경도인지장애 : 알쯔하이머병의 초기단계인가? Is it an Early Stage of Alzheimer's Disease?

한설희 대한치매학회 2003 Dementia and Neurocognitive Disorders Vol.2 No.2

Aging causes deterioration of various aspects of memory performance in norma adults In recent years. a great deal of interest has been generated around the concept of a boundary or transitional state between normal aging and dementia or, more specifically, Alzheimer's disease (AD). This condition has received a number of descriptions including incipient dementia. questionable dementia. age-associated cognitive decline, isolated memory impairment and mild cognitive impairment (MCI) Commonly accepted guidelines for MCI have been established-memory complaint, preferably corroborated by an informant. objective memory impairment for age and education. normal general cognition, preserved activities of daily living, and not demented The precise definitions need to be explicated. but these will probably simply be a refinement of a concept. rather than a major re-definition Importantly, clinical and neurobiological evidence suggests that patients with MCI are at an increased risk for developing AD. Current research efforts are geared with MCI are at an increased risk for developing AD. Current research efforts are geared towards intervention strategies aimed at preventing the development of AD among persons with MCI.

결절성경화증 환자에서의 SPECT 뇌영상 : 예비적 연구 A preliminary report

한설희,이상수,정승연 충북대학교 의과대학 충북대학교 의학연구소 1991 忠北醫大學術誌 Vol.1 No.1

간질발작을 포함한 전형적인 삼징후가 동반된 결절성경화증 환자를 대상으로 뇌파검사, 뇌전산화단층촬영술 및 단일광자방출단층촬영술을 시행하였다. 뇌전산화단층촬영술에서는 상의하석회화병소와 조영제증강이 뚜렷하지 않은 피질에 연한 저음영 소견이 관찰되었으며 이어서 시행한 단일광자방출단층촬영술에서는 뇌전산화단층촬영술 소견보다 더 광범위한 부위에 관류결손이 관찰되었다. 단일광자방출단층촬영술은 결절성경화증 환자에서 간질발현 병소인 피질결절을 발견하는데 있어서 전산화단층촬영술 및 뇌파검사보다 더 유용한 방법이며 치료방침 결정이나 예후판정에 있어서도 큰 도움을 줄 것으로 기대된다. Two patients with a well-established diagnosis of tuberous sclerosis and epilepsies as their principal clinical symptom were examined by conventional surface electroencephalography(EEG), computed tomography, and single photon emission computed tomography(SPECT) using the 99mTc hexamethyl prophyleneamine oxime(99mTc-HMPAO). The interictal EEG showed various abnormalities of poor localizing value. Brain computed tomography surely demonstrated subependymal calcifications, although the cortical lesions were not so conspicuous. However, the SPECT images of each patient clearly demonstrated decreased cerebral perfusion in cortical areas. It may be assumed that such perfusion defect areas represent the epileptic cortical tubers or those of altered myelination, which are characteristics of the disease.

