Effect of estrogen on autophagic response after stroke in mice

이수인 숙명여자대학교 대학원 2024 국내석사

폐경이 지난 여성에서 뇌졸중 발생률이 크게 증가하게 된다. 폐경이 지난 여성의 체내에는 에스트로겐이 부족하고 이것이 여성의 뇌졸중 발생률, 사망률, 재발률, 부작용의 발생 증가로 이어지게 된다. 뇌졸중 발생 시 뉴런에서는 다양한 작용이 중 하나인 autophagy가 일어나고 뇌졸중과 같은 스트레스에서 다양한 정도로 활성화되어 신경세포를 보호하는 역할을 한다. 따라서 본 연구에서는 여성에서 높게 발병되는 뇌졸중의 원인을 autophagy 연구를 통해 규명하고자 한다. 뇌졸중 후 에스트로겐(E2)에 의한 autophagy 반응을 작용을 연구하기 위해, aged and OVX mouse에 tMCAO를 수행하였다. 뇌경색의 개선 여부 및 뇌 조직 Western blot과 Immunofluorescence, qPCR를 통해 autophagy marker들의(LC3B, p62, LAMP1, CTSD, Transcription factor EB (TFEB), me-TFEB)의 단백질 및 mRNA 활성을 확인했다. 본 실험 결과를 통해서 E2 level 및 뇌졸중의 중증도에 따라 autophagy 반응이 다르게 나타나는 것을 알 수 있었다. 우선, 성별에 따른 뇌경색을 비교하면, female의 뇌경색 볼륨이 male보다 작았다. 뇌졸중의 중증도에 따라 비교하면, mild condition에서는 E2의 뇌경색의 개선된 것을 볼 수 있었던 반면, severe condition에서는 E2가 뇌경색이 악화되었다. young(3M) mice에서는 E2가 autophagy를 억제하는 반면, 체내에 E2 level이 적다고 생각되는 Aged (1Y) mice에서는 E2가 autophagy를 유도하는 것을 확인했다. 이것을 조직면역학적 관점으로 확인했을 때, LC3B와 LAMP1의 colocalization은 young female에서 E2 처리 시 감소하는 반면, aged female에서는 stroke 후 감소한 colocalization이 E2 처리 후 증가하는 경향을 발견했다. 여러 autophagy marker들 중 autophagy master regulator인 TFEB을 중점적으로 보았고, female에서 나이가 들수록 뇌에서 TFEB mRNA 발현이 감소했다. 또한 N2a cell의 hypoxia 그룹에서 E2 처리 시 TFEB의 mRNA 발현이 증가했다. Young female에서 TFEB 및 me-TFEB의 레벨을 확인한 결과 mild condition과 severe conition 모두에서 E2 처리 시 me-TFEB의 발현량이 증가했다. 하지만 Aged tMCAO mice에서는 TFEB과 me-TFEB의 발현 차이가 없었다. me-TFEB의 발현량을 성별에 따라 보았을 때, 조직학적으로 발현량이 다르며, striatum에서 female의 TFEB 발현량이 male보다 더 높았다. E2와 TFEB의 interaction을 밝히기 위해 estrogen receptor(ERs)와 TFEB을 이용해 진행한 ICC 및 PLA에서 다수의 colocalization 및 red signal을 확인할 수 있었다. 이는 ER과 TFEB이 같은 프로모터에 위치해 interaction을 함을 시사한다. E2에 의해 영향받는 자가포식 단계를 확인하기 위해 chloroquine(CQ)을 신경세포에 처리하였다. E2 처리 시 cell viability가 증가하고 immunoblot에서 E2와 CQ가 처리된 group에 LC3B가 증가한 것으로 보아 E2가 stroke 시 brain 자가포식을 촉진하고 E2가 자가포식 upstream 조절자임을 시사합니다. 따라서 E2 및 중증에 따른 TFEB의 증감으로 autophagy가 조절되고 그로 인해 뇌졸중에서의 E2에 의한 autophagy 반응을 정확히 규명하는 증거를 제공하고자 한다. The incidence of stroke is significantly higher in postmenopausal women. Decreased estrogen levels in postmenopausal women leads to increased risk of stroke and mortality, stroke recurrence, and stroke-related complications. Autophagy is a function of neurons that protects the nerve cells. Autophagic response is effected by neurons to varying extent in stress conditions such as stroke. Therefore, this study aims to identify the etiology of stroke, which has a high incidence in women, by assessing autophagic response. To investigate autophagic response to estrogen (E2) treatment after stroke, tMCAO was performed on aged and OVX mice. Resolution of brain infarction and the protein and mRNA activities of autophagy markers (LC3, p62, LAMP1, CTSD, transcription factor EB (TFEB), and methylated-TFEB) were assessed through Western blot, IHC staining, and qPCR of brain tissue. The results of this experiment show that autophagic response varies by E2 level and the severity of stroke. First, when comparing cerebral infarction by sex, females had lower infarct volumes. Further comparison by severity of stroke revealed that, in mild stroke conditions, E2 treatment resolves cerebral infarction, whereas in severe stroke conditions, E2 treatment exacerbated cerebral infarction. Our results confirm that E2 inhibits autophagy in young (3 months old) mice but promotes autophagy in aged (1 year old) mice. This difference is likely attributable to varying E2 levels in the body between these age groups. Immunohistochemistry analysis confirmed that the colocalization of LC3B and LAMP1 decreased during E2 treatment in young females, whereas the decrease in colocalization after stroke tended to increase with E2 treatment in aged females. Among several autophagy markers, we focused on TFEB, an autophagy master regulator, and found that TFEB mRNA expression in the brain decreases with age in females. Furthermore, TFEB mRNA expression increased upon E2 treatment in the hypoxia group of N2a cells. On investigating TFEB and methylated-TFEB levels in young female mice, we observed an increase in methylated-TFEB levels with E2 treatment in both mild and severe stroke conditions. However, TFEB and methylated-TFEB expression did not differ in aged tMCAO mice. Analysis of methylated-TFEB expression by sex, showed histochemical differences, and TFEB expression was higher in females than in males in the striatum. To investigate the interaction between E2 and TFEB, numerous colocalizations and red PLA signals were measured in ICC, and PLA was performed using estrogen receptors (ERs) and TFEB. Results show that ER and TFEB are located in the same promoter region and interact. To determine which stage of autophagy is affected by E2, neurons were treated with chloroquine (CQ). Cell viability increased with E2 treatment and LC3B levels increased in the E2 and CQ-treated group in immunoblot analyses. These findings suggest that E2 promotes autophagy in the brain after stroke and acts as an upstream regulator of autophagy. We aim to provide evidence that autophagy is regulated by increases or decreases in TFEB expression based on E2 level and stroke severity, which aids in better understanding of the autophagic response mediated by E2 in stroke.

