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 imagenRESUMEN
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 C57BLRESUMEN
ABSTRACT: Traumatic brain injury (TBI), a common neurosurgical condition, has well-known treatment guidelines. However, the mechanisms underlying the varying severity of brain edema secondary to TBI are largely unknown, leading to controversial treatments.This study seeks to measure edema volumes around brain contusions in different regions, analyze factors related to differences in edema volume and provide a theoretical basis for brain edema treatment.Data from 113 brain contusion patients treated at the Department of Neurosurgery of Fuzhou General Hospital from January 2017 to November 2019 were analyzed retrospectively. Based on computed tomography (CT) data, the patients were divided into the venous group (brain contusion in regions with large cortical veins, nâ=â47) and the nonvenous group (brain contusions in other regions, nâ=â66). Here, 3D Slicer software was used to calculate the brain contusion volume on the first CT obtained after injury and the brain contusion volume and its surrounding edema on the 5th day after injury. The brain contusion volume to surrounding edema volume ratio was calculated, and the number of patients who showed brain contusion progression requiring surgery was determined. Hematocrit (Hct), fibrinogen (Fg), and d-dimer levels within 6âhours and on the 5th day after admission were also compared.Patients in the venous group had a significantly increased percentage of area with edema around the brain contusion compared with patients in the nonvenous group (Pâ<â.05), and the 2 groups showed no significant difference in the number of patients with brain contusion progression or surgical treatment (Pâ>â.05) or Hct, Fg, or d-dimer (D-D) levels. For all patients, Hct, Fg, and D-D levels within 6âhours after admission were significantly different from those on the 5th day (Pâ<â.05 for all).Cortical venous obstruction may be the most important factor influencing edema around brain contusions. The Fg level decreased slightly, and the D-D level increased to its peak rapidly after mild-moderate TBI. This change was followed by a gradual increase in the former and a gradual decrease in the latter.
Asunto(s)
Contusión Encefálica/complicaciones , Edema Encefálico/clasificación , Adulto , Edema Encefálico/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Traumatic brain injury (TBI) constitutes a leading cause of death and disability. Patients with TBI and cerebral contusions developing pericontusional edema are occasionally given dexamethasone on the belief that this edema is similar to that of tumors, in which the beneficial effect of dexamethasone has been demonstrated. METHODS: The DEXCON TBI trial is a multicenter, pragmatic, randomized, triple-blind, placebo controlled trial to quantify the effects of dexamethasone on the prognosis of TBI patients with brain contusions and pericontusional edema. Adult patients who fulfill the elegibility criteria will be randomized to dexamethasone/placebo in a short and descending course: 4âmg/6âh (2âdays); 4âmg/8âhours (2âdays); 2âmg/6âhours (2âdays); 2âmg/8âhours (2âdays); 1âmg/8âhours (2âdays); 1âmg/12âhours (2âdays). The primary outcome is the Glasgow Scale Outcome Extended (GOSE) performed 1 month and 6âmonths after TBI. Secondary outcomes are: number of episodes of neurological deterioration; symptoms associated with TBI; adverse events; volume of pericontusional edema before and after 12âdays of treatment; results of the neuropsychological tests one month and 6âmonths after TBI. The main analysis will be on an "intention-to-treat" basis. Logistic regression will estimate the effect of dexamethasone/placebo on GOSE at one month and at 6âmonths, dichotomized in unfavorable outcome (GOSE 1-6) and favorable outcome (GOSE 7-8). Efficacy will also be analyzed using the 'sliding dichotomy'. An interim and safety analysis will be performed including patients recruited during the first year to calculate the conditional power. A study with 600 patients would have 80% power (2 sided alphaâ=â5%) to detect a 12% absolute increase (from 50% to 62%) in good recovery. DISCUSSION: This is a confirmative trial to elucidate the therapeutic efficacy of dexamethasone in a very specific group of TBI patients: patients with brain contusions and pericontusional edema. This trial could become an important milestone for TBI patients as nowadays there is no effective treatment in this type of patients. TRIAL REGISTRATION: eudraCT: 2019-004038-41; Clinical Trials.gov: NCT04303065.
