Serum assessment of traumatic axonal injury: the correlation of GFAP, t-Tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility.

OBJECTIVE: Diagnosis of traumatic axonal injury (TAI) is challenging because of its underestimation by conventional MRI and the technical requirements associated with the processing of diffusion tensor imaging (DTI). Serum biomarkers seem to be able to identify patients with abnormal CT scanning findings, but their potential role to assess TAI has seldomly been explored. METHODS: Patients with all severities of traumatic brain injury (TBI) were prospectively included in this study between 2016 and 2021. They underwent blood extraction within 24 hours after injury and imaging assessment, including DTI. Serum concentrations of glial fibrillary acidic protein, total microtubule-associated protein (t-Tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured using an ultrasensitive Simoa multiplex assay panel, a digital form of enzyme-linked immunosorbent assay. The Glasgow Outcome Scale-Extended score was determined at 6 months after TBI. The relationships between biomarker concentrations, volumetric analysis of corpus callosum (CC) lesions, and fractional anisotropy (FA) were analyzed by nonparametric tests. The prognostic utility of the biomarker was determined by calculating the C-statistic and an ordinal regression analysis. RESULTS: A total of 87 patients were included. Concentrations of all biomarkers were significantly higher for patients compared with controls. Although the concentration of the biomarkers was affected by the presence of mass lesions, FA of the CC was an independent factor influencing levels of UCH-L1 and NfL, which positioned these two biomarkers as better surrogates of TAI. Biomarkers also performed well in determining patients who would have had unfavorable outcome. NfL and the FA of the CC are independent complementary factors related to outcome. CONCLUSIONS: UCH-L1 and NfL seem to be the biomarkers more specific to detect TAI. The concentration of NfL combined with the FA of the CC might help predict long-term outcome.

Mechanical Thrombectomy for Acute Stroke in a 2-Month-Old Patient and Review of the Literature in Infancy.

Mechanical thrombectomy (MT) in pediatric stroke is supported by studies in adults, but there is controversy regarding younger patients. The main growth of intracranial vessels occurs up to 2 years when there can be more difficulties in MT.Description of the MT performed in a 2-month-old patient-the youngest infant published to date. We also review the literature on MT for stroke in infants.A 2-month-old patient presented with an awakening stroke secondary to an occlusion of the M1 segment of the left middle cerebral artery. A successful MT was performed with an aspiration device without clinically significant complications. An etiological study was completed, and neuroimaging showed focal cerebral arteriopathy. The 3-month outcome was excellent: the pediatric modified Rankin score was 0.Including this case, MT for acute stroke has been reported in only 10 infants. MT was successful in 90%, mostly using adult conventional stent retrievers. There were complications only in patients with mechanical circulatory support (MCS) devices; three patients died due to hemorrhagic transformation after MT and one patient died due to recurrent ischemic stroke.MT seems effective and safe in infants similarly to other pediatric ages. In children under 2 years of age, the presence of comorbidities requiring MCS devices is the main factor underlying poor prognosis.

Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?

OBJECTIVE: A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model. METHODS: The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients. RESULTS: Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, characterization of TAI lesions in the CC, and the presence of thalamic/basal ganglia lesions were independent prognostic factors. The performance of the proposed model was higher than that of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) model in the validation cohort. CONCLUSIONS: Very limited colocalization of hyperintensities (none for microbleeds) with FA values was discovered. DTI and conventional MRI provide complementary prognostic information, and their combination can improve the performance of traditional prognostic models.

Phase II Trial of Palbociclib in Recurrent Retinoblastoma-Positive Anaplastic Oligodendroglioma: A Study from the Spanish Group for Research in Neuro-Oncology (GEINO).

