Comparison of dyskinesia profiles after L-DOPA dose challenges with or without dopamine agonist coadministration
Comparison of dyskinesia profiles after L-DOPA dose challenges with or without dopamine agonist coadministration
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DOI：
10.1016/j.neuropharm.2023.109630
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发表时间：
2023-06-23
影响因子：
4.7
通讯作者：
Cenci, M. Angela
中科院分区：
文献类型：
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作者：
Grigoriou, Sotirios;Espa, Elena;Cenci, M. Angela
许多患有帕金森病（PD）的患者经历左旋多巴诱导的运动障碍（LID），接受多巴胺激动剂的辅助治疗，其对LID的功能影响尚不清楚。我们开始比较L-DOPA剂量挑战（包括或不包括多巴胺受体激动剂罗匹尼罗）后异常不自主运动（AIM）的时间和地形图。25例PD和运动障碍病史的患者顺序给予单独的左旋多巴（通常早晨剂量的150%）或随机顺序的左旋多巴和罗匹尼罗的等效组合。在给药前和给药后每30分钟由两名盲法评定者使用临床运动障碍评定量表（CDRS）评估不自主运动。在测试过程中，将传感器记录智能手机固定在患者的腹部。两名评估者的CDRS评分高度可靠，与加速度计数据训练的运动过度存在和严重程度模型一致。治疗之间的运动障碍时间曲线不同，因为与单独使用左旋多巴相比，左旋多巴-罗匹尼罗组合导致AIM的峰值严重程度较低，但持续时间较长。在AIMs曲线的峰值（60-120分钟），LDOPA诱导显著更高的总运动过度评分，而在结束阶段（240-270分钟），在L-DOPA-罗匹尼罗组合后，运动过度和肌张力障碍倾向于更严重（尽管仅对于项目，手臂肌张力障碍达到统计学显著性）。我们的研究结果为在抗运动障碍治疗的早期临床评价中引入L-DOPA-罗匹尼罗联合激发试验铺平了道路。此外，我们提出了一种机器学习方法来预测CDRS运动过度的严重程度，使用加速度计数据。
Many patients with Parkinson's disease (PD) experiencing L-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after L-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either L-DOPA alone (150% of usual morning dose) or an equipotent combination of L-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone was secured to the patients' abdomen during the test sessions. The two raters' CDRS scores were highly reliable and concordant with models of hyperkinesia presence and severity trained on accelerometer data. The dyskinesia time curves differed between treatments as the L-DOPA-ropinirole combination resulted in lower peak severity but longer duration of the AIMs compared with L-DOPA alone. At the peak of the AIMs curve (60-120 min), LDOPA induced a significantly higher total hyperkinesia score, whereas in the end phase (240-270 min), both hyperkinesia and dystonia tended to be more severe after the L-DOPA-ropinirole combination (though reaching statistical significance only for the item, arm dystonia). Our results pave the way for the introduction of a combined L-DOPA-ropinirole challenge test in the early clinical evaluation of antidyskinetic treatments. Furthermore, we propose a machine-learning method to predict CDRS hyperkinesia severity using accelerometer data.