the clinical factor alone and fusion radiomics features. RESULTS: Nineteen clinical factors, 513 radiomics features, and 116 locational features were considered. Among clinical factors, international normalized ratio, prothrombin time, and fibrinogen were enrolled for hematoma progression. As for GOS, treatment strategy, age, Glasgow Coma Scale score, and blood platelet were associated factors. Eight features for GOS and five features for hematoma progression were filtered by using sparse representation and locality preserving projection-combined method. Four nomograms were constructed. After fusion radiomics features, area under the curve of hematoma progression prediction increased from 0.832 to 0.899, whereas GOS prediction went from 0.794 to 0.844. CONCLUSIONS: A radiomic-based model that merges radiomics and clinical features is a noninvasive approach to predict hematoma progression and clinical outcomes of cerebral contusions in traumatic brain injury.