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.

Prognostic value of corpus callosum injuries in severe head trauma.

BACKGROUND: This study was performed to investigate the relationship between corpus callosum (CC) injury and prognosis in traumatic axonal injury (TAI). METHOD: We retrospectively reviewed 264 patients with severe head trauma who underwent a conventional MR imaging in the first 60 days after injury. They were selected from a prospectively collected database of 1048 patients with severe head trauma admitted in our hospital. TAI lesions were defined as areas of increased signal intensity on T2 and FLAIR or areas of decreased signal on gradient-echo T2. We attempted to determine whether any MR imaging findings of TAI lesions at CC could be related to prognosis. Neurological impairment was assessed at 1 year after injury by means of GOS-E (good outcome being GOS-E 4/5 and bad outcome being GOS-E <4). We adjusted the multivariable analysis for the prognostic factors according to the IMPACT studies: the Core model (age, motor score at admission, and pupillary reactivity) and the Extended model (including CT information and second insults). RESULTS: We found 97 patients (37 %) with TAI at CC and 167 patients (63 %) without CC lesions at MR. A total of 62 % of the patients with CC lesions had poor outcome, whereas 38 % showed good prognosis. The presence of TAI lesions at the corpus callosum was associated with poor outcome 1 year after brain trauma (p < 0.001, OR 3.8, 95 % CI: 2.04-7.06). The volume of CC lesions measured on T2 and FLAIR sequences was negatively correlated with the GOS-E after adjustment for independent prognostic factors (p = 0.01, OR 2.23, 95 % CI:1.17-4.26). Also the presence of lesions at splenium was statistically related to worse prognosis (p = 0.002, OR 8.1, 95 % CI: 2.2-29.82). We did not find statistical significance in outcome between hemorrhagic and non-hemorrhagic CC lesions. CONCLUSIONS: The presence of CC is associated with a poor outcome. The total volume of the CC lesion is an independent prognostic factor for poor outcome in severe head trauma.

Coil embolization of ruptured frontopolar artery aneurysm: case report.

Distal anterior cerebral artery aneurysms are infrequent. The most common location is at the bifurcation of the pericallosal and callosomarginal arteries. Cerebral artery anomalies can sometimes, at least partially, explain aneurysm formation in less common locations in relation to hemodynamic stress caused on the vascular wall. We report a very rare case of subarachnoid hemorrhage due to a ruptured frontopolar artery aneurysm as a part of an anomalous anterior cerebral artery complex that was, for the first time, treated with endovascular coiling.

Acute perfusion changes after spontaneous SAH: a perfusion CT study.

BACKGROUND: Perfusion computed tomography (CT) is a rapid technique that allows the measurement of acute disturbances in local and global cerebral blood flow in patients suffering stroke and spontaneous subarachnoid haemorrhage (SAH). The purpose of this study was to establish the relationship between different measures of brain perfusion made on dynamic-contrast CT reconstructions performed as soon as SAH has been diagnosed and the severity of the bleeding determined by the clinical grade, the extent of the bleeding and the outcome of the patients. METHODS: After the diagnosis of SAH by conventional CT, a perfusion CT was performed before CT angiography. All imaging studies were performed on a six-slice spiral CT scanner. All images were analysed using perfusion software developed by Philips, which produces perfusion CT quantitative data based on temporal changes in signal intensity during the first pass of a bolus of an iodinated contrast agent. Measurements of mean transient time (MTT), time to peak (TTP), cerebral blood volume (CBV) and cerebral blood flow (CBF) in volumes of interest corresponding to territories perfused by the major cerebral arteries were performed. Different data regarding severity of the bleeding-such as level of consciousness, amount of bleeding in conventional CT-were collected. All poor-grade patients received a ventriculostomy catheter so that ICP recordings were obtained. Also, the occurrence of delayed cerebral ischaemia (DCI) was recorded. Outcome was assessed by the Glasgow Outcome Scale 6 months after the bleeding. For statistical analysis, non-parametric correlations between variables were performed. FINDINGS: Thirty-nine patients have been included in the study since January 2007. In SAH patients there are increasing perfusion abnormalities as the severity of the bleeding increases. The most affected perfusion parameters are TTP and MTT, as they significantly increase with the clinical severity of the bleeding and the total volume of bleeding (P < 0.01, Spearman's Rho). When average MTT time is increased over 5.9 s there is a 20-fold (95% CI = 2.1-182) risk of poor outcome. All patients presenting this MTT time suffered from DCI. This value has a positive predictive value of 100% for DCI and 90% for a poor outcome. CONCLUSIONS: SAH causes cerebral blood flow abnormalities even in the acute phase of the illness, consisting mainly of an increase in circulation times (TTP and MTT), which are correlated with the severity of the bleeding.

