Hübers Annemarie, Kassubek Jan, Müller Hans-Peter, Broc Nicolas, Dreyhaupt Jens, Ludolph Albert C
Department of Clinical Neurosciences, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
Department of Neurology, University Hospital Ulm, Ulm, Germany.
Ther Adv Chronic Dis. 2021 Sep 13;12:20406223211044072. doi: 10.1177/20406223211044072. eCollection 2021.
Imaging studies showed affection of the corpus callosum (CC) in amyotrophic lateral sclerosis (ALS). Here, we sought to determine whether these structural alterations reflect on the functional level, using transcranial magnetic stimulation (TMS).
In 31 ALS patients and 12 controls, we studied mirror movements (MM) and transcallosal inhibition (TI) using TMS. Structural integrity of transcallosal fibres was assessed using diffusion tensor imaging.
TI was pathologic in 25 patients (81%), 22 (71%) showed MM. Loss of TI was observed in very early stages (disease duration <4 months). No correlation was found between TI/MM and fractional anisotropy of transcallosal fibres.
These results substantiate the body of evidence towards a functional involvement of the CC in early ALS beyond microstructural alterations.
TI may become a useful early diagnostic marker in ALS, even before descending tracts are affected. Diagnostic delay in ALS is high, often preventing patients from gaining access to therapeutic trials, and sensitive diagnostic tools are urgently needed. Our findings also provide insights into the pathophysiology of ALS, potentially supporting the so-called 'top-down' hypothesis, that is, corticoefferent (intracortical/corticospinal) propagation. Callosal affection in early stages might represent the 'missing link' to explain corticocortical disease-spreading.
影像学研究显示肌萎缩侧索硬化症（ALS）患者的胼胝体（CC）受到影响。在此，我们试图通过经颅磁刺激（TMS）来确定这些结构改变在功能层面上是否有体现。
我们对31例ALS患者和12名对照者进行研究，使用TMS来研究镜像运动（MM）和胼胝体抑制（TI）。使用扩散张量成像评估胼胝体纤维的结构完整性。
25例患者（81%）的TI呈病理性，22例（71%）出现MM。在疾病的极早期阶段（病程<4个月）就观察到TI丧失。未发现TI/MM与胼胝体纤维的分数各向异性之间存在相关性。
这些结果证实了有证据表明CC在早期ALS中存在功能受累，而非仅仅是微观结构改变。
TI可能成为ALS中一种有用的早期诊断标志物，甚至在下行传导束受影响之前。ALS的诊断延迟很高，常常使患者无法参与治疗试验，因此迫切需要敏感的诊断工具。我们的研究结果还为ALS的病理生理学提供了见解，可能支持所谓的“自上而下”假说，即皮质传出（皮质内/皮质脊髓）传播。早期的胼胝体受累可能是解释皮质间疾病传播的“缺失环节”。
