REM sleep behavior disorder and synucleinopathies

Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) is a somnipathy characterized by a physiological failure of skeletal muscle atonia during REM sleep. Such a brainstem pathway disruption, which directly affects the pontomedullary reticular formation, disrupts the descending inhibitory pathways that normally cause muscle paralysis. Patients then are much more likely to act out their dreams and will have complex, often violent dream-enactment behaviors that may cause injury and disrupt sleep continuity. Almost two decades of research have shown that RBD is potentially a crucial early indicator for synucleinopathies (brain diseases that are related to the accumulation of alpha-synuclein protein). These diseases include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Emerging biomarkers, neuroimaging results, and fluid-based biomarkers are discussed in the context of risk stratification and prediction of phenotypic pathophysiological transformation to overt neurodegenerative disease. Moreover, the chapter discusses how RBD provides a window for testing neuroprotective and disease-modifying therapies that may delay or prevent overt synucleinopathy. It also reviews current symptom management approaches that mix pharmacological treatment with non-pharmacological safety measures for injury prevention and neuromodulation technologies that target disrupted motor circuitry. Understanding the relationship between RBD and synucleinopathies offers a unique window into the earliest stages of neurodegeneration and presents new possibilities for early diagnosis, targeted treatment, and better patient outcomes.