Wessex Neurological Centre, Southampton General Hospital, Southampton, UK.
J Parkinsons Dis. 2012;2(3):189-98. doi: 10.3233/JPD-2012-120103.
Levodopa-induced dyskinesias (LID) belong to the most common dose-limiting adverse effects of levodopa therapy. "Peak-dose" LID occur with the maximum effect of medication, 'diphasic dyskinesias' have a "beginning- and end-of-dose" pattern, and the, "off-period dyskinesia" occur during off-periods, most frequently in the early mornings and are typically dystonic in nature. The majority of patients will have developed dyskinesias after 10 years of treatment, and about 40-50% after 5 years. Occurrence of LID appears to be related to dose and duration of treatment with levodopa and severity and duration of disease. In addition, patients with younger age of onset have been reported to have an earlier onset and higher rate of LID. The important aetiological role of non-physiological pulsatile stimulation of dopaminergic receptors is increasingly recognized and more continuous dopaminergic stimulation with the longer acting dopamine agonists has been shown to reduce and delay the onset of dyskinesias. LID may not have a significant effect on quality of life in patients with early disease or in very advanced disease stages. when often other problems arise, but in other patients they may be severely disabling. Treatment strategies to overcome LID include adjustment of timing, type and amount of dopaminergic medication, treatment with amantadine and, in treatment resistant cases, stereotactic surgery involving deep brain stimulation or lesioning procedures. A number of other pharmacological options are also being explored. Several methods for the assessment of LID are available to attempt accurate assessment of efficacy, although all of these have limitations, and further evidence on their utility if needed.
左旋多巴诱导的运动障碍(LID)属于左旋多巴治疗中最常见的剂量限制不良反应。“峰剂量”LID 发生在药物最大效果时,“双相运动障碍”具有“开始和结束剂量”模式,而“停药期运动障碍”发生在停药期间,最常见于清晨,通常是肌张力障碍。大多数患者在治疗 10 年后会出现运动障碍,约 50%在 5 年后。LID 的发生似乎与左旋多巴的剂量和治疗持续时间以及疾病的严重程度和持续时间有关。此外,发病年龄较早的患者报告称,LID 的发病较早,发生率较高。越来越多的人认识到非生理性脉冲式刺激多巴胺受体的重要病因作用,长效多巴胺激动剂更持续的多巴胺刺激已被证明可以减少和延迟运动障碍的发生。LID 可能不会对早期疾病或非常晚期疾病阶段的患者的生活质量产生重大影响。但在其他患者中,LID 可能会严重致残。克服 LID 的治疗策略包括调整多巴胺药物的时间、类型和剂量、使用金刚烷胺治疗,以及在治疗抵抗的情况下,采用立体定向手术,包括深部脑刺激或损毁术。目前还在探索其他一些药理学选择。有多种评估 LID 的方法可用于尝试准确评估疗效,尽管所有这些方法都存在局限性,如果需要,还需要进一步证明其有效性。