Sleep Disorders in Parkinson’s Disease
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and affects 1-2% of adults over the age of 65 years. Its cardinal motor features are bradykinesia, rigidity, and tremor at rest. However, non-motor features have also been recognized as important constituents of PD and have marked effects on quality of life. Sleep disorders were found to be the second most prevalent non-motor feature in the PRIAMO study and up to 90% of PD patients experience some form of sleep dysfunction.
Sleep is divided physiologically into REM (rapid eye movement) and NREM (non-rapid eye movement) stages. These stages run cyclically throughout the night. Sleep disorders in PD include insomnia (difficulty with initiation and/or maintenance of sleep), excessive daytime sleepiness (EDS), restless legs syndrome (RLS), periodic limb movement of sleep (PLMS), REM sleep behavioral disorder (RBD), and obstructive sleep apnea (OSA). The pathophysiology of sleep disorders in PD is likely multifactorial due to underlying damage to key regions involved in sleep regulation and/or side effects of medications. There is a loss of hypocretin neurons in PD patients; hypocretin is known to promote wakefulness. Alterations in hormonal rhythms such as those of cortisol and melatonin are also seen in PD patients.
Excessive daytime sleepiness can impair alertness and the ability to stay awake, and can cause patient safety issues. Altered sleep architecture and disrupted sleep patterns may lead to EDS, but medications, especially dopamine agonists, have also been shown to contribute. Restless legs syndrome can affect around 30% of patients and is characterized by a marked urge to move the legs during periods of rest, especially while trying to sleep, and is relieved by moving the legs. Dopamine dysfunction and iron deficiency have been implicated, along with renal disease, type 2 diabetes, and pregnancy. Periodic limb movement of sleep (PLMS) is present in up to 80% of individuals with RLS. Breathing disorders such as obstructive sleep apnea are also a recognized feature of PD and can contribute to EDS, headache, and fatigue in the morning. RBD occurs when patients lose the usual muscle atonia associated with REM sleep, leading to dream enactment behaviors and/or vocalizations. The dreams can be vivid, unpleasant, and frightening and can occasionally cause the patient to fall out of bed. Over 80% of individuals with RBD go on to develop an overt ɑ-synucleinopathy—disorders of the protein alpha-synuclein, which include PD, multiple system atrophy (MSA), and dementia with Lewy bodies (DLB).
Management of sleep disorders in PD patients begins with simple measures which aim to ensure good sleep hygiene and optimal management of motor symptoms with avoidance of wearing off in between doses, especially at night. Patients are advised to regularize bed times, avoid alerting substances such as nicotine and caffeine in late evening, minimize prolonged time in bed watching TV or reading, limit excess fluid intake in late evening hours, and avoid exercising later in the day. Management of EDS includes avoiding frequent naps during the day to ensure restful sleep at night, limiting use of sedating medications such as dopamine agonists (which can also cause sleep attacks without warning), managing OSA at night, and occasional use of alerting substances such as caffeine, modafinil, armodafinil, etc., during the day. Patients with RLS require lab work for iron deficiency, renal disease, and diabetes, with appropriate management including iron replacement therapy where applicable. It is prudent to avoid medications known to exacerbate RLS such as antidepressants, antihistamines and antidopaminergic agents. For more severe RLS requiring medication management, drugs such as dopamine agonists, levodopa-carbidopa, gabapentin, pregabalin, and (in rare cases) opiates can be tried. Management of OSA requires polysomnography (sleep study) along with use of CPAP/BIPAP machines which aren’t necessarily tolerated by all patients due to discomfort with machinery. RBD can potentially result in injury to patient or bed partner, hence altering the sleep environment to make it safer (sleeping with a mattress on the floor, moving furniture and placing cushions next to the bed) is recommended. Medication management of RBD includes use of over-the-counter melatonin with upward dose titration to optimal benefit (higher doses up to 50 mg may be required at times to see benefit) and the prescription medication clonazepam, both taken 1-2 hours prior to bed. Sleep disturbances are quite common in patients with PD and comprise the entire spectrum of sleep disorders. These can not only contribute to reduced quality of life but can also raise safety concerns, hence appropriate diagnosis and management of these disorders is crucial.
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About Author: by Shilpa Chitnis, M.D., Ph.D., FAAN, FANA Professor of Neurology at UT Southwestern Medical Center