BACKGROUND: The cell cycle checkpoint G1/S, dependent on cyclin-dependent kinase (CDK) 4 amplification/overexpression and retinoblastoma phosphorylation, is altered in most anaplastic oligodendrogliomas (AOs). OBJECTIVE: We aimed to evaluate the efficacy of palbociclib, an oral inhibitor of CDK4/6 with proven efficacy in breast cancer, in patients with AO. The primary endpoint was progression-free survival at 6 months. PATIENTS AND METHODS: We conducted a multicenter, open-label, phase II trial evaluating the efficacy and safety of palbociclib in patients with AO who progressed on radiotherapy and chemotherapy with histologically and molecularly confirmed grade 3 oligodendroglioma and conserved retinoblastoma protein (pRb) expression by immunohistochemistry. Patients were treated with palbociclib (125 mg/day) for 3/1 weeks on/off. RESULTS: Overall, 34 patients were enrolled across 10 hospitals in the Spanish Group of Neuro-Oncology (GEINO) study. The study was stopped early owing to the lack of efficacy, with 74% of evaluable patients progressing within 6 months, which was insufficient to consider palbociclib as an active drug in this population. Within the median follow-up of 12 months, the median progression-free survival was 2.8 months [95% confidence interval (CI) 2.6-3.1] and the median overall survival was 32.1 months (95% CI 5.1-59.2). There were no partial or complete responses; only 13 patients (38%) achieved stable disease as the best response. Palbociclib was well tolerated, with neutropenia (grade 3 or higher: 58.8%) and thrombocytopenia (grade 3 or higher: 14.7%) as the most common adverse events (AEs). Both AEs had no significant impact. CONCLUSION: Despite the good tolerance, palbociclib monotherapy did not show favorable efficacy against recurrent AO. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier NCT0253032 (retrospectively registered on 21 August 2015).

PREMIO SIXTO OBRADOR SENEC 2019: El uso de la secuencia Tensor de difusión como herramienta pronóstica en los pacientes con traumatismo craneoencefálico grave y moderado. Parte II: Análisis longitudinal de las características del Tensor de difusión y su relación con la evolución de los pacientes / SIXTO OBRADOR SENEC PRIZE 2019: Utility of diffusion tensor imaging as a prognostic tool in moderate to severe traumatic brain injury. Part II: Longitudinal analysis of DTI metrics and its association with patient's outcome

ANTECEDENTES Y OBJETIVOS: La lesión axonal traumática es considerada la principal causa de las alteraciones cognitivas y neuropsicológica de los pacientes tras traumatismo craneoencefálico (TCE). Además, existen algunas evidencias sobre la evolución dinámica de la lesión axonal traumática. La secuencia de RM Tensor de difusión (DTI, diffusion tensor imaging) se considera una técnica útil para la caracterización de la lesión axonal traumática, pero son escasos los estudios que hayan evaluado los cambios longitudinales de las características del DTI y su relación con la evolución de los pacientes. MATERIALES Y MÉTODOS: Ciento dieciocho pacientes con TCE moderado y grave fueron estudiados mediante RM-DTI en la fase subaguda precoz (<60 días) y otros estudios sucesivos a los 6 y/o 12 meses tras TCE. Se ha medido la anisotropía fraccionada, difusión axial y radial en las 3 porciones del cuerpo calloso (rodilla, cuerpo y esplenio) y se han comparado con los valores de un grupo control. Además, se ha determinado la situación clínica de los pacientes mediante la Glasgow Outcome Scale Extended al alta hospitalaria, 6 y 12 meses tras TCE. Para el análisis longitudinal de las características del DTI y su correlación con la evolución de los pacientes se han empleado pruebas no paramétricas y un análisis de regresión ordinal. RESULTADOS: A pesar de haber detectado cambios dinámicos en las características del DTI en las 3 porciones del cuerpo calloso, los pacientes continuaron mostrando valores de anisotropía fraccionada y difusión axial significativamente inferiores y valores de difusión radial mayores en comparación con los controles al final del periodo de estudio. También hemos encontrado diferencias en el patrón de cambio del DTI entre subgrupos de pacientes que presentaron evolución favorable. CONCLUSIONES: El perfil temporal del cambio en las características del DTI parece proporcionar información importante sobre la recuperación clínica de los pacientes tras TCE

BACKGROUND AND OBJECTIVES: Traumatic axonal injury is the main cause of the cognitive and neuropsychological situation of patients after head trauma (TBI). Additionally, there are some evidences about the dynamic evolution of traumatic axonal injury. Although the diffusion tensor MRI (DTI) sequence is considered a useful technique for modifying the extent of the traumatic axonal injury, few studies have evaluated the longitudinal changes in the characteristics of the DTI and its relation to evolution of patients. MATERIALS AND METHODS: We performed a prospective observational study in 118 patients with moderate to severe TBI. The study included clinical outcome assessment based on the Glasgow Outcome Scale Extended and serial DTI studies in the early subacute setting (< 60 days) and 6 and 12 months after injury. Fractional anisotropy, axial and radial diffusivities were measured in the 3 portions of corpus callosum (genu, body, splenium) at each time point and compared to normalized values from an age-matched control group. Longitudinal fractional anisotropy analysis and its correlation with patient improvement was also done by non-parametric testing and ordinal regression analysis. RESULTS: Although dynamic changes in DTI characteristics have been detected in the 3 portions of corpus callosum, patients continue to show lower fractional anisotropy and axial diffusivities values and higher radial diffusivities values compared to controls at the end of the period of study. We have also found differences in the pattern of DTI metrics change between subgroups of patients according with their favorable outcome CONCLUSIONS: The temporal profile of the change in DTI characteristics seems to provide important information about the clinical recovery of patients after TBI

