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1 대한한방내과학회지제 37 권 4 호 (2016 년 9 월 ) J. Int. Korean Med. 2016;37(4): 양승보 1, 김연진 1, 이형민 1, 이현중 1, 조승연 2, 박정미 2, 고창남 2, 박성욱 2 1 경희대학교대학원한방순환신경내과학교실, 2 경희대학교한의과대학순환 신경내과 Effects of Korean Medicine on Patients with Idiopathic Parkinson s Disease: A Retrospective Study Seung-bo Yang 1, Yeon-jin Kim 1, Hyung-min Lee 1, Hyun-joong Lee 1 Seung-yeon Cho 2, Jung-mi Park 2, Chang-nam Ko 2, Seong-uk Park 2 1 Dept. of Cardiology and Neurology of Clinical Korean Medicine, Graduate School, Kyung-Hee University 2 Dept. of Cardiology and Neurology of College of Korean Medicine, Kyung-Hee University ABSTRACT Objectives: The purpose of this study was to investigate the effects of Korean medicine on patients with idiopathic Parkinson s disease. Methods: The charts of 47 patients diagnosed with idiopathic Parkinson s disease in the Department of Internal Korean medicine, Stroke and Neurological Disorders Center, Kyung Hee University Hospital, Gangdong between August 2012 and July 2016 were reviewed. The Unified Parkinson s disease rating scale (UPDRS) was administered before and after treatment with Korean medicine. Results: Thee average UPDRS Ⅱ+Ⅲ, UPDRS Ⅱ, and UPDRS Ⅲ of the 47 patients decreased significantly from 22.26± 15.15, 10.19±7.53, and 12.06±8.35, respectively, pretreatment to 16.96±13.63, 7.47±6.44, and 9.49±7.73, respectively, post-treatment. The average postural instability and gait difficulty (PIGD), tremor, and bradykinesia also significantly improved post-treatment. Conclusions: These results provide evidence that Korean medicine can improve the activities of daily living and motor function of patients with idiopathic Parkinson s disease. In particular, Korean medicine may be effective for the treatment of PIGD, tremor, and bradykinesia. Key words: idiopathic Parkinson's disease, Korean medicine, Unified Parkinson's disease rating scale, postural instability and gait difficulty, tremor, bradykinesia Ⅰ. 서론 파킨슨병은퇴행성뇌질환으로, 운동기능장애뿐만아니라신경정신과적증상및비운동성징후들도포함하는복합적인병태를나타내는질환이다 1. 투고일 : , 심사일 : , 게재확정일 : 교신저자 : 박성욱서울시강동구동남로 892 강동경희대학교병원중풍뇌질환센터한방내과 TEL: FAX: seonguk.kr@gmail.com 파킨슨병의운동성증상으로는 tremor, bradykinesia, rigidity가특징적이며, PIGD(postural instability and gait difficulty) 는질환의후기에나타나게되는데, 이증상들을통틀어파킨슨병의 4대증상이라한다 2. 파킨슨병치료는 Levodopa, Dopamine agonists, Monoamine oxidase(mao) B inhibitors, Anticholinergic agents, Amantadine, Catechol-O-methyl transferase (COMT) inhibitors 등의약물치료법 3 과운동요법 4-6, 653

