Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas / Importancia pronóstica de las mutaciones del gen promotor de la transcriptasa inversa de la telomerasa en los meningiomas de alto grado

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were tthe only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Importancia pronóstica de las mutaciones del gen promotor de la transcriptasa inversa de la telomerasa en los meningiomas de alto grado / Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were the only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation.

BACKGROUND: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer. METHODS: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial next-generation sequencing panel in liquid biopsy. RESULTS: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR. CONCLUSIONS: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.

Reliability and accuracy of individual Alberta Stroke Program Early CT Score regions using a medical and a smartphone reading system in a telestroke network.

INTRODUCTION: The aim of this study was to assess individual regions of the Alberta Stroke Program Early CT Score in noncontrast head computed tomography interpretations using a smartphone in a telestroke network, by comparison to a medical monitor. METHODS: The review board of our institution approved this retrospective study. A factorial design with 188 patients, four radiologists and two reading systems was used. Accuracy and reliability were evaluated. RESULTS: Very good interobserver agreements were observed on the total Alberta Stroke Program Early CT Score for both the medical and smartphone reading systems, with intraclass correlation coefficients of 0.91 and 0.84 respectively. Interobserver agreements were moderate to very good for the medical reading system (all intraclass correlation coefficients >0.74), whereas they were fair to very good for the smartphone (intraclass correlation coefficients ranged from 0.31-0.81). All intraobserver agreements were good (intraclass correlation coefficient >0.64), except for internal capsule (0.48) and M2 (0.55) regions. The areas under the receiver-operating curve ranged from 0.69-0.89 for the medical system, while for the smartphone ranged from 0.44-0.86. No statistical differences were observed between medical and smartphone reading systems for each region (all p > 0.05). DISCUSSION: If radiologists are better trained in the evaluation of the lesions in the insula, the internal capsule and the M2 regions, the total and the dichotomised Alberta Stroke Program Early CT Score will be more precise. Hence, ruling out contraindications to thrombolysis administration will be improved, allowing assessment of head computed tomography in a telestroke network using a smartphone to be a common practice.

Effect of a High-Intensity Tandem Bicycle Exercise Program on Clinical Severity, Functional Magnetic Resonance Imaging, and Plasma Biomarkers in Parkinson's Disease.

Rationale: The optimal modality, intensity, duration, frequency, and dose-response of exercise as a therapy for Parkinson's Disease (PD) are insufficiently understood. Objective: To assess the impact of a high-intensity tandem bicycle program on clinical severity, biomarkers, and functional MRI (fMRI) in PD. Methods: A single-center, parallel-group clinical trial was conducted. Thirteen PD patients aged 65 or younger were divided in two groups: a control group and an intervention group that incorporated a cycling program at 80% of each individual's maximum heart rate (HR) (≥80 rpm), three times a week, for 16 weeks. Both groups continued their conventional medications for PD. At baseline and at the end of follow-up, we determined in all participants the Unified Parkinson's Disease Rating Scale, anthropometry, VO2max, PD biomarkers, and fMRI. Results: VO2max improved in the intervention group (IG) (+5.7 ml/kg/min), while it slightly deteriorated in the control group (CG) (-1.6 ml/kg/min) (p = 0.041). Mean Unified Parkinson's Disease Rating Scale (UPDRS) went down by 5.7 points in the IG and showed a small 0.9-point increase in the CG (p = 0.11). fMRI showed activation of the right fusiform gyrus during the motor task and functional connectivity between the cingulum and areas of the frontal cortex, and between the cerebellar vermis and the thalamus and posterior temporal gyrus. Plasma brain-derived neurotrophic factor (BDNF) levels increased more than 10-fold in the IG and decreased in the CG (p = 0.028). Larger increases in plasma BDNF correlated with greater decreases in UPDRS (r = -0.58, p = 0.04). Conclusions: Our findings suggest that high-intensity tandem bicycle improves motor function and biochemical and functional neuroimaging variables in PD patients. Trial registration number: ISRCTN 13047118, Registered on February 8, 2018.

