Dorsal nigral hyperintensity (DNH) abnormality associated with excessive iron deposition in the substantia nigra, is recognized as an imaging characteristic of Parkinson’s disease (PD) and can be effectively visualized using 7T MRI. This study was aimed to develop and validate the optimal DNH assessment method as a biomarker for PD, idiopathic rapid eye movement sleep behavior disorder (iRBD), and Parkinson-plus syndromes, and to explore the nigral iron deposition patterns in these diseases. Three-dimensional gradient-echo T2*-weighted images were acquired by 7T MRI from a total of 402 patients and 100 healthy controls (HCs) in two independent cohorts (development and validation cohorts). Seven methods, including four dichotomous methods and three DNH rating scales, were used to assess DNH and evaluate their diagnostic performance. R2* mapping and principal component analysis were performed to assess nigral iron deposition patterns. Bilateral DNH detection rates in the development cohort were 22.6

BACKGROUND:Freezing of gait (FOG) is a common gait disorder that often accompanies Parkinson's disease (PD). The current understanding of brain functional organization in FOG was built on the assumption that the functional connectivity (FC) of networks is static, but FC changes dynamically over time. We aimed to characterize the dynamic functional connectivity (DFC) in patients with FOG based on high temporal-resolution functional MRI (fMRI). METHODS:Eighty-seven PD patients, including 29 with FOG and 58 without FOG, and 32 healthy controls underwent resting-state fMRI. Spatial independent component analysis and a sliding-window approach were used to estimate DFC. RESULTS:Four patterns of structured FC 'states' were identified: a frequent and sparsely connected network (State I), a less frequent but highly synchronized network (State IV), and two states with opposite connecting directions between the visual network and the sensorimotor network (positively connected in State II, negatively connected in State III). Compared with the non-FOG group, patients with FOG spent significantly less time in State II and more time in State III. The longer dwell time in State III was correlated with more severe FOG symptoms. The fractional window of State III tended to correlate to visual-spatial and executive dysfunction in FOG. Moreover, fewer transitions between brain states and lower variability in local efficiency were observed in FOG, suggesting a relatively 'rigid' brain. CONCLUSIONS:This study highlights how visuomotor network dynamics are related to the presence and severity of FOG in PD patients, which provides new insights into understanding the pathophysiological mechanisms that underly FOG. © 2025 International Parkinson and Movement Disorder Society.

BACKGROUND AND OBJECTIVES:Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. METHODS:Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. RESULTS:We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. DISCUSSION:The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. CLASSIFICATION OF EVIDENCE:The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.

Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism.

BACKGROUND:Levodopa could induce orthostatic hypotension (OH) in Parkinson's disease (PD) patients. Accurate prediction of acute OH post levodopa (AOHPL) is important for rational drug use in PD patients. Here, we develop and validate a prediction model of AOHPL to facilitate physicians in identifying patients at higher probability of developing AOHPL.METHODS:The study involved 497 PD inpatients who underwent a levodopa challenge test (LCT) and the supine-to-standing test (STS) four times during LCT. Patients were divided into two groups based on whether OH occurred during levodopa effectiveness (AOHPL) or not (non-AOHPL). The dataset was randomly split into training (80%) and independent test data (20%). Several models were trained and compared for discrimination between AOHPL and non-AOHPL. Final model was evaluated on independent test data. Shapley additive explanations (SHAP) values were employed to reveal how variables explain specific predictions for given observations in the independent test data.RESULTS:We included 180 PD patients without AOHPL and 194 PD patients with AOHPL to develop and validate predictive models. Random Forest was selected as our final model as its leave-one-out cross validation performance [AUC_ROC 0.776, accuracy 73.6%, sensitivity 71.6%, specificity 75.7%] outperformed other models. The most crucial features in this predictive model were the maximal SBP drop and DBP drop of STS before medication (ΔSBP/ΔDBP). We achieved a prediction accuracy of 72% on independent test data. ΔSBP, ΔDBP, and standing mean artery pressure were the top three variables that contributed most to the predictions across all individual observations in the independent test data.CONCLUSIONS:The validated classifier could serve as a valuable tool for clinicians, offering the probability of a patient developing AOHPL at an early stage. This supports clinical decision-making, potentially enhancing the quality of life for PD patients.