혈관평활근세포에서 산화에너지대사 억제에 의한 아밀로이드전구단백질 대사의 변화

한문구,최웅,김헌식,안희열,한설희 대한치매학회 2002 Dementia and Neurocognitive Disorders Vol.1 No.1

Background: A reduction in the activity of cytochrome c oxidase(COX) has been recently identified in mitochondria from platelets and postmortem brain tissue of AD patients Sodium azide (NaN₃). a COX inhibitor, is an effective chemical agent producing energy shortage and oxidative stress both in vitro and in vivo system Furthermore it has been suggested that vascular compromise could be either directly involved AD pathogenesis or indirectly associated with triggering pathogenetic events leading to AD This study was performed to investigate amyloid precursor protein (APP) metabolism by inhibition of mitochondrial energy metabolism in cultured vascular smooth muslce cells (VSMCs) Materials and Methods: VSMCs isolated from the aorta of seven weeks old Spraque-Dawley rat were treated with NaN₃in a low concentration (100-500μM) or in a high concentration (1-100mM) Cellular proliferation and viability were determined by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenly)-2H-tetrazolium) assay Cellular APP was detected with N-terminal specific antibody 22C11. Celldeath was determined by observation of morphology and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end labeling stain (TUNEL) We used ginkgo biloba extract(EGb761) and melatonin as anti-oxidants to investigate the mechanism of latered APP metabolism Results: The viability of VSMCs was increased after treatment with 1 mM and 10mM NaN₃(p<0.05) unitl 3 hr and then dimnished Many TUNEL positive cells were found in 10mM and 100mM treatment group. but were not apoptotic in nature 22C11 immunoreactivity was not changed at 3 hr, 6hr, 12hr Anti-oxidants reduced cellular proliferation (p<0.05). but did not block TUNEL positivities and did not influence the 22C11 immunoreactivity In a low concentration NaN₃ treatment group the viability of VSMCs was increased concentration dependently(p<0.05) Immunoblot with 22C11 showed the concentration dependent decrease at 145 kDa, 125 kDa. and high molecular weight range (>160kDa) TUNEL staining showed DNA fragmentations and condensations of nuclear chromatin suggesting apoptosis After treatment with anti-oxidants, the cellular proliferation was more decreased (p<0.05), and TUNEL positive cell deaths were blocked Immunoreactivities of 125 kDa (immature APP). 145 kDa (mature APP). and higher molecular weight bands were recovered below 400μM of NaN₃ Immunoreactivity of 145 kDa was recovered in 100 μM NaN₃ treated group Conclusions: The presumed mechanism of low concentration COX inhibitor is the overproduction of reactive oxygen species resulting from a depression of the mitochondiral electron transport chain. whereas potential consequence of high concentration COX inhibitor might be related to decreassion of ATP synthesis and bioenergetic impairment Reactive oxygen radicals in response to low concentration COX inhibitor alter the processing of APP in VSMCs This investigation demonstrated analtered APP metabolism as a peripheral marker of AD Therefore VSMCs treated with low concentration COX inhibitor could be concsidered as a novel in vitro model of AD.

원발성진행성 실어증

한설희 충북대학교 의과대학 충북대학교 의학연구소 1996 忠北醫大學術誌 Vol.6 No.2

원발성진행성실어증은 수년간에 걸쳐 대뇌고위 기능중 언어영역만 고립적으로 침범되어 서서히 진행하는데 임상적으로 치매와 구별되어야 하는 비교적 드문 증후군이다. 저자는 최근에 62세 여자환자가 약 4년간에 걸쳐 서서히 진행한 언어장애를 주소로 본원 치매크리닉을 방문하여 신경심리검사, 뇌파검사, 뇌핵자기공면영상, 단일광자방출단층촬영술 등에서 전형적인 원발성진행성실어증으로 확인된 우리 나라 최초의 예를 경험하였기에 간단한 문헌고찰과 함께 보고하는 바이다. A 62-year-old right-handed woman presented with a progressive deterioration in her ability to name common object used in everyday life. Her initial language disturbance, word-finding difficulty, got worsened gradually over the next 4 years, She was able to point to the correct object when the word is provided by the examiner despite being unable to name it spontaneously. Her memory, attention, visuospatial skills and comportment were all intact. She is doing well in her daily living activities including taking care of herself, shopping and paying bills. MRI showed left perisylvian atrophy and dilated left frontal horn. SPECT study revealed decreased perfusion in left temporal lobe. Her clinical presentation together with the characteristic structural and functional neuroimaging findings were typical of 'primary progressive aphasia'.

백서 뇌에서의 Nitric Oxide Synthase를 함유한 신경세포의 분포에 관한 연구 : 해마 구조를 중심으로 An NADPH-diaphorase Histochemical Study

한설희 충북대학교 의과대학 충북대학교 의학연구소 1996 忠北醫大學術誌 Vol.6 No.1

뇌에 존재하는 어떤 종류의 신경세포는 nicotinamide adenin dinucleotide phosphate-diaphorase (NADPH-d) 활성을 함유하고 있어 조직화학 기법에 의해 특이성을 가지며 강하게 염색된다. NADPH-d에 염색되는 신경 세포들은 다양한 종류의 신경 독성과 퇴행성 신경변성에 대하여 강한 저항성을 나타내는 것으로 알려져 있다. 또한 NADPH-d는 formaldehyde에 저항성을 나타내는 조직화학적 특성을 가지고 있으며 이는 nitric oxide synthase (NOS) 성질과 동일하다. 따라서 NADPH-d는 formaldehyde로 고정된 신경조직에서 NOS의 활성을 가진 신뢰성 높은 조직화학지표로 생각된다. 본 연구에서는 백서 뇌조직 중 해마에서의 NOS표현을 알아보기 위해 NADPH-d 조직화학 기법을 사용하였다. Certain neurons in the brain are specifically and intensely stained by a histochemical method which demonstrates nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity. These NADPH-d positive neurons are known to exhibit high resistance to various neurotoxins and to neurodegeneration. NADPH-d is a formaldehyde-resistant histochemical activity which has been shown to be exerted by nitric oxide synthase (NOS). Thus NADPH-d serve as a reliable histochemical marker for NOS in formaldehyde-fixed sections of neural tissue, the present study uses NADPH-diaphorase histochemistry to see the expression of NOS in the rat hippocampus.

치매의 행동심리증상의 개관 : An Overview

한설희 대한치매학회 2004 Dementia and Neurocognitive Disorders Vol.3 No.1

Behavioral and psychological symptoms of dementia (BPSD) are among the most distressing manifestations of dementia and results in considerable social and economic burden. They are highly prevalent in Alzheimer's disease (AD) and other progressive degenerative dementias. BPSD are one of main reasons for premature institutionalization and are major causes of significant loss of quality-of-life for the patient and his/her family and caregivers. Recent investigations indicate that BPSD are not an epiphenomenona of cognitive impairment, but could be attributed to specific biological brain dysfunction. This brief review provides an overview of recent advances in the field of BPSD research.

Gerstmann 증후군을 동반한 교차 실어증 1례 : MRI 및 SPECT를 이용한 연구

한설희 충북대학교 의학연구소 2001 忠北醫大學術誌 Vol.11 No.1

교차실어증이란 오른손잡이 환자에서 우측 대뇌 반구 손상후에 언어장애(실어증)가 발생한 경우를 말한다.오른손잡이 실어증 환자의 약 1%-2%에서 교차실어증이 발생하는 것으로 알려져 있으나 구조적 병변이 잘 밝혀진 예는 드물다.더욱이 우뇌 손상과 관련된 좌, 우 지남력 상실, 수지 실인증, 계산불능증, 필기불능증의 4 가지 임상 특징을 가지는 Gerstmann 증후군의 예는 더욱 드물다.저자는 MRI 및 SPECT 뇌영상 검사로 우뇌 경색이 확인된 오른손잡이 환자에서 Gerstmann 증후군과 교차실어증이 동시에 발생한 드문 예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다. Crossed aphasia refers to disturbance of language following a right hemisphere lesion in right handed individuals.Although it is estimated to occur in 1% to 2% of all dextral aphasic, well documented cases of crossed aphasia continue to be rare.Moreover, it is also rare to see a Gerstmann's syndrome (left-right disorientation, finger agnosia, dyscalculia, and dysgraphia) in right hemispheric lesion.In this paper, the author presents one case of crossed aphasia associated with Gerstmann syndrome in monolingual right handed patient. This case is found interesting to be reported because it is a extremely rare condition where a crossed aphasia and a Gerstmann syndrome are simultaneously seen in the same patient.

