恩他卡朋对帕金森病大鼠的疗效

目的:观察恩他卡朋与左旋多巴/苄丝肼(美多芭)联用对帕金森病大鼠的治疗作用。方法:6-羟多巴(6-OHDA)毁损内侧前脑束(MFB)建立SD大鼠PD模型。成模大鼠腹腔注射不同剂量的美多芭与恩他卡朋,观测大鼠旋转圈数和持续时间。结果:单用恩他卡朋不能诱导PD大鼠旋转。采用美多芭(6.25、12.5mg·kg-1)和不同剂量的恩他卡朋(10、5、0mg·kg-1)联用的PD大鼠,旋转圈数明显增加、旋转时间也明显延长;恩他卡朋的剂量越大,旋转运动的持续时间越长,但出现旋转反应高峰的时间向后推迟。结论:足量的恩他卡朋可以加强左旋多巴的疗效,半量的恩他卡朋疗效欠佳。     

恩他卡朋添加治疗症状波动的帕金森病的自身对照临床研究

目的:探讨添加恩他卡朋治疗帕金森病患者剂末现象的疗效及安全性。方法:17例伴有剂末现象的帕金森病患者进行添加服用恩他卡朋前后对照。根据患者日记记录的“开”“关”时间、UPDRSⅡ/Ⅲ评分、左旋多巴每天剂量来综合评估。结果:12周观察显示恩他卡朋添加治疗帕金森病剂末现象能够显著延长“开”时间、缩短“关”时间、降低UPDRSⅡ/Ⅲ评分,没有发现严重不良事件及实验室的异常改变。结论:帕金森病伴有剂末现象患者添加恩他卡朋治疗有效、安全。     

恩他卡朋添加治疗对药效减退的帕金森病患者的疗效观察

目的 探讨恩他卡朋添加治疗对药效减退的帕金森病(PD)患者的疗效及安全性.方法 对4l例服用美多芭疗效减退的PD患者添加恩他卡朋治疗.在添加恩他卡朋治疗前和治疗后第1个月、2个月、3个月分别进行"统一PD评定量表(UPDRS)"评分及运动诱发电位(MEP)检查,比较各时间点美多芭的每日服用总量,并观察其不良反应.结果 添加恩他卡朋治疗后第1个月、2个月、3个月UPDRSⅡ和UPDRSⅢ评分均较添加治疗前明显下降,差异有统计学意义(均P＜0.05),美多芭每日服用总量也明显减少,与添加治疗前比较有统计学意义(均P＜0.05);MEP静息阈值(RMT)在治疗后第3个月明显升高(P＜0.05),潜伏期(CL)及皮质静息期(CSP)明显延长(均P＜0.05);无严重不良反应.结论 恩他卡朋添加治疗能有效改善美多芭药效减退PD患者的运动功能,且安全.     

恩他卡朋治疗帕金森病的新进展

儿茶酚-氧位-甲基转移酶（COMT）抑制剂是继左旋多巴（L-dopa）和多巴胺受体激动剂之后推入临床的治疗帕金森病（PD）的一类新药，可抑制外周COMT活性，延长L-dopa的半衰期和药时曲线下面积（AUC），能延长和增加L-dopa的生物利用度，但不影响达峰时间（Tmax）及达峰浓度（Cmax），是长期L-dopa治疗后出现疗效减退和开关现象等并发症时重要的辅助药物。恩他卡Eq（entacapone）被认为是较安全的COMT抑制剂。近几年的研究结果显示，在出现运动波动的PD患者中，恩他卡朋可减少L-dopa剂量，延长“开”期，明显缩短“关”期，并改善UPDRS的运动评分，提高生活质量。     

恩他卡朋治疗帕金森病剂末现象的临床观察

目的探讨恩他卡朋对PD患者剂末现象影响。方法选择40例出现剂末现象的PD患者进行相关资料分析,根据不同治疗方案分为普拉克索组和恩他卡朋组,入选患者治疗8周,分析恩他卡朋对PD剂末现象的疗效。结果恩他卡朋组疗效(90%)高于普拉克索组(60%),UPDRSⅡ评分低于普拉克索组,关期时间短于普拉克索组;恩他卡朋组异动症时间(2.3±0.6)h,低于普拉克索组的(2.7±1.0)h,差异均有统计学意义(P0.05)。结论恩他卡朋能够延长患者开期时间,缩短关期时间,改善剂末现象开期运动症状。     