Accuracy and Reliability of the Recommendation for IV Thrombolysis in Acute Ischemic Stroke Based on Interpretation of Head CT on a Smartphone or a Laptop.

OBJECTIVE. The objective of this study was to assess the accuracy and reliability of IV thrombolysis recommendations made after interpretation of head CT images of patients with symptoms of acute stroke displayed on smartphone or laptop reading systems compared with those made after interpretation of images displayed on a medical workstation monitor. MATERIALS AND METHODS. This retrospective study was institutional review board-approved, and the requirement for informed consent was waived. We used a factorial design including 2256 interpretations (188 patients, four neuroradiologists, and three reading systems). To evaluate the reliability, we calculated the intraobserver and interobserver agreements using the intraclass correlation coefficient (ICC) and the following interpretation variables: hemorrhagic lesions, intraaxial neoplasm, stroke dating (acute, subacute, and chronic), hyperdense arteries, and infarct size assessment. Accuracy equivalence tests were performed for the IV thrombolysis recommendation; for this variable, sensitivity, specificity, and ROC curves were evaluated. RESULTS. Good or very good interobserver and intraobserver agreements were obtained after interpretation of each variable. The IV thrombolysis recommendation showed very good interobserver agreements (ICC ≥ 0.85) and very good intraobserver agreements (ICC ≥ 0.81). For the IV thrombolysis recommendation, the AUC values (0.83-0.84) and sensitivities (0.94-0.95) were equivalent among all the reading systems at a 5% equivalent threshold. CONCLUSION. Our study found that mobile devices are reliable and accurate to help stroke teams to decide whether to administer IV thrombolysis in patients with acute stroke.

Evaluación radio-anatómica del receso del seno frontal en población colombiana / Radio-anatomic evaluation of the frontal sinus recess in colombian population

Objetivos: La cirugía endoscópica del seno frontal es quizá uno de los procedimientos más complejos en el manejo endoscópico de los senos paranasales debido a su localización y a las múltiples variantes anatómicas que pueden encontrarse durante su disección. Es indispensable conocer al detalle la anatomía quirúrgica de esta región en nuestra población, para optimizar la planeación quirúrgica de los pacientes. Actualmente en nuestro país se desconoce la frecuencia de estas variaciones. El objetivo del proyecto es evaluar la frecuencia de las variables anatómicas del seno frontal y realizar un estudio radio-anatómico en una muestra de pacientes en Colombia. Diseño del estudio: Observacional, descriptivo de tipo transversal. Métodos: Muestra aleatorizada de 406 tomografías computarizadas de senos paranasales que incluyeron 812 senos frontales recolectados durante el año 2018 Resultados: La celdilla suprabular fue la más comúnmente reportada con una frecuencia de 59.61%. La segunda celdilla fue la supra agger nasi con una frecuencia de 57.88%, seguido de la celdilla supra agger frontal (25.12%), celdilla suprabular frontal (22.17%), celdillas supraorbitarias (34.98%) y las celdilla frontal intersinusal (24,14%). La arteria etmoidal anterior se reportó colgante en un 31.28% y el diámetro AP más frecuente fue entre 5 -10 milímetros. Conclusiones: Para realizar una sinusotomía frontal endoscópica de forma adecuada es necesario conocer al detalle la anatomía del receso del seno frontal. Las diferentes variantes radio-anatómicas son muy frecuentes en el grupo poblacional estudiado. Creemos que este trabajo permitirá a los cirujanos un mejor entendimiento de esta región de difícil acceso quirúrgico en nuestra población. Palabras clave: Seno frontal, senos paranasales, seno clasificación frontal, cirugia endoscopica nasosinusal

