PDF(Pubmed)
Abstract：
UNASSIGNED: Preclinical studies in a mouse model have shown that SYNGAP1 haploinsufficiency results in an epilepsy phenotype with excessive GluA2-AMPA insertion specifically on the soma of fast-spiking parvalbumin-positive interneurons associated with significant dysfunction of cortical gamma homeostasis that was rescued by perampanel (PER), an AMPA receptor blocker. In this single case, we aimed to investigate the presence of dysregulated cortical gamma in a toddler with a pathogenic SYNGAP1 variant and report on the effect of low-dose PER on electroencephalogram (EEG) and clinical profile.
UNASSIGNED: Clinical data from physician\'s clinic notes; genetic testing reports; developmental scores from occupational therapy, physical therapy, speech and language therapy evaluations; and applied behavioral analysis reports were reviewed. Developmental assessments and EEG analysis were done pre- and post-PER.
UNASSIGNED: Clinically, the patient showed improvements in the developmental profile and sleep quality post-PER. EEG spectral power analysis in our patient revealed a loss of gamma power modulation with behavioral-state transitions similar to what was observed in Syngap1+/- mice. Furthermore, the administration of low-dose PER rescued the dysfunctional cortical gamma homeostasis, similar to the preclinical study. However, as in the epileptic mice, PER did not curb epileptiform discharges or clinical seizures.
UNASSIGNED: Similar to the Syngap1+/- mice, cortical gamma homeostasis was dysregulated in the patient. This dysfunction was rescued by PER. These encouraging results necessitate further validation of gamma dysregulation as a potential translational EEG biomarker in SYNAP1-DEE. Low-dose PER can be explored as a therapeutic option through clinical trials.
UNASSIGNED: Clinical data from physician\'s clinic notes; genetic testing reports; developmental scores from occupational therapy, physical therapy, speech and language therapy evaluations; and applied behavioral analysis reports were reviewed. Developmental assessments and EEG analysis were done pre- and post-PER.
UNASSIGNED: Clinically, the patient showed improvements in the developmental profile and sleep quality post-PER. EEG spectral power analysis in our patient revealed a loss of gamma power modulation with behavioral-state transitions similar to what was observed in Syngap1+/- mice. Furthermore, the administration of low-dose PER rescued the dysfunctional cortical gamma homeostasis, similar to the preclinical study. However, as in the epileptic mice, PER did not curb epileptiform discharges or clinical seizures.
UNASSIGNED: Similar to the Syngap1+/- mice, cortical gamma homeostasis was dysregulated in the patient. This dysfunction was rescued by PER. These encouraging results necessitate further validation of gamma dysregulation as a potential translational EEG biomarker in SYNAP1-DEE. Low-dose PER can be explored as a therapeutic option through clinical trials.
摘要：
■在小鼠模型中的临床前研究表明，SYNGAP1单倍体功能不全导致癫痫表型，其GluA2-AMPA插入过多，特别是在与皮质γ稳态的显着功能障碍相关的快速尖峰小清蛋白阳性中间神经元的体细胞上由perampanel（PER）挽救，AMPA受体阻断剂。在这种情况下，我们的目的是调查患有致病性SYNGAP1变异体的幼儿是否存在皮质γ异常调节,并报告低剂量PER对脑电图(EEG)和临床特征的影响.
■来自医生临床记录的临床数据；基因检测报告；职业治疗的发展评分，物理治疗,言语和语言治疗评估；以及应用行为分析报告进行了审查。在PER前后进行发育评估和脑电图分析。
■临床，患者在PER后表现出发育状况和睡眠质量的改善.我们患者的EEG频谱功率分析显示，行为状态转变的伽马功率调制损失与Syngap1/-小鼠中观察到的相似。此外，低剂量PER的施用拯救了功能失调的皮层γ稳态，类似于临床前研究。然而,就像癫痫小鼠一样，PER不能抑制癫痫样放电或临床癫痫发作。
■类似于Syngap1+/-小鼠，患者皮质γ稳态失调.这种功能障碍是由PER挽救的。这些令人鼓舞的结果需要进一步验证作为SYNAP1-DEE中潜在的翻译EEG生物标志物的γ失调。可以通过临床试验探索低剂量PER作为治疗选择。
■来自医生临床记录的临床数据；基因检测报告；职业治疗的发展评分，物理治疗,言语和语言治疗评估；以及应用行为分析报告进行了审查。在PER前后进行发育评估和脑电图分析。
■临床，患者在PER后表现出发育状况和睡眠质量的改善.我们患者的EEG频谱功率分析显示，行为状态转变的伽马功率调制损失与Syngap1/-小鼠中观察到的相似。此外，低剂量PER的施用拯救了功能失调的皮层γ稳态，类似于临床前研究。然而,就像癫痫小鼠一样，PER不能抑制癫痫样放电或临床癫痫发作。
■类似于Syngap1+/-小鼠，患者皮质γ稳态失调.这种功能障碍是由PER挽救的。这些令人鼓舞的结果需要进一步验证作为SYNAP1-DEE中潜在的翻译EEG生物标志物的γ失调。可以通过临床试验探索低剂量PER作为治疗选择。