Premio Sixto Obrador SENEC 2019: el uso de la secuencia tensor de difusión como herramienta pronóstica en los pacientes con traumatismo craneoencefálico grave y moderado. Parte I. Análisis de las características del tensor de difusión realizado durante la fase subaguda precoz / Sixto Obrador SENEC prize 2019: Utility of diffusion tensor imaging as a prognostic tool in moderate to severe traumatic brain injury. Part I. Analysis of DTI metrics performed during the early subacute stage

ANTECEDENTES Y OBJETIVOS: La lesión axonal traumática (LAT) contribuye significativamente a la mortalidad y morbilidad tras traumatismo craneoencefálico (TCE). Sin embargo, la caracterización de la LAT supone un reto diagnóstico para las técnicas de neuroimagen habitual. La secuencia de RM tensor de difusión (diffusion tensor imaging [DTI]) es capaz de detectar el grado de difusión de las moléculas de agua tisular y así inferir la afectación traumática de la sustancia blanca. El objetivo principal de este trabajo ha sido caracterizar la LAT a través de la secuencia DTI realizada en la fase subaguda precoz en nuestra serie de pacientes con TCE moderado y grave y evaluar si existe asociación con la evolución de los pacientes. MATERIALES Y MÉTODOS: Se ha realizado RM-DTI a 217 pacientes con TCE moderado y grave en la fase subaguda precoz tras el TCE (mediana = 19 días). El método de análisis elegido es por región de interés para calcular el valor medio de fractional anisotropy (FA) en 28 haces de sustancia blanca. Los valores obtenidos en los pacientes se han comparado con aquellos medidos en 58 sujetos sanos. RESULTADOS: Los resultados principales han sido que los pacientes, independientemente de la gravedad, demostraron valores de FA significativamente inferiores al grupo control en prácticamente todos los haces estudiados. Se detectó asociación entre el valor de FA y algunas variables clínicas de interés. Adicionalmente, los valores de FA de las tres porciones del cuerpo calloso, cíngulo y pedúnculos cerebrales se correlacionaron con la evolución del paciente evaluada a los 6 y 12 meses tras el TCE. CONCLUSIONES: El DTI es una herramienta útil para caracterizar la LAT y la detección de la reducción de FA en la fase subaguda precoz se relaciona con evolución desfavorable de los pacientes a medio y largo plazo

BACKGROUND AND OBJECTIVES: Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity after traumatic brain injury (TBI). Its identification is still a diagnostic challenge because of the limitations of conventional imaging techniques to characterized it. Diffusion tensor imaging (DTI) can indirectly identify areas of damaged white matter integrity by detecting water molecule diffusion alterations. Our main objective is to characterize the TAI using DTI at the early subacute stage in our series of moderate to severe TBI patients and to evaluate if there is a relationship between the information provided by the DTI and patient's outcome. MATERIALS AND METHODS: We have obtained DTI data from 217 patients with moderate to severe TBI acquired at a median of 19 days after TBI, and patient DTI metrics were compared with data obtained from 58 age-matched healthy controls. Region of interest method was applied to obtain mean fractional anisotropy (FA) value in 28 white matter fiber bundles susceptible to TAI. RESULTS: Our main results were that when we compared patients with controls, patients, regardless of TBI severity, showed significantly reduced mean FA in almost all region of interest measured. We found statistically significant correlation between FA metrics and some clinical characteristics. Additionally, the FA values of the three portions of Corpus callosum, Cingulum and cerebral peduncles measured at the early subacute stage were highly associated with outcome assessed at hospital discharge and at 6 and 12 months after TBI. CONCLUSIONS: We conclude that DTI is a useful tool to characterize TAI and the detection of FA reduction in the subacute stage after TBI is associated with long-term unfavorable outcome

SIXTO OBRADOR SENEC PRIZE 2019: Utility of diffusion tensor imaging as a prognostic tool in moderate to severe traumatic brain injury. Part II: Longitudinal analysis of DTI metrics and its association with patient's outcome. / PREMIO SIXTO OBRADOR SENEC 2019: El uso de la secuencia Tensor de difusión como herramienta pronóstica en los pacientes con traumatismo craneoencefálico grave y moderado. Parte II: Análisis longitudinal de las características del Tensor de difusión y su relación con la evolución de los pacientes.

