Department of Neurology, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
BMC Neurol. 2019 Oct 14;19(1):233. doi: 10.1186/s12883-019-1471-7.
Neurodegeneration with brain iron accumulation (NBIA) is characterized by pathological iron accumulation in the subcortical nuclei and the cortex. As age-related iron accumulation studies in these structures are lacking in healthy aging, we aimed to characterize the dynamics of age-dependent iron accumulation in subcortical nuclei in healthy aging and selected NBIA cases. This is fundamental to understand the natural age-related iron deposition in the healthy brain prior to using this marker as a potential prognostic or diagnostic tool in neurodegenerative disorders.
Susceptibility-weighted imaging (SWI) scans from 81 healthy volunteers (0-79 years) and four genetically confirmed patients suffering from NBIA (2-14 years) were obtained. We scored the presence or absence of pencil lining of the motor cortex and putamen and analyzed the normalized SWI signal intensity ratio (NSIR) in five subcortical nuclei.
In healthy subjects, an age-dependent increase of pencil lining occurred starting from the second decade of life and was present in all cases at the age of 50. In their first decade, NBIA patients showed no cortical pencil lining, but we did observe putaminal pencil lining at this stage. In healthy subjects, age and NSIR of all nuclei correlated positively and was particularly dynamic in early childhood until young adulthood in the globus pallidus, dentate nucleus and red nucleus, but not in the caudate nucleus and putamen. NBIA patients showed an increased NSIR in the globus pallidus only and not in the other subcortical nuclei compared to age-matched healthy subjects.
Cortical pencil lining is part of healthy aging. This should be considered when assessing this as a potential marker in NBIA diagnosis and prognosis. Putaminal pencil lining has the potential to become a specific marker for some subtypes of NBIA in the first decade of life, as it was only observed in NBIA and not in age-matched healthy subjects. NSIR in the subcortical nuclei during healthy aging was shown to be dynamic, accentuating the importance of having an age-dependent baseline.
神经退行性伴脑铁沉积（NBIA）的特征是纹状体和皮质下核病理性铁沉积。由于在健康衰老中缺乏这些结构的年龄相关性铁积累研究，我们旨在描述健康衰老中和选定的 NBIA 病例中皮质下核中与年龄相关的铁积累的动态。这对于理解健康大脑中与年龄相关的铁沉积是基础性的，这是在神经退行性疾病中使用该标志物作为潜在预后或诊断工具之前的前提。
从 81 名健康志愿者（0-79 岁）和 4 名遗传性确诊的 NBIA 患者（2-14 岁）中获得了磁敏感加权成像（SWI）扫描。我们对运动皮层和壳核的铅笔线的存在或不存在进行评分，并分析了 5 个皮质下核的归一化 SWI 信号强度比（NSIR）。
在健康受试者中，从第二个十年开始出现与年龄相关的铅笔线增加，并在 50 岁时在所有病例中出现。在他们的第一个十年中，NBIA 患者没有皮质铅笔线，但我们在这个阶段确实观察到壳核的铅笔线。在健康受试者中，年龄与所有核的 NSIR 呈正相关，并且在幼儿期至青年期在苍白球、齿状核和红核中特别活跃，但在尾状核和壳核中则不然。与年龄匹配的健康受试者相比，NBIA 患者仅在苍白球中显示 NSIR 增加，而在其他皮质下核中则没有。
皮质铅笔线是健康衰老的一部分。在评估其作为 NBIA 诊断和预后的潜在标志物时，应该考虑到这一点。壳核的铅笔线有可能成为生命早期某些 NBIA 亚型的特异性标志物，因为它仅在 NBIA 中观察到，而在年龄匹配的健康受试者中则没有。在健康衰老期间，皮质下核的 NSIR 显示出动态性，强调了具有年龄依赖性基线的重要性。
