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1 pissn eissn Brain & NeuroRehabilitation Vol. 9, No. 1, March, Original Article 편측공간무시뇌졸중환자에서동반된인지기능손상과기능적예후의관계 1 건국대학교병원재활의학과, 2 건국대학교의학전문대학원재활의학교실 정은화 1 ㆍ김보람 1,2 ㆍ이종민 1,2 Relationship between Comorbid Cognitive Impairment and Functional Outcomes in Stroke Patients with Spatial Neglect Eun Hwa Jeong, O.T., M.S. 1, Bo-Ram Kim, M.D., Ph.D. 1,2, Jongmin Lee, M.D., Ph.D. 1,2 1 Department of Rehabilitation Medicine, Konkuk University Medical Center, 2 Department of Rehabilitation Medicine, Konkuk University School of Medicine Objective: The aim of this study was to investigate relationships between cognitive impairment and functional outcomes in stroke patients with spatial neglect. Method: Twenty seven right hemisphere ischemic stroke patients who admitted to an inpatient rehabilitation unit were included. Patients were divided into two group based on KF-NAP scores: Neglect group (n=18) and non-neglect group (n=9). Neglect group (n=18) were subdivided into two groups by discharge FIM scores as poor outcome group (n=8, <70) and good outcome group (n=10, 70). Cognitive function assessments including attention (Attention & Calculation, Digit span test Forward), memory (Digit span test Backward, SVLT-Immediate recalls/delayed recalls) and visual perception (LOTCA-Visual perception/visuomotor organization), and stroke severity assessment including NIHSS, FMA, K-MMSE, and FIM were performed. Cognitive impairments and functional outcomes were compared between two groups. Results: There were significant differences in NIHSS, FMA (affected U/E, affected L/E), discharge FIM, FIM gain and LOTCA-visuomotor organization between Neglect group and non- neglect group (p<0.05). Among the patients with spatial neglect, there were significant differences in KF-NAP, K-MMSE and assessment scores of memory and visual perception between poor outcome group and good outcome group. Attention, memory and visual perception were significantly correlated with KF-NAP scores (p<0.05). Conclusion: Stroke patients with spatial neglect showed more severe impairment in cognitive, motor and general functional status, which resulted in delayed functional recovery. Spatial neglect patients with combined memory and visual perception impairment may show poor functional outcome. (Brain & NeuroRehabilitation 2016; 9: 37-47) Key Words: Cognitive impairment, Functional outcome, KF-NAP, Neglect, Stroke 서론 뇌졸중환자의인지기능손상은편측공간무시와같은공간인지장애를포함하며편측공간무시는뇌손상반대편공간에대한주의력, 공간지각과구성, 그리고외부자 Received: February 29, 2016, Revised : March 9, 2016, Accepted: March 15, 2016 Correspondence to: Jongmin Lee, Department of Rehabilitation Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea Tel: , Fax: leej@kuh.ac.kr 극에대한반응에영향을주는신경인지적장애이다. 1-5 편측공간무시환자는시각적, 청각적인문제가없음에도불구하고뇌손상반대측공간의물체또는사람을인지하는것에어려움이있으며, 뇌손상반대측공간으로의움직임실행에어려움을보인다. 4,5 따라서편측공간무시환자는대부분한쪽공간을무시한채일상생활을수행하기때문에면도, 세수와같은개인위생과옷입기등을오직신체의반만수행하거나쟁반의한쪽공간에있는음식을인식하지못하고특정공간으로의이동과탐색에어려움이있는등전반적인일상생 37