目的 探讨高频重复经颅磁刺激结合肢体功能训练对缺血性脑卒中患者神经电生理及平衡功能的影响.方法 纳入2021-05—2022-05沧州市人民医院诊治的106例缺血性脑卒中患者,对照组患者采取常规西药治疗和肢体功能训练,观察组患者在对照组的基础上采取高频重复经颅磁刺激结合肢体功能训练,2组各53例,对比治疗前后2组患者的NIHSS评分、Barthel指数、平衡功能(摆幅指数、轨迹长度、外周面积)、神经电生理相关指标[运动诱发电位(MEP)和中枢运动传导时间(CMCT)].结果 治疗后观察组NIHSS评分[(9.25±0.75)分对(11.69±1.12)分]、摆幅指数(4.21±0.45对5.99±0.79)、轨迹长度[(58.62±8.52)cm对(69.77±11.52)cm]、外周面积[(10.05±1.32)mm2对(15.45±2.11)mm2]、CMCT[(7.25±1.12)ms对(8.78±1.69)ms]、MEP[(21.02±1.63)ms对(22.66±2.83)ms]低于对照组,而Barthel指数[(68.11±8.69)分对(60.02±7.02)分]高于对照组(P<0.05).结论 高频重复经颅磁刺激结合肢体功能训练效果更为显著,能更好地改善缺血性脑卒中患者平衡功能及神经电生理.

ObjectivesMagnetic susceptibility changes in brain MRI of Wilson's disease (WD) patients have been described in subcortical nuclei especially the basal ganglia. The objectives of this study were to investigate its relationship with other microstructural and functional alterations of the subcortical nuclei and the diagnostic utility of these MRI-related metrics. MethodsA total of 22 WD patients and 20 healthy controls (HCs) underwent 3.0T multimodal MRI scanning. Susceptibility, volume, diffusion microstructural indices and whole-brain functional connectivity of the putamen (PU), globus pallidus (GP), caudate nucleus (CN), and thalamus (TH) were analyzed. Receiver operating curve (ROC) was applied to evaluate the diagnostic value of the imaging data. Correlation analysis was performed to explore the connection between susceptibility change and microstructure and functional impairment of WD and screen for neuroimaging biomarkers of disease severity. ResultsWilson's disease patients demonstrated increased susceptibility in the PU, GP, and TH, and widespread atrophy and microstructural impairments in the PU, GP, CN, and TH. Functional connectivity decreased within the basal ganglia and increased between the PU and cortex. The ROC model showed higher diagnostic value of isotropic volume fraction (ISOVF, in the neurite orientation dispersion and density imaging model) compared with susceptibility. Severity of neurological symptoms was correlated with volume and ISOVF. Susceptibility was positively correlated with ISOVF in GP. ConclusionMicrostructural impairment of the basal ganglia is related to excessive metal accumulation in WD. Brain atrophy and microstructural impairments are useful neuroimaging biomarkers for the neurological impairment of WD.

Freezing of gait (FOG) is a disabling gait disorder common in advanced stage of Parkinson’s disease (PD). The gait performance of PD-FOG patients is closely linked with visual processing. Here, we aimed to investigate the structural and functional change of visual network in PD-FOG patients. Seventy-eight PD patients (25 with FOG, 53 without FOG) and 29 healthy controls (HCs) were included. All the participants underwent structural 3D T1-weighted magnetic resonance imaging (MRI) and resting state functional MRI scan. Our results demonstrated a significant decrease of right superior occipital gyrus gray matter density in PD-FOG relative to non-FOG (NFOG) patients and healthy controls (PD-FOG vs. PD-NFOG: 0.33 ± 0.04 vs. 0.37 ± 0.05, p = 0.005; PD-FOG vs. HC: 0.37 ± 0.05 vs. 0.39 ± 0.06, p = 0.002). Functional MRI revealed a significant decrease of connectivity between right superior occipital gyrus and right paracentral lobule in PD-FOG compared to PD-NFOG (p = 0.045). In addition, the connectivity strength was positively correlated with gray matter density of right superior occipital gyrus (r = 0.471, p = 0.027) and negatively associated with freezing of gait questionnaire (FOGQ) score (r = -0.562, p = 0.004). Our study suggests that the structural and functional impairment of visual-motor network might underlie the neural mechanism of FOG in PD.

目的:探讨帕金森病(PD)同时伴有体位性低血压(OH)及卧位高血压(SH)患者的血流动力学、心脑血管发病率及高危因素的特征,以及对运动症状和非运动症状的影响.方法:入组PD合并OH患者198例,伴有SH 123例(SH组),不伴有SH 75例(无SH组).记录所有入组患者临床信息、实验室检查结果,进行各项运动及非运动症状临床量表的评估.进行卧立位试验及急性左旋多巴冲击试验,记录血压变化.比较2组间的基本临床信息,心脑血管疾病及风险因素,冲击试验服药前后血压的变化及量表评分.结果:伴有OH的PD患者中SH的发生率为62.1％.2组间年龄、性别、病程、左旋多巴等效剂量无明显差异.与无SH组相比,SH组同型半胱氨酸略高(P<0.05),余各项心脑血管疾病高危因素差异无统计学意义(P>0.05).SH组MDS-UPDRSⅢ运动功能总分及姿势步态异常得分更高(P<0.05);SH组在服药前卧立位试验及急性左旋多巴冲击试验后收缩压下降最大差值较高(P<0.05),但出现临床显著OH的发生率较低(P<0.05);无SH的PD-OH患者出现临床显著OH的风险是有SH的PD-OH患者的近3倍(OR=2.991,P=0.002).认知评估中,SH组的MMSE量表回忆能力子项、定向力子项、MoCA量表总分、视空间与执行功能子项、定向力子项的评分均低于无SH组(均P<0.05),但2组间认知障碍的发生率差异无统计学意义(P>0.05).结论:PD患者中合并OH及SH的发生率高,尚未发现PD-OH伴有SH增加心脑血管疾病风险,且SH对显著OH起到一定保护作用.PD-OH伴SH患者需注意跌倒和痴呆风险.

目的:本研究旨在探讨早发型帕金森病(EOPD)患者发生体位性低血压(OH)特征、可能的危险因素,以及OH对运动症状和非运动症状的影响.方法:入组131例EOPD患者.记录患者基本信息,进行各项运动及非运动症状临床量表的评估.测量并记录患者在急性美多巴冲击试验服药前、服药1、2、3h后卧立位血压测试,MDS-UPDRSⅢ运动症状评分,计算左旋多巴改善率.根据是否出现OH分为OH组和非OH组,比较2组的基本临床数据、各量表评分,分析OH的可能危险因素.结果:入组的131例EOPD患者纳入OH组69例,纳入无OH组62例.总OH发生率为52.7％,服药前OH发生率为25.8％,服药后为39.7％(P<0.05).OH组患者病程更长,卧位高血压、剂末现象的发生率更高,左旋多巴最大改善率更高,姿势步态异常得分更高(均P<0.05);OH组患者的冻结步态问卷(FOGQ)、Cleveland便秘评分系统(CCS)和帕金森病日常生活质量问卷调查(PDQ-39)量表评分得分更高(均P<0.05);Logistic回归分析显示卧位高血压(OR=11.057,P=0.000)和便秘(OR=1.170,P=0.019)是EOPD患者发生OH的高危因素.结论:OH是EOPD患者的常见自主神经受损表现,服用左旋多巴药物后更易发生.左旋多巴药物可使EOPD患者卧立位收缩压下降.卧位高血压和便秘是EOPD患者发生OH的高危因素.建议对PD患者进行服用抗PD药物后1～2 h的卧立位试验,明确卧位高血压及OH情况,辅助专科医生制定合适的治疗方案.

Background The pathophysiology of depression in Parkinson’s disease (PD) is not fully understood. Studies based upon functional MRI (fMRI) showed the alterations in the blood-oxygen-level-dependent (BOLD) fluctuations in multiple brain regions pertaining to depression in PD. However, large variance was observed across previous studies. Therefore, we conducted a meta-analysis to quantitatively evaluate the results in previous publications and completed an independent regions-of-interests (ROIs)-based analysis using our own data to validate the results of the meta-analysis. Methods We searched PubMed, Embase, and Web of Science to identify fMRI studies in PD patients with depression. Using signed differential mapping (SDM) method, we performed a voxel-based meta-analysis. Then, a validation study by using multiscale entropy (MSE) in 28 PD patients with depression and 25 PD patients without depression was conducted. The fMRI scan was completed in anti-depression-medication-off state. The ROIs of the MSE analysis were the regions identified by the meta-analysis. Results A total of 126 PD patients with depression and 153 PD patients without depression were included in meta-analysis. It was observed that the resting-state activities within the posterior cingulate gyrus, supplementary motor area (SMA), and cerebellum were altered in depressed patients. Then, in the validation study, these regions were used as ROIs. PD patients with depression had significantly lower MSE of the BOLD fluctuations in these regions (posterior cingulate gyrus: F = 0.856, p = 0.049; SMA: F = 0.914, p = 0.039; cerebellum: F = 0.227, p = 0.043). Conclusion Our study revealed that the altered BOLD activity in cingulate, SMA, and cerebellum of the brain were pertaining to depression in PD.

Background Depression is one typical mood disorder in Parkinson’s disease (DPD). The alterations in the resting-state brain activities are believed to be associated with DPD. These resting-state activities are regulated by neurophysiological components over multiple temporal scales. The multiscale dynamics of these spontaneous fluctuations are thus complex, but not well-characterized. Objective To characterize the complexity of the spontaneous blood-oxygen-level-dependent (BOLD) of fMRI in DPD. We hypothesized that (1) compared to non-depression PD (NDPD), the complexity in DPD would be lower; and (2) the diminished complexity would be associated with lower connections/communications between brain regions. Methods Twenty-nine participants (10 in DPD and 19 in NDPD) who were naïve to medications completed a resting-sate functional MRI scan. The BOLD complexity within each voxel was calculated by using multiscale entropy (MSE). The complexity of the whole brain and each of the 90 regions parcellated following automated-anatomical-labeling template was then obtained by averaging voxel-wised complexity across all brain regions or within each region. The level of connections of regions with diminished complexity was measured by their own global functional connectivity (FC). Results As compared to NDPD patients, the whole-brain complexity and complexity in 18 regions were significantly lower in DPD ( F > 16.3, p < 0.0005). Particularly, in eight of the 18 regions, lower complexity was associated with lower global FC (Beta = 0.333 ~ 0.611, p = 0.000 ~ 0.030). Conclusion The results from this pilot study suggest that the resting-state BOLD complexity may provide critical knowledge into the pathology of DPD. Future studies are thus warranted to confirm the findings of this study.

Objective To investigate the risk factors of motor complications in female patients with Parkinson's disease (PD) and the correlation between the occurrence of motor complications and sex hormone levels. Methods According to the occurrence and types of motor complications, 103 female PD patients were divided into two groups: patients with or without the wearing-off phenomenon, patients with or without dyskinesia. Binary logistic regression analysis was performed respectively to screen for the risk factors of the wearing-off phenomenon and dyskinesia in female PD patients. Results Among 103 female PD patients, 44 (42.72%) had motor complications. Patients with the wearing-off phenomenon and patients with dyskinesia had higher prolactin levels than patients without the wearing-off phenomenon and patients without dyskinesia, respectively. However, the difference was no longer significant when the two groups were corrected for multiple comparisons (P < 0.0028). Multivariate analysis found that younger age at onset and higher Hoehn-Yahr (H&Y) stage were identified as independent risk factors for the wearing-off phenomenon and younger age of onset was an independent risk factor for dyskinesia in female PD patients (P < 0.05). Conclusion Female PD patients have a higher incidence of motor complications. Younger age of onset and higher H&Y stage were the risk factors of the wearing-off phenomenon, and younger onset age was the risk factor of dyskinesia in female PD patients. There may be a certain correlation between the occurrence of motor complications and sex hormone levels in female PD patients, which requires further verification.

目的 分析帕金森病伴发不同程度抑郁的影响因素.方法 选取2017年5月至2019年12月于首都医科大学附属北京天坛医院神经病学中心运动障碍性疾病科住院的帕金森病患者322例.根据汉密尔顿抑郁量表评分分为帕金森无抑郁组(130例)、帕金森轻度抑郁组(136例)、帕金森中度抑郁组(55例)、帕金森重度抑郁组(1例),由于帕金森重度抑郁组仅有1例患者入组,故将其划入帕金森中度抑郁组.对各组一般临床资料迸行比较,采用有序logistic回归分析帕金森病伴发不同程度抑郁的影响因素.结果 三组年龄分层比较,差异无统计学意义(P>0.05),三组病程、统一帕金森病评定量表Ⅲ部分评分、简易精神状态检查量表、H-Y分期、性别、起病形式比较,差异均有统计学意义(均P<0.05).有序logistic回归,结果显示,病程长(OR=1.067,95％CI:1.009～1.129,)、统一帕金森病评定量表Ⅲ部分评分高(OR=1.051,95％CI:1.026～1.076,)是帕金森病伴发不同程度抑郁的独立危险因素(P<0.05).结论 病程长和统一帕金森病评定量表Ⅲ部分评分高是帕金森病伴发不同程度抑郁的独立危险因素,临床上应对帕金森病抑郁患者尽早筛查及有效干预,改善患者运动症状,加强心理沟通.

目的 观察并分析帕金森病(PD)患者伴发焦虑、抑郁与认知功能障碍的相关影响因素.方法 选取2016年1月—10月在首都医科大学附属北京天坛医院神经病学中心运动障碍性疾病科住院确诊的PD患者92例,进行统一帕金森病评定量表(UPDRS)、改良的Hoehn-Yahr分期、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)、蒙特利尔认知评估量表(MoCA)评测.了解PD患者焦虑、抑郁及认知功能障碍的发生率,并对PD患者伴发焦虑、抑郁与认知功能障碍的相关危险因素进行分析讨论.结果 本组92例PD患者伴有焦虑的占77.17％.伴有抑郁的占69.57％.logistic回归结果显示,男性是PD患者伴焦虑的保护因素(OR=0.24,P=0.048),病程长是PD患者伴焦虑的危险因素(OR=1.36,P=0.019),男性(OR=0.22,P=0.013)和高龄(OR=0.95,P=0.041)是PD患者伴抑郁的保护因素,UPDRS评分高是PD患者伴抑郁的危险因素(OR=1.08,P=0.007).MoCA评分显示PD患者认知功能障碍的占78.26％.logistic回归结果显示,受教育年限长是PD患者认知功能障碍的保护因素(OR=0.70,P<0.003).结论 焦虑、抑郁、认知功能障碍均是PD患者常见的非运动症状,发生率高,易受年龄、性别、病程、受教育年限等因素影响,而非运动症状对患者的整体治疗效果及生活质量均有明显影响.

目的 分析帕金森病伴发焦虑、抑郁的影响因素.方法 选取2016年1—10月于首都医科大学附属北京天坛医院住院确诊的135例帕金森病患者.通过进行统一帕金森病评定量表(UPDRS),改良的Hoehn-Yahr分期,汉密尔顿焦虑量表,汉密尔顿抑郁量表的评测,统计分析本组患者焦虑、抑郁的发生率,同时分析患者性别、年龄、文化程度、起病类型、病程、家族史等对焦虑、抑郁的影响.结果 本组帕金森病患者中,焦虑发病率为53.3％(72/135),抑郁发病率为65.2％(88/135).单因素分析发现无焦虑与有焦虑患者在病程、UPDRS评分、躯体因子得分、精神因子得分和二项总分方面差异均有统计学意义(均P<0.01);无抑郁与有抑郁患者在病程、UPDRS评分、各因子得分和七项因子总分方面差异均有统计学意义(均P<0.01).Logistic回归分析结果显示病程是帕金森病患者伴发焦虑和抑郁的影响因素,差异均有统计学意义(焦虑比值比=3.432,95％置信区间:1.539～7.657,P=0.003;抑郁比值比=2.237,95％置信区间:1.017～4.922,P=0.045).结论 焦虑、抑郁均是帕金森病最常见的非运动症状,发生率高,帕金森病患者的病程、运动症状严重程度与焦虑、抑郁明显相关,而病程相关性更加密切.

目的 探讨帕金森病不同程度抑郁患者汉密尔顿抑郁量表(HAMD)各因子分的差异及变化趋势.方法 2017年6月至2018年3月,选择北京天坛医院运动障碍科住院的原发性帕金森病患者168例,收集患者性别、年龄、病程、HAMD评分、统一帕金森综合评分量表Ⅲ(UPDRSⅢ)评分、改良Hoehn-Yahr分级(H-Y分级)、简易精神状态检查(MMSE)评分、抗帕金森药物最大改善率等临床资料.根据HAMD评分分为无抑郁组(n=61)、轻度抑郁组(n=68)和中度抑郁组(n=39).比较各组HAMD各因子分差异.结果 除轻度抑郁组日夜变化外,各因子分均随抑郁程度加重而显著增加(F>10.546,P<0.001);焦虑/躯体化所占比例下降,认知障碍、阻滞所占比例增加.结论 随着抑郁程度加重,帕金森病患者抑郁结构发生变化,焦虑/躯体化比例下降,认知障碍、阻滞比例增加.

Neuroinflammation and inner immune dysfunction are increasingly accepted as important components of the etiopathogenesis of Parkinson’s disease (PD). According to emerging evidence, a7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel, plays an important role in inflammatory reactions and is also expressed on the surface of T cells. In particular, regulatory T cells (Tregs) are critical for the maintenance of immunological tolerance. In the present study, we investigated the roles of α7nAChR in inhibiting inflammation and maintaining the immune balance in rats with 6-hydroxydopamine (6-OHDA)-induced lesions and the possible mechanisms regulating the proportion of Tregsin vivo. Adult male Wistar rats (n= 90) were subjected to a unilateral injection of 6-OHDA into the left medial forebrain bundle, and PNU-282987, an α7nAChR agonist, was intraperitoneally injected 2 h prior to the induction of lesions by 6-OHDA and again at days 1, 7, and 13 postlesion. Behavioral tests and immunohistochemical staining to detect the expression of tyrosine hydroxylase (TH) in the bilateral substantial nigra (SN) were performed. Subsequently, CD4+ T lymphocytes and the expression of forkhead/winged helix transcription factor p3 (Foxp3, which is a marker of Treg cells) in the SN were also assessed using immunofluorescence staining. The expression of glial fibrillary acidic protein (GFAP) in the SN was determined by performing immunohistochemical staining. Additionally, the protein levels of α7nAChR, extracellular signal-regulated kinase (Erk) phosphorylated-Erk (p-Erk) and Foxp3 in the ventral midbrain were determined using Western blotting, and the relative expression of the TNF-α, IL-1β, and IL-10 mRNAs were detected using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). We found that PNU-282987 significantly improved the motor deficits induced by 6-OHDA, reduced the loss of TH in the SN, suppressed the overactivation of GFAP+ cells and expression of related inflammatory cytokines, and increased the number of Foxp3+ cells. In addition, we also showed that PNU-282987 significantly increased the protein expression of the a7nAchR, p-Erk, and Foxp3 in 6-OHDA-lesioned rats (p< 0.05). These results indicated that α7nAChR activation could exert an anti-inflammatory effect and participate in the process of modulating the immune balance during 6-OHDA-induced injury, potentially through the α7nAChR/p-Erk/Foxp3 signaling pathway.

Objective: To prospectively investigate the feasibility of shear wave elastography (SWE) as a new quantitative and objective method for evaluating the stiffness of the gastrocnemius medialis (GM) muscle during passive stretching in patients with Parkinson's disease (PD). Materials and Methods: SWE of the GM muscle was performed in 28 patients with PD [13 female and 15 male; mean age +/- standard deviation (SD): 63.0 +/- 8.5 years] and 12 healthy controls (5 female and 7 male; mean age +/- SD: 59.3 +/- 6.4 years) during passive ankle rotation. A Young's modulus-ankle angle curve was constructed. The GM slack angle and baseline Young's modulus (E-0) were compared between the markedly symptomatic and mildly symptomatic sides of patients with PD, and healthy controls. Additionally, the correlation between the GM slack angle and the severity of rigidity, and the observer reproducibility of SWE in determining the GM slack angle were evaluated. Results: The GM slack angle was smaller on both the markedly and mildly symptomatic sides in patients with PD than in healthy controls (mean +/- SD of -29.13 degrees +/- 3.79 degrees and -25.65 degrees +/- 3.39 degrees, respectively, vs. -21.22 degrees +/- 3.52 degrees; p < 0.001 and p = 0.006, respectively). Additionally, in patients with PD, the GM slack angle on the markedly symptomatic side was smaller than that on the mildly symptomatic side (p = 0.003). The E-0 value was lower on both the markedly and mildly symptomatic sides in patients with PD than in healthy controls (mean +/- SD of 10.11 +/- 2.85 kPa and 10.08 +/- 1.88 kPa, respectively, vs. 12.23 +/- 1.02 kPa; p = 0.012 and p < 0.001, respectively). However, no significant difference was found between the markedly and mildly symptomatic sides in patients with PD (p = 0.634). A negative linear relationship was observed between the GM slack angle and lower limb rigidity score on the markedly symptomatic side in patients with PD (r =-0.719; p < 0.001). The intraclass correlation coefficients for observer reproducibility of SWE ranged from 0.880 to 0.951. Conclusion: The slack angle determined by SWE may be a useful quantitative and reproducible method for evaluating muscle stiffness in patients with PD.

INTRODUCTION:Emerging evidence has suggested that cerebral small vessel disease (CSVD) may worsen motor function and cognition in Parkinson's disease (PD). However, the effect of CSVD on anxiety and depression in patients with PD remains unknown. This study explored the multi-dimensional effects of CSVD on PD outcomes (motor, cognition, and depression/anxiety).METHODS:This cross-sectional study included 431 patients with PD from Beijing Tiantan Hospital from May 2016 to August 2019. CSVD imaging markers were assessed and the four-point CSVD burden score was calculated. Motor function (MDS-UPDRS III score and subscores), cognition (MMSE, MoCA), anxiety (HAMA), and depression (HAMD) were assessed in these patients. The associations of CSVD with these outcomes were analyzed using the Spearman's correlation and multivariable linear regression models.RESULTS:Motor dysfunction, cognitive impairment, depression, and anxiety were significantly worse in patients with severe CSVD than in those with mild CSVD. Multivariable linear regression showed that CSVD burden was significantly associated with motor dysfunction (MDS-UPDRS III score and rigidity and bradykinesia subscores), impaired cognition, and high levels of depression and anxiety. A marginally significant association was observed between CSVD burden and gait/postural instability in multivariable regression analysis. Among the CSVD imaging markers, white matter hyperintensity, number of lacunes, and microbleeds were positively correlated with the severity of motor, cognitive, and emotional impairments, while the perivascular space in the basal ganglia was only correlated with cognitive impairments.CONCLUSIONS:Comorbid CSVD may affect multiple functional domains in patients with PD. Management of cerebrovascular disease may improve PD outcomes.