恩他卡朋添加治疗症状波动的帕金森病的随机、双盲、安慰剂对照临床研究

目的:探讨添加恩他卡朋治疗PD患者剂末现象的疗效和安全性。方法:40例伴有剂末现象的PD患者进行随机、双盲、安慰剂、平行分组临床对照试验。根据患者日记记录的"开"、"关"期时间、UPDRS各部分评分、研究者总体评估变化量表和左旋多巴每日剂量来评定疗效。结果:恩他卡朋治疗12周时能显著延长"开"期时间、缩短"关"期时间,降低UPDRS评分,减少每日左旋多巴用量,研究者主观感觉65%的患者病情好转,与安慰剂组相比差异有显著意义。不良事件的发生率与安慰剂组相比差异无显著意义。结论:添加恩他卡朋治疗伴有剂末现象的PD患者安全、有效。     

恩他卡朋治疗帕金森病的疗效及对患者抗氧化应激反应的影响

目的探讨左旋多巴联合恩他卡朋治疗帕金森病(PD)的临床疗效及对患者抗氧化应激反应的影响。方法选取本院在2015年11月至2017年3月收治的PD患者84例,按照随机数字表法分为观察组和对照组,各42例,对照组给予左旋多巴口服治疗,观察组在此基础上联合恩他卡朋口服治疗,12w 1个疗程;观察两组患者临床疗效、统一PD评定定量表(UPDRS)、日常生活能力表(ADL)、非运动症状评价表(NMSS)评分及抗氧化应激反应的影响。结果 (1)观察组临床总有效率95.24%,对照组临床总有效率为80.95%,差异有统计学意义(χ~2=4.086,P=0.043);(2)治疗后2组患者UPDRS、ADL、NMSS评分明显低于治疗前,且观察组UPDRS、ADL、NMSS评分明显低于对照组,差异有统计学意义(P0.05);治疗后2组患者UPDRS-I评分比较差异无统计学意义(P0.05),观察组UPDRS-II、UPDRS-III评分明显低于对照组,差异有统计学意义(P0.05);(3)治疗后观察组IL-1β、IL-6、丙二醛(MDA)水平低于对照组,超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)水平高于对照组,差异有统计学意义(P0.05);(4)治疗期间观察组不良反应发生率为11.90%,对照组不良反应发生率为30.95%,差异有统计学意义(χ~2=4.525,P=0.033)。结论左旋多巴联合恩他卡朋治疗PD临床疗效显著,可明显提高患者运动功能和日常生活能力,改善患者清除自由基的能力,延缓氧化应激的进展,且不良反应少,有临床应用价值。     

左旋多巴联合恩他卡朋在帕金森病患者中的应用效果及安全性

目的 分析左旋多巴联合恩他卡朋在帕金森病患者中的应用效果及安全性。方法 选择2018—2019年在河南科技大学第二附属医院治疗的帕金森病患者78例,随机化原则分为2组,各39例。对照组给予左旋多巴治疗,观察组在对照组基础上加用恩他卡朋治疗,比较2组血清指标、帕金森评分量表-Ⅱ(UPDRS-Ⅱ)、UPDRS-Ⅲ评分及不良反应情况。结果 治疗后,观察组白细胞介素-1β(IL-1β)、IL-6、丙二醛(MDA)水平均明显低于对照组,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)水平较高,差异有统计学意义(P0.05);与对照组治疗后比较,观察组UPDRS-Ⅱ、UPDRS-Ⅲ评分均较低,差异有统计学意义(P0.05);观察组不良反应发生率(10.25%)与对照组(15.38%)比较,差异无统计学意义(P0.05)。结论 左旋多巴联合恩他卡朋治疗帕金森病效果较好,可有效改善患者血清水平,提高帕金森量表评分,且未增加不良反应发生率。     

