84 권재철 정용 나덕렬 Table 1. Proposed diagnostic criteria of corticobasal degeneration[5] Inclusion criteria Rigidity plus one cortical sign (apraxia, corti

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1 대한치매학회지 : 제 1 권제 2 호 2002 Journal of the Korean Dementia Association. 2002; 1: 83-9 파킨슨증상을동반한치매 : 피질기저핵변성 권재철 * 정용 나덕렬 성균관대학교의과대학삼성서울병원신경과학교실, 창원파티마병원신경과 * Dementia with Parkinsonism: Corticobasal Degeneration Jay C. Kwon, M.D.*, Yong Jeong, M.D., Duk L. Na, M.D. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology*, Changwon Fatima Hospital, Changwon, Korea Address for correspondence Duk L. Na, M.D. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul , Korea Tel: Fax: dukna@smc.samsung.co.kr Corticobasal degeneration (CBD) is one of the disorders that manifests as dementia plus parkinsonism. Symptoms or signs in CBD can be classified into cortical (cortical sensory loss, apraxia, alien limb, frontal release signs, dysphasia, and dementia), movement symptoms (akinetic-rigid syndrome, dysequilibrium, postural-action tremor, limb dystonia, myoclonus, other dyskinesias), and others (hyperreflexia, Babinski signs, supranuclear gaze palsy, levator inhibition, and dysarthria). Of these, essential signs for the diagnosis of CBD especially in its early stage include unilateral limb rigidity, bradykinesia, ideomotor apraxia, postural imbalance, unilateral limb dystonia, and cortical dementia. CT or MRI in patients with CBD usually shows asymmetric atrophy in the parietal and frontal area, which is rather nonspecific. SPECT or PET, in contrast, shows more widespread functional changes involving cortical regions (prefrontal, anterior cingulate, medial premotor, sensorimotor, posterior parietal, and superior temporal) as well as putamen or caudate nucleus. It has been reported that clinically diagnosed CDB patients may disclose histopathologic findings compatible with Alzheimer's disease, frontotempral dementia, progressive supranuclear palsy, or Creutzfeldt-Jacob disease. Recent achievements in molecular genetic studies in CBD, however, are expected to compliment clinical and neuroimaging findings in enhancing the diagnostic accuracy of CBD. Key Words: Corticobasal degeneration 서론피질기저핵변성 (Corticobasal degeneration, 이하 CBD) 을맨처음기술한사람은 Rebeiz 등이다 [1]. 이들은비대칭적인파킨슨증후군과실행증 (apraxia), 근간대증 (myoclonus) 그리고핵상주시마비 (supranuclear gaze palsy) 를보인환자들에서뇌부검상 corticodentatonigral degeneration with neuronal achromasia" 소견을보고하였다. 