2 언어치료 7, 식이조절등의비약물치료법등이있다. 하지만파킨슨병약물치료에따른운동성합병증으로 dyskinesia 와 wearing off 현상과 on-off 현상등이나타나기도하며, 약물자체의부작용을겪는경우도있고, 파킨슨병의대표적인치료약제인도파민제제가 PIGD 를개선시키지못하는한계 8,9 가있으므로보완대체의학에대한수요가늘고이에대한연구가활발히진행되고있다. Kim 등 10 의보고에따르면, 한국의파킨슨병환자의 76% 가보완대체의학치료를받고있으며 70.0% 는한약, 62.8% 는침치료, 26.6% 는부항치료, 9.6% 는뜸치료, 2.1% 는수지침치료를받는다고하여한의치료가많이사용되고있음을알수있다. 파킨슨병의운동성증상에대한침치료 11, 전침치료 12, 봉침치료 13 등의효과는여러연구를통해보고되어있다. 하지만한국의한의의료기관에서는파킨슨병치료에주로침, 약침, 봉침, 한약투여등의복합치료를시행하고있으나, 복합치료의구체적인효과에대한연구는부족한실정이다. 따라서본연구에서는특발성파킨슨병환자에게복합한의치료가파킨슨병의 tremor, bradykinesia, PIGD 각각의세부적지표에있어어떤효과가있는지알아보고자강동경희대학교병원중풍뇌질환센터한방내과의치료사례들을후향적으로차트분석했다. Ⅱ. 방법 1. 연구대상 2012년 8월 1일부터 2016년 7월 31일까지강동경희대학교병원중풍뇌질환센터한방내과에내원하여특발성파킨슨병으로치료받은환자중초진시 UPDRS 를평가를하고추후 UPDRS follow up 기록이남아있는환자를선별하여전자의무기록 (electronic medical records, EMR) 을확인하였다. 본연구는강동경희대한방병원의임상시험심사위원회 (institutional review board, IRB) 의승인을받았다 (KHNMC-OH-IRB ). 2. 치료방법 1) 침치료동방침구제작소직경 0.25 mm, 길이 30 mm의규격의일회용 stainless steel 호침을사용하여 15 분간유침하였다. 환자의상태에따라자침을하되, 주로백회 (GV20) 와양측풍지 (GB20), 합곡 (LI4), 곡지 (LI11), 족삼리 (ST36), 양릉천 (GB34), 삼음교 (SP6), 태충 (LR3) 등의혈위에자침하였다. 2) 봉침치료증류수에 1:20000으로희석한봉독 ( 한국유밀농원산 ) 을 1주일에 1회양측태충 (LR3), 양릉천 (GB34), 족삼리 (ST36), 곡지 (LI11), 풍지 (GB20) 에인슐린주사기로각각 0.1 cc씩주입하였다. 3) 한약치료환자의상태에따라적합한처방을투여하였다. 주로억간산, 청간소요산이나체간및망문문절을통해사상체질을변증하여사상체질처방을사용하였다. 탕약의경우 1일기준으로 2첩을 3회로나누어 120 cc씩매식후 2시간에복용하였고, 제제약은강동경희대한방병원에서조제한약을복용하였다. 4) 기타치료환자의주소증에따라필요시약침, 전침, 뜸, 부항치료등을추가적으로시행하였다. 5) 양약치료처음치료시도파민효현제, 도파민제제등의양약이투여되고있었던경우변동없이유지하였다. 3. 평가방법파킨슨병을평가하는데있어가장보편적으로많이사용되는지표는 UPDRS(unified Parkinson's disease rating scale) 이다 14. UPDRS는 I에서 Ⅵ 파트까지있고, 이중 Ⅱ는일상생활활동능력을평가하고, Ⅲ는운동기능을평가하는항목이다 15. 초진시 UPDRS 중 part Ⅱ와 part Ⅲ 평가를하였고, 한의치료시행한후평균 3-4개월후재진시 UPDRS 재평가를하였다. UPDRS 를통해 PIGD, 654

3 양승보 김연진 이형민 이현중 조승연 박정미 고창남 박성욱 tremor, bradykinesia의 score를계산하였다. PIGD score 는 UPDRS Ⅱ 13, 14, 15번항목의합과 UPDRS Ⅲ 29, 30번합의합계로계산하고, tremor score는 UPDRS Ⅱ 16번항목과 UPDRS Ⅲ 20, 21번항목의합으로계산하고, bradykinesia score는 UPDRS Ⅲ 23, 24, 25, 26번항목의합으로계산하였다. 4. 통계분석본연구의통계처리는 statistical program for social science(spss) v12.0을이용하였으며, 모든자료는 mean±standard deviation(sd) 으로나타내었다. 환자들의한의치료전후 UPDRS 변화는 paired t-test를이용하여분석하였다. Ⅲ. 결과 1. 일반적특성 2012년 8월 1일부터 2016년 7월 31일까지강동경희대학교병원중풍뇌질환센터한방내과에내원하여파킨슨증후군으로치료받은환자는총 431명이었다. 이중초진시 UPDRS 를평가를한환자는 189명이고추후 UPDRS follow up 기록이남아있는환자는 92명이었다. 이들중다음과같은기준을만족하는환자들은총 47명이었다. 1) 특발성파킨슨병으로진단받은자 2) 초진시 UPDRS 평가를하고 10회이상진료받은후 UPDRS 재평가를받은자 3) UPDRS 재평가기간이 8개월이내인자 4) 복용하는양약의변동이없는자 47명의파킨슨병환자들의성별은남자 21명, 여자 26명이었고, 대상자들의평균연령은 64.2±8.61 세였다. 