Coordination of Manipulative Forces in Parkinson''s Disease

The coordination of manipulative forces was examined in 10 subjects with Parkinson's disease (PD) both OFF and ON medication while they grasped and lifted a small object using the precision grip. The development of grip (squeeze) force and load (vertical lifting) force was recorded and compared to a group of age-matched control subjects. Subjects with PD often exhibited a prolonged delay between the first digit contact with the object and initiation of the lifting drive. These subjects also exhibited stepwise increases in force, with regular oscillations in the force rates. However, once the vertical drive began, the main increase in grip and load force generally was in parallel and most other temporal aspects of the force coordination were similar to those of the control subjects. The extent to which the movement initiation was delayed was related to the stage of the disease, and most subjects improved ON medication. When the object was held in the air, subjects with PD used a grip force level which was similar to that of the control subjects, and all subjects adjusted their grip force according to the surface texture. Furthermore, they exhibited proper reflexive corrections to sudden changes in load (object perturbations), suggesting intact sensorimotor integration. We conclude that the most obvious impairments in the coordination of this task were delayed initiation of the grip–lift sequence and tremor-like oscillations superimposed on otherwise normal force.     

Reaction Time Deficits and Parkinson''s Disease

GAUNTLETT-GILBERT, J. AND V.J. BROWN. Reaction time deficits and Parkinson's disease. NEUROSCI BIOBEHAV REV 22 (6) 865–881, 1998.—Controversy surrounds the existence and nature of reaction time deficits in Parkinson's disease. Three areas of research are reviewed: the use of precues to speed movement (motor preprogramming), the effects of medication on reaction time, and simple reaction times. No evidence is found for a motor preprogramming deficit, and the presence of a parkinsonian reaction time deficit after medication withdrawal is found to be dependent upon experimental design and the withdrawal method used. Parkinson's disease is found to cause a consistent deficit in simple reaction time. A quantitative analysis of past studies reveals that a parkinsonian reaction time deficit is more likely to be present in tasks that controls can perform with a fast reaction time. This relationship between deficit and control group reaction time applies to choice, but not simple, reaction time tasks. Many studies compare patient and control choice reaction times across experimental conditions that cause control reaction time to vary. The authors of these studies should consider whether their results can be explained in terms of the simple relationship between patient reaction time deficit and control reaction time before drawing more complex conclusions from their data.     

胰岛素受体后信号传导与帕金森病

目前认为胰岛素不仅是单纯的内分泌激素，至少在中枢神经系统中还是一种神经营养因子，能调节包括多巴胺能神经元在内的多种神经系统的功能。胰岛素、其受体和受体后偶联下游系统构成了胰岛素信号通路，调节神经细胞的生长、增殖和防止其凋亡。其抗凋亡机制主要与胰岛素及胰岛素受体（IR）结合后，导致IR的自身磷酸化，激活磷脂酰肌醇-3-激酶和蛋白激酶B传导通路有关。     

Anticipatory Control of Manipulative Forces in Parkinson''s Disease

In a previous study we found that subjects with Parkinson's disease (PD) had an impaired capability to initiate and sequence successive movement phases during lifts of small objects using the precision grip, and that they had regular oscillations in the force rates. The present study examined whether these subjects could use anticipatory control, in which the force output is scaled prior to liftoff, based on the object's physical properties. Subjects lifted an instrumented test object between the tips of the thumb and index finger while the employed grip force, load force (vertical lifting force), and corresponding time derivatives were recorded. In the first experiment, the object's weight was varied to assess its influence on the isometric force output. Subjects with PD scaled the isometric force increase according to the object's weight. In another experiment, the weight changed in proportion to the volume to determine whether subjects could make associative transformations between visual size information and the weight of the object. Subjects with PD still scaled the forces toward the expected weight, proportional to the volume of the object. Finally, programmed adjustments in force to sudden self-induced load changes were examined while subjects dropped a disk with one hand into a plate attached to the bottom of the grip instrument, held with the other hand. Subjects with PD had preparatory increases in the grip force prior to the disk contact, which matched the change in load, though may have been more dependent on visual feedback. We conclude that subjects with PD are capable of using anticipatory control to parameterize the isometric force output during a familiar lifting task.     

Task-Dependent Deficits during Object Release in Parkinson''s Disease

The present study examined fingertip forces during the replacement and release of an instrumented object on a table in eight subjects with Parkinson's disease (PD) both off and on medication and eight age-matched control subjects. Subjects performed the task at (1) their preferred speeds and (2) as fast as possible. During performance of the task at preferred speed, the duration of object replacement, the rate, and duration of force decrease following table contact for PD subjects were similar to that observed in the control subjects and were unaffected by medication. In contrast, the rates were significantly lower and durations longer in the PD subjects when the task was performed as fast as possible irrespective of medication. A similar result was obtained when subjects were asked to release their pinch force from predefined force levels while the object was fixed to the table surface. These results emphasize the importance of considering task requirements in order to delineate the specific task parameters associated with the movement impairments in Parkinson's disease.     