Objectives: Endoscopic frontal sinus surgery is perhaps, one of the most complex procedures in the endoscopic sinus surgery, due to its anatomical location and the multiple anatomical variants that can be found. It is essential to know in detail the anatomy of this region in order to obtain a better understanding for the surgical planning. Currently, the frequency of these anatomical variations remains unknown in our country. Therefore, the objective of the study is to evaluate the frequency of the anatomical variants of the frontal sinus and to carry out a radio-anatomic study in a sample of patients from Colombia. Study design: Observational, cross-sectional descriptive. Methods: Randomized sample of 406 CT scan of the paranasal sinuses that included 812 frontal sinuses collected during the year 2018. Results: The supra bulla cell was the most frequently reported with a frequency of 59.61%. The second cell was the supra agger (57.88%) followed by supra agger frontal cell (25.12%), supra bulla frontal cell (22.17%), supraorbital ethmoid cells (34,98%) and frontal septal cell (24,14%) . The anterior ethmoidal artery was found hanging in 31.28% and the most frequent AP diameter was between 5 -10 mm. Conclusions: To perform an appropriate endoscopic frontal sinusotomy, it is necessary to know in detail the anatomy of the frontal sinus recess. The different radio-anatomical variants of the frontal sinus are very frequent in the population group studied. We believe that this study will allow surgeons to obtain a better understanding of this anatomical region of difficult surgical access.

Systemic management of malignant meningiomas: A comparative survival and molecular marker analysis between Octreotide in combination with Everolimus and Sunitinib.

PURPOSE: To compare the effectiveness of octreotide/everolimus vs. sunitinib for the systemic treatment of recurrent aggressive meningiomas. METHODS: 31 patients with recurrent or refractory WHO II or WHO III meningiomas were examined in two reference centers in Colombia. Patients who had systemic treatment (sunitinib, everolimus/octreotide) and a complete follow-up were included. Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRß and VEGFR2, their expression was correlated with outcomes. RESULTS: Twenty-two patients (72%) were female with a median age of 55 years (SD±15.3). The most prevalent histology was anaplastic meningioma in 20 patients (65%) with 48% of patients suffering from three previous relapses before the start of systemic treatment. A total of 14 patients received combination therapy with octreotide/everolimus, 11 received sunitinib and the remaining 6 received other second-line agents. Median OS was 37.3 months (95%CI 28.5-42.1) and the PFS during the treatment with everolimus/octreotide (EO) and sunitinib (Su) was 12.1 months (95%CI 9.2-21.1) and 9.1 months (95%CI 6.8-16.8); p = 0.43), respectively. The OS of the group treated with the EO→Su→Bev sequence (1st/2nd/3rd line) was 6.5 months longer than the Su→EO→Bev sequence (36.0 vs. 29.5 months) (p = 0.0001). When analyzing molecular markers, the positive PDGFRß and negative VEGFR2 expression were associated with longer survival both in OS and PFS. CONCLUSION: Sunitinib and octreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRß expression are associated with better outcomes.

Evaluation of the Accuracy Equivalence of Head CT Interpretations in Acute Stroke Patients Using a Smartphone, a Laptop, or a Medical Workstation.

PURPOSE: To evaluate and compare the clinical performance of observers interpreting head CT images from patients with symptoms of acute stroke with a medical workstation or a smartphone or laptop reading system. MATERIALS AND METHODS: Our institutional review board approved this retrospective study and waived the requirement for informed consent. We employed a factorial design including 2,256 interpretations (188 patients × 4 neuroradiologists × 3 reading systems). Accuracy equivalence tests, at a threshold of 5% and 10%, were performed for the following variables: detection of imaging contraindications for intravenous recombinant tissue-type plasminogen activator administration (eg, hemorrhagic lesions), ischemic lesions, hyperdense arteries, and acute ischemic lesions. For each clinical variable, the sensitivity, specificity, and receiver operating characteristic (ROC) curves were evaluated. RESULTS: For each variable, the shapes of the ROC curves were very similar for all of the reading systems, indicating similar observer performance with different specificities and sensitivities. For all the clinical variables, the areas under the ROC curves were equivalent for all of the reading systems at a 10% threshold and were equivalent at a 5% threshold for hemorrhagic lesions, hyperdense middle cerebral artery, and acute ischemic lesion in the middle cerebral artery territory. There was no more than 30 seconds of difference between the reading time of the mobile devices compared with that for the medical workstation. CONCLUSION: The results of this pilot study showed equivalent diagnostic accuracy when using smartphone and laptops compared with medical monitors to interpret head CT images of patients with symptoms of acute stroke.