2 Brain & NeuroRehabilitation 2016; 9: 활에문제가발생하게된다. 6,7 이러한편측공간무시는병변부위에따라나타나는임상양상이다양하기때문에정확한진단과평가로써실제일상생활에서의수행동안좌우공간에대한반응을관찰하는것이중요하다. 7 유은영등 (2006) 은국내임상에서주로사용하는편측공간무시평가는직선이분검사 (Line bisection) (47.9%) 와알버트검사 (Albert s test) (36.8) 라고보고하였는데, 5 이평가들은간단하기때문에편측공간무시의선별검사로적용할수있으나기능적수행에서편측공간무시와관련된임상양상을확인할수없고, 9 고유수용성감각또는운동기능에서나타날수있는편측공간무시를평가할수없다는제한점이있다. 10 따라서편측공간무시의명확한확인을위해 Catherin Bergego 척도 (Catherin Bergego Scale) 또는케슬러파운데이션무시평가 (Kessler Foundation Neglect Assessment Process, KF-NAP) 와같은기능적평가가도움이된다. 11 여러연구보고에의하면편측공간무시는장애수준과연관이있으며편측공간무시에의해전반적인일상생활의수행도가떨어지게되어급성기재활입원기간의연장과기능적예후에심각한부정적영향을준다. 12,13 이러한편측공간무시는대부분두정엽과관련되어우측중대뇌동맥에손상이있는뇌졸중환자에게서나타나는것으로알려져있으나, 두정엽, 측두엽및전두엽의손상과결합하여나타나기도하며편측공간무시를보이는환자중약 40% 는좌측대뇌반구의손상에의해서도나타난다. 14 즉, 편측공간무시는주의집중, 기억력, 지각과같은여러가지인지기능을포함하는인지기능망 (cognitive network) 손상의결과로발생할수있으며, 이러한인지기능손상의동반이잠재적으로편측공간무시악화와입원기간의연장및기능적회복을지연시킬수있다 작업기억 16, 시지각기능 17 등의인지영역이편측공간무시와관련이있다는연구들이있었으나, 이들연구들에서의편측공간무시는 line bisection, albert test 등의지필검사를기반으로진단한것이어서일상생활의기능적수행에서편측공간무시의확인에제한이있었다. 이에본연구에서는케슬러파운데이션무시평가 (KF-NAP) 을이용하여편측공간무시를평가하여편측공간무시의유무에따른인지기능의동반손상정도를확인하고, 편측공간무시환자에서여러인지영역중기능적예후에영향을주는영역에대해알아보고자하였다. 연구대상및방법 1) 연구대상 2014년 9월부터 2015년 9월까지건국대학교병원재활의학과에입원한뇌졸중환자 91명중본연구의대상자선정기준에해당하는 27명을대상자로하였다. 본연구의대상자선정기준은 1) 컴퓨터단층촬영 (CT) 또는자기공명영상촬영 (MRI) 을통해뇌졸중진단을받은초발성뇌경색환자, 2) 우측대뇌반구손상, 3) 실어증이없는경우. 4) 의식수준이명료하여 2단계이상의지시따르기가가능한경우, 5) 시각및청각적문제가없는환자등으로하였다 (Fig. 1). 전체대상자의평균연령은 67.6세, 성별은남자 14명, 여자 13명이었고, 병변위치는전대뇌동맥 (Anterior Cerebral Artery, ACA) 뇌경색환자가 7.4%, 중대뇌동맥 (Middle Cerebral Artery, MCA) 뇌경색환자가 92.6% 이었다 (Table 1). 2) 연구과정우측대뇌반구뇌경색환자 27명을대상으로편측공간무시를확인하기위한 KF-NAP 평가를시행하여편측공 Fig. 1. Inclusion criteria in this study. 38

3 정은화외 2 인 : 편측공간무시뇌졸중환자에서동반된인지기능손상과기능적예후의관계 Table 1. Comparison of Characteristics and Cognitive Function in Neglect Group and Non-neglect Group Total N=27 Neglect N=18 Non-neglect N=9 Age (years) 67.6 ± ± ± 7.7 SEX Male 14 (51.9) 11 (61.1) 3 (33.3) Female 13 (48.1) 7 (38.9) 6 (66.7) Lesion location ACA 2 (7.4) 2 (11.1) 0 (0) MCA 25 (92.6) 16 (88.9) 9 (100) Initial NIHSS* 9.2 ± ± ± 2.9 Initial FMA Affected total* 42.8 ± ± ± 38.1 Affected U/E* 27.6 ± ± ± 28.3 Unaffected U/E 61.0 ± ± ± 1.1 Affected L/E* 15.3 ± ± ± 10.5 Unaffected L/E 30.6 ± ± ± 1.1 Initial FIM* 68.9 ± ± ± 18.2 Discharge FIM* 80.7 ± ± ± 15.7 FIM gain* 11.8 ± ± ± 12.5 Initial K-MMSE 21.1 ± ± ± 4.5 A&C (K-MMSE) 2.0 ± ± ± 2.1 Digit span-f 5.7 ± ± ± 2.1 Digit span-b 2.7 ± ± ± 0.9 SVLT-IR 14.1 ± ± ± 3.4 SVLT-DR 4.2 ± ± ± 1.4 LOTCA-VP 13.1 ± ± ± 0.7 LOTCA-VMO* 14.3 ± ± ± 6.2 Values are mean ± standard deviation or N (%). A&C: Attention & Calculation, Digit span-f: Digit span test-forward, Digit span-b: Digit span test-backward, SVLT-IR: SVLT-Immediate recalls, SVLT-DR: SVLT-Delayed recalls, LOTCA-VP: LOTCA-Visual perception, LOTCA-VMO: LOTCA- Visuomotor organization. Mann-Whitney test by *p<0.05. 