Nocturnal and sleep problems in PD

Transcription

1 4 rd Congress of the European Academy of Neurology Lisbon, Portugal, June 16-19, 2018 Teaching Course 11 EAN/MDS-ES: Evidence-based medicine in the treatment disabling motor and non-motor trouble in Parkinson's disease - Level 2 Nocturnal and sleep problems in PD Claudia Trenkwalder Kassel, Germany ctrenkwalder@gmx.de

2 Consultant/Expert Mundipharma, Britannia, Abbvie, UCB, Benevolent, Orion, Novartis Grants/Research M.J. Fox, European grant: program Horizon 2020 Honoraria/Speakers UCB, Mundipharma, Vifor, Grünenthal Book for PD patients (Schattauer publisher), PDSS2 Scale, European patent on Dyskinesias of PD Commercial interest no Sleep Disturbance in the night and changes of daytime alertness including somnolence and severe sleepiness are among the most frequent non-motor symptoms in Parkinson s Disease (PD). Recent numbers vary substantially, between 40-60% of PD patients may suffer from insomnia, 30-59% from REM sleep behavior disorder and 30% from excessive daytime sleepiness. RLS symptoms increase with advanced stages, with approximately 5-7% in de novo PD patients. Insomnia and Sleep Disruption Falling asleep in PD is often less distressing compared to maintaining sleep. Even years before PD has been diagnosed, many patients suffer from insomnia, as shown by primary care physicians in the UK. Insomnia includes problems falling asleep, mainting sleep and early awakenings. In the early phase of the disease these problems are intrinsic to PD, but lateron also promoted and reinforced by motor disability with nocturnal akinesia, painful dystonia, restless legs syndrome and further non-motor symptom such as dysuria, anxiety and depressed mood. Sleep maintenance 1

3 is often disturbed by two to five long awakenings during the night (twice more than controls), and it may increase with disease stage. Restless Legs Syndrome (RLS) and Dystonia Painful sensations at night are common and may also include restless legs syndrome in 12-21% og PD patients, which should always be specifically questioned about nocturnal painful phenomenons. RLS should also be differentiated form painful off-dystonia, which occurs more often in the early morning hours, when dopaminergic medications are wearing-off. There is still a debate, whether RLS is more frequent in PD patients compared to the general population, and if RLS is an early feature of PD, or even associated with PD medication. Several studies found an association with increasing dopaminergic medication over time in PD and the incidence of RLS. Prevalence rates were similar in de novo PD patients compared to age-matched controls in several studies from various countries. Two recent population based large studies from the US, however, describe an increased incidence of PD in patients with previous RLS. Diagnosis ascertainment of RLS in population based studies, however, remains difficult, and can interfer with other sleep disorders such as insomnia or RBD. In one of these studies, only patients with severe RLS over the first 4 years after diagnosis had a higher incidence of PD compared to non-rls controls. Other hypothesis claim, that RLS delineates a dopaminergic overstimulation in PD patients. Treatment of RLS in PD patients includes both levodopa or long-acting dopamine agonists such as rotigotine patch or even opioids to relief symptoms. Therapeutic studies of RLS in PD are not available, and any recommendation reflects only expert opinion. 2

4 Nocturnal Akinesia In addition to dystonia, severe nighttime bradykinesia may occur in more advanced stages of the disease. Bradykinetic patients have difficulties to turn in bed, re-adjust blankets or pillow, and get up at night to walk to the toilets. Some patients report many sleep interruptions to get up and pass urine, not knowing, if they wake up first and then walk to the toilet, or if they feel the urge to pass urine, and therefore wake up. Treatment of nocturnal akinesia includes an increase of dopaminergic stimulation at night. Long-acting Levodopa preparation have been tested, but evidence of efficacy in nocturnal akinesia was not proven. Ropinirole sustained release and rotigotine patch showed efficacy in placebo controlled studies to improve nocturnal akinetic symptoms and early morning-dystonia. REM Sleep Behavior Disorder Idiopathic RBD is defined by the International Classification of Sleep Disorders in its current 2014 version (ICSD-3) and is often associated with nightmares and violent behaviors. Patients with idiopathic RBD can fall out of bed or even hurt their bedpartner without memorizing the event in the next morning. Examples of RBD characterized by vocalizations, jerky movements of the extremities or the whole body, bed falls or complex movements are shown in videos taken from REM sleep recordings by polysomnography. Typically vocalizations are associated with motor events and the spectrum goes from murmuring, talking and laughing up to screaming. In the polysomnography an increased muscle tone of the chin during REM sleep with phasic and tonic activities can be recorded. RBD, first described by Carlos Schenck and Mark Mahowald, sometimes also called Schenck-Syndrome, is now recognized as a prodromal state of 3

