Clinic for Neurology, University Medical Center Göttingen, Göttingen, Germany.
Clinic for Neurology, University Medical Center Göttingen, Göttingen, Germany; Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Neuroimage Clin. 2023;39:103474. doi: 10.1016/j.nicl.2023.103474. Epub 2023 Jul 8.
Genetic generalized epilepsy (GGE) is the most common form of generalized epilepsy. Although individual patients with GGE typically present without structural alterations, group differences have been demonstrated in GGE and some GGE subtypes like juvenile myoclonic epilepsy (GGE-JME). Previous studies usually involved only small cohorts from single centers and therefore could not assess imaging markers of multiple GGE subtypes.
We performed a diffusion MRI mega-analysis in 192 participants consisting of 126 controls and 66 patients with GGE from four different cohorts and two different epilepsy centers. We applied whole-brain multi-site harmonization and analyzed fractional anisotropy (FA), as well as mean, radial and axial diffusivity (MD/RD/AD) to assess differences between controls, patients with GGE and the common GGE subtypes, i.e. GGE with generalized tonic-clonic seizures only (GGE-GTCS), GGE-JME and absence epilepsy (GGE-AE). We also analyzed relationships with patients' response to anti-seizure-medication (ASM).
Relative to controls, we identified decreased anisotropy and increased RD in patients with GGE. We found no significant effects of disease duration, age of onset or seizure frequency on diffusion metrics. Patients with JME had increased MD and RD when compared to controls, while patients with GGE-GTCS showed decreased MD/AD when compared to controls. Compared to patients with GGE-AE, patients with GGE-GTCS had lower AD/MD. Compared to patients with GGE-GTCS, patients with GGE-JME had higher MD/RD and AD. Moreover, we found lower FA in patients with refractory when compared to patients with non-refractory GGE in the right cortico-spinal tract, but no significant differences in patients with active versus controlled epilepsy.
We provide evidence that clinically defined GGE as a whole and GGE-subtypes harbor marked microstructural differences detectable with diffusion MRI. Moreover, we found an association between microstructural changes and treatment resistance. Our findings have important implications for future full-resolution multi-site studies when assessing GGE, its subtypes and ASM refractoriness.
遗传性全面性癫痫（GGE）是最常见的全面性癫痫类型。尽管个别 GGE 患者通常无结构改变，但在 GGE 及某些 GGE 亚型（如青少年肌阵挛性癫痫（GGE-JME））中已发现组间差异。以往的研究通常仅涉及来自单个中心的小队列，因此无法评估多种 GGE 亚型的影像学标志物。
我们对来自四个不同队列和两个不同癫痫中心的 192 名参与者（包括 126 名对照和 66 名 GGE 患者）进行了弥散 MRI 荟萃分析。我们应用全脑多部位协调，并分析了各向异性分数（FA）以及平均弥散度（MD）、径向弥散度（RD）和轴向弥散度（AD），以评估对照组、GGE 患者和常见 GGE 亚型（即仅有全面性强直阵挛发作的 GGE、GGE-JME 和失神性癫痫）之间的差异。我们还分析了这些差异与患者对抗癫痫药物反应之间的关系。
与对照组相比，GGE 患者的各向异性降低，RD 增加。我们未发现疾病持续时间、发病年龄或发作频率对弥散指标有显著影响。与对照组相比，JME 患者的 MD 和 RD 增加，而 GGE-GTCS 患者的 MD/AD 降低。与 GGE-AE 患者相比，GGE-GTCS 患者的 AD/MD 较低。与 GGE-GTCS 患者相比，GGE-JME 患者的 MD/RD 和 AD 较高。此外，我们发现右侧皮质脊髓束中难治性 GGE 患者的 FA 值低于非难治性 GGE 患者，但在活动期癫痫与控制期癫痫患者之间无显著差异。
我们提供的证据表明，临床上定义的 GGE 整体及其亚型存在明显的弥散 MRI 可检测到的微观结构差异。此外，我们发现微观结构变化与治疗抵抗之间存在关联。我们的研究结果对于未来评估 GGE、其亚型和抗癫痫药物反应性的全分辨率多部位研究具有重要意义。
