Geriatric Rehabilitation 2012; 2: Review Article 파킨슨병에서나타나는자세이상및보행장애의재활 김형섭 고동진 1 김용욱 1 국민건강보험일산병원재활의학과, 1 연세대학교의과대학재활의학교실및재활의학연구소 Rehabilitatio
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1 Review Article 파킨슨병에서나타나는자세이상및보행장애의재활 김형섭 고동진 1 김용욱 1 국민건강보험일산병원재활의학과, 1 연세대학교의과대학재활의학교실및재활의학연구소 Rehabilitation for Postural Abnormalities and Gait Disturbances in Parkinson s Disease Hyoung Seop Kim, M.D., Dong Jin Koh, M.D. 1, and Yong Wook Kim, M.D., Ph.D. 1 Department of Rehabilitation Medicine, National Health Insurance Ilsan Hospital, Gyeonggi Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine Seoul , Korea Abstract Postural abnormalities and gait disturbances are frequent and disabling complication of Parkinson s disease. The postural abnormalities include camptocormia, antecollis, retrocollis, PISA syndrome and scoliosis. The gait disturbances include the gait festination and the freezing of gait. The evidence to date suggests that postural abnormalities and gait disturbances have a multi-factorial pathophysiology and are poorly improved by levodopa medication. Improved understanding of the mechanism underlying postural abnormality and gait disturbance in Parkinson s disease might ultimately lead us to more comprehensive management strategies for these disabling and drug-refractory complications. Key Words Comprehensive management, Gait disturbances, Parkinson s disease, Postural abnormalities 접수일 : 2012년 5월 31일게재승인일 : 2012년 6월 2일교신저자 : 김용욱주소 : 서울서대문구성산로 250 연세대학교의과대학재활의학교실 Tel : Fax : ywkim1@yuhs.ac 본논문은 2010년교육과학기술부한국연구재단의기본연구지원사업 ( ) 의지원을받아작성된논문임. 서론 파킨슨병은안정시진전, 경축및서동을특징으로하는만성퇴행성신경질환으로세가지주증상이외에자세및보행장애가흔하게관찰된다. 이는기능적수준을저하시키는합병증으로대부분질환의병기와연관되어나타난다. 파킨슨병에서관찰되는자세이상은배굴증 (camptocormia), 경전굴 (antecollis) 및경후굴 (retrocollis), PISA 증후군, 척추측만증등으로나타나며, 대부분의경우환자가서있을때자세의방향성과안정성에영향을미친다. 1,2 또한, 보행장애는 대부분종종걸음 (festinating gait) 으로시작하여병기가진행될수록보행동결 (freezing of gait) 의형태로변화하며 3 보행시균형장애를유발하여쉽게낙상을초래한다. 이에본논문에서는파킨슨병에서관찰되는자세이상의종류와치료, 대표적인보행장애인보행동결의특징및치료에대해서알아보고자한다. 37
2 본론 1) 파킨슨병에서나타나는자세이상 (1) 발병기전 파킨슨병에서관찰되는자세이상은축성자세이상 (axial postural abnormality) 의형태로나타난다. 2 축성자세이상은대부분웅크린자세로부터시작되며, 1 발병기전은아직명확하게밝혀지지않았다. 그러나, 기저핵의기능저하로인한근육긴장이상, 고유감각과운동감각의손상, 경축, 도파민계약물사용과연관된증상등의중추성기전과근육병증, 척수및연부조직의변화등의말초성기전이자세이상을유발하는것으로알려져있다. 1,2 (2) 배굴증 (Capmtocormia) 배굴증이란웅크린자세가심해진증상으로, 흉추및요추부의심한굴곡을보여굴곡척추증후군 (bent spine syndrome) 이라고도한다. 2 임상적으로배굴증은서있거나걸을때흉 요추부굴곡이 45도이상이고, 앙아위자세로누웠을때굴곡이소실되는경우에진단한다 (Fig. 1A). 4 유병률은파킨슨병에서약 % 이며, 유전적요인으로인해아시아인에서더많이나타나고, 병기및연령과상관관계가있으며, 일반적으로파킨슨병발병후약 7-8년이경과하면나타난다. 