Gelineau-Morel Rose, Dlamini Nomazulu, Bruss Joel, Cohen Alexander Li, Robertson Amanda, Alexopoulos Dimitrios, Smyser Christopher D, Boes Aaron D
Division of Neurology, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA.
University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
medRxiv. 2024 Apr 8:2024.04.06.24305421. doi: 10.1101/2024.04.06.24305421.
Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia.
Three cohorts of pediatric patients with lesion-induced dystonia were identified. The lesion etiologies included hypoxia, kernicterus, and stroke versus comparison subjects with acquired lesions not associated with dystonia. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with dystonia.
Multivariate lesion-symptom mapping showed that lesions of the putamen (stroke: r = 0.50, p <0.01; hypoxia, r = 0.64, p <0.001) and globus pallidus (kernicterus, r = 0.61, p <0.01) were associated with dystonia. Lesion network mapping using normative connectome data from healthy children demonstrated that these regional findings occurred within a common brain-wide network that involves the basal ganglia, anterior and medial cerebellum, and cortical regions that overlap the cingulo-opercular and somato-cognitive-action networks.
We interpret these findings as novel evidence for a unified dystonia brain network that involves the somato-cognitive-action network, which is involved in higher order coordination of movement. Elucidation of this network gives insight into the functional origins of dystonia and provides novel targets to investigate for therapeutic intervention.
肌张力障碍是一种运动障碍，其定义为非自愿性肌肉收缩导致异常姿势或扭曲及重复性动作。传统上，肌张力障碍被认为是基底神经节的一种疾病，但成人特发性肌张力障碍和损伤性肌张力障碍的最新研究结果表明，运动网络功能障碍更为广泛，涉及基底神经节、小脑、运动前皮质、感觉运动区和额顶叶区域。尚不清楚小儿损伤性肌张力障碍的不同病因之间是否共享类似的网络。
确定了三组小儿损伤性肌张力障碍患者队列。损伤病因包括缺氧、核黄疸和中风，与之对比的是有后天性损伤但与肌张力障碍无关的受试者。采用多变量损伤-症状映射和损伤网络映射来评估与肌张力障碍相关的解剖结构和网络。
多变量损伤-症状映射显示，壳核损伤（中风：r = 0.50，p <0.01；缺氧，r = 0.64，p <0.001）和苍白球损伤（核黄疸，r = 0.61，p <0.01）与肌张力障碍相关。使用来自健康儿童的标准连接组数据进行的损伤网络映射表明，这些区域发现发生在一个全脑共同网络内，该网络涉及基底神经节、小脑前叶和中叶以及与扣带回-岛盖和躯体-认知-行动网络重叠的皮质区域。
我们将这些发现解读为存在一个统一的肌张力障碍脑网络的新证据，该网络涉及躯体-认知-行动网络，参与运动的高级协调。对这个网络的阐释有助于深入了解肌张力障碍的功能起源，并为治疗干预研究提供新的靶点。