恩他卡朋治疗帕金森病的多中心、随机、双盲、安慰剂对照临床研究

目的　研究恩他卡朋作为左旋多巴的辅助药物治疗帕金森病患者剂末现象的疗效和安全性。方法　帕金森病伴剂末现象患者 2 0 9例的 12周、多中心、随机、双盲、安慰剂、平行分组对照临床试验。根据患者日记记录的“开”和“关”期时间、统一帕金森病评定量表 (UPDRS)各部分评分、研究者总体评估变化量表和左旋多巴每日剂量评定疗效。结果　恩他卡朋治疗 12周时意向性治疗(ITT)人群“开”的时间自基线的 (7 4± 1 8)h/d延长至 (9 1± 2 5 )h/d ;“关”的时间自基线的 (6 8±2 2 )h/d缩短至 (5 2± 2 8)h/d ;UPDRS Ⅲ平均得分自基线的 36 7± 11 3减少至 30 0± 14 4 ;左旋多巴每日剂量 (mg/d)自基线的 5 89 2± 2 6 4 3减少至 4周的 5 6 1 5± 2 4 8 1;总体评估变化量表检查显示 6 9 9%的医生主观感觉到病情好转。与安慰剂组相比差异均有显著意义。常见的不良事件是多巴胺能反应 ,但是与安慰剂组相比差异均无显著意义。结论　恩他卡朋是有效而安全的治疗帕金森病伴剂末现象的辅助药物。     

美多芭联合恩他卡朋治疗对帕金森病患者血浆同型半胱氨酸水平的影响

目的探讨美多芭联合恩他卡朋治疗对帕金森病(PD)患者血浆同型半胱氨酸(Hcy)水平的影响。方法选取30名健康体检者作为对照组,20例未服用过左旋多巴(LD)制剂的PD患者为未服药组,63例美多芭治疗的PD患者为美多芭组,49例美多芭联合恩他卡朋治疗的PD患者为联合组。检测患者外周血中的LD稳态峰浓度并进行统一PD评分量表Ⅲ(UPDRSⅢ)的评分。检测所有研究对象的血浆Hcy水平。结果联合组患者LD血浆浓度明显高于美多芭组(P0.05)。美多芭组及联合组患者UPDRSⅢ评分均明显低于未服药组(均P0.05)。与对照组比较,未服药组、美多芭组及联合组患者血浆Hcy水平均明显升高(均P0.05);且美多芭组患者血浆Hcy水平明显高于未服药组及联合组(均P0.05)。结论美多芭联合恩他卡朋能显著降低PD患者血浆Hcy水平,对PD治疗有积极意义。     

Specific impairment of visual spatial covert attention mechanisms in Parkinson's disease

Visual deficits in early and high level processing nodes have been documented in Parkinson's disease (PD). Non-motor high level visual integration deficits in PD seem to have a cortical basis independently of a low level retinal contribution. It is however an open question whether sensory and visual attention deficits can be separated in PD. Here, we have explicitly separated visual and attentional disease related patterns of performance, by using bias free staircase procedures measuring psychophysical contrast sensitivity across visual space under covert attention conditions with distinct types of cues (valid, neutral and invalid). This further enabled the analysis of patterns of dorsal-ventral (up-down) and physiological inter-hemispheric asymmetries. We have found that under these carefully controlled covert attention conditions PD subjects show impaired psychophysical performance enhancement by valid attentional cues. Interestingly, PD patients also show paradoxically increased visual homogeneity of spatial performance profiles, suggesting flattening of high level modulation of spatial attention. Finally we have found impaired higher level attentional modulation of contrast sensitivity in the visual periphery, where mechanisms of covert attention are at higher demands.These findings demonstrate a specific loss of attentional mechanisms in PD and a pathological redistribution of spatial mechanisms of covert attention.     

Voice abnormalities and their relation with motor dysfunction in Parkinson's disease

Objective – To evaluate changes in perceptual and several acoustic parameters of voice in patients with Parkinson’s disease (PD) and to find out any relation with these parameters and motor components of Unified Parkinson’s Disease Rating Scale (UPDRS) in this patient group. Materials and methods – Twenty patients with PD (12 male and 8 female) were given objective and subjective voice tests and results were compared with those of 20 age‐ and sex‐matched controls. Patient's perceptual voice analysis was assessed using GRBAS scale including Grade of Dysphonia, Roughness, Breathiness, Asthenia and Strain items. Measurements for objective voice analysis, acoustic assessment tests including frequency perturbation [jitter (jitt)%], intensity perturbation [shimmer (shim)%], noise to harmonic ratio (NHR), fundamental frequency (F0), variability of fundamental frequency (vF0), diadochokinetic rate (DDK) and maximum phonation time (MPT) were used. An assessment of disability caused by voice disorders was scored according to the Voice Handicap Index (VHI) by the patient. All subjects also underwent videolaryngostroboscopic (VLS) examination. Motor components of UPDRS and acoustic parameters of voice were investigated for any correlations. Results – Compared with controls, roughness (P = 0.15), breathiness (P = 0.004) and asthenia (P = 0.031) values of males and breathiness (P = 0.043) and asthenia (P = 0.023) values of females were higher in patients with PD. Mean VHI scores of patients with PD were higher for both male and female patients (P = 0.0001 for male, P = 0.002 for female). The mean values for MPT (P = 0.02) and DDK (P = 0.025) were shorter in patients with PD. Jitt%, shim% and mean F0 values were similar among the two groups. But mean vF0 values were significantly higher in male patients with PD (P = 0.05). On VLS examination, non‐closure glottic pattern was found to be more frequent in the PD group. Conclusion – Although it is well known that pathophysiological changes in PD affect the voice, the present study found only few significant correlations between motor component of UPDRS and voice parameters.     

