From Melbourne Neuropsychiatry Centre (P.R., W.T.S., A.H.M., V.L.C., D.V., C.P., M.W.), the Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
Psychiatry Neuroimaging Laboratory (P.R., R.J.R., A.E.L., N.M., M.E.S.).
AJNR Am J Neuroradiol. 2023 Jul;44(7):768-775. doi: 10.3174/ajnr.A7894. Epub 2023 Jun 22.
While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls.
A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses.
We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity.
Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders.
虽然脑铁失调已在几种神经退行性疾病中观察到，但它与尼曼-匹克 C 型进行性神经退行性变的关系尚不清楚。尼曼-匹克 C 型患者和尼曼-匹克 C 型动物模型中均有报道称存在系统性铁异常。在本研究中，我们使用定量磁化率映射磁共振成像（quantitative susceptibility mapping MR imaging，QS-MRI）比较了尼曼-匹克 C 型患者与健康对照者的脑铁。
一组 10 例青少年和成年起病的尼曼-匹克 C 型患者和 14 例年龄和性别匹配的健康对照者接受了 7T 脑部磁共振成像检查，包括 T1 和定量磁化率采集。对两组之间的 QS-MRI 进行全脑容积探测性体素比较。进一步比较 ROI（丘脑、海马体、壳核、尾状核和苍白球）的平均 QS 值。对包括 Iturriaga 量表上的疾病严重程度、认知功能和社会职业功能评估量表在内的临床特征与区域性容积、QS 值之间的相关性进行了探讨，作为二次分析。
与对照组相比，我们观察到尼曼-匹克 C 型患者的丘脑体积减小，双侧丘脑底核簇的 QS 值升高。在尼曼-匹克 C 型患者中，丘脑底核簇的 QS 值升高与双侧丘脑体积减小相关。此外，右丘脑底核簇的 QS 值升高与疾病严重程度相关。
我们的研究结果提示尼曼-匹克 C 型疾病中存在丘脑底核铁沉积，这与丘脑萎缩和疾病严重程度相关。这一初步证据支持了铁与尼曼-匹克 C 型神经退行性变之间的联系，与其他神经退行性疾病的现有文献一致。