Xantoastrocitoma pleomórfico anaplásico recurrente y respuesta a la combinación de carmustine y bevacizumab, un reporte de caso / Recurrent pleomorphic anaplastic xanthoastrocytoma and response to combination of carmustine and bevacizumab, a case report

RESUMEN Se expone el caso de una mujer de 19 años a quien se le realizó el diagnóstico de un xantoastrocitoma pleomórfico anaplásico parietooccipital izquierdo, neoplasia poco frecuente que suele presentarse en la población pediátrica y en los adultos jóvenes. Dicho tumor debuta generalmente con crisis convulsivas y sus características histológicas patognomónicas son el pleomorfismo celular, la vacuolización lipídica de su citoplasma y la reactividad a la proteína ácida fibrilar glial (PAFG) y S100. El estudio de nuevos marcadores que puedan brindar otras oportunidades terapéuticas ha permitido encontrar mutaciones en el oncogén BRAF. Este tumor presenta una variante anaplásica más agresiva que se trata con cirugía y quimiorradiación. En nuestro caso, después de varias progresiones a otras intervenciones, se utilizó bevacizumab y carmustine como tratamiento de segunda línea con respuesta completa.

SUMMARY The case of a young woman of 19-years-old is presented; whom the diagnosis was made of a left parietal-occipital xanthoastrocytoma pleomorphic anaplastic; this neoplasia is rare and usually affects the pediatric and young adult population. This generally debuts with seizures and their pathognomonic histologic characteristics are the pleomorphic cells with cytoplasmatic lipid vacuolation and the reactivity of glial fibrillary acidic protein (GFAP) and S100. The study of new markers that may provide other therapeutic opportunities has allowed finding mutations in the BRAF oncogene. This tumor has a more aggressive anaplastic variant that is treated with surgery and chemoradation. In our case after several progressions to other interventions, we used bevacizumab and carmustine as second-line treatment obtaining complete response.

Mobile device for thrombolysis decisions for telestroke / Dispositivo móvil para decisiones de trombólisis mediante Telestroke

Abstract Aim: This study compares the reliability of brain CT interpretations performed using a diagnostic workstation and a mobile tablet computer in a telestroke context. Methods: A factorial design with 1,452 interpretations was used. Reliability was evaluated using the Fleiss' kappa coefficient on the agreements of the interpretation results on the lesion classification, presence of imaging contraindications to the intravenous recombinant tissue-type plasminogen activator (t-PA) administration, and on the Alberta Stroke Program Early CT Score (ASPECTS). Results: The intra-observer agreements were as follows: good agreement on the overall lesion classification (κ= 0.63, p<0.001), very good agreement on hemorrhagic lesions (κ= 0.89, p<0.001), and moderate agreements on both without acute lesion classification and acute ischemic lesion classification (κ= 0.59 and κ= 0.58 respectively, p<0.001). There was good intra-observer agreement on the dichotomized-ASPECTS (κ= 0.65, p<0.001). Conclusions: The results of our study allow us to conclude that the reliability of the mobile solution for interpreting brain CT images of patients with acute stroke was assured, which would allow efficient and low-cost telestroke services.

