Balfroid Tom, Warren Aaron E L, Dalic Linda J, Aeby Alec, Berlangieri Salvatore U, Archer John S
Department of Medicine, The University of Melbourne, Heidelberg, Victoria, Australia; Department of Pediatric Neurology, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), Université Libre de Bruxelles (ULB), Brussels, Belgium.
Department of Medicine, The University of Melbourne, Heidelberg, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia; Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Epilepsy Res. 2023 May;192:107131. doi: 10.1016/j.eplepsyres.2023.107131. Epub 2023 Mar 30.
Lennox Gastaut syndrome (LGS) can be conceptualised as a "secondary network epilepsy", in which the shared electroclinical manifestations reflect epileptic recruitment of a common brain network, despite a range of underlying aetiologies. We aimed to identify the key networks recruited by the epileptic process of LGS using interictal 2-deoxy-2-(F)fluoro-D-glucose positron emission tomography (F-FDG-PET).
Group analysis of cerebral F-FDG-PET, comparing 21 patients with LGS (mean age = 15 years) and 18 pseudo-controls (mean age = 19 years), studied at Austin Health Melbourne, between 2004 and 2015. To minimise the influence of individual patient lesions in the LGS group, we only studied brain hemispheres without structural MRI abnormalities. The pseudo-control group consisted of age- and sex-matched patients with unilateral temporal lobe epilepsy, using only the hemispheres contralateral to the side of epilepsy. Voxel-wise permutation testing compared F-FDG-PET uptake between groups. Associations were explored between areas of altered metabolism and clinical variables (age of seizure onset, proportion of life with epilepsy, and verbal/nonverbal ability). Penetrance maps were calculated to explore spatial consistency of altered metabolic patterns across individual patients with LGS.
Although not always readily apparent on visual inspection of individual patient scans, group analysis revealed hypometabolism in a network of regions including prefrontal and premotor cortex, anterior and posterior cingulate, inferior parietal lobule, and precuneus (p < 0.05, corrected for family-wise error). These brain regions tended to show a greater reduction in metabolism in non-verbal compared to verbal LGS patients, although this difference was not statistically significant. No areas of hypermetabolism were detected on group analysis, although ∼25 % of individual patients showed increased metabolism (relative to pseudo-controls) in the brainstem, putamen, thalamus, cerebellum, and pericentral cortex.
Interictal hypometabolism in frontoparietal cortex in LGS is compatible with our previous EEG-fMRI and SPECT studies showing that interictal bursts of generalised paroxysmal fast activity and tonic seizures recruit similar cortical regions. This study provides further evidence that these regions are central to the electroclinical expression of LGS.
Lennox-Gastaut综合征（LGS）可被视为一种“继发性网络癫痫”，尽管存在多种潜在病因，但该综合征共同的电临床表型反映了一个共同脑网络的癫痫性激活。我们旨在通过发作间期2-脱氧-2-（F）氟-D-葡萄糖正电子发射断层扫描（F-FDG-PET）来确定LGS癫痫发作过程中激活的关键网络。
对大脑F-FDG-PET进行组间分析，比较2004年至2015年间在墨尔本奥斯汀健康中心研究的21例LGS患者（平均年龄15岁）和18例假对照组（平均年龄19岁）。为尽量减少LGS组个体患者病变的影响，我们仅研究无结构MRI异常的脑半球。假对照组由年龄和性别匹配的单侧颞叶癫痫患者组成，仅使用癫痫对侧的脑半球。采用体素水平的置换检验比较两组间的F-FDG-PET摄取情况。探究代谢改变区域与临床变量（癫痫发作起始年龄、癫痫病程占生命的比例以及语言/非语言能力）之间的关联。计算穿透图以探究LGS个体患者间代谢模式改变的空间一致性。
尽管在个体患者扫描的视觉检查中并不总是容易发现，但组间分析显示包括前额叶和运动前皮质、前扣带回和后扣带回、顶下小叶和楔前叶在内的区域网络存在代谢减低（p<0.05，经家族性错误校正）。与语言型LGS患者相比，这些脑区在非语言型LGS患者中往往显示出更大程度的代谢减低，尽管这种差异无统计学意义。组间分析未检测到代谢增高区域，尽管约25%的个体患者在脑干、壳核、丘脑、小脑和中央周围皮质显示代谢增加（相对于假对照组）。
LGS患者额顶叶皮质的发作间期代谢减低与我们之前的脑电图功能磁共振成像（EEG-fMRI）和单光子发射计算机断层扫描（SPECT）研究结果相符，这些研究表明，发作间期的广泛性阵发性快速活动和强直发作可激活相似的皮质区域。本研究进一步证明这些区域是LGS电临床表现的核心。
