Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

Bilateral Implantation of Centromedian‐Parafascicularis Complex and GPi: A New Combination of Unconventional Targets for Deep Brain Stimulation in Severe Parkinson Disease

Objectives. Traditional deep brain stimulation (DBS) at the subthalamic nucleus (STN) has proved to be efficacious on core Parkinsonian symptoms. However, very disabling l ‐dopa–induced abnormal involuntary movements (AIMs) and axial signs are slightly affected, suggesting that we target less conventional targets. Our candidates for DBS were the globus pallidus internus (GPi) plus the intralaminar thalamic complex (Pf or CM), given its extensive functional links with basal ganglia nuclei. Materials and Methods. The routine utilization of our innovative stereotactic apparatus allows us to implant, at the same time, both the CM‐Pf complex together with the GPi in six Parkinson disease patients. Both intraoperative and postoperative neurophysiologic assessments helped us recognize functional subregions while optimizing implantation of electrodes. Unified Parkinson disease rating scale (UPDRS) motor scores, AIMs, and freezing were carefully blindly evaluated for each condition. Results. A significant amelioration of UPDRS scores was achieved by simultaneous activation of both targets. CM‐Pf activation was only slightly effective in reducing rigidity and akinesia, but more efficacious on freezing. Not surprisingly, AIMs were peculiarly decreased by the activation of the permanent electro‐catheter in the posteroventral GPi. Conclusions. These findings confirm that, in selected patients, it is conceivable to target structures other than the conventional STN in order to maximize clinical benefit.     

氩氦刀的原理与应用中的优势和不足

氩氯刀是目前肿瘤治疗的新方法，其原理是通过组织细胞急冻急升温的方法实现的，比手术、化疗、放疗治疗方法简单，副作用小，费用低。但也存在冷冻后的问题，其适应证也受到限制。     

冷冻(断裂)复型电镜技术的应用

本文简单介绍冷冻断裂复型电镜技术在国内、外的概况,並阐明了该项新技术的独特作用和具体的操作步骤;在制作生物样品时所需的仪器设备和试剂的配制等内容。     

Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson''s disease

To assess the effect of levodopa on distinct freezing of gait (FOG) subtypes in patients with 'off' FOG. Nineteen patients (12 men, mean age 62.0 +/- 8.4 years) with Parkinson's disease and clinically significant FOG during 'off' states were videotaped whilst walking 130 m during 'off' and 'on' states. Three independent observers characterized the type, duration, and clinical manifestations and quantified FOG by analyzing the videotapes. Their combined mean scores were used for statistical analysis. The intra-class correlation coefficient assessed inter-observer reliability. Wilcoxon and Friedman tests evaluated differences in mean frequencies of FOG characteristics. During 'off' states, FOG was elicited by turns (63%), starts (23%), walking through narrow spaces (12%) and reaching destinations (9%). These respective values were only 14, 4, 2 and 1% during 'on' states (P < 0.011). Moving forward with very small steps and leg trembling in place were the most common manifestations of FOG; total akinesia was rare. Most FOG episodes took <10 s and tended to be shorter during 'on' states. Levodopa significantly decreased FOG frequency (P < 0.0001) and the number of episodes with akinesia (P < 0.001). Distinction amongst FOG subtypes enables evaluation of distinctive therapeutic response. Levodopa helps in reducing the frequency and duration of 'off'-related FOG.     

SD大鼠骨组织冷冻预处理温度的选择

目的 探讨冷冻预处理温度对骨组织超微结构的影响，为吻合血管同种异体骨保存移植提供依据。方法 以15％二甲基亚砜(DMSO)为低温保护剂，采用两步冷冻步骤，对SD大鼠骨组织进行-45，-50，-55，-60，-65和-70℃冷冻预处理，-196℃液氮保存1周，复温后光镜和透射电镜观察。结果 温度-55℃冷冻预处理和液氮保存的大鼠骨组织超微结构保持良好，其余温度组的骨细胞轻度水肿，线粒体肿胀，嵴破坏，细胞核有固缩现象，部分骨细胞变性明显，甚者细胞膜不连续。结论 骨组织冷冻预处理温度在-50～-60℃之间，-55℃是最佳温度值，可获得最大部分生物活性的骨组织。     

Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait.

The aim of this study was to examine the association between freezing of gait (FOG) and quality of life (QoL) in patients with Parkinson's disease (PD). PD patients (n = 118) completed the PDQ-39 (QoL) and FOG-Q questionnaires. Disease severity was assessed by the Hoehn and Yahr (H&Y) staging and the Unified Parkinson's Disease Rating Scale (UPDRS). The relations between those parameters were assessed using regression models. 66 men and 52 women (mean age 65.8 +/- 10.2 years, UPDRS total score 48.4 +/- 17.1, disease duration 8.5 +/- 5.8 years, H&Y stage 2.7 +/- 0.8) participated. FOG severity had a significant effect on QoL (P < 0.0015), accounting for disease severity assessed by UPDRS. Specifically, FOG severity was correlated with all the dimensions of the PDQ-39 except for stigma and social support, as follows: with mobility, bodily discomfort, activity of daily living (ADL) (P < 0.005 in all), with emotional, communication, and cognition (P < 0.05 in all). FOG severity (FOG-Q) was also found to affect a modified PDQ total score, without the mobility aspect (P = 0.0081). FOG should be viewed as a highly important symptom with regard to QoL of PD patients beyond its effect on gait and mobility. On the basis of the present results, special attention should be given to FOG in the treatment of patients with PD.     

断指冷冻伤后再植的临床经验

目的 探讨断指冷冻伤后再植术前的复温方式及术后注意事项。方法 对在低温环境下丢弃或保存不当而致指体冷冻伤的9例11指，采取自然复温(22～28℃)和温盐水复温(38～42℃)。对冷冻指体复温后，行再植手术。结果 再植术后完全存活6例，部分成活3例。结论 ①温盐水复温方式值得推荐；②指体冷冻伤不应一概列为断指再植禁忌证；③术后积极处理各种并发症是提高断指再植成活率的重要保证。     

Peculiarities of external respiration as a marker of activity of cell respiratory enzymes in rat brain

Rats with catatonic freezing are characterized by low motor and explorative activity in the open field test and specific pattern of external respiration, so-called strenuous respiration, which is accompanied by a higher activity of the respiratory enzymes succinate dehydrogenase and NADH dehydrogenase in the hippocampus and motor cortex. No dependencies on the brain structure and animal age are noted. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 138–140, August, 1997