대한임상신경생리학회지 17(1):17-23, 2015 eissn 2288-1026 pissn 1229-6414 http://dx.doi.org/10.14253/kjcn.2015.17.1.17 Original Article 파킨슨병의중증도에따른수면장애 동아대학교의과대학신경과학교실 Sleep Disturbances in Patients with Parkinson s Disease according to Disease Severity Su-Yun Lee, Sang-Myung Cheon, Jae Woo Kim Department of Neurology, College of Medicine, Dong-A University, Busan, Korea Background: Sleep-related disturbances and sleep disorders are common in Parkinson s disease (PD) and have a great impact on daily life of PD patients. This study was done to find the sleep characteristics and sleep disturbing factors in PD patients according to disease severity through clinical interview and polysomnographic (PSG) study. Methods: Fifty patients with PD (22 males, age 60.6 ± 6.4, Hoehn and Yahr (HY) stage 2.7 ± 1.0) were recruited and thoroughly interviewed about their sleep. PSG was performed on the patients taking routine antiparkinsonian medications. Patients were grouped into mild and moderate/severe group according to HY stage, and the results were compared between each group. Results: Ninety-four percent of total patients had one or more sleep-related disturbances based on the interview or PSG. On interview, the moderate/severe group complained more insomnia and REM sleep behavior disorder (RBD) than mild group. In PSG findings, the moderate/severe group showed lower sleep efficiency, longer sleep latency, REM sleep latency, waking time after sleep onset, and higher prevalence of RBD. Conclusions: In this study, most patients with PD had sleep disturbances. Clinical interview and PSG findings revealed deterioration of sleep quality along the disease severity. Our results suggest that sleep disturbances in PD patients are prevalent and warrant clinical attention, especially to the patients with advanced disease. (Korean J Clin Neurophysiol 2015;17:17-23) Key Words: Parkinson, Sleep, Polysomnography Received 23 October 2014; received in revised form 20 February 2015; accepted 10 June 2015. 서 론 율신경계이상, 감각이상과통증등의다양한비운동증상을동반하며, 이러한비운동증상은환자나보호자의삶의운동완만, 진전, 경직, 자세불안정성을특징으로하는파질을저하시키는주요한원인으로생각되고있다. 1,2 그중킨슨병은, 운동증상뿐아니라정신장애나수면장애, 자수면장애는보고에따라유병률이다양한데, 국내외를포함하여 38% 에서 98% 까지보고되어있다. 