Brain & N eurorehabilitation Vol. 2, No. 1, March, 2009 아급성기뇌졸중환자의인지기능회복 서울대학교의과대학분당서울대학교병원재활의학교실, 1 경상대학교병원재활의학과 오민균 1 ㆍ임종엽ㆍ백남종 Recovery of Post-stroke Cognitive Function during Subacute Stage Min-Kyun Oh, M.D. 1, Jong Youb Lim, M.D. and Nam-Jong Paik, M.D., Ph.D. Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 1 Department of Rehabilitation Medicine, Gyeongsang National University Hospital Objective: The purpose of this study is to find the change in post-stroke cognitive function during subacute phase, and to investigate factors associated with this change. Method: The cognitive function was evaluated using Mini-Mental Status Examination (MMSE) at the beginning of rehabilitation (mean 23.1 ± 12. days after onset) and discharge (mean 88.1 ± 29.8 days after onset) in 5 stroke patients. At the same time functional status was also evaluated using modified Rankin Scale (mrs), National Institutes of Health Stroke Scale (NIHSS) and modified Barthel Index (MBI). Then we compared the improvements of MMSE scores between two time period according to age, sex, stroke profile, and initial functional status. We also determined the correlation between cognitive and functional gain. Results: MMSE scores improved from rehabilitation start to discharge (3.14 ± 5.4, p = ). MMSE scores improved more when patients were male, older than 5 years, and had hemorrhagic and cortical lesions (p<0.05). And, MMSE scores improved more when patients had a higher functional level initially (mrs 2, NIHSS 1, MBI 75), (p<0.05) and improvement of MMSE score was significantly correlated with initial MBI score (r = 0.351, p<0.05 ). Conclusion: Cognitive function recovered during subacute phase of stroke, and improvement of cognitive function at this phase were associated with sex, age, stroke profiles, initial functional status. These results would provide us an information to plan cognitive rehabilitation in these patients. (Brain & NeuroRehabilitation 2009; 2: 71-77) Key Words: cognition, function, recovery, rehabilitation, stroke 서론 뇌졸중은신체적기능장애뿐만아니라인지기능의저하도동반되어 1,2 일상생활동작과사회생활에제한을주고삶의질을감소시키는결과를초래할수있다. 3,4 그러므로뇌졸중환자의치료초기부터정확한인지기능평가와치료가필요한데 5 뇌졸중후인지기능장애의유병률은인지기능장애를정의하는기준, 뇌졸중발병으로부터의시간, 선택된환자군에따라 11. 5.3% 로다양하게보고되고있다. 1,-9 뇌졸중후인지장애와연관된위험인 접수일 : 2009 년 1 월 23 일, 1 차심사일 : 2009 년 2 월 일게재승인일 : 2009 년 3 월 9 일교신저자 : 백남종, 경기도성남시분당구구미로 43-707, 분당서울대학교병원재활의학과 Tel: 031-787-7731, Fax: 031-787-5 E-mail: njpaik@snu.ac.kr 자로는여성, 고령, 낮은교육수준, 우울증, 뇌졸중의중증도 (severity), 좌측뇌병변 (left hemispheric lesion), 피질하병변 (subcortical lesion), 편측무시 (unilateral neglect), 구음장애 (dysarthria), 요실금 (urinary incontinence) 등이보고되고있으나, 1,,10-13 아직통일된의견이없는실정이다. 14 뇌졸중후인지기능저하의자연적경과와회복에대한몇몇연구에의하면시간경과에따라인지기능이향상될수있다고하였으나, 15-17 뇌졸중후아급성기에인지기능회복이어느정도일어나는지또한그러한회복에미치는요인은어떠한것들이있는지에대하여는아직연구가미미한실정이다. 이는향후지속적인인지재활치료가필요한환자나이차적으로혈관성치매가발생할수있는환자군을조기에발견하고치료방침을정하는데있어중요한문제이기도하다. 이에본연구에서는뇌졸중후아급성기에서인지기능 71
Brain& NeuroRehabilitation:2009; 2: 71 77 의변화양상을살펴보고, 이에영향을미치는요인들을알아보고자하였다. Table 1. Characteristics of Patients Age (years) Sex 1) 연구대상 Stroke type Lesion location Lesion site 연구대상및방법 뇌졸중초회발병으로입원치료를받았던환자를대상으로하였으며이중시력및청력장애, 실어증, 전신상태불량과그밖에여러가지이유로협조가되지않아 MMSE의수행이불가능하였던환자를제외한 5명을대상으로하였으며대상자의연령분포는 30세에서 107세로연령은 8.8 ± 13.2세였고, 성별분포는남자 31명, 여자 명이었다. 뇌졸중의유형은뇌출혈 명, 뇌경색 명이었으며, 뇌병변의위치는우측대뇌반구에병변이있는경우가 명, 좌측대뇌반구에병변이있는경우가 명, 양측병변인경우가 명이었다. 뇌병변의병소는피질병변이 명, 피질하병변이 명, 피질-피질하병변이 14명, 천막하병변이 11명이었다 (Table 1). 본연구의프로토콜은임상심의윤리위원회의승인을받았다. 2) 연구방법 연구대상환자모두를대상으로인지기능과기능적수준을평가하였다. 인지기능은 MMSE (Mini-Mental Status Examination) 을이용하여숙련된재활의학과의사가뇌졸중후재활치료시작시 (Time 1, 발병후 23.1 ± 12.일, 범위 55일 ) 와재활치료후퇴원시혹은발병후 3개월째 (Time 2, 발병후 88.1 ± 29.8일, 범위 44 181 일 ) 2회평가하였고, 같은시기에 mrs (modified Rankin Scale), NIHSS (National Institutes of Health Stroke Scale), MBI (modified Barthel Index) 를이용하여환자의기능적 <5 5 Male Female Infarct Hemorrhage Right hemisphere Left hemisphere Bilateral hemisphere Cortical Subcortical Cortical-subcortical Infratentorial Number of patients (n = 5) 31 14 11 수준과신경학적회복정도를평가하였다. 3) 통계처리통계분석은 SPSS 12.0을사용하였다. 뇌졸중후 Time 1에평가된 MMSE 의총점에대하여성별, 연령별, 뇌졸중의유형별, 뇌병변의위치별, 뇌병변의병소별로독립표본 t 검정과분산분석 (ANOVA) 을이용하여비교하였고뇌졸중후 Time 1과 Time 2, 2회평가된 MMSE의 5가지 ( 지남력, 기억등록, 주의집중과계산, 기억회상, 언어능력 ) 각항목별점수와총점에대하여대응표본 t 검정을시행하여비교하였고, 성별, 연령, 뇌졸중의유형및위치, 초기의기능적수준과 MMSE 점수의변화와의연관성은공분산분석 (ANCOVA) 을사용하여분석하였다. 또한초기의 mrs, NIHSS 및 MBI, 그리고 NIHSS 및 MBI의향상정도와 MMSE 점수의향상정도와의상관성은 Pearson 상관분석을통하여알아보았다. 결과 1) 재활치료시작시성별, 연령별, 뇌졸중의유형별, 뇌병변의위치별, 뇌병변의병소별 MMSE 점수비교재활치료시작시 Time 1시기의각군간의 MMSE 점수는성별로는남자는 18. ± 9.8점, 여자는 17.0 ± 9.5점이었고성별간차이는통계적으로유의하지는않았다 (p = 0.548). 연령별로는 5세이상인경우.0 ± 9.1점, 5세미만인경우 22.5 ± 9.4점이었고통계적으로유의한차이가있었다 (p = 0.022). 뇌졸중의유형별로는뇌출혈은 15.7 ± 11.2점, 뇌경색은 18.7 ± 8.8점이었고뇌졸중유형별차이는통계적으로유의하지는않았다 (p = 0.129). 뇌병변의위치별로는우측대뇌반구에병변이있는경우.9 ± 10.7점, 좌측대뇌반구에병변이있는경우 19.0 ± 8.2점, 양측병변인경우 17.3 ± 11.2점이었고뇌병변의위치별차이는통계적으로유의하지는않았다 (p = 1.000). 뇌병변의병소별로는피질병변이 7. ± 10.5 점, 피질하병변이 20.3 ± 8.7점, 피질-피질하병변이 14.5 ± 9.4점 4명, 천막하병변이 22.2 ±.0점이었고피질병변과피질하병변, 피질병변과천막하병변간에통계적으로유의한차이가있었다 (p = 0.014, 0.010) (Table 2). 2) 재활치료시작시와퇴원시 MMSE의향상 MMSE의총점은 Time 1 시기에 17.9 ± 9.점에서 Time 2 시기에 21.0 ± 7.4점으로 3.1 ± 5.4점증가하였다 (p = ). 각항목별로는지남력은 0.9 ± 2.3 (p = 72
오민균외 2 인 : 아급성기뇌졸중환자의인지기능회복 Table 2. Initial MMSE Score according to Demographic Variables and Stroke Features Variables No. of Pts. Initial MMSE p value Gender Age (years) Stroke type Laterality Lesion location Male Female 5 <5* Hemorrhage Infarct Rt. hemiplegia Lt. hemiplegia Bilateral Cortical Subcortical Cortical-subcortical Infratentorial 31 14 11 18. ± 9.8 17.0 ± 9.5.0 ± 9.1 22.5 ± 9.4 15.7 ± 11.2 18.7 ± 8.8.9 ± 10.7 19.0 ± 8.2 17.3 ± 11.2 7. ± 10.5 20.3 ± 8.7 14.5 ± 9.4 22.2 ±.0 0.548 0.022 0.129 1.000 0.014 Values are mean ± standard deviations. *p<0.05 by independent t-test, Group difference: subcortical = infratentorial>cortical = cortical-subcortical, MMSE: Mini-Mental Status Examination. Table 3. Improvement of Mini-Mental Status Examination Score From Rehabilitation Admission to Discharge Orientation Registration Attention and alculation Language Recall Total Rehabilitation admission. ± 3.7 2.5 ± 1.1 2.1 ± 2.0.0 ± 2.9 0.7 ± 1.1 17.9 ± 9. Discharge 7.4 ± 3.2* 2.9 ± 0.4* 2.4 ± 1.9 7.1 ± 1.9* 1.2 ± 1.3* 21.0 ± 7.4* p value 0.00 0.002 0.135 0.001 0.001 Values are mean ± standard deviation. *p<0.05 by paired t-test. 0.00), 기억등록은 0.4 ± 0.9 (p = 0.002), 기억회상은 0.5 ± 1.2 (p = 0.001), 언어능력은 1.0 ± 2.2 (p = 0.001) 점으로통계적으로유의하게증가하였다. 그러나주의집중과계산은평균 0.3 ± 1.4 (p = 0.135) 으로증가하였으나통계적으로유의하지는않았다 (Table 3). 3) 성별, 연령, 뇌졸중의유형및위치, 초기기능적수준에따른 MMSE 점수의변화 성별및연령에따른 MMSE 총점의변화량은여성보다남성에서, 5세미만보다 5세이상의연령에서통계적으로유의하게증가하였다 (p<0.05). 뇌졸중의유형별로는뇌경색보다뇌출혈에서 MMSE가더증가되었으며 (p<0.05), 초기의기능적수준에따라서는초기mRS (mrs 2) 와 NIHSS가좋았을경우 (NIHSS 1) 더유의하게증가되었다 (p<0.05). MBI 는초기점수가 90점이상인경우가 1명밖에없어서 75점을기준으로나누어분석하였는데, 초기기능상태가좋았을경우 (MBI 75) 가그렇지않았을경우 에비해 MMSE가통계적으로유의하게더많이증가되었다 (p<0.05). 그러나, 뇌졸중의좌우병소위치에따른 MMSE 점수의증가정도는차이가없었다. 뇌졸중의병소별로는, 피질병변이피질하병변, 피질-피질하병변및천막하병변에비해통계적으로유의하게 MMSE가증가되었다 (p<0.05). 그외나머지병소간에는 MMSE 변화의차이는관찰되지않았다 (Table 4). 4) 초기기능적수준및기능적향상정도와 MMSE 점수의향상과의상관관계초기 mrs, NIHSS, MBI 점수중에서는초기 MBI 점수만이 MMSE 향상정도와통계적으로유의한상관관계가있었다 (r = 0.351, p<0.05). mrs 변화량, NIHSS 변화량및 MBI 변화량중에서는 NIHSS 변화량만이 MMSE 향상정도와통계적으로유의한상관관계가있었다 (r = 0.548, p<0.05) (Table 5). 고찰 뇌졸중후인지기능의저하는흔한합병증중의하나로, 재활치료에있어불량한예후인자로알려져있다. 1,18 인지기능저하와뇌졸중은밀접한관련이있어인지기능저하환자에서뇌졸중발생이더흔하고 19 더심한증상을나타내며 20 뇌졸중의재발빈도역시더흔한것으로알려져있고, 21 뇌졸중환자에서치매의위험도가 3배정도높은것으로알려져있다. 22 여러연구에서기저인지상태 (baseline cognitive status) 가뇌졸중환자의치료후기능적회복에주요한영향을미친다고알려져있고, 23- 또한 73
Brain& NeuroRehabilitation:2009; 2: 71 77 Table 4. Improvement of MMSE Score according to Demographic Variables, Stroke Features and Initial Functional Levels Variables No. of Pts. MMSE p value Gender Age (years) Stroke type Laterality Lesion location Initial mrs Initial NIHSS Initial MBI Male* Female 5* <5 Hemorrhage* Infarct Rt. hemiplegia Lt. hemiplegia Bilateral Cortical* Subcortical Cortical-subcortical Infratentorial 2* 3 1* >1 75* <75 31 14 11 9 47 4 5 51 3.2 ± 4. 3.00 ±.35 3.18 ± 5.41 3.0 ± 5.5 5. ± 5.52 2.30 ± 5.22 2.20 ± 3.87 3.92 ±.55 3.83 ±.18 11.7 ± 8.52 2.28 ± 3.95 3.50 ± 4. 0.00 ± 2.57 4.11 ± 8.21 2.9 ± 4.83.00 ± 10.32 2.7 ± 4.72 5.0 ± 10.95 2.90 ± 4.71 1.000 0.020 Values are mean ± standard deviations. *p<0.05 by ANCOVA (Analysis of Covariance). Covariate is an initial MMSE score. Group difference: cortical>subcortical = cortical-subcortical = infratentorial, MMSE: Mini-Mental Status Examination, mrs: modified Rankin Scale, NIHSS: National Institutes of Health Stroke Scale, MBI: modified Barthel Index. Table 5. Pearson s Correlation between MMSE gain and Initial Functional Level and Functional Gain Orientation Registration Attention and calculation Recall Language Total Initial mrs Initial NIHSS Initial MBI mrs NIHSS MBI 0.057 0.004 0.172 0.045 0.475* 0.427* 0.374* 0.50* 0.543* 0.09 0.524* 0.1 0.075 0.088 0.152 0.035 0.3 0.097 0.243 0.199 0.154 0.043 0.200 0.03 0.097 0.238 0.0* 0.015 0.590* 0.171 0.049 0.174 0.351* 0.001 0.548* 0.292 Values are γ by Pearson correlation. *p<0.05 by Pearson correlation. : Difference between time 1 and time 2 (Functional gain). MMSE: Mini-Mental Status Examination, mrs: modified Rankin Scale, NIHSS: National Institutes of Health Stroke Scale, MBI: modified Barthel Index. 이때의인지기능이재활치료후퇴원시기능적상태를예측할수있는결정가치 (determination value) 가있어뇌졸중후조기에그리고기본적인인지기능평가가이루어져야한다고권고되고있다. 18 본연구에서는뇌졸중후인지기능평가를위해간이정신상태검사 (mini-mental status examination; MMSE) 를사용하였다. MMSE는침상에서의인지기능평가에있어표준화된도구로, 인지기능을간편하고객관적으로측정할수있어널리사용되어지며, 타당도역시잘정립되어있다. 2 또한연속적인평가를할수있어시간경과에따른인지기능의악화및호전여부를평가할수있다. 27 지남력 (orientation), 기억등록 (registration), 주의집중및계산 (attention and calculation), 기억회상 (recall), 언어능력 (language) 으로구성되어있으며, 최고점수는 30점으로점수가많을수록인지기능이잘보존되고있음을의미하며 24점미만이면인지기능장애가있음을의미한다. 2 뇌졸중후인지기능의변화에대해 Appelros 등 28 에따르면뇌졸중후 1주부터 1년사이에는 MMSE 점수가 1점증가한다고한반면, Sachdev 등 29 에따르면뇌졸중후 3 개월부터 1년사이에는 MMSE 점수가 0.83점감소한다고하였고, Ballard 등 17 은뇌졸중후 3개월에서 15개월까지 1년간의추적관찰시 50% 의환자에서인지기능의향상 74
오민균외 2 인 : 아급성기뇌졸중환자의인지기능회복 이있었고 % 에서 MMSE 점수가 2점이상향상되었다고보고하였다. 이렇듯연구간인지기능변화의차이는뇌졸중발병으로부터의시간, 뇌졸중의중증도, 선택된환자군등에따른차이로생각되는데, 본연구에서는뇌졸중발병후약 1개월 (23.1 ± 12.일 ) 에서약 3개월 (88.1 ± 29.8일 ) 사이아급성기에 MMSE의총점은평균 3.14점증가되었다. 따라서뇌졸중후아급성기에는어느정도의인지기능의호전을기대할수있을것이라사료되나, 그이후의변화에대하여는본연구에서는다루지못하였고 MMSE의 5가지 ( 지남력, 기억등록, 주의집중과계산, 기억회상, 언어능력 ) 각항목별변화에대한추가적인연구가필요할것으로생각된다. 또한본연구에서성별, 연령에따른 MMSE 점수의향상은남성과 5세이상의연령에서더유의하게관찰되었다. 5세이상의연령에서 MMSE 점수의향상이유의한것은예상밖의결과였지만, 재활치료시작시 MMSE 점수가 5세미만인경우보다낮아점수의향상폭이더컷을것으로여겨지나기존의여러연구들 10,30-32 에의하면성별및연령과인지기능의연관성에대해서는아직도논란이있는상태이다. 뇌졸중의유형별로는 Nys 등 33 은뇌출혈에서뇌경색보다인지기능장애의발생빈도가 배정도높다고보고하였으며이는광범한두개내압의영향일것으로고찰하였고 Kelly 등 34 의연구에의하면재활치료입원당시뇌출혈에서뇌경색보다인지기능장애와기능적장애가더심하였으나회복의정도는뇌출혈에서더많았다고보고하였다. 본연구에서는뇌경색보다뇌출혈에서 MMSE가더유의하게향상되어 Kelly 등 34 의연구와비슷한결과를보였다. Pohjasvaara 등 30 의연구에서는뇌졸중의아형 (subtype) 과인지기능사이에상관관계가없었고, Kase 등 12 의연구에서는뇌졸중후 개월추적관찰에서깊은병변 (deep lesion) 과얕은병변 (superficial lesion) 의비교시얕은병변이깊은병변에비해뇌졸중후 MMSE 점수차이가컸지만통계적으로유의하지는않았다고보고하였다. 반면 Szatmari등 35 은다발성피질하경색 (multiple subcortical infarct) 에서뇌졸중후인지기능저하의위험도가높다고보고하였는데이는피질하경색환자에서인지기능의장애는피질하구조자체의직접적인영향, 즉피질하구조의저관류 (hypoperfusion) 또는기능적분리 (functional disconnection) 로설명되고있다. 33 본연구에서는피질병변이다른병변에비해통계적으로유의하게 MMSE 변화가커서 Kase 등 12 의연구와비슷한결과를보였다. 또한, 인지기능장애가기능적회복수준에크게영향을미치는것으로알려져있는데, 3 Appelros 37 의연구에서는뇌졸중후 1년간추적관찰에서인지기능장애가있는환 자에서 mrs 점수가 1.8점더높게나타나기능적회복이불량하였다고하였고, 김등 38 의연구에서는뇌졸중환자에서재활치료시작시와퇴원시 MMSE의증가값은 FIM (functional independence measure) 과 MBI의증가값과통계학적으로유의한연관성이있어서인지기능의향상이기능적회복과관련이있다고보고하였다. 본연구에서는초기의기능적수준에따라서인지기능의향상이어떻게다른가를알아보고자하였는데초기기능적수준이좋을경우 (mrs 2, MBI 75, NIHSS 1) 그렇지않을경우보다통계적으로유의하게보다많은 MMSE 점수의향상이관찰되었다 (p<0.05). 또한, 초기의 MBI와 MMSE 의향상정도가상관관계가있었다. 이는뇌졸중초기의기능적수준이아급성기의뇌졸중환자의인지기능회복과연관이있다는것을의미하며, 초기의기능적수준이좋을수록인지기능의회복정도가많을것으로기대된다고볼수있다. 그러나본연구는인지장애에중요한영향을미치는것으로알려진교육수준, 30,39 우울증 여부를고려하지못했다는점과표본수가작았다는제한점이있다. 그러나본연구결과를통하여뇌졸중후아급성기에인지기능이향상되는것을확인하였고그향상에미치는요인들을알아낼수있었다. 결론 결론적으로본연구에의하면아급성기의뇌졸중환자에서인지기능은향상되며, 남자, 5세이상, 뇌출혈, 피질병변에서인지기능이보다많이향상되며, 초기의기능적상태가좋을수록인지기능의향상이더욱많다. 이러한정보는향후뇌졸중환자에서인지기능의회복을예측하고이와관련된재활치료계획을수립하는데많은도움을줄수있을것이라생각된다. 참고문헌 1) Tatemichi TK, Desmond DW, Stern Y, Paik M, Sano M, Bagiella E. Cognitive impairment after stroke: frequency, patterns, and relationship to functional abilities. J Neurol Neurosurg Psychiatry. 1994;57:202-207 2) Barba R, Martinez-Espinosa S, Rodriguez-Garcia E, Pondal M, Vivancos J, Del Ser T. Poststroke dementia: clinical features and risk factors. Stroke. 2000;31:1494-1501 3) Shimoda K, Robinson RG. The relationship between social impairment and recovery from stroke. Psychiatry. 1998; 1: 101-111 4) Anderson CS, Linto J, Stewart-Wynne EG. A population- 75
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