치료받은기간은 ±42.03일, 치료받은횟수는 19.36±7.33회였다 (Table 1). Table 1. General Chacteristics of Idiopathic Parkinson's Disease Patients Chacteristics Patients (n=47) Mean of age (year) 64.2±8.61 Sex (N) Man 21 Woman 26 Duration of treatment (day) ±42.03 Number of treatment 19.36±7.33 Values are mean±standard deviation or number. 2. UPDRS Ⅱ와 Ⅲ의변화초진시파킨슨병환자들의평균 UPDRS Ⅱ+Ⅲ, Ⅱ와 Ⅲ는각각 22.26±15.15, 10.19±7.53, 12.06±8.35 이었으나, 치료후에는 16.96±13.63, 7.47±6.44, 9.49±7.73 로유의하게감소하였다 (p<0.05, Table 2). 이는각각처음에비하여 23.81%, 26.69%, 21.31% 감소한수치이다. Table 2. Changes in Unified Parkinson's Disease Rating Scale Ⅱ and Unified Parkinson's Disease Rating Scale Ⅲ after Treatment in Idiopathic Parkinson's Disease Patients Before After p-value* UPDRS** Ⅱ+Ⅲ 22.26± ± UPDRS Ⅱ 10.19± ± UPDRS Ⅲ 12.06± ± Values are mean±standard deviation. *p-value is calculated by paired t test. **UPDRS : unified Parkinson's disease rating scale 3. PIGD score의변화초진시파킨슨병환자들의평균 PIGD score는 4.13±3.65 이었으나, 치료후에는 3.00±3.26 로유의하게감소하였다 (p<0.05). 이는처음에비하여 27.36% 감소한수치이다. PIGD의세부항목으로는 falling, freezing, walking, gait가치료전후유의하게감소하였다 (p<0.05, Table 3). 655

4 Table 3. Changes in Postural Instability and Gait Difficulty Related Unified Parkinson's Disease Rating Scale after Treatment in Idiopathic Parkinson's Disease Patients Before After p-value* Total PIGD** score 4.13± ± Falling 0.47± ± Freezing 0.55± ± Walking 1.11± ± Gait 1.15± ± Postural stability 0.85± ± Values are mean±standard deviation. *p-value is calculated by paired t test. **UPDRS : unified Parkinson's disease rating scale 4. Tremor score의변화초진시파킨슨병환자들의평균 tremor score는 2.49±1.67 이었으나, 치료후에는 1.94±1.63 로유의하게감소하였다 (p<0.05). 이는처음에비하여 22.09% 감소한수치이다. Tremor 의세부항목으로는 tremor 와 rest tremor가치료전후유의하게감소하였다 (p<0.05, Table 4). Table 4. Changes in Tremor Related Unified Parkinson's Disease Dating Scale after Treatment in Idiopathic Parkinson's Disease Patients Before After p-value* Total tremor score 2.49± ± Tremor 1.11± ± Rest tremor 0.81± ± Action tremor 0.57± ± Values are mean±standard deviation. *p-value is calculated by paired t test. 5. Bradykinesia score의변화초진시파킨슨병환자들의평균 bradykinesia score는 3.83±3.18 이었으나, 치료후에는 3.02±3.12로유의하게감소하였다 (p<0.05). 이는처음에비하여 21.15% 감소한수치이다. Bradykinesia 의세부항목으로는 finger taps, hand movements, rapid alternating movements of the hands 가치료전후유의하게감소하였다 (p<0.05, Table 5). Table 5. Changes in Bradykinesia Related Unified Parkinson's Disease Rating Scale after Treatment in Idiopathic Parkinson's Disease Patients Before After p-value* Total bradykinesia score 3.83± ± Finger taps 0.85± ± Hand movements 1.02± ± Rapid alternating movements of the 1.11± ± hands Leg agility 0.85± ± Values are mean±standard deviation. *p-value is calculated by paired t test. Ⅳ. 