5 임상증상은대부분보행장애가나타날때시작되어 PISA증후근과동반되며점진적으로진행되나일부에서는수개월내에빠른진행을보일수있다. 6 또한, 병전에요추부 에퇴행성척추질환등의문제가있었거나수술을받은경우에많이발생하는것으로알려져있고, 배굴증이장기간지속되는경우척추부관절구축이진행되어호흡곤란을일으키기도한다. 6 배굴증의약물치료는도파민계약물에반응이적고, 65세이하에서나타나는경우항콜린계약물을사용할수있다. 2 또한, 척추주위근에보툴리눔독소를주사해볼수있으며, 최근에는시상하부또는뇌각뇌교핵에심부뇌자극술이시도되고있다. 또한, 척추보조기를사용하여요추부전만을증가시켜통증을줄여주고균형감각을호전시킬수있다. (3) 경전굴 (Antecollis) 경전굴은머리및경추부의전방굴곡을말하며 Dropped head syndrome이라고도한다 (Fig. 1B). 파킨슨병의경우 5-8% 의유병률을보이지만다계통위축증에서보다많이발생한다. 2 일반적으로여자와경축및운동불능 (akinesia) 증상이우세한경우많이나타나며파킨슨질환을진단받은후수년이지나야발생한다. 7 이학적검사에서경추부신전근근력은대부분정상이지만흉쇄유돌근의과수축양상을관찰할수있고, 증상발생후빠른시일내에경추부관절구축을유발할수있다. 경전굴의진단은다른경추부질환을감별하기위해영상의학적검사가꼭필요하다. 또한, 경전굴은도파민약물사용과연관되어많이발생하므로 (off-state phenomenon이거나도파민약물과민으로인한증상 ) 증상발생시도파민계약물의용량조절이필요하다. 약물치료로는근육이완제인 clonazepam을사용할수있고흉쇄유돌근과견갑올림근에보툴리눔독소주사치료및경추부보조기를사용 Fig. 1. Postural abnormalities in Parkinson s disease. A: Camptocromia, B: Antecollis, C: PISA syndrome 38
3 김형섭외 2 인 : 파킨슨병에서나타나는자세이상및보행장애의재활 하여도움을받을수있다. 8 (4) 경후굴 (Retrocollis) 경후굴은과도한경추부신전으로인한증상으로축성경축 (axial rigidity) 과관련이있으며진행성핵상마비나향정신성약물을장기간사용한환자에서흔하게나타나지만파킨슨병에서는드물다. 9 (5) PISA 증후군 PISA 증후군은몸통의과도한외측굴곡을보이는증상으로누워있을때는없어지지만보행시심해져측만증의전구증상으로간주되기도한다 (Fig. 1C). PISA증후군의진단기준은아직확립되지않았으나, 앙아위자세에서는나타나지않고보행시몸통의외측굴곡이 15도이상 ( 적어도 10도이상 ) 인경우의심할수있다. 유병률은약 8-90% 로다양하게보고되고있고, 10 일반적으로만성기에나타나며수개월동안빠른진행을보일수도있다. 2 경전굴과유사하게도파민계약물의사용과연관되어나타나는증상으로생각되며약물을변경하거나용량을증량할때나타날수있다. 또한향정신성약물, 항우울제, 항콜린제등의사용과관련되어나타나기도한다. 11 PISA 증후군환자에서신경근병증또는척수병증이동반되어있는경우수술적치료가고려되어야하나, 척추측만증이동반되어있는경우수술적치료의효과에대해서는아직명확하지않다. 2 측만증이없이 PISA 증후군만나타난경우도파민계약물의용량조절과함께항콜린계약물또는향정신성약물인 clozapine을사용해볼수있고척추주위 근육에보툴리눔독소주사치료와척추보조기를이용한치료를시도해볼수있다. 또한최근에는뇌심부자극술이시도되고있다. 2 2) 파킨슨병에서나타나는보행장애 (1) 발병기전파킨슨병에서나타나는보행장애는발병초기종종걸음으로시작하여병기가진행될수록보행동결의양상을보인다. 이러한보행동결의발병기전은현재까지정확하게밝혀지고있지않지만, 이전의많은연구에서도파민을포함한노르에피네프린등의뇌신경전달물질의부족, 12 기저핵손상으로인한신경해부학적기능장애, 13 고유감각전달및감각-운동통합의장애, 14,15 정신기능장애 16 등이관여하는것으로알려져있다. (2) 보행동결 (Freezing of gait) 보행동결이란걷기시작할때, 걷는도중, 또는걷다가돌아설때보행을지속적으로유지할수없는단기간동안나타나는동작의억제를말한다. 3,17 보행중보행동결이발생한대부분의환자는 발이땅바닥에붙어있는듯한느낌 을가지며, 심한경우움직임이전혀없는보행의중단까지나타날수있어보행동결은파킨슨병에서낙상의중요한원인으로작용한다. 보행동결은파킨슨병이외에순보행동결증후군, 혈관성파킨슨증, 진행성핵상마비, 정상압수두증, 다계통위축증등에서도흔하게나타난다. 18 파킨슨병에서관찰되는보행동결은발병후약 5-10년이 Year o Progression Free ing o gait Fig. 2. Onset of freezing of gait according to the disease progression in Parkinson s disease. 39
