Neuroimaging of Sleep Disturbances in Movement Disorders

Abstract

Sleep dysfunction is recognized as a distinct clinical manifestation in movement disorders, often reported early on in the disease course. Excessive daytime sleepiness, rapid eye movement sleep behavior disorder and restless leg syndrome, amidst several others, are common sleep disturbances that often result in significant morbidity. In this article, we review the spectrum of sleep abnormalities across atypical Parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as well as Parkinson's disease (PD) and Huntington's disease (HD). We also explore the current concepts on the neurobiological underpinnings of sleep disorders, including the role of dopaminergic and non-dopaminergic pathways, by evaluating the molecular, structural and functional neuroimaging evidence based on several novel techniques including magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Based on the current state of research, we suggest that neuroimaging is an invaluable tool for assessing structural and functional correlates of sleep disturbances, harboring the ability to shed light on the sleep problems attached to the limited treatment options available today. As our understanding of the pathophysiology of sleep and wake disruption heightens, novel therapeutic approaches are certain to transpire.

Keywords: Parkinson's disease; REM behavior sleep disorder; atypical Parkinsonism; excessive daytime sleepiness; magnetic resonance imaging; neuroimaging; positron emission tomography; sleep.

Figure 1

Summary of sleep disturbances found in movement disorders. Movement disorders exhibit some overlap in sleep disturbances. PSP and CBS are tauopathies (green), PD and MSA are synucleinopathies (yellow) and HD is a hereditary disorder (blue). PSP, progressive supranuclear palsy; CBS, corticobasal syndrome; PD, Parkinson's disease; MSA, multiple system atrophy; HD, Huntington's disease; EDS, excessive daytime sleepiness; RBD, REM behavior sleep disorder, RLS, restless leg syndrome; PLMD, periodic limb movement disorder; OSA, obstructive sleep apnoea.

Figure 2

Sleep patterns and stages. (A) A complete sleep cycle typically takes, on average, between 90 and 110 min. There are two fundamental types of sleep: rapid eye movement (REM) sleep and non-REM sleep, which can be divided into stages I–IV. These non-REM stages correspond to the accumulating depth of sleep, as reflected by the progressive emergence of high-voltage, low-frequency brain wave activity, which dominate the deepest stages of non-REM sleep (stage III and IV, also identified as slow-wave sleep). Cardinal wave activity of stage II are sleep spindle and K-complex waveforms, who's timings are influenced by a slow oscillation (<1 Hz). REM sleep, also identified as active or paradoxical sleep, is characterized by wake-like, high-frequency, low-amplitude activity and atonia (i.e., low muscle tone). (B) During each of the four to five cycles that transpire each night of adult human sleep, non-REM (blue bars) and REM sleep (red bars) alternate. During the earlier proportion of the night, non-REM sleep is deeper, occupying a disproportionately large amount of time, particularly within the first cycle where the REM stage may be brief or terminated. As the night progresses, non-REM sleep becomes shallow, with more of each cycle being allocated to REM. A reliable oscillator times the sustained period of length of the non-REM and REM cycle, of which the amplitude varies according to extrinsic factors.