Berger Alexandre, Beckers Elise, Joris Vincent, Duchêne Gaëtan, Danthine Venethia, Delinte Nicolas, Cakiroglu Inci, Sherif Siya, Morrison Enrique Ignacio Germany, Sánchez Andres Torres, Macq Benoit, Dricot Laurence, Vandewalle Gilles, El Tahry Riëm
Department of Clinical Neuroscience, Institute of Neuroscience, Catholic University of Louvain, Brussels, Belgium.
Synergia Medical SA, Mont-Saint-Guibert, Belgium.
Front Neurosci. 2024 Feb 13;18:1296161. doi: 10.3389/fnins.2024.1296161. eCollection 2024.
The locus coeruleus-norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This system is known to prevent seizure development and induce long-term plastic changes, particularly with the release of norepinephrine in the hippocampus. However, the requisites to become responder to the therapy and the mechanisms of action are still under investigation. Using MRI, we assessed the structural and functional characteristics of the locus coeruleus and microstructural properties of locus coeruleus-hippocampus white matter tracts in patients with drug-resistant epilepsy responding or not to the therapy. Twenty-three drug-resistant epileptic patients with cervical vagus nerve stimulation were recruited for this pilot study, including 13 responders or partial responders and 10 non-responders. A dedicated structural MRI acquisition allowed localization of the locus coeruleus and computation of its contrast (an accepted marker of LC integrity). Locus coeruleus activity was estimated using functional MRI during an auditory oddball task. Finally, multi-shell diffusion MRI was used to estimate the structural properties of locus coeruleus-hippocampus tracts. These characteristics were compared between responders/partial responders and non-responders and their association with therapy duration was also explored. In patients with a better response to the therapy, trends toward a lower activity and a higher contrast were found in the left medial and right caudal portions of the locus coeruleus, respectively. An increased locus coeruleus contrast, bilaterally over its medial portions, correlated with duration of the treatment. Finally, a higher integrity of locus coeruleus-hippocampus connections was found in patients with a better response to the treatment. These new insights into the neurobiology of vagus nerve stimulation may provide novel markers of the response to the treatment and may reflect neuroplasticity effects occurring in the brain following the implantation.
蓝斑 - 去甲肾上腺素系统被认为与迷走神经刺激的临床效果有关。已知该系统可预防癫痫发作的发展并诱导长期的可塑性变化，特别是通过海马体中去甲肾上腺素的释放。然而，对该疗法产生反应的必要条件和作用机制仍在研究中。我们使用磁共振成像（MRI）评估了耐药性癫痫患者中，对该疗法有反应或无反应者的蓝斑结构和功能特征以及蓝斑 - 海马白质束的微观结构特性。本前瞻性研究招募了23名接受颈迷走神经刺激的耐药性癫痫患者，其中包括13名有反应者或部分反应者以及10名无反应者。通过专门的结构MRI采集来定位蓝斑并计算其对比度（蓝斑完整性的公认标志物）。在听觉oddball任务期间，使用功能MRI估计蓝斑活性。最后，使用多壳扩散MRI估计蓝斑 - 海马束的结构特性。比较了有反应者/部分反应者和无反应者之间的这些特征，并探讨了它们与治疗持续时间的关联。在对该疗法反应较好的患者中，分别在蓝斑的左内侧和右尾侧部分发现了活性降低和对比度升高的趋势。双侧内侧部分蓝斑对比度增加与治疗持续时间相关。最后，在对治疗反应较好的患者中发现蓝斑 - 海马连接的完整性更高。这些对迷走神经刺激神经生物学的新见解可能提供治疗反应的新标志物，并可能反映植入后大脑中发生的神经可塑性效应。