Resumen Objetivo: Este estudio compara la confiabilidad de interpretaciones de TAC de cráneo simple realizadas utilizando una estación de trabajo de diagnóstico y un computador tableta en un contexto de teleACV. Métodos: Se utilizó un diseño factorial con 1,452 interpretaciones. La confiabilidad se evaluó utilizando el coeficiente kappa de Fleiss en las concordancias sobre los resultados de la interpretación en la clasificación de la lesión, la presencia de contraindicaciones en la imagen para la administración intravenosa del activador del plasminógeno tisular (AP-t) y con el Alberta Stroke Programme Early CT Score (ASPECTS). Resultados: Se obtuvieron las siguientes concordancias intraobservadores: buena concordancia en la clasificación general de la lesión (κ= 0.63, p<0.001), muy buena concordancia en lesiones hemorrágicas (κ= 0.89, p< 0.001), y concordancia moderada en ambos sin clasificación de lesión aguda y clasificación de lesión isquémica aguda (κ= 0.59 y κ= 0.58 respectivamente, p<0.001). Hubo una buena concordancia intraobservadores en el ASPECTS dicotomizado (κ= 0.65, p<0.001). Conclusiones: Los resultados de nuestro estudio permiten concluir que la confiabilidad de la solución móvil para la interpretación de imágenes de TAC de cráneo simple de pacientes con accidente cerebrovascular agudo (ACV) estaba garantizada, lo que permitiría servicios de teleACV eficientes y de bajo costo.

Mobile device for thrombolysis decisions for telestroke.

AIM: This study compares the reliability of brain CT interpretations performed using a diagnostic workstation and a mobile tablet computer in a telestroke context. METHODS: A factorial design with 1,452 interpretations was used. Reliability was evaluated using the Fleiss' kappa coefficient on the agreements of the interpretation results on the lesion classification, presence of imaging contraindications to the intravenous recombinant tissue-type plasminogen activator (t-PA) administration, and on the Alberta Stroke Program Early CT Score (ASPECTS). RESULTS: The intra-observer agreements were as follows: good agreement on the overall lesion classification (κ= 0.63, p<0.001), very good agreement on hemorrhagic lesions (κ= 0.89, p<0.001), and moderate agreements on both without acute lesion classification and acute ischemic lesion classification (κ= 0.59 and κ= 0.58 respectively, p<0.001). There was good intra-observer agreement on the dichotomized-ASPECTS (κ= 0.65, p<0.001). CONCLUSIONS: The results of our study allow us to conclude that the reliability of the mobile solution for interpreting brain CT images of patients with acute stroke was assured, which would allow efficient and low-cost telestroke services.

OBJETIVO: Este estudio compara la confiabilidad de interpretaciones de TAC de cráneo simple realizadas utilizando una estación de trabajo de diagnóstico y un computador tableta en un contexto de teleACV. MÉTODOS: Se utilizó un diseño factorial con 1,452 interpretaciones. La confiabilidad se evaluó utilizando el coeficiente kappa de Fleiss en las concordancias sobre los resultados de la interpretación en la clasificación de la lesión, la presencia de contraindicaciones en la imagen para la administración intravenosa del activador del plasminógeno tisular (AP-t) y con el Alberta Stroke Programme Early CT Score (ASPECTS). RESULTADOS: Se obtuvieron las siguientes concordancias intraobservadores: buena concordancia en la clasificación general de la lesión (κ= 0.63, p<0.001), muy buena concordancia en lesiones hemorrágicas (κ= 0.89, p< 0.001), y concordancia moderada en ambos sin clasificación de lesión aguda y clasificación de lesión isquémica aguda (κ= 0.59 y κ= 0.58 respectivamente, p<0.001). Hubo una buena concordancia intraobservadores en el ASPECTS dicotomizado (κ= 0.65, p<0.001). CONCLUSIONES: Los resultados de nuestro estudio permiten concluir que la confiabilidad de la solución móvil para la interpretación de imágenes de TAC de cráneo simple de pacientes con accidente cerebrovascular agudo (ACV) estaba garantizada, lo que permitiría servicios de teleACV eficientes y de bajo costo.

Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma.

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.

Ruling Out Brain CT Contraindications prior to Intravenous Thrombolysis: Diagnostic Equivalence between a Primary Interpretation Workstation and a Mobile Tablet Computer.

