Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia with dream-enactment behaviors occurring during REM sleep and associated with the lack of the physiological REM sleep muscle atonia. It can be isolated and secondary to other neurological or medical conditions. Isolated RBD heralds in most cases a neurodegenerative condition due to an underlying synucleinopathy and consequently its recognition is crucial for prognostic implications. REM sleep without atonia on polysomnography is a mandatory diagnostic criterion. Different conditions may mimic RBD, the most frequent being obstructive sleep apnea during sleep, non-REM parasomnia, and sleep-related hypermotor epilepsy. These diseases might also be comorbid with RBD, challenging the evaluation of disease severity, the treatment choices and the response to treatment evaluation. Video-PSG is the gold standard for a correct diagnosis and will distinguish between different or comorbid sleep disorders. Careful history taking together with actigraphy may give important clues for the differential diagnosis. The extreme boundaries of RBD might also be seen in more severe and complex conditions like status dissociatus or in the sleep disorders’ scenario of anti IgLON5 disease, but in the latter both clinical and neurophysiological features will differ. A step-by-step approach is suggested to guide the differential diagnosis.
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