Clinical ReviewExcessive daytime sleepiness in parkinsonism
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.
References* (105)
- et al.
Pathophysiology of the basal ganglia in Parkinson's disease
Trends Neurosci
(2000) - et al.
Hypocretin (orexin) deficiency in human narcolepsy
Lancet
(2000) Sleep attacks (sleep episodes) with pergolide
Lancet
(2000)- et al.
Sleep attacks and Parkinson's disease treatment
Lancet
(2000) - et al.
Excessive daytime sleepiness in Parkinson's disease as assessed by Epworth Sleepiness Scale (ESS)
Sleep Med
(2003) - et al.
Levodopa motor complications in Parkinson's disease
Trends Neurosci
(2000) - et al.
Parkinson's disease and sleep
Sleep Med Rev
(2003) - et al.
‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975) - et al.
Assessment of sleepiness and unintended sleep in Parkinson's disease patients taking dopamine agonists
Sleep Med
(2003) - et al.
The effects of lesions of cathecolamin-containing neurons upon monoamine content of the brain and EEG and behavioral waking in the cat
Brain Res
(1973)
Brain structures and mechanisms involved in the control of cortical activation and wakefulness, with emphasis on the posterior hypothalamus and histaminergic neurons
Sleep Med Rev
Activity of mesencephalic dopamine and non-dopamine neurons across stages of sleep and waking in the rat
Brain Res
A novel effect of MPTP: the selective suppression of paradoxical sleep in cats
Brain Res
Continuous positive air pressure eliminates nocturnal stridor in multiple system atrophy. Barcelona Multiple System Atrophy Study Group
Lancet
Modafinil for the treatment of excessive daytime sleepiness in Parkinson's disease: a case-report
Parkinsonism Relat Disord
An essay on the shaking palsy
The night-time problems of Parkinson's disease
Clin Neuropharmacol
Troubles du sommeil dans la maladie de Steele-Richardson [in French]
Rev Neurol (Paris)
REM sleep behavior disorders in multiple system atrophy
Neurology
REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease
Neurology
Waking up to sleep episodes in Parkinson's disease
Mov Disord
Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole
Neurology
Sleep episodes in Parkinson's disease: a wake-up call
Mov Disord
Emerging views of dopamine in modulating sleep/wake state from an unlikely source: PD
Neurology
Pharmacologie, somnolence diurne anormale, ‘attaques de sommeil’ et médicaments antiparkinsoniens
Rev Neurol
Genetic classification of primary neurodegenerative disease
Science
The pathology of Parkinson's disease
Adv Neurol
Low levels of ventricular CSF orexin/hypocretin in advanced PD
Neurology
A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale
Sleep
Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the Epworth Sleepiness Scale: failure of the MSLT as a gold standard
J Sleep Res
Development of daytime somnolence over time in Parkinson's disease
Neurology
Evaluation of somnolence in Parkinson's disease: comparison with age- and sex-matched controls
Neurology
Sleep attacks and antiparkinsonian drugs: a pilot prospective pharmacoepidemiologic study
Clin Neuropharmacol
Excessive daytime sleepiness and sudden-onset sleep in Parkinson Disease. A survey by the Canadian Movement Disorder Group
JAMA
Falling asleep while driving: are drivers aware of prior sleepiness ?
Int J Legal Med
Predictors of sudden onset of sleep in Parkinson's disease
Mov Disord
Evaluation of sleep and driving performance in six patients with Parkinson's disease reporting sudden onset of sleep under dopaminergic medication: a pilot study
Mov Disord
Polysomnographic characterization of pergolide-induced sleep attacks in idiopathic PD
Neurology
Predictors of impaired daytime sleep and wakefulness in patients with Parkinson's disease treated with older (ergot) vs. newer (nonergot) dopamine agonist
Arch Neurol
FAST TRACK: daytime sleepiness in Parkinson's disease
J Sleep Res
Parkinson's disease and sleepiness: an integral part of PD
Neurology
Successful treatment of excessive daytime sleepiness in Parkinson's disease
J Neurol
Pramipexole-induced somnolence and episodes of daytime sleep
Mov Disord
Sudden daytime sleep onset in Parkinson's disease: polysomnographic recordings
Mov Disord
Unawareness of naps in Parkinson's disease and in disorders with excessive daytime sleepiness
Neurology
Hallucinations, REM sleep and Parkinson's disease
Neurology
Juvenile Parkinson's disease with REM sleep behavior disorder, sleepiness, and daytime REM onset
Neurology
Visual hallucinations as REM sleep behavior disorders in patients with Parkinson's Disease
Mov Disord
Hallucinations and sleep-wake cycle in PD: A 24-hour continuous polysomnographic study
Neurology
Daytime sleepiness and other sleep disorders in Parkinson's disease
Neurology
Cited by (0)
- *
The most important references are denoted by an asterisk.