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Background: Isolated rapid-eye movement (REM) sleep behavior disorder (iRBD) is characterized by abnormal behaviors in REM sleep and is considered as a prodromal symptom of alpha-synucleinopathies. Resting-state functional magnetic resonance imaging (rsfMRI) studies have unveiled altered functional connectivity (rsFC) in patients with iRBD. However, the associations between intra- and inter-network rsFC with clinical symptoms and neuropsychological functioning in iRBD remain unclear., Objective: To characterize intra- and inter-network rsFC in iRBD patients using a data-driven approach and to assess its associations with clinical features and cognitive functioning., Methods: Forty-two patients with iRBD and 45 healthy controls (HC) underwent rsfMRI and comprehensive neuropsychological testing. Resting-state networks were characterized using independent component analyses. Group differences in intra- and inter-network rsFC and their associations with clinical and neuropsychological data were studied. A threshold of corrected P < 0.05 was used in all the analyses., Results: iRBD patients displayed lower intra-network rsFC within basal ganglia, visual, sensorimotor, and cerebellar networks, relative to HC. Mean rsFC strength within the basal ganglia network positively correlated with processing speed and negatively with the non-motor symptoms in iRBD patients. Reduced inter-network rsFC between sensorimotor and visual medial networks was observed in iRBD patients, which was associated with global cognitive status., Conclusions: iRBD is characterized by both reductions in intra-network rsFC in cortical and subcortical networks and inter-network dysconnectivity between sensorimotor and visual networks. Abnormalities in intra- and inter-network rsFC are associated with cognitive performance and non-motor symptoms, suggesting the utility of both rsFC measures as imaging markers in prodromal alpha-synucleinopathies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The diagnosis of isolated REM sleep behavior disorder (IRBD) requires video polysomnography (V-PSG) showing increased muscle activity and abnormal behaviors in REM sleep., Objective: To describe in IRBD the behavioral manifestations occurring during REM sleep in the diagnostic V-PSG., Methods: This is a systematic audiovisual V-PSG analysis of consecutive IRBD patients. According to the International RBD Study Group recommendations, REM sleep movements and vocalizations were classified into categories and severity., Results: We analyzed the V-PSG of 62 IRBD patients with a mean age of 67.6 ± 8.1 years. Of 6,330 30-s epochs of REM sleep, 55.1% epochs exhibited motor events, 5.5% contained vocalizations and 39.4% were silent. Among the epochs with motor manifestations, 66.1% contained simple minor movements, 25.0% simple major and 8.9% complex movements. Motor severity of the epochs was mild in 82.2%, moderate in 13.2% and severe in 4.6%. Most movements were bilateral (62.4%) and located in the upper limbs (42.5%). Of the epochs with vocalizations, 61.5% were simple minor, 20.7% complex and 17.8% simple major of mild (72.7%), moderate (23.0%) and severe (4.3%) severity. Complex movements occurred in 87.1% of the patients and complex vocalizations in 38.7%., Conclusions: In IRBD, the most common manifestations in REM sleep are simple minor movements and vocalizations of mild intensity. Complex movements are observed during REM sleep in most patients but are much less frequent than simple minor and major motor events. These findings should be considered for the routine diagnosis of IRBD when reviewing the V-PSG studies., Competing Interests: Declarations. Conflicts of interest: The authors had no financial disclosures and no conflict of interests concerning the research related to the current study. Ethics approval: The ethical committee of the Hospital Clinic de Barcelona approved this study (HCB/2023/0962)., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Anti-IgLON5 disease was identified 10 years ago, thanks to the discovery of IgLON5 antibodies and the joint effort of specialists in sleep medicine, neuroimmunology, and neuropathology. Without this collaboration, it would have been impossible to untangle fundamental aspects of this disease. After the seminal description in 2014, today there is growing evidence that most patients present a chronic progressive course with gait instability, abnormal movements, bulbar dysfunction, and a sleep disorder characterized by nonrapid eye movement and REM parasomnias, and obstructive sleep apnea with stridor. Unlike other autoimmune encephalitides, the response to immunotherapy is suboptimal. Neuropathologic studies in patients with a prolonged clinical course showed a novel 3-repeat and 4-repeat neuronal tauopathy mainly involving the hypothalamus and tegmentum of the brainstem. The absence of tau deposits in the brain of patients who died early, the demonstration that IgLON5 antibodies cause an irreversible decrease in cell-surface levels of IgLON5, and a disorganization of the neuronal cytoskeleton suggest that the disease is primarily autoimmune and the tauopathy a secondary event. After a decade, we now know the disease much better, but important issues still need to be addressed. We have to gather more information on the natural course of the disease, develop better treatments, and identify robust predictors of outcome. More basic research is needed on the physiology of IgLON5, how antibodies disrupt its function, and the downstream effects leading to neurodegeneration. Finally, better designed passive transfer and active immunization models are needed to confirm the pathogenic effect of IgLON5 antibodies.