Skalabrin E J, Laws E R, Bennett J P
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Mov Disord. 1998 Sep;13(5):775-81. doi: 10.1002/mds.870130504.
Stereotactic posteroventral pallidotomy (PVP) as a treatment for Parkinson's disease (PD) symptoms has been increasingly used in moderate-advanced disease. We examined the pharmacodynamic responses of PD patients to single oral levodopa doses and intravenous levodopa infusions before and after PVP surgery. Nine subjects with advanced PD received a single oral dose and ramped intravenous levodopa infusions before and 3-5 weeks after unilateral PVP. Timed motor tasks, Unified Parkinson's Disease Rating Scale (UPDRS) evaluations, and ordinal dyskinesia rating were performed after oral levodopa and during i.v. levodopa infusions. Serum prolactin and dopa levels were measured during the levodopa infusions. Overall timed motor but not motor UPDRS scores were improved after PVP in both the worst ("off") and best ("on") states. Contralateral but not ipsilateral limb dyskinesias were substantially reduced at all serum (dopa) levels after PVP. Ipsilateral and contralateral timed motor performance at low serum (dopa) levels was improved by PVP. Walking speeds at all serum (dopa) levels were not changed by PVP. Serum prolactin was reduced equally by increasing (dopa) preoperatively and postoperatively. PVP significantly and favorably altered oral and intravenous levodopa pharmacodynamics by improving bilateral limb motor function and contralateral dyskinesia but did not alter walking speed. PVP appears to widen significantly the therapeutic window for levodopa in PD.
立体定向后腹侧苍白球切开术（PVP）作为治疗帕金森病（PD）症状的方法，已越来越多地应用于中晚期疾病。我们研究了PD患者在PVP手术前后对单次口服左旋多巴剂量和静脉注射左旋多巴输注的药效学反应。9名晚期PD患者在单侧PVP术前和术后3 - 5周接受了单次口服剂量和递增静脉注射左旋多巴输注。在口服左旋多巴后以及静脉注射左旋多巴输注期间，进行了定时运动任务、统一帕金森病评定量表（UPDRS）评估和有序运动障碍评分。在左旋多巴输注期间测量血清催乳素和多巴水平。PVP术后，在最差（“关”）和最佳（“开”）状态下，整体定时运动评分而非运动UPDRS评分均得到改善。PVP术后，在所有血清（多巴）水平下，对侧而非同侧肢体运动障碍均显著减轻。在低血清（多巴）水平下，PVP改善了同侧和对侧的定时运动表现。PVP未改变所有血清（多巴）水平下的步行速度。术前和术后增加（多巴）剂量时，血清催乳素降低程度相同。PVP通过改善双侧肢体运动功能和对侧运动障碍，显著且有利地改变了口服和静脉注射左旋多巴的药效学，但未改变步行速度。PVP似乎显著拓宽了PD患者左旋多巴的治疗窗口。