간무시가있는것으로나타난무시군과비무시군의두군으로분류하였다. 모든환자에서주의집중력, 기억력, 시지각능력등의인지기능영역에대한인지기능평가를시행하였고, 뇌졸중중증도를확인하기위한한글판미국국립보건원뇌졸중척도 (National Institutes of Health Stroke Scale, NIHSS), 푸글-마이어운동검사 (Fugl-Meyer motor assessment, FMA) 및한글판간이정신상태검사 (Korean-Minimental Status Examination, K-MMSE) 를시행하였다. 뇌졸중중증도평가, KF-NAP 및인지기능평가는재활의학과전과후 7일이내초기평가로실시하였으며, 평가지침및방법은각각 2015년개정판KF-NAP 매뉴얼 18 과서울신경심리검사매뉴얼 19 에따라시행하였다. 기능적예후를측정하기위해퇴원시기능적독립수준측정 (Functional Independent Measure, FIM) 점수를평가하였으며입원시 FIM 점수와퇴원시 FIM 점수의차이로기능적회복 (FIM gain) 정도를확인하였다. 또한, 편측공간무시가있는환자에서동반된인지기능손상과기능적예후의상관관계를확인하기위해퇴원시 FIM 점수를이용하여편측공간무시환자 18명을좋은예후와나쁜예후의두군으로분류하여분석하였다. 본연구에서는퇴원시 FIM 점수가 70점미만일경우나쁜예후로정의하였다. 24 3) 연구도구 (1) 주의집중력평가가 ) 숫자바로따라외우기 (Digit span test-forward): 숫자바로따라외우기는첫시행이 3개의숫자로시작하며매단계마다외워야하는순자의수가한개씩더해져서 9개의숫자를외우도록한다. 채점은피험자가정확하게수행한단계의숫자자리수로표시한다. 19 나 ) 주의집중및계산 (Attention & Calculation): 주의집중및계산은한글판간이정신상태검사 (Korean-Mini Mental State Examination, K-MMSE) 항목중하나로숫자 100에서 7을연속적으로 5번빼는계산능력을평가한다. 환자가오답을말하여도검사자는답을수정하거나틀렸다는표현을하지않고 5단계까지계속시행하여정답만점수를준다. 19 (2) 기억력평가가 ) 숫자거꾸로따라외우기 (Digit span test-backward): 숫자거꾸로따라외우기는숫자바로따라외우기에서제시한것과유사한일련의숫자들을듣고그숫자들을역순으로말하게하는과제로서같은검사방식으로실시하고점수를측정한다. 19 나 ) 서울언어학습검사 (Seoul Verbal Learning Test, SVLT): 서울언어학습검사는기억등록및기억회상에대한평가로, 즉각회상 (Immediate recalls) 의경우낱말 20개를불러준후생각나는대로말하도록하고, 지연회상 (Delayed recalls) 은 3차시행후 20분이경과하였을때평가한다. 20분동안의경과시간에는비언어적과제를실시하도록한다. 채점은반응순서나오답수에상관없이맞은낱말당 1점을준다. 19 (3) 시지각기능평가가 ) 로웬스테인작업치료인지평가 (Loewenstein Occupational Therapy Cognitive Assessment, LOTCA): LOTCA 는뇌손상환자의인지지각검사로사용되는표준화된평가도구이며, 4가지주요영역과 20개의하위검사로구성된다. 본연구에서실시한시각적지각능력 (visual perception) 영역은물체인식, 모양인식, 겹쳐진그림구분, 물체항상성의하위검사로구성되고시운동구성능력 (Visuomotor organization) 영역은그림따라그리기, 퍼즐 39

4 Brain & NeuroRehabilitation 2016; 9: 맞추기, 블록디자인, 페그보드꽂기, 시계그리기의하위검사로구성된다. 각하위검사항목당점수는 1점으로최고 4점, 최하 1점으로채점한다. 21 (4) 편측공간무시평가가 ) 케슬러파운데이션무시평가 (Kessler Foundation Neglect Assessment Process, KF-NAP): KF-NAP은 Catherin Bergego 척도 (Catherin Bergego Scale) 의제한점을보완하여편측공간무시의평가도구로개발한것으로 CBS보다구체적인방법과지시사항을제공한다. 22,23 KF-NAP의목적은일상생활동작수행동안편측공간무시증상을평가하고뇌손상이후기능수준을포괄적인임상평가를통해예측하기위한것으로 KF-NAP은환자의집, 입원병동, 외래병동등다양한장소에서평가가가능하다. 11 평가는시선방향, 사지인식, 청각주의, 개인소지품, 옷입기, 몸단장하기, 길찾기, 충돌, 식사, 식사후청결의 10개항목으로구성된다. 각항목은수행정도에따라 0점 ( 무시없음 ), 1점 ( 경도무시 ), 2점 ( 중등도무시 ), 3점 ( 중증무시 ) 으로점수를측정하며평가가생략된항목이있는경우 ( 총점 / 평가한항목수 )*10= 최종점수의공식으로점수를구한다. 최종점수에근거하여무시없음 (0점), 경도무시 (1점 10 점 ), 중등도무시 (11점 20점), 중증무시 (21점 30점) 로무시정도를구분한다. 11 (5) 기능적예후평가가 ) 기능적독립수준측정 (Functional Independent Measure, FIM): FIM은일상생활에서환자의기능정도를평가하는척도로 18개항목의일상생활동작항목들을평가한다. 