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十二指肠左旋多巴和阿扑吗啡输注治疗晚期帕金森病的运动并发症

[Duodenale levodopa and apomorphine infusion for motor complications in advanced Parkinson's disease].

作者信息

Antonini Angelo, Jost Wolfgang H

机构信息

Department of Neuroscience, University of Padua, Padua, Italy.

Parkinson-Klinik Ortenau, Wolfach.

出版信息

Fortschr Neurol Psychiatr. 2018 Sep;86(S 01):S5-S9. doi: 10.1055/a-0646-4164. Epub 2018 Aug 14.

Abstract

Development of motor fluctuations and dyskinesia characterizes the transition from the early to the advanced Parkinson stage. Current oral therapeutic strategies aim at increasing the number of levodopa administrations and extending its benefit by the association of enzyme blockers (MAO- and COMT-inhibitors) and dopamine agonists. However, as disease progresses, mobility becomes progressively dependent on levodopa absorption and plasma bioavailability, resulting in disabling motor complications. If patients continue to experience off time with functional impact on activities of daily living after best oral medication adjustments, implementation of infusion therapies with apomorphine or levodopa, and surgical techniques should be considered. Compared with pulsatile oral therapy implementation of apomorphine and levodopa infusion determines more continuous striatal dopamine receptors stimulation resulting in significant reduction of off-time and dyskinesia, particularly peak-dose. However, long-term experience with these treatments shows that motor complications are not abolished by continuous receptor stimulation suggesting that synaptic plasticity and connectivity changes are not easily reversed once they are established. Early intervention ideally would target patients as soon as motor complications begin rather than at late stage. Preliminary evidence from early deep brain stimulation or early pump treatment suggests that this is feasible but before it is implemented in clinical practice it would require a detailed cost-benefit analysis.

摘要

运动波动和异动症的出现标志着帕金森病从早期向晚期的转变。目前的口服治疗策略旨在增加左旋多巴的给药次数,并通过联合酶抑制剂(单胺氧化酶和儿茶酚-O-甲基转移酶抑制剂)和多巴胺激动剂来延长其疗效。然而,随着疾病进展,运动能力逐渐依赖于左旋多巴的吸收和血浆生物利用度,从而导致致残性运动并发症。如果患者在进行最佳口服药物调整后仍出现影响日常生活活动的“关”期,应考虑采用阿扑吗啡或左旋多巴输注疗法以及手术技术。与口服脉冲式治疗相比,阿扑吗啡和左旋多巴输注疗法能更持续地刺激纹状体多巴胺受体,从而显著减少“关”期和异动症,尤其是峰值剂量时的异动症。然而,这些治疗方法的长期经验表明,持续的受体刺激并不能消除运动并发症,这表明一旦突触可塑性和连接性发生改变,就不容易逆转。理想情况下,早期干预应在运动并发症一开始就针对患者,而不是在晚期。早期深部脑刺激或早期泵治疗的初步证据表明这是可行的,但在临床实践中实施之前,需要进行详细的成本效益分析。

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