From the Department of Neurology, Neurointensive Care and Neurorehabilitation (B.C.P., G.K., J.H., L.R., E.T.), Neuroscience Institute (B.C.P., G.K., J.H., M.K., E.T.), and Department of Child and Adolescent Psychiatry (L.R.), Christian Doppler University Hospital, Paracelsus Medical University, Centre for Neuroscience Salzburg, Member of the European Reference Network, EpiCARE, Austria; Department of Clinical & Experimental Epilepsy (B.C.P., F.X., L.C., J.S.D., M.J.K., B.W.), UCL Queen Square Institute of Neurology, London; Chalfont Centre for Epilepsy (B.C.P., F.X., L.C., J.S.D., M.J.K., B.W.), Chalfont St. Peter, United Kingdom; Department of Neurology (L.C.), Inselspital, Sleep-Wake-Epilepsy-Center, Bern University Hospital, University of Bern, Switzerland; Department of Psychology (M.K.), University of Salzburg, Austria; Department of Neurology (C.V.), Epilepsy Center, University Hospital of the Ludwig-Maximilians-University of Munich, Germany; Department of Public Health, Health Services Research and Health Technology Assessment (E.T.), UMIT-University of Health Sciences, Medical Informatics and Technology, Hall in Tirol; and Karl Landsteiner Institute for Neurorehabilitation and Space Neurology (E.T.), Salzburg, Austria.
Neurology. 2024 Oct 22;103(8):e209802. doi: 10.1212/WNL.0000000000209802. Epub 2024 Sep 20.
Neuroimaging studies have so far identified structural changes in individuals with juvenile myoclonic epilepsy (JME) when compared with controls. However, the underlying mechanisms of drug-resistant JME remain unknown. In this study, we aimed at characterizing the structural underpinnings of drug-resistant JME using MRI-derived cortical morphologic markers.
In this prospective cross-sectional 2-center study, T1-weighted MRI and neuropsychological measures of verbal memory and executive function were obtained in individuals with drug-resistant and drug-responsive JME recruited from epilepsy outpatient clinics and healthy controls. We performed vertexwise measurements of cortical thickness, surface area, and local gyrification index (LGI). Vertexwise group comparisons were corrected for multiple comparisons at a familywise error (FWE) of 0.05. The neuropsychological profile of disease subgroups was analyzed through principal component analysis.
We studied 42 individuals with drug-resistant JME (mean age 29 ± 11 years, 50% female), 37 with drug-responsive JME (mean age 34 ± 10, years, 59% female), and 71 healthy controls (mean age 21 ± 9 years, 61% female). Surface area was increased in participants with drug-resistant JME in the left temporal lobe (Cohen = 0.82 [-0.52 to -1.12], < 0.05) when compared with the drug-responsive group. Although no cortical thickness changes were observed between disease subgroups, drug-resistant and drug-sensitive participants showed discrete cortical thinning against controls (Cohen = -0.42 [-0.83 to -0.01], < 0.05; Cohen = -0.57 [-1.03 to -0.11], < 0.05, respectively). LGI was increased in the left temporal and occipital lobes in drug-resistant participants (Cohen = 0.60 [0.34-0.86], < 0.05) when contrasting against drug-sensitive participants, but not controls. The composite executive function score was reduced in drug-resistant individuals compared with controls and drug-sensitive individuals (-1.74 [-2.58 to -0.90], < 0.001 and -1.29 [-2.25 to -0.33], < 0.01, respectively). Significant correlations were observed between executive function impairment and increased surface area in the precuneus and medial prefrontal regions ( = -0.79, < 0.05) in participants with drug-resistant JME.
We identified a developmental phenotype in individuals with drug-resistant JME characterized by changes in cortical surface area and folding complexity, the extent of which correlates with executive dysfunction. No association was observed between cortical thickness and disease severity. Our findings support a neurodevelopmental basis for drug resistance and cognitive impairment in JME.
迄今为止，神经影像学研究已经发现青少年肌阵挛癫痫（JME）患者与对照组相比存在结构变化。然而，耐药性 JME 的潜在机制仍不清楚。在这项研究中，我们旨在使用 MRI 衍生的皮质形态学标志物来描述耐药性 JME 的结构基础。
在这项前瞻性的 2 中心研究中，我们在癫痫门诊招募了耐药性和反应性 JME 患者以及健康对照者，获取了他们的 T1 加权 MRI 和言语记忆和执行功能的神经心理学测量结果。我们对皮质厚度、表面积和局部脑回指数（LGI）进行了顶点测量。对组间比较进行了多重比较校正，以达到家族错误（FWE）为 0.05 的水平。通过主成分分析分析疾病亚组的神经心理学特征。
我们研究了 42 名耐药性 JME 患者（平均年龄 29±11 岁，50%为女性）、37 名反应性 JME 患者（平均年龄 34±10 岁，59%为女性）和 71 名健康对照者（平均年龄 21±9 岁，61%为女性）。与反应性组相比，耐药性 JME 患者的左侧颞叶表面积增加（Cohen = 0.82[-0.52 至 -1.12]， <0.05）。虽然在疾病亚组之间没有观察到皮质厚度变化，但耐药性和敏感性参与者相对于对照组表现出离散的皮质变薄（Cohen = -0.42[-0.83 至 -0.01]， <0.05；Cohen = -0.57[-1.03 至 -0.11]， <0.05）。耐药性参与者的左侧颞叶和枕叶 LGI 增加（Cohen = 0.60[0.34-0.86]， <0.05），与反应性参与者相比，但与对照组相比没有差异。与对照组和反应性参与者相比，耐药性个体的综合执行功能评分降低（-1.74[-2.58 至 -0.90]， <0.001 和-1.29[-2.25 至 -0.33]， <0.01）。在耐药性 JME 患者中，执行功能障碍与扣带回和内侧前额叶区域的皮质表面积增加之间存在显著相关性（ = -0.79， <0.05）。
我们发现耐药性 JME 患者存在发育表型，其特征是皮质表面积和折叠复杂度发生变化，其程度与执行功能障碍相关。皮质厚度与疾病严重程度之间没有关联。我们的发现支持 JME 中耐药性和认知障碍的神经发育基础。