3-8 파킨슨병과관련성이높은것으로알려진수면질환으로는주간과다졸 Address for correspondence; Sang-Myung Cheon 림증 (Excessive daytime sleepiness), 렘수면행동장애 (REM Department of Neurology, Dong-A University Hospital, College of sleep behavior disorder; RBD), 하지불안증후군 (Restless legs Medicine, Dong-A University, 26, Daesingongwon-ro, Seo-gu, Busan 602-715, Korea syndrome, RLS) 등이있고, 낮은수면효율 (sleep efficiency) Tel: +82-51-240-5266 Fax: +82-51-244-8338 과수면분절 (sleep fragmentation) 등수면의질적인저하도 E-mail: sangmcheon@gmail.com Copyright 2015 by The Korean Society of Clinical Neurophysiology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
알려져있다. 9,10 이러한파킨슨병환자의수면장애는수면중운동증상, 야뇨등의자율신경학적이상, 또는도파민성약물치료로인한변화등의이차적인원인뿐아니라, 질병자체의진행으로인한, 수면과각성을조절하는뇌줄기를비롯한뇌의여러부위의신경세포의소실이원인이될수있다. 11 수면다원검사 (Polysomnography; PSG) 는검사장비가필요하고시간과비용이든다는단점이있으나, 객관적이고많은정보를준다는점에서수면의특성을파악할수있는가장표준적인검사법이다. 따라서 PSG는파킨슨병과수면질환의상관성이나파킨슨병환자의양적, 질적인수면의특성을연구하는것에도유용하다. 본연구에서는면담과 PSG를통해파킨슨병환자의수면을방해하는요인과수면질환및수면의구조적인특징을알아보고자하였고, 임상적인특징특히질병의중등도에따라차이가있는지살펴보았다. 대상과방법 1. 대상본원파킨슨병센터에서파킨슨병으로진단되어약물치료받고있는환자중무작위로 PSG 시행에동의한 50명의환자를대상으로하였다. 파킨슨병의진단은영국파킨슨병학회뇌은행 (UK Parkinson s disease society brain bank) 의기준에따랐으며, 12 자세한설문조사가힘들정도의인지기능장애나뇌경색등의다른신경과적질환을가지고있는환자들은배제하였다. 2. 방법 1) 임상적특징의평가나이나성별등의기본적인인구학적특성외발병나이, 발병시주증상, 유병기간과치료기간, 레보도파동등용량 (levodopa-equivalent dose, LED), Hohen and Yahr stage(hy) 를조사하였고, Unified Parkinson Disease Rating Scale (UPDRS) 의운동증상검사중에서안정시진전 (Tremor at rest), 강직 (Rigidity), 손가락두드리기 (Finger taps), 다리민첩도 (Leg agility) 의 4가지항목의합을구하여환자의운동증상점수로간주하였다. 또한한국판 Mini-Mental State Examination (K-MMSE) 점수를구하여나이와교육수준을고려하여이상유무를판단하였다. 2) 수면일기와면담을통한수면조사수면일정, 수면질환의유무, 수면방해요소에대한조 사를하였다. 수면일정은수면일기를이용하여총수면시간, 잠이들때까지시간, 깬횟수, 수면후깨있는시간을알아보고, 지난일주일간낮잠의횟수와잠을제대로자지못한날수를조사하였다. 또한환자, 그리고잠자리를같이하는보호자를대상으로면담을통하여불면증, 코골이, RLS의유무를판단하고임상적으로 RBD가의심되는지여부와낮에졸린정도를조사하였는데, 불면증의경우에는잠들기가힘들거나, 잠을계속유지하기어렵거나, 너무일찍깨서다시잠들지못하는증상들을모두포함하였다. 또한임상적으로 RBD가의심되는 RBD 의증은, 보호자가보았을때꿈의내용이행동으로나타나거나본인이명확하게행동으로표현한다고한경우로간주하였으며, 낮에졸린정도는 1~5점까지점수화하였다 (1: 전혀졸리지않다, 2: 가끔졸리다, 3: 종종졸리다, 4: 자주졸리다, 5: 아주자주졸리다 ). 그리고야뇨, 돌아눕기힘듦, 생생한꿈, 요통, 근경련통, 굳어져깨기 (rigidity), 하지간대성경련 (leg jerk) 등수면을방해하는요소에대한조사를하여빈도에따라점수화하였다 (1: 0회 / 주, 2: 1-2회 / 주, 3: 2-3회 / 주, 4: 4-5회 / 주, 5: 6회이상 / 주 ). 