Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer's disease (ALFASleep project): protocol for an observational study

INTRODUCTION: The growing worldwide prevalence of Alzheimer's disease (AD) and the lack of effective treatments pose a dire medical challenge. Sleep disruption is also prevalent in the ageing population and is increasingly recognised as a risk factor and an early sign of AD. The ALFASleep project aims to characterise sleep with subjective and objective measurements in cognitively unimpaired middle/late middle-aged adults at increased risk of AD who are phenotyped with fluid and neuroimaging AD biomarkers. This will contribute to a better understanding of the pathophysiological mechanisms linking sleep with AD, thereby paving the way for the development of non-invasive biomarkers and preventive strategies targeting sleep. METHODS AND ANALYSIS: We will invite 200 participants enrolled in the ALFA+ (for ALzheimer and FAmilies) prospective observational study to join the ALFASleep study. ALFA+ participants are cognitively unimpaired middle-aged/late middle-aged adults who are followed up every 3 years with a comprehensive set of evaluations including neuropsychological tests, blood and cerebrospinal fluid (CSF) sampling, and MRI and positron emission tomography acquisition. ALFASleep participants will be additionally characterised with actigraphy and CSF-orexin-A measurements, and a subset (n=90) will undergo overnight polysomnography. We will test associations of sleep measurements and CSF-orexin-A with fluid biomarkers of AD and glial activation, neuroimaging outcomes and cognitive performance. In case we found any associations, we will test whether changes in AD and/or glial activation markers mediate the association between sleep and neuroimaging or cognitive outcomes and whether sleep mediates associations between CSF-orexin-A and AD biomarkers. ETHICS AND DISSEMINATION: The ALFASleep study protocol has been approved by the independent Ethics Committee Parc de Salut Mar, Barcelona (2018/8207/I). All participants have signed a written informed consent before their inclusion (approved by the same ethics committee). Study findings will be presented at national and international conferences and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04932473

Concomitant completeley ossified trigeminal pore and Dorello’s canal

Commonly, the trigeminal and abducens nerve course to the middle cranial fossa, beneath the tentorial border (posterior petroclinoid dural ligament) and, respectively, beneath Grüber’s petrosphenoidal ligament, in Dorello’s canal. It is hereby reported a rare unilateral association of anatomic variants which was found when the brain computed tomography angiography of a 56 y.o. male patient was observed. On the left side the tentorial border was ossified above the petrous apex, resulting a tentorial bar long of 1.96 cm that transformed the trigeminal pore into a completely ossified one. On that side was also found an ossified petrosphenoidal ligament determining a completely ossified Dorello’s canal. On the opposite side a 2.9 mm long clinoid bar extended from the posterior clinoid process to the anterior one. Although these bars are not common for humans they should be documented in computed tomography in cases with associated trigeminal neuralgia and abducens nerve palsy

Elevations in High-Sensitive Cardiac Troponin T and N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Serum Can Predict the Development of Anthracycline-Induced Cardiomyopathy.

BackgroundAnthracyclines remain the cornerstone of the treatment in many cancers including lymphomas, leukemia and sarcomas, and breast cancer. The cardiomyopathy that develops from anthracyclines can lead to heart failure and decreased survival. Multiple mechanisms are involved in the pathophysiology of anthracycline-induced heart failure.Study questionWe hypothesize that anthracycline-induced cardiac (AIC) pathology can be monitored using a panel of blood biomarkers including high-sensitive cardiac troponin T (hs-cTnT) for myocyte necrosis and N-terminal prohormone brain natriuretic peptide (NT-proBNP) for parietal stress.Study designA prospective, institutionally approved study recruited all patients with cancer scheduled to start anthracycline chemotherapy in the Transylvania University cancer clinics.Measures and outcomesTransthoracic 2D echocardiography and the measurements of NT-proBNP and hs-cTnT plasma levels were performed at the beginning of the study and 3 months and 6 months after anthracycline treatment initiation.ResultsThe plasma levels of hs-cTnT at 3 months (rho = 0.439, P = 0.0001) and 6 months (rho = 0.490, P = 0.0001) are correlated with AIC occurrence. For a cutoff value of hs-cTnT at 3 months > 0.008 ng/mL, we obtained 66.7% sensitivity and 67.9% specificity for developing AIC at 6 months, with a 54.5% positive predictive value and a 87.8% negative predictive value. The NT-proBNP serum levels at 3 months (rho = 0.495, P = 0.0001) and 6 months (rho = 0.638, P = 0.0001) are correlated with an AIC diagnosis at 6 months. For a cutoff value of NT-proBNP at 3 months >118.5 pg/mL, we obtained 80% sensitivity and 79.2% specificity for evolution to AIC at 6 months, with 52.2% positive predictive value and 93.3% negative predictive value.ConclusionsIn anthracycline-treated cancer patients, the increase in plasma levels of NT-proBNP and of hs-cTnT can predict the development of anthracycline-induced cardiomyopathy. Early identification of at-risk patients will potentially allow for targeted dose reductions and will diminish the number of patients developing cardiac pathology

