Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.

BACKGROUND: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. RESULTS: CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. DISCUSSION: In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. HIGHLIGHTS: This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.

Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice.

INTRODUCTION: We developed a multimarker blood test result interpretation tool for the clinical dementia practice, including phosphorylated (P-)tau181, amyloid-beta (Abeta)42/40, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). METHODS: We measured the plasma biomarkers with Simoa (n = 1199), applied LASSO regression for biomarker selection and receiver operating characteristics (ROC) analyses to determine diagnostic accuracy. We validated our findings in two independent cohorts and constructed a visualization approach. RESULTS: P-tau181, GFAP, and NfL were selected. This combination had area under the curve (AUC) = 83% to identify amyloid positivity in pre-dementia stages, AUC = 87%-89% to differentiate Alzheimer's or controls from frontotemporal dementia, AUC = 74%-76% to differentiate Alzheimer's or controls from dementia with Lewy bodies. Highly reproducible AUCs were obtained in independent cohorts. The resulting visualization tool includes UpSet plots to visualize the stand-alone biomarker results and density plots to visualize the biomarker results combined. DISCUSSION: Our multimarker blood test interpretation tool is ready for testing in real-world clinical dementia settings. HIGHLIGHTS: We developed a multimarker blood test interpretation tool for clinical dementia practice. Our interpretation tool includes plasma biomarkers P-tau, GFAP, and NfL. Our tool is particularly useful for Alzheimer's and frontotemporal dementia diagnosis.

Characterization of white matter hyperintensities in Down syndrome.

INTRODUCTION: In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. METHODS: In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. RESULTS: In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. DISCUSSION: WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. HIGHLIGHTS: White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.

Diagnostic performance of plasma pTau217, pTau181, Aß1-42 and Aß1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

BACKGROUND: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown. METHODS: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aß1-42/Aß1-40 ratio. Plasma pTau217, pTau181, Aß1-42 and Aß1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aß1-42/Aß1-40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis. RESULTS: Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aß1-42/Aß1-40 ratio was lower in A + compared to A-. pTau181 and the Aß1-42/Aß1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau217, and 0.88 (95% CI 0.84-0.92) for both pTau181 and Aß1-42/Aß1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%. CONCLUSION: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Executive Summary of the Spanish Guidelines for the Diagnosis and Management of Imported Febrile Illnesses from the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Imported Pathology Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (GEPI-SEIMC), the Spanish Society of Family and Community Medicine (SEMFYC), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Emergency Medicine (SEMES).

The Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Family and Community Medicine (SEMFYC) have prepared a consensus statement on the diagnosis and management of patients with imported febrile illnesses. Twenty authors with different backgrounds and representing different healthcare perspectives (ambulatory primary care, travel and tropical medicine specialists, emergency medicine, hospital care, microbiology and parasitology and public health), identified 39 relevant questions, which were organised in 7 thematic blocks. After a systematic review of the literature and a thoughtful discussion, the authors prepared 125 recommendations, as well as several tables and figures to be used as a consulting tool. The present executive summary shows a selection of some of the most relevant questions and recommendations included in the guidelines.

Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome.

BACKGROUND AND OBJECTIVES: Cerebral hemorrhages are an exclusion criterion and potential adverse effect of antiamyloid agents. It is, therefore, critical to characterize the natural history of cerebral microbleeds in populations genetically predisposed to Alzheimer disease (AD), such as Down syndrome (DS). We aimed to assess microbleed emergence in adults with DS across the AD spectrum, defining their topography and associations with clinical variables, cognitive outcomes, and fluid and neuroimaging biomarkers. METHODS: This cross-sectional study included participants aged 18 years or older from the Down-Alzheimer Barcelona Neuroimaging Initiative and Sant Pau Initiative on Neurodegeneration with T1-weighted and susceptibility-weighted images. Participants underwent comprehensive assessments, including apolipoprotein E (APOE) genotyping; fluid and plasma determinations of beta-amyloid, tau, and neurofilament light; cognitive outcomes (Cambridge Cognitive Examination and modified Cued Recall Test); and vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia). We manually segmented microbleeds and characterized their topography. Associations between microbleed severity and AD biomarkers were explored using between-group comparisons (none vs 1 vs 2+) and multivariate linear models. RESULTS: We included 276 individuals with DS and 158 healthy euploid controls (mean age = 47.8 years, 50.92% female). Individuals with DS were more likely to have microbleeds than controls (20% vs 8.9%, p < 0.001), with more severe presentation (12% with 2+ vs 1.9%). Microbleeds increased with age (12% 20-30 years vs 60% > 60 years) and AD clinical stage (12.42% asymptomatic, 27.9% prodromal, 35.09% dementia) were more common in APOEε4 carriers (26% vs 18.3% noncarriers, p = 0.008), but not associated with vascular risk factors (p > 0.05). Microbleeds were predominantly posterior (cerebellum 33.66%; occipital 14.85%; temporal 21.29%) in participants with DS. Associations with microbleed severity were found for neuroimaging and fluid AD biomarkers, but only hippocampal volumes (standardized ß = -0.18 [-0.31, -0.06], p < 0.005) and CSF p-tau-181 concentrations (ß = 0.26 [0.12, 0.41], p < 0.005) survived regression controlling for age and disease stage, respectively. Microbleeds had limited effect on cognitive outcomes. DISCUSSION: In participants with DS, microbleeds present with a posterior, lobar predominance, are associated with disease severity, but do not affect cognitive performance. These results suggest an interplay between AD pathology and vascular lesions, implicating microbleeds as a risk factor limiting the use of antiamyloid agents in this population.

