PDF(Pubmed)
Abstract：
Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between. After commencing perampanel, individuals had higher task-related activations in left orbitofrontal cortex (OFC), fewer task-related activations in the subcortical regions including the left thalamus and left caudate, and lower task-related thalamocaudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).
摘要：
Perampanel,突触后α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的非竞争性拮抗剂，对控制双侧强直阵挛性癫痫发作有效，但也已知会增加愤怒情绪。使用统计参数映射衍生的激活和任务调节的功能连接（心理生理相互作用）度量，我们调查了14名局灶性癫痫患者，他们两次进行了言语流畅性功能磁共振成像，在加药治疗前后。为了比较，我们纳入了28名癫痫患者，临床特征倾向匹配，他们有两次扫描，但两者之间的ASM制度没有变化。在开始Perampanel之后,个体在左额叶皮质（OFC）中具有较高的任务相关激活，在皮层下区域，包括左丘脑和左尾状，任务相关的激活较少，与任务相关的丘脑-尾状和尾状-底质连通性较低。在左OFC与前肌和左内侧额叶之间观察到与任务相关的连通性降低。我们的结果强调了与双侧强直-阵挛性癫痫发作（丘脑和尾状核）的受益治疗效果相关的大脑区域，以及伴随愤怒和侵略（OFC）增加的perampanel的不良情感副作用。