BACKGROUND AND OBJECTIVES: Traumatic axonal injury is the main cause of the cognitive and neuropsychological situation of patients after head trauma (TBI). Additionally, there are some evidences about the dynamic evolution of traumatic axonal injury. Although the diffusion tensor MRI (DTI) sequence is considered a useful technique for modifying the extent of the traumatic axonal injury, few studies have evaluated the longitudinal changes in the characteristics of the DTI and its relation to evolution of patients. MATERIALS AND METHODS: We performed a prospective observational study in 118 patients with moderate to severe TBI. The study included clinical outcome assessment based on the Glasgow Outcome Scale Extended and serial DTI studies in the early subacute setting (<60 days) and 6 and 12 months after injury. Fractional anisotropy, axial and radial diffusivities were measured in the 3 portions of corpus callosum (genu, body, splenium) at each time point and compared to normalized values from an age-matched control group. Longitudinal fractional anisotropy analysis and its correlation with patient improvement was also done by non-parametric testing and ordinal regression analysis. RESULTS: Although dynamic changes in DTI characteristics have been detected in the 3 portions of corpus callosum, patients continue to show lower fractional anisotropy and axial diffusivities values and higher radial diffusivities values compared to controls at the end of the period of study. We have also found differences in the pattern of DTI metrics change between subgroups of patients according with their favorable outcome CONCLUSIONS: The temporal profile of the change in DTI characteristics seems to provide important information about the clinical recovery of patients after TBI.

Sixto Obrador SENEC prize 2019: Utility of diffusion tensor imaging as a prognostic tool in moderate to severe traumatic brain injury. Part I. Analysis of DTI metrics performed during the early subacute stage. / Premio Sixto Obrador SENEC 2019: el uso de la secuencia tensor de difusión como herramienta pronóstica en los pacientes con traumatismo craneoencefálico grave y moderado. Parte I. Análisis de las características del tensor de difusión realizado durante la fase subaguda precoz.

BACKGROUND AND OBJECTIVES: Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity after traumatic brain injury (TBI). Its identification is still a diagnostic challenge because of the limitations of conventional imaging techniques to characterized it. Diffusion tensor imaging (DTI) can indirectly identify areas of damaged white matter integrity by detecting water molecule diffusion alterations. Our main objective is to characterize the TAI using DTI at the early subacute stage in our series of moderate to severe TBI patients and to evaluate if there is a relationship between the information provided by the DTI and patient's outcome. MATERIALS AND METHODS: We have obtained DTI data from 217 patients with moderate to severe TBI acquired at a median of 19 days after TBI, and patient DTI metrics were compared with data obtained from 58 age-matched healthy controls. Region of interest method was applied to obtain mean fractional anisotropy (FA) value in 28 white matter fiber bundles susceptible to TAI. RESULTS: Our main results were that when we compared patients with controls, patients, regardless of TBI severity, showed significantly reduced mean FA in almost all region of interest measured. We found statistically significant correlation between FA metrics and some clinical characteristics. Additionally, the FA values of the three portions of Corpus callosum, Cingulum and cerebral peduncles measured at the early subacute stage were highly associated with outcome assessed at hospital discharge and at 6 and 12 months after TBI. CONCLUSIONS: We conclude that DTI is a useful tool to characterize TAI and the detection of FA reduction in the subacute stage after TBI is associated with long-term unfavorable outcome.

Endoscopic Transnasal Trans-Sphenoidal Approach for Pituitary Adenomas: A Comparison to the Microscopic Approach Cohort by Propensity Score Analysis.

BACKGROUND: Despite some evidence for the adoption of endoscopic transnasal trans-sphenoidal surgery (ETSS) for pituitary adenomas, the advantages of this technique over the traditional approach have not been robustly confirmed. OBJECTIVE: To compare ETSS with the microscopic sublabial trans-septal trans-sphenoidal surgery (MTSS) for pituitary adenomas. METHODS: We retrospectively reviewed 2 cohorts of ETSS and MTSS performed at our institution from 1995 to 2017. Patient characteristics, surgical data, and outcomes were recorded prospectively. We performed a univariate and multivariable analysis to determine the best surgical approach. To improve the quality of the results, we matched the distribution of patient characteristics between groups by propensity score (PS) method. RESULTS: A total of 187 procedures (90 MTSS, 97 ETSS) were reviewed. We found better results in the ETSS group in terms of gross total resection (P = .002) and hormone-excess secretion control (P = .014). There was also a lower incidence of cerebrospinal fluid leakage (P = .039), transitory diabetes insipidus (P = .028), and postoperative hypopituitarism (P = .045), as well as a shorter hospital length of stay (P < .001). After PS matching, we confirmed by multivariable logistic regression analysis an increased odds ratio of gross total resection for the ETSS (3.910; 95% CI 1.720-8.889; P = .001). CONCLUSION: By PS method, our results suggest that the ETSS provides advantages over the traditional MTSS approach for tumor resection. Better control of secreting tumors and a lower rate of most complications also support the selection of the ETSS approach for the treatment of pituitary adenomas.

