Goldstein David S, Holmes Courtney, Bentho Oladi, Sato Takuya, Moak Jeffrey, Sharabi Yehonatan, Imrich Richard, Conant Shielah, Eldadah Basil A
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA.
Parkinsonism Relat Disord. 2008 Dec;14(8):600-7. doi: 10.1016/j.parkreldis.2008.01.010. Epub 2008 Mar 5.
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).
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 2h after 6-[18F]fluorodopa injection, septal myocardial radioactivity measured 8min after 6-[18F]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.
PUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[18F]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-[18F]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).
PD and MSA feature low PUT:OCC ratios of 6-[18F]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-[18F]fluorodopa-derived radioactivity, cardiac 6-[18F]fluorodopamine-derived radioactivity, and olfactory testing separate PD from MSA.
生物标志物对于神经退行性疾病如帕金森病（PD）的诊断和治疗测试越来越重要。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与多系统萎缩（MSA）。
对77例PD患者、57例MSA患者和87例对照者，在注射6-[18F]氟多巴2小时后测量壳核（PUT）、尾状核（CAU）、枕叶皮质（OCC）和黑质（SN）的放射性浓度，在注射6-[18F]氟多巴胺8分钟后测量隔区心肌放射性，检测脑脊液和血浆儿茶酚，或进行嗅觉测试（宾夕法尼亚大学嗅觉识别测试（UPSIT））。构建受试者工作特征曲线，显示给定特异性下的测试敏感性。
PD和MSA中6-[18F]氟多巴衍生放射性的PUT:OCC、CAU:OCC和SN:OCC比值同样较低（与对照组相比，p<0.0001、p<0.0001、p=0.003），脑脊液二羟基苯乙酸（DOPAC）和多巴浓度也是如此（各p<0.0001）。PD中PUT:SN和PUT:CAU比值低于MSA（p=0.004；p=0.005）。脑脊液DOPAC与PUT:OCC比值呈正相关（r=0.61，p<0.0001）。心肌6-[18F]氟多巴胺衍生放射性可区分PD与MSA（在80%特异性时敏感性为83%，在神经源性直立性低血压患者中敏感性为100%）。只有PD患者嗅觉缺失；只有MSA患者嗅觉正常（在80%特异性时敏感性为61%）。
PD和MSA的特征是6-[18F]氟多巴衍生放射性的PUT:OCC比值低以及脑脊液DOPAC和多巴浓度低，这验证了神经影像学和神经化学方法，但无法区分这两种疾病。6-[18F]氟多巴衍生放射性的PUT:SN和PUT:CAU比值、心肌6-[18F]氟多巴胺衍生放射性以及嗅觉测试可将PD与MSA区分开来。