Recognition of emotional prosody is altered after subthalamic nucleus deep brain stimulation in Parkinson's disease

The recognition of facial emotions is impaired following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD). These changes have been linked to a disturbance in the STN's limbic territory, which is thought to be involved in emotional processing. This was confirmed by a recent PET study where these emotional modifications were correlated with changes in glucose metabolism in different brain regions, including the amygdala and the orbitofrontal regions that are well known for their involvement in emotional processing. Nevertheless, the question as to whether these emotional changes induced by STN DBS in PD are modality-specific has yet to be answered. The objective of this study was therefore to examine the effects of STN DBS in PD on the recognition of emotional prosody.An original emotional prosody paradigm was administered to twenty-one post-operative PD patients, twenty-one pre-operative PD patients and twenty-one matched controls. Results showed that both the pre- and post-operative groups differed from the healthy controls. There was also a significant difference between the pre and post groups. More specifically, an analysis of their continuous judgments revealed that the performance of the post-operative group compared with that of the other two groups was characterized by a systematic emotional bias whereby they perceived emotions more strongly.These results suggest that the impaired recognition of emotions may not be specific to the visual modality but may also be present when emotions are expressed through the human voice, implying the involvement of the STN in the brain network underlying the recognition of emotional prosody.     

Dilemma in Parkinson’s Treatment; Levodopa Monotherapy May be the Best Choice

IntroductionSeveral treatment strategies have been claimed for Parkinson's disease (PD) so far. However, there remains controversies over the best possible treatment. The aim of this study is to compare Levodopa monotherapy versus Pramipexole in combination with Levodopa L in patients with PD with regards to the efficacy and side effects.MethodsPatients being treated with levodopa alone and Pramipexole add-on therapy to Levodopa were enrolled in the study. Factors regarding efficacy and side effects were assessed and analyzed between both groups by appropriate tests.Results176 Patients were enrolled in the study. Results showed significant higher total MDS-UPDRS (worse total disease severity score) among patients being treated with Pramipexole add-on therapy which was particularly higher in parts 1 (Mentation, behavior and mood), 2 (Activity of daily living) and 3 (Motor examination) (P-values < 0.05). Psychosis global score with significantly higher frequency of hallucination and depression, statistically higher in combination therapy group compared to Levodopa monotherapy group (P-value < 0.05). Patients in the Pramipexole add-on group reported lower scores of Health-related quality of life (HRQoL) (P-value < 0.05). Significant correlation was between disease duration and psychosis score among Levodopa monotherapy group (P-value < 0.05).ConclusionsCompared to Levodopa monotherapy, Add-on therapy with Pramipexole shows less efficiency yet more side effects. This indicates that single administration of Levodopa still remains the best available treatment for Parkinson's disease.     

STN vs. Pallidal Stimulation in Parkinson Disease: Improvement With Experience and Better Patient Selection

Objectives. This is a prospective study to determine the outcomes of subthalamic nucleus (STN) vs. globus pallidus internus (GPi) deep brain stimulation (DBS) at our institution. Materials and Methods. We studied a total of 39 patients — 29 with STN and 10 with GPi DBS over a period of up to 6 years. Mean ages in the two groups were similar (59 and 60 years, respectively) and disease duration prior to implantation was similar (9.6 and 11.7 years, respectively). Unified Parkinson Disease Rating Scale (UPDRS) was recorded preoperatively and at follow‐up (at least at 6‐month intervals). Medications also were recorded, and each patient's levodopa equivalent units (LEU) were calculated. Results were analyzed using a paired Student's t‐test. Results. LEU reduced significantly (p < 0.05) in the STN group (5.7 to 3.7) but not the GPi group. Both targets significantly improved part 3 and part 4 scores of the UPDRS but GPi DBS did not improve part 2 scores (activities of daily living). STN DBS had much better outcome on the motor “off” scores of the UPDRS, whereas GPi only improved tremor. A comparison of the “earliest 10” and “most recent 10” STN patients showed a significant improvement in outcome in the most recent cases. Conclusions. In our group, STN was more effective for alleviating the symptoms of Parkinson disease, even in older patients with significant dyskinesias. Better patient selection and greater experience have led to more improvement in the more recent patients.     