이후많은임상적또는병리학적연구를통해소뇌이상이없고주로대뇌피질과기저핵에이상이있음이밝혀져, cortico-basal ganglionic degeneration (CBGD) 이라고주로불리어졌다. 특히유럽에서는 corticobasal degeneration (CBD) 라는용어가많이사용되었다. CBD 의특징적인증상은손, 팔, 다리등에나타나는비대칭적증상, 국소적인경직 (rigidity) 과구축 (contracture) 을동반한근이긴장증 (dystonia) 과말실행증 (speech apraxia), 진전 (tremor), 근간대증, 피질감각의저하, 파킨슨증상등이있다. 그외에언어장애, 구음장애, 전두엽기능장애, 우울증, 무감동 (apathy), 과민 (irritability) 그리고초조 (agitation) 등이있다 [2]. 병리학적으로 CBD로확인된환자들을대상으로수행한연구결과, CBD의진단을정확하게예측할수있는가장중요한임상적인소견은다음과같은것들이었다. 사지이긴장증 (limb dystonia), 관념운동실행증 (ideomotor apraxia), 근간대증 (myoclonus), akinetic-rigid syndrome ( 병의초기에보행장애와균형장애를동반하지않음 )[3, 4]. 이러한임상특징을바탕으로진단기준 (Table 1) 이발표되기도하였다 [5]. 신경병리학적으로 CBD는 progressive supranuclear palsy (PSP), Pick병과중복되는소견이많아서구별하기힘들다 [6, 7]. 연구자들은정확한진단을위해서는병리학적소견이나임상적인지표중어느한가지만고려하기보다는, 둘다고려해야만한다고주장한다. 최근 tau-positive inclusion이 CBD에서발견되고, 유전자연구로 tauopathy와관련된 chromosome 17의여러가지돌연변이가발견됨으로써진단율이높아질것으로기대된다. 본글에서는 CBD의임상적특징, 신경영상소견, 병리소견에대해살펴보고자한다. 83

2 84 권재철 정용 나덕렬 Table 1. Proposed diagnostic criteria of corticobasal degeneration[5] Inclusion criteria Rigidity plus one cortical sign (apraxia, cortical sensory loss or alien limb phenomenon) Asymmetric rigidity, dystonia, and focal reflex myoclonus Quantification of clinical features Rigidity: easily detectable without reinforcement Apraxia: more than simple use of limb as object; clear absence of cognitive or motor deficit sufficient to explain disturbance Cortical sensory loss: preserved primary sensation; asymmetric Alien limb phenomenon: more than simple levitation Dystonia: focal in limb; present at rest at onset Myoclonus: reflex myoclonus spreads beyond stimulated digits Exclusion criteria Early dementia (This will exclude some patients who have CBD, but whose illness cannot clinically be distinguished from other primary dementing diseases.) Early vertical gaze palsy Rest tremor Severe autonomic disturbances Sustained responsiveness to levodopa Lesions on imaging studies indicating another pathologic process is responsible 본 론 Table 2. Clinical features of corticobasal degeneration in 64 cases[8] 1. 임상적특징 Previous cases* (n=28) Present cases (n=64) Total (%) (n=64) 1) 임상소견의요약과인구의학적특성 CBD의임상소견에대한연구는여러편있었고그결과는비교적비슷하게보고되었다. Rinne 등은 64명에대한연구에서임상양상을피질성징후, 운동질환, 그리고그외소견으로나누어 Table 2와같은결과를얻었다 [8]. 