Assessment of Neurological Deterioration in Subjects with LINCL

婴儿晚期类脂褐质沉积症(LINCL)是一种罕见的、进展迅速的溶酶体蓄积性疾病。患者的罕见以及依赖于基因的非均匀进展的可能性意味着可获得的描绘疾病发展自然历史的数据有限。本研究的主要重点是使用临床评定量表和磁共振成像方法来确定LINCL的自然病史，并为LINCL儿童的神经状况和实验性治疗的影响评估提供客观和敏感的替代指标。为了实现这一目标，我们有三个目标：(1)招募LINCL儿童并进行一系列神经学评估和MRI研究；(2)利用这些数据，扩展现有定量MRI参数的频谱，得出正常范围，并与神经状态和特定突变相关；以及(3)从MRI数据中提取其他参数，包括脑亚结构体积、磁共振波谱和局部扩散加权成像的局部代谢物水平。总之，这些参数将适用于未来LINCL新疗法的临床研究，并应适用于其他神经系统溶酶体储存性疾病。

Late infantile ceroid lipofuscinosis (LINCL) is a rare, rapidly progressing lysosomal storage disease. The rareness of the patients as well as the possibility of non-uniform progression depending on genotype mean that limited data is available that delineates the natural history of disease progression. The primary focus of this study is to use clinical rating scales and magnetic resonance imaging methods to define the natural history of LINCL and to provide objective and sensitive surrogates for neurological status and for the assessment of the impact of experimental treatments in children with LINCL. To achieve this goal we have 3 aims: (1) Recruit children with LINCL and perform serial neurological assessments and MRI studies; (2) Using this data, expand the spectrum of existing quantitative MRI parameters and derive normal ranges and correlate with neurological status and specific mutations; and (3) Extract additional parameters from MRI data including volumes of brain substructures, local metabolite levels by magnetic resonance spectroscopy and local diffusion weighted imaging. Together, these parameters will be applicable to future clinical studies of novel therapies for LINCL, and should be transferable to other neurological lysosomal storage diseases.