Diagnostic performance of plasma pTau 217, pTau 181, Aß 1-42 and Aß 1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

BACKGROUND: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown. METHODS: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A+) or negative (A-) according to CSF Aß1-42/Aß1-40 ratio. Plasma pTau217, pTau181, Aß1-42 and Aß1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aß1-42/Aß1-40 ratio. We analyzed the potential of pTau217 to predict amyloidosis in CSF. RESULTS: Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aß1-42/Aß1-40 ratio was lower in A + compared to A-. pTau181 and the Aß1-42/Aß1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau217, and 0.88 (95% CI 0.84-0.92) for both pTau181 and Aß1-42/Aß1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (x4.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%. CONCLUSION: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Utilidad de las secuencias funcionales por resonancia magnética en el estudio de los tumores óseos y de partes blandas. Revisión imaginológica / Difusion and Functional Sequences: Utility in the Study of Bone and Soft Tissue Tumors. Pictorial Review

La resonancia magnética es la técnica de imagen de elección para diagnosticar, caracterizar, estadificar, realizar el seguimiento y valorar la respuesta al tratamiento de los tumores musculoesqueléticos. Para estos fines se utilizan las secuencias convencionales. Desde hace algunos años se han comenzado a implementar nuevas técnicas avanzadas, como la secuencia en fase y fase opuesta, difusión, perfusión y espectroscopia, que en conjunto se denominan técnicas funcionales, las cuales proporcionan información más específica del comportamiento, fisiología, metabolismo y biología molecular del tumor. Estas secuencias son no invasivas, aportan información adicional cualitativa, cuantitativa, metabólica y vascular por lo que deberían utilizarse de manera rutinaria en el momento de realizar el diagnóstico y, especialmente, en el seguimiento de los tumores óseos y de partes blandas. En este artículo se revisa la técnica de dichas secuencias, particularmente la secuencia de difusión, mediante casos ilustrativos de nuestros hospitales: Hospital Pablo Tobón Uribe y Hospital Universitario Quirón Salud de Madrid. También se revisarán las aplicaciones e importancia de un análisis combinado de estas nuevas herramientas, que aportarán información adicional para adecuada caracterización, enfoque diagnóstico y respuesta al tratamiento de las lesiones tumorales en el sistema musculoesquelético

Magnetic resonance imaging (MR) is the preferred technique for the diagnosis, characterization, staging, follow-up and assessment of response to treatment of musculoskeletal tumors. Conventional sequences help to classify these lesions. Recently new evolving functional MR sequences with advanced techniques have been implemented, such as phase sequence, opposite phase, diffusion, perfusion and spectroscopy, which provide specific information about the behavior, physiology, metabolism and molecular biology of the tumor. These sequences are non-invasive and provide additional qualitative, quantitative, metabolic and vascular information, making them important for the diagnosis and monitoring of bone and soft tissue tumors. This article reviews the technique of these sequences, particualrly the diffusion technique, using illustrative cases from the Hospital Pablo Tobon Uribe (Medellin ­ Colombia) and the University Hospital Quirón Salud (Madrid ­ Spain). We aim to review the utility and importance of a combined analysis of these new tools, which will provide additional information for adequate characterization, diagnosis and response to treatment of tumor lesions in the musculoskeletal system.