3) PSG 를통한수면조사모든환자에게평소의항파킨슨약물을유지한상태에서표준수면다원검사 (standard polysomnography) 를시행하였다. 채널로는뇌파 (electroencephalogram; C3-A2, C4-A1, O1-A2, O2-A1), 안전도 (electrooculogram), 턱근전도 (chin electromyogram), 다리근전도 (leg electromyogram), 심전도 (electrocardiogram), 코골이 (snoring sound), 가슴-배호흡운동, 혈중산소포화농도, 호흡기류 (nasal pressure transducer and thermistor), 몸의위치를사용하였고, 2007년개정된미국수면학회 (American Academy of Sleep Medicine, AASM) 의규칙에따라수면의단계를분석하고, 또한 AASM 의규칙에따라수면효율 (Sleep efficiency(%)), 수면잠복기 (sleep latency(min)), 렘수면잠복기 (REM latency(min)), 수면후깨어있는시간 (wake time after sleep(min)), 각성지수 (Arousal index), 무호흡저호흡지수 (Apnea-Hypopnea index, AHI), 주기사지운동지수 (Periodic limb movement index, PLMI) 를구하였다. 13 4) PSG 를이용한수면질환의판정국제수면질환분류기준 2판 (The international classification of sleep disorders, 2nd ed., ICSD-2) 에따라 PSG에서 REM sleep without atonia가확인되거나렘수면동안이상행동이관찰된경우에 RBD로진단하였고, AHI가 5를초과하는경우를수면호흡장애 (sleep-related disordered breathing, SRDB), 18 Korean J Clin Neurophysiol / Volume 17 / June 2015
Sleep Disturbances in Parkinson s Disease PLMI가 15를초과하는경우를명백하게주기사지운동지수가증가되어있는것 (significantly increased PLMI) 으로정의하였다. 14 5) 통계분석 SPSS프로그램 (version 18.0) 을사용하여, 교차분석에서는 Pearson chi-square test와 Fisher s exact test, 평균치비교분석에는비모수적방법인 Mann-Whitney U test, 상관관계분석에는 Pearson correlation test를사용하였다. 결과 1. 임상적특징전체 50명의평균나이는 60.6 ± 6.4세였고, 그중남자는 22명 (44%) 이었다. 파킨슨병의발병나이는평균 54.5 ± 6.8 세, 발병시주증상은떨림증이 22명 (44%), 서동증-강직이 28명 (56%) 이었다. 평균유병기간은 6.0 ± 3.4년, 평균치료기간은 3.7 ± 2.9년이었으며, LED 는하루평균 700.1 ± 603.1 mg이었다. 평균운동증상점수는 10.8 ± 5.4, 평균 HY 단계는 2.7 ± 1.0, 평균 K-MMSE 점수는 26.3 ± 4.1였다. 이들을 H-Y stage 에따라서경증의환자군 (HY I, II) 과중등도이상의환자군 (HY III, IV, V) 으로나누었을때중등도이상의환자군에서유병기간과치료기간이길고, 운동증상점수와 LED가높은것을확인할수있었다 (Table 1). 1) 수면일기와면담을통한수면조사결과질환의중증도에따라나누어비교하였을때, 중등도이상의환자군에서총수면시간은짧고, 자다가깬횟수와깬시간, 그리고지난 1주간비회복성수면의횟수 (Number of nights with non-restorative sleep during past week) 가증가함을알수있었다. 또한수면잠복기나낮잠의횟수도증가하는경향이있었으나통계적인유의성은없었다. 수면질환에대한면담결과에서는불면증이 58%, RBD 의증이 52%, 코골이가 52%, RLS 22% 의빈도로확인되었으며전체환자의 88% 가이네가지중하나이상을호소하였고주간졸림정도는가끔혹은종종졸린다고응답한비율이높았다. 환자를질환의중증도에따라나누었을때, 불면증과 RBD 의증은중등도이상의환자군에서더높은빈도로관찰되었다. 반면코골이와 RLS, 그리고주간졸림정도는질환의중증도와연관성이없었다 (Table 2). 또한빈도에따라점수화한수면방해요소조사에서, 전체환자에서는야뇨가가장높은점수를보였고, 그다음이돌아눕기힘듦순이었으며, 이두가지모두중등도이상의환자군에서통계적으로유의하게더높은점수를보였다. 