5 neurodegenerative diseases associated with misprocessing of intracellular alpha-synuclein, thus facilitating the identification of an at-risk population. This hypothesis originates from long-term observations of spectacular, violent RBD cases in sleep centers, when patients with severe REM sleep episodes developed a Parkinson syndrome up to 18 years later. In clinically manifest PD, several studies have shown an association between RBD and a more severe course of the disease, cognitive impairment, postural instability and increased autonomic failures. Data from a large cohort of PD patients in various stages of the disease support the concept that RBD precedes a more advanced stage of neurodegeneration, suggesting RBD as a possible clinical progression marker. Several prodromal signs of RBD can be observed in de novo PD populations, such as small jerky movements during REM sleep, defined as REM-Behavioral Events (RBE), associated with dreaming contents, that may now be defined as prodromal RBD. Therapy of RBD in patients with PD consists of small doses of clonazepam (0.5-1mg) or melatonin (6-12mg) at night. Open studies and expert opinion is available, RCTs in PD patients are still lacking. Effects of Medication on Sleep In some patients, effect on sleep of dopaminergic agonists (which have been considered as stimulants for a long time) when given at bedtime, can be observed. At the extreme of this spectrum, some patients may use supra-optimal doses of levodopa and dopamine agonists day and night, and stay awake and hyperactive at night, using computers, gambling, having compulsive shopping on internet, or having hypersexuality, thus severly affecting quality of sleep and sleep efficacy. 4

6 For assessments of sleep in PD, several sleep scales have been validated and are currentl yin use for clinical practice and research. The most widely used scales to asseess nocturnal disabilities and sleep in PD are SCOPA-Sleep Scale and PDSS-2 (Parkinson Disease Sleep Scale, version2). These scales can also be used to assess efficacy of nocturnal treatments. In PD, the information brought by videopolysomnography is important and useful, provided that all aspects of the disease, including REM sleep and nocturnal wake are carefully analyzed. The video monitoring allows primaily to diagnose RBD, but also to recognize some other frequent nightrelated motor problems in PD, including cramps, dystonia, tremor, even dyskinesias and restless legs behavior and periodic limb movements in sleep and wakefulness. Sleep scoring may be particularly difficult and time-consuming in patients with PD, as many artefacts by moving impede the correct scoring. Video-analysis is also helpful in identifying sleep stages, as RBD may be confused with wakeful behaviors, and stridor needs to be identified. Currently, video-polysomnography is the only diagnostic tool to identify RBD properly, whereas scales are screening instruments with more or less sufficient sensitivity and specificity for RBD. In future studies, sleep should be used as an early marker for neurodegeneration and may include not only RBD, but also insomnia, sleep maintenance and subtle motor changes in non-rem sleep. 5

7 References Review Articles: Chahine LM, Amara AW, Videnovic A. A systematic review of the literature on disorders of sleep and wakefulness in Parkinson's disease from 2005 to Sleep Med Rev Aug 31. pii: S (16) doi: /j.smrv [Epub ahead of print] Review Postuma RB, Berg D. Advances in markers of prodromal Parkinson disease. Nat Rev Neurol Oct 27;12(11): doi: /nrneurol Review. Trenkwalder C, Arnulf I, Postuma R: Chapt. 87- Parkinsonism, In: Kryger M, Roth T, Dement W: Principles and Practice of Sleep Medicine, 6 th edition, Elsevier Saunders, Philadelphia, Restless legs syndrome associated with major diseases a systematic review and new concept. Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J. Neurology Apr 5;86(14): doi: /WNL Review. Original Publications: Comella CL, Nardine TM, Diederich NJ, Stebbins GT. Sleep-related violence, injury, and REM sleep behaviour disorder in Parkinson s disease. Neurology 1998; 51: Frauscher B, Iranzo A, Gaig C, et al. Normative EMG values during REM sleep for the diagnosis of REM sleep behavior disorder. Sleep 2012;35: Hagell P, Westergren A, Janelidze S, Hansson O. The Swedish SCOPA-SLEEP for assessment of sleep disorders in Parkinson's disease and healthy controls. Qual Life Res Oct;25(10): doi: /s Jacobs ML, Dauvilliers Y, St Louis EK, McCarter SJ, Romenets SR, Pelletier A, Cherif M, Gagnon JF, Postuma RB. Risk Factor Profile in Parkinson's Disease Subtype with REM Sleep Behavior Disorder. J Parkinsons Dis. 2016;6(1): doi: /JPD Mollenhauer B, Trautmann E, Sixel-Doring F, et al. Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology 2013;81: Muntean ML, Trenkwalder C, Walters AS, Mollenhauer B, Sixel-Doring F. REM Sleep Behavioral Events and Dreaming. J Clin Sleep Med

8 Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 1996; 46: Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med 2013;14: Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Prediagnostic presentations of Parkinson's disease in primary care: a case-control study. Lancet Neurol Jan;14(1): Sixel-Döring F, Trautmann E, Mollenhauer B, Trenkwalder C. Associated factors for REM sleep behavior disorder in Parkinson s disease. Neurology 2011; 77: Sixel-Döring F, Zimmermann J, Wegener A, Mollenhauer B, Trenkwalder C. The evolution of REM sleep behavior disorder in early Parkinson s disease. SLEEP 2015; 39: Trenkwalder C, Kohnen R, Högl B, Metta V, Sixel-Döring F, Frauscher B, Hülsmann J, Martinez-Martin P, Chaudhuri KR. Parkinson's disease sleep scale--validation of the revised version PDSS-2. Mov Disord Mar;26(4): doi: /mds Trenkwalder C, Kies B, Rudzinska M, Fine J, Nikl J, Honczarenko K, Dioszeghy P, Hill D, Anderson T, Myllyla V, Kassubek J, Steiger M, Zucconi M, Tolosa E, Poewe W, Surmann E, Whitesides J, Boroojerdi B, Chaudhuri KR; Recover Study Group.. Rotigotine effects on early morning motor function and sleep in Parkinson's disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord Jan;26(1):90-9. doi: /mds

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