Hyperechogenicity of the Substantia Nigra in Parkinson''s Disease

Substantia nigra (SN) was assessed by transcranial sonography (TCS) in 47 Parkinson's disease (PD) patients and in 39 healthy volunteers. A semiquantitative echogenicity scale was created with arbitrary values ranging from 1 to 5, zones with grade >or=3 and larger than 0.19 cm(2) were recorded as hyperechogenic SN. TCS examination of SN as a diagnostic test for PD in our study showed 87.2% sensitivity and 94.9% specificity.     

Diorthosubstituted Polychlorinated Biphenyls in Caudate Nucleus in Parkinson''s Disease

As it had previously been demonstrated that there were reduced brain dopamine concentrations in monkeys who had been given polychlorinated biphenyls (PCBs) chronically, we hypothesized that organochlorine compounds in general, and PCBs in particular, might be important in the pathogenesis of Parkinson's disease (PD). In a study of caudate nucleus obtained post mortem from patients with Parkinson's disease and from controls, there were significantly higher concentrations of the organochlorine insecticide dieldrin and the PCB congener 153 in the PD tissue. DDE, PCB congener 180, and total PCBs (matched with a commercial preparation) also tended to be higher in Parkinson's disease tissue. We think that this is important preliminary evidence that diorthosubstituted PCBs may contribute to the pathogenesis of Parkinson's disease, and a greater presence of organochlorine insecticides in the PD tissue suggests that this may be in part the explanation for the association between PD and rural living.     

司来吉兰治疗帕金森病新进展

司来吉兰是一种选择性不可逆的单胺氧化酶B抑制剂，目前不仅作为帕金森病（PD）早期的一线治疗药物，而且作为PD晚期的辅助治疗药物被广泛运用。司来吉兰治疗PD具有独特的优势，能够改善早期PD的症状和体征，延缓其进程，保护神经元；对晚期PD辅助左旋多巴治疗也有较好的疗效。但其也有不良反应。本文介绍司来吉兰在临床应用的进展。     

居住环境和工作环境因素对帕金森病的作用

目的 研究环境因素对帕金森病发病的影响。方法 采用病例对照的研究方法,研究变量包括居住环境,工作环境及饮用水等。结果 病例组44例,对照组36例。在众多的环境暴露因素中,病例组中喝井水的比例(50％)和接触过化肥的比例(18.1％)高于对照组,且有显著性差异,分别是x~2=5.15,P=0.02和x~2=5.15,P=0.03,其他的环境暴露如农药的接触,种农作物,合成树脂的接触以及居住在农村等病例组与对照组之间无显著性差异。研究了居住在农村和用井水的相互作用发现,居住环境和饮井水之间无交互作用,即x~2=1.48,P=0.22和x~2=1.11,P=0.29,喝井水与PD的关系是相对独立的。以未曾饮用井水作为参照,饮用时间<9年是其4.1倍(OR=4.1,P<0.01),饮用时间10～20年时OR=1.13,饮用时间>20年OR=1.17,随着饮用时间的延长,这种关系有所减弱,但危险性仍高于未曾饮用井水者。结论 环境因素中井水的饮用与PD的发病可能有关。     

α-突触核蛋白及其在帕金森病发病中的可能机制

α-突触核蛋白（AS）足Lewy体的重要组成成分。AS基因定位于第4号染色体，其突变型与常染色体显性遗传性帕金森病（PD）的发病密切相关。在PD中，AS出现了折叠错误和排列混乱。AS的聚集能力，特别是在氧化应激状态下，被认为是其病理机制的核心，AS的异常聚集和降解障碍导致蛋白酶的抑制和多巴胺能神经元的死亡。因此，AS致病形式对认识PD的发生有重要意义。     

灵芝孢子粉对帕金森病黑质神经细胞caspase-3影响的实验研究

目的：研究灵芝孢子对帕金森病（PD）大鼠模型黑质神经细胞caspase-3的影响。方法：SD大鼠随机分为3组，PD组：经立体定向向黑质部注入6-羟多巴（6-OHDA）；灵芝孢子组：先用灵芝孢子粉灌胃3d，立体定向注入6-OHDA，继续灌胃4周；正常对照组：立体定向注入抗坏血酸生理盐水。实验大鼠4周处死后用免疫组化、原位杂交检测caspase-3及其mRNA的阳性细胞数，Western blot检测caspase-3的半定量。结果：灵芝孢子组术侧黑质caspase-3及其mRNA阳性神经元数量较PD组明显降低，Western blot显示caspase-3蛋白较PD组显著降低。结论：灵芝孢子能够降低caspase-3的表达，对PD大鼠有脑保护作用。