OBJECTIVE: The aim of this study was to evaluate the equivalence of brain CT interpretations performed using a diagnostic workstation and a mobile tablet computer, in a telestroke service. MATERIALS AND METHODS: The ethics committee of our institution approved this retrospective study. A factorial design with 1452 interpretations was used. The assessed variables were the type of stroke classification, the presence of contraindications to the tPA administration, the presence of a hyperdense intracranial artery sign (HMCA), and the Alberta Stroke Program Early CT Score (ASPECTS) score. These variables were evaluated to determine the effect that the reading system had on their magnitudes. RESULTS: The achieved distribution of observed lesions using both the reading systems was not statistically different. The differences between the two reading systems to claim equivalence were 1.6% for hemorrhagic lesions, 4.5% for cases without lesion, and 5.2 for overall ischemic lesion. Equivalence was achieved at 2.1% for ASPECTS ≤ 6, 6.5% for the presence of imaging contraindication to the tPA administration, and 7.2% for the presence of HMCA. CONCLUSION: The diagnostic performance for detecting acute stroke is likely equivalent whether a tablet computer or a diagnostic workstation is used or not.

Isolated giant cerebral varix - A diagnostic and therapeutic challenge: A case report.

BACKGROUND: Isolated giant cerebral varix (IGV) is an uncommon vascular lesion that represents a diagnostic challenge and requires dynamic vascular studies for its characterization. The IGV is considered a benign, low-flow venous lesion with very low risk of bleeding that might cause secondary symptoms mainly due to compression of the adjacent parenchyma. CASE DESCRIPTION: A 12-year-old female patient with non-contributory medical history presented with headache for the last 2 months. Upon admission, her neurological examination was unremarkable. Magnetic resonance imaging (MRI) and computed tomography angiography (CTA) images demonstrated a large varicose dilation of the superficial Sylvian vein, located anterior to the left temporal pole, with no evidence of abnormal arteriovenous connections or tumoral lesions. This finding was considered incidental and unrelated to her symptoms. In this case, we considered that the combination of CTA and MRIs was enough to establish an accurate diagnosis, excluding the need to perform invasive imaging studies. Taking into account these considerations, the patient was managed with conservative treatment and has been followed up for 1 year, remaining asymptomatic. CONCLUSION: Cerebral IGVs are rare vascular lesions that are treated conservatively when asymptomatic and surgically in the case of rupture or compression of adjacent structures. Given our observation of a high unlikelihood of vascular connections to arteries, and the information obtained with non-invasive imaging techniques such as CTA and MRI was enough to make a clinical decision and avoid the evaluation with invasive procedures.

Genotyping low-grade gliomas among Hispanics.

BACKGROUND: Low-grade gliomas (LGGs) are classified by the World Health Organization as astrocytoma (DA), oligodendroglioma (OD), and mixed oligoastrocytoma (OA). TP53 mutation and 1p19q codeletion are the most-commonly documented molecular abnormalities. Isocitrate dehydrogenase (IDH) 1/2 mutations are frequent in LGGs; however, IDH-negative gliomas can also occur. Recent research suggests that ATRX plays a significant role in gliomagenesis. METHODS: We investigated p53 and Olig2 protein expression, and MGMT promoter methylation, 1p19q codeletion, IDH, and ATRX status in 63 Colombian patients with LGG. The overall survival (OS) rate was estimated and compared according to genotype. RESULTS: The most common histology was DA, followed by OD and OA. IDH1/2 mutations were found in 57.1% and MGMT+ (positive status of MGMT promoter methylation methyl-guanyl-methyl-transferase gene) in 65.1% of patients, while overexpression of p53 and Olig2 was present in 30.2% and 44.4%, respectively, and 1p19q codeletion in 34.9% of the patients. Overexpression of ATRX was analyzed in 25 patients, 16% tested positive and were also mutations in isocitrate dehydrogenase and negative 1p19q-codelition. The median follow-up was 15.8 months (95% CI, 7.6-42.0) and OS was 39.2 months (95% CI, 1.3-114). OS was positively and significantly affected by MGMT+, 1p19q codeletion, surgical intervention extent, and number of lobes involved. Multivariate analysis confirmed that MGMT methylation status and 1p19q codeletion affected OS. CONCLUSIONS: This is the first study evaluating the molecular profile of Hispanic LGG patients. Findings confirmed the prognostic relevance of MGMT methylation and 1p19q codeletion, but do not support IDH1/2 mutation as a relevant marker. The latter may be explained by sample size and selection bias. ATRX alterations were limited to patients with DA and were mutations in isocitrate dehydrogenase and negative 1p19q-codelition.