발병시에좌우비대칭적으로나타나는것은 CBD가다른신경퇴행성질환들과구별되는가장큰특징이다. Wenning 등은부검상확인된 14예의 CBD환자의 50% 에서첫발병이비대칭적인손의부자연스러움 (clumsiness) 이었다라고보고하였다 [4]. 발병 3년후에병원에첫방문했을때는편측경직 (79%), 서동증 (71%), 관념운동실행증 (64%), 자세균형불안정 (45%), 편측이긴장증 (43%), 그리고피질성치매 (36%) 를보였다. 8 센터에서모은 147명의환자에대한연구에서는다음의특징들이가장흔하였다 ; 파킨슨증후군 (100%), 고위인지기능장애 (93%), 실행증 (82%), 보행장애 (80%), 이긴장증 (71%), 진전 (55%), 근간대증 (55%), alien hand (42%), 피질성감각소실 (33%), 치매 (25%)[9]. 발병당시의평균연령은 63±7.7 세였고발병에서부터사망까지는평균 7.9±0.7년이걸렸다 ( ). 이러한소견은 Rinne 등이보고한 36명의 CBD환자에대한임상적특징에대한연구와비교적일치하였다. Rinne 등의연구에서는발병연령이 60.9±9.7 년이었다. Riley 등의연구에서는발병연령이 60세 (51-71세) 였고남자가여자보다조금더많았다 ( 남자 : 여자 =3:2)[10]. 국내에서는 Lee 등이 6증례의 probable CBD환자의임상증상을보고하였고이는외국의보고와비슷하였다 [11]. Movement disorder Akinetic-rigid syndrome (100) Dysequilibrium (73) Postural-action tremor (48) Limb dystonia (67) Reflex myoclonus (67) Cerebral cortical signs Sensory loss (45) Apraxia (84) Alien limb (47) Frontal release signs (48) Dementia (31) Dysphasia (16) Other manifestations Hyperreflexia (70) Babinski signs (48) Supranuclear gaze palsy (59) Levator inhibition (20) Dysarthria (53) Other dyskinesias (28) *Includes cases from Rebeiz et al. (1968), Anonymous Case Records of the Massachusetts General Hospital (1985), Watts et al. (1985), Greene et al. (1990), Lippa et al. (1990), Paulus and Selim (1990) and Riley et al. (1990). Includes cases of Obeso et al. (1985), Gibb et al. (1989) and Sawle et al. (1991). CBD 의임상적특징을세분하여살펴보면다음과같다. 2) 관념운동실행증 (Ideomotor apraxia) 실행증 (apraxia) 이란과거에반복, 학습된기술적인동작 (skilled movement) 의장애를말하며이장애가마비 (paralysis), 감각이상 (sensory loss), 실조증 (ataxia), 운동성질환

3 파킨슨증상을동반한치매 : 피질기저핵변성 85 (movement disease), 알아듣기능력의장애 (poor comprehension) 등에의한것이아닐경우에만해당된다 [12, 13]. 실행증에는여러가지유형이있으나 CBD에서보이는실행증은관념운동실행증 (ideomotor apraxia) 이다. 관념운동실행증이란명령이주어졌을때간단한몸짓 ( 예를들면, 경례하는동작 ) 이나도구사용흉내 ( 예를들면, 망치질하기또는김밥써는흉내 ) 를행하지못하는경우를말한다. 오류형태는다양하며, 이에대한자세한내용은 Kwon 등의연구에기술되어있다 [14]. 관념운동실행증은 CBD의주로초기부터나타난다 [15, 16]. 심해지면검사자의간단한손가락모양도따라하지못한다. 드물게검사자의손가락모양을따라할때환자의손이검사자의손에달라붙는현상을볼수있다. Kwon 등은 CBD환자의증례연구에서 hand gesture 과제를시켰을때보이는 manual approach behavior를보고하였다 [17]. 그들은이행동을우측두정엽기능저하로인한시공간능력장애를극복하기위한보상적인행동이라고하였다. 알쯔하이머환자 (AD) 에서보이는관념운동실행증과마찬가지로도구를실제로사용하면수행능력이향상된다 [18]. 관념운동실행증의기전에는두가지가있다. 첫째는이러한동작들을어떻게수행할것인가에대한기억모음 (representation, 또는 praxicon이라고도불림 ) 을상실하여생긴다는것이다 (representational deficit). 둘째는기억모음들은이상이없지만그안에있는정보를동작으로정확하게수행해야하는데이단계에서장애가있는경우이다 (production-execution deficit). Jacobs 등은 4명의 CBD환자를대상으로한연구에서 CBD와관련된실행증은기억모음들은유지되어있는반면실행단계에서이상을보이는관념운동실행증이라고주장하였다 [19]. 