하위평가항목은 1) 개인위생 ( 식사하기, 몸단장하기, 목욕하기, 화장실사용, 옷입기 ), 2) 대소변조절, 3) 이동하기 ( 침대-의자-의자차, 욕조 ), 4) 보행 ( 걷기 / 의자차이동, 계단오르기 ) 의운동기능과 5) 의사소통능력 ( 표현, 이해 ), 6) 사회적인지능력 ( 사회적소통, 문제해결, 기억력 ) 등으로구성된다. 각세부평가항목은수행정도에따라 7등급으로구분하는데, 독립적수행은 7점, 전적으로도움이필요한경우 1점을준다. 20,24 4) 분석방법 (1) 통계적분석통계적분석은 SPSS 17을이용하였다. 전체대상자에서무시군과비무시군그리고편측공간무시환자에서좋은예후군와나쁜예후군간의연령, 성별, 병변위치, KF-NAP, NIHSS, FMA, K-MMSE 점수, 퇴원시 FIM 점수, 기능회복정도 (FIM improvement), 및인지기능손상항목비교의통계적유의성검정은 Mann-Whitney 검정으로분석하였다. 편측공간무시환자의기능적예후에부정 적영향을미치는인지기능손상항목에대한분석은공분산분석 (Analysis of covariance) 를이용하였고, 편측공간무시중증도와인지기능손상및병변의수에대한통계적유의성은 Spearman 상관분석을하였으며병변위치의분석은카이제곱검정을하였다. 모든분석은 p<0.05 일때통계적으로유의한것으로하였다. (2) 해부학적분석뇌졸중유형및위치와인지기능손상이동반된병변의분석은급성기에촬영된컴퓨터단층촬영 (CT) 또는자기공명영상촬영 (MRI) 자료를이용하여 Moeller 와 Rief 25 의방법과신경해부문헌들을참고하여침범된영역을분석하였다. 편측공간무시와관련된것으로보고된피질및피질하부영역을관심영역 (region of interest) 으로두고병변의유 / 무를평가하였다. 관심영역은다음과같다 ; 상위전두회 (Superior frontal gyrus), 중간전두회 (Middle frontal gyrus), 하위전두회 (Inferior frontal gyrus), 상위두정소엽 (Superior parietal lobule), 미상핵 (Caudate nucleus), 시상 (Thalamus), 하위두정소엽 (Inferior parietal lobule), 속섬유막앞다리 (Internal capsule anterior limb), 속섬유막뒷다리 (Internal capsule posterior limb), 창백핵 (Globus pallidus) 과조가비핵 (Putamen) 으로이루어진기저핵 (Basal ganglia), 섬피질 (Insular cortex), 해마 (Hippocampus), 상위측두회 (Superior temporal gyrus), 중간측두회 (Middle temporal gyrus) (Fig. 2) 결과 1) 일반적특성및인지기능비교총 27명의대상자중무시군은 18명, 비무시군은 9명이었다., 평균연령은무시군 66.3 ± 11.8세, 비무시군 70.1 ± 7.7세이었고, 성별은무시군에서남자 11명 (61.1%), 여자 7명 (38.9%), 비무시군에서남자 3명 (33.3%), 여자 6명 (66.7%) 이었다. 병변위치는무시군에서전대뇌동맥 (Anterior Cerebral Artery, ACA) 이 2명 (11.1%), 중대뇌동맥 (Middle Cerebral Artery, MCA) 이 16명 (88.9%) 이었고, 비무시군은 9명모두중대뇌동맥이었다. 무시군과비무시군은두군간에나이, 성별, 및병변위치는통계적으로유의한차이가없었다 (Table 1). 뇌졸중중증도는 NIHSS 점수가무시군 10.8 ± 3.8, 비무시군 5.4 ± 2.9 이었고, 병변반대측 FMA점수는무시군 32.6 ± 25.9, 비무시군 63.3 ± 38.1로무시군이중증도가높았고 (p<0.05) 입원시 FIM 점수는무시군 60.0 ± 18.1, 비무시군 86.7 ± 18.2로무시군의기능적수준이낮았다 (p<0.05). K-MMSE 점수는무시군 19.7 ± 6.3, 비 40

5 정은화 외 2인 편측 공간무시 뇌졸중 환자에서 동반된 인지기능 손상과 기능적 예후의 관계 Fig. 2. Anatomical analysis methods. Specific lesions related to spatial neglect. 1. Superior frontal gyrus, 2. Middle frontal gyrus, 3. Inferior frontal gyrus, 4. Superior parietal lobule, 5. Caudate nucleus, 6. Thalamus, 7. Inferior parietal lobule, 8. Internal capsule anterior limb, 9. Basal ganglia, 10. Insular cortex, 11. Internal capsule-posterior limb, 12. Hippocampus, 13. Superior temporal gyrus 14. Middle temporal gyrus. Table 2. Comparison of Cognitive Function and Functional Outcomes in Neglect Group and Non-neglect Group by ANCOVA Analysis Neglect group A&C (K-MMSE) Digit span-f Digit span-b SVLT-IR* SVLT-DR LOTCA-VP LOTCA-VMO D/C FIM* FIM gain* Non-neglect group Mean ± SD 95% CI Mean ± SD 95% CI 1.8 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± p Values are mean ± standard deviation. A&C: Attention & Calculation, Digit span-f: Digit span test-forward, Digit span-b: Digit span test-backward, SVLT-IR: SVLT-Immediate recalls, SVLT-DR: SVLT-Delayed recalls, LOTCA-VP: LOTCA-Visual perception, LOTCA-VMO: LOTCA- Visuomotor organization, D/C FIM: Discharge FIM. ANCOVA by *p

