원저접수번호 :09-029(2 차 -0710) 80 세이상고령환자에서발생한뇌경색의임상과영상특징 : 단일기관연구 가톨릭대학교의과대학여의도성모병원신경과 임은예왕민정박형은최유진이지연김우준조아현 Clinical and Radiological Characteristics of Ischemic Stroke in the 80 Year-Old or Older: A Single Center Study Eun Ye Lim, MD, Min Jeong Wang, MD, Hyung Eun Park, MD, Eu Jene Choi, MD, Ji-Yeon Lee, RN, Woojoon Kim, MD, PhD, A-Hyun Cho, MD, PhD Department of Neurology, Yeouido St. Mary s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea Background: The risk profiles and stroke presentations may differ between elderly stroke patients and their younger counterparts. The most appropriate stroke-management regime for a better outcome can only be achieved with knowledge of the characteristics of elderly stroke patients. This study compared the clinical and radiological characteristics of elderly ( 80 years) ischemic stroke patients with those aged <80 years. Methods: Consecutive acute ischemic stroke patients were enrolled. The following parameters were obtained for each patient: clinical variables [i.e., risk factors, initial National Institutes of Health Stroke Scale (NIHSS) score, mode of onset, in-hospital complications, and modified Rankin scale (mrs) score at 3 months], radiological variables, and clinicoradiological discrepancies. Results: Of the 436 enrolled patients, 60 (13.8%) were elderly. The proportion of men was lower among the elderly than among those patients aged >80 years (40.0% vs. 63.3%; p=0.001), while their initial NIHSS score was higher (median, 4 vs. 3; p=0.033). Furthermore, an unclear stroke onset (46.4% vs. 32.8%; p=0.049) and clinicoradiological discrepancies (13.8% vs. 5.7%; p=0.044) were more common among the elderly. The proportions of subjects with stroke of undetermined cause (30.0% vs. 18.0%; p=0.019) and multiple circulation infarctions (23.3% vs. 12.6%, p=0.030) were higher among the elderly. A favorable outcome (mrs score of 0 or 1) was more common in the younger stroke patients (57.5% vs. 25.9%, p<0.0001). Multivariate analysis revealed that younger age, male gender, and initial stroke severity were significantly associated with a favorable outcome. Conclusions: These results indicate that stroke presentation in the elderly differs from that of their younger counterparts in terms of clinical and radiological variables. J Korean Neurol Assoc 31(4):234-238, 2013 Key Words: Ischemic stroke, Elderly, Clinical outcome, Diffusion-weighted imaging Received March 26, 2013 Revised June 27, 2013 Accepted June 27, 2013 *A-Hyun Cho, MD, PhD Department of Neurology, Yeouido St. Mary s Hospital, The Catholic University of Korea College of Medicine, 10 63-ro, Yeongdeungpo-gu, Seoul 150-713, Korea Tel: +82-2-3779-2433 Fax: +82-2-782-8654 E-mail: ahyun@catholic.ac.kr *This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No.2012R1A1B5000477) 서론 뇌졸중발생은노화에따라급격히증가한다. 1 평균수명이늘어나면서우리나라에서는고령인구가급증하고뇌졸중환자의대부분이고령환자가되었다. 2010년시행한한국인구조사에서는 80세이상이전체인구의 12.6% 를차지한다. 2,3 따라서고령인구에서의뇌졸중은사회경제비용과관련하여공공의료의주된관심사가되고있다. 234 대한신경과학회지제 31 권제 4 호, 2013
80 세이상고령환자에서발생한뇌경색의임상과영상특징 : 단일기관연구 그럼에도불구하고출혈변환, 나쁜임상예후, 임상근거부족의이유로 80세이상의환자는혈전용해술과같은적극적인뇌졸중치료에서배제되어왔다. 4-6 이러한상황에서 80세이상고령환자에서발생하는뇌졸중의임상및영상특징을잘파악하는것이향후최선의치료를하는데반드시필요하다. 따라서저자들은 80세이상뇌경색환자가 80세미만의환자에비하여임상과영상특징이어떻게다른지를비교하고자한다. 대상과방법 2007년 2월부터 2009년 1월까지증상발생 7일이내내원한급성뇌경색환자를연속적으로등록하여후향분석을하였다. 모든환자는뇌확산강조영상 (diffusion-weighted image) 을포함한뇌MRI, CT혈관조영술또는 MR혈관조영술, 혈액검사, 심장검사 ( 심장초음파검사와홀터검사 ) 를하였다. 급성뇌경색은신경계이상이있으면서뇌확산강조영상에서고신호강도를보이며영상의학과판독이급성뇌경색에합당한경우로정의하였다. 혈전용해치료는미국뇌졸중협회진료지침에따라환자의나이에상관없이적응기준에해당하는환자에한하여동의를받은경우시행하였다. 7 임상변수로나이, 성별, 위험인자 ( 고혈압, 당뇨병, 고지질혈증, 흡연 ), 뇌졸중발생시정황 (modes of stroke onset), 증상발생에서내원하기까지의시간 (onset-to-door time), 입원당시발생한합병증을조사하였다. 뇌졸중발생시정황은발생시각이 분명한경우 (clear onset) 와 불분명한경우 (unclear onset) 로나누었으며, 불분명한경우를다시 기상시뇌졸중, 시각을정확히보고할수없는경우 ( 쓰러진후타인에게발견된경우, 언어장애로인하여시각을보고할수없는경우 ) 로나누었다. 기상시뇌졸중이나시각을정확히보고할수없는 경우는마지막으로정상이었던시각을발생시각으로간주하였다. 입원당시신경계결손의중등도는 NIH뇌졸중척도를사용하여평가하였다. 임상예후를알기위하여 3개월째수정 Rankin척도를측정하였다. 3개월째수정Rankin척도가 0 또는 1인경우를좋은예후로정의하였다. 뇌경색아형은 TOAST 분류기준에따라소혈관질환 (small vessel disease), 큰동맥질환 (large artery disease), 심장성뇌경색 (cardiogenic infarction), 원인미정 (undetermined cause), 기타원인 (other cause) 으로분류하였다. 8 뇌확산강조영상에서보이는뇌경색병변을분석하여순환영역을좌전방순환 ( 좌측전대뇌동맥, 좌측중대뇌동맥 ), 우전방순환 ( 우측전대뇌동맥, 우측중대뇌동맥 ) 과후방순환 ( 후대뇌동맥, 척추동맥, 뇌바닥동맥 ) 으로세개로나누고두개이상의단일순환영역에존재하는경우를다발순환 (multiple circulations) 영역으로분류하였다 (Fig. 1). 뇌졸중전문가가판단할때뇌확산강조영상에서보이는뇌경색병변이임상증상과일치하지않는경우임상-영상불일치 (clinico-radiological discrepancy) 로정의하였다 (Fig. 2). 즉, 신경계증상 ( 의식저하, 두통또는어지럼 ) 으로내원하여뇌영상촬영을하고작은급성뇌경색병변이 DWI에서발견되었으나환자의신경계이상을뇌경색병변만으로모두설명할수없는경우를말한다. 80세이상환자군과, 80세미만환자군의임상변수, 뇌경색병변의양상, 임상예후를비교분석하였으며좋은예후와관련이있는인자를분석하였다. 명목변수중합병증발생률, 뇌경색병변, 임상예후, 성별, 고혈압, 고지질혈증, 흡연율, 뇌경색아형은 Chi-square test로분석하였고혈전용해치료율, 임상-영상불일치는 Fisher s exact test를하여비교하였다. Mann- Whitney s U test를사용하여증상발생에서내원까지의시간, NIH뇌졸중척도를비교하였다. 나이의비교는 Student s t test 를사용하였다. 좋은임상예후와관련있는인자를찾기위하 A B C D Figure 1. An 89-year-old woman presented with sudden onset of left sided weakness. Diffusion-weighted MRI shows acute ischemic lesions on right anterior (A, B) and posterior (C, D) circulations (multiple circulations). J Korean Neurol Assoc Volume 31 No. 4, 2013 235
임은예왕민정박형은최유진이지연김우준조아현 여이분형로지스틱회귀분석을하였다. 양측검정으로하여 p<0.05을유의수준으로정하였다. 모든분석은 SPSS 18.0으로하였다. 결과 연구기간동안등록된환자는총 436명이었고 60 (13.8%) 명이 80세이상이었다. 전체환자의평균연령과표준편차는 A B C Figure 2. An 81-year-old woman was admitted because of acute confusion. She did not have any medication history nor laboratory abnormality. Diffusion-weighted MRI shows tiny acute ischemic lesion on right cerebellum (A, B) with patent cerebral vessels (C). This case demonstrates clinico-radiological discrepancy. Table 1. Clinical, radiological and outcome variables of the younger and the elderly The younger The elderly (<80 yr-old, n=376) ( 80-yr-old, n=60) p value Age (mean, SD) 62.6±12.6 84.7±3.8 <0.0001 Sex (male, n, %) 238 (63.3) 24 (40.0) 0.001 HTN (n, %) 225 (60.8) 44 (73.3) 0.084 DM (n, %) 128 (34.5) 13 (21.7) 0.054 Hyperlipidemia (n, %) 87 (24.6) 13 (22.0) 0.745 Smoking (n, %) 131 (36.0) 9 (15.0) 0.002 Onset to door time, (hr, median, IQR) 13 (4-48.0) 18 (3.13-34.8) 0.752 Mode of onset 0.002 Clear onset 215 (57.2) 30 (50.0) Unclear onset On awakening 84 (22.3) 15 (25.0) Unable to report 21 (5.6) 11 (18.3) No record 56 (14.9) 4 (6.7) Clinico-Radiological discrepancy (n, %) Discrepant 20 (5.7) 8 (13.8) 0.044 Correlated 328 (94.3) 50 (86.2) Initial NIHSS (median, IQR) 3 (1-6) 4 (2-9) 0.033 Favorable outcome (n, %) 188 (57.5) 14 (25.9) <0.0001 Stroke subtypes (n, %) 0.019 SVD 79 (21.1) 10 (16.7) LVD 126 (33.8) 19 (31.7) CE 67 (18.0) 13 (21.7) Undetermined 67 (18.0) 18 (30.0) Other 34 (9.1) 0 (0) Lesion pattern Multiple circulations 47 (12.6) 14 (23.3) 0.030 Complications in hospital 28 (7.5) 26 (43.3) <0.0001 Thrombolysis 20 (5.4) 6 (10.0) 0.153 SD; standard deviation, HTN; hypertension, DM; diabetes, IQR; interquartile range, NIHSS; national institutes of health stroke scale, SVD; small vessel disease, LVD; large vessel disease, CE; cardioembolism. 236 대한신경과학회지제 31 권제 4 호, 2013
80 세이상고령환자에서발생한뇌경색의임상과영상특징 : 단일기관연구 65.6±14.1세였고 262 (60.1%) 명이남자였다. Table 1은 80세이상환자군과 80세미만환자군의임상변수, 영상변수, 예후변수를비교한결과이다. 80세이상환자군을 80세미만환자군과비교할때, 남자비율 (40.0% vs. 63.3%; p=0.001) 이낮았고병원도착당시 NIH뇌졸중척도 (median [interquartile range], 4 [2-9] vs. 3 [1-6], p=0.033) 가 80세이상환자군에서높았다. 당뇨병, 고혈압, 고지질혈증의비율은양군에서차이가없었다. 그러나흡연율은 80세미만환자군에서더높았다 (9/60, 15% vs. 131/376, 36%, p=0.009). 뇌졸중발생시정황에대한분석결과, 불분명한경우 가 80세이상환자군에서유의하게많았다 (26/56, 46.4% vs. 105/320, 32.8%, p=0.049). 뇌졸중발생시정황에대한기록이없는경우가 80세이상환자군, 80 세미만의환자군에서각각 56명, 4명이었으며, 기상시뇌졸중 이 84명, 15명, 시각을정확히보고할수없는경우 가 21명, 11명이었다. 임상-영상불일치 역시 80세이상환자군에서유의하게많았다 (8/60, 13.8% vs. 20/376, 5.7%, p=0.044). TOAST 뇌졸중분류에의한뇌경색아형중원인미정 (undetermined cause) 이 80세이상환자군에서유의하게많았다 (18/60, 30.0% vs. 67/376, 18.0%, p=0.019). 세명의환자에서일과성허혈발작을보였다. 뇌경색병변을분석하였을때다발순환뇌경색 (multiple circulations infarction) 이 80세이상환자군에서유의하게많았다 (14/60, 23.3% vs. 47/376, 12.6%, p=0.030). 입원당시발생한합병증은폐렴 (n=19), 요로감염 (n=7), 심근경색 (n=3), 출혈합병증 (n=11), 뇌졸중후경련 (n=1), 급성신부전 (n=4), 기타 (n=9) 가있었다. 이러한합병증은 80세이상환자군에서더흔하게발생하였다 (26/60, 43.4% vs. 28/376, 7.5%, p<0.0001). 3개월후임상예후는 80세미만환자군이더좋았다 (188/327, 57.5% vs. 14/54, 25.9%, p<0.0001). 다중로지스틱회 귀분석에서는남자, 입원당시경미한뇌졸중증상 ( 초기 NIH 뇌졸중척도 4미만 ), 80세미만의연령이좋은임상예후와연관된인자였다 (Table 2). 고찰 본연구는 80세이상환자군과 80세미만환자군에서발생한급성뇌경색의임상과영상특징을비교하였다. 중국환자를대상으로조사한연구에서도본연구와비슷하게약 11.5% 가 80세이상환자였다. 9 그결과에따르면고령환자에서고혈압, 심방세동, 관상동맥질환이유의하게많았고고령환자들이적극적인치료를받지못하고장애율과사망률이높았다. 9-11 본연구에서는흡연력을제외한위험인자의차이는없었다. 본연구가기존의유사연구와비하여새로운점은, 뇌졸중발생시정황, 임상-영상불일치, 뇌경색병변의양상에대한분석을추가하였다는점이다. 고령환자에서뇌졸중발생시정황이불분명한경우가더많았다. 즉, 혼자있을때증상이발생하여타인에의해발견이되거나증상을뇌졸중으로인식하지못하거나언어또는의식장애때문에증상발생시각을정확히보고하지못하는경우가많다는것이다. 이러한점은고령인급성뇌경색환자의빠른내원과적합한치료를위하여고령환자에대한지속적인관찰과뇌졸중에대한적극적인교육이필요함을시사한다. 80세이상환자에서임상증상과징후가뇌확산강조영상에서보이는급성뇌경색병변으로는충분히설명되지않는경우즉, 임상-영상불일치 가많았다. 이러한점은임상의사가뇌졸중을의심하고진단하는데어려움을줄수있다. 따라서고령환자를진찰할때는보다자세한병력청취와진찰이필 Table 2. Multiple logistic regression model: factors related to favorable clinical outcome Odds ratio 95% CI Elderly Age<80 Reference Age 80 or more 0.289 0.130-0.642 Sex Female Reference Male 2.098 1.225-3.592 Hypertension No Reference Yes 1.009 0.589-1.729 DM No Reference Yes 0.963 0.553-1.677 Onset to door time within 6 hr Time more than 6 Reference Time within 6 0.753 0.437-1.299 NIHSS less than 4 NIHSS 4 or more Reference NIHSS less than 4 8.960 5.310-15.120 DM; diabetes, NIHSS; national institutes of health stroke scale. J Korean Neurol Assoc Volume 31 No. 4, 2013 237
임은예왕민정박형은최유진이지연김우준조아현 요하며비록모호한신경계증상으로왔다하더라도급성뇌경색때문일가능성은항상염두에두어야한다. 마지막으로 80세이상환자에서다발순환뇌경색 (multiple circulation infarction) 과원인미정 (undetermined cause) 의뇌졸중아형이많은것은고령환자에서암, 감염같은기타질환이함께존재할수있기때문이라고생각하며추후이에대한조사가필요할수있다. 12-15 본연구의제한점은첫째, 이연구가단일기관에서시행되었고후향조사하였기때문에연구결과를일반화하기에는부족하다. 둘째, 임상-영상불일치를정의하는데있어객관성이떨어질수있다. 그러나기타임상변수에대하여정보를주지않은상태에서숙련된뇌졸중전문가에의해진행되어이점을최소한으로줄이려노력하였다. REFERENCES 1. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE, et al. Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 2005;366:1773 1783. 2. Organization for Economic Cooperation and Development. OECD Economic Surveys: Korea 2010. Available from: URL:http:// www. oecd.org/dataoecd/14/34/45432048.pdf. Accessed April 2011. 3. 2010 Population and Housing Census, Korea statistical information service. Available from: URL:http://kosis.kr/ 4. Berrouschot J, Rother J, Glahn J, Kucinski T, Fiehler J, Thomalla G. Outcome and severe hemorrhagic complications of intravenous thrombolysis with tissue plasminogen activator in very old (>80 Years) stroke patients. Stroke 2005;36:2421-2425. 5. European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25:457-507. 6. Chen CI, Iguchi Y, Grotta JC, Garami Z, Uchino K, Shaltoni H, et al. Intravenous TPA for very old stroke patients. Eur Neurol 2005; 54:140-144. 7. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655-1711. 8. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41. 9. Wang D, Hao Z, Tao W, Kong F, Zhang S, Wu B, et al. Acute ischemic stroke in the very elderly Chinese: risk factors, hospital management and one-year outcome. Clin Neurol Neurosurgery 2011;113: 442-446. 10. Olindo S, Cabre P, Deschamps R, Chatot-Henry C, Rene-Corail P, Fournerie P, et al. Acute stroke in the very elderly epidemiological features, stroke subtypes, management, and outcome in Martinique, French West Indies. Stroke 2003;34:1593-1597. 11. Auriel E, Gur AY, Uralev O, Brill S, Shopin L, Karni A, et al. Characteristics of first ever ischemic stroke in the very elderly: profile of vascular risk factors and clinical outcome. Clin Neurol Neurosurgery 2011;113:654-657. 12. Roh JK, Kang DW, Lee SH, Yoon BW, Chang KH. Significance of acute multiple brain infarction on diffusion-weighted imaging. Stroke 2000;31:688-694. 13. Saito K, Moriwakia H, Oe H, Miyashitaa K, Nagatsukaa K, Uenob S, et al. Mechanisms of bihemispheric brain infarctions in the anterior circulation on diffusion-weighted images. AJNR Am J Neuroradiol 2005;26:809 814. 14. Bogousslavsky J, Cachin C, Regli F, Despland PA, Van Melle G, Kappenberger L. Cardiac sources of embolism and cerebral infarction--clinical consequences and vascular concomitants: the Lausanne Stroke Registry. Neurology 1991;41:855-859. 15. Cho AH, Kim JS, Jeon SB, Kwon SU, Lee DH, Kang DW. Mechanism of multiple infarcts in multiple cerebral circulations on diffusion-weighted imaging. J Neurol 2007;254:924-930. 238 대한신경과학회지제 31 권제 4 호, 2013