혈관 내 재개통 시술을 한 급성 뇌졸중 환자에서 병인과 시술 방법에 따른 재개통 비율에 대한 분석

정수 울산대학교 대학원 2022 국내석사

Objective To investigate the efficacy of the concurrent use of both contact aspiration and stent-retriever in stroke patients with emergent large vessel occlusion according to the stroke mechanism, especially highlighting cancer-associated stroke Methods We retrospectively analyzed consecutive ischemic stroke patients who had undergone endo-vascular thrombectomy. Eligible patients were dichotomized according to the ischemic stroke etiology: Cancer-associated stroke vs. non-cancer-associated stroke group. Cancer-associated stroke was defined as cryptogenic stroke with active cancer. The combined technique was defined as the concurrent use of contact aspiration and stent-retriever at least once at any stage of the thrombectomy procedure. Successful recanalization was defined as a modified TICI grade 2b or 3 at the end of the procedure. Univariate and multivariate logistic regression models for having successful recanalization were established and analyzed. Results A total of 393 patients (mean age, 68.8 years; 216 males [55.0%]) were enrolled. Among them, 56 patients (14.2%) were assigned to the cancer-associated stroke group. The recanalization rate (69.6% vs. 91.7%, P<0.001) and the proportion of a 3-month good clinical outcome (25.5% vs. 42.0%, P = 0.025) were lower in the cancer-associated stroke group. In the univariate and multivariate analysis of the whole cohort, the combined technique was not associated with successful recanalization (OR = 0.99, 95% CI, 0.471 - 2.099, P = 0.988). However, the interaction term between the combined technique and ischemic stroke mechanism was independently associated with successful recanalization (P = 0.032). In multivariate analysis of the cancer-associated stroke group, the combined technique was independently associated with successful recanalization (OR = 5.795, 95% CI, 1.164 - 28.861, P = 0.032). Conclusion The combined technique was associated with successful recanalization in cancer-associated stroke patients with emergent large vessel occlusion.

Association study of microRNA binding site in 5, 10-Methylenetetrahydrofolate reductase (MTFHR) and Thymidylate synthetase (TS) gene polymorphisms with ischemic stroke risk

김정오 차의과학대학교 대학원 2014 국내석사

Stroke is the third most common cause of death in many developed countries, and 80% of strokes are ischemic in origin. In South Korea, stroke is the most frequent cause of death after cancer and is more frequent than heart disease. MicroRNAs (miRNAs) are small molecules that post-transcriptional regulate the expression of a large number of protein-coding genes in metazoans, and are suggested to play important roles in fine-tuning immune mechanisms and disease responses. Polymorphisms in either miRNAs or their gene targets may have a significant impact on gene expression by abolishing, weakening or creating miRNA binding sites. In this respect, importance of genetic polymorphisms is associated with the fact that they have significant consequences on the protein and receptor functions. However, no identifiable genetic factor is yet established in ischemic stroke, and further genetic research need to be conducted, especially in genes that are involved in ischemic stroke. We conducted a case&control study of 1000 individuals who were screened for the six of 3'-UTR miRNA binding site polymorphisms (MTHFR 2572C>A [rs4846049], MTHFR 4869C>G [rs1537514], MTHFR 5488C>T [rs3737967], MTHFR 6685T>C [rs4846048], TS 1100T>C [rs699517], TS 1170A>G [rs2790]) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were enrolled from March 2003 to June 2008 at the Department of Neurology at Bundang Medical Center, CHA University by consecutive referral. The Institutional Review Board at Bundang CHA Medical Center approved the study protocol. A total of 589 patients (mean age SD: 62.63 10.89 years, men: 41.7 %) with ischemic stroke were enrolled. Ischemic stroke was diagnosed by a rapid developing neurological symptoms and concurrent acute infarction documented by brain magnetic resonance imaging (MRI). A total of 411 subjects without any history of neurological disorders were enrolled as controls (mean age SD: 62.82 10.61 years, men: 42.1%). MTHFR 2572C>A, TS 1100T>C and TS 1170A>G polymorphisms were significantly associated with ischemic stroke prevalence. MTHFR 2572CA+AA genotype was synergic effect for stroke incidence in low folate level or high Homocysteine level. MTHFR and TS allele combination analysis was risky correlation with stroke in MTHFR 2572 A allele and TS 1100 C allele. However, haplotype with MTHFR 4869 C allele or MTHFR 6685 C allele were resistance related to stroke risk. In addition, haplotype of TS 1170 G allele was demonstrated prevention for stroke prevalence. Gene-gene interaction effects by MDR method investigated that show to changing result for stroke prevalence according to TS 1100 / 1170 alleles rather than MTHFR allele combination. In Conclusion, this study suggests that 3'-UTR miRNA binding site polymorphisms in MTHFR 2572 and TS gene may be clinically useful biomarkers for prevention and prognosis management of ischemic stroke. 뇌졸중은 많은 선진국의 3대 사망원인으로, 뇌졸중의 80%는 허혈성 뇌졸중으로 인해서이다. 대한민국에서 성인 사망원인은 암, 심장질환과 더불어 뇌졸중이 많다. 마이크로 RNA는 후성유전학적인 활동을 하는 작은 분자로 전사 후 조절인자로 많은 단백질 코딩 유전자 발현을 조절하며, 면역 메카니즘과 질병에 대한 반응의 정상 및 대응의 중요한 역할 한다고 제안되고 있다. 이러한 마이크로 RNA 또는 마이크로 RNA가 표적으로 하는 유전자 부위의 다형은 유전자 발현을 막거나, 약하시키거나, 새롭게 만들어 낼 수 있으므로 상당히 유의한 중요성을 가진다. 이러한 점에서 유전적 다형의 중요성은 단백질과 수용기 기능에 대해서 큰 영향을 미치게 되는 요인으로 생각할 수 있다. 허혈성 뇌졸중에서 유전적 요인에 대해 밝혀진 것이 없지만, 앞으로의 유전학 연구에 허혈성 뇌졸중과 관계된 연구, 특히나 유전자 연구에 큰 선도연구가 될 것이다. 우리는 환자군과 대조군 1000명을 대상으로 5, 10-methylenetetrahydrofolate reductase (MTFHR)와 thymidylate synthase (TS) 유전자의 3’ 비번역부위가 가지는 마이크로 RNA 결합 부위의 유전적 다형이 (MTHFR 2572C>A [rs4846049], MTHFR 4869C>G [rs1537514], MTHFR 5488C>T [rs3737967], MTHFR 6685T>C [rs4846048], TS 1100T>C [rs699517], TS 1170A>G [rs2790]) 허혈성 뇌졸중의 발병에 미치는 영향 연구를 PCR-PFLR로 실시하였다. 허혈성 환자군은 2003년 3월에서 2008년 6월까지 분당차병원 신경과에서 모집하였다. 모집한 환자군은 총 589명 (평균나이, 표준편차 62.63, 10.89, 남자: 41.7%) 이다. 허혈성 뇌졸중의 진단은 MRI를 통한 급격한 신경학적 증후와 급성 경색을 판단하였다. 대조군은 총 411명으로 신경학적 이상이 없는 사람들로 모집했다 (평균나이, 표준편차: 62.82, 10.61, 남자: 42.1%). MTHFR 2572C>A, TS 1100T>C and TS 1170A>G의 다형은 허혈성 뇌졸중의 발병과 상당한 연관성이 있었다. MTHFR 2572CA+AA 유전자형은 낮은 엽산 수치와 높은 호모시스테인 수치와 결합한 상호작용 효과에서 허혈성 뇌졸중 발병 위험이 상승되는 효과를 보였다. MTHFR과 TS 유전자의 대립형질 조합 분석은 MTHFR 2572A와 TS 1100C 대립형질이 허혈성 뇌졸중 발병에 연관성이 있음을 알 수 있었다. 하지만 MTHFR 4869C, 6685C 또는 TS 1170G 대립 형질은 발병 저항과 연관이 있음을 알 수 있었다. MDR 방법을 기반으로 하여 유전자-유전자 상호작용의 대립형질 분석은 MTHFR 유전자보다 TS 유전자의 대립형질에 의한 뇌졸중 발병이 크게 좌우됨을 알 수 있었다. 이 연구에서 우리는 MTFHR과 TS 유전자의 3’ 비번역 부위가 가지는 마이크로 RNA 결합 부위의 유전적 다형이 허혈성 뇌졸중과 충분한 관련이 있으며, 허혈성 뇌졸중의 진단 및 예방, 예후에 잠재적인 생물학적 지표로서 사용될 수 있을 것이라고 생각한다.

뇌졸중 발생위험요인과 NIH Stroke Scale의 관련성

곽빛나래 충북대학교 2021 국내석사

뇌졸중은 전 세계적으로 사망의 주요 원인 인 뇌혈관 질환으로 편마비, 언어 장애, 지각 장애, 감각 및 운동 기능 장애가 생존하더라도 남아있는 만성 질환이다. 국내에서는 응급 의료 체계 구축, 뇌졸중 중환자 실 확충, 재관류 치료율 증가 등으로 뇌졸중 사망률이 점차 감소하고 있으나 여전히 위험한 질병이다. 뇌졸중은 혈전 용해 외에 효과가 없기 때문에 예방이 가장 중요하다. 뇌졸중을 예방하기 위해서는 뇌졸중을 유발하는 요인이 뇌졸중 중증도에 영향을 미치는 요인을 찾아야한다. 현재 많은 연구에서 뇌졸중을 유발하는 요인은 많이 밝혀졌다. 하지만 뇌졸중 중증도에 영향을 미치는 요인과 관련된 연구는 비교적 적으므로 본 연구에서는 뇌졸중 중증도에 영향을 주는 요인을 조사 하였다. 먼저 뇌졸중 위험인자가 무엇이 있는지 알아보았고 그 인자들이 중증도에 어떻게 영향을 주는지 문헌고찰을 통하여 알아보았다. 그리고 중증도에 영향을 주는 요인을 설정하고 통계학적으로 분석하기 위해서 NIHSS점수를 이용하였다. NIHSS점수란 현재 뇌졸중 환자의 신경학적 중증도와 그 변화를 객관적으로 평가하기 위하여 개발된 도구로써 널리 사용되고 있는 비선형 서열 척도이다. 뇌졸중 중증도에 영향을 주는 요인과 NIHSS 점수를 단변량 분석과 다중 회귀 분석을 통해 알아보았고 그 결과 여성의 경우, 나이가 많은 경우, 심방세동이 있는 경우 NIHSS 점수가 더 높게 나타났다. 이는 여성의 경우, 나이가 많은 경우, 심방 세동 병력이 있는 경우 뇌졸중의 중증도가 더 높아진다고 설명할 수 있다. Stroke is a cerebral vascular disease that is the leading cause of death worldwide, and is a chronic disease in which hemiplegia, speech impairment, sensory and motor dysfunction have survived. In Korea, stroke mortality is decreasing due to the establishment of an emergency medical system, expansion of stroke intensive care units, and increase in reperfusion treatment rates, but it is still a dangerous disease. Because stroke has no effect other than dissolving blood clots, prevention is the most important. In order to prevent stroke, it is necessary to find out the effect that causes the stroke to affect the stroke. Currently, many studies have found many findings that cause stroke. However, there are relatively few studies related to the factors influencing stroke severity, so this study investigated the factors that affect stroke severity. First, what are the risk factors for stroke, and how those factors affect the severity through a literature review. In addition, the NIHSS score was used to set the factors affecting the severity and to analyze statistically. The NIHSS score is a nonlinear sequence scale that is widely used as a tool developed to objectively evaluate the neurological severity and change of stroke patients. Factors influencing stroke severity and NIHSS scores were investigated through univariate analysis and multiple regression analysis. As a result, the NIHSS score was higher in women, elderly people, and atrial fibrillation. This may explain that in women, older people, and a history of atrial fibrillation increase the severity of stroke.

Longitudinal impact of depression on quality of life in stroke patients

김은송 전남대학교 2018 국내석사

Objective : Stroke is associated with significant long-term morbidity and poor quality of life (QOL). Depression is one of the most common complications after stroke and has been associated with QOL cross-sectionally. We investigated the longitudinal impact of depression in the acute phase of stroke on QOL 1 year after stroke. Methods : In total, 423 patients were evaluated 2 weeks after stroke, and 288 (68%) were followed 1 year later. QOL was assessed using the World Health Organization Quality of Life-Abbreviated form (WHOQOL-BREF) at baseline and follow-up. Depression was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria; demographic and clinical characteristics data, including stroke severity, were obtained at baseline. The longitudinal associations of post-stroke depression (PSD) at baseline with QOL across two evaluation points were assessed using a repeated-measures analysis of variance. Results : The WHOQOL-BREF scores were significantly and persistently lower 1 year after stroke in patients with PSD at baseline compared with those without PSD at baseline independent of demographic and clinical characteristics, including stroke severity. Conclusion : PSD in the acute phase of stroke is an independent predictor of QOL in both the acute and chronic phases of stroke. Our findings underscore the importance of evaluating depression in the acute phase of stroke.

SystemChangeTM-Stroke: A Systems Approach to Healthy Living after Stroke in Thailand

Komton, Vilailert Case Western Reserve University ProQuest Dissertat 2018 해외박사(DDOD)

Stroke is a chronic disease and stroke recovery is a dynamic process that requires long-term lifestyle changes. For stroke patients, modifying lifestyle behaviors and daily routines are key to stroke recovery and secondary prevention. However, to date, the best strategy to maximize lifestyle changes in Thai stroke patients remains unknown. There is an emphasis on using individualized and systems approaches to change habits. Recently, evidence suggests SystemCHANGE(tm) as a promising new behavior change approach focusing on modifying families’ daily routines by using a series of small self-designed experiments. The purpose of this study was to investigate the effectiveness of SystemCHANGE(tm) on healthy eating, physical activity, and medication adherence over a 3-month period in Thai adults following stroke. A hundred and ten subjects were randomly recruited from a list of consecutive patients discharged from stroke units at King Chulalongkorn Memorial Hospital (KCMH), Bangkok, and Hua-Hin Hospital (HHH), Prachuap Khiri Khan, Thailand to the study. Subjects were randomly assigned to SystemCHANGE(tm)-Stroke and Enhanced Usual Care equally. The SystemCHANGE(tm)-Stroke intervention consisted of an initial home visit, 4 face-to-face group sessions, and 3 coaching telephone calls delivered by trained registered nurses (RNs). Data were collected at baseline and at 3 months following completion of the program using an in-person interview about health behaviors, potential mediators and potential moderators. A hundred and eight subjects completed the study. Data were analyzed using analysis of covariance and multiple linear regression.Results indicated that SystemCHANGETM-Stroke was effective to change healthy eating, number of MET-minutes/day, number of minutes/day in moderate and vigorous physical activity, number of minutes/day in walking and medication adherence. Systems thinking, social support and patient activation were found to be underlying mechanisms of SystemCHANGETM. Lower income households consumed less healthy food as compared to those who earned more income. Subjects in KCMH had greater response to the SystemCHANGETM- Stroke intervention on physical activity. Findings from this study provide empirical evidence that support the effectiveness of SystemCHANGE(tm), specifically in Thai people. SystemCHANGE(tm), focusing on systems thinking skills and process improvement, shows promise to promote health behavior change. Future research should consider examining the effectiveness of SystemCHANGE(tm) over a longer period and in different populations, as well as the inclusion of systems thinking as an important factor for health behavior change.

Multimodal Stroke Magnetic Resonance Imaging for Clinical and Pre-clinical Research

손정표 성균관대학교 일반대학원 2020 국내박사

Stroke is a leading cause of morbidity and death, caused by blocked cerebral blood flow. Acute ischemic stroke can be treated by revascularization of occluded vessels; however, the number of patients who can be treated in this manner is still limited and predicting treatment efficacy is difficult. Therefore, the development of magnetic resonance imaging (MRI) techniques to detect salvageable brain tissue to aid in selection of patients who can be treated is crucial. MRI can also be used in the later stages of ischemic stroke to assess spontaneous or therapy-induced recovery. However, considering that the lesion location and severity are varied with each patient, generalizing the mechanism of recovery is difficult. Therefore, it is crucial to develop MRI techniques for investigating functional recovery after stroke. In the present study, I developed multimodal MRI techniques to select patients who could be treated from both the acute to late phases of stroke, to predict outcome, and assess their functional recovery. In Part 1, I developed a novel MRI technique to evaluate collateral circulation by post-processing of dynamic susceptibility contrast-enhanced magnetic resonance perfusion (DSC-MRP) images. I also confirmed that the DSC-MRP-derived collateral grading system developed from this study could be used to select patients that can receive therapy, and to predict their prognosis. In Part 2, I developed an MRI-based monitoring method to assess the therapeutic efficacy of using mesenchymal stem cells (MSCs) in an experimental stroke model, using diffusion tensor imaging (DTI). In Part 3, functional MRI (fMRI) was used to investigate optimal MRI parameters for detection of recovery following treatment with MSC-derived extracellular vesicles (EVs). In addition, I also investigated characteristics of blood oxygen level-dependent fMRI signals. In conclusion, multimodal MRI techniques can be used as promising tools for early diagnosis, predicting prognosis, and monitoring therapy-induced recovery after stroke.

Factors Affecting Recovery of Motor Function during the Subacute Phase after First-ever Stroke : 초발 뇌졸중 환자의 아급성기 운동 기능 회복 관련 요인 분석

김정현 성균관대학교 일반대학원 2017 국내석사

연구 배경 및 목적: 많은 뇌졸중 환자들은 뇌졸중 발병 후 많은 경우에서 운동 기능 장애와 일상생활동작 수행에 어려움이 나타난다. 이에 뇌졸중 환자에서 나타나는 운동기능 장애는 중요한 보건 의료 문제로 대두되고 있다. 아급성기의 집중적인 재활치료는 뇌졸중 환자의 운동 기능 회복에 도움을 주는 것으로 알려져 있다. 하지만 아급성기의 운동 기능 회복에 미치는 영향 인자에 대한 연구는 부족한 실정이다. 이데 본 연구에서는 초발 뇌졸중 환자를 대상으로 아급성기 운동 기능 회복 관련 요인을 분석하고자 하며, 아급성기의 집중적 재활치료가 뇌졸중 발병 3개월 후 운동 기능 회복에 미치는 영향을 살펴보고자 한다. 연구 방법: 본 연구는 Korean Stroke Cohort for Functioning and Rehabilitation 연구의 중간 결과로, 발병 후 3개월 시점에 기능 평가를 시행한 초발 뇌졸중 환자 5,662명의 운동 기능에 대해 분석하였다. 뇌졸중 발병 후 3개월 시점의 Fugl-Meyer assessment (FMA)와 9-hole pegboard test (9HPT) 결과와 관련된 요인을 분석하기 위해 다중회귀분석과 이분형로지스틱 회귀분석을 시행하였다. 또한 집중 입원 재활치료의 효과를 분석하기 위해 초기 급성기 치료 후 퇴원 장소에 따라 2개의 그룹(재활 전문 입원 치료를 받은 그룹과 일반적 입원 치료를 받은 그룹)으로 분리하였다. 양군에서 FMA 점수 변화량을 독립표본 t 검정을 통해 분석하였다. 연구 결과: 본 연구의 대상자 중 뇌경색 환자가 79.9%, 뇌출혈 환자가 20.1% 이었다. 뇌졸중 발병 후 3개월 시점 FMA 평가를 통해 운동 기능 장애를 가진 환자는 51.6% 이었으며, 9HPT 수행 결과가 비정상적이거나 평가 수행을 하지 못한 대상자는 64.5%이었다. 발병 후 3개월 시점의 운동 기능 회복 관련 요인은 초기 입원 기간 동안의 합병증 유무, 발병 7일의 운동 기능 수준, 입원 기간이었으며, 9HPT으로 측정된 손기능 회복 관련 요인은 초기 입원 기간 동안의 불면증 여부와 발병 7일의 상지 운동 기능 수준, 운동 재활 치료의 양이었다. 초기 급성기 치료 후 63.8% 환자는 집으로, 26.5% 환자는 전문 입원 재활 치료를 위한 재활의학과 또는 전문병원으로, 9.5% 환자는 일반 입원 치료를 위한 의료기관으로 퇴원하였다. 재활 전문 입원 치료를 받은 그룹은 일반적 입원 치료를 받은 그룹보다FMA 전체 변화량, FMA 상지 변화량, FMA 하지 변화량에서 유의하게 향상되었다 (p<0.001). 특히, 초기 운동 기능의 중증도, 중도 손상 환자에서, 재활 전문 입원 치료를 받은 그룹이 보다 유의한 운동 기능이 향상을 보였다. 상지 운동 기능 회복의 유의한 차이는 초기 운동 기능 손상이 심하거나 중등도 손상인 경우에서, 하지 운동 기능 회복의 유의한 차이는 초기 운동 기능 손상이 심하거나 경도 손상인 경우에서 재활 전문 입원 치료를 받은 그룹이 보다 유의한 향상을 보였다 (p<0.05). 결론 및 토의: 발병 후 7일 째 운동 기능 수준과 초기 입원 기간 동안의 뇌졸중 환자 관리는 뇌졸중 발병 후 3개월 시점의 운동 기능 회복에 있어 가장 중요한 영향 인자였다. 또한 아급성기의 전문 재활 입원 치료는 3개월 시점의 운동 기능 회복을 증진시키는데 효과적이었다. 아급성기의 체계적인 뇌졸중 관리는 초발 뇌졸중 환자에서 발병 후 3개월 시점 운동 기능 회복 향상에 효과적인 치료 방법임을 확인할 수 있었다. Background: Stroke is the leading cause of serious, long-term disability. Many stroke survivors suffered from some degree of motor disabilities. Mobility-related disability emerging from neurologic injury is a global problem of pressing affair. However, predictive recovery factors in the subacute phase are still not well understood, especially motor function factors in terms of a relationship between physical disability and early intensive rehabilitation after stroke. Objective: The objectives of this study are to identify the factors associated with recovery of motor function in the first-ever subacute stroke patients and to support the evidence that intensive rehabilitation during the subacute phase after acute care can improve motor function at 3 months after stroke. Method: This study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation Study, focusing on motor function of first-time stroke patients who completed face-to-face motor function assessment at 3 months after onset (N=5,662). A multiple linear regression analysis and multiple binary logistic regression analysis were used to analyze factors that potentially associated with Fugl-Meyer assessment (FMA), 9-hole pegboard test (9HPT) at 3 months after stroke. To evaluate the effectiveness of intensive inpatient motor rehabilitation after acute care, the patients were divided into two groups by discharge destination after acute stroke care; the specialized inpatient rehabilitation care (SR) group and the general medical inpatient care (GC) group. To compare the mean of FMA score changes from time of discharge after acute stroke care to 3 months after stroke was performed by independent t-test. Result: Of the patients in this study, 79.9% suffered from ischemic stroke and 20.1 % experienced hemorrhagic stroke. The proportions of patients with motor function impairment with FMA at 3 months after onset were 51.6%. The proportion of the patient who perform the abnormal or not-testable hand dexterity with 9HPT after 3 months after onset were 64.5%. The factors associated motor recovery at 3 months after stroke were the presence of complications during the hospitalization and initial motor function at 7 day, and the duration of hospitalization. For hand function, measured by 9HPT at 3 months after stroke, the absence of insomnia during hospitalization, the upper limb function at 7 day and the amount of motor rehabilitation were independent recovery factors during the subacute phase. Among patient after acute care, 63.8% of patients were discharged to their home, 26.5% of patients were discharged to continue the specific rehabilitation treatment, and 9.5% of patients were discharged to other hospital for the general medical inpatient care. The SR group has significantly greater the difference of motor improvement in in total, upper limb and lower limb than the GC group (p<0.001). Patients with the severe and marked motor impairment were significantly difference of motor improvement at 3 month between the SR and GC groups (p<0.05). In the patients with severe and moderate upper limb motor impairments, there was a significantly higher improvement in the SR group compared with the GC group. In the patients with severe and mild motor lower limb motor impairment, the SR group showed a significantly higher improvement compared with the SR group (p<0.001). Conclusion: Motor function at 7 day and acute hospitalization care were most significantly relating factors associated with on motor recovery at 3 months in first-ever stroke patient. In addition, specialized inpatients rehabilitation treatment during subacute phase can be effective to facilitate motor function improvement at 3 months in stroke patients. The systematic stroke care during subacute phase may be beneficial to enhance motor recovery at 3 months after onset in first-ever stroke patients.

뇌졸중 환자의 스트레스 요인이 삶의 질에 미치는 영향 : 뉴만의 체계이론 적용

최은정 전북대학교 일반대학원 2021 국내석사

Relationship between Stroke, Disability and Mental Distress of Productive Ages Population in East Borneo (Based on Indonesia Basic Health Research 2013)

한나 코이릴 서울대학교 대학원 2020 국내석사

Background: Stroke is the major cause of death in many countries. Stroke prevalence in Indonesia increased from 7% in 2013 to 10.9% in 2018. The highest prevalence of stroke in Indonesia, East Borneo province, increased 2 times from 7% to 14% in 5 years. Depression and anxiety also become the most common emotional disturbances after stroke. Post-stroke depression (PSD) is highly prevalent among stroke survivors and is associated with significant morbidity and mortality. This study was population-based study as there has been a little research about this topic and they mainly used hospital-based study design. Objectives: The general objective of this study was to know the correlation between post-stroke disability and mental distress at productive age (15 – 64 years) in East Borneo. Some specific objectives are to know whether severity level of disability has association with mental distress, whether stroke has association with the severity level of disability, whether stroke with disability synergistically increased the chance of having mental distress and whether other individual characteristics such as gender, employment status, age group, education level, marital status associated with mental distress. Methods: Data was taken from the Basic Health Research Survey in 2013 with a total sample of 15277 people. Variables in this research were independent variables including disability level, stroke status and individual characteristics such as gender, age group, employment status, education level, and marital status. The dependent variable was the mental distress status. The data were analysed using univariate analysis to describe each variable with the frequency and percentage distribution and using spearman correlation and logistic regression to see the relationship between the 2 variables. The software used in this analysis process was SPSS and R software Results: Disability level had enough correlation with mental distress. People with high disability level were more likely to develop mental distress. While education level, gender, employment status, marital status, age group and stroke have weak correlation with mental distress. Based on logistic regression results, being female, older, married, having stroke, having high disability by stroke and having no education background significantly increases the risk of having mental distress (p-value <0.05). On the other hand, being stroke-high disabled and unemployed were not significantly increase the risk of having mental distress (p-value > 0.05). Diagnosed as stroke also correlated with having more severe disability. Being stroke significantly increase the risk of having more severe disability (p-value <0.05). Conclusion: As most of stroke and disabled people living in East Borneo are in their peak of productive ages and have significant tendency of having mental distress, it would be better if government did some intervention such as early screening for mental distress and providing some training to live their life without feeling burdensome to people around them. Keywords: Stroke, Disability, Mental distress, Women 배경 : 뇌졸중은 많은 국가에서 주요 사망 원인이다. 인도네시아의 뇌졸중 유병률은 2013 년 7 %에서 2018 년 10.9 %로 증가했다. 인도네시아 보르네오 주에서 가장 높은 뇌졸중 유병률은 5 년 동안 7 %에서 14 %로 2 배 증가했다. 우울증과 불안은 뇌졸중 후 가장 흔한 정서적 장애가 된다. 뇌졸중 후 우울증 (PSD)은 뇌졸중 생존자들 사이에서 널리 퍼져 있으며 상당한 이환율 및 사망률과 관련이 있다. 이 연구는 주제에 대해 인구 기반 조사를 이용한 연구이다. 목표 :이 연구의 일반적인 목표는 이스트 보르네오의 생산 연령 (15 – 64 세)에서 뇌졸중 후 장애와 정신건강문제 사이의 상관 관계를 파악하는 것이 있다. 주체적인 목표는 중증 장애 수준이 정신건강문제과 관련이 있는지, 뇌졸중이 중증 장애 수준과 관련이 있는지, 장애가 있는 뇌졸중이 정신건강문제를 가질 가능성을 증가시키고 성별, 고용 상태, 연령과 같은 기타 개인 특성과의 연관성이 있는지 착안하고자 한다 방법 : 이 연구는 2013년 인도네시아 기초 건강 조사에 참여한 총 15227 명의 자료를 분석하였다. 이 연구의 변수는 장애 수준, 뇌졸중 상태 및 성별, 연령 그룹, 고용 상태, 교육 수준 및 결혼 상태와 같은 개인 특성을 포함한 변수이다. 종속 변수는 정신 문제 상태였다. 정신건강문제의 측정은 SRQ-20 설문을 이용하여 유무로 정의하였고, 장애의 측정은 WHODAS-12 도구를 이용하여 장애 정도를 4수준으로 범주화하였다. 데이터는 일 변량 분석을 사용하여 빈도 및 백분율 분포를 갖는 각 변수를 설명하고 스피어맨 상관 및 로지스틱 회귀를 사용하여 두 변수 간의 관계를 확인하였다. 이 분석에 사용 된 소프트웨어는 SPSS 및 R 소프트웨어이다. 결과 : 장애 수준은 정신건강문제과 관련이 있었다. 장애 수준이 높은 사람들은 정신건강문제를 겪을 가능성이 더 컸다. 교육 수준, 성별, 결혼 여부, 연령 그룹 및 뇌졸중은 정신건강문제의 상관 관계가 약한 반면, 고용 상태는 거의 상관 관계가 없었다. 로지스틱 회귀 분석 결과에 따르면, 여성, 노인, 결혼, 취업, 뇌졸중, 뇌졸중으로 인한 장애가 많고 교육 배경이 없는 경우 정신건강문제가 발생할 위험이 크게 증가한다 (p- 값 <0.05). 반면에, 뇌졸중에 의해 장애가 있다고 해서 정신건강문제의 위험이 크게 증가하지는 않는다 (p- 값> 0.05). 뇌졸중은 또한 더 심각한 장애를 갖는 것으로 나타났다. 뇌졸중이되면 더 심각한 장애가 발생할 위험이 상당히 높아진다 (p- 값 <0.05). 결론 : 이스트 보르네오에 거주하는 대부분의 뇌졸중 및 장애인은 생산성이 가장 높은시기에 정신건강문제를 겪는 경향이 있으므로 정부가 정신건강문제를 조기에 선별하고 훈련을 제공하는 등의 개입을하는 것이 필요하다. 키워드 : 뇌졸중, 장애, 정신건강문제, 여자들