Getts Daniel R, Balcar Vladimir J, Matsumoto Izuru, Müller Marcus, King Nicholas J C
The Discipline of Pathology, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
J Neurochem. 2008 Mar;104(5):1167-76. doi: 10.1111/j.1471-4159.2007.05171.x. Epub 2008 Jan 17.
Viral encephalitis affects approximately 7.5 people/100 000 and carries a high rate of morbidity and mortality. Most patients with viral encephalitis will develop some form of seizure during the infectious process, and of those who survive encephalitic disease, approximately 4-20% will develop epilepsy. Arthropod-borne (arbo)viruses are the leading cause of viral encephalitis in the world today, with between 10% and 35% of patients infected with these viruses displaying some form of seizure. Several neurotropic DNA viruses, including Herpes and cytomegalovirus also commonly cause seizures in infected patients. In the clinical setting, the cause of seizures seen during viral encephalitis is usually attributed to acute febrile responses. However, it has become apparent that the mechanisms behind seizure generation during viral encephalitis are likely to be much more complicated. For example, CD4(+) and CD8(+) T cells possibly through their secretion of interferon-gamma, appear to play an important role in determining neuronal responses when challenged with kainic acid. In addition, the ability of the human immunodeficiency virus, transactivating protein to modulate NMDA signaling possibly triggering seizures, highlights the fact that elements of the antiviral response and even virally derived proteins are capable of directly manipulating neuronal function. Understanding the complex relationships between the CNS, the immune system, and invading pathogens is a critical step in understanding the pathogenesis of seizures seen during viral infections and informing the development of novel therapies.
病毒性脑炎的发病率约为每10万人中有7.5人患病，且发病率和死亡率都很高。大多数病毒性脑炎患者在感染过程中会出现某种形式的癫痫发作，而在脑炎疾病幸存者中，约4%-20%会发展为癫痫。节肢动物传播的（虫媒）病毒是当今世界病毒性脑炎的主要病因，感染这些病毒的患者中有10%至35%会出现某种形式的癫痫发作。几种嗜神经性DNA病毒，包括疱疹病毒和巨细胞病毒，也常导致感染患者癫痫发作。在临床环境中，病毒性脑炎期间出现癫痫发作的原因通常归因于急性发热反应。然而，很明显，病毒性脑炎期间癫痫发作背后机制可能要复杂得多。例如，CD4(+)和CD8(+) T细胞可能通过分泌γ干扰素，在受到海人藻酸刺激时，似乎在决定神经元反应方面发挥重要作用。此外，人类免疫缺陷病毒反式激活蛋白调节NMDA信号传导可能引发癫痫发作，这突出了抗病毒反应的要素甚至病毒衍生蛋白能够直接操纵神经元功能这一事实。了解中枢神经系统、免疫系统和入侵病原体之间的复杂关系，是理解病毒感染期间癫痫发作发病机制以及为新型疗法的开发提供信息的关键一步。
