Lau Meghann W, Lee Ryan W, Miyamoto Robin, Jung Eun Sol, Yanjanin Farhat Nicole, Yoshida Shoko, Mori Susumu, Gropman Andrea, Baker Eva H, Porter Forbes D
Research Department, Shriners Hospitals for Children, Honolulu, HI 96822, USA.
John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
Diseases. 2016 Sep 8;4(3):29. doi: 10.3390/diseases4030029.
Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI) of the corpus callosum and brainstem, which has shown that microstructural disorganization is associated with NPC1 severity. This study investigates the utility of cerebellar DTI in clinical severity assessment. We hypothesize that cerebellar volume, fractional anisotropy (FA) and mean diffusivity (MD) negatively correlate with NIH NPC neurological severity score (NNSS) and motor severity subscores. Magnetic resonance imaging (MRI) was obtained for thirty-nine NPC1 subjects, ages 1-21.9 years (mean = 11.1, SD = 6.1). Using an atlas-based automated approach, the cerebellum of each patient was measured for FA, MD and volume. Additionally, each patient was given an NNSS. Decreased cerebellar FA and volume, and elevated MD correlate with higher NNSS. The cognition subscore and motor subscores for eye movement, ambulation, speech, swallowing, and fine motor skills were also statistically significant. Microstructural disorganization negatively correlated with motor severity in subjects. Additionally, Miglustat therapy correlated with lower severity scores across ranges of FA, MD and volume in all regions except the inferior peduncle, where a paradoxical effect was observed at high FA values. These findings suggest that DTI is a promising prognostication tool.
1型尼曼-匹克病（NPC1）是一种快速进展的神经退行性疾病，其特征是晚期内体和溶酶体内胆固醇蓄积，目前尚无可靠的影像学标志物用于预后评估和治疗管理。研究发现小脑体积缩小与疾病严重程度相关，而胼胝体和脑干的扩散张量成像（DTI）显示微观结构紊乱与NPC1严重程度相关。本研究探讨小脑DTI在临床严重程度评估中的应用价值。我们假设小脑体积、分数各向异性（FA）和平均扩散率（MD）与美国国立卫生研究院（NIH）NPC神经严重程度评分（NNSS）和运动严重程度子评分呈负相关。对39名年龄在1至21.9岁（平均 = 11.1，标准差 = 6.1）的NPC1患者进行了磁共振成像（MRI）检查。采用基于图谱的自动化方法，测量每位患者小脑的FA、MD和体积。此外，每位患者都接受了NNSS评分。小脑FA和体积减小以及MD升高与较高的NNSS相关。认知子评分以及眼动、行走、言语、吞咽和精细运动技能的运动子评分也具有统计学意义。微观结构紊乱与受试者的运动严重程度呈负相关。此外，米格鲁司他治疗与除下橄榄核外所有区域的FA、MD和体积范围内较低的严重程度评分相关，在下橄榄核高FA值时观察到了矛盾效应。这些发现表明DTI是一种有前景的预后评估工具。