부검으로 확진된 알쯔하이머병 1예 : An Autopsy Report

한설희,이건국,양기화,장순환 대한치매학회 2002 Dementia and Neurocognitive Disorders Vol.1 No.1

While the clinical diagnostic accuracy of probable Alzheimer′s disease (AD) is 87-96% with a diagnostic sensitivity/specificity of 0 81-0 87, the unequivocal diagnosis of AD rests on histopathological evidence at brain autopsy and/or biopsy We report here a 92-year-old woman whose clinical presentation suggested a far advanced Alzheimer′s disease Formal neuropsychological evaluations were not applicable due to severe cognitive impairments With a relatively good general physical condition she could walk with aid during her last days no focal neurological signs were noted on a detailed examination Brain MRI revealed a diffuse cortical atrophy with a marked reduction in the hippocampal volume The brain obtained weighted 780g The cerebral hemispheres examined after fixation disclosed moderately severe atrophy in prefrontal and temporal lobes on coronal section, the hippocampus was likewise severely atrophied the lateral ventricles were moderately dilated On microscope examination, there were numerous senile plaques and neurofibrillary tangles in the neocortices. hippocampus and amyglada, compatible with advanced Alzheimer′s disease In summary we report the first Korean autopsy-proven case with advanced Alzheimer′s disease.

치매환자의 비인지 기능장애에 관한 예비적 연구

한설희 충북대학교 의과대학 충북대학교 의학연구소 1999 忠北醫大學術誌 Vol.9 No.2

연구목적: 행동장애/행동이상(behavioral disturbances)는 치매환자에서 비교적 흔히 관찰되는 증상이기는 하나 기억장애와 같은 인지기능이상이 두드러진 현상이기 때문에 최근까지 연구대상에서 제외되어 있었다. 그러나 환자들이 나타내는 비인지기능 증상들 (non-cognitive symptoms; NCS)은 치매의 진단, 예후 및 치료에 있어 매우 중요한 의미를 갖는다. 본 연구의 목적은 치매환자의 NCS의 임상적 특징을 면밀히 파악하여 향후 치매환자의 치료에 있어 인지기능을 개선시키려는 노력 이외에 NCS에 대한 적극적인 치료방침을 마련하는 데 있다. 대상 및 방법: 충북대학교병원 치매크리닉에 내원한 환자중 DSM IV 및 NINDS-ADRDA 진단기준에 맞는 알쯔하이머형 치매환자 42명, NINDS-AIREN 진단기준에 적합한 혈관성치매환자 13명, 혼합형치매환자 12명을 대상으로하여 이상행동적도를 평가하였다. 결과: 치매척도인 Hasegawa scale과 행동척도인 Behavioral Rating Scalerks의 상관지수는 0.805로 상당한 유의성이 관찰되었다. 질병의 종류에 무관하게 과격한 행동, 밤-낮의 뒤바뀜, 초조증 등이 가장 흔히 관찰되는 행동장애이었다. 결론: 본 연구의 결과 치매환자의 치료에 있어 비인지기능장애의 중요성을 인식할 수 있었으며 이를 조기에 발견 치료해줌으로써 환자들를 돌보는 간호인력이나 보호자들의 삶의 질을 향상시키는데 많은 기여를 할 것으로 기대된다. 비인지기능 장애의 발병기전을 밝히기 위하여 향후 좀더 잘 기획된 전향적 방법으로 치매환자에서 비인지기능 장애가 어떻게 진행되는 가에 대한 추시 연구가 필요할 것으로 생각된다. Purpose: Behavioral symptoms in dementias, although common, have not received much attention until recently. This report attempts to describe the frequencies and characteristics of such symptoms in patients with dementia. Materials and Methods : The author cross-sectionally investigated the prevalence, phenomenolgy, and clinical correaltes of noncognitive symptoms (NCS) in a consecutive series of 67 patients with dementia (42 with Alzheimer's disease, 13 with vascular dementia, 12 with mixed dementia). Cognitive function was rated using the Hasegawa scale and NCS was measured with modified Behavioral Rating Scale (BRS). Results: The correlation between Hasegawa scale and BRS was 0.805 at the time of initial evaluation. Among various delusional symptoms, picture sign was noted only in patients with Alzheimer's disease. Aggressive behavior, day-night-disturbances, and agitation were most frequently observed NCS regardless of disease entities. Conclusion: The findings of the present study underlie the importance of NCS in the management of patients with dementia. Further longitudinal study using well-designed structured interview should be performed to clarify the evolution of NCS in patients with dementia.

