Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients
Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients
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DOI：
10.3389/fneur.2019.01217
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发表时间：
2019-11-21
影响因子：
3.4
通讯作者：
Ko, Ji Hyun
中科院分区：
文献类型：
--
作者：
Aljuaid, Maram;Booth, Samuel;Ko, Ji Hyun
背景：帕金森病（PD）的最前沿治疗是左旋多巴。当患者用左旋多巴治疗时，脑血流量增加，而包括壳核在内的关键皮质下区域的脑代谢率降低。这种现象在左旋多巴诱导的运动障碍（LID）患者中尤其明显。方法：为了研究临床确定的抗帕金森病药物的作用，10名PD患者（5名LID患者和5名无LID患者）在开和关药物时均使用FDG-PET（葡萄糖代谢探针）和灌注MRI（脑血流探针）进行扫描。患者还进行了静息状态功能磁共振成像检测多巴胺介导的皮质-纹状体连接的变化。通过比较FDG-PET和灌注MRI数据来量化血流-葡萄糖代谢分离的程度。结果如下：在壳核中发现了显著的相互作用效应（成像方式x药物;血流-葡萄糖代谢分离）（p = 0.023）。事后分析显示，抗帕金森病药物治疗一贯正常化的病理高代谢状态的壳核，而混合效应，观察到脑血流的变化。与没有LID的患者相比，这种分离在LID患者中尤其突出。与之前的研究不同，在评估皮质-纹状体功能连接时未观察到这种分化。结论：我们证实了临床确定的抗帕金森病药物治疗后，FDG-PET和灌注MRI之间的纹状体神经血管分离。我们进一步提出了一种新的分析方法，仅使用ON条件扫描来量化壳核中的解离程度，壳核-丘脑高灌注/低代谢指数（PHI），其可能有潜力用作LID的生物标志物（正确分类10例患者中的8例）。为了更广泛地使用PHI，需要进行更大规模的验证研究。
Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID). Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data. Results: A significant interaction effect (imaging modality x medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed. Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.