Asunto(s)
Antiinflamatorios/uso terapéutico , Contusión Encefálica/tratamiento farmacológico , Edema Encefálico/tratamiento farmacológico , Dexametasona/uso terapéutico , Contusión Encefálica/complicaciones , Edema Encefálico/etiología , Método Doble Ciego , Humanos , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not. DESIGN: Multicentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI). RESULTS: From a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy. CONCLUSIONS AND RELEVANCE: Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.
Asunto(s)
Contusión Encefálica/diagnóstico por imagen , Hemorragia Encefálica Traumática/diagnóstico por imagen , Adelgazamiento de la Corteza Cerebral/diagnóstico por imagen , Epilepsia Postraumática/diagnóstico por imagen , Lóbulo Frontal/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Lóbulo Temporal/diagnóstico por imagen , Adulto , Contusión Encefálica/complicaciones , Hemorragia Encefálica Traumática/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Reglas de Decisión Clínica , Biología Computacional , Electroencefalografía , Epilepsia Postraumática/epidemiología , Epilepsia Postraumática/etiología , Femenino , Lóbulo Frontal/patología , Escala de Coma de Glasgow , Hipocampo/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Estudios Prospectivos , Lóbulo Temporal/patología , Factores de Tiempo , Adulto JovenRESUMEN
Several studies have reported a strong association between semantic system impairment and LARC error production. However, our patient with a left temporal lobe contusion, including the fusiform gyrus, showed LARC errors even in two-Kanji compound words, the meanings of which the patient understood. Also, the poor results of lexical decision and picture naming suggested problems in orthographic and phonological retrieval. From these results, we concluded that at least some LARC errors are independent of semantic impairment, and other explanations are needed for this type of error.
Asunto(s)
Afasia/etiología , Contusión Encefálica/complicaciones , Dislexia/etiología , Lóbulo Temporal/lesiones , Anciano , Afasia/fisiopatología , Contusión Encefálica/diagnóstico por imagen , Dislexia/fisiopatología , Femenino , Humanos , Japón , Reconocimiento Visual de Modelos/fisiología , Lóbulo Temporal/diagnóstico por imagenAsunto(s)
Lesiones Traumáticas del Encéfalo/fisiopatología , Fármacos Neuromusculares no Despolarizantes/uso terapéutico , Rocuronio/uso terapéutico , Hemorragia Subaracnoidea Traumática/fisiopatología , Sugammadex/uso terapéutico , Accidentes de Tránsito , Contusión Encefálica/complicaciones , Contusión Encefálica/diagnóstico , Contusión Encefálica/fisiopatología , Contusión Encefálica/terapia , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Manejo de la Enfermedad , Humanos , Intubación Intratraqueal/métodos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Examen Neurológico , Hemorragia Subaracnoidea Traumática/complicaciones , Hemorragia Subaracnoidea Traumática/diagnóstico , Hemorragia Subaracnoidea Traumática/terapiaRESUMEN
INTRODUCTION: Controlling of secondary traumatic brain injuries (TBI) is necessary due to its salient effect on the improvement of patients with TBI and the final outcomes within early hours of trauma onset. This study aims to investigate the effect of intravenous tranexamic acid (TAX) administration on decreased hemorrhage during surgery. METHODS: This double-blind, randomized, and placebo-controlled trial was conducted on patients referring to the emergency department (ED) with IPH due to brain contusion within 8 h of injury onset. The patients were evaluated by receiving TXA and 0.9% normal saline as a placebo. The following evaluation and estimations were performed: intracranial hemorrhage volume after surgery using brain CT-scan; hemoglobin (Hb) volume before, immediately after, and six hours after surgery; and the severity of TBI based on Glasgow Coma Score (GCS). RESULTS: 40 patients with 55.02 ± 18.64 years old diagnosed with a contusion and intraparenchymal hemorrhage. Although the (Mean ± SD) hemorrhage during surgery in patients receiving TXA (784.21 ± 304.162) was lower than the placebo group (805.26 ± 300.876), no significant difference was observed between two groups (P=0.83). The (Mean ± SD) Hb volume reduction immediately during surgery (0.07 ± 0.001 and 0.23 ± 0.02) and six hours after surgery (0.04 ± 0.008 and 0.12 ± 0.006) was also lower in TXA group but had no significant difference (P = 0.89 and P = 0.97, respectively). CONCLUSION: Using TXA may reduce the hemorrhage in patients with TBI, but this effect, as in this study, was not statistically significant and it is suggested that a clinical trial with a larger population is employed for further investigation.
