online ML Comm CLINICAL ARTICLE J Kor Neurotraumatol Soc 2010;6: ISSN 우리나라에서두부외상후지속적식물상태와최소의식상태환자의여명추정방법 순천향대학교의과대학천안병원신경외과학교실 심재현. 이

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1 online ML Comm CLINICAL ARTICLE J Kor Neurotraumatol Soc 2010;6: ISSN 우리나라에서두부외상후지속적식물상태와최소의식상태환자의여명추정방법 순천향대학교의과대학천안병원신경외과학교실 심재현. 이경석. 김라선. 도재원. 윤일규. 배학근 A Method for Estimation of the Life Expectancy for the Persistent Vegetative State and Minimally Conscious State after Craniocerebral Trauma in Korea Jae-Hyun Shim, MD, Kyeong-Seok Lee, MD, Ra-Sun Kim, MD, Jae-Won Doh, MD, Il-Gyu Yun, MD and Hack-Gun Bae, MD Department of Neurosurgery, Chonan Hospital, College of Medicine, Soonchunhyang University, Chonan, Korea Objective: Estimation of the life expectancy (LE) for patients in a persistent vegetative state (PVS) or minimally conscious state (MCS) depends on the statistical probability. Since the statistics of LE increases year by year, we should update the ratio of expected life spans based on the recent data. Methods: We searched recent (after January 2000 to June 2010) articles on the LE and PVS using PubMed. We excluded letters or comments. Using data from the literature review and the life table of Korean National Statistical Office, we proposed a scheme estimating the LE for PVS and MCS patients after head injuries. Results: There were three papers on the mortality or LE of PVS or MCS patients. To diagnose PVS and MCS correctly, we should use the revised coma recovery scale. The reported LE of PVS and MCS patients was longer than when the Lee s scheme was applied. The ratio of LE would be 10-25% for PVS, 20-40% for MCS fed by others, and 40-70% for MCS self fed. Conclusion: We reviewed diagnostic criteria for the PVS and MCS. For updated estimation of the individual LE for PVS or MCS, we proposed a method based on the recent data from the literature review. (J Kor Neurotraumatol Soc 2010;6: ) KEY WORDS: Life expectancy ㆍ Mortality ㆍ Persistent vegetative state ㆍ Craniocerebral trauma. 서 론 지속적식물상태 (persistent vegetative state: PVS) 또는최소의식상태 (minimally conscious state: MCS) 인사람의여명 (life expectancy) 은보통사람들의평균여명에비해명백히짧으리라본다. 그러나구체적으로특정인의여명이얼마나단축될지는알수없다. 하지만손해 Received: October 10, 2010 / Revised: October 12, 2010 Accepted: November 6, 2010 Address for correspondence: Kyeong-Seok Lee, MD Department of Neurosurgery, Chonan Hospital, College of Medicine, Soonchunhyang University, 8 Sooncheonhyang 2-gil, Dongnam-gu, Chonan , Korea Tel: , Fax: kslshl@schmc.ac.kr 를배상하거나보상하는경우에는모른다고무시할수없으며, 과학적으로가장가능성이높은경우를추정하여제시할수밖에없다. 10,11) 물론 PVS나 MCS의여명을추정하는일은결국통계에의한확률에의존하지않을수없다. 그동안우리나라에는두부외상후유장애인의여명을추정할수있는자료가거의없어서 Lee 11) 가제시한다른나라의통계적자료와우리나라의여명통계에근거하여장애정도에따른여명비율을반영하는방법이가장많이이용된것으로보인다. 인류의평균수명은, 특히선진국들을중심으로해마다증가하고있고, 의료기술의발달로중증환자의생명도그만큼길어질수있다. 따라서 2000 년이후발표된 PVS와 MCS 의여명과관련된문헌을조사분석하여 PVS와 MCS의 110 Copyright 2010 Journal of Korean Neurotraumatology Society