그리고이같은실행증은보조운동영역 (supplementary motor area) 의이상으로생길수있다고주장하였다. 3) 파킨슨증후군 (Parkinsonism) 서동증과경직등의파킨슨증상들은 CBD환자가처음병원을방문했을때가장흔하게관찰되는징후들이다. 진전은대부분은 postural 또는 action시에보인다. 진전은서서히진행하여결국에는근간대성 jerk의양상으로발전한다. 팔에서전형적인경직, 이긴장성자세를관찰할수있는데, 어깨의신전, 팔꿈치나손목의굴곡, 손가락의 clawing 등이흔히볼수있는소견들이다. CBD에서보이는사지구축 (contracture) 은주로 alien hand 가생긴후보이는데이런소견들은다른 parkinson plus syndrome에서보다는흔하다 [20]. 4) 근간대증 (Myoclonus) 국소적근간대증은주로한쪽팔에침범하는데안정시에도존재하고, 수의적운동이나감각자극에의해서악화된다 (reflex myoclonus). 이는전형적인피질성근간대증 (cortical myoclonus) 과비슷하지만전기생리학적으로는다르다 [21]. 전형적인피질성근간대증은증가된 SEP (somatosensory-evoked potential) 가비교적길게 (50 msec in hand) 보이고 cortical discharge가근간대증이나타나기전에보이지만, CBD 에서보이는양상은 SEP의증가와는관계가없고짧게관찰된다 (40 msec). Strafella 등은 CBD에서보이는근간대증은직접적인감각피질경로의강조로인해서보이는현상이고, 전형적인피질성근간대증은비정상적인감각-운동의 cortical relay의장애로인해서생기는현상이라고주장하였다 [22]. 5) 안구운동징후 (Eye sign) 주로자발적단속성안구운동 (voluntary saccadic eye movement) 의시작장애, hypometric saccade, 운동범위의제한등을관찰할수있다. 검사자의손을주시하게한후환자의머리를움직였을때는운동범위의제한은관찰되지않는다. 이는핵상주시마비를시사하는소견이다. 신경학적검사상폭주 (convergence) 장애와상하좌우주시장애가보일수있다. 그러나 PSP와는달리상하주시장애는경미하고대개상방주시만침범되는경우가대부분이다. Vidailhet 등은 CBD에서수평단속운동잠복기증가와 apraxia score' 는밀접한관계가있다고주장하였다 [23]. 6) Alien limb sign Alien limb sign은대개발병으로부터평균 1년후 (1-2년의범위 ) 에생긴다. 환자들은자신의팔이불수의적으로움직이고, 때때로반대편의팔이움직이는것을방해하거나심지어는잡는것을경험한다. 그들은 제멋대로움직인다 ', 내가원하는동작을하지않으려고한다 ' 또는 팔이내팔이아닌것같다 ' 라고표현한다. CBD에서보이는 alien limb sign은주로운동증상을동반하는 motor 또는 anterior alien hand syndrome인데이는시상, 뇌량팽대부 (splenium of corpus callosum), 그리고측두두정엽의병변때문에생기는 sensory 또는 posterior alien hand syndrome과는구별된다 [24]. 7) 치매 (Dementia) CBD에서의치매는연구자의관점에따라서다르게평가된듯하다. CBD의추체외로증상에비중을둔연구에서는대개진행된후에치매가생긴다고주장하였지만, 피질증상에비중을둔연구에서는치매가가장흔한특징이고초기에나타날수도있다고주장하는연구도있었다 [25]. 최근에는 CBD의인지기능에대한연구에관심이높아지고있다. CBD와 AD의신경심리학적특징을비교한연구에서 CBD 환자는즉각회상과지연회상을더잘수행하였으나, praxis, 손가락두드리기속도 (finger tapping speed), 운동 programming 등은잘수행하지못하였다. CBD와 AD에서모두주의

4 86 권재철 정용 나덕렬 집중, 언어유창성 (verbal fluency), 이름대기 (confrontation naming) 의수행에장애가있었다. 그리고, CBD에서 Geriatric depression scale상우울증상이훨씬많았다 [26, 27]. 전반적으로 PSP에서보이는수행장애증후군 (dysexecutive syndrome) 이유사하게관찰되지만 CBD에서는운동수행 (motor execution) 과 praxis 에서더큰장애를보였다. 8) 그외소견들이전의보고에의하면, CBD에서실어증이매우드물거나병이진행된후에나타난다고알려져있었다. 그러나 Frattali 등의연구에의하면명칭실어증, 브로카실어증또는초피질운동실어증이 CBD에서주로보이는언어장애이고비교적흔한소견이었다 [28]. 그리고구음장애나연하장애도보인다고보고하였다. 2. Neuroimaging 1) Brain CT와 MRI 보통 CBD진단에신경영상은도움은주지만특이적이지는않다. 한연구에서 15명의 CBD환자중 14명에서 CT소견이비정상이었다. 