Asunto(s)
Antifibrinolíticos/administración & dosificación , Pérdida de Sangre Quirúrgica/prevención & control , Contusión Encefálica/cirugía , Hemorragia Encefálica Traumática/prevención & control , Ácido Tranexámico/administración & dosificación , Adulto , Anciano , Contusión Encefálica/complicaciones , Contusión Encefálica/tratamiento farmacológico , Hemorragia Encefálica Traumática/etiología , Hemorragia Encefálica Traumática/mortalidad , Método Doble Ciego , Femenino , Escala de Coma de Glasgow , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Velocidad del Flujo Sanguíneo , Edema Encefálico/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Fallo Renal Crónico/terapia , Arteria Cerebral Media/diagnóstico por imagen , Diálisis Renal/efectos adversos , Estado Epiléptico/fisiopatología , Resistencia Vascular , Anciano , Barrera Hematoencefálica/metabolismo , Contusión Encefálica/complicaciones , Contusión Encefálica/diagnóstico por imagen , Contusión Encefálica/metabolismo , Contusión Encefálica/fisiopatología , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Edema Encefálico/metabolismo , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/metabolismo , Hemorragia Cerebral Traumática/complicaciones , Hemorragia Cerebral Traumática/diagnóstico por imagen , Hemorragia Cerebral Traumática/metabolismo , Hemorragia Cerebral Traumática/fisiopatología , Trastornos de la Conciencia/etiología , Trastornos de la Conciencia/metabolismo , Trastornos de la Conciencia/fisiopatología , Cefalea/etiología , Cefalea/metabolismo , Cefalea/fisiopatología , Hematoma Subdural Agudo/complicaciones , Hematoma Subdural Agudo/diagnóstico por imagen , Hematoma Subdural Agudo/metabolismo , Hematoma Subdural Agudo/fisiopatología , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/metabolismo , Masculino , Arteria Cerebral Media/fisiopatología , Monitoreo Fisiológico , Náusea/etiología , Náusea/metabolismo , Náusea/fisiopatología , Flujo Pulsátil , Estado Epiléptico/etiología , Estado Epiléptico/metabolismo , Ultrasonografía Doppler Transcraneal , Vómitos/etiología , Vómitos/metabolismo , Vómitos/fisiopatologíaRESUMEN
Arginine vasopressin (AVP) is a chemical signal in the brain that influences cerebral vascular resistance and brain water permeability. Increases in AVP contribute to the pathophysiology of brain edema following traumatic brain injury (TBI). These effects are mediated through AVP V1a receptors that are expressed in cortical and subcortical brain areas. This exploratory study characterizes the effects of a novel, V1a receptor antagonist, AVN576, on behavioral and magnetic resonance imaging (MRI) measures after severe TBI. Male Sprague Dawley rats were impacted twice producing contusions in the forebrain, putative cerebral edema, and cognitive deficits. Rats were treated with AVN576 after initial impact for 5 days and then tested for changes in cognition. MRI was used to assess brain injury, enlargement of the ventricles, and resting state functional connectivity. Vehicle treated rats had significant deficits in learning and memory, enlarged ventricular volumes, and hypoconnectivity in hippocampal circuitry. AVN576 treatment eliminated the enlargement of the lateral ventricles and deficits in cognitive function while increasing connectivity in hippocampal circuitry. These data corroborate the extensive literature that drugs selectively targeting the AVP V1a receptor could be used to treat TBI in the clinic.
