Sleep Disorders in Adults with Prader-Willi Syndrome: Review of the Literature and Clinical Recommendations Based on the Experience of the French Reference Centre

Prader–Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients’ caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures

Automated hippocampal segmentation in 3D MRI using random undersampling with boosting algorithm

The automated identification of brain structure in Magnetic Resonance Imaging is very important both in neuroscience research and as a possible clinical diagnostic tool. In this study, a novel strategy for fully automated hippocampal segmentation in MRI is presented. It is based on a supervised algorithm, called RUSBoost, which combines data random undersampling with a boosting algorithm. RUSBoost is an algorithm specifically designed for imbalanced classification, suitable for large data sets because it uses random undersampling of the majority class. The RUSBoost performances were compared with those of ADABoost, Random Forest and the publicly available brain segmentation package, FreeSurfer. This study was conducted on a data set of 50 T1-weighted structural brain images. The RUSBoost-based segmentation tool achieved the best results with a Dice’s index of (Formula presented.) (Formula presented.) for the left (right) brain hemisphere. An independent data set of 50 T1-weighted structural brain scans was used for an independent validation of the fully trained strategies. Again the RUSBoost segmentations compared favorably with manual segmentations with the highest performances among the four tools. Moreover, the Pearson correlation coefficient between hippocampal volumes computed by manual and RUSBoost segmentations was 0.83 (0.82) for left (right) side, statistically significant, and higher than those computed by Adaboost, Random Forest and FreeSurfer. The proposed method may be suitable for accurate, robust and statistically significant segmentations of hippocampi

Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer's dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis

Overnight caudo-rostral displacement of the fluid accumulated in the legs (new physiopathologic approach of obstructive sleep apnea and therapeutic perspectives)

Les apnées obstructives du sommeil (AOS) sont grevées d'une importante morbi-mortalité et leur prévalence est élevée. Les AOS se caractérisent par des épisodes répétés de collapsus des voies aériennes supérieures (VAS), mais la physiopathologie de ce collapsus reste imparfaitement élucidée. Nous montrons ici, chez des hommes non obèses, un lien fort et indépendant entre la fréquence d apnées et hypopnées pendant le sommeil (index d apnées-hypopnées [IAH]) et la quantité de fluide déplacé des jambes vers la région cervicale qui survient la nuit au cours du sommeil. Nous montrons aussi, chez des hommes non obèses présentant des AOS et un mode de vie sédentaire et chez des patients présentant des AOS et souffrant d insuffisance veineuse chronique, que la prévention de l accumulation de liquide dans les membres inférieurs pendant la journée, au moyen des bas de contention, et par conséquence du déplacement rostral de ce fluide pendant la nuit,diminue la gravité des AOS. Ces données démontrent sans ambiguïté que l'accumulation de fluide au niveau des membres inférieurs pendant la journée est un facteur favorisant du collapsus des VAS caractéristique des AOS, et ceci au travers de la redistribution de ce liquide vers la partie supérieure du corps (dont la région cervicale) lors du passage en position couchée. Du point de vue thérapeutique, nous avons démontré qu'entraver l accumulation de liquide au niveau des membres inférieurs a un effet bénéfique sur les AOS. Les données issues des travaux regroupés au sein de cette thèse contribuent à une meilleure connaissance de la physiopathologie des AOS et ouvrent par ailleurs un certain nombre de perspectives thérapeutiquesPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Postural lung volume reduction, expiratory flow limitation, and orthopnoea in diaphragmatic weakness: Preliminary observations

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Diagnostic approach to sleep disordered-breathing among patients with grade III obesity

International audienceSleep apnea test (SAT) is a cost-effective approach to evaluate subjects without associated comorbidities suspected for obstructive sleep apnea (OSA), a disorder particularly common in obese subjects. The association of obesity with awake hypercapnia (carbon dioxide arterial pressure, PaCO2 ≥45 mmHg) defines the obesity-hypoventilation syndrome (OHS), which in turn results in increased morbidity and mortality compared to simple OSA. Isolated hypoventilation during sleep in obese patients (obesity-related sleep hypoventilation, ORSH) is now considered as an early stage of OHS. The aim of this study was to assess the performance of SAT in diagnosing OSA and predicting the presence of ORHS among patients with grade III obesity without awake hypercapnia. Methods: Over a 14-months period, patients with grade III obesity (body mass index≥40 kg/m 2) presenting moderate-to-severe OSA (apnea-hypopnea index [AHI]≥15) upon SAT and normal awake PaCO2 at arterial blood gas analysis, systematically underwent in-lab nocturnal polysomnography combined with transcutaneous carbon dioxide pressure (PtcCO2) monitoring. Results: Among 48 patients included in the study, 16 (33%) presented an AHI<15 upon polysomnography and 14 (29%) had ORSH. The test revealed no difference in ORSH prevalence between patients with AHI <15 or ≥15 (31% vs. 25%). No SAT variables were independently associated with increased PtCO2. Conclusions: This study shows that SAT overestimates OSA severity and ORSH affects one third of patients with grade III obesity without awake hypercapnia and with moderate-to-severe OSA at SAT, suggesting how polysomnography combined with PtCO2 monitoring is the most appropriate diagnostic approach for OSA and ORSH in this population

Targeted delivery of anti-cancer drug sorafenib through magnetic solid lipid nanoparticles

Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular carcinoma and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its insolubility and severe toxic side-effects. The aim of this study is to develop and characterize sorafenib-loaded magnetic nanovectors to deliver and accumulate drug just to the disease site with the help of a remote magnetic field. Sorafenib and superparamagnetic iron oxide nanoparticles were encapsulated in solid lipid nanoparticles (SLNs) by a hot homogenization technique, by using cetyl palmitate as lipid matrix. Biological effects were evaluated in vitro on human hepatocarcinoma HepG2. Our results confirm the possibility to prepare stable SLNs able to kill cancer cells through sorafenib cytotoxic effect, and to enhance/localize this effect in a desired area thanks to the magnetically- driven accumulation of the drug