Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Brain. 2024 Jun 3;147(6):1975-1981. doi: 10.1093/brain/awae094.
Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify their shared connections throughout the brain. This analysis yielded a common network that included basal ganglia, thalamic and brainstem nuclei, as well as the cerebellum. Comparison of this network with gene expression profiles associated with the dopamine system revealed spatial overlap specifically with the gene coding for dopamine receptor type 2 (DRD2), as defined by a large-scale transcriptomic database of the human brain. Furthermore, spatial overlap with DRD2 and DRD3 gene expression was specific to brain lesions associated with oculogyric crises when contrasted to lesions that led to other movement disorders. Our findings identify a common neural network causally involved in the occurrence of oculogyric crises and provide a pathophysiological link between lesion locations causing this syndrome and its most common pharmacological cause, namely DRD2 blockade.
眼肌危象是一种急性的、持续性的、通常是向上的、眼球共轭性偏斜的发作。眼肌危象通常是由于急性 D2 多巴胺受体阻断引起的，但导致这种症状的大脑区域仍然难以捉摸。在这里，我们使用了来自 14 例先前报道的病变诱导性眼肌危象病例的数据，并采用病变网络映射来识别它们在整个大脑中的共同连接。这项分析产生了一个共同的网络，包括基底神经节、丘脑和脑干核，以及小脑。将这个网络与与多巴胺系统相关的基因表达谱进行比较，显示出与多巴胺受体 2 (DRD2) 的基因编码有特定的空间重叠，这是由人类大脑的大规模转录组数据库定义的。此外，当与导致其他运动障碍的病变相比，与眼肌危象相关的病变与 DRD2 和 DRD3 基因表达的空间重叠是特异性的。我们的发现确定了一个共同的神经网络，该网络与眼肌危象的发生有因果关系，并为导致这种综合征的病变位置与其最常见的药理学原因（即 DRD2 阻断）之间提供了一种病理生理学联系。
