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BACKGROUND: Isolated rapid eye movement sleep behavioral disorder (iRBD) can precede neurodegenerative diseases. There is an urgent need for biomarkers to aid early intervention and neuroprotection. OBJECTIVE: The aim is to assess quantitative motor, cognitive, and brain magnetic resonance imaging (MRI) characteristics in iRBD patients. METHODS: Thirty-eight polysomnography-confirmed iRBD patients and 28 age- and sex-matched healthy controls underwent clinical, cognitive, and motor functional evaluations, along with brain MRI. Motor tasks included nine-hole peg test, five-times-sit-to-stand test, timed-up-and-go test, and 4-meter walking test with and without cognitive dual task. Quantitative spatiotemporal gait parameters were obtained using an optoelectronic system. Brain MRI analysis included functional connectivity (FC) of the main resting-state networks, gray matter (GM) volume using voxel-based morphometry, cortical thickness, and deep GM and brainstem volumes using FMRIB's Integrated Registration and Segmentation Tool and FreeSurfer. RESULTS: iRBD patients relative to healthy subjects exhibited a poorer performance during the nine-hole peg test and five-times-sit-to-stand test, and greater asymmetry of arm-swing amplitude and stride length variability during dual-task gait. Dual task significantly worsened the walking performance of iRBD patients more than healthy controls. iRBD patients exhibited nonmotor symptoms, and memory, abstract reasoning, and visuospatial deficits. iRBD patients exhibited decreased FC of pallidum and putamen within the basal ganglia network and occipital and temporal areas within the visuo-associative network, and a reduced volume of the supramarginal gyrus. Brain functional alterations correlated with gait changes. CONCLUSIONS: Subtle motor and nonmotor alterations were identified in iRBD patients, alongside brain structural and functional MRI changes. These findings may represent early signs of neurodegeneration and contribute to the development of predictive models for progression to parkinsonism. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Background: First-line use of bevacizumab for glioblastoma (GBM) was evaluated in 2 phase 3 randomized controlled trials (RCT), demonstrating an impact on progression-free survival but not overall survival (OS). However, the crossover events of these trials raised concerns regarding the reliability of this latter analysis. In this study, we conducted an external control-based reassessment of the bevacizumab efficacy in newly diagnosed GBM (ndGBM) against the standard Stupp protocol. Methods: A systematic review of the literature was conducted to identify the phase 3 RCTs in ndGBM incorporating the Stupp protocol as an arm. For the selected studies, we extracted individual patient survival pseudodata of the Stupp protocol arm by digitizing the Kaplan-Meier plots. A comprehensive pipeline was established to select suitable control studies as external benchmarks. Results: Among the 13 identified studies identified in our systematic review, 4 studies resulted as comparable with the AVAglio trial and 2 with the RTOG 0825. Pooled individual patient pseudodata analysis showed no differences in terms of OS when bevacizumab was added to the Stupp protocol. Conclusions: The external-controlled-based reassessment of the bevacizumab treatment in ndGBM confirmed its lack of efficacy in extending OS. Our study includes a summary table of individual patient survival pseudodata from all phase 3 RCTs in ndGBM employing the Stupp protocol and provides a pipeline that offers comprehensive guidance for conducting external control-based assessments in ndGBM.