Asunto(s)
Antagonistas de los Receptores de Hormonas Antidiuréticas/farmacología , Contusión Encefálica/diagnóstico por imagen , Edema Encefálico/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Cognición/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Contusión Encefálica/complicaciones , Contusión Encefálica/tratamiento farmacológico , Contusión Encefálica/fisiopatología , Edema Encefálico/etiología , Edema Encefálico/fisiopatología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/fisiopatología , Neuroimagen Funcional , Hipocampo/diagnóstico por imagen , Hipocampo/fisiopatología , Ventrículos Laterales/diagnóstico por imagen , Ventrículos Laterales/patología , Imagen por Resonancia Magnética , Aprendizaje por Laberinto , Tamaño de los Órganos , Ratas , Receptores de VasopresinasRESUMEN
BACKGROUND: Measuring optic nerve sheath diameter (ONSD), an indicator to predict intracranial hypertension, is noninvasive and convenient, but the reliability of ONSD needs to be improved. Instead of using ONSD alone, this study aimed to evaluate the reliability of the ratio of ONSD to eyeball transverse diameter (ONSD/ETD) in predicting intracranial hypertension in traumatic brain injury (TBI) patients. METHODS: We performed a prospective study on patients admitted to the Surgery Intensive Care Unit. The included 52 adults underwent craniotomy for TBI between March 2017 and September 2018. The ONSD and ETD of each eyeball were measured by ultrasound and computed tomography (CT) scan within 24 h after a fiber optic probe was placed into lateral ventricle. Intracranial pressure (ICP) > 20 mmHg was regarded as intracranial hypertension. The correlations between invasive ICP and ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and CT-ONSD were each analyzed separately. RESULTS: Ultrasound measurement was successfully performed in 94% (n = 49) of cases, and ultrasound and CT measurement were performed in 48% (n = 25) of cases. The correlation efficiencies between ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and ICP were 0.613, 0.498, and 0.688, respectively (P < 0.05). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the ultrasound-ONSD/ETD ratio and CT-ONSD/ETD ratio were 0.920 (95% CI 0.877-0.964) and 0.896 (95% CI 0.856-0.931), respectively. The corresponding threshold values were 0.25 (sensitivity of 90%, specificity of 82.3%) and 0.25 (sensitivity of 85.7%, specificity of 83.3%), respectively. CONCLUSION: The ratio of ONSD to ETD tested by ultrasound may be a reliable indicator for predicting intracranial hypertension in TBI patients.
Asunto(s)
Lesiones Traumáticas del Encéfalo/fisiopatología , Ojo/diagnóstico por imagen , Hipertensión Intracraneal/diagnóstico por imagen , Nervio Óptico/diagnóstico por imagen , Adulto , Contusión Encefálica/complicaciones , Contusión Encefálica/fisiopatología , Lesiones Traumáticas del Encéfalo/complicaciones , Hemorragia Cerebral Traumática/complicaciones , Hemorragia Cerebral Traumática/fisiopatología , Ojo/patología , Femenino , Escala de Coma de Glasgow , Hematoma Epidural Craneal/complicaciones , Hematoma Epidural Craneal/fisiopatología , Hematoma Intracraneal Subdural/complicaciones , Hematoma Intracraneal Subdural/fisiopatología , Humanos , Hipertensión Intracraneal/diagnóstico , Hipertensión Intracraneal/etiología , Masculino , Persona de Mediana Edad , Nervio Óptico/patología , Técnicas de Cultivo de Órganos , Estudios Prospectivos , Reproducibilidad de los Resultados , Hemorragia Subaracnoidea Traumática/complicaciones , Hemorragia Subaracnoidea Traumática/fisiopatología , Tomografía Computarizada por Rayos X , UltrasonografíaAsunto(s)
Accidentes por Caídas , Servicio de Urgencia en Hospital , Amigos/psicología , Hematoma Intracraneal Subdural/diagnóstico por imagen , Relaciones Médico-Paciente , Contusión Encefálica/complicaciones , Hematoma Intracraneal Subdural/etiología , Humanos , Traumatismos de la Rodilla/etiología , Traumatismos de la Rodilla/terapia , Relaciones Profesional-Familia , Pronóstico , Derivación y Consulta , Revelación de la VerdadRESUMEN
Micrographia is a rare neurological finding in isolation. Most cases of isolated micrographia have been found in association with focal ischemia of the left basal ganglia. Here, we present a case of post-traumatic micrographia stemming from contusion to the left basal ganglia.