6 Brain & NeuroRehabilitation 2016; 9: 무시군 24.0 ± 4.5로두군간에통계적으로유의한차이가없었고인지기능평가항목중주의집중력, 기억력평가항목은유의한차이가없었으나시지각기능평가항목중로웬스테인작업치료인지평가-시운동구성능력 (LOTCA Visuomotor organization) 은무시군에서저하되어있었다 (p<0.05) (Table 1). 2) 편측공간무시에따른기능적예후기능적예후는퇴원시 FIM 점수가무시군 68.1 ± 21.5, 비무시군 ± 15.7로무시군의퇴원시 FIM 점수가유의하게저하되어있었고 (p<0.05). 입원시 FIM 점수는무시군 60.0 ± 18.1, 비무시군 86.7 ± 18.2로무시군의입원시 FIM 점수가유의하게저하되어있었다 (p<0.05). 기능적회복정도인 FIM gain 점수는무시군 8.1 ± 7.3, 비무시군 19.2 ± 12.5로무시군에서유의하게저하되어있었다 (p<0.05) (Table 1). 3) 공분산분석에의한편측공간무시에따른인지기능및기능적예후입원시 FIM 점수와 NIHSS 점수를보정한공변량분석결과서울언어학습검사 즉각회상 (SVLT-Immediate recalls) 이무시군에서 9.9 ± 51.9 (95% CI, ), 비무시군 16.1 ± 1.2 (95% CI, ) 로무시군에서유의하게저하되어있었고 (p<0.05), 퇴원시 FIM 점수는무시군에서 77.0 ± 2.4 (95% CI, ), 비무시군에서 88.1 ± 3.7 (95% CI, ) 로무시군에서유의하게저하되어있었다 (p<0.05). FIM gain은무시군에서 8.0 ± 2.4 (95% CI, ), 비무시군에서 19.1 ± 3.7 (95% CI, ) 으로무시군에서유의하게저하되어있었다 (p<0.05) (Table 2). 4) 편측공간무시환자의기능적예후에따른일반적특성편측공간무시환자 18명중나쁜예후군은 8명, 좋은예후군은 10명이었다. 평균연령은나쁜예후군 69.9 ± 9.4세, 좋은예후군 63.5 ± 13.2이었고, 성별은좋은예후군에서남자 4명 (50%), 여자 4명 (50%), 나쁜예후군에서남자 7명 (70%), 여자 3명 (30%) 이었다. 병변위치는나쁜예후군에서전대뇌동맥 (Anterior Cerebral Artery, ACA) 이 1명 (12.5%), 중대뇌동맥 (Middle Cerebral Artery, MCA) 이 7명 (87.5%) 이었고좋은예후군에서전대뇌동맥 (Anterior Cerebral Artery, ACA) 이 1명 (10%), 중대뇌동맥 (Middle Cerebral Artery, MCA) 이 9명 (90%) 이었다. 나쁜예후군과좋은예후군은두군간나이, 성별, 병변위치에서통계학 Table 3. Comparison of Characteristics and Cognitive Function in Neglect group by Functional Outcomes Total N=18 Poor outcome N=8 Good outcome N=10 Age (years) 66.3 ± ± ± 13.2 SEX Male 11 (61.1) 4 (50) 7 (70) Female 7 (38.9) 4 (50) 3 (30) Lesion location ACA 2 (11.1) 1 (12.5) 1 (10) MCA 16 (88.9) 7 (87.5) 9 (90) KF-NAP* 14.4 ± ± ± 2.8 Initial NIHSS 10.8 ± ± ± 3.2 Initial FMA Affected U/E* 20.8 ± ± ± 20.0 Unaffected U/E 58.8 ± ± ± 10.0 Affected L/E* 11.8 ± ± ± 11.3 Unaffected L/E 29.1 ± ± ± 14.2 Initial FIM* 60.0 ± ± ± 9.2 FIM gain* 8.1 ± ± ± 7.8 Initial K-MMSE* 19.7 ± ± ± 3.3 A&C (K-MMSE) 1.6 ± ± 1.4 Digit span-f 5.7 ± ± 2.0 Digit span-b 2.7 ± ± 1.5 SVLT-IR** 14.0 ± ± 6.2 SVLT-DR** 4.2 ± ± 3.1 LOTCA-VP** 12.2 ± ± 1.1 LOTCA-VMO** 12.0 ± ± 4.9 Values are mean ± standard deviation or N (%). A&C: Attention & Calculation, Digit span-f: Digit span test-forward, Digit span-b: Digit span test-backward, SVLT-IR: SVLT-Immediate recalls, SVLT-DR: SVLT-Delayed recalls, LOTCA-VP: LOTCA-Visual perception, LOTCA-VMO: LOTCA- Visuomotor organization. Mann-Whitney test by *p<0.05, **p<0.01. 적으로유의한차이가없었다 (Table 3). 뇌졸중중증도는 NIHSS 점수와병변반대측 FMA점수가나쁜예후군과좋은예후군의두군간통계적으로유의한차이가없었으나무시중증도는 KF-NAP점수가나쁜예후군 18.3 ± 8.0, 좋은예후군 11.3 ± 2.8로나쁜예후군의중증도가높은것으로나타났다 (p<0.05). 입원시 FIM 점수가무시군 46.3 ± 17.5, 비무시군 70.9 ± 9.2로무시군의입원시 FIM 점수가유의하게저하되어있었다 (p<0.05). 기능적회복정도인 FIM gain 점수는무시군 8.1 ± 7.3, 비무시군 19.2 ± 12.5로무시군에서유의하게저하되어있었다 (p<0.05). K-MMSE 점수는나쁜예후군 16.0 ± 7.4, 좋은예후군 22.6 ± 3.3로나쁜예후군의인지기능이저하되어있었다 (p<0.05) (Table 3). 5) 편측공간무시환자의기능적예후에따른인지기능비교 편측공간무시환자에서시행한인지기능평가영역중 42

