Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy
Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy
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DOI：
10.1016/j.parkreldis.2008.01.010
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发表时间：
2008-12-01
影响因子：
4.1
通讯作者：
Eldadah, Basil A.
中科院分区：
文献类型：
--
作者：
Goldstein, David S.;Holmes, Courtney;Eldadah, Basil A.
目的：生物标志物在帕金森病（PD）等神经退行性疾病的诊断和治疗试验中越来越重要。本研究比较了神经影像学、神经化学和嗅觉潜在生物标志物，以检测中枢多巴胺（DA）缺乏并区分PD和多系统萎缩（MSA）。在77例PD、57例MSA和87例对照受试者中，壳核（PUT）、尾状核（CAU）、枕叶皮质（OCC）在6-[F-18]氟多巴注射后2小时测量黑质（SN），在6-[F-18]氟多巴注射后8分钟测量隔心肌放射性，测定CSF和血浆儿茶酚，或测试嗅觉（宾夕法尼亚大学嗅觉鉴定试验（UPSIT））。受试者工作特征曲线的构建，显示在给定specificity.Results测试灵敏度：6-[F-18]氟多巴衍生放射性的PUT：OCC，CAU：OCC，SN：OCC比率在PD和MSA中同样低（与对照组相比，p < 0.0001，p < 0.0001，p = 0.003）; CSF二羟苯乙酸（DOPAC）和DOPA浓度也是如此（p < 0.0001，每个）。PD组的PUT：SN和PUT：CAU比值低于MSA组（p=0.004; p=0.005）。CSF DOPAC与PUT：OCC比值呈正相关（r=0.61，p < 0.0001）。心肌6-[F-18]氟多巴胺衍生放射性区分PD和MSA（在神经源性直立性低血压患者中，灵敏度为83%，特异性为80%，灵敏度为100%）。只有PD患者嗅觉缺失;结论：PD和MSA的特征是6-[F-18]-氟多巴衍生放射性的PUT：OCC比值低，CSF中DOPAC和DOPA浓度低，神经影像学和神经化学方法交叉验证，但不能区分疾病。6-[F-18]氟多巴衍生放射性、心脏6-[F-18]氟多巴衍生放射性和嗅觉检测的PUT：SN和PUT：CAU比值将PD与MSA分开。(c)爱思唯尔有限公司出版
Objective: Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA).Methods: In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2 h after 6-[F-18]fluorodopa injection, septal myocardial radioactivity measured 8 min after 6-[F-18]fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test sensitivities at given specificities.Results: PUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[F-18]fluorodopa-derived radioactivity were similarly low in PD and MSA (p < 0.0001, p < 0.0001, p = 0.003 compared to controls); as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p < 0.0001, each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p=0.004; p=0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p < 0.0001). Myocardial 6-[F-18]fluorodopamine-derived radioactivity distinguished PD from MSA (83% sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic hypotension). Only PD patients were anosmic; only MSA patients had normal olfaction (61% sensitivity at 80% specificity).Conclusions: PD and MSA feature low PUT:OCC ratios of 6-[F-18]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:CAU ratios of 6-[F-18]fluorodopa-derived radioactivity, cardiac 6-[F-18]fluorodopamine-derived radioactivity, and olfactory testing separate PD from MSA. (c) Published by Elsevier Ltd.