Parkinson. ior disorder RBD restless legs syndrome RLS. Parkinson Parkinson s disease PD James Parkinson wearing off

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1 1 Parkinson 2 Parkinson * ** ** ** *** Key Words : Parkinson s disease, sleep disorders, Parkinson disease sleep scale, insomnia, excessive daytime sleepiness Parkinson Parkinson s disease PD James Parkinson 1817 Comella PD PD REM sleep behavior disorder RBD PD Lewy Parkinson Disease Sleep Scale PDSS 2 3 PD PDSS PD 4 PD PD sleep bene fit 5 PD I PD PD REM sleep behav ior disorder RBD restless legs syndrome RLS PD 6 PD PD PD wearing off II PD PD RBD RBD RBDSQ 7, 8 PD EFNS/MDS ES PD RBD 9 Beck Beck depression in ventory II BDI II PDSS RLS PDSS 2 10, 11 Pathophysiology and Management of Sleep Disorders in Patients with Parkinson s Disease. Masayuki MIYAMOTO, Koichi HIRATA, Keisuke SUZUKI : Department of Neurology Dokkyo Medical University School of Medicine Tomoyuki MIYAMOTO : Department of Neurology Dokkyo Medical University Koshigaya Hospital 166

2 polysomnogra phy PSG PD PSG K complex REM sleep with out atonia RWA PLMS III PD PD Table brotizolam zopiclone zolpidem 15 eszopiclone 16 MaassPDPDSS 2 PD specific motor symptoms RLS PD spe cific non motor symptoms sleep specific symptoms 17 PD PD PD Parkinson rotigotine ropinirole 18, 19 nortriptyline SSRI sertraline fluvoxamine pramipexole 15 D1 oxybutynin flavoxate 15 RBDclonazepam 15 Table 1 Treatment strategies of insomnia in Parkinson s disease Idiopathic insomnia sleep hygyne short acting benzodiazepine receptor agonist Difficulty initiating sleep brotizolam, zopiclone, Difficulty maintaining sleep, waking zolpidem, eszopiclone up too early or poor sleep quality Nocturnal problems PD specific motor symptoms Optimazed PD treatment regimen L DOPA/DCI dopamine agonist rotigotine, ropinirole prolonged release Effect of dopaminergic drugs Optimazed PD treatment regimen Noctruria D1 receptor agonists, oxybutynin, flavoxate Depression nortriptyline, SSRI, pramipexole REM sleep behavior disorder secure the bed environment, clonazepam Restless legs syndrome Dopamine agonist pramipexole, rotigotine Gabapentin Enacarbil, clonazepam IV PD Adams Stokes PD Gar cia Borreguero OndoPD PD 23 PD PD PD PD Table 2 PD , 26 histamine dopamine 167