Primary melanoma of the cauda equina: Case report and review of the literature.

The authors report the case of an 82 year-old woman with a primary malignant melanoma of the cauda equina resembling lumbar schwannoma in the MRI study. Melanocytic neoplasms are very rare but they should be included in the differential diagnosis of lesions involving the spinal nerves. The treatment of choice for these lesions is complete resection followed by radiotherapy. The outcomes reported in the literature are variable and are associated with the age of presentation, histopathological findings, extent of surgical resection and absence of metastatic lesions.

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.

Risk Factors, Radiological and Clinical Outcomes in Subclinical and Clinical Pituitary Apoplexy.

BACKGROUND: Pituitary apoplexy (PA) can be symptomatic, namely acute apoplexy (APA), or asymptomatic or subclinical (SPA). OBJECTIVE: To describe the clinical characteristics and evolution of the patients with APA compared to SPA Patients and methods: Retrospective, longitudinal database analysis. RESULTS: We identified 58 patients with PA, and 37 accomplished the inclusion criteria (17 men, median age 47.7 years). A total of 29 (78.4%) had APA (17 underwent surgery, and 12 were conservatively managed), and 8 (21.6%) had SPA. The presence of non-functioning pituitary adenoma (NFPA) odds ratio (OR): 29.36 (95% confidence interval (CI): 1.86-462.36) and the largest size OR 1.10 (95% CI: 1.01-1.2) elevated the risk of having surgery. Hypopituitarism developed in 35.1% without significant differences between APA and SPA. In non-surgical patients, adenoma volume shrunk spontaneously at one year magnetic resonance imaging (MRI), without statistical differences between the conservatively treated and SPA group. CONCLUSIONS: APA is more frequent in larger NFPAs, and this subset of patients has a higher risk of surgery. Hypopituitarism is quite frequent even in patients with SPA, and, therefore, long-term follow-up is mandatory. In the non-surgical group, the pituitary tumour shrinkage is clinically relevant after one year of PA. Consequently, surgery indication in NFPA should be delayed and reassessed if patients remain asymptomatic.

Activity and Resistance of a Brain-Permeable Paradox Breaker BRAF Inhibitor in Melanoma Brain Metastasis.

The therapeutic benefit of approved BRAF and MEK inhibitors (BRAFi/MEKi) in patients with brain metastatic BRAF V600E/K-mutated melanoma is limited and transient. Resistance largely occurs through the restoration of MAPK signaling via paradoxical BRAF activation, highlighting the need for more effective therapeutic options. Aiming to address this clinical challenge, we characterized the activity of a potent, brain-penetrant paradox breaker BRAFi (compound 1a, C1a) as first-line therapy and following progression upon treatment with approved BRAFi and BRAFi/MEKi therapies. C1a activity was evaluated in vitro and in vivo in melanoma cell lines and patient-derived models of BRAF V600E-mutant melanoma brain metastases following relapse after treatment with BRAFi/MEKi. C1a showed superior efficacy compared with approved BRAFi in both subcutaneous and brain metastatic models. Importantly, C1a manifested potent and prolonged antitumor activity even in models that progressed on BRAFi/MEKi treatment. Analysis of mechanisms of resistance to C1a revealed MAPK reactivation under drug treatment as the predominant resistance-driving event in both subcutaneous and intracranial tumors. Specifically, BRAF kinase domain duplication was identified as a frequently occurring driver of resistance to C1a. Combination therapies of C1a and anti-PD-1 antibody proved to significantly reduce disease recurrence. Collectively, these preclinical studies validate the outstanding antitumor activity of C1a in brain metastasis, support clinical investigation of this agent in patients pretreated with BRAFi/MEKi, unveil genetic drivers of tumor escape from C1a, and identify a combinatorial treatment that achieves long-lasting responses. SIGNIFICANCE: A brain-penetrant BRAF inhibitor demonstrates potent activity in brain metastatic melanoma, even upon relapse following standard BRAF inhibitor therapy, supporting further investigation into its clinical utility.