고찰및결론 본연구를통하여특발성파킨슨병환자에게평균약 3-4개월동안약 20회정도의한의치료시 UPDRS Ⅱ와 UPDRS Ⅲ에서유의한효과가있는것을확인할수있었다. 본연구결과, 한의치료후 UPDRS Ⅱ+Ⅲ, Ⅱ와 Ⅲ는각각 5.30점, 2.72점, 2.57점만큼유의하게호전되었다. UPDRS Ⅱ+Ⅲ 는 5-8점, UPDRS Ⅲ는 점정도감소하는것이임상적으로유효한최소변동폭 (minimal clinically important change) 으로알려져있다 따라서본연구결과를통해파킨슨병환자의 UPDRS Ⅱ+Ⅲ, Ⅱ와 Ⅲ 개선에있어한의치료가유효하다는것을확인할수있다. Zhang 등 19 에따르면, 12개의연구에서파킨슨병환자에 TCM과양약투여를병용시행한군이양약단독투여군보다 UPDRS Ⅱ가평균 2.14 호전이된것에비해본연구에서는 2.72 호전되어더좋은효과를보였고, 14개의연구에서 TCM과양약투여를병용시행한군이양약단독투여군보다 UPDRS Ⅲ가평균 2.45 호전이된것에비해본 656

5 양승보 김연진 이형민 이현중 조승연 박정미 고창남 박성욱 연구에서는 2.57 호전되어역시더좋은효과를보였다. TCM에서는한약, 침, 뜸, 부항, 추나, 마사지, 기공등을시행하여본연구에비해추나, 마사지, 기공등을더받는경우가있으나, 본연구에서는약침, 봉침치료를더시행한차이가있다. PIGD score 는본연구결과, 한의치료후 4.13±3.65 에서 3.00±3.26로 27.36% 감소하여유의하게호전되었다. PIGD 에한의치료가유의한효과를보이는것은파킨슨병의대표적인치료약제인도파민제제가 PIGD 를개선시키지못하므로 8,9 더욱의미가있다. PIGD 5개항목중 falling, freezing, walking, gait 등의 4개항목에서모두유의한개선효과를보였으나, postural stability는유의한차이를보이지않았다. 하지만 Cho 등 13 에따르면파킨슨병환자에침치료와봉독치료를통해 Berg balance scale 상에서유의한개선효과가있음을보고하였고, Toosizadeh 등 12 에따르면파킨슨병환자에서전침치료시행후 stabilogram 으로일반인에비해증가된 ratio of medial-lateral(ml) center of gravity(cog) sway to anterior-posterior(ap) sway(cog ML/AP) 가감소되어전침치료가 postural stability 에유효하다는것을확인한바있고, 이등 20 에따르면한양방복합치료를통해 UPDRS Ⅲ 중 postural stability 가개선됨을보고한바있다. 따라서본연구에서 postural stability 단일항목에유의한차이를보이지않았지만, 봉침, 전침등의치료를통해서 postural stability를개선할수있는효과가있을것으로예상되며, 향후이에대한추가적인효과및기전연구가필요할것으로사료된다. Tremor score 는본연구결과, 한의치료후 2.49±1.67 에서 1.94±1.63로 22.09% 감소하여유의한차이를보였다. 특히 tremor 정도와 resting tremor를감소시키는것을확인하였다. Shulman 등 11 은침치료가파킨슨병환자가주관적으로느끼는떨림증상을개선한다고보고하였고, Ishikawa 등 21 은가미소요산엑스제 (TJ-24) 가약인성파킨슨증후군환자의떨림개선에유의한효과가있다고보고하였다. 또 한 Wang 등 22 은전침치료가파킨슨병환자의 tremor 증상을호전시킨다는것을보고하였다. 이를통해본연구에서사용된침치료, 전침치료가 tremor 증상을완화시키는데기여했을것으로추정된다. 또한향후본연구에서사용된약침, 봉침이침치료와어떤차이가있는지에대한효과및기전연구가필요할것으로사료된다. Bradykinesia score는본연구결과, 한의치료후 3.83±3.18에서 3.02±3.12로 21.15% 감소하여유의한차이를보였다. Wang 등 22 은전침치료가파킨슨병환자의 bradykinesia 증상을개선시켰는데, 특히 bradykinesia-rigidity type과 mixed type에서더좋은효과를보였다고보고하였다. Wang 등 22 은파킨슨병환자에게전침치료를 2개월동안 3일에 1번씩시행하여 bradykinesia score(mean±sd) 가 9.0±6.3 에서 7.4±5.9 로감소하였다고보고하였는데, 본연구와피험자 baseline severity 에서차이가많이나며, 본연구는전침을선택적으로시행하여주로자침만을시행한경우가많았고, 치료기간및횟수도본연구에서더적은등에서차이가있었다. 따라서전침치료를시행하고, 치료를조금더높은빈도로시행한다면더좋은효과가있을것으로기대되며, 향후파킨슨병의 type과 severity 등에따른치료효과의차이에대한추가적인연구가필요할것으로사료된다. 약처방은환자의상태에따라투여하였다. Kim 등 23 에따르면기존의파킨슨병연구는다양한처방및약재를사용하여한약치료에따른파킨슨병치료효과에대한 review 를하기어려우며, 대조군과비교하였을때한약치료에따른특이적인효과를명확하게발견하기어려웠다고보고하였다. 억간산 24, 열다한소탕 25,26, 청심열다탕 27, 향사양위탕 28, 소합향원 29, 소속명탕 30 등다양한복합처방과여러단일한약재추출물이나한약재성분추출물에서의신경보호작용에대한연구는이미보고된바있는데, 한의의료기관에서는단일한약재보다는한약복합처방을주로사용하므로향후복합처방에 657