3 Table 2 Treatment strategies of excessive daytime sleepiness in Parkinson s disease Effects of medications Dopamine agonists Dose reduction or switch to another drug Sedatives Eliminate if possible Poor sleep quality PD specific motor symptoms Optimazed PD treatment regimen Obstructive sleep apnea nasal CPAP therapy Arousal disorder due to PD Modafinil pathology Caffeine MAO B inhibitor selegiline arousal system 27 PD narcolepsy like phenotype 28 D2/D3 pramipexole ropinirole 29 bromocriptine cabergoline pergolide 30 Ondo ventral tegmental area VTA D2/D3 22 PD D2 D3 D4 polymorphism 31 D2 polymorphism 32 preprohypocretin polymorphism 33 Table 2 PD continuous positive airway pressure CPAP PDmodafinil caffeine Modafinil 2 34, caffeine MAO Bselegiline selegiline 2.5mg/day 1 37 PD 38 selegiline L amphetamine L methamphetamine MAO A V PD quality of life QOL COI 1 Comella CL : Sleep disorders in Parkinson s disease. Sleep Med Clin 3 : , Chaudhuri KR, Pal S, DiMarco A et al : The Parkinson s dis ease sleep scale: a new instrument for assessing sleep and noc turnal disability in Parkinson s disease. J Neurol Neurosurg Psychiatry 73 : , : , Suzuki K, Okuma Y, Hattori N et al : Characteristics of sleep disturbances in Japanese patients with Parkinson s disease. A study using Parkinson s disease sleep scale. Mov Disord 22 : , Marsden CD On off phenomena : in Parkinson s disease. In : Rinne UK,Klinger M, Stamm G, editors, Parkinson s disease : current progress, problems and management, Amsterdam, Elsevier 1980, p Diederich NJ, Comella CL : Sleep Disturbances in Parkinson s Disease. In : Sleep and movement Disorders, 2nd ed, Oxford University Press, NY, 2013, p Stiasny Kolster K, Mayer G, Schäfer S et al : The REM sleep behavior disorder screening questionnaire a new diagnostic instrument. Mov Disord 22 : , Miyamoto T, Miyamoto M, Iwanami M et al : The REM sleep behavior disorder screening questionnaire : validation study of a Japanese version. Sleep Med 10 : , Berardelli A, Wenning GK, Antonini A et al : EFNS/MDS ES/ ENS corrected recommendations for the diagnosis of Parkin son s disease. Eur J Neurol 20 : 16 34, Trenkwalder C, Kohnen R, Högl B et al : Parkinson s Disease Sleep Scale Validation of the Revised Version PDSS 2. Mov Disord 26 : , Suzuki K, Miyamoto M, Miyamoto T et al : Nocturnal distur bances and restlessness in Parkinson s disease : using the Jap anese version of the Parkinson s disease sleep scale 2. J Neu 168

4 rol Sci : 76 81, Moro de Casillas ML, Riley DE : Insomnia. In Parkinson s dis ease and Nonmotor Dysfunction, Pfeiffer RF, Bodis Wollner I ed, Humana Press Inc., Totowa, NJ, 2005, p Trotti LY, Rye DB : Neurobiology of sleep : the role of dopamine in Parkinson s disease. In Non motor symptoms of Parkinson s disease, Chaudhuri KR, Tolosa E, Schapira A, Poewe W ed, Oxford university press, Oxford, New York, 2009, p Peeraully T, Yong MH, Chokroverty S et al : Sleep and Parkin son s disease : a review of case control polysomnography stud ies. Mov Disord 27 : , Parkinson 2011 Parkinson 2011 p Menza M, Dobkin RD, Marin H et al : Treatment of insomnia in Parkinson s disease : a controlled trial of eszopiclone and placebo. Mov Disord 25 : , Maass A, Reichmann H : Sleep and non motor symptoms in Parkinson s disease. J Neural Transm 120 : , Trenkwalder C, Kies B, Rudzinska M : Rotigotine effects on early morning motor function and sleep in Parkinson s disease : a double blind, randomized, placebo controlled study RECOVER. Mov Disord 26 : 90 99, Dusek P, Busková J, R zicka E et al : Effects of ropinirole pro longed release on sleep disturbances and daytime sleepiness in Parkinson s disease. Clin Neuropharmacol 33 : , Parkinson 30 : , Garcia Borreguero D, Larrosa O, Bravo M : Parkinson s dis ease and sleep. Sleep Med Rev 7 : , Ondo WG, Dat Vuong K, Khan H et al : Daytime sleepiness and other sleep disorders in Parkinson s disease. Neurology 7 : , Suzuki K, Miyamoto T, Miyamoto M et al : Excessive daytime sleepiness and sleep episodes in Japanese patients with Parkinson s disease. J Neurol Sci 71 : 47 52, Brodsky MA, Godbold J, Roth T et al : Sleepiness in Parkinson s disease : a controlled study. Mov Disord 18 : , Thannickal TC, Lai YY, Siegel JM : Hypocretin orexin cell loss in Parkinson s disease. Brain 130 : , Fronczek R, Overeem S, Lee SYY et al : Hypocretin orexin loss in Parkinson s disease. Brain 130 : , Arnulf I, Leu Semenescu S : Sleepiness in Parkinson s disease. Parkinsonism Relat Disord 15 Suppl 3 : S , Arnulf I, Konofal E, Merino Andreu M et al : Parkinson s dis ease and sleepiness : an integral part of PD. Neurology 58 : , Frucht S, Rogers JD, Greene PE et al : Falling asleep at the wheel : motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 52 : , Paus S, Brecht HM, Koster J et al : Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson s disease. Mov Disord 18 : , Paus S, Seeger G, Brecht HM et al : Association study of dop amine D2, D3, D4 receptor and serotonin transporter gene polymorphisms with sleep attacks in Parkinson s disease. Mov Disord 19 : , Rissling I, Geller F, Bandmann O et al : Dopamine receptor gene polymorphisms in Parkinson s disease patients reporting sleep attacks. Mov Disord 19 : , Rissling I, Korner Y, Geller F et al : Preprohypocretin polymor phisms in Parkinson disease patients reporting sleep at tacks. Sleep 28 : , Högl B, Saletu M, Brandauer E et al : Modafinil for the treat ment of daytime sleepiness in Parkinson s disease : A double blind, randomized, crossover, placebo controlled polygraphic trial. Sleep 25 : 62 66, Adler CH, Caviness JN, Hentz JG et al : Randomized trial of modafinil for treating subjective daytime sleepiness in pa tients with Parkinson s disease. Mov Disord 18 : , Ondo WG, Fayle R, Atassi F et al : Modafinil for daytime som nolence in Parkinson s disease : double blind, placebo con trolled parallel trial. J Neurol Neurosurg Psychiatry 76 : , Parkinson selegiline 24 : , Parkinson selegiline 28 : ,

