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2.
Acta Neurochir (Wien) ; 166(1): 377, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316131

RESUMEN

BACKGROUND: Cortical contusions are common in moderate-severe traumatic brain injury (TBI). Cortical contusions often expand, potentially causing neuro-worsening several hours to days post-trauma. While contusion expansion (CE) may affect outcome, potential clinical and radiological markers that can predict CE have been insufficiently explored. In the present single-center retrospective observational cohort study, we evaluated clinical outcome by the Glasgow Outcome Scale extended (GOSE) scale and evaluated risk factor for CE. METHOD: Adult TBI patients > 18 years of age, and of all injury severities, were included. Main variables of interest were low platelet count, defined as < 150 × 109/L, presence of bifrontal contusions and CE, defined as absolute contusion volume increase in cm3. Factors associated with CE and clinical outcome according to GOSE were analyzed. RESULTS: Between 2012-2022, 272 patients were included. Contusion size on admission correlated positively with CE, as did the Marshall and Rotterdam radiological classification scores. Bifrontal contusions were significantly larger at admission, experienced larger CE, and had a worse outcome than contusions in other locations. Patients with a platelet count < 150 × 109/L experienced a greater volume CE and had a worse outcome when compared to patients with a normal platelet count. In a multivariate analysis, CE remained significantly associated with a poor outcome six months post- injury. CONCLUSION: Contusion volume at admission, Marshall CT classification and Rotterdam CT score, positively correlated to CE. Bifrontal contusions and a platelet count < 150 × 109/L were associated with CE, and a poor clinical outcome. Large CE volumes were associated with a worse clinical outcome, and CE was per se associated with outcome in a multivariate analysis. Management of these risk factors for CE in the acute post-injury setting may be needed to attenuate contusion expansion and to improve clinical outcome in TBI patients suffering from cortical contusion injuries.


Asunto(s)
Contusión Encefálica , Lesiones Traumáticas del Encéfalo , Humanos , Masculino , Femenino , Estudios Retrospectivos , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Recuento de Plaquetas , Contusión Encefálica/diagnóstico por imagen , Anciano , Escala de Consecuencias de Glasgow
3.
Neurosurg Rev ; 47(1): 597, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39261322

RESUMEN

The popularity of electric scooters (ES) during the last five years due to climate neutrality and public availability led to increased numbers in traffic accidents with significant injuries. This study was conducted to overview e-scooter related computed tomography (CT) positive traumatic brain injuries, exploring circumstances, clinical course, outcomes and possible relations to behavioral patterns. We retrospectively reviewed medical data of all patients treated in our center during the period 2019 to 2023, medical records were analysed and statistically processed. This review included 45 patients, 75.7% were males and median age was 40 years old. Patient numbers did not differ between weekdays, working days versus weekends and time of the day. Eighty percent of patients were injured from falling off the scooter, the rest were hit by another vehicle while riding. None of the patients were known using helmet, significant alcohol intoxication was found in 68.8% of cases. The most common traumatic intracranial features were subarachnoid hemorrhage (55.6%), followed by brain contusions (48.9%), epidural (26.7%), subdural (26.7%) hemorrhages. Age had a positive correlation with alcohol intoxication (r = 0.596, p = 0.007) and poor outcomes (r = 0.522, p = 0.004), also, men over 40 years old were more likely to undergo surgery (p = 0.024), meanwhile operated patients suffered more infections (p = 0.011) and more often ended with poor outcomes (p < 0.001).


Asunto(s)
Accidentes de Tránsito , Lesiones Traumáticas del Encéfalo , Tomografía Computarizada por Rayos X , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Estudios Retrospectivos , Adulto Joven , Anciano , Adolescente , Contusión Encefálica , Intoxicación Alcohólica/epidemiología
4.
Injury ; 55(6): 111589, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38704918

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Modelos Animales de Enfermedad , Animales , Porcinos , Contusión Encefálica/fisiopatología , Humanos , Presión Intracraneal/fisiología , Fenómenos Biomecánicos , Lesiones Traumáticas del Encéfalo/fisiopatología , Encéfalo/fisiopatología
6.
Neurocrit Care ; 41(2): 511-522, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38506969

