Parkinson's Disease最新文献_第6页

The Priority Goals and Underlying Impairments Contributing to Goal-Related Problems of People with Parkinson’s Disease Receiving a Community-Based Rehabilitation Program 接受社区康复计划的帕金森病患者的优先目标和导致目标相关问题的潜在障碍

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-04-12 DOI: 10.1155/2024/9465326

Sarah J. Davies, Hannah L. Gullo, Emmah Doig

Background. Goal setting is a core rehabilitation practice in Parkinson’s disease (PD). Targeting therapy towards specific goals leads to greater improvements in performance and psychosocial outcomes. Goal setting in PD is feasible, and although the nature of goals has been described in previous studies, the underlying impairments related to goals have not been described. Understanding the nature of goals ensures that interventions for people with PD are aligned with their needs and priorities. Understanding the underlying impairments highlights which symptoms have the biggest impact on daily life and is necessary for planning appropriate interventions to target them. Aim. To describe the nature of the goals of people with PD; the underlying impairments related to goals; and to compare differences between high and low priority goals. Method. Deductive content analysis was used to map goal statements to the international classification of function (ICF) activity and participation category and to map therapist field notes detailing the primary underlying impairment to the ICF Body Functions category. These results were then compared across goal priority rankings. Results. 88 goals of 22 people with PD were analysed. We found that people with PD set diverse goals across all chapters of the ICF Activity and Participation category, with “self-care” goals making up the highest proportion of goals. The primary underlying impairment related to the goals was predominantly related to impairments in “mental functions” under the Body Functions category. Regardless of goal priority, most goal-related underlying impairments were found to be in the “mental functions” category. Conclusion. The goals of this sample of community-dwelling people with PD highlight their diverse needs and priorities. These findings indicate that nonmotor symptoms, namely, executive dysfunction and amotivation most commonly impact the performance of and participation in activities of greatest importance to people with PD. This trial is registered with ACTRN12621001483842.

背景。目标设定是帕金森病（PD）的核心康复实践。针对特定目标进行治疗可大大改善患者的表现和心理社会效果。帕金森病的目标设定是可行的，尽管之前的研究已经描述了目标的性质，但与目标相关的潜在障碍尚未得到描述。了解目标的性质可确保对帕金森氏症患者的干预符合他们的需求和优先事项。了解潜在障碍可突出哪些症状对日常生活的影响最大，这对于规划针对这些症状的适当干预措施非常必要。目的描述帕金森病患者目标的性质；与目标相关的潜在障碍；比较高优先级目标和低优先级目标之间的差异。方法。使用演绎内容分析法将目标陈述与国际功能分类（ICF）的活动和参与类别进行映射，并将治疗师的现场记录与国际功能分类的身体功能类别进行映射，详细说明主要的潜在障碍。然后将这些结果与目标优先级进行比较。结果。对 22 名帕金森氏症患者的 88 个目标进行了分析。我们发现，帕金森氏症患者在《国际功能、残疾和健康分类》的 "活动和参与 "类别的所有章节中设定了不同的目标，其中 "自我护理 "目标所占比例最高。与目标相关的主要基本损伤主要与身体功能类别下的 "精神功能 "损伤有关。无论目标的优先级如何，大多数与目标相关的潜在损伤都属于 "心理功能 "类别。结论这些居住在社区的帕金森病患者的目标突出了他们的不同需求和优先事项。这些研究结果表明，非运动症状，即执行功能障碍和缺乏动力，最常影响帕金森病患者从事和参与最重要的活动。该试验的注册号为 ACTRN12621001483842。

{"title":"The Priority Goals and Underlying Impairments Contributing to Goal-Related Problems of People with Parkinson’s Disease Receiving a Community-Based Rehabilitation Program","authors":"Sarah J. Davies, Hannah L. Gullo, Emmah Doig","doi":"10.1155/2024/9465326","DOIUrl":"https://doi.org/10.1155/2024/9465326","url":null,"abstract":"Background. Goal setting is a core rehabilitation practice in Parkinson’s disease (PD). Targeting therapy towards specific goals leads to greater improvements in performance and psychosocial outcomes. Goal setting in PD is feasible, and although the nature of goals has been described in previous studies, the underlying impairments related to goals have not been described. Understanding the nature of goals ensures that interventions for people with PD are aligned with their needs and priorities. Understanding the underlying impairments highlights which symptoms have the biggest impact on daily life and is necessary for planning appropriate interventions to target them. Aim. To describe the nature of the goals of people with PD; the underlying impairments related to goals; and to compare differences between high and low priority goals. Method. Deductive content analysis was used to map goal statements to the international classification of function (ICF) activity and participation category and to map therapist field notes detailing the primary underlying impairment to the ICF Body Functions category. These results were then compared across goal priority rankings. Results. 88 goals of 22 people with PD were analysed. We found that people with PD set diverse goals across all chapters of the ICF Activity and Participation category, with “self-care” goals making up the highest proportion of goals. The primary underlying impairment related to the goals was predominantly related to impairments in “mental functions” under the Body Functions category. Regardless of goal priority, most goal-related underlying impairments were found to be in the “mental functions” category. Conclusion. The goals of this sample of community-dwelling people with PD highlight their diverse needs and priorities. These findings indicate that nonmotor symptoms, namely, executive dysfunction and amotivation most commonly impact the performance of and participation in activities of greatest importance to people with PD. This trial is registered with ACTRN12621001483842.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"35 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140574180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Home-Based Titration with Duodenal Infusion of Levodopa-Carbidopa Intestinal Gel in People with Parkinson’s Disease: An Observational Feasibility Study 帕金森病患者在家中通过十二指肠输注左旋多巴-卡比多巴肠凝胶进行滴定：观察性可行性研究

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-04-08 DOI: 10.1155/2024/5522824