4 경과한시점에서많이발생하는데 (Fig. 2), 이시기는파킨슨병초기에시작한도파민계약물치료의효과가좋은시기를지나약물치료반응이서서히감소하기시작하는시점을의미하며, 이러한이유로보행동결은도파민계약물치료에잘반응하지않는특징을가지고있다. 19 (3) 보행동결의임상적특징파킨슨병에서나타나는보행동결의임상적특징은보행환경에따라구분할수있는데, 걷는도중방향을전환할때발생하는 turning hesitation, 걷기를시작할때발생하는 starting hesitation, 좁은공간을지나갈때나타나는 tight-quarters hesitation, 목적지에도착하기직전에나타나는 destination hesitation으로분류할수있다 보행동결은일반적으로시간및공간적제한이있는상황에서많이발생하며, 이와는반대로, 환자의발앞에있는선을넘어가는경우보행동결이사라지고정상보행으로전환되는데이를 역설운동 (kinesia paradoxa) 이라고한다. 24 즉, 대부분의보행동결은시간및공간에대한스트레스가가중된상황에서발생하거나악화되지만, 적당한수준의스트레스상황에서는종종보행동결을호전시킨다. 또한, 보행시인지기능을필요로하는업무수행이동반되든가, 또는이중업무를수행하는경우에보행동결을관찰할수있고, 보행동결이발생한환자에서그정도를악화시킬수있다. 18 (4) 보행동결의치료보행동결은치료가매우어려운보행장애이다. 현재까지시도되고있는치료는감각자극 ( 청각, 시각, 촉각 ) 을이용한보행훈련, 약물치료, 운동치료및수술적치료가시도되고있지만그효과에대해서는아직이견이많다. 가 ) 감각자극을이용한보행훈련 : 감각자극을통한보행훈련의효과는 Nieuwboer 등이 (RESCUE trial) 3가지감각자극 ( 시각, 청각, 촉각 ) 을이용하여 3주간치료프로그램적용후임상적으로보행양상, 균형감, 보행동결의정도, 보행속도등이호전됨을보고하였는데치료직후 6주간은호전이있었으나이후에는치료효과가지속되지않았다고하였다. 25 그러나현재까지청각자극 ( 메트로놈을이용하여일정간격의소리가나오면걷는연습을하는방법 ) 26 및시각자극 ( 바닥에선을그어넘어가게하는방법 ) 27 을이용한보행훈련이보행동결을줄이는데매우효과적인방법이라고보고되고있다. 28,29 나 ) 약물치료 : 일반적으로보행동결은약물효과가저하된 off-state 시에많이나타난다. 이는레보도파에의한도파민효과가저하되는것과연관성이있는것으로알려져있기때문에도파민약물의용량을증가시켜보행동결을줄여줄수있다. 19 그러나, 아직까지도파민계약물의효과가감소되어발생하는지또는증가되어발생하는지에대한명확한결론이없는상태이다. 30 또한, 도파민계약물이외에도노르에프네프린전구물질인 L-threo-DOPS가사용되었는데이는진행된파킨슨병에서나타나는무동증이노르에피네프린의저하와관련되어있음에근거하였다. 30 또한최근에는 methylphenidate를사용하여보행동결의호전을보고한연구가발표되고있다 다 ) 운동치료 : 최근에파킨슨병환자에서운동치료가육체적기능상태, 균형감, 보행, 근력및삶의질에긍정적인효과를보인다는연구들이많이발표된후운동치료가보행동결에도효과가있을것이라고제기되고있다. 이에최근에는답차를이용한보행훈련, 댄스치료, motor imagery를이용한보행훈련등의연구들이많이진행되고있다. 15 라 ) 수술적치료 : 심부뇌자극술 (deep brain stimulation) 이보행동결의증상을호전시키는것으로되어있다. 현재까지가장효과적으로알려져있는수술법은시상하핵자극술로일반적으로양측자극술이단측자극술보다효과적으로알려져있다. 35 수술적치료는 off-state에나타나는보행동결에효과적이지만 on-state에나타나는보행동결에는아직효과가알려져있지않고수술적치료에있어서가장중요한점은대상환자군의선정이며이에관하여는아직도많은연구가진행중이다. 15 결론 파킨슨병에서관찰되는자세이상및보행장애는대부분의경우축성증상이동반되거나병기가진행된경우나타나며도파민계약물치료에반응이적은증상으로알려져있다. 이러한자세이상과보행장애는파킨슨병환자에서균형능력의감소로인해낙상의발생을증가시켜골절의위험도를높이는것으로알려져있다. 현재까지자세이상과보행동결에대한연구는많이진행되고있지만발병기전및치료법에대해서명확하게알려져있지않은것이현실이다. 향후, 파킨슨병환자의유병기간이길어지면서자세이상과보행장애, 낙 40
5 김형섭외 2 인 : 파킨슨병에서나타나는자세이상및보행장애의재활 상및골절은지속적으로증가할것으로생각된다. 이에파킨슨병환자의진료시자세및보행과연관된동반증상들에대한세심한주의가필요하며활동저하로인한근력감소및균형장애에대한포괄적재활치료가같이시행되어야할것이다. 이와함께, 자세이상및보행장애를진단한경우약물치료, 감각자극보행훈련, 운동치료및수술적치료등의포괄적접근을통해진단초기에적절한치료법이적용되어야할것으로생각한다. References 111 Benatru I, Vaugoyeau M, Azulay JP. Postural disorders in Parkinson s disease. Neurophysiol Clin 2008;38: Doherty KM, van de Warrenburg BP, Peralta MC, Silveira Moriyama L, Azulay J, Gershanik OS, et al. Postural deformities in Parkinson s disease. Lancet Neurol 2011;10: Giladi N, Kao R, Fahn S. Freezing phenomenon in patients with parkinsonian syndromes. Mov Disord 1997;12: McCluskey LF. Camptocormia: pathogenesis, classification, and response to therapy. Neurology 