A Novel EGFRvIII T-Cell Bispecific Antibody for the Treatment of Glioblastoma.

T-cell bispecific antibodies (TCB) are engineered molecules that bind both the T-cell receptor and tumor-specific antigens. Epidermal growth factor receptor variant III (EGFRvIII) mutation is a common event in glioblastoma (GBM) and is characterized by the deletion of exons 2-7, resulting in a constitutively active receptor that promotes cell proliferation, angiogenesis, and invasion. EGFRvIII is expressed on the surface of tumor cells and is not expressed in normal tissues, making EGFRvIII an ideal neoantigen target for TCBs. We designed and developed a novel 2+1 EGFRvIII-TCB with optimal pharmacologic characteristics and potent antitumor activity. EGFRvIII-TCB showed specificity for EGFRvIII and promoted tumor cell killing as well as T-cell activation and cytokine secretion only in patient-derived models expressing EGFRvIII. Moreover, EGFRvIII-TCB promoted T-cell recruitment into intracranial tumors. EGFRvIII-TCB induced tumor regression in GBM animal models, including humanized orthotopic GBM patient-derived xenograft models. Our results warrant the clinical testing of EGFRvIII-TCB for the treatment of EGFRvIII-expressing GBMs.

Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment.

Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from treatment with immune checkpoint inhibitors (ICI) and the degree and phenotype of the immune cell infiltration has been used to predict response to ICI. However, the anatomical location of brain lesions limits access to tumor material to characterize the immune phenotype. Here, we characterize immune cells present in brain lesions and matched cerebrospinal fluid (CSF) using single-cell RNA sequencing combined with T cell receptor genotyping. Tumor immune infiltration and specifically CD8+ T cell infiltration can be discerned through the analysis of the CSF. Consistently, identical T cell receptor clonotypes are detected in brain lesions and CSF, confirming cell exchange between these compartments. The analysis of immune cells of the CSF can provide a non-invasive alternative to predict the response to ICI, as well as identify the T cell receptor clonotypes present in brain metastasis.

Spontaneous hemorrhage into a lumbar synovial cyst.

Lumbar synovial cysts frequently present with back pain, chronic radiculopathy and/or progressive symptoms of spinal canal compromise. These cysts generally appear in the context of degenerative lumbar spinal disease. Few cases of spontaneous hemorrhage into synovial cysts have been reported in the literature.

Ruptured dissecting cerebral aneurysms in young people: report of three cases.

Intracranial arterial aneurysms in the pediatric population are rare. Among these, dissecting aneurysms are the most frequent, followed by saccular, infectious, and posttraumatic. It is widely known that aneurysmal rupture is uncommon in the first two decades of life. Spontaneous dissecting aneurysms (SDAs) of the middle cerebral artery (MCA) affecting young individuals most frequently present as occlusive syndrome with ischemia, although bleeding and subarachnoid hemorrhage can also occur. Between March 2006 and January 2008, three young patients (20 months, 8 and 20 years old) were surgically treated for MCA SDA in the Neurosurgical Department of "12 de Octubre" Hospital of Madrid. These patients showed hemorrhage as primary radiological finding, and all of them underwent surgical operation. Aneurysms were always treated by trapping, with aneurysmectomy in one case, but no distal extra-intracranial (EC-IC) bypass was performed. In two cases, the histological examination of the aneurysm's wall evidenced signs of subintimal dissection with widespread disruption of the internal elastic lamina and media with neointima formation and intramural hemorrhage. Although bleeding is an uncommon presenting sign of SDAs, they should be suspected in young people showing hemorrhage at CT scan. Early surgical treatment and, if possible, preoperative neuroimaging evaluation of intracranial vessels should be performed to reduce the mortality in these patients despite a higher postoperative morbidity. From a technical point of view, surgical trapping of the aneurysm seems to be a reasonable treatment strategy especially in an emergency basis. However, whenever possible, an EC-IC bypass could help diminish the ischemic morbidity associated with these aneurysms.