7 정은화외 2 인 : 편측공간무시뇌졸중환자에서동반된인지기능손상과기능적예후의관계 주의집중력영역은숫자바로따라외우기 (Digit span test-forward) 와주의집중및계산 (Attention & Calculation) 항목에서나쁜예후군과좋은예후군두군간에통계적으로유의한차이가없었다. 기억력영역중숫자거꾸로따라외우기 (Digit span test-backward) 는두군간에유의한차이가없었으나, 서울언어학습검사 즉각회상 (SVLT-Immediate recalls) 의평균점수는나쁜예후군에서 14.0 ± 7.4점, 좋은예후군에서 18.5 ± 6.2점으로나쁜예후군에서통계적으로유의하게감소되어있었다 (p<0.01). 서울언어학습검사 지연회상 (SVLT-Delayed recalls) 은각각평균 4.2 ± 3.6점, 6.5 ± 3.1점으로나쁜예후군에서통계적으로유의하게감소되어있었다 (p<0.01). 시지각기능영역에서는로웬스테인작업치료인지평가-시각적지각능력 (LOTCA Visual perception) 에서나쁜예후군과좋은예후군의평균점수가각각 12.2 ± 4.3점, 15.1 ± 1.1점으로유의한차이를나타냈고 (p<0.01) 로웬스테인작업치료인지평가-시운동구성능력 (LOTCA Visuomotor organization) 항목은나쁜예후군평균점수 12.0 ± 5.1점, 좋은예후군평균점수 14.2 ± 4.9 점으로두군간유의한차이를보였다 (p<0.05) (Table 3). 유의한상관관계를보였다 (p<0.01) (Table 3). 주의집중및계산항목은통계적으로유의한상관관계가없었다 (p>0.05) (Table 4). 7) 편측공간무시의해부학적분석전체연구대상자중무시군 18명과비무시군 9명에서편측공간무시와관련된영역의침범여부를분석하였다 무시군에서는중간전두회 (Middle frontal gyrus) 가 67%, 섬피질 (Insular cortex) 이 56%, 하위전두회 (Inferior frontal gyrus), 하위두정소엽 (Inferior parietal lobule) 과중간측두회 (Middle temporal gyrus) 가각각 50%, 상위측두회 (Superior temporal gyrus) 가 44% 로가장많이침범된것으로나타났으며비무시군에서는기저핵 (Basal ganglia) 이 56% 로가장많이침범되어있었다. 두군간에통계적으로유의한차이를나타낸병변위치는중간전두회 (Middle frontal gyrus), 하위두정소엽 (Inferior parietal lobule), 상위측두회 (Superior temporal gyrus), 중간측두회 (Middle temporal gyrus) 및섬피질 (Insular cortex) 이었다 (p<0.05) (Table 5). 6) 편측공간무시중증도와인지기능의상관관계 편측공간무시환자의 KF-NAP 점수와각인지기능평가검사의상관관계는숫자바로따라외우기 (Digit span test Forward) (r=.561) (p<0.05), 서울언어학습검사- 즉각회상 (SVLT- Immediate recalls) (r=.456) (p<0.05), 서울언어학습검사-지연회상 (SVLT- Delayed recalls) (r=.581) (p<0.05), 로웬스테인작업치료인지평가-시각적지각능력 (LOTCA-Visual perception) (r=.783) (p<0.001) 과로웬스테인작업치료인지평가-시운동구성능력 (LOT- CA-Visuomotor organization) (r=.687) 에서통계적으로 Table 4. Correlation between Neglect Severity and Cognitive Impairment Coefficient KF-NAP Attention & Calculation Digit span test-forward* Digit span test-backward SVLT-Immediate recalls* SVLT-Delayed recalls* LOTCA -Visual perception*** LOTCA -Visuomotor organization** Spearman Correlation by *p<0.05, **p<0.01, ***p< p Table 5. Comparison of Lesion Location between Neglect Group and Noneglect Group Lesion Neglect (N=18) No neglect (N=9) SFG 1 (6) 0 (0) MFG* 12 (67) 1 (11) IFG 9 (50) 1 (11) SPL 4 (22) 0 (0) IPL* 9 (50) 0 (0) STG* 8 (44) 0 (0) MTG* 9 (50) 0 (0) P-O-J 4 (22) 0 (0) Hippo 1 (6) 0 (0) I* 10 (56) 1 (11) Cn 4 (22) 1 (11) BG 7 (39) 5 (56) Th 0 (0) 2 (22) IC-Al 1 (6) 0 (0) IC-Pl 0 (0) 1 (11) PVWM-A 4 (22) 3 (33) PVWM-P 6 (33) 0 (0) Values are N (%), Kai-square test by *p<0.05. Abbreviation: SFG: Superior frontal gyrus, MFG: Middle frontal gyrus, IFG: Inferior frontal gyrus, SPL: Superior Parietal lobule, IPL: Inferior Parietal lobule, STG: Superior Temporal gyrus, MTG: Middle Temporal gyrus, P-O-J: Parieto-occipital junction, Hippo: Hippocampus, I: Insular, Cn: Caudate nucleus, BG: basal ganglia, Th: Thalamus, IC-Al: Internal capsule-anterior limb, IC-Pl: Internal capsule-posterior limb, PVWM-A: Periventricular white matter-anterior part, PVWM-P: Periventricular white matter-posterior part. 43

8 Brain & NeuroRehabilitation 2016; 9: ) 편측공간무시중증도와병변수의상관관계전체연구대상자중편측공간무시가있는것으로나타난무시군 18명의 KF-NAP 점수와 Table 5의편측공간무시와관련된주요병변위치에서침범된영역수의스피어만상관분석을통해상관관계분석한결과통계적으로유의한상관관계는없었다 (r=.076) (p=0.764). 고찰 본연구는뇌졸중후발생하는편측공간무시와인지기능의동반손상정도를확인하고, 편측공간무시환자에서여러인지영역중기능적예후에영향을주는영역에대해알아보고자시행된연구이다. 뇌졸중의발생은신체적, 감각적기능에대한손상뿐아니라인지기능의손상을가져오며인지기능의손상은편측공간무시와같은공간지각능력의장애를포함한다. 30,31 편측공간무시는병변반대측공간으로의지각 (perception) 과표상 (representation) 에문제가생기는것으로사실상뇌졸중의기능적예후에편마비 (hemiplegia) 보다더큰부정적영향을줄수있다. 31,32 편측공간무시장애는대부분중대뇌동맥뇌졸중의결과로써우측대뇌반구의손상에의해발생하기때문에두정엽손상 (parietal lesion) 과가장연관이있는것으로알려져있으나많은환자들에서두정엽, 측두엽그리고전두엽손상의결합으로발생된다. 26,27 또한이와같은피질영역과관련한피질하병변 (subcortical lesion) 으로인해서도편측공간무시가발생할수있다. 28,29 즉, 하나의특정해부학적영역이편측공간무시증상을나타나게하는것이아니며손상영역에따라주의집중력, 기억력, 시각적지각능력, 시운동조직능력과같은인지장애를동반할수있고이로인해편측공간무시의중증도및기능회복에차이가있을수있다. 33,34 이에본연구는편측공간무시장애가있는뇌졸중환자의인지기능손상과기능적예후의관계를알아보기위해시행하였으며본연구의대상자선정기준에해당하는 27 명의대상자중 KF-NAP 을시행하여편측공간무시가있는것으로나타난무시군 18명과편측공간무시가없는것으로나타난비무시군 9명의두군으로나누었다. 그결과두군간에뇌졸중초기평가중 NIHSS 점수, 병변반대측상하지 FMA 점수, 퇴원시 FIM 점수및기능회복정도 (FIM gain) 에서통계적으로유의한차이를보였으며, 인지기능평가항목중로웬스테인작업치료인지평가- 시운동구성능력 (LOTCA-Visuomotor organization) 에서유 의한차이를보였다. 따라서이전연구결과들과마찬가지로뇌졸중환자에서편측공간무시가있는환자는편측공간무시가없는환자보다뇌졸중중증도가심하고인지및운동기능의전반적인기능적상태가좋지않기때문에기능적회복이지연될수있다는것을알수있었다. 35,36 무시군과비무시군의인지기능과기능적예후에영향을미칠수있는입원시 FIM 점수와뇌졸중중증도의척도인 NIHSS 점수를보정한공변량분석결과서울언어학습검사 즉각회상 (SVLT-Immediate recalls), 퇴원시 FIM 점수그리고 FIM gain에서두군간유의한차이가있는것으로나타나편측공간무시증상이인지기능과기능적예후및회복에영향을준다는것을본연구결과를통해알수있었다. 편측공간무시가있는환자에서인지기능손상의동반과기능적예후의관계를확인하기위해퇴원시 FIM 점수를기준으로 18명의대상자들을좋은예후군 10명과나쁜예후군 8명의두군으로분류하였다. 퇴원시 FIM 점수가 70점미만일경우퇴원후재활병원과같은다른기관으로퇴원을함으로써재원기간이연장되거나집으로퇴원하더라도지속적인주의와도움이필요하다는연구결과에따라본연구의기능적예후기준은 FIM 점수 70점이상과 70점미만으로정의하였다. 20 나쁜예후군과좋은예후군의뇌졸중중증도를확인하기위해실시한 NIHSS 점수, FMA 초기평가점수에서두군사이에유의한차이가없었으나 KF-NAP, K-MMSE, 인지기능검사영역중기억력, 시지각기능평가에서두군간에유의한차이가있었다. 따라서인지기능손상이편측공간무시환자의임상적특징으로나타날수있고인지기능손상의동반으로인해전반적인기능적수준이저하될수있다는이전연구들과마찬가지로본연구에서도편측공간무시와인지기능손상이동반되면기능적예후가나쁘다는결과를확인할수있었다. 37 특히본연구에서는인지기능영역중기억력과시지각기능의손상이편측공간무시환자의기능적예후에부정적영향을미치는것으로나타났다. Baddely와 Hitch (1974) 는기억력의체계에대해서주의집중조절체계 (attention control system), 주요실행기능 (central executive) 이청각및시공간적정보를위한부수적인저장구조라고설명하였다. 38 편측공간무시환자는구조적, 임상적으로주의집중및실행기능에문제를보이고이는기억력체계와연관이되기때문에기억력의손상이동반되는것으로사료된다. 또한편측공간무시환자는병변반대측공간을향한강한편향성을보이기때문에무시측에대한공간적불균 44

9 정은화외 2 인 : 편측공간무시뇌졸중환자에서동반된인지기능손상과기능적예후의관계 형으로인하여시각적인지기능의손상이발생하게된다. 39 따라서편측공간무시환자는병변반대측공간으로움직임의실행에어려움을보일뿐만아니라개인위생, 식사, 이동하기와같은일상생활수행에서시지각문제로인해전반적인기능수준이저하되어기능적예후에부정적인영향을미칠수있다. 본연구결과에서편측공간무시환자의 KF-NAP 점수와주의집중력, 기억력, 시지각기능이통계적으로유의한상관관계를보여편측공간무시가주의집중력, 기억력, 시지각과관련된인지영역들과연관성이있고편측공간무시환자에게인지기능손상이동반되면무시증상이악화될수있음을알수있었다. 편측공간무시와관련된뇌영역은아직확실히밝혀져있지않은데본연구에서시행한해부학적분석에서는무시군에서중간전두회 (Middle frontal gyrus) 가 67% 로가장많이침범되었고섬피질 (Insular cortex) 이 56%, 하위두정소엽 (Inferior parietal lobule), 중간측두회 (Middle temporal gyrus) 와하위전두회 (Inferior frontal gyrus) 가각각 50% 에서침범된것으로분석되었다. 작업기억과편측공간무시가연관이있다고보고한 LaBar (1999) 등의연구에서는공간적주의집중과작업기억이전두두정영역 (Frontoparietal site) 의신경망으로연결되어해부학적으로연관되는특징을가진다고하였다. 40 또한하위전두회 (inferior frontal gyrus) 는부적절한반응을억제하는주의집중스위치의역할로써특정기억을회상할때다른기억들을억제시키는기억기능에관여하며 41,42 하위두정소엽 (inferior parietal lobule) 은해마 (hippocampus) 와신경망을이루는것으로알려져있어, 43 본연구결과에서침범된구조들은기억력에관여하는부위들이었다. 한편 Corbetta 등 (2011) 은편측공간무시는주의집중을포함하는인지기능연결의손상으로인한결과이며전두안와영역 (frontal eye field) 앞쪽과두정내구 (intraparietal sulcus) 뒤쪽을포함하는등쪽주의집중망 (Dorsal attention network, DAN) 과하위전두영역 (Inferior frontal gyrus) 앞쪽에서측두두정접합 (temporoparetal junction) 뒤쪽으로우측바깥영역을연결하는배쪽주의집중망 (Ventral attention network, VAN) 이관여한다고보고하였다. 두가지연결이모두편측공간무시증상에연관되지만최근연구에서는주의집중유지, 각성, 집중의재설정 (reorientation) 의기능을하는배쪽주의집중망 (ventral attention network, VAN) 이백색질의연결을포함하여편측공간무시의병변으로제안되고있으며 44 본연구결과에서침범된구조들과연관이있었다. 따라서배쪽주의집중망 (ventral attention network, VAN) 과관련된구조들이편측공간무시환자의주의집중뿐만아니라 관련된인지기능인기억력과시지각기능에영향을줄수있을것으로사료된다. 본연구의해부학적분석결과와이전연구들을비교해보면 Karnath 등 (2004) 이 140명의우측대뇌반구손상의뇌졸중환자를대상으로편측공간무시가있는무시군 (78 명 ) 과편측공간무시가없는비무시군 (62명) 을대상으로편측공간무시환자의화소단위의통계분석 (voxel-based statistical analysis) 을한연구에서무시군이비무시군과비교하여피질수준에서상위측두회 (Superior temporal gyrus) 와섬피질 (Insular cortex) 영역에서유의한차이가있었고피질하부수준에서미상핵 (Caudate nucleus) 과조가비핵 (Putamen) 이유의한차이가있었다고보고하였다. 26 편측공간무시의회복예측과관련한연구에서 Karnath 등 (2010) 은우측대뇌반구손상뇌경색환자 54명을대상으로급성기와만성기뇌졸중환자의무시중증도에관한해부학적분석을하였는데, 그결과급성기 ( 뇌경색발병이후평균 12.4일 ) 에서가장많이손상된영역은상위측두회 (Superior temproal gyrus) 가 21% 이었고이어서중간측두회 (Middle temproal gyrus) 가 16%, 하위두정소엽 (Inferior parietal lobule) 이 8%, 섬피질 (Insular cortex) 이 5%, 하위전두회 (Inferior frontal gyrus) 가 4% 손상되었다고하였다. 27 본연구에서는전체대상자중 KF-NAP 평가에의하여편측공간무시가있는것으로나타난무시군과편측공간무시가없는것으로나타난비무시군의병변위치및무시중증도의관계를분석하였고그결과무시중증도와병변의수사이에서의미있는상관관계는없었으며두군간통계적으로유의한차이를나타낸병변위치는중간전두회 (Middle frontal gyrus), 하위두정소엽 (Inferior parietal lobule), 상위측두회 (Superior temporal gyrus), 중간측두회 (Middle temporal gyrus) 그리고섬피질 (Insular cortex) 이었다. 즉, 본연구결과와비교하여이전연구결과의비율은조금씩다르게보고되었으나침범된구조들사이에는연관이있었다. 또한침범된영역이많을수록편측공간무시중증도가심한것은아니며편측공간무시와관련된특정영역들의병변이무시중증도에영향을준다는것을본연구결과를통해알수있었다. 그러나, 본연구에참여한대상자수가적으며, 편측공간무시군과비무시군에서입원시 FIM 점수에따른중증도가일치되지않았다는점에서본연구결과에제한이있다. 따라서추후좀더많은뇌졸중환자를대상으로편측공간무시와동반인지기능손상영역및인지기능의손상여부가기능적예후에미치는영향등에대한연구가필요할것이다. 45

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