Department of Neurology and Clinical Neurophysiology of the Academic Medical Center, Amsterdam, The Netherlands.
Exp Neurol. 2013 Sep;247:623-9. doi: 10.1016/j.expneurol.2013.02.017. Epub 2013 Mar 6.
Myoclonus-dystonia (MD) is a movement disorder characterized by myoclonic jerks, dystonic postures and psychiatric co-morbidity. A mutation in the DYT11 gene underlies half of MD cases. We hypothesize that MD results from a dysfunctional basal ganglia network causing insufficient inhibitory motor control. To test this hypothesis functional MRI (fMRI) was performed using a validated "Go/No go" task, in order to localize blood-oxygen-level dependence (BOLD) effects corresponding to Response Inhibition (RI).
Twenty-four MD patients (fifteen DYT11 positive) and 24 matched controls responded with a button press to Go (Go-Response) or No go (referred to as 'Stop') cues, resulting in analyses of accurate response suppression to Stop cues (Stop-Inhibit), and incorrect responses to Go cues (Go-Inhibit), or to Stop cues (Stop-Response).
Response accuracy in patients was impaired due to frequent Go-Inhibit errors. Image analysis of the Stop-Inhibit contrast demonstrated frontal, caudate and cingular activity in both groups. Compared to controls, MD patients showed increased primary motor cortex and insular activation. During Go-Inhibit trials, patients revealed increased activity in the contralateral thalamus (ventral lateral nucleus) and dorso-lateral-prefrontal cortex. In a post-hoc analysis comparing MD patients, DYT11 positive patients demonstrated anterior cerebellum hyperactivation on all contrasts and increased putaminal activation in the Stop-Response contrast.
This study demonstrates a distinct association of motor symptoms in MD with the ventral lateral nucleus of the thalamus. Cerebellar dysfunction distinguishes DYT11 positive from negative patients. We suggest that MD might be best considered as a disorder of the cortico-ponto-cerebello-thalamo-cortical system.
肌阵挛-肌张力障碍（MD）是一种以肌阵挛抽搐、肌张力障碍姿势和精神共病为特征的运动障碍。DYT11 基因突变是 MD 病例的一半原因。我们假设 MD 是由于基底神经节网络功能障碍导致运动抑制控制不足引起的。为了测试这一假设，我们使用经过验证的“Go/No go”任务进行了功能磁共振成像（fMRI），以定位与反应抑制（RI）相对应的血氧水平依赖（BOLD）效应。
24 名 MD 患者（15 名 DYT11 阳性）和 24 名匹配的对照者用按钮按压对 Go（Go-Response）或 No go（称为“Stop”）线索做出反应，从而对准确抑制对 Stop 线索的反应（Stop-Inhibit）、对 Go 线索的错误反应（Go-Inhibit）或对 Stop 线索的反应（Stop-Response）进行分析。
由于频繁的 Go-Inhibit 错误，患者的反应准确性受损。Stop-Inhibit 对比的图像分析显示两组患者的额、尾状核和扣带回活动。与对照组相比，MD 患者的初级运动皮层和岛叶活动增加。在 Go-Inhibit 试验中，患者显示对侧丘脑（腹外侧核）和背外侧前额叶皮质的活性增加。在比较 MD 患者的事后分析中，DYT11 阳性患者在所有对比中表现出前脑小脑过度激活，并在 Stop-Response 对比中显示出纹状体的激活增加。
本研究表明 MD 的运动症状与丘脑腹外侧核有明显的关联。小脑功能障碍将 DYT11 阳性患者与阴性患者区分开来。我们认为 MD 可能最好被视为皮质-桥脑-小脑-丘脑-皮质系统的障碍。