Longitudinal Analysis of Corpus Callosum Diffusion Tensor Imaging Metrics and Its Association with Neurological Outcome.

Traumatic axonal injury (TAI) is the main cause of cognitive and psychological disfunction after a traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique for indirect assessment of white matter (WM) integrity after a TBI. Scattered WM alterations and its relationship with patient severity have been discovered in normal appearing conventional magnetic resonance imaging (MRI) studies based on DTI sequences. However, there is a lack of large sample studies on the longitudinal changes of DTI metrics to be used to determine the temporal profile after head injury and its association with patient outcome. We performed a prospective observational study in 118 moderate-to-severe TBI patients. The study included clinical outcome assessment based on the Glasgow Outcome Scale Extended (GOSE) and serial DTI studies in the early subacute setting (< 60 days) and 6 and 12 months after injury. Fractional anisotropy (FA) and axial and radial diffusivities (AD and RD, respectively) were measured in the three portions of corpus callosum (genu, body, splenium) at each time-point and compared with normalized values from an age-matched control group. Longitudinal FA analysis and its correlation with patient improvement also was done by non-parametric testing and ordinal regression analysis. Our main results indicated that between all the time-points, dynamic changes in DTI metrics in all three portions of corpus callosum were detected, but TBI patients continued to show significantly lower FA and AD values and higher RD values compared with controls. We also have discovered differences in the change of DTI metrics among different time-points in patient subgroups according with their outcome improvement. In conclusion, even without normalization of DTI metrics in the long-term, knowledge of the temporal profile of change in DTI metrics can provide important information about patients' clinical recovery after TBI.

Perfusion MRI grading diffuse gliomas: Impact of permeability parameters on molecular biomarkers and survival / Utilidad de la RM perfusión en la gradación de los gliomas difusos: relación entre parámetros de permeabilidad, marcadores moleculares y supervivencia

Background and purpose: Our objectives were: (1) compare dynamic susceptibility-weighted (DSC) and dynamic contrast-enhanced (DCE) permeability parameters, (2) evaluate diagnostic accuracy of DSC and DCE discriminating high- and low-grade tumors, (3) analyze relationship of permeability parameters with overall (OS) and progression-free survival (PFS) and (4) assess differences in high-grade tumors classified according to molecular biomarkers. Materials and methods: 49 patients with histologically proved diffuse gliomas underwent DSC and DCE imaging. Parametric maps of cerebral blood volume (CBV), CBV-leakage corrected, volume transfer coefficient (Ktrans), fractional volume of the extravascular extracellular space (EES) (Ve), fractional blood plasma volume (Vp) and rate constant between EES and blood plasma (Kep) were calculated. High-grade gliomas were also classified according to isocitrate dehydrogenase (IDH), alpha-thalassemia/mental retardation syndrome X-linked (ATRX) and O6-methylguanine-dna-methyltransferase promoter methylation (MGMT) status. Results: There is correlation between parameters leakage, Ktrans and Vp. ROC curve analysis showed significance in both Ktrans and Ve for glioma grading. Threshold value of 0.075 for Ve generated the best combination of sensitivity (80%) and specificity (75%) in tumor gradation. Leakage was the only permeability parameter related to OS (P=0.006) and PFS (0.012); with prolonged survival for leakage values lower than 1.2. IDH-mutated high-grade tumors showed lower leakage and Ktrans values. High-grade tumors with loss of ATRX presented lower leakage and Vp values. Conclusions: Both DSC and DCE permeability parameters serve as non-invasive method for glioma grading. Leakage was the unique permeability parameter related to survival and the best discriminating high-grade gliomas classified according to IDH and ATRX status

Introducción y objetivos: 1) Evaluar la utilidad de los parámetros de permeabilidad para clasificar gliomas de alto y bajo grado; 2) Analizar diferencias de permeabilidad de glioblastomas clasificados según marcadores moleculares; 3) Analizar la relación de la permeabilidad con la supervivencia global (SG) y libre de progresión (SLP), y 4) Comparar parámetros de perfusión T1 y T2*. Material y métodos: Cuarenta y nueve pacientes con gliomas difusos confirmados histológicamente fueron estudiados con perfusión T1 y T2*. Calculamos los mapas paramétricos del volumen sanguíneo cerebral (CBV), CBV-leakage corregido, constante de permeabilidad (Ktrans), fracción de volumen vascular (Vp), fracción de volumen del espacio intersticial (Ve) y coeficiente de extracción (Kep). El análisis histológico se basó en criterios OMS 2007 y los glioblastomas se clasificaron según mutación de genes isocitrato deshidrogenasa (IDH), Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) y metilguanidina-ADN metiltransferasa (MGMT). Resultados: Incluimos 28 varones y 21 mujeres (16-78 años). Los gliomas se clasificaron en 41 tumores de alto grado y 8 de bajo grado. Leakage se correlacionó con SG y SLP; y mostró correlación lineal con Ktrans y Vp. Los gliomas de alto y de bajo grado mostraron diferencias en los valores de leakage, Ktrans, Vp y Ve. Leakage fue el parámetro que mejor discriminó los glioblastomas clasificados según mutación IDH y ATRX. Conclusión: La perfusión T1 y T2* sirven para clasificar a los gliomas difusos en función del grado tumoral. Leakage se relaciona con la SG y SLP y es el parámetro que mejor discrimina glioblastomas clasificados en función de IDH y ATRX

Perfusion MRI grading diffuse gliomas: Impact of permeability parameters on molecular biomarkers and survival.

BACKGROUND AND PURPOSE: Our objectives were: (1) compare dynamic susceptibility-weighted (DSC) and dynamic contrast-enhanced (DCE) permeability parameters, (2) evaluate diagnostic accuracy of DSC and DCE discriminating high- and low-grade tumors, (3) analyze relationship of permeability parameters with overall (OS) and progression-free survival (PFS) and (4) assess differences in high-grade tumors classified according to molecular biomarkers. MATERIALS AND METHODS: 49 patients with histologically proved diffuse gliomas underwent DSC and DCE imaging. Parametric maps of cerebral blood volume (CBV), CBV-leakage corrected, volume transfer coefficient (Ktrans), fractional volume of the extravascular extracellular space (EES) (Ve), fractional blood plasma volume (Vp) and rate constant between EES and blood plasma (Kep) were calculated. High-grade gliomas were also classified according to isocitrate dehydrogenase (IDH), alpha-thalassemia/mental retardation syndrome X-linked (ATRX) and O6-methylguanine-dna-methyltransferase promoter methylation (MGMT) status. RESULTS: There is correlation between parameters leakage, Ktrans and Vp. ROC curve analysis showed significance in both Ktrans and Ve for glioma grading. Threshold value of 0.075 for Ve generated the best combination of sensitivity (80%) and specificity (75%) in tumor gradation. Leakage was the only permeability parameter related to OS (P=0.006) and PFS (0.012); with prolonged survival for leakage values lower than 1.2. IDH-mutated high-grade tumors showed lower leakage and Ktrans values. High-grade tumors with loss of ATRX presented lower leakage and Vp values. CONCLUSIONS: Both DSC and DCE permeability parameters serve as non-invasive method for glioma grading. Leakage was the unique permeability parameter related to survival and the best discriminating high-grade gliomas classified according to IDH and ATRX status.

The added prognostic value of magnetic resonance imaging in traumatic brain injury: The importance of traumatic axonal injury when performing ordinal logistic regression.

BACKGROUND AND PURPOSE: This study was performed to investigate the prognostic value of traumatic axonal injury (TAI) in severe head trauma. METHODS: We attempted to determine whether any MR imaging findings of TAI could be related to prognosis in 264 patients with severe head trauma. We performed an ordinal logistic regression, adjusted for the prognostic factors according to the IMPACT studies, adding each MR feature related to prognosis one at a time. A new prognostic model was described by adding these MR features to the classic prognostic factors. The model was externally validated in a prospective series. Harrel's c-statistic and ordinal c-index (ORC) were calculated to measure its predictive accuracy. RESULTS: We found 178 patients with TAI lesions. Lesions in the basal ganglia/thalamus, corpus callosum (CC) and brain stem were associated with poor outcome (P < 0.01). The highest OR was for TAI lesions in the splenium (OR: 2.6) and brain stem dorsal lesions (OR: 3.1). We only found significant differences in outcome between haemorrhagic and non-haemorrhagic TAI lesions in the subgroup of patients with white matter and basal ganglia/thalamus lesions (P = 0.01). We obtained a superior discriminatory capacity by adding these MR findings to the previous prognostic model (Harrel's c-statistic 0.72 and ORC 0.7) in a prospective series of 93 patients. CONCLUSIONS: The prognostic model including MR findings maintained a superior discriminatory capacity than that obtained for the model with the classic prognostic factors alone.