Disomía uniparental-duplicación paterna de la región del cromosoma 11p15.5 como causa de displasia mesenquimatosa placentaria / Placental mesenchymal dysplasia due to uniparental disomy/paternal duplication of 11p15.5

Resumen ANTECEDENTES La displasia mesenquimatosa de la placenta es una enfermedad rara que en la ecografía se observa con vesículas en forma de racimo de uvas. Puede provocar complicaciones en el embarazo, como: restricción del crecimiento intrauterino, muerte intrauterina y parto pretérmino. CASO CLÍNICO Paciente de 31 años con displasia mesenquimatosa placentaria diagnosticada en la ecografía del primer trimestre de embarazo. Se apreció una zona con formaciones econegativas de 14 x 20 mm, con escasa captación del doppler color y que terminó de confirmarse en el segundo trimestre, con una biopsia corial. El embarazo trascurrió con normalidad hasta la semana 33, que fue cuando se detectó la restricción del crecimiento intrauterino. Debido a la alta incidencia de complicaciones obstétricas derivadas de éste se decidió la inducción del parto en la semana 37 de la gestación. CONCLUSIONES El diagnóstico de displasia mesenquimatosa placentaria requiere seguimiento estrecho del embarazo e inducir su finalización entre las semanas 37-38 para aminorar las complicaciones perinatales.

Abstract BACKGROUND Placental mesenchymal dysplasia is a rare disease of the placenta which presents with vesicles in the form of a cluster of grapes on ultrasound. It can cause pregnancy complications such as: intrauterine growth restriction, intrauterine death, and preterm birth CLINICAL CASE A 31-year-old patient with placental mesenchymal dysplacia diagnosed on the ultrasound of the first trimester of pregnancy, in which an area with 14 x 20 mm econegative formations was observed with little uptake of the color Doppler and which was confirmed in the second trimester by corial biopsy of that area. The pregnancy was normal until week 33, after which an intrauterine growth restriction was detected. Due to the high incidence of obstetric complications of this entity, an induction of labor was decided at week 37 of gestation. CONCLUSIONS Whenever this type of pathology is diagnosed, it is recommended a close follow-up of pregnancy and an induction of labor around 37-38 weeks of gestation, due to the perinatal complications presents.

Sarcoma sinovial monofásico de tipo fibroblástico. Evaluación diagnóstica por RM y postratamiento mediante ADC: Presentación de un caso / Monophasic Fibroblastic Synovial Sarcoma. Diagnostic and Post-Treatment Assessment by MRI and ADC: Case Report

El sarcoma sinovial representa entre el 2 al 10 % de todas las malignidades primarias de tejidos blandos, situándose en el cuarto lugar en frecuencia de los sarcomas de tejidos blandos. Es una neoplasia clasificada por la WHO (World Health Organization) bajo la categoría de tumores de diferenciación incierta, considerándose una malignidad entre intermedio y alto grado. El tratamiento estándar es la escisión quirúrgica, sin embargo, por su alta recurrencia y en los casos en que se asocia a metástasis o márgenes positivos después de la resección, se han planteado otros tratamientos como la quimio y radioterapia. La imaginología juega un papel importante en el diagnóstico, la estadificación y evaluación de la respuesta al tratamiento. Nuevas técnicas como el uso de difusión y mapas de ADC (Apparent Diffusion Coefficient, o coeficiente de difusión aparente) en resonancia magnética (RM) son útiles para evaluar las lesiones tumorales y la respuesta al tratamiento. En este artículo se presenta el caso de un paciente con un sarcoma sinovial monofásico, el diagnóstico por imágenes y evaluación del tratamiento mediante técnicas avanzadas de resonancia magnética como la difusión

Synovial sarcomas represent 2 to 10% of all the primary tissue malignancies and occupy the fourth place in the list of most common soft tissue sarcomas. According to the World Health Organization (WHO), this neoplasm is classified under the category of tumors of uncertain differentiation and is considered an intermediate to high-grade malignancy. Although the standard treatment is surgical excision, alternative treatments such as radiotherapy and chemotherapy have been proposed due to its high rate of recurrence in cases when it is associated with metastasis or positive resection margins. Imaging plays a key role in the diagnosis, staging and assessment of treatment of this disease. New techniques in Magnetic Resonance Imaging such as diffusion and Apparent Diffusion Coefficient (ADC) mapping are useful to further characterize these neoplastic lesions and to assess treatment response. In this article we present a patient with monophasic synovial sarcoma in which the use of these new imaging techniques was essential for the diagnosis and evaluation post-treatment.