8명은침범된대뇌반구의두정엽위축이있었고, 6 명은양쪽의두정엽위축이있었다 [10]. Soliveri 등은비대칭적인전두 -두정엽의위축이 PSP와의구별에도움이된다고주장하였다 [29]. 2) Brain FDG-PET Yamauchi 등은 8명의 CBD환자와 36명의정상인을비교한 PET 연구에서뇌량의체부 (body) 의위축이인지장애와연관이있다고주장하였다 [30]. 미상핵, 조가비핵, 그리고상측두, 하두정엽의비대칭적인대사감소가특징적이었다 [31-33]. 3) Brain SPECT Okuda 등은 10명의 CBD환자와 16명의 AD환자에서 SPECT를이용해서 rcbf (regional cerebral blood flow) 를비교하였다 [34]. CBD환자에서는전전두엽, 전대상회 (anterior cingulate), 내측전운동 (medial premotor), 감각운동피질, 두정엽뒤쪽, 그리고상측두엽의 rcbf가감소되어있었고, AD에서는전전두엽, 두정엽뒤쪽, 상측두엽에서감소되어있었다. 두군을비교했을때 CBD에서전대상회, 감각운동피질, 시상, 기저핵의 rcbf가 AD에비해서더감소되어있었다. 그리고전전두엽하부, 감각운동피질의좌우차이가 AD에비해서의미있게증가되어있었다. 3. 병리학적소견 CBD의병리학적특징에대한연구는그동안많이보고되었다 [35-40]. 그러나 CBD, PSP, Pick병등의임상적, 병리학적 소견이중복되는점이많아더많은연구가요구되어왔다. Boeve 등은임상적으로진단된 13명의 CBD환자들을병리학적으로관찰한결과 7명은 CBD, 2명은 AD, 그리고 PSP, Pick 병, Creutzfeldt-Jakob병 (CJD), non-specific neurodegenerative disorder 각각한명이었다고보고하였다 [40]. 공통적인소견으로비대칭적인 neuronal loss와 ballooned, achromatic cortical neuron을동반한 gliosis가주로중심피질영역의전과후영역에나타나고, 흑질 (substantia nigra) 과기저핵의변성등이다 [6, 41-43]. Achromatic neural inclusion은대뇌피질뿐만아니라, 시상, 하시상핵 (subthalamic nucleus), 적핵 (red nucleus), 흑질등에서도관찰된다. Ballooned (chromatolytic, achromasic) neuron들은 anti-alphab crystallin에강한면역반응을보이고, anti-ubiquitin에도약하게면역반응을보인다. Feany와 Dickson[44] 은이러한 ballooned neuron은 CBD에특이적이지않은반면 tau-containing distal astrocytic process는 CBD의매우특징적인병리학적소견이라고주장하였다. Tau-containing distal astrocytic process는 amyloidand microglia-negative astrocytic plaques" 를만들어 miliary-like tau positive structure의 cluster로관찰된다. AD를비롯한다른신경퇴행성질환에서흔히보이는 tau 단백질의인산화 (phosphorylation) 는 CBD에서특징적으로관찰되지않는다. CBD에서도 tau는두개가짝을이루어나선형 (twisted filament) 의구조를이루는데, AD에서 periodicity가 80 nm인반면 CBD에서는 290 nm정도이다. Pick병에서관찰되는피질영역의 neurofibrillary tangle이나 Pick body가 CBD에서도존재하지만 Pick병과는달리해마에는존재하지않는다. 1) Tauopathy로서 CBD Beta-amyloid deposit 없이뇌에퇴행성변화를일으키는질환중 CBD를비롯해서 PSP, Pick병그리고 frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) 등에서는뇌부검에서특징적으로 tau filament가많이관찰된다. FTDP-17는 FTD와파킨슨양상을보이는 13 가계의특징적인임상적, 병리학적소견이 chromosome 17q21-22와관련된다는연구로인해처음소개되었다 [45]. Chromosome 17에는 tau gene이존재하는데, 지난몇년간여러가계에서 tau gene의다양한돌연변이가확인되었다. 그리고여러연구들을통해서 tau 단백질이신경퇴행성질환에서중요한역할을할것이라고여겨지고있다. 이러한가계내의돌연변이로인한질환외에 tau의변형 (alteration, polymorphism) 으로인한질환들도확인되었다. 그중에서가장특징적인질환이 threerepeat tau isoform을가진 dementia with Pick bodies (DPB) 과 four-repeat tau isoform을가진 CBD이다. 최근까지의연구결과 tau polymorphism이 sporadic PSP와 CBD의위험인자로생각되어진다 [46-48].

