Evaluation of disease progression in INCL by MR spectroscopy.
Evaluation of disease progression in INCL by MR spectroscopy.
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DOI：
10.1002/acn3.222
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发表时间：
2015-08
影响因子：
5.3
通讯作者：
Mukherjee AB
中科院分区：
文献类型：
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作者：
Baker EH;Levin SW;Zhang Z;Mukherjee AB
婴儿神经元蜡样脂褐质沉积症 (INCL) 是一种毁灭性的神经退行性贮积病，由棕榈酰蛋白硫酯酶 1 缺乏引起，会损害溶酶体水解酶对棕榈酰化蛋白（蜡样物质成分）的降解。随后的溶酶体蜡样积累导致神经元损伤。作为评估半酒石酸氢盐和 N-乙酰半胱氨酸治疗效果的试点研究的一部分，我们使用磁共振波谱 (MRS) 定量测量了大脑代谢物水平。来自更大规模治疗和随访研究的两名患者的子集对五个解剖部位进行了连续定量单体素 MRS 检查。获取三个回波时间以估计代谢物 T2。测量的代谢物水平包括脑脊液部分体积的校正。将 INCL 患者与由无症状和症状轻微的 C 型尼曼-匹克病患者组成的参考组进行比较。在 INCL 患者中，初始测量时所有部位的 N-乙酰天冬氨酸 (NAA) 异常低，并且在整个随访期间进一步下降。在大脑（病程早期受影响）中，胆碱和肌醇最初升高，随后在随访期间下降，而在小脑和脑干（后期受影响）中，胆碱和肌醇最初正常，随后升高。我们患者的胆碱和肌醇水平与在两种 INCL 小鼠模型中观察到的神经炎症模式一致。基于该疾病的进展性、不可逆性，NAA 预计会持续下降。 INCL 中代谢物水平的进展先前尚未量化；因此，本研究的结果可以为未来治疗干预的定量评估提供参考。
Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury. As part of a pilot study to evaluate treatment benefits of cysteamine bitartrate and N-acetylcysteine, we quantitatively measured brain metabolite levels using magnetic resonance spectroscopy (MRS). A subset of two patients from a larger treatment and follow-up study underwent serial quantitative single-voxel MRS examinations of five anatomical sites. Three echo times were acquired in order to estimate metabolite T2. Measured metabolite levels included correction for partial volume of cerebrospinal fluid. Comparison of INCL patients was made to a reference group composed of asymptomatic and minimally symptomatic Niemann-Pick disease type C patients. In INCL patients, N-acetylaspartate (NAA) was abnormally low at all locations upon initial measurement, and further declined throughout the follow-up period. In the cerebrum (affected early in the disease course), choline and myo-inositol were initially elevated and fell during the follow-up period, whereas in the cerebellum and brainstem (affected later), choline and myo-inositol were initially normal and rose subsequently. Choline and myo-inositol levels in our patients are consistent with patterns of neuroinflammation observed in two INCL mouse models. Low, persistently declining NAA was expected based on the progressive, irreversible nature of the disease. Progression of metabolite levels in INCL has not been previously quantified; therefore the results of this study serve as a reference for quantitative evaluation of future therapeutic interventions.