6 대한연구가더많이필요할것으로사료된다. 박등 31 은파킨슨병이한의학적으로病因은주로風火痰瘀및肝脾腎心虛이고, 이에따라肝腎陰虛, 氣血兩虛, 痰熱內阻, 氣滯血瘀의임상유형으로분류할수있다고하였다. 또한이등 19 은파킨슨병환자의사상체질에따른사상체질처방투여가포함된한양방복합치료를시행한치험례나열다한소탕 32, 지황백호탕 33 을투여한치험례도보고된바있다. 향후파킨슨병에대한사상체질이론을포함한한의학적변증증형과처방표준안을확립하고이에대한연구가필요할것으로사료된다. 또한파킨슨병의비운동성증상인인지장애, 우울, 불안등의기분장애, 수면장애, 피로감, 자율신경장애등의증상에대한한의치료의효과에대한연구도필요할것으로사료된다. 본연구를통하여파킨슨병의 tremor, bradykinesia, PIGD 증상각각대한한의치료의효과를확인할수있었다. 향후위에서제시한각증상및치료법별로추가적인연구를위한참고가될수있도록본연구결과를보고하는바이다. Acknowledgments This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology(NRF ). 참고문헌 1. Langston JW. The Parkinson's complex: parkinsonism is just the tip of the iceberg. Ann Neurol 2006; 59(4): Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol 1999;56(1): Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA 2014; 311(16): Shulman LM, Katzel L, Ivey FM, Sorkin JD, Favors K, Anderson KE, et al. Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease. JAMA Neurol 2013;70(2): Li F, Harmer P, Fitzgerald K, Eckstrom E, Stock R, Galver J, et al. Tai Chi and Postural Stability in Patients with Parkinson s Disease. NEJM 2012;366(6): Hirsch MA, Toole T, Maitland CG, Rider RA. The effects of balance training and high-intensity resistance training on persons with idiopathic Parkinson's disease. Arch Phys Med Rehabil 2003;84(8): Herd CP, Tomlinson CL, Deane KH, Brady MC, Smith CH, Sackley CM, et al. Speech and language therapy versus placebo or no intervention for speech problems in Parkinson's disease. Cochrane Database Syst Rev 2012;15(8):CD Kwakkel G, de Goede CJ, van Wegen EE. Impact of physical therapy for Parkinson's disease: a critical review of the literature. Parkinsonism Relat Disord 2007;13: Robert AH, Kelly EL, Rajesh P, Theresa AZ. A translation of Parkinson s disease: Questions and answers. 4th ed. Seoul: Panmun Book Co.; 2005, p. 99, Kim SR, Lee TY, Kim MS, Lee MC, Chung SJ. Use of complementary and alternative medicine by Korean patients with Parkinson's disease. Clin Neurol Neurosurg 2009;111(2): Shulman LM, Gruber-Baldini AL, Anderson KE, Fishman PS, Reich SG, Weiner WJ. The clinically important difference on the unified 658

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar