Spatiotemporal gait changes with use of an arm swing cueing device in people with Parkinson’s disease

Impaired arm swing is a common motor symptom of Parkinson’s disease (PD), and correlates with other gait impairments and increased risk of falls. Studies suggest that arm swing is not merely a passive consequence of trunk rotation during walking, but an active component of gait. Thus, techniques to enhance arm swing may improve gait characteristics. There is currently no portable device to measure arm swing and deliver immediate cues for larger movement. Here we test report pilot testing of such a device, ArmSense (patented), using a crossover repeated-measures design. Twelve people with PD walked in a video-recorded gym space at self-selected comfortable and fast speeds. After baseline, cues were given either visually using taped targets on the floor to increase step length or through vibrations at the wrist using ArmSense to increase arm swing amplitude. Uncued walking then followed, to assess retention. Subjects successfully reached cueing targets on >95% of steps. At a comfortable pace, step length increased during both visual cueing and ArmSense cueing. However, we observed increased medial-lateral trunk sway with visual cueing, possibly suggesting decreased gait stability. In contrast, no statistically significant changes in trunk sway were observed with ArmSense cues compared to baseline walking. At a fast pace, changes in gait parameters were less systematic. Even though ArmSense cues only specified changes in arm swing amplitude, we observed changes in multiple gait parameters, reflecting the active role arm swing plays in gait and suggesting a new therapeutic path to improve mobility in people with PD.     

帕金森病患者自动思维的特征及与社会支持状况的相关性研究

目的了解帕金森病患者自动思维特点和社会支持情况。方法采用自动思维问卷（ATQ）、汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）,对98例帕金森病患者进行问卷调查及相关因素分析。结果本组患者ATQ得分为（50.63±13.56）分,42例存在抑郁状态,其抑郁状态与负性自动思维呈正相关,与社会支持呈负相关。结论 帕金森病患者抑郁状态与负性自动思维相关,应该重视社会支持系统对改善帕金森病患者抑郁状态的作用,以提高患者生活质量。     

Impaired autophagy in microglia aggravates dopaminergic neurodegeneration by regulating NLRP3 inflammasome activation in experimental models of Parkinson’s disease

Microglia-mediated inflammation plays an important role in the pathogenesis of several neurodegenerative diseases including Parkinson’s disease (PD). Recently, autophagy has been linked to the regulation of the inflammatory response. However, the potential role of microglial autophagy in the context of PD pathology has not been characterized. In the present study, we investigated whether impaired microglial autophagy would affect dopaminergic neurodegeneration and neuroinflammation both in vivo and in vitro. In vitro, BV2 microglial cells were exposed to LPS in the presence or absence of autophagy-related gene 5 (Atg5) small interference RNA (Atg5-siRNA). For in vivo study, microglial Atg5 conditional knockout (Atg5^flox/flox; CX3CR1-Cre) mice and their wild-type littermates (Atg5^flox/flox) were intraperitoneally injected with MPTP to induce experimental PD model. Our results revealed that disruption of autophagy by Atg5-siRNA aggravated LPS-induced inflammatory responses in BV2 cells and caused greater apoptosis in SH-SY5Y cells treated with BV2 conditioned medium. In mice, impaired autophagy in microglia exacerbated dopaminergic neuron loss in response to MPTP. The mechanism by which the deficiency of microglial autophagy promoted neuroinflammation and dopaminergic neurodegeneration was related to the regulation of NLRP3 inflammasome activation. These findings demonstrate that impairing microglial autophagy aggravates pro-inflammatory responses to LPS and exacerbates MPTP-induced neurodegeneration by modulating NLRP3 inflammasome responses. We anticipate that enhancing microglial autophagy may be a promising new therapeutic strategy for PD.     

Impulsive conditions in Parkinson's disease: A pharmacosurveillance-supported list

Background“Impulse Control Disorders” are behavioral conditions (e.g., gambling, hypersexuality), which are increasingly reported as reactions to dopamine agonists in Parkinson's disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease focuses only on 6 behaviors. Nonetheless, impulsivity could affect the entire range of human practices. Because of their heterogeneity and undefined boundaries, it is not clear what conditions should be considered as Impulse Control Disorders. This results in poorly standardized scientific literature and underdiagnosis.ObjectiveWe aimed to create a comprehensive list of possible manifestations of drug-induced Impulse Control Disorders in Parkinson's disease and test it on pharmacosurveillance data.MethodsPubMed was used to identify reviews in English about Impulse Control Disorders in Parkinson's disease. Mentioned conditions were charted and translated to the lexicon of MedDRA, ICD-11, and DSM-5. The relevant MedDRA terms were used to test potential association with dopamine agonists on the FDA Adverse Event Reporting System.Results50 reviews published between 2001 and 2020 were identified. 66 conditions were collected as possible Impulse Control Disorders. Pathological gambling, shopping, eating and sexuality, dopamine dysregulation syndrome, hobbyism and punding were the most frequently mentioned, together with leisure activities, body-focused compulsivity, disruptive, impulse control and conduct disorders, and substance abuse. All these conditions were disproportionately reported with dopamine agonists, except for substance abuse.ConclusionsWe defined a potential extended list of ICDs, which, along with its conversion to international taxonomies, can support the identification of drug-induced conditions in pharmacovigilance archives, as well as monitoring processes in clinical practice.     

中西医结合治疗帕金森病的现状和研究进展

从中成药、古方化裁、自拟处方、针刺配合西药联合西药四个方面对近二十年治疗帕金森病的文献进行分析与总结。通过阐述中医与西医结合，充分体现了其对西医减毒增效，诊断辨证的互补优势。     

帕金森病患者睡眠障碍的多导睡眠图、多次睡眠潜伏期试验分析

目的 使用多导睡眠图、多次睡眠潜伏期试验客观分析帕金森病(PD)患者睡眠障碍特征.方法 对26例临床确诊的PD患者(PD组)和31名无明显中枢神经系统疾病的对照者(对照组)行全夜可移动视频多导睡眠监测及次日多次睡眠潜伏期试验,分析比较2组患者睡眠结构及平均睡眠潜伏期、入睡期快速眼球运动(REM)睡眠(SOREMPs)、睡眠发作(Sas)情况.结果 PD组N2睡眠期百分比(32.8%±13.1%)、REM睡眠期百分比(8.6%±5.3%)、平均睡眠潜伏期[(9.6±4.4)min]较对照组[40.2%±9.1%、11.5%±5.1%、(15.7±3.1)min]明显降低(t=-2.515、-2.054、-6.164,P＜0.05),PD组醒觉指数[(41.8±32.1)次/h]较对照组[(28.6±11.0)次/h]明显升高(t=2.151,P＜0.05).PD患者中出现日间过度瞌睡(EDS)7例(7/26,26.9%),明显高于对照组(1/31,3.2%;×2=4.764,P＜0.05).多元逐步线性回归分析显示校正睡眠效率、呼吸暂停低通气指数、醒觉指数,PD患者平均睡眠潜伏期的缩短与年龄(β=-0.328)、左旋多巴等效剂量(β=-0.008)的增加呈线性相关(t=-2.829、-2.352,均P＜0.05).PD组有5例(5/26,19.2%)出现SOREMPs,3例(11.5%)出现Sas,而对照组均无出现SOREMPs和Sas.结论 PD患者睡眠结构改变和EDS较常见,虽然PD患者中Sas不多见,但临床医师需提高警惕.     

Computer analysis of the tonic, phasic, and kinesthetic activity of pallidal discharges in parkinson patients

OBJECTIVE

Intraoperative analysis of microrecording data during pallidotomy often depends on subjective interpretation of the oscilloscope signal, especially during the analysis of phasic activity. The goals of this project were: 1) to develop an inexpensive system that allowed on-line, objective characterization of single-unit pallidal discharges, and 2) to have objective criteria to differentiate the internal part (GPi) from the external part (GPe) of the globus pallidus.

METHODS

A computer program was developed that allowed the analysis of firing rates (mean, median, and quartiles), spike count per unit time, and interspike interval (ISI) histograms with Chi-square statistical evaluation. Indices were developed that measured phasic activity, including burst index (BI) for the measurement of bursts, pause index (PI) for the measurement of pauses, and pause ratio (PR) for analysis of time spent in pauses. Single-unit activity of 152 GPe and 203 GPi cells in 47 Parkinson patients were digitized using the computer soundcard during pallidotomy and analyzed using this software.

RESULTS

GPe discharges had a mean firing rate = 42 Hz, BI = 0.81, PI = 0.21, and PR = 1.41. GPi had a mean firing rate = 81, BI = 1.61, PI = 0.04, and PR = 0.21. The PR was the best index that differentiated GPe from GPi, followed by PI, BI, and firing rates, in that order. Kinesthetic cells were recorded equally in GPe from GPi, and their responses to generalized movements were not significantly different.

CONCLUSION

(1) Signal analysis using the digitization process of a computer sound card and dedicated software is satisfactory for the objective “on-line” and “off-line” analysis of microrecordings (including phasic activity); (2) PI and PR are most helpful in differentiating neurons of GPi from those of GPe; (3) no single parameter can differentiate GPe from GPi activity in all cases; and (4) unlike the findings in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, GPe and GPi of Parkinson patients have similar prevalence of kinesthetic cells and similar responses to generalized somatotopic effects.