Cardiac Stasis Imaging, Stroke and Silent Brain Infarcts in Patients with Non-Ischemic Dilated Cardiomyopathy.

Cardioembolic stroke is one of the most devastating complications of non-ischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation are hampered by the risk of bleeding. Indices of cardiac blood stasis may account for the risk of stroke and be useful to individualize primary prevention treatments. We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary endpoint integrated a history of ischemic stroke or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV, its residence time (RT) maps and its derived stasis indices. Of the 89 recruited patients, 18 showed a positive endpoint: 9 had a history stroke or TIA and 9 were diagnosed with SBIs in the brain imaging. Averaged RT, performed good to identify the primary endpoint (AUC (95% CI)= 0.75 (0.61-0.89), p= 0.001). When accounting only for identifying a history of stroke or TIA, AUC for was 0.92 (0.85-1.00) with and odds ratio= 7.2 (2.3 - 22.3) per cycle, p< 0.001. These results suggest that, in patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiography may account for the burden of stroke.

Stasis imaging predicts the risk of cardioembolic events related to acute myocardial infarction: the ISBITAMI study.

INTRODUCTION AND OBJECTIVES: In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI. METHODS: We designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, RT, of blood inside the left ventricle and assessed its performance to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking. RESULTS: A total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. RT (OR, 3.73; 95%CI, 1.75-7.9; P<.001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P=.004) showed complementary prognostic value. The bivariate model showed a c-index=0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value. CONCLUSIONS: In patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging. Registered at ClinicalTrials.gov (NCT02917213).

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4.

SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract. In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls. We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volume bilaterally, as well as an inward deformation, mainly in the sensory-motor thalamic regions in patients with pure HSP and a mutation in SPG4. We also observed a significant negative correlation between the shape of the thalamus and clinical scores (the Spastic Paraplegia Rating Scale score and disease duration). Moreover, we found a 'Group × Age' interaction that was closely related to the severity of the disease. No differences in volume or in shape were found in the remaining subcortical structures studied. Our results suggest that changes in structure of the thalamus could be an imaging biomarker of disease progression in pHSP.

Methotrexate-Induced Subacute Neurotoxicity Surrounding an Ommaya Reservoir in a Patient with Lymphoma.

BACKGROUND Intraventricular administration of methotrexate (MTX) using an Ommaya reservoir is a useful therapeutic maneuver for malignant CNS involvement in patients with hematological malignancies. MTX-induced subacute neurotoxicity is a rare complication that typically progresses with involvement of the basal ganglia. Local toxicity due to misplaced catheters has been described, although the impact of normally positioned catheters on toxicity is not clear. CASE REPORT We report the case of a 21-year-old man diagnosed with stage IV diffuse large B-cell lymphoma who experienced a central nervous system relapse. While receiving intraventricular MTX using an Ommaya reservoir and systemic MTX, he experienced sudden left-side hemiparesis. All diagnostic tests were negative except for altered MRI findings with FLAIR hyperintensity in the basal ganglia and restricted diffusion in the same location that followed the track of the Ommaya catheter. The syndrome resolved after administration of high-dose steroids, and the patient received subsequent MTX courses without recurrence. CONCLUSIONS MTX-induced neurotoxicity is a rare adverse event related to systemic and intrathecal administration of the drug. Many cases of Ommaya-related CNS symptoms have been described, although most were related to misplaced or malfunctioning catheters. Here we present a case of subacute MTX toxicity affecting the area around a correctly positioned catheter, suggesting that the catheter track could be more susceptible to MTX-induced toxicity.

Modelo predictivo clínico-radiológico para diagnosticar tuberculosis pulmonar activa / Predictive clinical-radiological model for diagnosing active pulmonary tuberculosis

Resumen: Introducción: El objetivo de este estudio fue desarrollar un modelo predictivo sobre la presencia de tuberculosis pulmonar activa utilizando datos clínico-epidemiológicos y hallazgos de radiografía simple (Rx) y tomografía computadorizada (TC) de tórax. Material y métodos: Se realizó un estudio observacional, retrospectivo, descriptivo y analítico, que recopiló 22 variables clínico-epidemiológicas, 11 hallazgos radiológicos en Rx de tórax y 23 en la TC, que se realizaron en pacientes con sospecha clínica de tuberculosis pulmonar durante un período de 10 años. Se aplicó un modelo de regresión logística multivariado a los predictores potenciales de cultivo positivo, obteniendo un modelo predictivo. Resultados: Se recogieron 1.540 pacientes con sospecha clínica de tuberculosis a los que se les realizó Rx y TC torácico. El cultivo fue positivo en 101 casos. Se utilizó un proceso de eliminación hacia atrás para obtener el mejor conjunto de variables predictivas. Se obtuvieron 24 variables que fueron significativas (6 clínicas, 5 de Rx y 13 de TC) y se les asignó una puntuación. A la suma de estas puntuaciones se restó la edad en años multiplicada por 0,03. El modelo sugiere el diagnóstico de tuberculosis pulmonar activa en pacientes con una puntuación superior a 1,845. Obtuvo una sensibilidad de 85,1%, especificidad de 83,6%, valor predictivo positivo de 26,6%, y valor predictivo negativo de 98,7%. El área bajo la curva ROC fue de 0,9163. Conclusión: Este sistema de puntuación basado en criterios clínico-epidemiológicos y hallazgos radiológicos puede ayudar a diagnosticar tuberculosis pulmonar activa en casos de sospecha diagnóstica.