Hernia medular transdural idiopática: presentación de dos casos y revisión de la literatura / Idiopathic transdural medullary hernia: presentation of two cases and review of the literature

INTRODUCCIÓN: la Hernia Medular Transdural Idiopática es una causa poco frecuente de mielopatía progresiva con presentación clínica variable, el diagnóstico se hace frecuentemente con una imagen de Resonancia Magnética. El manejo es principalmente quirúrgico con buenos resultados generalmente. CASOS CLÍNICOS: se presenta el caso de una paciente de sexo femenino de 57 años con cuadro de un año de evolución con parestesias en las extremidades y debilidad del hemicuerpo derecho, el diagnóstico de Hernia Medular Transdural Idiopática se hizo con imágenes de Resonancia Magnética y con una Mielografía por TAC. En el segundo caso una paciente de 46 años con dolor cervical y parestesias en los miembros inferiores. Los estudios con Resonancia Magnética demostraron una Hernia Medular Transdural. En los dos casos dado que no presentaban síntomas limitantes ni progresivos se decidió manejo conservador. CONCLUSIÓN: la Hernia Medular Transdural es una patología que se debe considerar como diagnóstico diferencial en los pacientes con clínica de compromiso medular progresivo, el diagnóstico adecuado y el manejo oportuno puede beneficiar a los pacientes otorgándoles un buen pronóstico

INTRODUCTION: idiopathic spinal cord herniation (ISCH) is an infrequent cause of progressive myelopathy with a variable clinical presentation. As such, the diagnosis is frequently made by means of magnetic resonance imaging (MRI). Treatment is largely surgical with generally good outcomes. CASE REPORTS: we present two cases. The first was a 57-year old female with a year-long history of numbness in all extremities and weakness in the right side of her body, in whom the diagnosis of ISCH was made by MRI and CT myelography. The second patient was a 46-year old female with neck pain and lower limb paresthesia. Additional MRI studies revealed ISCH. Due to the non-progressive nature of symptoms, conservative management was provided to both patients. CONCLUSION: idiopathic spinal cord herniation is a pathology that must be considered among differential diagnoses in patients with clinical evidence of progressive spinal compromise. An accurate diagnosis and prompt treatment often leads to a good clinical outcome

Alteración de la marcha en un paciente post-trasplante hepático / Gait disturbance after hepatic trasplantation

Los síndromes linfoproliferativos postrasplante (PTLD, por sus siglas en inglés) constituyen una complicación relativamente frecuente entre los receptores de trasplante de órgano sólido o de médula ósea. Representan un amplio espectro de lesiones, que oscilan desde los cambios histológicos tempranos producidos por la infección del virus de Epstein-Barr hasta las neoplasias de alto grado con respuestas variables a las intervenciones terapéuticas. El compromiso del sistema nervioso central (SNC) se ha descrito hasta en 22% de los casos, 12% de ellos en forma primaria, asociados a un peor pronóstico; en general el abordaje diagnóstico y terapéutico no está estandarizado, en parte, debido a la limitación fisiológica que implica la barrera hematoencefálica. El tratamiento tiene opciones limitadas; se acepta el uso de metotrexate a altas dosis o de rituximab intravenoso o intratecal. A continuación, se presenta el caso de un hombre de 76 años, receptor de un trasplante hepático por hemocromatosis, quien a los 6 años postrasplante consulta por alteración de la marcha. Tras documentar una lesión intra-axial, la biopsia por estereotaxia documenta un PTLD tardío, primario con lesión única en SNC. Después de la reducción inicial de la inmunosupresión, el tratamiento con rituximab y metotrexate intravenosos a altas dosis durante cinco ciclos, se logró respuesta parcial en este paciente, con toxicidad renal leve.