BACKGROUND: 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.

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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.
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.
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.
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.

BACKGROUND: Patients with traumatic brain injury (TBI) with large contusions make up a specific TBI subtype. Because of the risk of brain edema worsening, elevated cerebral perfusion pressure (CPP) may be particularly dangerous. The pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) are new promising perfusion targets based on cerebral autoregulation, but they reflect the global brain state and may be less valid in patients with predominant focal lesions. In this study, we aimed to investigate if patients with TBI with significant contusions exhibited a different association between PRx, CPP, and CPPopt in relation to functional outcome compared to those with small/no contusions.
METHODS: This observational study included 385 patients with moderate to severe TBI treated at a neurointensive care unit in Uppsala, Sweden. The patients were classified into two groups: (1) significant contusions (> 10 mL) and (2) small/no contusions (but with extra-axial or diffuse injuries). The percentage of good monitoring time (%GMT) with intracranial pressure > 20 mm Hg; PRx > 0.30; CPP < 60 mm Hg, within 60-70 mm Hg, or > 70 mm Hg; and ΔCPPopt less than - 5 mm Hg, ± 5 mm Hg, or > 5 mm Hg was calculated. Outcome (Glasgow Outcome Scale-Extended) was assessed after 6 months.
RESULTS: Among the 120 (31%) patients with significant contusions, a lower %GMT with CPP between 60 and 70 mm Hg was independently associated with unfavorable outcome. The %GMTs with PRx and ΔCPPopt ± 5 mm Hg were not independently associated with outcome. Among the 265 (69%) patients with small/no contusions, a higher %GMT of PRx > 0.30 and a lower %GMT of ΔCPPopt ± 5 mm Hg were independently associated with unfavorable outcome.
CONCLUSIONS: In patients with TBI with significant contusions, CPP within 60-70 mm Hg may improve outcome. PRx and CPPopt, which reflect global cerebral pressure autoregulation, may be useful in patients with TBI without significant focal brain lesions but seem less valid for those with large contusions. However, this was an observational, hypothesis-generating study; our findings need to be validated in prospective studies before translating them into clinical practice.

Hemorrhagic progression of contusion (HPC) often occurs early in cerebral contusions (CC) patients, significantly impacting their prognosis. It is vital to promptly assess HPC and predict outcomes for effective tailored interventions, thereby enhancing prognosis in CC patients. We utilized the Attention-3DUNet neural network to semi-automatically segment hematomas from computed tomography (CT) images of 452 CC patients, incorporating 695 hematomas. Subsequently, 1502 radiomic features were extracted from 358 hematomas in 261 patients. After a selection process, these features were used to calculate the radiomic signature (Radscore). The Radscore, along with clinical features such as medical history, physical examinations, laboratory results, and radiological findings, was employed to develop predictive models. For prognosis (discharge Glasgow Outcome Scale score), radiomic features of each hematoma were augmented and fused for correlation. We employed various machine learning methodologies to create both a combined model, integrating radiomics and clinical features, and a clinical-only model. Nomograms based on logistic regression were constructed to visually represent the predictive procedure, and external validation was performed on 170 patients from three additional centers. The results showed that for HPC, the combined model, incorporating hemoglobin levels, Rotterdam CT score of 3, multi-hematoma fuzzy sign, concurrent subdural hemorrhage, international normalized ratio, and Radscore, achieved area under the receiver operating characteristic curve (AUC) values of 0.848 and 0.836 in the test and external validation cohorts, respectively. The clinical model predicting prognosis, utilizing age, Abbreviated Injury Scale for the head, Glasgow Coma Scale Motor component, Glasgow Coma Scale Verbal component, albumin, and Radscore, attained AUC values of 0.846 and 0.803 in the test and external validation cohorts, respectively. Selected radiomic features indicated that irregularly shaped and highly heterogeneous hematomas increased the likelihood of HPC, while larger weighted axial lengths and lower densities of hematomas were associated with a higher risk of poor prognosis. Predictive models that combine radiomic and clinical features exhibit robust performance in forecasting HPC and the risk of poor prognosis in CC patients. Radiomic features complement clinical features in predicting HPC, although their ability to enhance the predictive accuracy of the clinical model for adverse prognosis is limited.

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BACKGROUND: The objective of this research was to examine the impact of the monocyte-to-lymphocyte ratio (MLR) on the advancement of hematoma after cerebral contusion.
METHODS: The clinical information and laboratory test findings of people with cerebral contusion were retrospectively analyzed. Using the tertiles of MLR, the study participants were categorized into three groups, enabling the evaluation of the correlation between MLR and the advancement of hematoma after cerebral contusion.
RESULTS: Among the cohort of patients showing progression, MLR levels were significantly higher compared with the nonprogress group (P < 0.001). The high MLR group had a significantly higher proportion of patients with hematoma progression compared with the medium and low MLR groups. However, the medium MLR group had a lower proportion of patients with hematoma progression compared with the low MLR group. High MLR levels were independently linked to a higher risk of hematoma progression (Odds Ratio 3.546, 95% Confidence Interval 1.187-10.597, P = 0.024). By incorporating factors such as Glasgow Coma Scale score on admission, anticoagulant/antiplatelet therapy, white blood cell count, and MLR into the model, the predictive performance of the model significantly improved (area under the curve 0.754).
CONCLUSIONS: Our study suggests that MLR may serve as a potential indicator for predicting the progression of hematoma after cerebral contusion. Further research is necessary to investigate the underlying pathological and physiological mechanisms that contribute to the association between MLR and the progression of hematoma after cerebral contusion and to explore its clinical implications.

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.
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.
CONCLUSIONS: 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.
UNASSIGNED: Оценить связь черепно-мозговой травмы (ЧМТ), полученной до дебюта рассеянного склероза (РС), со скоростью прогрессирования неврологических расстройств и маркерами проницаемости гематоэнцефалического барьера, воспаления, демиелинизации и глиоза в цереброспинальной жидкости.
UNASSIGNED: В проспективном контролируемом рандомизированном исследовании приняли участие 88 больных ремиттирующим РС Алтайского края России с/без ЧМТ до дебюта РС (n=44; 19 мужчин, 25 женщин в каждой группе). Нарастание инвалидизации оценивали ретроспективно. Плеоцитоз, уровень белка, альбумина, С-реактивного белка, TNF-α, основного белка миелина, белка S100 измеряли в цереброспинальной жидкости в подгруппах пациентов (n=14 в каждой из групп) в периоды ремиссии и обострения РС.
UNASSIGNED: В группе больных с ЧМТ до дебюта РС документированы сотрясение и ушиб головного мозга легкой степени у 35 (79,5%) и 9 (20,5%) пациентов соответственно. У 72,5% больных ЧМТ была в возрасте старше 15 лет. Скорость прогрессирования PC была выше в группе больных с ЧМТ по сравнению с группой больных без ЧМТ (0,76±1,28 и 0,40±0,43 балла EDSS в год соответственно; p=0,014). ЧМТ до дебюта РС повышает риск нарастания инвалидизации более чем на 0,25 балла EDSS в год (ОШ 2,74; 95% ДИ 1,10—6,85; p=0,029). Ни при обострении, ни в период ремиссии РС не найдено межгрупповых различий исследованных показателей цереброспинальной жидкости.
UNASSIGNED: Сотрясение или ушиб головного мозга легкой степени тяжести до развития РС могут быть факторами, влияющими на прогрессирование неврологического дефицита. Представляется актуальным исследование механизмов неблагоприятного влияния ЧМТ на прогрессирование РС.

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.