2006;66: Djaldetti R, Mosberg Galili R, Sroka H, Merims D, Melamed E. Camptocormia (bent spine) in patients with Parkinson s disease--characterization and possible pathogenesis of an unusual phenomenon. Mov Disord 1999;14: Lepoutre AC, Devos D, Blanchard Dauphin A, Pardessus V, Maurage CA, Ferriby D, et al. A specific clinical pattern of camptocormia in Parkinson s disease. J Neurol Neurosurg Psychiatry 2006;77: Jorens PG, Eycken MP, Parizel GA, Martin JJ. Antecollis in parkinsonism. Lancet 1989;1: van de Warrenburg BP, Cordivari C, Ryan AM, Phadke R, Holton JL, Bhatia KP, et al. The phenomenon of disproportionate antecollis in Parkinson s disease and multiple system atrophy. Mov Disord 2007;22: Papapetropoulos S, Baez S, Zitser J, Sengun C, Singer C. Retrocollis: classification, clinical phenotype, treatment outcomes and risk factors. Eur Neurol 2008;59: Yokochi F. Lateral flexion in Parkinson s disease and Pisa syndrome. J Neurol 2006;253 Suppl 7: Villarejo A, Camacho A, Garca-Ramos R, Moreno T, Penas M, Juntas R, et al. Cholinergic-dopaminergic imbalance in Pisa syndrome. Clin Neuropharmacol 2003;26: Panisset M. Freezing of gait in Parkinson s disease. Neurol Clin 2004;22:S53-S Takakusaki K, Tomita N, Yano M. Substrates for normal gait and pathophysiology of gait disturbances with respect to the basal ganglia dysfunction. J Neurol 2008;255 Suppl 4: Abbruzzese G, Berardelli A. Sensorimotor integration in movement disorders. Mov Disord 2003;18: Boonstra TA, van der Kooij H, Munneke M, Bloem BR. Gait disorders and balance disturbances in Parkinson s disease: clinical update and pathophysiology. Curr Opin Neurol 2008;21: Giladi N, Hausdorff JM. The role of mental function in the pathogenesis of freezing of gait in Parkinson s disease. J Neurol Sci 2006;248: Fahn S. The freezing phenomenon in parkinsonism. Adv Neurol 1995;67: Okuma Y. Freezing of gait in Parkinson s disease. J Neurol 2006;253 Suppl 7: Giladi N. Medical treatment of freezing of gait. Mov Disord 2008;23 Suppl 2:S Giladi N, McDermott MP, Fahn S, Przedborski S, Jankovic J, Stern M, et al. Freezing of gait in PD: prospective assessment in the DATATOP cohort. Neurology 2001;56: Snijders AH, Nijkrake MJ, Bakker M, Munneke M, Wind C, Bloem BR. Clinimetrics of freezing of gait. Mov Disord. 2008;23 Suppl 2:S Okuma Y, Yanagisawa N. The clinical spectrum of freezing of gait in Parkinson s disease. Mov Disord. 2008;23 Suppl 2:S
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