Asunto(s)
Agrafia/etiología , Ganglios Basales/lesiones , Contusión Encefálica/complicaciones , Adolescente , Hemorragia Encefálica Traumática/complicaciones , Lesión Axonal Difusa/complicaciones , Humanos , MasculinoRESUMEN
In severe traumatic brain injury (TBI), contusions often are worsened by contusion expansion or hemorrhagic progression of contusion (HPC), which may double the original contusion volume and worsen outcome. In humans and rodents with contusion-TBI, sulfonylurea receptor 1 (SUR1) is upregulated in microvessels and astrocytes, and in rodent models, blockade of SUR1 with glibenclamide reduces HPC. SUR1 does not function by itself, but must co-assemble with either KIR6.2 or transient receptor potential cation channel subfamily M member 4 (TRPM4) to form KATP (SUR1-KIR6.2) or SUR1-TRPM4 channels, with the two having opposite effects on membrane potential. Both KIR6.2 and TRPM4 are reportedly upregulated in TBI, especially in astrocytes, but the identity and function of SUR1-regulated channels post-TBI is unknown. Here, we analyzed human and rat brain tissues after contusion-TBI to characterize SUR1, TRPM4, and KIR6.2 expression, and in the rat model, to examine the effects on HPC of inhibiting expression of the three subunits using intravenous antisense oligodeoxynucleotides (AS-ODN). Glial fibrillary acidic protein (GFAP) immunoreactivity was used to operationally define core versus penumbral tissues. In humans and rats, GFAP-negative core tissues contained microvessels that expressed SUR1 and TRPM4, whereas GFAP-positive penumbral tissues contained astrocytes that expressed all three subunits. Förster resonance energy transfer imaging demonstrated SUR1-TRPM4 heteromers in endothelium, and SUR1-TRPM4 and SUR1-KIR6.2 heteromers in astrocytes. In rats, glibenclamide as well as AS-ODN targeting SUR1 and TRPM4, but not KIR6.2, reduced HPC at 24 h post-TBI. Our findings demonstrate upregulation of SUR1-TRPM4 and KATP after contusion-TBI, identify SUR1-TRPM4 as the primary molecular mechanism that accounts for HPC, and indicate that SUR1-TRPM4 is a crucial target of glibenclamide.
Asunto(s)
Contusión Encefálica/metabolismo , Hemorragias Intracraneales/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Receptores de Sulfonilureas/metabolismo , Canales Catiónicos TRPM/metabolismo , Adulto , Anciano , Animales , Encéfalo/metabolismo , Contusión Encefálica/complicaciones , Progresión de la Enfermedad , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Hemorragias Intracraneales/etiología , Masculino , Persona de Mediana Edad , Ratas , Regulación hacia ArribaRESUMEN
Hemophagocytic Lymphohistiocytosis (HLH), is an uncommon, aggressive and life threatening syndrome of excessive immune activation. We report an unusual case of HLH, in a 34 year old male, who was admitted with Subarachnoid hemorrhage and cerebellar contusion in a Neurosurgical Intensive care unit, whose trigger is not clear.