Neuropsychological alterations and neuroradiological findings in patients with post-traumatic concussion: results of a pilot study

Introduction: Mild traumatic brain injury brain injury (mTBI) has traditionally been considered to cause no significant brain damage since symptoms spontaneously remit after a few days. However, this idea is facing increasing scrutiny. The purpose of this study is to demonstrate the presence of early cognitive alterations in a series of patients with mTBI and to link these findings to different markers of brain damage. Methods: We conducted a prospective study of a consecutive series of patients with mTBI who were evaluated over a 12-month period. Forty-one (3.7%) of the 1144 included patients had experienced a concussion. Patients underwent a routine clinical evaluation and a brain computed tomography (CT) scan and were also administered a standardised test for post-concussion symptoms within the first 24 h of mTBI and also 1-2 weeks later. The second assessment also included a neuropsychological test battery. The results of these studies were compared to those of a control group of 28 healthy volunteers with similar characteristics. Twenty patients underwent a magnetic resonance imaging (MRI) scan. Results: Verbal memory and learning were the cognitive functions most affected by mTBI. Seven out of the 20 patients with normal CT findings displayed structural alterations on MR images, which were compatible with diffuse axonal injury in two cases. Conclusions: Results from this pilot study suggest that early cognitive alterations and structural brain lesions affect a considerable percentage of patients with post-concussion syndrome following mTBI. Resumen: Introducción: Los traumatismos craneoencefálicos leves (TCE-L) han sido tradicionalmente considerados acontecimientos sin repercusiones cerebrales significativas, cuya sintomatología remite espontáneamente en unos días. Sin embargo, estos hechos son cada vez más cuestionados. Este estudio pretende objetivar la existencia de alteraciones cognitivas precoces en una serie de pacientes con TCE-L y relacionar los hallazgos con distintos marcadores de lesión cerebral. Métodos: Estudio prospectivo de una cohorte de pacientes con un TCE-L valorados de forma consecutiva durante 12 meses. De un total de 1.144 pacientes, se seleccionó a 41 (3,7%) que habían presentado una conmoción cerebral. Además de la valoración clínica habitual y de la práctica de una tomografía computarizada (TC) cerebral, los pacientes fueron estudiados mediante un test estandarizado para síntomas posconmocionales en las primeras 24 h después del TCE-L y al cabo de 1-2 semanas y, coincidiendo con la segunda valoración, mediante una batería neuropsicológica. Los resultados se compararon con los de un grupo de 28 voluntarios sanos de características parecidas. En 20 pacientes se practicó una resonancia magnética (RM) craneal. Resultados: En este análisis exploratorio, la memoria y el aprendizaje verbal fueron las funciones cognitivas más afectadas después del TCE-L. Siete de los 20 pacientes con TC cerebral normal presentaron alteraciones estructurales visibles por RM, que en dos casos fueron compatibles con la presencia de lesión axonal difusa. Conclusiones: Los resultados de este estudio piloto sugieren la presencia de alteraciones cognitivas precoces y lesiones cerebrales estructurales en un porcentaje no despreciable de pacientes que han presentado una conmoción cerebral recuperada después de un TCE-L. Keywords: Mild traumatic brain injury, Neuropsychological alterations, Diffuse axonal injury, Sport Concussion Assessment Tool 2, Susceptibility-weighted imaging, Post-concussion syndrome, Palabras clave: Traumatismo craneoencefálico leve, Déficits neuropsicológicos, Lesión axonal difusa, Sport Concussion Assessment Tool 2, Susceptibility weighted imaging, Síndrome posconmociona

