Elsevier

Sleep Medicine Reviews

Volume 9, Issue 3, June 2005, Pages 185-200
Sleep Medicine Reviews

Clinical Review
Excessive daytime sleepiness in parkinsonism

https://doi.org/10.1016/j.smrv.2005.01.001Get rights and content

Summary

Excessive daytime sleepiness (EDS) can affect 20–50% of patients with Parkinson's disease (PD), whereas sleep attacks (SA), which are sleep episodes without prodroma, seem infrequent. EDS is associated with more advanced disease, higher doses of levodopa-equivalent, and sometimes the use of dopamine agonists. Patients at risk for SA have higher Epworth sleepiness scores (ESS) (although an important subset of patients under-score on this scale) and a more frequent use of ergot or non-ergot dopamine agonists. Polysomnography is a valuable tool in patients with PD, because sleep apnea may occur in 20% of patients, whereas a specific narcolepsy-like phenotype, identified on multiple-sleep latency tests, occurs in patients with most severe EDS; this suggests a lesion in sleep-wake systems. Removal or replacement of a recently introduced dopamine agonist may offer some relief for EDS. If not, the adjunction of modafinil has a good benefit—risk ratio in patients with PD. EDS (and sometimes the narcolepsy-like phenotype) may also affect patients with atypical parkinsonism, such as dementia with Lewy bodies, multiple-system atrophy, and progressive supranuclear palsy.

Introduction

Severe night-time sleep troubles were described as early as 1817 by James Parkinson,1 and have been reported since as excessively common in patients suffering from Parkinson's disease (PD),2 progressive supranuclear palsy,3 multiple-system atrophy,4 and dementia with Lewy bodies.5 However, the neurology community has only recently realised that excessive daytime sleepiness (EDS) can also be a disabling and potentially dangerous symptom in patients with parkinsonism.6 The starting point for this interest was the report of severe sleep attacks (SA) in patients treated with the new non-ergotic dopamine agonists pramipexole and ropinirole.7 The attention now given to such sleep attacks is possibly because they involve several groups: (1) patients who are at risk of road accidents but need to drive because of their walking disability; (2) society and its representatives for issuing driving licences, because road accidents can endanger the patient and other road users; (3) the pharmaceutical companies, who do not want to be held responsible for concealing a life-threatening side-effect, but also do not want to lose a potential high-growth market; (4) national and federal drug agencies, because they need to record new side-effects and react rapidly to inform prescribing neurologists and patients of this new risk; (5) neurologists who, having neglected this putative side-effect in patients with PD in the past, need to determine the benefit ratio of treatment, inform their patients, be able to detect the first signs, and also endorse a potential responsibility;6, 8 (6) pharmacologists, sleep researchers, and neuroscientists, because the dopaminergic system was long-time considered as an awakening system, and because the incompletely understood mechanisms of sleep attacks and sleepiness in patients with PD could shed new light on dopamine modulation of sleep-wake state.9, 10 Such SA have since been described in patients treated with ergotic dopamine agonists, levodopa, and catechol O-methyl transferase inhibitors. In addition, as addressed recently, night-time sleep troubles (including sleep deprivation caused by nocturnal pain and akinesia) and sleep fragmentation caused by sleep apnea and periodic leg movements are also a potential cause of EDS. The disease itself may eventually affect the sleep-wake system, as suggested by the report of narcolepsy-like sleepiness in treated and untreated patients with PD.35, 36 The effect of EDS on familial and social life can be severe enough to require drug treatment, such as modafinil, which seems to be compatible with the multi-treatment of patients with Parkinson's disease. The major topics discussed in this review include the clinical and pathological aspects of parkinsonism; the epidemiology of EDS and SA; the polysomnographic aspect of sleepiness; the putative mechanisms of sleepiness; sleepiness in disorders related to PD; and treatment of EDS.

Section snippets

Clinical features of parkinsonism

PD is a progressive neurodegenerative illness that affects about 1 million patients in North America. Parkinsonism includes a slowness of usual movements (akinesia), increased muscle tone (hypertonia), loss of postural reflexes, and possibly a rest tremor. The most frequent cause of this movement disorder is PD, which affects about 1% of middle-aged patients, with 85% sporadic and 15% genetic cases. Parkinsonism is also observed in other related neurodegenerative diseases: (1) patients

Excessive daytime sleepiness is more frequent and more severe in patients with Parkinson's disease than in controls

EDS refers to a disabling trend to nod or fall asleep in various situations that interferes with familial, professional, and social life. The most widely used scale is the Epworth Sleepiness Scale (ESS), which scores the tendency to fall asleep (from 0–3) during eight everyday situations.16 It ranges from 0–24, and abnormal somnolence is considered as a value greater than 10.17 Case-controlled epidemiological studies conducted in various countries consistently found higher ESS scores and a

Multiple-sleep latency test and 24-h polysomnography

In addition to epidemiological studies, several sleep studies aimed at characterizing the nature of sleepiness and SA have used 24-h ambulatory, in-hospital polysomnography or overnight polysomnography followed by MSLT or MWT. In two unselected prospective series of 27 and 80 patients with PD seen in the movement disorder clinics of the university hospital of Atlanta29 and Toronto,28 the MSLT latency was 11.0±6.1 (standard deviation) min and 12.1±5.1 min, respectively; 19 and 18.8% of the

Mechanisms of excessive daytime sleepiness

The mechanisms of sleepiness in PD have been investigated mostly using multivariate analysis of factors (age, sex, characteristics of the PD, of sleep, type and doses of drugs) in large epidemiological studies or in restricted laboratory studies. Interventional studies (removing or adding a drug), neuropathological data, and animal models of PD as other means of studying sleepiness in PD are rare. The aim of the epidemiological studies was also to identify the subset of patients at risk for EDS

Excessive daytime sleepiness in disorders related to Parkinson's disease

Other neurodegenerative diseases causing parkinsonism are progressive supranuclear palsy (a tauopathy), multiple-system atrophy, and dementia with Lewy bodies disease (the latter two being synucleopathies). So far, EDS has been poorly studied in these diseases, apart from our recent series. To our knowledge, no SA has been reported in these patients.

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