Asunto(s)
Linfohistiocitosis Hemofagocítica/diagnóstico , Adulto , Anticonvulsivantes/efectos adversos , Contusión Encefálica/complicaciones , Humanos , Linfohistiocitosis Hemofagocítica/complicaciones , Masculino , Infecciones por Parvoviridae/complicaciones , Fenitoína/efectos adversos , Hemorragia Subaracnoidea/complicacionesRESUMEN
Direct traumatic optic neuropathy (TON) is a devastating condition and clinical challenge. Its adequate treatment remains controversial. Hyperbaric oxygen (HBO2) therapy has been proposed as an adjunctive treatment for eye disease but has rarely been used in optic neuropathy. The patient was a 57-year-old woman who had direct TON and brain injury after contusion injury. After receiving delayed HBO2 therapy her visual acuity got better - from hand motion to 6/60 - along with improvement of visual field and color vision. She was treated at 2.5 atmospheres absolute for 100 minutes, five times a week, for a total of 61 sessions. Our case highlights that HBO2 may be beneficial as an alternative treatment for direct TON, particularly when combined with brain injury. Although this entity is promising, further randomized controlled trials will be needed to clarify the efficacy of HBO2 in the treatment of direct TON.
Asunto(s)
Contusión Encefálica/complicaciones , Oxigenoterapia Hiperbárica/métodos , Enfermedades del Nervio Óptico/terapia , Traumatismos del Nervio Óptico/complicaciones , Femenino , Humanos , Persona de Mediana Edad , Enfermedades del Nervio Óptico/etiología , Traumatismos del Nervio Óptico/diagnóstico por imagen , Resultado del TratamientoRESUMEN
OBJECTIVE: The goal of the Chronic Effects of Neurotrauma Consortium (CENC) study is to explore the effects of concussions among Service Members and Veterans. A factor model was fit to selected neuropsychological measures to identify potentially useful relationships between assessments collected on CENC-enrolled participants. METHOD: 492 post-9/11 participants with combat exposure were enrolled across four VA study sites. Participants completed assessments including concussion history, neurocognitive functioning, and self-report questionnaires. Exploratory factor analyses (EFA) using four different methods with varimax and promax rotations were used to analyse the cognitive variables. Final model selection was based on factor loadings towards simple structure. RESULTS: The scree plot suggested the number of factors to be extracted was between 4 and 5. EFA produced a 5-factor MINRES model with promax rotation that resulted in a factor loading with variables loading on only one factor with a predefined threshold (0.40). Variables loaded on five cognition domains: list learning, working memory/executive skills, cognitive control, fluency, and memory. CONCLUSION: These results provide reasonable evidence that data collected from the CENC neuropsychological battery can be reduced to five clinically useful factors. This will enable us to use the factors for further study of the impact of concussion on neurodegeneration.
Asunto(s)
Contusión Encefálica/complicaciones , Contusión Encefálica/psicología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Pruebas Neuropsicológicas , Adulto , Estudios de Cohortes , Análisis Factorial , Femenino , Humanos , Pruebas de Inteligencia , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Autoinforme , VeteranosRESUMEN
OBJECTIVES: We aimed to investigate the prevalence and pattern of cognitive dysfunction in patients with traumatic bifrontal contusions and their association with functional outcome. MATERIALS AND METHODS: We prospectively recruited patients with bifrontal contusions in a regional neurosurgical center in Hong Kong over a 2-year period. Functional outcome was assessed by modified Rankin Scale (mRS), and cognitive outcomes were assessed by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a comprehensive neuropsychological battery. RESULTS: We recruited 34 patients with traumatic bifrontal contusions over a 2-year period. Nine (26%) patients had craniotomy for evacuation of left or right frontal contusions. Functional outcome using mRS was significantly correlated with cognitive outcomes using MMSE or MoCA. The effect of cognitive outcome using MMSE or MoCA persisted after adjustments of age, sex, admission Glasgow Coma Scale, and surgery. In patients who completed the comprehensive neuropsychological assessments, cognitive impairment in at least one of the neuropsychological tests was noted in 73% of them. CONCLUSIONS: Cognitive dysfunction had a significant impact on functional outcome, and treatment strategy should be developed to minimize them.