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Lesiones Traumáticas del Encéfalo , Cuidados Críticos , Presión Intracraneal , Humanos , Masculino , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Femenino , Persona de Mediana Edad , Adulto , Anciano , Presión Intracraneal/fisiología , Contusión Encefálica/fisiopatología , Circulación Cerebrovascular/fisiología , Adulto Joven
7.
Front Immunol ; 15: 1336862, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38545111

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Neutrófilos , Humanos , Masculino , Persona de Mediana Edad , Femenino , Monocitos , Estudios Retrospectivos , Estudios Prospectivos , Linfocitos , Pronóstico
8.
J Neurotrauma ; 41(11-12): 1337-1352, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38326935

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Hematoma , Tomografía Computarizada por Rayos X , Humanos , Pronóstico , Masculino , Femenino , Hematoma/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Adulto , Contusión Encefálica/diagnóstico por imagen , Anciano , Progresión de la Enfermedad , Adulto Joven , Adolescente , Aprendizaje Automático , Estudios Retrospectivos , Radiómica
11.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(7. Vyp. 2): 72-76, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-37560837

RESUMEN

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.


Asunto(s)
Conmoción Encefálica , Contusión Encefálica , Lesiones Traumáticas del Encéfalo , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Masculino , Humanos , Femenino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/líquido cefalorraquídeo , Estudios Prospectivos , Estudios Retrospectivos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico
13.
Neurotherapeutics ; 20(6): 1472-1481, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37306928

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Edema Encefálico , Contusiones , Humanos , Contusión Encefálica/tratamiento farmacológico , Gliburida/uso terapéutico , Gliburida/farmacología , Edema Encefálico/tratamiento farmacológico , Ensayos Clínicos como Asunto , Contusiones/tratamiento farmacológico , Receptores de Sulfonilureas/genética , Receptores de Sulfonilureas/metabolismo , Hemorragia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Medicine (Baltimore) ; 102(18): e33522, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37145014

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Traumatismos Craneocerebrales , Laceraciones , Masculino , Humanos , Persona de Mediana Edad , Hematoma/etiología , Lóbulo Frontal/diagnóstico por imagen , Contusión Encefálica/complicaciones , Contusión Encefálica/diagnóstico por imagen
15.
Acta Neurochir (Wien) ; 165(11): 3207-3215, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36877329

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Hematoma Subdural Crónico , Humanos , Masculino , Femenino , Estudios Retrospectivos , Hematoma Subdural Crónico/diagnóstico por imagen , Hematoma Subdural Crónico/cirugía , Espacio Subdural/cirugía , Trepanación/efectos adversos , Trepanación/métodos , Drenaje/efectos adversos , Drenaje/métodos , Contusión Encefálica/cirugía , Catéteres , Resultado del Tratamiento , Recurrencia
16.
J Neurosurg ; 139(3): 840-847, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36790020

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Ratas , Femenino , Animales , Potenciales Evocados Motores/fisiología , Parálisis
17.
Crit Care Med ; 51(2): e45-e59, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36661464

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Edema Encefálico , Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Animales , Masculino , Ratones , Teorema de Bayes , Contusión Encefálica/complicaciones , Contusión Encefálica/tratamiento farmacológico , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Modelos Animales de Enfermedad , Endofenotipos , Gliburida/farmacología , Gliburida/uso terapéutico , Imagen por Resonancia Magnética , Ratones Endogámicos C57BL
18.
Sci Rep ; 12(1): 20574, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36446999

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Contusiones , Epilepsia Postraumática , Humanos , Estudios Prospectivos , Convulsiones
19.
Neurol India ; 70(5): 2053-2058, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36352608

RESUMEN

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.


Asunto(s)
Contusión Encefálica , Neoplasias Meníngeas , Meningioma , Neoplasias de la Base del Cráneo , Humanos , Meningioma/patología , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/etiología , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/patología , Estudios Retrospectivos , Contusión Encefálica/etiología , Contusión Encefálica/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Factores de Riesgo , Base del Cráneo/cirugía , Base del Cráneo/patología , Resultado del Tratamiento
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