그외의수면방해요소는그영향이미미하였고, 하지간대성경련 (leg jerk) 을제외하고는질환의중증도에따른차이도뚜렷하지않았다 (Table 2). 2. PSG 결과 PSG에서질환의중증도에따른수면단계의차이점은발견되지않았다. 하지만중등도이상의환자군에서수면효율이떨어지고, 수면잠복기와수면후깨어있는시간이긴것으로확인되었다. 그외총수면시간, 각성지수, AHI, PLMI에서는통계적유의성이없었다. PSG를통해 RBD는 52%, 수면호흡장애 24%, 명백하게증가된 PLMI 22% 의빈도로진단되었는데, 전체환자중 68% 가이세가지중의하나이상을가지고있었고 RBD는중등도이상의환자군에서더많이관찰되었다 (Table 3). Table 1. Clinical characteristics according to disease severity Hoehn and Yahr stage (n) 1-2 (29) 3-5 (21) Total (50) p-value Age (years) 60.4 ± 5.8 60.8 ± 7.2 60.6 ± 6.4 ns Sex (Male : Female) 10 : 19 12 : 9 22 : 28 ns K-MMSE * 27.1 ± 2.5 25.2 ± 5.5 26.3 ± 4.1 ns Duration of disease (years) 4.6 ± 2.4 8.1 ± 3.4 6.0 ± 3.4 < 0.001 Duration of treatment (years) 2.7 ± 1.9 5.2 ± 3.5 3.7 ± 2.9 0.011 L-DOPA equivalent dose # (mg/day) 464.9 ± 273.3 1025.5 ± 771.6 700.1 ± 603.1 0.002 Motor score 8.6 ± 4.3 13.7 ± 5.6 10.8 ± 5.4 0.001 Hoehn and Yahr stage 2.1 ± 0.4 3.5 ± 0.5 2.7 ± 1.0 * Korean version of Mini-Mental State Examination # Levodopa-equivalent dose Sum of UPDRS items 20 ( tremor at rest ), 22 ( rigidity ), 23 ( finger taps ), 26 ( leg agility ) ns, not significant Korean J Clin Neurophysiol / Volume 17 / June 2015 19
Table 2. Sleep schedule, sleep disorders and disturbing factors based on interview Hoehn and Yahr stage (n) 1-2 (29) 3-5 (21) Total (50) p-value Total sleeping time (hours/night) 6.59 ± 1.33 5.24 ± 1.32 6.01 ± 1.48 0.002 Sleep latency (hours) 0.41 ± 0.30 0.73 ± 1.15 0.55 ± 0.79 ns Number of waking at night 1.93 ± 1.19 3.14 ± 1.62 2.45 ± 1.50 0.001 Waking time during sleep (hours/night) 0.39 ± 0.58 1.27 ± 1.10 0.77 ± 0.94 0.001 Number of naps during past week 2.61 ± 3.01 4.21 ± 5.03 3.30 ± 4.04 ns Number of nights with non-restorative sleep 1.61 ± 0.83 2.29 ± 0.78 1.90 ± 0.87 0.006 Insomnia (n) 41.4% (12) 81.0% (17) 58.0% (29) 0.005 REM-sleep behavior disorder (n) 37.9% (11) 71.4% (15) 52.0% (26) 0.019 Snoring (n) 55.2% (16) 47.6% (10) 52.0% (26) ns Restless legs syndrome (n) 17.2% (5) 28.6% (6) 22.0% (11) ns Daytime sleepiness (1-5) * 2.64 ± 1.10 2.67 ± 1.35 2.65 ± 1.20 ns Nocturia # 3.6 ± 1.6 4.5 ± 1.2 4.0 ± 1.5 0.037 Turning difficulty # 1.3 ± 0.9 2.6 ± 1.5 1.8 ± 1.4 < 0.001 Vivid dreaming # 1.3 ± 0.6 1.5 ± 0.7 1.4 ± 0.7 ns Back pain # 1.6 ± 1.4 1.4 ± 1.0 1.5 ± 1.2 ns Cramping pain # 1.4 ± 0.9 1.5 ± 1.0 1.4 ± 1.0 ns Rigidity # 1.0 ± 0.2 1.3 ± 0.6 1.1 ± 0.5 ns Leg jerk # 1.1 ± 0.3 1.6 ± 1.2 1.3 ± 0.9 0.033 * Scored by severity. Scored by frequency of event. ns, not significant. Table 3. Polysomnographic findings Hoehn and Yahr stage (n) 1-2 (29) 3-5 (21) Total (50) p-value Total sleep time (min.) 471.9 ± 63.0 494.3 ± 89.7 481.3 ± 75.3 ns N1 sleep (%) 14.8 ± 14.4 17.1 ± 11.8 15.7 ± 13.3 ns N2 sleep (%) 57.7 ± 13.0 52.7 ± 13.6 55.6 ± 13.3 ns N3 sleep (%) 8.2 ± 8.8 12.4 ± 10.3 10.0 ± 9.6 ns REM sleep (%) 19.5 ± 8.6 17.9 ± 10.8 18.7 ± 9.5 ns Sleep efficiency (%) 81.7 ± 12.0 71.4 ± 13.2 77.4 ± 13.4 0.006 Sleep latency (min.) 17.8 ± 28.6 27.3 ± 19.3 21.8 ± 25.3 0.005 REM sleep latency (min.) 113.6 ± 65.8 152.7 ± 94.5 130.0 ± 80.6 ns Wake time after sleep onset (min.) 85.6 ± 50.7 142.4 ± 72.9 109.4 ± 66.6 0.009 Arousal index (/hour) 8.1 ± 3.3 7.0 ± 4.0 7.6 ± 3.6 ns Apnea-Hypopnea index (/hour) 4.9 ± 8.6 5.4 ± 7.9 5.1 ± 8.3 ns PLM index * (/hour) 7.4 ± 11.2 11.4 ± 20.7 9.1 ± 15.8 ns REM-sleep behavior disorder 37.9% (11) 71.4% (15) 52.0% (26) 0.025 Sleep-related disordered breathing 17.2% (5) 33.3% (7) 24.0% (12) ns Significantly increased PLMI 20.7% (6) 23.8% (5) 22.0% (11) ns * Periodic limb movement index. ns, not significant. 20 Korean J Clin Neurophysiol / Volume 17 / June 2015
Sleep Disturbances in Parkinson s Disease PSG결과와파킨슨병의임상적특징들의상관관계를살펴본결과, LED가증가할수록 1단계수면의비율이증가되는것이관찰되었다. 또한수면효율은유병기간과 LED, 운동점수가증가할수록떨어지고, 수면잠복기는유병기간과치료기간이증가할수록길어졌다. 그외렘수면잠복기와치료기간, 그리고수면후깬시간과운동점수사이 에서통계적유의성이있었다 (Table 4). 면담을통해 RBD 의증으로판단되었던 26명 (52%) 의환자중 24명의환자는 PSG 상에서도 RBD로진단되었으며, 나머지 2명은 PSG 상에서는음성이었다. 하지만반대로면담에서 RBD가없을것으로예상되었던환자중 2명은 PSG상에서 RBD가진단되었다. PSG 상에서 RBD로진단 Table 4. Correlations between PSG parameters and clinical characteristics Duration of symptom (years) Total sleep time (min.) r = -.227 p =.112 N1 sleep (%) r =.217 p =.129 N2 sleep (%) r = -.229 p =.110 N3 sleep (%) r =.238 p =.096 REM sleep (%) r = -.224 p =.119 Duration of treatment (years) r = -.183 p =.205 r =.254 p =.075 r = -.145 p =.316 r =.051 p =.724 r = -.207 p =.149 Sleep efficiency (%) r = -.321 r = -.196 p =.023 * p =.173 Levodopa equivalent dose (mg/day) r = -.049 p =.735 Motor score # r =.043 p =.767 r =.369 r =.151 p =.008 * p =.294 r = -.221 p =.122 r = -.192 p =.183 r = -.016 p =.912 Sleep latency (mins) r =.297 p =.036 * r =.337 p =.017 * r =.204 p =.155 REM sleep latency (mins) r =.212 p =.139 Wake time after sleep onset (mins) r =.236 p =.099 r =.350 r =.229 p =.013 * p =.109 r =.122 p =.397 r = -.284 p =.046 * r =.110 p =.448 r =.062 p =.669 r = -.313 r = -.294 p =.027 * p =.038 * r =.275 p =.053 # Sum of UPDRS items 20 ( tremor at rest ), 22 ( rigidity ), 23 ( finger taps ), 26 ( leg agility ). * p < 0.05. r =.034 p =.817 r =.105 p =.466 r =.292 p =.040 * Table 5. Comparison between patients with and without REM sleep behavior disorder (RBD) Total (50) RBD (26) NRBD (24) p-value Age (years) 61.5 ± 6.3 59.6 ± 6.4 ns Duration of disease (years) 7.1 ± 3.5 4.9 ± 2.9 0.029 Duration of treatment (years) 4.3 ± 3.1 3.1 ± 2.6 ns L-DOPA equivalent dose (mg/day) 850.9 ± 717.0 537.2 ± 403.5 ns Motor score * 11.3 ± 4.6 10.1 ± 6.2 ns Hoehn and Yahr stage 2.9 ± 0.8 2.4 ± 0.9 0.018 K-MMSE 25.8 ± 4.8 26.8 ± 3.3 ns MMSEC # (n) 26.9% (7) 4.2% (1) 0.030 Total sleep time (mins) 483.5 ± 67.6 479.0 ± 84.3 ns Sleep efficiency (%) 74.7 ± 15.6 80.3 ± 9.9 ns Sleep latency 29.2 ± 30.9 13.8 ± 14.1 0.012 REM sleep latency (mins) 145.4 ± 92.2 113.4 ± 63.6 ns * Sum of UPDRS items 20 ( tremor at rest ), 22 ( rigidity ), 23 ( finger taps ), 26 ( leg agility ). # Number of patients with abnormal K-MMSE score corrected for age and educational level. ns, not significant. Korean J Clin Neurophysiol / Volume 17 / June 2015 21
된환자들은그렇지않은환자보다유병기간이길고 HY 단계가증가되어있었고수면잠복기가더길게관찰되었다. 그리고 RBD로확인된환자들은 K-MMSE 점수가나이와학력을고려한정상표준평균보다 2SD 이상낮은비정상적인경우가더흔하게관찰되었다 (Table 5). 고찰본연구에서, 면담을통한조사에서는 88% 의환자가불면증, RBD 의증, 코골이, RLS 중하나이상의증상을가지고있었고, PSG결과에서는 68% 의환자가 RBD나수면호흡장애가있거나, PLMI 가증가되어있었다. 면담결과와 PSG결과를합칠경우 50명중 3명을제외한 94% 의환자들에게서수면장애가있는것으로확인되었는데, PSG결과에서수면호흡장애가없는단순코골이와면담에서만 RBD 가있었던경우를제외하더라도 92% 의환자는하나이상의수면장애를보여파킨슨병환자들의높은수면장애의유병률을확인할수있었다. 수면방해요소로는야뇨, 돌아눕기힘듦을가장높은빈도로응답하였고, 중증도에따라차이를보여중증환자일수록수면방해가더심해지는원인으로생각해볼수있겠다. 이는돌아눕기힘듦다음으로화장실방문이파킨슨병환자의수면방해요소로가장많이작용한다는 Lees 등의자료와유사한결과이며 Parkinson s disease sleep scale (PDSS) 를이용한다른보고와도유사하다. 3,15 PSG를사용한파킨슨병환자의다른수면연구들을살펴보면, Happe 등은 PSG의여러결과값들이질병의중증도나유병기간과연관이없다고하였고, Yong 등은유병기간과는상관이없으나수면효율은 H&Y가증가할수록떨어지는것으로말하였다. 16,17 반면에 Diederich 등은유병기간이길수록수면효율은떨어지고수면잠복기는늘어나나, 운동증상과는관련이없다고하였으며, Norlinah 등은수면효율, 수면잠복기모두 UPDRS와상관관계가있다고하는등연구에따라다양한결과를보고하였다. 18,19 본연구에서는수면효율의감소, 수면잠복기의증가모두질환의중증도, 그리고유병기간과상관관계가있음을보였다. 한편깊은수면단계와 REM 수면단계가유병기간과음의상관관계를가진다는보고가있었으나, 본연구에서는일부결과를제외하고는질환의중증도나유병기간에따른수면단계의차이를발견하지못하였다. 18 PSG를통해수면호흡장애가 24% 의빈도로진단되었는데, 이는일반인을대상으로시행한한코호트연구결과에서, 50세부터 70세사이의남성이 43.2%, 여성이 27.8% 의 빈도로 AHI가 5 이상이측정되더라는결과와비교해보았을때, 파킨슨병환자에서수면호흡장애가더흔하다고말하기는힘든결과다. 20 또한파킨슨병환자와대조군의수면무호흡증빈도를비교한여러연구에서도다양한결과들이제시되어있어파킨슨병환자와수면무호흡또는수면호흡장애의관계를단정하기는힘들어보인다. 17,21-25 파킨슨병환자에서 RBD의유병률은 15-60% 정도로알려져있는데, 본연구에서는 52% 의환자가 PSG를통해 RBD 로진단되었다. 11 RBD가있는환자군에서 MMSE 가낮은환자가통계적으로유의하게많았는데, 이는 RBD가있는파킨슨병환자들이 RBD가없는환자들에비해경도인지장애가더많다는다른연구와비슷하다. 26 더나아가 RBD 가있는환자군에서치매가더많이발병한다는전향적연구를봤을때, RBD가있는환자들의인지기능에대해보다자세한검사와면밀한추적관찰이필요하겠다. 27 본연구결과에서, 대부분의파킨슨병환자들이크고작은수면장애를가지고있으며, 유병기간이길어지고질환이중해질수록수면의질적인저하가있을수있음을 PSG 를이용한객관적인수치로확인할수있었다. 그러나파킨슨병을가지지않은대조군을설정하지못하여파킨슨병환자들과일반인들의차이를명확히밝히지못한점과항파킨슨약물을그대로투여하면서 PSG를시행하여수면에미치는질환자체의영향력만을평가하지못한점, 그리고평소특별히수면장애를호소한환자들은아니었으나, PSG 검사에동의한환자들만을대상으로하였기때문에이로인한선택편향 (Selection Bias) 으로수면장애유병률에영향을주었을가능성이있는점등은이연구의한계라하겠다. REFERENCES 1. Chaudhuri KR, Healy DG, Schapira AH, National Institute for Clinical Excellence. Non-motor symptoms of parkinson's disease: Diagnosis and management. Lancet Neurol 2006;5:235-245. 2. Poewe W. Non-motor symptoms in parkinson's disease. Eur J Neurol 2008;15:14-20. 3. Lees AJ, Blackburn NA, Campbell VL. The nighttime problems of parkinson's disease. Clin Neuropharmacol 1988;11: 512-519. 4. Ahn TB, Jeon BS. Sleep disturbance and sleep-related disorders in parkinson s disease. J Korean Neurol Assoc 2002;20:365-372. 5. Tandberg E, Larsen JP, Karlsen K. Excessive daytime sleepiness and sleep benefit in parkinson's disease: A community-based study. Mov Disord 1999;14:922-927. 6. Suzuki K, Miyamoto M, Miyamoto T, Iwanami M, Hirata K. 22 Korean J Clin Neurophysiol / Volume 17 / June 2015
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