Abstract:Introduction: The objective of this study was to develop a predictive model on the presence of active pulmonary tuberculosis using clinical-epidemiological data and findings of chest radiography and thoracic computed tomography (CT). Material and methods: An observational, retrospective, descriptive and analytical study was conducted, which collected 22 clinical and epidemiological variables, 11 radiological findings on chest x-ray and 23 on CT that were performed in patients with clinical suspicion of pulmonary tuberculosis during a period of 10 years. A multivariate logistic regression model was applied to the potential predictors of positive culture, obtaining a predictive model. Results: We collected 1,540 patients with clinical suspicion of tuberculosis who underwent radiography and thoracic CT. The culture was positive in 101 cases. A backward elimination process was used to obtain the best set of predictive variables. We obtained 24 variables that were significant (6 clinical, 5 of chest plain films and 13 of CT) and were assigned a score. The sum of these scores was subtracted from the age in years and multiplied by 0.03. The model suggests the diagnosis of active pulmonary tuberculosis in patients with a score higher than 1.845. The model obtained a sensitivity of 85.1%, specificity of 83.6%, positive predictive value of 26.6, and negative predictive value of 98.7%. The area under the ROC curve was 0.9163. Conclusion: This scoring system based on clinical-epidemiological criteria and radiological findings can help rule out active pulmonary tuberculosis in cases of diagnostic suspicion.

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism.

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

Palatal and Oromandibular Tremor Secondary to Degenerative Olivary Hypertrophy After Ependymoma Surgery.

Palatal tremor (PT) is a rare movement disorder that involves pharynx, tongue, and other facial muscles. Symptomatic PT is due to lesions on the dentate-rubro-olivary pathways. We present an illustrative case of PT due to degenerative olivary hypertrophy after ependymoma surgery.

Exclusion criteria vs reality: dual BRAF/MEK inhibition and radiotherapy in a patient with melanoma metastatic to the brain and ECOG 3.

BACKGROUND: Prognosis of metastatic melanoma is changing due to advances in immunotherapy and targeted therapy. However, management of patients with brain metastases in day-to-day practice continues to be a challenge. CASE REPORT: We describe a 40-year-old woman diagnosed with symptomatic brain metastases from cutaneous melanoma and Eastern Cooperative Oncology Group 3. She was treated, off label, with BRAF inhibitor (dabrafenib) + MEK inhibitor (trametinib) and radiotherapy. There was significant, long-lasting, response (17 months), no clinically relevant toxicity, and clear improvement in quality of life. CONCLUSIONS: This case is an example of real-life application of advances in targeted therapy.

Added value of advanced over conventional magnetic resonance imaging in grading gliomas and other primary brain tumors.

BACKGROUND: Although conventional MR imaging (MRI) is the most widely used non-invasive technique for brain tumor grading, its accuracy has been reported to be relatively low. Advanced MR techniques, such as perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI), and magnetic resonance spectroscopy (MRS), could predict neoplastic histology, but their added value over conventional MRI is still open to debate. METHODS: We prospectively analyzed 129 patients diagnosed with primary brain tumors (118 gliomas) classified as low-grade in 30 cases and high-grade in 99 cases. RESULTS: Significant differences were obtained in high-grade tumors for conventional MRI variables (necrosis, enhancement, edema, hemorrhage, and neovascularization); high relative cerebral blood volume values (rCBV), low relative apparent diffusion coefficients (rADC), high ratio of N-acetyl-aspartate/creatine at short echo time (TE) and high choline/creatine at long TE. Among conventional MRI variables, the presence of enhancement and necrosis were demonstrated to be the best predictors of high grade in primary brain tumors (sensitivity 95.9%; specificity 70%). The best results in primary brain tumors were obtained for enhancement, necrosis, and rADC (sensitivity 98.9%; specificity 75.9%). Necrosis and enhancement were the only predictors of high grade in gliomas (sensitivity 97.6%; specificity 76%) when all the magnetic resonance variables were combined. CONCLUSIONS: MRI is highly accurate in the assessment of tumor grade. The combination of conventional MRI features with advanced MR variables showed only improved tumor grading by adding rADC to conventional MRI variables in primary brain tumors.

Risa y llanto patológico autolimitado debido a un hematoma protuberancial en un paciente con enfermedad moyamoya / Self-limiting pathological laughter and crying due to a pontine haematoma in a patient with moyamoya disease

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Differential diagnosis of T2 hyperintense brainstem lesions: Part 1. Focal lesions.

Brainstem lesions can be classified as focal or diffuse. Magnetic resonance imaging is the most suitable imaging modality for evaluating these lesions. As a rule, focal lesions are not large and have well-defined margins. Causes include tumors, vascular malformations, demyelinating diseases, brain abscesses, hypertrophic olivary degeneration, and dilated Virchow-Robin spaces. Differential diagnoses of these numerous entities mandates a review of magnetic resonance imaging findings in conjunction with epidemiologic aspects, clinical features, and other medical test results.

Differential diagnosis of T2 hyperintense brainstem lesions: Part 2. Diffuse lesions.

Diffuse brainstem lesions are poorly defined, often large abnormalities and include tumors (gliomas and lymphomas) vasculitis (Behçet's disease), traumatic brainstem injury, degenerative disorders (Wallerian degeneration), infections, processes secondary to systemic conditions (central pontine myelinolysis, hypertensive or hepatic encephalopathy), and ischemic pathology (leukoaraiosis). Magnetic resonance imaging is the most appropriate imaging modality to use in evaluating lesions of this type, but often findings are nonspecific. Therefore, radiologists need to bear in mind such additional information as patient age and clinical features in making a differential diagnosis.