Progression from Unilateral to Bilateral Parkinsonism in Early Parkinson Disease: Implication of Mesocortical Dopamine Dysfunction by PET
Progression from Unilateral to Bilateral Parkinsonism in Early Parkinson Disease: Implication of Mesocortical Dopamine Dysfunction by PET
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DOI：
10.2967/jnumed.110.076802
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发表时间：
2010-08-01
影响因子：
9.3
通讯作者：
Ouchi, Yasuomi
中科院分区：
文献类型：
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作者：
Yagi, Shunsuke;Yoshikawa, Etsuji;Ouchi, Yasuomi
目前尚不清楚为什么一些单侧帕金森综合征的早期帕金森病 (PD) 患者在诊断后不久就会发展为双侧帕金森综合征，因为 Hoehn 和 Yahr (HY) 1 期患者和其他患者长期保持稳定。在这里，我们使用 PET 和多巴胺转运蛋白放射性示踪剂 C-11-2-B-甲氧基-3B-(4-氟苯基)托烷 (C-11-CFT) 检查了大脑多巴胺能系统的体内变化，以阐明早期转化者多巴胺系统的病理生理学特征。方法：12 名患有 HY 1 期疾病的初治 PD 患者和 8 名年龄匹配的健康受试者参与了本研究。根据统一帕金森病评定量表，每月对他们的帕金森病进行临床评估，直到他们的 HY 1 期（单侧帕金森病）疾病转变为 2 期（双侧帕金森病）疾病。后续研究的终点是转换时间。感兴趣区域分析用于检查中皮质（伏核、尾状核、眶额皮质）和黑质纹状体（壳核）多巴胺投射区域中的 C-11-CFT 结合。在 PD 组内对这些 PET 数据和临床参数进行了多重回归分析。结果：组间比较显示，无论转换持续时间如何，所有临床诊断为 HY 1 期的 PD 患者双侧纹状体 C-11-CFT 结合显着减少（受影响，-46%；未受影响，-35%）。回归分析显示健侧伏隔核和眶额皮层C-11-CFT结合水平与转换间隔呈显着正相关。这种正相关表明，看似完好一侧的中皮质多巴胺系统功能障碍越严重，帕金森病向完好一侧发展的速度就越快（双侧帕金森病）。结论：即使在 HY 1 期 PD 患者中，双侧纹状体 C-11-CFT 结合减少的发现证实多巴胺系统的分子变化先于临床表型，表明 PET 在检测疾病早期异常方面具有优势。在诊断为 HY 1 期帕金森病后不久，帕金森病就向未受影响的一侧扩散，可能与中皮质多巴胺功能障碍的程度有关。
It is still unclear why some early Parkinson disease (PD) patients with unilateral parkinsonism develop bilateral parkinsonism soon after the diagnosis is made as Hoehn and Yahr (HY) stage 1 and others remain stable for a long time. Here, we examined in vivo changes in the brain dopaminergic system using PET with a dopamine transporter radiotracer, C-11-2-B-carbomethoxy- 3B-(4-fluorophenyl) tropane (C-11-CFT), to elucidate the pathophysiologic characteristics of the dopamine system in early converters. Methods: Twelve drug-naive PD patients with HY stage 1 disease and 8 age-matched healthy subjects participated in this study. Clinical evaluation of their parkinsonism was performed monthly until their HY stage 1 (unilateral parkinsonism) disease had become stage 2 (bilateral parkinsonism) disease according to the Unified Parkinson Disease Rating Scale. The endpoint of the follow-up study was the time of the conversion. Region-of-interest analysis was used to examine C-11-CFT binding in the mesocortical (nucleus accumbens, caudate, orbitofrontal cortex) and nigrostriatal (putamen) dopamine projection regions. Multiregression analyses between these PET data and clinical parameters were performed within the PD group. Results: Between-group comparisons showed that, irrespective of the duration of conversion, all PD patients clinically diagnosed at HY stage 1 had a significant reduction in C-11-CFT binding in the bilateral striatum (affected, -46%; unaffected, -35%). Regression analysis showed that the level of C-11-CFT binding in the nucleus accumbens and orbitofrontal cortex on the unaffected side was significantly positively correlated with the conversion interval. This positive correlation indicates that the more severe a dysfunction presents in the mesocortical dopamine system on the seemingly intact side, the more rapidly the parkinsonism proceeds to the intact side (bilateral parkinsonism). Conclusion: The finding of bilateral reduction in the striatal C-11-CFT binding even in HY stage 1 PD patients confirms that molecular changes in the dopamine system precede clinical phenotype, suggesting an advantage of PET for detecting an early abnormality of the disease. The spread of parkinsonism to the unaffected side soon after the diagnosis of HY stage 1 PD may be related to the degree of mesocortical dopamine dysfunction.