Trine Hørmann Thomsen, Nick Schou Nielsen, Asher Lou Isenberg, Michael Hougaard Møller, Jesper Bøje Clausen, Inge Mona Schack Frederiksen, Louise Olsen, Mahsa Javidi, Jeanet Vilhelmsen, Marc Klee Olsen, Bo Biering-Sørensen

Background. Testing and titration of the right levodopa equivalent dose are usually performed during a hospital admission. However, optimal dose titration in people with Parkinson’s disease (PwPs) may depend on home environment, emotional stress, and physical activity of everyday life. Objective. Firstly, to evaluate the feasibility and safety of a home-based LCIG titration program and patients’/caregivers’ satisfaction. Secondly, to identify barriers and facilitators for home-based titration. Method. This study assesses the feasibility and safety of home-based titration of levodopa duodenal infusions with the use of self-reported evaluation questionnaires with open-ended questions included, registration of total time used, and number of contacts/visits. A telemedicine solution was used to remotely monitor the patients, adjust treatment, and provide support and guidance to patients and caregivers. Results. Ten of 12 PwPs (5 females and 7 males) completed the total titration program. Eight of the 12 PwPs were dependent on help. These 8 PwPs also had a high burden of nonmotor symptoms (NMS). Cognitive impairments varied in severity (range 16–30). Time spent with home visits was on average 93.4 minutes (ranging from 35 to 180 minutes), and the length of the total titration (LCIG initiation to termination of titration) was on average 3.4 days with 2–5 (mean 3.2) contacts/visits with PD team members. The average score on the satisfaction evaluation questionnaires was lower in the caregiver group (mean 31.8) than the PwP outcome (mean 36.2). Conclusions. Telehealth-assisted home-based titration programs are feasible due to the length of the titration period, number of contacts, and time spent in PwPs’ private homes, are rated satisfactory and safe by PwPs and caregivers, and may be a substitute for in-hospital treatment. Clinical recommendations including facilitators and barriers from a patient/caregiver perspective are displayed. This trial is registered with NCT4196647.

背景。测试和滴定合适的左旋多巴等效剂量通常在入院时进行。然而，帕金森病患者的最佳剂量滴定可能取决于家庭环境、情绪压力和日常生活中的体力活动。研究目的首先，评估基于家庭的 LCIG 滴定计划的可行性和安全性，以及患者/护理人员的满意度。其次，确定居家滴定的障碍和促进因素。方法。本研究通过使用自我报告评估问卷（包括开放式问题）、登记所用总时间和联系/访问次数，评估左旋多巴十二指肠输液居家滴注的可行性和安全性。远程医疗解决方案用于远程监控患者、调整治疗方案以及为患者和护理人员提供支持和指导。结果。12 名患者中有 10 名（5 名女性和 7 名男性）完成了整个滴定计划。在这 12 名患者中，有 8 名需要依赖他人的帮助。这 8 名患者的非运动症状（NMS）负担也很重。认知障碍的严重程度各不相同（范围在 16-30 之间）。家访时间平均为 93.4 分钟（从 35 分钟到 180 分钟不等），整个滴定过程（从开始使用 LCIG 到终止滴定）平均为 3.4 天，与 PD 小组成员接触/家访 2-5 次（平均 3.2 次）。护理人员组满意度评估问卷的平均得分（平均 31.8 分）低于患者组（平均 36.2 分）。结论远程医疗辅助家庭滴定项目是可行的，因为滴定时间长、接触次数多、在患者私人家中花费的时间少，患者和护理人员对其满意度和安全性的评价也很高，可以替代院内治疗。临床建议包括从患者/护理者角度出发的促进因素和障碍。该试验已在 NCT4196647 上注册。

{"title":"Home-Based Titration with Duodenal Infusion of Levodopa-Carbidopa Intestinal Gel in People with Parkinson’s Disease: An Observational Feasibility Study","authors":"Trine Hørmann Thomsen, Nick Schou Nielsen, Asher Lou Isenberg, Michael Hougaard Møller, Jesper Bøje Clausen, Inge Mona Schack Frederiksen, Louise Olsen, Mahsa Javidi, Jeanet Vilhelmsen, Marc Klee Olsen, Bo Biering-Sørensen","doi":"10.1155/2024/5522824","DOIUrl":"https://doi.org/10.1155/2024/5522824","url":null,"abstract":"Background. Testing and titration of the right levodopa equivalent dose are usually performed during a hospital admission. However, optimal dose titration in people with Parkinson’s disease (PwPs) may depend on home environment, emotional stress, and physical activity of everyday life. Objective. Firstly, to evaluate the feasibility and safety of a home-based LCIG titration program and patients’/caregivers’ satisfaction. Secondly, to identify barriers and facilitators for home-based titration. Method. This study assesses the feasibility and safety of home-based titration of levodopa duodenal infusions with the use of self-reported evaluation questionnaires with open-ended questions included, registration of total time used, and number of contacts/visits. A telemedicine solution was used to remotely monitor the patients, adjust treatment, and provide support and guidance to patients and caregivers. Results. Ten of 12 PwPs (5 females and 7 males) completed the total titration program. Eight of the 12 PwPs were dependent on help. These 8 PwPs also had a high burden of nonmotor symptoms (NMS). Cognitive impairments varied in severity (range 16–30). Time spent with home visits was on average 93.4 minutes (ranging from 35 to 180 minutes), and the length of the total titration (LCIG initiation to termination of titration) was on average 3.4 days with 2–5 (mean 3.2) contacts/visits with PD team members. The average score on the satisfaction evaluation questionnaires was lower in the caregiver group (mean 31.8) than the PwP outcome (mean 36.2). Conclusions. Telehealth-assisted home-based titration programs are feasible due to the length of the titration period, number of contacts, and time spent in PwPs’ private homes, are rated satisfactory and safe by PwPs and caregivers, and may be a substitute for in-hospital treatment. Clinical recommendations including facilitators and barriers from a patient/caregiver perspective are displayed. This trial is registered with NCT4196647.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"38 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140574402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Focused Ultrasound Thalamotomy for Tremor Relief in Atypical Parkisnsonism 聚焦超声丘脑切开术缓解非典型帕金森氏症患者的震颤

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-03-05 DOI: 10.1155/2024/6643510

Alon Sinai, Maria Nassar, Lev Shornikov, Marius Constantinescu, Menashe Zaaroor, Ilana Schlesinger

Background. Magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) VIM-thalamotomy has established efficacy and safety in tremor relief in patients with essential tremor and Parkinson’s disease. The efficacy and safety in patients with atypical parkinsonism have not been reported. Objective. To report on the efficacy and safety of FUS VIM-thalamotomy in 8 patients with parkinsonism, multiple system atrophy-Parkinsonian type (MSA-P) (n = 5), and dementia with Lewy bodies (DLB) (n = 3). Methods. Tremor was assessed in the treated hemibody using the Clinical Rating Scale for Tremor (CRST). The motor Unified MSA Rating Scale (UMSAR) was used in the MSA-P and motor sections of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) in DLB patients. Cognition was measured using the Montreal Cognitive Assessment (MoCA). Results. In MSA-P and DLB patients, there was immediate tremor relief. CRST scores measured on the treated side improved compared to baseline. During the follow-up of up to 1 year tremor reduction persisted. The change in CRST scores at different time points did not reach statistical significance, probably due to the small sample size. Adverse events were transient and resolved within a year. Conclusions. In our experience, FUS VIM-thalamotomy was effective in patients with MSA-P and DLB. Larger, controlled studies are needed to verify our preliminary observations.

背景。磁共振成像（MRI）引导下的聚焦超声（FUS）VIM-丘脑切开术对缓解本质性震颤和帕金森病患者的震颤具有疗效和安全性。但对非典型帕金森病患者的疗效和安全性尚未见报道。目的报告 FUS VIM-胼胝体切开术在 8 例帕金森病、多系统萎缩-帕金森病型（MSA-P）（n = 5）和路易体痴呆（DLB）（n = 3）患者中的疗效和安全性。研究方法使用震颤临床评分量表（CRST）评估治疗半身的震颤情况。在DLB患者的MSA-P和统一帕金森病评定量表（UPDRS-III）的运动部分使用运动统一MSA评定量表（UMSAR）。认知能力采用蒙特利尔认知评估（MoCA）进行测量。结果MSA-P和DLB患者的震颤症状立即得到缓解。与基线相比，治疗侧的 CRST 评分有所提高。在长达 1 年的随访期间，震颤的缓解仍在持续。可能由于样本量较小，不同时间点的 CRST 评分变化未达到统计学意义。不良反应均为一过性，并在一年内缓解。结论根据我们的经验，FUS VIM-丘脑切开术对 MSA-P 和 DLB 患者有效。我们需要更大规模的对照研究来验证我们的初步观察结果。

{"title":"Focused Ultrasound Thalamotomy for Tremor Relief in Atypical Parkisnsonism","authors":"Alon Sinai, Maria Nassar, Lev Shornikov, Marius Constantinescu, Menashe Zaaroor, Ilana Schlesinger","doi":"10.1155/2024/6643510","DOIUrl":"https://doi.org/10.1155/2024/6643510","url":null,"abstract":"Background. Magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) VIM-thalamotomy has established efficacy and safety in tremor relief in patients with essential tremor and Parkinson’s disease. The efficacy and safety in patients with atypical parkinsonism have not been reported. Objective. To report on the efficacy and safety of FUS VIM-thalamotomy in 8 patients with parkinsonism, multiple system atrophy-Parkinsonian type (MSA-P) (n = 5), and dementia with Lewy bodies (DLB) (n = 3). Methods. Tremor was assessed in the treated hemibody using the Clinical Rating Scale for Tremor (CRST). The motor Unified MSA Rating Scale (UMSAR) was used in the MSA-P and motor sections of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) in DLB patients. Cognition was measured using the Montreal Cognitive Assessment (MoCA). Results. In MSA-P and DLB patients, there was immediate tremor relief. CRST scores measured on the treated side improved compared to baseline. During the follow-up of up to 1 year tremor reduction persisted. The change in CRST scores at different time points did not reach statistical significance, probably due to the small sample size. Adverse events were transient and resolved within a year. Conclusions. In our experience, FUS VIM-thalamotomy was effective in patients with MSA-P and DLB. Larger, controlled studies are needed to verify our preliminary observations.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"536 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140035731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease 转染存活的多巴胺神经元中的 BDNF 基因并持续服用普拉克索可恢复双侧帕金森病大鼠模型的正常运动行为

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-02-21 DOI: 10.1155/2024/3885451

Alina Benítez-Castañeda, Verónica Anaya-Martínez, Armando de Jesús Espadas-Alvarez, Ana Luisa Gutierrez-Váldez, Luis Fernando Razgado-Hernández, Patricia Emmanuelle Reyna-Velazquez, Liz Quintero-Macias, Daniel Martínez-Fong, Benjamín Florán-Garduño, Jorge Aceves

In Parkinson’s disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson’s model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy.

在帕金森病（PD）中，黑质纹状体神经支配的逐渐退化会导致纹状体中刺神经元（MSN）树突棘的萎缩和缺失。这种损失会破坏皮质神经元的传导，损害运动行为，并产生非运动症状。黑质神经元表达脑源性神经营养因子（BDNF）和多巴胺 D3 受体，两者都能保护多巴胺神经元和 MSN 的棘。为了使运动症状和非运动症状恢复正常，我们在双侧大鼠帕金森病模型中评估了一种联合疗法。通过微型渗透泵输注首选 D3 激动剂普拉克索（PPX）四个半月，并在 PPX 开始后一个月；使用非病毒转染 NTS-polyplex 载体将 BDNF 基因转染到存活的黑质细胞中。在持续输注 PPX 的同时过表达 BDNF 基因，可恢复运动协调、平衡、正常步态和工作记忆。恢复还与纹状体投射神经元树突棘平均数量以及黑质和腹侧被盖区TH阳性神经元数量的恢复有关。这些积极的结果为进一步临床研究这种前景广阔的疗法铺平了道路。

{"title":"Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease","authors":"Alina Benítez-Castañeda, Verónica Anaya-Martínez, Armando de Jesús Espadas-Alvarez, Ana Luisa Gutierrez-Váldez, Luis Fernando Razgado-Hernández, Patricia Emmanuelle Reyna-Velazquez, Liz Quintero-Macias, Daniel Martínez-Fong, Benjamín Florán-Garduño, Jorge Aceves","doi":"10.1155/2024/3885451","DOIUrl":"https://doi.org/10.1155/2024/3885451","url":null,"abstract":"In Parkinson’s disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson’s model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"193 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improvement by Medication Less than Expected in Parkinson’s Disease: Blinded Evaluation of Levodopa Response 帕金森病患者用药后的病情改善低于预期：左旋多巴反应的盲法评估

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-02-21 DOI: 10.1155/2024/2649578

Mette Niemann Johansen, Anna Handberg, Mohamed El Haddouchi, Josefine Grundtvig, Steen Rusborg Jensen, Lisette Salvesen, Annemette Løkkegaard

Background. The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson’s disease, PD. Objective. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. Methods. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson’s Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck’s Depression Inventory (BDI). Results. In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤30%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients’ self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. Conclusions. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient’s subjective evaluation.

背景。最新的运动障碍协会（MDS）诊断标准要求，帕金森病（Parkinson's disease，PD）患者必须对药物治疗有良好且持续的反应，才能被诊断为帕金森病。研究目的本研究旨在评估由运动障碍专家确诊的一组疑似帕金森病患者对左旋多巴的反应。方法在暂停使用多巴胺能药物 6 次半后，进行急性左旋多巴挑战试验（LDCT）。统一帕金森病评分量表的运动部分在关机状态和 LDCT（开机）后进行。良好效果的定义是改善了 30%。采用视频协议确保了标准化的运动检查，并对UPDRS-III关机和开机状态进行了盲测。此外，还纳入了一组年龄匹配的对照受试者（CS），但没有进行LDCT检查。所有参与者都接受了蒙特利尔认知评估（MoCA）和贝克抑郁量表（BDI）的评估。结果统计分析共纳入 37 名患者。21名患者的病情改善率低于30%，16名患者的病情改善率为30%。LDCT 显示，运动型 UPDRS 的总体平均改善率为 27.3%。在43.2%的患者中，LDCT显示的效果与患者自我感觉的医学评估之间存在差异。与CS相比，PD患者的MoCA评分明显更低，抑郁症状更多。结论。我们利用 LDCT 显示了左旋多巴的急性疗效，改善幅度约为 30%。虽然这为在 MDS 诊断标准中使用这一限制提供了支持，但在某些患者中，低于 30% 的急性效果应被视为可以接受。我们的研究凸显了药物对运动症状影响的客观测量与患者主观评价之间的差异。

{"title":"Improvement by Medication Less than Expected in Parkinson’s Disease: Blinded Evaluation of Levodopa Response","authors":"Mette Niemann Johansen, Anna Handberg, Mohamed El Haddouchi, Josefine Grundtvig, Steen Rusborg Jensen, Lisette Salvesen, Annemette Løkkegaard","doi":"10.1155/2024/2649578","DOIUrl":"https://doi.org/10.1155/2024/2649578","url":null,"abstract":"Background. The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson’s disease, PD. Objective. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. Methods. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson’s Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck’s Depression Inventory (BDI). Results. In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤30%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients’ self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. Conclusions. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient’s subjective evaluation.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"773 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preoperative Attention/Memory Problem Affects the Quality of Life of Parkinson's Disease Patients after Deep Brain Stimulation: A Cohort Study. 术前注意力/记忆力问题影响深部脑刺激术后帕金森病患者的生活质量：一项队列研究

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-02-07 eCollection Date: 2024-01-01 DOI: 10.1155/2024/3651705

Ying Gao, Jue Wang, Linbin Wang, Dianyou Li, Bomin Sun, Xian Qiu

Objectives: The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up.

Methods: Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively.

Results: Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (β = 0.869, P < 0.001) and the preoperative attention/memory subscore (β = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL).

Conclusion: Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.

研究目的本研究旨在探讨眼下核深部脑刺激术（STN-DBS）后1年随访期间非运动症状（NMS）对生活质量（QoL）结果的影响：本研究纳入了在2020年4月至2021年8月期间接受脑下核深部刺激术（STN-DBS）的93名帕金森病（PD）患者。研究人员通过自行设计的问卷收集了患者的人口统计学信息。分别使用统一帕金森病评分量表-III（UPDRS-III）、非运动症状量表（NMSS）和8项帕金森病问卷（PDQ-8）评估运动症状和非运动症状的严重程度以及生活质量（QoL）：在UPDRS-III评分、NMSS汇总指数（SI）以及六个领域（睡眠/疲劳、情绪/认知、感知问题/幻觉、注意力/记忆力、泌尿系统和性功能）的子评分方面，基线值与6个月和12个月随访值之间存在显著差异。相关性分析显示，术前 NMSS SI 与七个领域（心血管、睡眠/疲劳、情绪/认知、感知问题/幻觉、注意力/记忆力、胃肠道和泌尿系统）的子分数和 ΔPDQ-8 之间存在正相关。此外，术前 PDQ-8 SI（β = 0.869，P < 0.001）和术前注意力/记忆力子分数（β = -0.154，P = 0.026）对术后生活质量（QoL）的改善具有预测作用：结论：脑深部刺激术（DBS）使患者的非运动症状（NMS）在1年随访时得到改善，同时观察到NMS与患者生活质量（QoL）之间存在相关性。值得注意的是，术前注意力/记忆力问题的严重程度是影响 STN-DBS 术后 1 年生活质量的 NMS 最重要的预测因素。

{"title":"Preoperative Attention/Memory Problem Affects the Quality of Life of Parkinson's Disease Patients after Deep Brain Stimulation: A Cohort Study.","authors":"Ying Gao, Jue Wang, Linbin Wang, Dianyou Li, Bomin Sun, Xian Qiu","doi":"10.1155/2024/3651705","DOIUrl":"10.1155/2024/3651705","url":null,"abstract":"Objectives: The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up.Methods: Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively.Results: Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (β = 0.869, P < 0.001) and the preoperative attention/memory subscore (β = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL).Conclusion: Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"2024 ","pages":"3651705"},"PeriodicalIF":3.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Systematic Review and Meta-Analysis of the Efficacy and Safety of Rasagiline or Pramipexole in the Treatment of Early Parkinson’s Disease 关于拉沙吉林或普拉克索治疗早期帕金森病的疗效和安全性的系统回顾和荟萃分析

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-01-16 DOI: 10.1155/2024/8448584

Pauli Seppänen, Markus M. Forsberg, Miia Tiihonen, Heikki Laitinen, Selena Beal, David C. Dorman

Background. Rasagiline or pramipexole monotherapy has been suggested for the management of early Parkinson’s disease (PD). The aim of this research was to systematically review the clinical efficacy and safety of rasagiline or pramipexole in early PD (defined as disease duration ≤5 years and Hoehn and Yahr stage of ≤3). Methods. Randomized controlled trials (RCTs) of rasagiline or pramipexole for early PD published up to September 2021 were retrieved. Outcomes of interest included changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III and the incidence of adverse events. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated, and heterogeneity was measured with the I² test. Results. Nine rasagiline and eleven pramipexole RCTs were included. One post hoc analysis of one rasagiline study was included. Five studies for each drug were included in meta-analyses of the UPDRS scores. The rasagiline meta-analysis focused on patients receiving 1 mg/day. Rasagiline and pramipexole significantly improved UPDRS Part II and III scores when compared to placebo. Significant heterogeneity among the studies was present (I² > 70%). Neither rasagiline nor pramipexole increased the relative risk for any adverse events, serious adverse events, or adverse events leading to withdrawal when compared with placebo. Conclusion. Applying a Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to summarize the evidence, we found moderate confidence in the body of evidence for the efficacy of rasagiline or pramipexole in early PD, suggesting further well-designed, multicenter comparative RCTs remain needed.

背景。有人建议使用拉沙吉林或普拉克索单药治疗早期帕金森病（PD）。本研究旨在系统回顾拉沙吉林或普拉克索治疗早期帕金森病（病程≤5年，Hoehn和Yahr分期≤3期）的临床疗效和安全性。研究方法检索截至2021年9月发表的拉沙吉林或普拉克索治疗早期帕金森病的随机对照试验（RCT）。研究结果包括统一帕金森病评分量表（UPDRS）第二部分和第三部分的变化以及不良事件的发生率。计算了标准化平均差 (SMD)、比值比 (OR) 和 95% 置信区间 (CI)，并通过 I2 检验测量了异质性。研究结果共纳入了九项拉沙吉林和十一项普拉克索的 RCT 研究。还纳入了对一项拉沙吉林研究的事后分析。每种药物均有五项研究被纳入UPDRS评分的荟萃分析。拉沙吉林的荟萃分析主要针对每天服用1毫克的患者。与安慰剂相比，拉沙吉林和普拉克索能明显改善UPDRS第二部分和第三部分的评分。研究之间存在明显的异质性（I2 >70%）。与安慰剂相比，拉沙吉林和普拉克索均未增加任何不良事件、严重不良事件或导致停药的不良事件的相对风险。结论应用建议、评估、发展和评价分级法（GRADE）对证据进行总结，我们发现拉沙吉林或普拉克索对早期帕金森病疗效的证据可信度为中等，这表明仍需进一步开展设计良好的多中心对比性RCT研究。

{"title":"A Systematic Review and Meta-Analysis of the Efficacy and Safety of Rasagiline or Pramipexole in the Treatment of Early Parkinson’s Disease","authors":"Pauli Seppänen, Markus M. Forsberg, Miia Tiihonen, Heikki Laitinen, Selena Beal, David C. Dorman","doi":"10.1155/2024/8448584","DOIUrl":"https://doi.org/10.1155/2024/8448584","url":null,"abstract":"Background. Rasagiline or pramipexole monotherapy has been suggested for the management of early Parkinson’s disease (PD). The aim of this research was to systematically review the clinical efficacy and safety of rasagiline or pramipexole in early PD (defined as disease duration ≤5 years and Hoehn and Yahr stage of ≤3). Methods. Randomized controlled trials (RCTs) of rasagiline or pramipexole for early PD published up to September 2021 were retrieved. Outcomes of interest included changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III and the incidence of adverse events. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated, and heterogeneity was measured with the I2 test. Results. Nine rasagiline and eleven pramipexole RCTs were included. One post hoc analysis of one rasagiline study was included. Five studies for each drug were included in meta-analyses of the UPDRS scores. The rasagiline meta-analysis focused on patients receiving 1 mg/day. Rasagiline and pramipexole significantly improved UPDRS Part II and III scores when compared to placebo. Significant heterogeneity among the studies was present (I2 > 70%). Neither rasagiline nor pramipexole increased the relative risk for any adverse events, serious adverse events, or adverse events leading to withdrawal when compared with placebo. Conclusion. Applying a Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to summarize the evidence, we found moderate confidence in the body of evidence for the efficacy of rasagiline or pramipexole in early PD, suggesting further well-designed, multicenter comparative RCTs remain needed.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"7 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alprazolam Reduces Freezing of Gait (FOG) and Improves FOG-Related Gait Deficiencies 阿普唑仑可减少步态冻结 (FOG) 并改善与 FOG 相关的步态缺陷

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2024-01-09 DOI: 10.1155/2024/3447009

Abdullah Al Jaja, Téa Sue, Margaret Prenger, Ken N. Seergobin, Jessica A. Grahn, Penny A. MacDonald

Background. Freezing of gait (FOG) is an intractable motor symptom in Parkinson’s disease (PD) that increases fall risk and impairs the quality of life. FOG has been associated with anxiety, with experimental support for the notion that anxiety itself provokes FOG. We investigated the effect of acute anxiety reduction via alprazolam on FOG in PD. Methods. In ten patients with PD, FOG, and normal cognition, we administered 0.25 mg alprazolam in one session and placebo in another, in counterbalanced order. At each session, on separate days, patients walked on a pressure-sensitive walkway. Using Oculus Rift virtual-reality goggles, patients walked along a plank that appeared to be (a) level with the floor, in the low-anxiety condition or (b) raised high above the ground, in the high-anxiety conditions. In this way, we assessed the impacts of anxiety and alprazolam (i.e., anxiety reduction) on FOG frequency and other gait parameters. Results. FOG events appeared only in the high-anxiety conditions. Alprazolam significantly reduced subjective and objective measures of anxiety, as well as the prevalence of FOG (). Furthermore, alprazolam improved swing time ()

背景。步态冻结（FOG）是帕金森病（PD）的一种难治性运动症状，会增加跌倒风险并影响生活质量。步态冻结与焦虑有关，实验支持焦虑本身会引发步态冻结的观点。我们研究了通过阿普唑仑减轻急性焦虑对帕金森病 FOG 的影响。研究方法我们对 10 名患有帕金森病、FOG 和正常认知能力的患者分别施用 0.25 毫克阿普唑仑和安慰剂，以平衡顺序进行。在每个疗程的不同日子里，患者在压力敏感的人行道上行走。患者使用 Oculus Rift 虚拟现实眼镜，沿着一块木板行走，这块木板(a) 看起来与地面持平，处于低焦虑状态；(b) 看起来高出地面，处于高焦虑状态。通过这种方法，我们评估了焦虑和阿普唑仑（即减轻焦虑）对 FOG 频率和其他步态参数的影响。结果显示只有在高度焦虑的情况下才会出现 FOG 事件。阿普唑仑能显著降低主观和客观焦虑程度以及 FOG 的发生率（）。此外，阿普唑仑还改善了所有条件下的摆动时间（）和步态变异性，尤其是在高架平板试验中。解释。我们的研究结果表明：（1）焦虑会诱发 FOG；（2）阿普唑仑会同时减轻焦虑和 FOG。阿普唑仑还能进一步改善步态稳定性（即摆动时间和步态变异性）。这些研究结果表明，焦虑会引发帕金森病患者的 FOG。治疗焦虑症可以减轻 FOG 并改善步态稳定性，从而为治疗帕金森病中这一棘手的致残症状提供了新的治疗途径。

{"title":"Alprazolam Reduces Freezing of Gait (FOG) and Improves FOG-Related Gait Deficiencies","authors":"Abdullah Al Jaja, Téa Sue, Margaret Prenger, Ken N. Seergobin, Jessica A. Grahn, Penny A. MacDonald","doi":"10.1155/2024/3447009","DOIUrl":"https://doi.org/10.1155/2024/3447009","url":null,"abstract":"Background. Freezing of gait (FOG) is an intractable motor symptom in Parkinson’s disease (PD) that increases fall risk and impairs the quality of life. FOG has been associated with anxiety, with experimental support for the notion that anxiety itself provokes FOG. We investigated the effect of acute anxiety reduction via alprazolam on FOG in PD. Methods. In ten patients with PD, FOG, and normal cognition, we administered 0.25 mg alprazolam in one session and placebo in another, in counterbalanced order. At each session, on separate days, patients walked on a pressure-sensitive walkway. Using Oculus Rift virtual-reality goggles, patients walked along a plank that appeared to be (a) level with the floor, in the low-anxiety condition or (b) raised high above the ground, in the high-anxiety conditions. In this way, we assessed the impacts of anxiety and alprazolam (i.e., anxiety reduction) on FOG frequency and other gait parameters. Results. FOG events appeared only in the high-anxiety conditions. Alprazolam significantly reduced subjective and objective measures of anxiety, as well as the prevalence of FOG (<svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"></path></g></svg>). Furthermore, alprazolam improved swing time (<svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-113\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"><use xlink:href=\"#g113-47\"></use></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"><use xlink:href=\"#g113-54\"></use></g></svg>)","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"7 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139409450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Cell Analyses Reveal Necroptosis’s Potential Role in Neuron Degeneration and Show Enhanced Neuron-Immune Cell Interaction in Parkinson’s Disease Progression 单细胞分析揭示坏死在神经元退化中的潜在作用，并显示帕金森病进展过程中神经元与免疫细胞的相互作用增强

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2023-12-19 DOI: 10.1155/2023/5057778

Xiaomei Zeng, Zhifen Han, Kehan Chen, Peng Zeng, Yidan Tang, Lijuan Li

Parkinson’s disease (PD) is a common neuron degenerative disease among the old, characterized by uncontrollable movements and an impaired posture. Although widely investigated on its pathology and treatment, the disease remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) has been applied to the area of PD, providing valuable data for related research. However, few works have taken deeper insights into the causes of neuron death and cell-cell interaction between the cell types in the brain. Our bioinformatics analyses revealed necroptosis-related genes (NRGs) enrichment in neuron degeneration and selecting the cells by NRGs levels showed two subtypes within the main degenerative cell types in the midbrain. NRG-low subtype was largely replaced by NRG-high subtype in the patients, indicating the striking change of cell state related to necroptosis in PD progression. Moreover, we carried out cell-cell interaction analyses between cell types and found that microglia (MG)’s interaction strength with glutamatergic neuron (GLU), GABAergic neuron (GABA), and dopaminergic neuron (DA) was significantly upregulated in PD. Also, MG show much stronger interaction with NRG-high subtypes and a stronger cell killing function in PD samples. Additionally, we identified CLDN11 as a novel interaction pattern specific to necroptosis neurons and MG. We also found LEF1 and TCF4 as key transcriptional regulators in neuron degeneration. These findings suggest that MG were significantly overactivated in PD patients to clear abnormal neurons, especially the NRG-high cells, explaining the neuron inflammation in PD. Our analyses provide insights into the causes of neuron death and inflammation in PD from single-cell resolution, which could be seriously considered in clinical trials.

帕金森病（Parkinson's disease，PD）是一种常见的老年神经元退行性疾病，其特征是无法控制的运动和姿势受损。尽管人们对该病的病理和治疗进行了广泛研究，但对该病的了解仍然不够深入。单细胞 RNA 测序（scRNA-seq）已被应用于老年痴呆症领域，为相关研究提供了宝贵的数据。然而，很少有研究深入探讨神经元死亡的原因以及大脑中各类型细胞之间的细胞-细胞相互作用。我们的生物信息学分析揭示了神经元变性中富集的坏死相关基因（NRGs），并根据NRGs水平对细胞进行筛选，结果显示中脑主要变性细胞类型中有两种亚型。在患者中，NRG低亚型大部分被NRG高亚型所取代，这表明在帕金森病进展过程中，与坏死相关的细胞状态发生了显著变化。此外，我们还进行了细胞间相互作用分析，发现小胶质细胞（MG）与谷氨酸能神经元（GLU）、GABA能神经元（GABA）和多巴胺能神经元（DA）的相互作用强度在帕金森病中显著上调。同时，在帕金森病样本中，MG 与 NRG 高亚型的相互作用更强，细胞杀伤功能更强。此外，我们还发现 CLDN11 是坏死神经元和 MG 特异的新型相互作用模式。我们还发现 LEF1 和 TCF4 是神经元变性的关键转录调节因子。这些发现表明，MG在帕金森病患者中被过度激活，以清除异常神经元，尤其是NRG高的细胞，从而解释了帕金森病中神经元炎症的原因。我们的分析从单细胞解析的角度揭示了帕金森病神经元死亡和炎症的原因，可在临床试验中认真考虑。

{"title":"Single-Cell Analyses Reveal Necroptosis’s Potential Role in Neuron Degeneration and Show Enhanced Neuron-Immune Cell Interaction in Parkinson’s Disease Progression","authors":"Xiaomei Zeng, Zhifen Han, Kehan Chen, Peng Zeng, Yidan Tang, Lijuan Li","doi":"10.1155/2023/5057778","DOIUrl":"https://doi.org/10.1155/2023/5057778","url":null,"abstract":"Parkinson’s disease (PD) is a common neuron degenerative disease among the old, characterized by uncontrollable movements and an impaired posture. Although widely investigated on its pathology and treatment, the disease remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) has been applied to the area of PD, providing valuable data for related research. However, few works have taken deeper insights into the causes of neuron death and cell-cell interaction between the cell types in the brain. Our bioinformatics analyses revealed necroptosis-related genes (NRGs) enrichment in neuron degeneration and selecting the cells by NRGs levels showed two subtypes within the main degenerative cell types in the midbrain. NRG-low subtype was largely replaced by NRG-high subtype in the patients, indicating the striking change of cell state related to necroptosis in PD progression. Moreover, we carried out cell-cell interaction analyses between cell types and found that microglia (MG)’s interaction strength with glutamatergic neuron (GLU), GABAergic neuron (GABA), and dopaminergic neuron (DA) was significantly upregulated in PD. Also, MG show much stronger interaction with NRG-high subtypes and a stronger cell killing function in PD samples. Additionally, we identified CLDN11 as a novel interaction pattern specific to necroptosis neurons and MG. We also found LEF1 and TCF4 as key transcriptional regulators in neuron degeneration. These findings suggest that MG were significantly overactivated in PD patients to clear abnormal neurons, especially the NRG-high cells, explaining the neuron inflammation in PD. Our analyses provide insights into the causes of neuron death and inflammation in PD from single-cell resolution, which could be seriously considered in clinical trials.","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"234 1 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138741636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease 帕金森病中 PGLYRP2 变异 rs892145 的等位基因分布的性别差异

IF 3.2 4区医学 Q3 CLINICAL NEUROLOGY

Parkinson's Disease

Pub Date : 2023-12-09 DOI: 10.1155/2023/6502727

Caroline Ran, Karin Wirdefeldt, Olof Sydow, Per Svenningsson, Rochellys Diaz Heijtz

Introduction. Parkinson’s disease (PD) is a complex multifactorial disease, involving genetic susceptibility, environmental risk factors, and gene-environmental interactions. The microbiota-gut-brain axis is hypothesized to play a role in the pathophysiology of PD, and peptidoglycan recognition proteins (PGLYRPs), which modulate the gut microbiota, are, therefore, relevant candidate genes for PD. Methods. Using quantitative real-time PCR, we genotyped three PGLYRP variants (rs892145, rs959117, and rs10888557) and performed an association analysis in 508 PD patients and 585 control individuals. We further conducted a meta-analysis of rs892145 and analyzed PGLYRP2 gene expression in lymphocytes from patients with PD and controls. Results. Although initial analysis of the three variants rs892145, rs959117, and rs10888557 and a meta-analysis of rs892145 did not reveal any association between the selected variants and PD, we found an interaction between sex and genotype for rs892145, with a marked difference in the allele distribution of rs892145 between male and female patients. As compared to controls, the T allele was less common in female patients (odds ratio = 0.76, <svg height="8.68572pt" style="vertical-align:-0.0498209pt" version="1.1" viewbox="-0.0498162 -8.6359 8.15071 8.68572" width="8.15071pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g></svg> = 0.04) and more common in male patients (odds ratio = 1.29, <svg height="8.68572pt" style="vertical-align:-0.0498209pt" version="1.1" viewbox="-0.0498162 -8.6359 8.15071 8.68572" width="8.15071pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"></use></g></svg> = 0.04). No difference was found in PGLYRP2 gene expression between PD patients and controls (<svg height="8.68572pt" style="vertical-align:-0.0498209pt" version="1.1" viewbox="-0.0498162 -8.6359 8.15071 8.68572" width="8.15071pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"></use></g></svg> = 0.38), nor between sexes (<svg height="8.68572pt" style="vertical-align:-0.0498209pt" version="1.1" viewbox="-0.0498162 -8.6359 8.15071 8.68572" width="8.15071pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"></use></g></svg> = 0.07). Discussion. Overall, this genetic screening in Swedish PD patients does not support previous results demonstrating associations of PGLYRP variants with the risk of PD. Meta-analysis of rs892145 revealed pronounced heterogeneity between previously published studies which is likely to have influenced the results. Taken together, the genetic and gene expression analyses suggest a possi

简介：帕金森病（PD）是一种复杂的多因素疾病。帕金森病（PD）是一种复杂的多因素疾病，涉及遗传易感性、环境风险因素以及基因与环境的相互作用。据推测，微生物群-肠道-大脑轴在帕金森病的病理生理学中发挥作用，而肽聚糖识别蛋白（PGLYRPs）能调节肠道微生物群，因此是帕金森病的相关候选基因。研究方法利用定量实时 PCR 技术，我们对三个 PGLYRP 变体（rs892145、rs959117 和 rs10888557）进行了基因分型，并对 508 名 PD 患者和 585 名对照者进行了关联分析。我们进一步对 rs892145 进行了荟萃分析，并分析了 PGLYRP2 基因在 PD 患者和对照组淋巴细胞中的表达。结果。尽管对三个变异体rs892145、rs959117和rs10888557的初步分析以及对rs892145的荟萃分析并未发现所选变异体与帕金森病之间存在任何关联，但我们发现rs892145的性别与基因型之间存在交互作用，男性和女性患者之间的rs892145等位基因分布存在明显差异。与对照组相比，T等位基因在女性患者中较少见（几率比=0.76，=0.04），而在男性患者中较常见（几率比=1.29，=0.04）。在PGLYRP2基因表达方面，帕金森病患者与对照组（= 0.38）和性别间（= 0.07）均无差异。讨论总体而言，此次对瑞典帕金森病患者进行的基因筛查并不支持之前证明 PGLYRP 变异与帕金森病风险相关的结果。对 rs892145 进行的元分析表明，以前发表的研究之间存在明显的异质性，这很可能影响了研究结果。综上所述，遗传和基因表达分析表明，PGLYRP2的遗传变异与帕金森病的性别差异之间可能存在联系。由于我们的研究样本量有限，这些结果需要在独立队列中验证后才能得出结论。

{"title":"Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease","authors":"Caroline Ran, Karin Wirdefeldt, Olof Sydow, Per Svenningsson, Rochellys Diaz Heijtz","doi":"10.1155/2023/6502727","DOIUrl":"https://doi.org/10.1155/2023/6502727","url":null,"abstract":"Introduction. Parkinson’s disease (PD) is a complex multifactorial disease, involving genetic susceptibility, environmental risk factors, and gene-environmental interactions. The microbiota-gut-brain axis is hypothesized to play a role in the pathophysiology of PD, and peptidoglycan recognition proteins (PGLYRPs), which modulate the gut microbiota, are, therefore, relevant candidate genes for PD. Methods. Using quantitative real-time PCR, we genotyped three PGLYRP variants (rs892145, rs959117, and rs10888557) and performed an association analysis in 508 PD patients and 585 control individuals. We further conducted a meta-analysis of rs892145 and analyzed PGLYRP2 gene expression in lymphocytes from patients with PD and controls. Results. Although initial analysis of the three variants rs892145, rs959117, and rs10888557 and a meta-analysis of rs892145 did not reveal any association between the selected variants and PD, we found an interaction between sex and genotype for rs892145, with a marked difference in the allele distribution of rs892145 between male and female patients. As compared to controls, the T allele was less common in female patients (odds ratio = 0.76, <svg height=\"8.68572pt\" style=\"vertical-align:-0.0498209pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 8.15071 8.68572\" width=\"8.15071pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g></svg> = 0.04) and more common in male patients (odds ratio = 1.29, <svg height=\"8.68572pt\" style=\"vertical-align:-0.0498209pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 8.15071 8.68572\" width=\"8.15071pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-81\"></use></g></svg> = 0.04). No difference was found in PGLYRP2 gene expression between PD patients and controls (<svg height=\"8.68572pt\" style=\"vertical-align:-0.0498209pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 8.15071 8.68572\" width=\"8.15071pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-81\"></use></g></svg> = 0.38), nor between sexes (<svg height=\"8.68572pt\" style=\"vertical-align:-0.0498209pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 8.15071 8.68572\" width=\"8.15071pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-81\"></use></g></svg> = 0.07). Discussion. Overall, this genetic screening in Swedish PD patients does not support previous results demonstrating associations of PGLYRP variants with the risk of PD. Meta-analysis of rs892145 revealed pronounced heterogeneity between previously published studies which is likely to have influenced the results. Taken together, the genetic and gene expression analyses suggest a possi","PeriodicalId":19907,"journal":{"name":"Parkinson's Disease","volume":"9 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138561686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0