Review ArticleOverview of sleep disturbances and their management in Parkinson plus disorders
Introduction
Sleep is a basic and indispensable physiological requirement. Sleep disturbances often result in the poor quality of life in patients with neurodegenerative disorders [1,2]. Sleep disturbance is one of the commonly reported non-motor symptoms (NMS) in patients with Parkinson's disease (PD) as well as in those with Parkinson plus disorders [3,4]. Sleep disturbances are well studied in patients with PD. In fact, sleep-wake disturbances have been described as one of the premotor symptoms of PD [5,6]. However, the literature on sleep disturbances in Parkinson plus disorders such as multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS) is not as robust as that in PD. This is perhaps because of the relatively lower prevalence of Parkinson plus disorders [7]. Nevertheless, as sleep disturbances are common in Parkinson plus disorders, it is important to know the spectrum of sleep disorders and their impact on the quality of life in these patients. As the synucleinopathies (MSA, DLB) often differ from tauopathies (PSP, CBS), insights into the associated sleep disturbances may improve the understanding in certain aspects of the pathological substrates of the Parkinson plus disorders. This article comprehensively reviews the spectrum of sleep disturbances in the Parkinson plus disorders and discusses the practical approach to their management.
We followed the relevant criteria of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to review the literature [8]. We searched PubMed and MEDLINE till December 2019 using a combination of words “Sleep disturbance” with additional search terms such as: “Synucleinopathy”, “Tauopathy”, “multiple system atrophy”, “dementia with Lewy bodies”, “progressive supranuclear palsy”, and “corticobasal syndrome” (Fig. 1). During the initial screening of the abstracts/full texts, the publications that were published in languages other than English were excluded. After removing the duplicates, the references from the articles were also thoroughly searched for any missed articles. A total of 116 articles were included for this review. Details of keywords used for database search and search results are provided in Table 1.
Section snippets
Sleep disturbances in Multiple System Atrophy (Table 2)
MSA is an adult-onset, sporadic, neurodegenerative disorder. The prevalence of MSA is 4–5/100,000 in the population [9]. The commonly reported sleep disorders in patients with MSA include Rapid Eye Movement (REM) sleep behaviour disorder (RBD), sleep-disordered breathing (SDB), reduced and fragmented sleep, and excessive daytime sleepiness [10].
Sleep disturbances in patients with DLB (Table 3)
Dementia with Lewy bodies (DLB) is the second most common type of dementia which is characterized by α-synuclein neuronal inclusions (Lewy bodies, and Lewy neurites), accompanied by neuronal loss. It is usually presented with cognitive impairment (progressive and fluctuating cognitive decline) along with psychiatric (complex as well as detailed visual hallucinations) and motor impairments (Parkinsonism) [46,47]. Sleep disorders are common in DLB, ranging from 44% to 55%, with RBD being one of
Sleep disturbances in patients with PSP (Table 4)
PSP is characterized by the deposition of tau protein and neuropil threads in the pallidum, subthalamic nucleus, substantia nigra, striatum, red nucleus, pontine tegmentum, oculomotor nucleus, medulla, and the dentate nucleus [69,70]. Postural instability is a common early feature of PSP. Besides, other parkinsonian signs such as tremor, rigidity, bradykinesia, and other extrapyramidal signs such as myoclonus and dystonia may complicate the course of PSP. In addition to these core features,
Sleep disturbances in patients with CBS (Table 5)
CBS is a rare syndrome having a distinctive clinical picture with the involvement of the cortex and basal ganglia dysfunction [85]. CBS features include an asymmetric limb rigidity, dystonia, cognitive impairment and ideomotor and/or limb apraxia [86]. The features of CBS often overlap with that of frontotemporal dementia (FTD), AD, and PSP.
The classic presentation is with asymmetric limb rigidity, dystonia, and ideomotor apraxia. CBS is increasingly also recognized to present with features
Pathophysiology of sleep disorders
Sleep is divided into two independent stages: NREM and REM stage. NREM is further divided into three stages (N1, N2 and N3). This classification was given by the American Academy of Sleep Medicine (AASM) task force. The neuroanatomical substrates for NREM sleep include sleep promoting neurons in the ventrolateral preoptic and median reoptic neurons of the anterior hypothalamus. In addition, there are wake promoting neurons in the tuberomammillary nuclei of the posterior hypothalamus, basal
Approach to patients with sleep disorders
Detailed history and examination are a key to diagnose sleep disorders in these patients. This should include detailed sleep history using a sleep questionnaire. The sleep questionnaire should include questions pertaining to sleep complaints, sleep patterns, any abnormal behaviour during sleep, difficulty in initiating or maintaining sleep, daytime sleepiness, daytime functioning, snoring, abnormal limb movements and/or vocalizations etc. Patients should be advised to maintain a sleep diary or
Treatment options for sleep in Parkinson plus disorders
Clonazepam and melatonin have traditionally been used to ameliorate RBD-associated symptoms [107]. However, two recent randomized, placebo-controlled, double-blinded trials reported no significant benefit with the use of melatonin for the treatment of RBD [108,109]. However, previous studies on melatonin reported reduction not only in the severity of the injurious behaviour but also in the amount of REM sleep without atonia (with a starting dose of 3 mg/d and up to a dose of 12 mg/d) [110].
Limitations
There are few limitations in our review. Most of the studies included in our review have a small sample size. The diagnosis of sleep disturbances in these studies were based on sleep questionnaires in majority that is prone for recall and selection bias. In addition, patients can have confounding factors also such as depression, anxiety that can contribute to sleep disturbances. Hence, large scale systematic studies that includes polysomnography are required to address these sleep disorders in
Conclusions
A wide spectrum of sleep disturbances may complicate the disease course of patients with Parkinson plus disorders. Certain sleep disorders such as RBD provides a useful clue towards the nature of the underlying pathology. For example, RBD is a common feature of synucleinopathies whereas it is relatively rare in tauopathies. As sleep disturbances substantially worsen the quality of life of the patients who are already burdened with the relentless course of the Parkinson plus disorders, it is
Financial Disclosure/Conflict of Interest
None of the authors has any financial disclosure to make or have any conflict of interest.
Source of funding
None.
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