Baker E H, Levin S W, Zhang Z, Mukherjee A B
From the Department of Radiology and Imaging Sciences (E.H.B.), Clinical Center, National Institutes of Health, Bethesda, Maryland
Program on Endocrinology and Molecular Genetics (S.W.L., Z.Z., A.B.M.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
AJNR Am J Neuroradiol. 2017 Feb;38(2):376-382. doi: 10.3174/ajnr.A4978. Epub 2016 Oct 20.
Infantile neuronal ceroid lipofuscinosis 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, resulting in rapid neurodegeneration and childhood death. As part of a project studying the treatment benefits of a combination of cysteamine bitartrate and -acetyl cysteine, we made serial measurements of patients' brain volumes with MR imaging.
Ten patients with infantile neuronal ceroid lipofuscinosis participating in a treatment/follow-up study underwent brain MR imaging that included high-resolution T1-weighted images. After manual placement of a mask delineating the surface of the brain, a maximum-likelihood classifier was applied to determine total brain volume, further subdivided as cerebrum, cerebellum, brain stem, and thalamus. Patients' brain volumes were compared with those of a healthy population.
Major subdivisions of the brain followed similar trajectories with different timing. The cerebrum demonstrated early, rapid volume loss and may never have been normal postnatally. The thalamus dropped out of the normal range around 6 months of age; the cerebellum, around 2 years of age; and the brain stem, around 3 years of age.
Rapid cerebral volume loss was expected on the basis of previous qualitative reports. Because our study did not include a nontreatment arm and because progression of brain volumes in infantile neuronal ceroid lipofuscinosis has not been previously quantified, we could not determine whether our intervention had a beneficial effect on brain volumes. However, the level of quantitative detail in this study allows it to serve as a reference for evaluation of future therapeutic interventions.
婴儿神经元蜡样脂褐质沉积症是一种由棕榈酰蛋白硫酯酶1缺乏引起的严重神经退行性贮积病，该酶缺乏会损害溶酶体水解酶对棕榈酰化蛋白（蜡样质的成分）的降解。随之而来的溶酶体蜡样质蓄积会导致神经元损伤，进而引发快速的神经退行性变和儿童期死亡。作为一项研究酒石酸半胱胺和N-乙酰半胱氨酸联合治疗效果的项目的一部分，我们利用磁共振成像对患者的脑容量进行了连续测量。
10名参与治疗/随访研究的婴儿神经元蜡样脂褐质沉积症患者接受了脑部磁共振成像检查，其中包括高分辨率T1加权图像。在手动放置勾勒脑表面的蒙版后，应用最大似然分类器确定全脑容量，并进一步细分为大脑、小脑、脑干和丘脑。将患者的脑容量与健康人群的脑容量进行比较。
脑的主要亚结构遵循相似的轨迹，但时间不同。大脑显示出早期、快速的容量损失，出生后可能从未正常过。丘脑在6个月左右脱离正常范围；小脑在2岁左右；脑干在3岁左右。
根据之前的定性报告，预计会出现快速的脑容量损失。由于我们的研究没有设置未治疗组，且之前尚未对婴儿神经元蜡样脂褐质沉积症患者脑容量的进展进行量化，因此我们无法确定我们的干预措施是否对脑容量有有益影响。然而，本研究的定量细节水平使其能够作为评估未来治疗干预措施的参考。
