黑质神经黑色素作为帕金森病疾病进展的影像学生物标志物

Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson's Disease.

作者信息

Fabbri Margherita, Reimão Sofia, Carvalho Miguel, Nunes Rita G, Abreu Daisy, Guedes Leonor Correia, Bouça Raquel, Lobo Patricia P, Godinho Catarina, Coelho Miguel, Gonçalves Nilza C, Rosa Mario Miguel, Antonini Angelo, Ferreira Joaquim J

机构信息

Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

Department of Neurological Imaging, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.

出版信息

J Parkinsons Dis. 2017;7(3):491-501. doi: 10.3233/JPD-171135.

DOI:10.3233/JPD-171135

PMID:28671143

Abstract

BACKGROUND

A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson's disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression.

OBJECTIVE

to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages.

METHODS

A comparative cross-sectional study was performed, analyzing SN-NM MRI signal in LSPD (Schwab and England Activities of Daily Living Scale score <50 or Hoehn Yahr Stage [HY] >3), comparing this group with de novo, 2-5 year PD and controls. SN-NM signal area and CR values for the internal and lateral SN regions were obtained with semi-automated methods.

RESULTS

13 LSPD, 12 de novo patients with PD, 10 PD patients with a 2-5 year disease duration, and 10 controls were included. NM signal area was significantly decreased in LSPD compared to de novo PD (P-value = 0.005; sensitivity: 75%; specificity 92% and AUC: 0.86). In the lateral SN region, a decrease in the CR was detected in all PD groups compared to controls; despite not reaching statistical significance, a slight increment was observed comparing LSPD to 2-5 year PD. NM signal area significantly correlated with HY (R = -0.37; P < 0.05) and Movement disorder Society Unified Parkinson's Disease Rating Scale part II (MDS-UPDRS) (R = -0.4; P < 0.05) while a weak correlation was found with MDS-UPDRS part III (R = -0.26; P: 0.1).

CONCLUSION

SN area evaluated by NM-sensitive MRI may be a promising biomarker of nigral degeneration and disease progression in PD patients.

摘要

背景

一种特定的T1加权磁共振成像（MRI）序列已被证明能够检测黑质（SN）神经黑色素（NM）信号变化，即使在疾病早期阶段，也能准确地区分帕金森病（PD）患者与对照组。然而，尚不清楚在疾病后期这些黑质变化会如何，以及它们是否可作为疾病进展的标志物。

目的

研究与疾病早期阶段相比，晚期帕金森病（LSPD）患者黑质神经黑色素区域丢失和对比率（CR）强度变化的模式。

方法

进行了一项比较性横断面研究，分析LSPD患者（施瓦布和英格利希日常生活活动量表评分<50或霍恩-亚尔分期[HY]>3）的黑质神经黑色素MRI信号，并将该组与初发、病程2 - 5年的帕金森病患者及对照组进行比较。采用半自动方法获取黑质内部和外侧区域的神经黑色素信号面积和对比率值。

结果

纳入13例LSPD患者、12例初发帕金森病患者、10例病程2 - 5年的帕金森病患者和10例对照组。与初发帕金森病患者相比，LSPD患者的神经黑色素信号面积显著降低（P值 = 0.005；敏感性：75%；特异性92%；曲线下面积：0.86）。在黑质外侧区域，与对照组相比，所有帕金森病组的对比率均降低；尽管未达到统计学显著性，但与病程2 - 5年的帕金森病患者相比，LSPD患者有轻微升高。神经黑色素信号面积与HY（R = -0.37；P < 0.05）和运动障碍协会统一帕金森病评定量表第二部分（MDS - UPDRS）（R = -0.4；P < 0.05）显著相关，而与MDS - UPDRS第三部分的相关性较弱（R = -0.26；P：0.1）。