Horvath Andras Attila, Csernus Emoke Anna, Lality Sara, Kaminski Rafal M, Kamondi Anita
Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
Department of Neurology, National Institute of Clinical Neurosciences, Budapest, Hungary.
Front Neurosci. 2020 Oct 15;14:557416. doi: 10.3389/fnins.2020.557416. eCollection 2020.
Cognitive impairment is a common and seriously debilitating symptom of various mental and neurological disorders including autism, attention deficit hyperactivity disorder, multiple sclerosis, epilepsy, and neurodegenerative diseases, like Alzheimer's disease. In these conditions, high prevalence of epileptiform activity emerges as a common pathophysiological hallmark. Growing body of evidence suggests that this discrete but abnormal activity might have a long-term negative impact on cognitive performance due to neuronal circuitries' remodeling, altered sleep structure, pathological hippocampo-cortical coupling, and even progressive neuronal loss. In animal models, epileptiform activity was shown to enhance the formation of pathological amyloid and tau proteins that in turn trigger network hyperexcitability. Abolishing epileptiform discharges might slow down the cognitive deterioration. These findings might provide basis for therapeutic use of antiepileptic drugs in neurodegenerative cognitive disorders. The aim of our review is to describe the data on the prevalence of epileptiform activity in various cognitive disorders, to summarize the current knowledge of the mechanisms of epileptic activity in relation to cognitive impairment, and to explore the utility of antiepileptic drugs in the therapy of cognitive disorders. We also propose future directions for drug development and novel therapeutic interventions targeting epileptiform discharges in these disorders.
认知障碍是包括自闭症、注意力缺陷多动障碍、多发性硬化症、癫痫以及神经退行性疾病（如阿尔茨海默病）等各种精神和神经疾病中常见且严重削弱功能的症状。在这些疾病中，癫痫样活动的高发生率是一种常见的病理生理特征。越来越多的证据表明，这种离散但异常的活动可能由于神经元回路重塑、睡眠结构改变、病理性海马-皮质耦合甚至神经元进行性丧失而对认知表现产生长期负面影响。在动物模型中，癫痫样活动被证明会增强病理性淀粉样蛋白和tau蛋白的形成，进而引发网络兴奋性过高。消除癫痫样放电可能会减缓认知衰退。这些发现可能为在神经退行性认知障碍中使用抗癫痫药物进行治疗提供依据。我们综述的目的是描述各种认知障碍中癫痫样活动的发生率数据，总结目前关于癫痫活动与认知障碍相关机制的知识，并探讨抗癫痫药物在认知障碍治疗中的效用。我们还提出了针对这些疾病中癫痫样放电的药物开发和新型治疗干预的未来方向。