2 Jae-Hyun Shim, et al. 진단기준과시대에맞는여명감정이가능하기위한여명추정방법을살펴보고자한다. 대상및방법 2000년 1월부터 2010 년 6월까지발표된영문문헌을 Pub- Med를이용해검색하였다. 검색에이용한핵심단어는여명과 PVS였다. 문헌은영문으로, 기간은최근 10년으로제한하였고, 편지 (letter) 나논평 (comment) 은제외하였다. 모두 6개의논문이검색되었으나, 이중사망률이나여명을다룬논문은 3개뿐이었고, 다른논문들은윤리적측면을다룬논문이었다. 이들 3개의논문 2,3,19) 과다른방법으로찾은문헌들을대상으로 PVS와 MCS의여명에영향을주는요소와평균여명또는평균여명단축을조사하였다. 그리고이자료들을이용하여나이와성별 PVS와 MCS의여명을산출하는방법을고안하였다. 결과 지속적식물상태와최소의식상태의정의와진단기준식물상태란정의상 각성 ( 覺醒 ) 이가능하나인식 ( 認識 ) 은불가인상태 (awakefullness without awareness) 를말한다. 13) MCS는식물상태처럼외부자극에대해적절한반응을보이지는못하지만, 일부의식이남아있음을확인할수있는경우를말한다. 7) 그러나 PVS나 MCS 를정확하게진단할수있는검사방법은없다. 여러진단기준들이있지만, 잘못진단된경우도적지않다. 이를좀더객관적으로평가하기위한방법으로개정혼수회복지수 (Coma Recovery Scale-Revised: CRS-R) 8) 가개발되었다 (Table 1). PVS는 CRS-R 로청각반응 2점이하, 시 각반응 1점이하, 운동반응 2점이하, 구강언어반응 2점이하, 의사소통 0점, 그리고각성반응이 2점이하이어야한다. 청각반응이 3~4 점, 또는시각반응 2~5 점, 또는운동반응 3~5점, 또는구강언어반응 3점, 또는의사소통 1점이면 MCS라고진단할수있으며, 운동반응이 6점이거나의사소통이 2점이면 MCS에서회복된것으로판단한다. 16) PVS와 MCS의여명 PubMed를이용해검색한 2000년이후발표된 PVS와 MCS의여명과관련된논문은 3개였다 (Table 2). 이들논문에는 PVS나 MCS가의식을되찾는평균시기나확률, 그리고평균생존기간에대한자료가발표되었으나, 이자료만으로특정 PVS나 MCS의여명을바로구할수는없다. 2007년 Shavelle 등 17) 은 1,723 예의 PVS와 3,598예의 10세이상두부외상후유장애인의자료에근거하여 PVS와 MCS의나이별여명을보고하였다. MCS의경우거동 (mobility) 여부가여명에큰영향을주고, 거동이불가한경우에는식사를혼자서할수있는지없는지가여명에큰영향을주는요소라고한다. 이자료에는이런기준에따라일반사람들의남녀평균여명과함께 10세별 PVS와걷지못하고식사도혼자서는할수없는사람의여명이다른두부외상후유장애인의여명과함께제시되어있다. 이자료에서구한 PVS와 MCS의여명비율을통계청이발표한 2008년우리나라남녀평균여명에그비율그대로각각적용하여산출여명 (calculated life expectancy: CLE) 을구하였다. 한편 Lee 11) 가제안한여명비율의산술평균을 2008년우리나라남녀평균여명에적용하여평균산출여명 (mean calculated life expectancy; mcle) 을구하였다. 곧, PVS 또는 MCS의여명을일반인여명으로나눈비율을우리나라평균여명에곱하여 CLE 를구하고, Lee가제안한여명비율의산술평균 (10~30% 라 TABLE 1. JFK coma recovery scale-revised 8) Items Auditory function scale Visual function scale Motor function scale Oromotor/verbal function scale Communication scale Arousal scale Scores 0-None, 1-Auditory startle, 2-Local, ization to sound, 3-Reproducible movement to command, 4-Consistent movement to command 0-None, 1-Visual, startle, 2-Fixation, 3-Visual pursuit, 4-Object localization: reaching, 5-Object recognition 0-None/flaccid, 1-Abnormal posturing, 2-Flexion withdrawal, 3-Localiza, tion to noxious stimulation, 4-Object manipulation, 5-Automatic motor response, 6-Functional object use 0-None, 1-Oral reflexive movement, 2-Vocalization/oral movement, 3-Intelligible verbalization 0-None, 1-Non-functional: intentional, 2-Functional: accurate, 3-Oriented 0-Unarousable, 1-Eye opening with stimulation, 2-Eye opening w/o stimulation, 3-Attention, 111

3 Estimation of Life Expectancy of PVS & MCS in Korea TABLE 2. Summary of the recent reports on PVS or MCS Author (year) Data or method Key findings Beis et al. 3) (2009) 47 patients in PVS & MCS, retrospective study over 18 years Recovering arousal: 7 traumatic patients Average time: 28.4 (11-65) months Average age: 28 (19-42) years Death: 30 patients Average life span from admission: 45.8 years Ashwal 2) (2005) Multi-society task force report on children in posttraumatic PVS, published 1994 Recovering consciousness After 3month: 56% After 6month: 31% After 12month: likely to be permanent Median survival: 3.0 years Less than 1years: 2.6 years Aged 2-6years: 5.2 years Lipe expectancy Diagnosed in 1980: 3.6 years Diagnosed in 1990: 7.2 years Strauss et al. 20) (2000) 3-15 years aged children, PVS (n=564) Immobile MCS (n=705) Mobile MCS (n=3,806) 8-year survival PVS: 63% Immobile MCS: 65% Mobile MCS: 81% Mobility is more important in predicting survival than the level of consciousness. PVS: persistent vegetative state, MCS: minimally conscious state 면 20%) 을우리나라평균여명에곱하여 mcle를구하였다. PVS와혼자서식사할수없는 MCS, 그리고혼자서식사할수있는 MCS의여명을그래프로비교하였다. PVS의여명은남녀모두 CLE나 mcle의수치가 Shavelle 등 17) 의보고와비슷하였다 (Figure 1). 혼자서식사를할수없는 MCS의여명도 mcle는남녀모두 20세와 30세에서 Shavelle 등 18) 의보고보다조금낮았으나 CLE는남녀모두비슷하였다 (Figure 2). 혼자서식사를할수있는 MCS의여명은남녀모두 CLE는 Shavelle 등의보고 17) 와비슷하였으나 mcle는남녀모두 10~20% 정도더낮았다 (Figure 3). 이자료에따르면 PVS, 혼자서식사할수없는 MCS, 그리고혼자서식사할수있는 MCS의여명은각각일반인여명의 21%, 42%, 그리고 68% 에해당한다. 17) 이수치는미국에서직접조사한자료를통계학적으로다루어얻은수치라는점에서그의미가매우크지만, 영양상태나개개인의건강상태, 또는사회경제적여건을고려하지않고단일수치로결정되어개인차를보정하거나반영할수있는여지가거의없다. 한편 Lee 11) 가제안한두부외상후유장애인의여명비율중 PVS와거동불가한중증장애의여명비율은 PVS가 10~25%, 거동불가한중증장애가 20~50% 로조건과상태에따라적정비율을선택할수있다. 다만혼자서식사를할수있는 MCS의여명은 Lee 11) 의여명비율이상대적으로낮기때문에이부분을전체적으로약 15~20% 정 Ratio (%) Shavelle et al. mcle (M) FIGURE 1. Life expectancy of the PVS. PVS: persistent vegetative state, CLE: calculated life expectancy, mcle: mean calculated life expectancy, M: male, F: female. 도상향조정하여여명비율표를개정하였다 (Table 3). 고 PVS Age (year) 찰 CLE (M) mcle (F) CLE (F) 지속적식물상태종합연구위원회 (The Multi-Society Task Force on Persistent Vegetative State: M- STF on PVS) 는 1994 년식물상태의진단기준으로자신 과주변을전혀인식하지못하여어떠한형태로든의사소 통이전혀되지않으며, 반사적인반응이외의수의적인동작 이나행동이전혀없음을객관적으로확인할수있는 7 가 지조건을제시하였다. 13) 한편, 2002년 Giacino 등 7) 은 112 J Kor Neurotraumatol Soc 2010;6:

4 Jae-Hyun Shim, et al. PVS 의진단기준에합당하지않은일부미미한의식이있 는경우를 MCS 라고명명하고혼수와식물상태, 그리고 잠긴증후군 (locked-in syndrome) 을각각구별하였다. 그리고진단기준으로간단한지시를따르거나, 예 / 아니 오반응을말이나동작으로보이거나 ( 정확도는불문 ), 알 아들을수있는말, 반사가아닌목적있는행동, 예를들 면적절한웃거나우는반응이나질문에대한답변이나행 동, 물건을알고만지거나잡는행동, 물건을따라서보거 Ratio (%) Shavelle et al. mcle (M) CLE (M) mcle (F) CLE (F) FIGURE 2. Life expectancy of the MCS, fed by others. MCS: minimally conscious state, CLE: calculated life expectancy, m- CLE: mean calculated life expectancy, M: male, F: female. Ratio (%) MCS, fed by others Age (year) Shavelle et al. mcle (M) MCS, self fed Age (year) CLE (M) mcle (F) CLE (F) FIGURE 3. Life expectancy of the MCS, self fed. MCS: minimally conscious state, CLE: calculated life expectancy, mcle: mean calculated life expectancy, M: male, F: female. 나주시하는행동등이있을때 MCS로진단할수있다고제시하였다. 또한기능적의사소통이나서로다른두물건의기능적이용에해당하는소견이하나또는둘다있을때 MCS에서벗어났다고판단할수있다고하였다. PVS나 MCS의진단은진찰을통해반응을보는행동평가가표준진단방법이다. 12) 다양한검사를이용해 PVS를진단하려는시도가있으나, 6,14) 지속적식물상태를정확하게진단할수있는검사가없기때문에오진을한경우가 37~ 43% 에이른다는보고도있다. 1,5,16) 이러한오진을줄이기위한방법으로여러가지방법들이발표되었는데, 8,9,18,20) 이중에서도 CRS-R이 MCS의진단에가장예민하다고한다. 16) 따라서 PVS나 MCS의여명을추정할때에는 CRS-R 을이용하여의식상태를객관적으로평가해야한다. PVS는의식이없는데비해 MCS는미약하더라도의식이있는경우이며, 의식의존재는그자체만으로도생존가능성을높인다고알려져있으나, MCS의경우에는의식하나만으로여명이증가하지않았으며, 거동능력 (mobility) 이더중요한영향은준다고한다. 20) 1994년발표된논문에서는 PVS의여명이대부분 2~5년이며 10년을넘는경우는드물다고하였다. 13) 그러나 2007년 Shavelle 등 17) 이보고한자료에서는 10세 PVS의평균여명이 12년으로, 50세 PVS의평균여명도 7년으로길어졌다. PVS나 MCS의여명에영향을주는요소들로다음과같은요소들이알려져있는데, 나이는젊을수록, 성별로는여자의여명이길다고한다. 또한다친뒤생존기간이길수록, 거동능력이있을수록, 자력으로식사를할수있을때, 인식과소통능력이좋을수록, 간질발작이없을수록여명이길다고하였다. 그리고다친연도가늦을수록여명이길어지는데, 1980년에식물상태로진단받은경우여명은 3.6년이었지만, 1990년에진단받은경우는 7.2 년으로 10년사이에여명이두배증가하였다고한다. 2) 따라서우리나라에서도최근자료에의해여명비율을수정할필요가있다. 그밖에도교육정도, 뇌손상의깊이, 두부외상종류 ( 관통 / 둔기 ), 혼수기간, 의식상태와외상후기억상실기간, 행동 TABLE 3. Estimated ratio of life expectancy of the PVS and MCS Outcome Characteristics Ratio (%) Persistent vegetative state Frequent complications or poorly nourished Well nourished without complications Minimally conscious state Fed by others Poor all 3 functions* 1 good function in 3 functions* Self fed 1 good function in 3 functions* 2 good functions in 3 functions* Good all 3 functions* *: Intelligence, Rolling, and Hand use. PVS: persistent vegetative state, MCS: minimally conscious state

5 Estimation of Life Expectancy of PVS & MCS in Korea 장애, 그리고유전자 (APOE 4) 나간호의질등도여명이나생존율에영향을줄수있다고한다. 17) Shavelle 등 17) 의자료에서는 PVS, 혼자서식사할수없는 MCS, 그리고혼자서식사할수있는 MCS의여명은각각일반인여명의 21%, 42%, 그리고 68% 에해당하는데, Lee 11) 의여명비율은 10~25%, 20~35%, 그리고 30~50% 로조금낮게제시되어있다. 또한전자에는여명이하나의수치로제시되어조정이불가한반면, Lee의여명비율은범위를제시하여조정이가능하며, 특히거동불가한중증장애의경우밥먹기, 손쓰기, 몸굴리기, 지능등네가지기능에따라여명을더자세히추정할수있는장점이있다. Shavelle 등 17) 의자료는미국의여명비율이라는점을고려할때혼자서식사할수없는 MCS의여명 20~35% 를 20~40% 로, 그리고혼자서식사할수있는 MCS의여명 30~50% 를 40~70% 로상향조정하면우리나라의여건에합당한수치가되리라본다. 혼자서식사할수있는 MCS 의여명비율이평균 68% 로조금높아보이지만, 2004년 Brown 등 4) 의보고에따르면중등도와중증두부외상환자의경우치사율이매우높지만, 6개월이상생존했을때에는경도두부외상환자의생존율과비슷했다는점과보통여명을감정하는시기는 1년이상생존한경우라는점을고려하면이비율을반영하는것이적절하리라본다. 한편, Shavelle 등 17) 의자료는여명을단일수치로정해성별과 10세별로다르게제시하였으나, 이를일반인여명에대한여명비율로보면해당일반인남녀의여명이나이별로다르기때문에, 남녀각 10세별여명에해당여명비율을곱하여얻은수치와크게다르지않았다. 나이와성별에따른여명의차이는일반인여명의나이와성별로반영할수있기때문에이를다시반영하지않았다. 그밖에여명에영향을주는요소들중자력식사여부나거동능력, 지적능력이나소통능력등은어느항목의여명비율을적용할지결정하기위한자료로활용하고, 다친뒤생존기간이나간질발작, 영양상태나사회경제적여건등은실제개개인의여명을추정할때산술적으로구한수치를조정할때활용하는것이더좋으리라본다. 예를들면혼자서밥을먹을수없고, 손을쓰지못하며, 몸도돌리지못하고지적능력도매우낮은 20세남자 MCS 환자라면여명비율이 년의 20~30% 에해당하여계산상 11.4~17.1 년이되는데, 보통은중간값인 14.3 년을선택하지만, 여러조건이좋으면상한쪽수치를택하고, 여러조건이나쁘면하한쪽수치를선택하는것이무난하리라본다. 결 론 최근발표된 PVS 와 MCS 의여명과관련된문헌을조 사분석하여 PVS 와 MCS 의진단기준을살펴보았다. 또한 이들자료에근거하여시대에맞는여명감정이가능하기 위한여명추정방법을제안하였다. 중심단어 : 여명 사망률 지속적식물상태 두부외상. REFERENCES 1) Andrews K, Murphy L, Munday R, Littlewood C. Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit. BMJ 313:13-16, ) Ashwal S. Recovery of consciousness and life expectancy of children in a vegetative state. Neuropsychol Rehabil 15: , ) Beis JM, Seyer JL, Brugerolle B, Le Chapelain L, Thisse MO, Mainard D, et al. [Care protocol for persistent vegetative states (PVS) and minimally conscious state (MSC) in Lorraine: retrospective study over an 18-year period]. Ann Phys Rehabil Med 52: , ) Brown AW, Leibson CL, Malec JF, Perkins PK, Diehl NN, Larson DR. Long-term survival after traumatic brain injury: a population-based analysis. NeuroRehabilitation 19:37-43, ) Childs NL, Mercer WN, Childs HW. Accuracy of diagnosis of persistent vegetative state. Neurology 43: , ) Gawryluk JR, D Arcy RC, Connolly JF, Weaver DF. Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques. BMC Neurol 10:11, ) Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, et al. The minimally conscious state: definition and diagnostic criteria. Neurology 58: , ) Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale- Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil 85: , ) Iyer VN, Mandrekar JN, Danielson RD, Zubkov AY, Elmer JL, Wijdicks EF. Validity of the FOUR score coma scale in the medical intensive care unit. Mayo Clin Proc 84: , ) Lee KS. Estimation of the life expectancy for the disabled persons after head injury. J Korean Neurosurg Soc 25: , ) Lee KS. Medical Consideration on the Reparation and Compensation, ed 4. Seoul: Joongangmunhwasa, pp , ) Majerus S, Gill-Thwaites H, Andrews K, Laureys S. Behavioral evaluation of consciousness in severe brain damage. Prog Brain Res 150: , ) Medical aspects of the persistent vegetative state (1). The Multi- Society Task Force on PVS. Medical aspects of the persistent vegetative state, part I. N Engl J Med 330: , ) Owen AM, Coleman MR. Detecting awareness in the vegetative state. Ann N Y Acad Sci 1129: , ) Schnakers C, Majerus S, Giacino J, Vanhaudenhuyse A, Bruno MA, Boly M, et al. A French validation study of the Coma Recovery Scale-Revised (CRS-R). Brain Inj 22: , ) Schnakers C, Vanhaudenhuyse A, Giacino J, Ventura M, Boly M, Majerus S, et al. Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment. BMC Neurol 9:35, ) Shavelle RM, Strauss DJ, Day SM, Ojdana KA. Life Expectancy. In: Zasler ND, Katz DI, Zafonte RD (eds), Brain Injury Medicine: Principles and Practice. New York: Demos Medical Pub- 114 J Kor Neurotraumatol Soc 2010;6:

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386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon