Assessment of Neurological Deterioration in Subjects with LINCL

晚期婴儿蜡样质脂褐质沉积症（LINCL）是一种罕见的、进展迅速的溶酶体沉积病。患者的罕见性以及取决于基因型的非均匀进展的可能性意味着可用于描述疾病进展的自然史的数据有限。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定义LINCL的自然史，并提供客观和敏感的神经系统状态的替代品，并评估实验性治疗对LINCL儿童的影响。为了实现这一目标，我们有3个目标：（1）招募LINCL儿童并进行系列神经系统评估和MRI研究;（2）使用这些数据，扩展现有定量MRI参数的范围并导出正常范围，并与神经系统状态和特定突变相关;以及（3）从包括脑子结构体积的MRI数据中提取附加参数，通过磁共振波谱和局部扩散加权成像确定局部代谢物水平。总之，这些参数将适用于LINCL新疗法的未来临床研究，并应可转移到其他神经系统溶酶体贮积病。

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.