Endometritis tuberculosa sin foco primario y dolor pélvico crónico / Tuberculous endometritis with no primary focus and chronic pelvic pain

Antecedentes: La tuberculosis genital y la endometritis tuberculosa es una forma de tuberculosis que continúa siendo frecuente en los países en desarrollo y habitualmente es secundaria a un foco primario pulmonar. Puede cursar de forma asintomática, o bien, producir síntomas como infertilidad primaria o secundaria, alteraciones menstruales o dolor pélvico crónico, entre otros. Caso clínico: Se presenta el caso de una paciente de 47 años en estudio por ginecología y urología por dolor pélvico crónico y sintomatología urinaria inespecífica de aproximadamente 6 meses de evolución. La ecografía transvaginal muestra contenido intracavitario escaso sugerente de piometra e imágenes trabeculares compatibles con sinequias uterinas. Mediante aspirado endometrial se extrae pus y muestra endometrial que se remite para estudio anatomopatológico. Tras el informe anatomopatológico que diagnostica inflamación crónica granulomatosa necrotizante, se solicita estudio por PCR y cultivo para micobacteriumm tuberculosis, siendo ambos positivos para el microorganismo. De este modo, se diagnosticó como endometritis tuberculosa sin existir afectación de otros órganos tras el estudio completo. Se realizó tratamiento con etambutol hidrocloruro, isoniacida, pirazinamida y rifampicina durante 2 meses y pirazinamida e isonicida durante 7 meses adicionales. Al final del tratamiento, la paciente mostraba clara mejoría de los síntomas y a la ecografía desaparición de la colección intracavitaria uterina.

Background: Genital tuberculosis and endometritis tuberculosa is a form of tuberculosis which remains prevalent in developing countries and is usually secondary to a pulmonary primary focus. It may be asymptomatic, or may produce symptoms such as primary or secondary infertility, menstrual disorders or chronic pelvic pain, among others. Clinical case: We present the case of a patient of 47-year who was studied by ginecology and urology for chronic pelvic pain and unspecific urinary symptoms since about 6 months. In transvaginal ultrasound pyometra and trabecular images compatible with uterine synechiae were observed. Endometrial samples were obtaining and sent for histopathologic examination which was informed of chronic necrotizing granulomatous inflammation. We asked for PCR and culture for tuberculosis micobacteriumm, both being positive for the microorganism. Thus, she was diagnosed of endometritis tuberculosa without involvement of other organs after complete study. She performed a treatment with ethambutol hydrochloride, isoniazid, rifampicin and pyrazinamide for 2 months and pyrazinamide and isoniazid for 7 months. At the end of treatment, the patient showed clear improvement of symptoms and disappearance of uterine intracavitary collection in the ultrasonographic study.

Describen la utilidad de la resonancia magnética en el diagnóstico del cáncer de cerviz: [revisión] / Advances in imaging diagnosis, scheduling and radiotherapy for cervical cancer: [review]

La resonancia magnética (RM) es una herramienta de gran ayuda para la evaluación del cáncer de cérvix. Cuando se integra junto a los hallazgos clínicos, permite optimizar el plan de tratamiento. En el cáncer de cérvix la RM es superior a otras modalidades de diagnóstico por imágenes, tanto para la estadificación local como para la identificación de recurrencias locales. Esta preferencia se debe al desarrollo de nuevas secuencias y antenas, la introducción de nuevos agentes de contraste y la evidencia acumulada durante los últimos años de la gran eficacia de la RM en la evaluación y manejo del cáncer de cérvix. Las principales limitaciones de la estadificación clínica son la evaluación del parametrio, la invasión de la pared pélvica, la extensión proximal del tumor y la evaluación de las metástasis línfáticas. La RM es la técnica más precisa para el estudio de estas estructuras, ya que tiene un importante papel para determinar el volumen tumoral, la localización, el estadio y la extensión proximal con vistas a una posible cirugía con preservación de la fertilidad. En un futuro cercano, el desarrollo de nuevas técnicas incrementará su potencial en el diagnóstico y seguimiento de estas pacientes. La secuencia ponderada en difusión es una técnica recientemente introducida basada en difusión molecular, muy útil para discriminar entre lesiones benignas y malignas y para el estudio de diseminación peritoneal.