Melamed Eldad, Ziv Ilan, Djaldetti Ruth
Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Sackler School of Medicine, Tel Aviv University, Israel.
Mov Disord. 2007 Sep;22 Suppl 17:S379-84. doi: 10.1002/mds.21680.
After several years of smooth and stable response to levodopa, many patients develop motor fluctuations manifested by "on" and "off" phases. There are various subtypes of motor fluctuations that have different underlying mechanisms and therapeutical strategies. The "wearing off" phenomenon may be mainly due to the loss of stratial dopamine storage capacity and short levodopa half-life. The "delayed on" and "no-on" phenomena may be due to impaired absorption of oral levodopa. Management include various combined approaches, such as administration of small multiple daily doses of levodopa, controlled release, dispersible and soluble levodopa formulations, oral dermal- patch and subcutaneous dopamine agonists, MAO-B and COMT inhibitors, and surgical approaches, i.e., subthalamic deep brain stimulation. Future strategies may include gene therapy (e.g., intrastriatal GDNF) or transplantation of stem cells that can either produce and release dopamine or generate trophical factors.
在对左旋多巴进行数年平稳且稳定的反应后，许多患者会出现以“开”和“关”期为表现的运动波动。运动波动有多种亚型，其潜在机制和治疗策略各不相同。“剂末现象”可能主要归因于纹状体多巴胺储存能力的丧失以及左旋多巴半衰期较短。“延迟开”和“无开期”现象可能是由于口服左旋多巴吸收受损所致。治疗方法包括多种联合方案，如每日多次小剂量给予左旋多巴、控释、可分散和可溶的左旋多巴制剂、口服皮肤贴片和皮下多巴胺激动剂、单胺氧化酶B（MAO - B）和儿茶酚 - O - 甲基转移酶（COMT）抑制剂，以及手术方法，即丘脑底核深部脑刺激。未来的策略可能包括基因治疗（例如纹状体内胶质细胞源性神经营养因子）或移植能够产生和释放多巴胺或生成营养因子的干细胞。
