Metabolic correlates of levodopa response in Parkinson's disease
Metabolic correlates of levodopa response in Parkinson's disease
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DOI：
10.1212/wnl.57.11.2083
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发表时间：
2001-12-11
期刊：
影响因子：
9.9
通讯作者：
Eidelberg, D
中科院分区：
文献类型：
--
作者：
Feigin, A;Fukuda, M;Eidelberg, D
目的：探讨左旋多巴对帕金森病患者静息态脑代谢的影响。背景：在以前的研究中，作者使用[F-18]氟脱氧葡萄糖（FDG）和PET来量化PD的局部代谢异常。他们发现，这种疾病的特征是可重复的特定异常PD相关模式（PDRP）。在这项研究中，作者使用静脉注射左旋多巴来量化多巴胺替代对局部代谢和PDRP网络活性的影响。他们验证了多巴胺能治疗的临床反应与这些代谢变化相关的假设。研究方法：作者使用FDG/PET测量了7例PD患者的静息状态局部脑代谢（年龄，59.4 ± 4.2岁; Hoehn和Yahr分期，1.9 ± 0.7，平均值± SD）;受试者在停用左旋多巴和单独滴定恒速IV左旋多巴输注期间进行扫描。作者使用统计参数映射来确定这种干预发生的局部脑代谢的显著变化。他们还定量了左旋多巴诱导的PDRP表达变化。左旋多巴的代谢变化与通过统一PD评定量表（PDRS）运动评分变化测量的临床改善相关。结果如下：左旋多巴输注可改善GRS运动评分（30.6% ± 12.0%，p < 0.002），并显著降低左侧壳核、右侧丘脑、双侧小脑和左侧初级运动皮质的局部葡萄糖代谢（p < 0.001）。苍白球代谢的改变与临床上的改善有显著相关性（p < 0.01）。左旋多巴输注也导致PDRP表达显著下降（p = 0.01）。左旋多巴介导的PDRP活性的变化与临床上的ADRS运动评分的改善显著相关（r =-0.78，p < 0.04）。结论：左旋多巴降低PD患者壳核、丘脑和小脑的脑代谢。此外，左旋多巴减少PD相关的模式活动，网络抑制的程度与临床改善相关。帕金森病患者对多巴胺能治疗的反应可以通过调节皮质-纹状体-苍白球-丘脑皮质通路来确定。
Objective: To assess the effects of levodopa on resting-state brain metabolism in PD. Background: In previous studies the authors used [F-18] fluorodeoxyglucose (FDG) and PET to quantify regional metabolic abnormalities in PD. They found that this disease is characterized reproducibly by a specific abnormal PD-related pattern (PDRP). In this study the authors used IV levodopa infusion to quantify the effects of dopamine replacement on regional metabolism and PDRP network activity. They tested the hypothesis that clinical response to dopaminergic therapy correlates with these metabolic changes. Methods: The authors used FDG/PET to measure resting-state regional brain metabolism in seven patients with PD (age, 59.4 +/- 4.2 years; Hoehn and Yahr stage, 1.9 +/- 0.7, mean +/- SD); subjects were scanned both off levodopa and during an individually titrated constant-rate IV levodopa infusion. The authors used statistical parametric mapping to identify significant changes in regional brain metabolism that occurred with this intervention. They also quantified levodopa-induced changes in PDRP expression. Metabolic changes with levodopa correlated with clinical improvement as measured by changes in Unified PD Rating Scale (UPDRS) motor scores. Results: Levodopa infusion improved UPDRS motor ratings (30.6% +/- 12.0%, p < 0.002) and significantly decreased regional glucose metabolism in the left putamen, right thalamus, bilateral cerebellum, and left primary motor cortex (p < 0.001). Changes in pallidal metabolism correlated significantly with clinical improvement in UPDRS motor ratings (p < 0.01). Levodopa infusion also resulted in a significant (p = 0.01) decline in PDRP expression. The changes in PDRP activity mediated by levodopa correlated significantly with clinical improvement in UPDRS motor ratings (r = -0.78, p < 0.04). Conclusion: Levodopa reduces brain metabolism in the putamen, thalamus, and cerebellum in patients with PD. Additionally, levodopa reduces PD-related pattern activity, and the degree of network suppression correlates with clinical improvement. The response to dopaminergic therapy in Patients with PD may be determined by the modulation of cortico-striato-pallido-thalamocortical pathways.