Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Ann Neurol. 2019 Oct;86(4):517-526. doi: 10.1002/ana.25566. Epub 2019 Aug 23.
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease with adult onset dystonia and subsequent parkinsonism. Postmortem and imaging studies revealed remarkable striatal pathology, with a predominant involvement of the striosomal compartment in the early phase. Here, we aimed to disentangle sequential neurodegeneration in the striatum of XDP patients, provide evidence for preferential loss of distinct striatal areas in the early phase, and investigate whether iron accumulation is present.
We used multimodal structural magnetic resonance imaging (voxel-based morphometry and relaxometry) in 18 male XDP patients carrying a TAF1 mutation and 19 age-matched male controls.
Voxel-based relaxometry and morphometry revealed (1) a cluster in the anteromedial putamen showing high iron content and severe atrophy (-55%) and (2) a cluster with reduced relaxation rates as a marker for increased water levels and a lower degree of atrophy (-20%) in the dorsolateral putamen. Iron deposition correlated with the degree of atrophy (ρ = -0.585, p = 0.011) and disease duration (ρ = 0.632, p = 0.005) in the anteromedial putamen. In the dorsolateral putamen, sensorimotor putamen atrophy correlated with disease severity (ρ = -0.649, p = 0.004).
This multimodal approach identified a patchy pattern of atrophy within the putamen. Atrophy is advanced and associated with iron accumulation in rostral regions of the striatum, whereas neurodegeneration is moderate and still ongoing in dorsolateral areas. Given the short disease duration and predominant dystonic phenotype, these results are well in line with early and preferential degeneration of striosome-rich striatal areas in XDP. ANN NEUROL 2019;86:517-526.
X 连锁型肌张力障碍-帕金森病（XDP）是一种成年起病的以肌张力障碍为特征，随后出现帕金森病的神经退行性疾病。尸检和影像学研究显示纹状体存在显著的病理学改变，在早期阶段主要累及纹状体区。在此，我们旨在阐明 XDP 患者纹状体的进行性神经退行性变，为早期阶段特定纹状体区域的选择性缺失提供证据，并探讨是否存在铁积累。
我们使用多模态结构磁共振成像（基于体素的形态测量学和弛豫率测量）对 18 名携带 TAF1 突变的 XDP 男性患者和 19 名年龄匹配的男性对照进行研究。
基于体素的弛豫率和形态测量学显示：（1）前内侧壳核有一个簇，表现为高铁含量和严重萎缩（-55%）；（2）背外侧壳核有一个簇，表现为弛豫率降低，表明水含量增加，萎缩程度较低（-20%）。前内侧壳核的铁沉积与萎缩程度（ρ=-0.585，p=0.011）和疾病持续时间（ρ=0.632，p=0.005）相关。背外侧壳核的感觉运动壳核萎缩与疾病严重程度相关（ρ=-0.649，p=0.004）。
这种多模态方法在壳核内识别出一种局灶性萎缩模式。萎缩是高级的，与纹状体前部的铁积累有关，而背外侧区域的神经退行性变则处于中度且仍在进行中。鉴于疾病持续时间短，且以肌张力障碍为主，这些结果与 XDP 中富含纹状体的纹状体区早期和优先变性完全一致。