5 파킨슨증상을동반한치매 : 피질기저핵변성 감별진단비대칭적인 akinetic rigid syndrome이있을때가장먼저배제해야할질환은 idiopathic Parkinson's disease (IPD) 이다. CBD를 IPD와구별할수있는첫째특징은도파민약제에대한효과가없다는것이다. 둘째로고려할사항은피질이상에의한징후 ( 예를들면, 실행증또는피질성감각소실 ) 와추체로징후가존재한다는것이다. CBD에서보이는안구운동징후또한 IPD에서보이는징후에비해서는더심하다. IPD에서보이는근이긴장증은주로하지에서보이고대부분치료와관련된증상들이라서 CBD와구별된다. 근간대증과자세성진전도전형적인 IPD에서보이는안정시진전과는확실히구분된다. Akinetic rigid syndrome이핵상주시마비와같이있을때는 PSP를의심해야하는데 CBD와의구별이쉽지않다. 그러나 PSP의가장흔한증상은균형장애와예기치않게넘어지는것 (unexpected falls) 이다 [49]. 또한가장특징적인증상은 PSP 는대칭적인체간 (axial) 및근위부의경직이주된증상인반면, CBD는한쪽의경직과이긴장증이더흔한증상이다. 그리고실행증, 근간대증, 피질성감각소실은 PSP에서는보이지않는다. MRI 소견이 CBD와의구별에도움을줄수있는데 PSP는뇌피질의위축은심하지않은데중뇌의위축이비정상적으로심하다. 또한철침착 (iron deposition) 으로인한양쪽창백핵 (globus pallidus) 과조가비핵의후외측부위의신호감소가관찰된다. PSP의안구운동징후는초기에 hypometria와 slowness 가있다가상하주시 ( 특히하방주시 ) 에제한이보이는것이다. 이러한안구운동징후는 CBD와 PSP 모두에서보일수있는데, CBD보다는 PSP에서더초기에심하게관찰된다. PSP에서보이는인지장애는주로전두엽기능장애나전두엽해리징후 (frontal releasing sign) 가관찰되는반면에 CBD에서는보속증이나 alien limb 징후가동반되는경우가흔하다. 국소적인뇌의퇴행성증후군은 AD의특징일수도있다. 병리학적으로증명된 AD환자중에서반대쪽팔의불수의적운동이나감각저하로나타나는우측두정엽증상을보인환자가보고된바있다 [50]. 그외에처음에는편마비로시작한후서서히진행하여결국에는실행증과치매로나타나는경우 [51] 와이긴장증, alien hand, 근간대증, 실행증, 기억장애를보이는병리학적으로확인된 AD 환자도보고된바있다 [52]. 국내에서도 CBD의임상양상을보였으나조직검사상 AD로진단된증례가보고되었다 [53]. 무동증 (akinesia) 과경직같은추체로외증상이 presenile AD에서흔히보일수있지만이러한경우는대개대칭적으로보이고 [54], 사지운동이실제서동증을보이는경우는드물다 [55]. Primary progressive aphasia (PPA) 도국소적대뇌증후군을보이는질환이다 [56]. PPA의병리학적소견은 non-specific neuronal loss, gliosis 와 spongiform change인데, 일부환자에서는 CBD와같은 neuronal achromasia 소견을보인경우도있 다 [57]. 그러나 PPA는사지의운동증상이나징후는없다. Creutzfeldt-Jakob diseas (CJD) 에서도추체외로징후와근간대증이관찰된다. 그러나전신적인근간대증, 빨리진행되는치매, periodic discharge를동반하는비정상적인뇌파소견등이 CBD와구별되는소견들이다. 5. 치료 CBD환자의 L-dopa에대한효과는거의없다. 이는다른 parkinsonism plus dementia와구별되는특징이기도하다. 생화학적연구에서 CBD에서정상인에비해선조체와흑질에도파민농도가감소되어있었다 [10]. 치료는주로증상적인치료에국한되어있고효과는그리좋지않다. 다만근간대증은 clonazepam으로호전될수있고, 통증성경직이나이긴장증이 botulinum toxin 주사로호전될수있다는보고가있다 [58]. 도파민성약물은거의효과가없다. 6. 예후 Wenning 등은초기에서동증또는전두엽기능장애를보이거나진전, 경직, 서동증의세가지중두가지를보이는경우에는예후가좋지않다고보고하였다 [4]. 초기의발병이팔이아닌다리부터시작하여보행장애가진행되는환자나균형잡기장애가있는환자에서대체적으로예후가좋지않았다 [8]. 이미언급한것처럼발병부터사망까지걸리는시간은평균 8년정도이다. 결론이상에서 CBD의임상양상, 신경영상학적소견과병리학적소견에대해서살펴보았다. CBD는드물지만비교적특징적인임상양상들을보이고신경영상검사를통해진단율을더욱높일수있다. 최근에발전하는유전자검사들은진단뿐만아니라치료에도획기적인전환을가져올것으로기대된다. 그동안주로연구되어온파킨슨증상등의피질하징후외에실행증이나치매등의피질징후에대한연구도많은발전이있을것으로기대된다. 참고문헌 1. Rebeiz JJ, Kolodny EH, Richardson EP. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968; 18: Litvan I, Cummings JL, Mega M. Neuropsychiatric features of corticobasal degeneration. J Neurol Neurosurg Psychiatry 1998; 65; Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, et al.

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Dementia2 Today s Topics Memory Impairment & Dementia Age Associated Memory Impairment Dementia Definition of dementia Depression Schizophrenia Mental retardation Delirium : Not final diagnosis term, but symptomatologic