Alteraciones neuropsicológicas y hallazgos neurorradiológicos en pacientes con conmoción cerebral postraumática. Resultados de un estudio piloto

Resumen: Introducción: Los traumatismos craneoencefálicos leves (TCE-L) han sido tradicionalmente considerados acontecimientos sin repercusiones cerebrales significativas, cuya sintomatología remite espontáneamente en unos días. Sin embargo, estos hechos son cada vez más cuestionados. Este estudio pretende objetivar la existencia de alteraciones cognitivas precoces en una serie de pacientes con TCE-L y relacionar los hallazgos con distintos marcadores de lesión cerebral. Métodos: Estudio prospectivo de una cohorte de pacientes con un TCE-L valorados de forma consecutiva durante 12 meses. De un total de 1.144 pacientes, se seleccionó a 41 (3,7%) que habían presentado una conmoción cerebral. Además de la valoración clínica habitual y de la práctica de una tomografía computarizada (TC) cerebral, los pacientes fueron estudiados mediante un test estandarizado para síntomas posconmocionales en las primeras 24 h después del TCE-L y al cabo de 1-2 semanas y, coincidiendo con la segunda valoración, mediante una batería neuropsicológica. Los resultados se compararon con los de un grupo de 28 voluntarios sanos de características parecidas. En 20 pacientes se practicó una resonancia magnética (RM) craneal. Resultados: En este análisis exploratorio, la memoria y el aprendizaje verbal fueron las funciones cognitivas más afectadas después del TCE-L. Siete de los 20 pacientes con TC cerebral normal presentaron alteraciones estructurales visibles por RM, que en 2 casos fueron compatibles con la presencia de lesión axonal difusa. Conclusiones: Los resultados de este estudio piloto sugieren la presencia de alteraciones cognitivas precoces y lesiones cerebrales estructurales en un porcentaje no despreciable de pacientes que han presentado una conmoción cerebral recuperada después de un TCE-L. Abstract: Introduction: Mild traumatic brain injury (mTBI) has traditionally been considered to cause no significant brain damage since symptoms spontaneously remit after a few days. However, this idea is facing increasing scrutiny. The purpose of this study is to demonstrate the presence of early cognitive alterations in a series of patients with mTBI and to link these findings to different markers of brain damage. Methods: We conducted a prospective study of a consecutive series of patients with mTBI who were evaluated over a 12-month period. Forty-one (3.7%) of the 1144 included patients had experienced a concussion. Patients underwent a routine clinical evaluation and a brain computed tomography (CT) scan, and were also administered a standardised test for post-concussion symptoms within the first 24 hours of mTBI and also 1 to 2 weeks later. The second assessment also included a neuropsychological test battery. The results of these studies were compared to those of a control group of 28 healthy volunteers with similar characteristics. Twenty patients underwent an MRI scan. Results: Verbal memory and learning were the cognitive functions most affected by mTBI. Seven out of the 20 patients with normal CT findings displayed structural alterations on MR images, which were compatible with diffuse axonal injury in 2 cases. Conclusions: Results from this pilot study suggest that early cognitive alterations and structural brain lesions affect a considerable percentage of patients with post-concussion syndrome following mTBI. Palabras clave: Traumatismo craneoencefálico leve, Déficits neuropsicológicos, Lesión axonal difusa, Sport Concussion Assessment Tool 2, Susceptibility weighted imaging, Síndrome posconmocional, Keywords: Mild traumatic brain injury, Neuropsychological alterations, Diffuse axonal injury, Sport Concussion Assessment Tool 2, Susceptibility-weighted imaging, Post-concussion syndrom

Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study

Background The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. Methods CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Findings Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13–15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30–66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOS