렘수면행동장애의 치료 - JSM

1 24 Treatment of REM Sleep Behavior DisorderHye-Jin Moon, , Hyunwoo Nam, of Neurology, Boramae Hospital, Seoul National University, Seoul, KoreaREM sleep behavior disorder (RBD) is clinically characterized by the intermittent loss of normal skeletal muscle atonia during rapid eye movement (REM) sleep with the appearance of elaborate motor activity associated with dream mentation. Clonazepam, a sedating benzodiazepine, is currently regarded as the treatment of choice for RBD. In patients with contraindications to clonazepam, in those unresponsive to clonazepam, or in whom tolerance or serious side effects are observed, a therapeutic trial with melatonin up to 12 mg is recommended. The effect of acetylcholinesterase inhibitors and dopaminergics on RBD symptoms needs future validation. There is no clear evidence of beneficial effect of bilateral subthalamic nucleus stimulation despite the improvement of the sleep architecture.

2 Key Words : REM sleep behavior disorder, Clonazepam, Melatonin, Pramipexole, Levodopa J Kor Sleep Soc / Volume 6 / June, 2009* Address of correspondenceHyunwoo Nam, , Professor, Department of Neurology, Boramae Hospital,Shindaebang 2-dong 395, Dongjak-ku, Seoul, Korea, 156-707 Tel: +82-2-870-2471 Fax: +82-2-870-3866E-mail: (REM sleep behavior disorder, RBD) (atonia) , , 2 (Internatio-nal Classification of Sleep Disorders 2nd edition, 2005) , , , (para-somnia) .1 ,2 -synucleinopathies3 , . , , , 65% ,4.

3 , , , 79%~96% ,5,6 .. 1. Clonazepam Clonazepam , , / June, 200925 Table 1. Clonazepam treatment data Population studied (n)Dosage (mg)PSGR esultsSchenck CH. et RBD and RBD associated with other disorders (57) ~ (n=8)Full control ( ), partial control ( )Olson EJ. et RBD and RBD associate with neurological disorders (38) ~ control (55%), partial control (32%)Lapierre O. et RBD (5) ~2 Yes in REM phasic EMG activity RBD, REM sleep behavior disorder; PSG, polysomnographyTable 2. Polysomnographic data on acute (first night) effects of clonazepam in 8 patients with typical chronic RBD8 Sleep measures(mean SD)The night before clonazepam treatmentThe night of clonazepam treatment 1 Total sleep time, mins ( ) ( ) 2 Sleep efficacy, % ( ) ( ) 3 Sleep latency, ( ) ( ) 4 REM latency, ( ) ( ) 5 Stage 1% ( ) ( ) 6 Stage 2% ( ) ( ) 7 Stage 3/4% ( ) ( ) 8 REM % ( ) ( ) RBD, REM sleep behavior disorder.

4 ~ mg qd hs 87~90% .5-7 Clonazepam Schenck CH , 57 , 51 ,7 Mayo Clinic series 6 87% (Tabel 1). Clonazepam , , , , . clonazepam .8 clonazepam , . clona-zepam , , , , . clonazepam , clonazepam .Clonazepam , . , clonazepam (Tabel 2), . Schenck CH clonazepam phasic locomotor activity.

5 Activation-synthesis model clonazepam dream action pattern generator locomotor pattern generator ,8 . 2. MelatoninMelatonin , clonazepam . 1997 Kunz Bes 64 melatonin 9 , . Takeuchi 10 15 13 . , %tonic REM activity . melatonin pg/mL , 15 10 30 pg/mL . melatonin melatonin . Boeve 26 Table 3. Melatonin treatment dataPopulation studied (n)Dosage (mg)PSGR esults Takeuchi N. et RBD (15)3~9 Yes in RBD symptoms (87%), in REM tonic EMG activity Boeve BF. et associate with neurological disorders (14)3~12 ( clonazepam) NoFull control (6/14), markedly improved but not control (4/14)RBD, REM sleep behavior disorder; PSG, polysomnography 11 clonazepam melatonin addic-tive effect (Tabel 3).

6 Melatonin melatonin .9 Clonazepam addictive effect , clonazepam phasic EMG activity melatonin tonic EMG activity .10,11 Melatonin , , , .11 3. Pramipexole Levodopa , stri-atal presynaptic dopaminergic transporter ,12 nigrostiratal dopaminergic innervation 13 . , ,4 14 nigrostriatal dopaminergic system . Levodopa . Fantini 8 pramipexole ( ~1 mg/d) , 5 .15 simple motor behavior , . pramipexole clonazepam melatonin , . Kumru Iranzo , pramipexole.

7 16 . Levodopa , Adrian Tan 3 levodopa vivid dream , .17 Levodopa , , . 4. Carbamazepine carbamazepine . Bamford carbamazepine 100 mg tid 75% .18 , , carbamazepine imipramine 3 .19 , , carbamazepine imipramine . 5. Donepezil rivastigmine 21 acetylcholine esterase , / June, 200927 , . Ringman donepezil(10-15 mg qd) 3.

8 20 .11,21 Rivastigmine dementia with Lewy bodies case series .23 6. Bilateral subthalamic stimulation bilateral subthalamic stimul-ation , 2 . Iranzo 11 , .24 Arnulf bilateral subthalamic stimulation , (WASO) , .25 clonazepam( ~2 mg qd hs) , clonazepam , , , , clonazepam , melatonin(~12 mg ) . Clonazepam melatonin , pramipexole acetylch-oline esterase inhibitor .. ,26 MAO ,27 SSRI28.

9 29 REFERENCES1. Atlas Task Force of the American Sleep Disorders Association (ASDA). The International Classification of Sleep Disorders - Diagnostic and Coding Manual. Minnesota: Rochester; Nightingale S, Orgill JC, Ebrahim IO, de Lacy SF, Agrawal S, Williams AJ. The association between narcolepsy and REM behavior disorder (RBD). Sleep Med 2005;6 Boeve BF, Silber MH, Fermann TJ, Lucas JA, Parisi JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord 2001;16 Schenck CH, Bundlie SR, Mahowald MW. REM behavior disorder (RBD): delayed emergence of parkinsonism and/or dementia in 65% of older men initially diagnosed with idiopathic RBD, and an analysis of the minimum and maximum tonic and/or phasic electromyographic abnormalities found during REM sleep.

10 Sleep 2003;26 (Suppl) Schenck CH, Hurwitz TD, Mahowald MW. REM sleep behaviour disorder: an update on a series of 96 patients and a review of the world literature. J Sleep Res 1993;2 Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behavior disorder: demographic, clinical and laboratory findings in 93 cases. Brain 2000;123 Lapierre O, Montplaisir J. Polysomnographic features of REM sleep behavior disorder: development of a scoring method. Neurol-ogy 1992; 42 Schenck CH, Mahowald MW. Polysomnographic, neurologic, psychiatric, and clinical outcome report on 70 consecutive cases with REM sleep behavior disorder (RBD) : sustained clonazepam efficacy in of 57 treated patients. Cleve Clin J Med 1990;57(Suppl) Kunz D, Bes F. Melatonin effects in a patient with severe REM sleep behavior disorder: case report and theoretical considerations.