Functional brain networks in DYT1 dystonia
Functional brain networks in DYT1 dystonia
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DOI：
10.1002/ana.410440304
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发表时间：
1998-09-01
影响因子：
11.2
通讯作者：
Fahn, S
中科院分区：
文献类型：
--
作者：
Eidelberg, D;Moeller, JR;Fahn, S
早发性特发性扭转肌张力障碍（ITD）是一种常染色体显性多动性运动障碍，伴有不完全扭转，与染色体9 q34上DYT 1基因的3个碱基对缺失相关。为了确定DYT 1肌张力障碍患者脑功能障碍的代谢底物，我们用[F-18]氟脱氧葡萄糖和正电子发射断层扫描对7名无症状DYT 1携带者和10名受影响DYT 1携带者以及14名正常志愿者进行了扫描。我们发现，DYT 1肌张力障碍介导的表达两个独立的区域代谢协方差模式。第一种模式，在对未表现出的基因携带者的分析中确定，被称为无运动（MF）。这种异常模式的特点是增加代谢活动的豆状核，小脑，和补充运动区。MF模式存在于DYT 1携带者和无临床表现，并持续在DYT 1肌张力障碍患者中，其中不自主运动被睡眠抑制。第二种模式，在分析受影响的基因携带者在休息时持续收缩，被指定为运动相关（MR）。这种模式的特征是中脑、小脑和丘脑的代谢活动增加。MR模式的表达增加清醒DYT 1患者持续肌张力障碍，与DYT 1载体谁是不受影响的或谁有肌张力障碍，只有行动，以及正常对照组。在受影响的DYT 1患者中，MR受试者评分随睡眠显著下降，但在正常对照组中则无此现象。这些发现表明DYT 1基因的多态性比以前假设的要大得多。ITD通过分别与基因状态和异常运动相关的功能性脑网络的相互作用来介导。
Early-onset idiopathic torsion dystonia (ITD) is an autosomal dominant hyperkinetic movement disorder with incomplete penetrance, associated with a 3 base-pair deletion in the DYT1 gene on chromosome 9q34. To determine the metabolic substrates of brain dysfunction in DYT1 dystonia, we scanned 7 nonmanifesting and 10 affected DYT1 carriers and 14 normal volunteers with [F-18] fluorodeoxyglucose and positron emission tomography. We found that DYT1 dystonia is mediated by the expression of two independent regional metabolic covariance patterns. The first pattern, identified in an analysis of nonmanifesting gene carriers was designated movement free (MF). This abnormal pattern was characterized by increased metabolic activity in the lentiform nuclei, cerebellum, and supplementary motor areas. The MF pattern was present in DYT1 carriers with and without clinical manifestations and persisted in DYT1 dystonia patients in whom involuntary movements were suppressed by sleep. The second pattern, identified in an analysis of affected gene carriers with sustained contractions at rest, was designated movement related (MR). This pattern was characterized by increased metabolic activity in the midbrain, cerebellum, and thalamus. The expression of the MR pattern was increased in waking DYT1 patients with sustained dystonia, compared with DYT1 carriers who were unaffected or who had dystonia only on action, as well as normal controls. MR subject scores declined significantly with sleep in affected DYT1 patients but not in normal controls. These findings indicate the penetrance of the DYT1 gene is considerably greater than previously assumed. ITD is mediated through the interaction of functional brain networks relating separately to gene status and to abnormal movement.