Tumor cell vanishing with radiological changes suggesting progression in IDH-mutated diffuse astrocytoma treated only with surgery.

The radiological diagnosis of glioma progression is still challenging. A 33-year-old woman diagnosed with a frontal tumor underwent awake craniotomy with total tumor resection. The diagnosis was IDH-mutated diffuse astrocytoma, WHO grade II. The patient did not receive additional radiotherapy or chemotherapy. Periodic MRI scans showed a T2/FLAIR nodular enlargement which appeared de novo and grew slowly and gradually until 4 years post surgery. The patient underwent a second craniotomy to completely resect the T2/FLAIR hyperintensity. In the histological and molecular study of the second resection, no tumor cells were identified. We could hypothesize that the reactive changes favored by surgery could explain the ongoing radiologic findings.
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What Can Be Learned from Diffusion Tensor Imaging from a Large Traumatic Brain Injury Cohort?: White Matter Integrity and Its Relationship with Outcome.

Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity after traumatic brain injury (TBI), but its identification is still a diagnostic challenge because of the limitations of conventional imaging techniques to characterized it. Diffusion tensor imaging (DTI) can indirectly identify areas of damaged white matter (WM) integrity by detecting water molecule diffusion alterations. Therefore, DTI may improve detection and description of TAI lesions after TBI. We have obtained DTI data from 217 patients with moderate to severe TBI acquired at a median of 19 days after TBI, and patient DTI metrics were compared with data obtained from 58 age-matched healthy controls. Region of interest (ROI) method was applied to obtain mean fractional anisotropy (FA) value in 28 WM fiber bundles susceptible to TAI. Our main results were that when we compared patients with controls, patients, regardless of TBI severity, showed significantly reduced mean FA in almost all ROI measured. We found statistically significant correlation between FA metrics and some demographic, clinical, and conventional imaging characteristics. Additionally, these FA metrics were highly associated with outcome assessed at hospital discharge and at 6 and 12 months after TBI. We conclude that FA reduction in the subacute stage after TBI assessed by DTI may be a useful prognostic factor for long-term unfavorable outcome.

Resonancia magnética en el traumatismo craneal grave: estudio comparativo de las diferentes secuencias de resonancia magnética convencional y su valor diagnóstico en la lesión axonal difusa / Magnetic resonance in traumatic brain injury: a comparative study of the different conventional magnetic resonance imaging sequences and their diagnostic value in diffuse axonal injury

Objetivo: El objetivo de este estudio es determinar qué secuencias de resonancia magnética (RM) convencional diagnostican de manera más sensible las lesiones asociadas a lesiones axonales difusas (LAD) en pacientes con TCE grave. Material y métodos: Se analizaron de manera retrospectiva los datos de 264 pacientes con TCE grave y RM realizada dentro de las primeras 8 semanas tras el TCE. Se recogieron todas las variables clínicas potencialmente relacionadas con el pronóstico de los enfermos, así como los datos dla tomografía computarizada inicial. A todos los enfermos se les practicó un estudio de RM convencional con secuencias spin-eco potenciadas en T1 y T2, secuencia FLAIR y eco de gradiente T2 (EGRT2*). Las diferentes LAD visualizadas fueron caracterizadas según su localización y clasificadas siguiendo las escalas de Gentry y Firsching en cada secuencia. Se calculó el grado de concordancia entre la clasificación obtenida en las diferentes secuencias y la obtenida de forma definitiva por el paciente, así como el área bajo la curva ROC de cada una de ellas con respecto al pronóstico final de los pacientes. Resultados: En las secuencias T2, FLAIR y EGRT2* se visualizan las LAD de manera adecuada en más del 80% de los casos. En FLAIR se visualizan mejor las LAD hemisféricas a nivel subcortical y el EGRT2* resalta las LAD hemorrágicas. En nuestra serie hemos visto que el grado de concordancia para diagnosticar LAD entre las secuencias T2, FLAIR y EGRT2* es alto (0,8). La secuencia T2 es la que tuvo un valor más alto en las curvas ROC tanto en la clasificación de Gentry (0,68; IC 95%: 0,61-0,76; p<0,001, Nagerlkerke-R2 0,26) como en la de Firsching (0,64; IC 95%: 0,57-0,72; p<0,001, Nagerlkerke-R2 0,19), seguida de la secuencia FLAIR y de la EGRT2*. Se observó, tras realizar un análisis multivariable, que las clasificaciones de Gentry y Firsching determinadas de forma independiente en cada secuencia se relacionaban con el pronóstico final de los enfermos al año del traumatismo (p<0,02). Conclusiones: Para el diagnóstico adecuado de LAD en el TCE grave recomendamos la realización de una RM convencional en fase subaguda que incluya al menos las secuencias T2, FLAIR y eco de gradiente en los diferentes planos de corte. Estos hallazgos aumentan el valor pronóstico de los modelos descritos en el TCE grave