5 Pathophysiology and Management of Sleep Disorders in Patients with Parkinson s Disease Masayuki MIYAMOTO*, Koichi HIRATA*, Keisuke SUZUKI*, Tomoyuki MIYAMOTO** *Department of Neurology Dokkyo Medical University School of Medicine, Tochigi, Japan **Department of Neurology Dokkyo Medical University Koshigaya Hospital, Saitama, Japan The sleep wake disturbances, i.e. altered sleep and vigi lance, are among the most frequent non motor symptoms in patients with Parkinson s disease PD. As impaired sleep quality and sleep fragmentation due to nighttime problems are associated with daytime motor function and a negative impact on the quality of life of the PD patients. The nighttime sleep problems are caused by various fac tors including nocturnal motor symptoms, psychiatric symptoms e.g. mood disorder, hallucination, psychosis, medication use, nocturia, pain, circadian cycle disruptions or comorbidity with primary sleep disorders such as rest less legs syndrome, periodic limb movements, rapid eye movement sleep behavior disorder, or sleep apnea syn drome. Nocturnal motor symptoms such as worsened rigid ity, tremor, dystonia, akinesia or medication related dyski nesis can lead to nocturnal awakening and sleep maintenance insomnia, a common form of insomnia in PD. Parkinson Disease Sleep Scale PDSS is useful in the evaluation of nocturnal symptoms in PD. Excessive daytime sleepiness may result from these noc turnal sleep disturbances, be caused by the medications used to treat PD or sedatives, or be intrinsic to PD itself. In this matter, the cause of sleep wake disturbances in PD is multifactorial, reflecting PD related pathology, vari ous aspects of PD related motor and non motor symptoms and co morbidity of primary sleep disorders. Treatment of sleep wake disturbances in PD is complex and often re quires multiple therapeutic strategies. Early recognition of and active intervention for sleep wake disturbances is of great importance. Appropriate evaluation and management of sleep disorders are essen tial to improve the quality of life of patients with PD. 170