Brüggemann N, Rosales R L, Waugh J L, Blood A J, Domingo A, Heldmann M, Jamora R D, Münchau A, Münte T F, Lee L V, Buchmann I, Klein C
Department of Neurology, University of Lübeck, Lübeck, Germany.
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Eur J Neurol. 2017 May;24(5):680-686. doi: 10.1111/ene.13256. Epub 2017 Feb 25.
X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset movement disorder associated with striatal atrophy. As the dopaminergic system has not yet been systemically studied in this basal ganglia model disease, it is unclear whether nigrostriatal dysfunction contributes to parkinsonism in XDP.
Pre- and post-synaptic dopaminergic function was assessed in XDP. A total of 10 jod-benzamide (IBZM) single-photon emission computed tomography (SPECT) images were obtained for nine patients aged 42.3 ± 9.5 years (SD; range 30-52) and one asymptomatic mutation carrier (38 years), and four ioflupane (FP-CIT) SPECT images were obtained for four patients, aged 41.5 ± 11.6 years (range 30-52 years). Structural magnetic resonance imaging was also performed for all mutation carriers and 10 matched healthy controls.
All patients were men who suffered from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism. IBZM SPECT images were pathological in 8/9 symptomatic patients with distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, and unremarkable in the asymptomatic mutation carrier. Longer disease duration was correlated with lower IBZM binding ratios. All subjects exhibited slightly reduced FP-CIT uptake values compared to controls for each analyzed region (-37% to -41%) which may be linked to basal ganglia volume loss. Visual inspection revealed physiological FP-CIT uptake in 1/4 patients.
This nuclear imaging study provides evidence that the functional decline of post-synaptic dopaminergic neurotransmission is related to disease duration and ongoing neurodegeneration. Given the severe striatal cell loss which could be verified with post-synaptic nuclear imaging, both parkinsonism and dystonia in XDP are probably mainly due to striatal dysfunction.
X连锁肌张力障碍-帕金森综合征（XDP）是一种与纹状体萎缩相关的遗传性神经退行性成人起病的运动障碍。由于尚未在这种基底节模型疾病中对多巴胺能系统进行系统研究，因此尚不清楚黑质纹状体功能障碍是否导致XDP中的帕金森综合征。
对XDP患者的突触前和突触后多巴胺能功能进行评估。共为9名年龄42.3±9.5岁（标准差；范围30 - 52岁）的患者和1名无症状突变携带者（38岁）获取了10张碘-苄酰胺（IBZM）单光子发射计算机断层扫描（SPECT）图像，为4名年龄41.5±11.6岁（范围30 - 52岁）的患者获取了4张碘氟烷（FP - CIT）SPECT图像。还对所有突变携带者和10名匹配的健康对照进行了结构磁共振成像检查。
所有患者均为男性，患有严重的、致残性节段性或全身性肌张力障碍，并伴有不同程度的帕金森综合征。8/9有症状患者的IBZM SPECT图像呈病理性，尾状核和壳核突触后示踪剂摄取明显减少，而无症状突变携带者的图像无明显异常。病程较长与较低的IBZM结合率相关。与对照组相比，所有受试者每个分析区域的FP - CIT摄取值均略有降低（-37%至-41%），这可能与基底节体积减少有关。目视检查显示4名患者中有1名的FP - CIT摄取正常。
这项核成像研究提供了证据，表明突触后多巴胺能神经传递的功能下降与病程和持续的神经退行性变有关。鉴于突触后核成像证实存在严重的纹状体细胞丢失，XDP中的帕金森综合征和肌张力障碍可能主要是由于纹状体功能障碍所致。