Objective: To compare the identification capability of traumatic axonal injury (TAI) by different sequences on conventional magnetic resonance (MR) studies in traumatic brain injury (TBI) patients. Material and methods: We retropectevely analyzed 264 TBI patients to whom a MR had been performed in the first 60 days after trauma. All clinical variables related to prognosis were registered, as well as the data from the initial computed tomography. The MR imaging protocol consisted of a 3-plane localizer sequence T1-weighted and T2-weighted fast spin-echo, FLAIR and gradient-echo images (GRET2*). TAI lesions were classified according to Gentry and Firsching classifications. We calculated weighted kappa coefficients and the area under the ROC curve for each MR sequence. A multivariable analyses was performed to correlate MR findings in each sequence with the final outcome of the patients. Results: TAI lesions were adequately visualized on T2, FLAIR and GRET2* sequences in more than 80% of the studies. Subcortical TAI lesions were well on FLAIR and GRET2* sequences visualized hemorrhagic TAI lesions. We saw that these MR sequences had a high inter-rater agreement for TAI diagnosis (0.8). T2 sequence presented the highest value on ROC curve in Gentry (0.68, 95%CI: 0.61-0.76, p<0.001, Nagerlkerke-R2 0.26) and Firsching classifications (0.64, 95%CI 0.57-0.72, p<0.001, Nagerlkerke-R2 0.19), followed by FLAIR and GRET2* sequences. Both classifications determined by each of these sequences were associated with poor outcome after performing a multivariable analyses adjusted for prognostic factors (p<0.02). Conclusions: We recommend to perform conventional MR study in subacute phase including T2, FLAIR and GRET2* sequences for visualize TAI lesions. These MR findings added prognostic information in TBI patients

[Magnetic resonance in traumatic brain injury: A comparative study of the different conventional magnetic resonance imaging sequences and their diagnostic value in diffuse axonal injury]. / Resonancia magnética en el traumatismo craneal grave: estudio comparativo de las diferentes secuencias de resonancia magnética convencional y su valor diagnóstico en la lesión axonal difusa.

OBJECTIVE: To compare the identification capability of traumatic axonal injury (TAI) by different sequences on conventional magnetic resonance (MR) studies in traumatic brain injury (TBI) patients. MATERIAL AND METHODS: We retropectevely analyzed 264 TBI patients to whom a MR had been performed in the first 60 days after trauma. All clinical variables related to prognosis were registered, as well as the data from the initial computed tomography. The MR imaging protocol consisted of a 3-plane localizer sequence T1-weighted and T2-weighted fast spin-echo, FLAIR and gradient-echo images (GRET2*). TAI lesions were classified according to Gentry and Firsching classifications. We calculated weighted kappa coefficients and the area under the ROC curve for each MR sequence. A multivariable analyses was performed to correlate MR findings in each sequence with the final outcome of the patients. RESULTS: TAI lesions were adequately visualized on T2, FLAIR and GRET2* sequences in more than 80% of the studies. Subcortical TAI lesions were well on FLAIR and GRET2* sequences visualized hemorrhagic TAI lesions. We saw that these MR sequences had a high inter-rater agreement for TAI diagnosis (0.8). T2 sequence presented the highest value on ROC curve in Gentry (0.68, 95%CI: 0.61-0.76, p<0.001, Nagerlkerke-R2 0.26) and Firsching classifications (0.64, 95%CI 0.57-0.72, p<0.001, Nagerlkerke-R2 0.19), followed by FLAIR and GRET2* sequences. Both classifications determined by each of these sequences were associated with poor outcome after performing a multivariable analyses adjusted for prognostic factors (p<0.02). CONCLUSIONS: We recommend to perform conventional MR study in subacute phase including T2, FLAIR and GRET2* sequences for visualize TAI lesions. These MR findings added prognostic information in TBI patients.