Cardiac 123I-MIBG scintigraphy can assess the disease severity and phenotype of PD

Objective: Cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy studies of patients with idiopathic Parkinson's disease (PD) found decreased uptake. Whether this decrease is associated with clinical severity as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the phenotypes of PD has not been determined. Methods: Cardiac MIBG scintigraphy was performed on 34 patients with PD, 7 with multiple system atrophy (MSA), 4 with dementia with Lewy bodies (DLB), and 11 normal controls (NCs). Early and delayed MIBG heart/mediastinum (H/M) ratios were evaluated. PD severity was assessed by the Hoehn and Yahr (H–Y) stage and UPDRS. Patients were grouped in two phenotypes, tremor and postural instability gait difficulty (PIGD)-dominant groups based on UPDRS components. Associations between MIBG uptake and age at onset, UPDRS, and disease phenotype were analyzed in each group. Results: The early H/M ratio was significantly lower in patients with PD (1.45±0.207) than in the NCs (2.08±0.231), and in those with MSA (1.99±0.284), but not in those with DLB (1.29±0.0435). The delayed H/M ratio for PD (1.33±0.276) also was significantly decreased as compared to the ratios for NCs (2.17±0.286) and MSA (2.16±0.414) but not DLB (1.16±0.0949). The early H/M ratio was significantly correlated with both UPDRS score and age at onset, whereas the delayed H/M ratio only was significantly correlated with age at onset. The PIGD-dominant group had significantly higher UPDRS scores and lower H/M ratios than the tremor-dominant group. Conclusion: Cardiac MIBG scintigraphy can be used to differentiate PD from MSA and NC, and to determine the disease severity and phenotypes of PD.     

Pain due to osteoarthritis may impair the early outcome of deep brain stimulation in Parkinson's disease

Objective

To analyse postoperative pain due to osteoarthritis in patients with Parkinson's disease submitted to bilateral subthalamic nucleus stimulation.

Methods

Fifty-three parkinsonian patients (mean age, 59.9 ± 8.3 years; mean disease duration, 11.5 ± 4.2 years) referred for subthalamic nucleus stimulation were enrolled. Patients were prospectively asked to refer and describe any pain due to osteoarthritis they experienced at any time during the preoperative period and within the 6 postoperative months. Pre-existing pain due to osteoarthritis, therapeutic changes, parkinsonian motor disability and weight gain were assessed as explanatory factors for occurrence pain due to osteoarthritis after surgery.

Results

After surgery, thirty patients (57%) complained of pain due to osteoarthritis whereas all demonstrated great functional improvement. Twenty (67%) among the 30 experienced similar pain sensation before surgery. Symptoms occurred rapidly, between 4 and 26 postoperative weeks. Multiple stepwise regression analysis showed that pre-existing pain due to osteoarthritis, 6-month postoperative UPDRS III motor score and axial sub-score improvements in the off-drug/on-stimulation condition were accurate independent predictors of pain due to osteoarthritis after surgery (F(8, 41) = 2.20, p < 0.047).

Conclusion

Our results highlight the high prevalence of pain due to osteoarthritis arising shortly after subthalamic implantation. An accurate pain and osteo-articular assessment should be performed preoperatively in parkinsonian candidates for subthalamic nucleus stimulation in order to limit occurrence of complications in the early postoperative period.     

Levodopa-induced sleepiness in the Parkinson variant of multiple system atrophy.

Recent observations suggest that levodopa can induce irresistible sleep onset in multiple system atrophy (MSA). Therefore, we assessed sleepiness during a levodopa challenge in 17 MSA compared with 23 Parkinson's disease (PD) patients using the Stanford Sleepiness Scale (SSS). SSS scores during the levodopa challenge compared with baseline were significantly increased in the MSA compared with the PD group. These findings suggest greater potential of levodopa to induce sleepiness in MSA compared with PD, which may be related to differences in basal ganglia and brainstem pathology between the two disorders.