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.

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.

A rare case of an intramedullary metastasis of a myxopapillary ependymoma.

BACKGROUND: Myxopapillary ependimoma (MPE) is a benign slow-growing tumor, and it has been designated histologically as a Grade I neoplasm according to the 2016 World Health Organization classification. Despite the benign character, dissemination and metastasis have occasionally been reported. The retrograde dissemination to other levels of the neuraxis is extremely rare, being more frequent to the intracranial compartment. CASE DESCRIPTION: We hereby present a case of medullary metastasis of cauda equina MPE, with a history of having undergone a subtotal resection and postoperative adjuvant radiotherapy. The patient presents complaints of night dorsal pain attributable to intradural metastasis twenty-one years after the first surgical intervention. CONCLUSION: The case reported highlights the importance of long follow-up in patients with MPE, since the possibility of secondary seeding to distant craniospinal sites or local spinal sites after surgery, and radiotherapy should be considered in metastatic disease.

Kir6.2, the Pore-Forming Subunit of ATP-Sensitive K+ Channels, Is Overexpressed in Human Posttraumatic Brain Contusions.

Brain contusions (BCs) are one of the most frequent lesions in patients with moderate and severe traumatic brain injury (TBI). BCs increase their volume due to peri-lesional edema formation and/or hemorrhagic transformation. This may have deleterious consequences and its mechanisms are still poorly understood. We previously identified de novo upregulation sulfonylurea receptor (SUR) 1, the regulatory subunit of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and other channels, in human BCs. Our aim here was to study the expression of the pore-forming subunit of KATP, Kir6.2, in human BCs, and identify its localization in different cell types. Protein levels of Kir6.2 were detected by western blot (WB) from 33 contusion specimens obtained from 32 TBI patients aged 14-74 years. The evaluation of Kir6.2 expression in different cell types was performed by immunofluorescence in 29 contusion samples obtained from 28 patients with a median age of 42 years. Control samples were obtained from limited brain resections performed to access extra-axial skull base tumors or intraventricular lesions. Contusion specimens showed an increase of Kir6.2 expression in comparison with controls. Regarding cellular location of Kir6.2, there was no expression of this channel subunit in blood vessels, either in control samples or in contusions. The expression of Kir6.2 in neurons and microglia was also analyzed, but the observed differences were not statistically significant. However, a significant increase of Kir6.2 was found in glial fibrillary acidic protein (GFAP)-positive cells in contusion specimens. Our data suggest that further research on SUR1-regulated ionic channels may lead to a better understanding of key mechanisms involved in the pathogenesis of BCs, and may identify novel targeted therapeutic strategies.

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.

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.

Molecular Diagnosis of Diffuse Gliomas through Sequencing of Cell-Free Circulating Tumor DNA from Cerebrospinal Fluid.

Purpose: Diffuse gliomas are the most common primary tumor of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumor specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumor DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies.Experimental Design: We performed an analysis of IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B gene mutations in two tumor cohorts from The Cancer Genome Atlas (TCGA) including 648 diffuse gliomas. We also performed targeted exome sequencing and droplet digital PCR (ddPCR) analysis of these seven genes in 20 clinical tumor specimens and CSF from glioma patients and performed a histopathologic characterization of the tumors.Results: Analysis of the mutational status of the IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B genes allowed the classification of 79% of the 648 diffuse gliomas analyzed, into IDH-wild-type glioblastoma, IDH-mutant glioblastoma/diffuse astrocytoma and oligodendroglioma, each subtype exhibiting diverse median overall survival (1.1, 6.7, and 11.2 years, respectively). We developed a sequencing platform to simultaneously and rapidly genotype these seven genes in CSF ctDNA allowing the subclassification of diffuse gliomas.Conclusions: The genomic analysis of IDH1, IDH2, TP53, ATRX, TERT, H3F3A, and HIST1H3B gene mutations in CSF ctDNA facilitates the diagnosis of diffuse gliomas in a timely manner to support the surgical and clinical management of these patients. Clin Cancer Res; 24(12); 2812-9. ©2018 AACR.

[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.