갑상선 결절의 초음파 유도하 세침흡인 검사의 유용성

배일헌,한기석,차상훈,김성진,박길선,한설희,김동호 충북대학교 의학연구소 2002 忠北醫大學術誌 Vol.12 No.2

연구목적: 본 연구의 목적은 초음파 유도 하에 갑상선 결절을 경피적 흡인 생검 할 때 검체 획득률을 알아 보고, 검체 획득률에 영향을 주는 요소들을 알아보고자 하였다. 대상 및 방법: 갑상선 결절이 있어 초음파 유도하 경피적 흡인 생검을 하였던 132명 (12-71; 평균 42세) 환자의 결절 215예를 대상으로 전향적 연구를 시행하였다. 2000년 9월부터 2001년 2월까지 62명의 환자의 결절 111예에서 21-gauge 세침을 이용하였고, 2001년 3월부터 9월까지 70명의 환자의 결절 104예에서 20-gauge 절단침을 이용하였다. 초음파 유도하 경피적 흡인 생검의 검체 획득률을 구하였고, 결절 단경이 1 ㎝ 이하와 1 ㎝ 초과, 결절의 성상, 촉지여부에 따라 검체 확득률에 차이가 있는지 비교 분석하였다. 통계적 분석은 Chisquare test로 검증하였다 (p<0.05). 결과: 총 215예 중 188예에서 적절한 검체가 얻어져 전체 검체 획득률은 87.4%이었다. 낭성 결절 (78.8%)보다 고형 결절 (90.2%)에서 더 높은 검체 획득율을 보였으나, 결절의 크기(≤1 ㎝:85.7% vs. >1 ㎝:88.7%)와 촉지 여부 (촉지되는 결절: 87.5% vs. 촉지되지 않는 결절:87.4%)에 따라서는 유의한 차이를 보이지 않았다. 결론: 갑상선 결절의 초음파 유도하 경피적 흡인 생검은 높은 검체 획득율을 보이며, 결절의 크기, 촉지 여부에 따른 차이는 없으나, 고형 결절에서 낭성 결절보다 높은 검체 획득율을 보인다. Purpose: The purpose of this study is to evaluate the acquisition rate of adequate specimen in ultrasound-guided percutaneous needle aspiration biopsy (US-PCNB) of thyroid nodules and to find the factors influencing the acquisition rate. Materials and Methods: We conducted a prospective study in 132 patients (mean age 47 years: range 12-71) who had 215 nodules. Aspiration biopsy was performed with 21-gauge fine needles for 111 nodules (62 patients) and with 20-gauge cutting needles for 104 nodules (70 patients). We calculated overall acquisition rate of adequate specimen of US-PCNB and compared acquisition rates according to nodule size, nature and palpability. Results: Total acquisition rate of adequate specimen was 87.4%. The acquisition rate of adequate specimen of solid nodules (90.2%) was higher than that of cystic nodules (78.8%). The size of nodules did not affect the acquisition rate of specimen (≤1 ㎝:85.7% vs. >1 ㎝:88.7%). The palpability of nodules also cause no difference the acquisition rate (palpable: 87.5% vs. non-palpable:87.4%). Conclusion: US-guided PCNB of thyroid nodules was high acquisition rate of adequate specimen. There was no statistically significant difference according to size and palpability of nodules but was according to nature of nodules in the acquisition rate of adequate specimen.