Viruses and the immune system: their roles in seizure cascade development.
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.
Getts
Daniel R
DR
The Discipline of Pathology, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia. dgetts@med.usyd.edu.au
Balcar
Vladimir J
VJ
Matsumoto
Izuru
I
Müller
Marcus
M
King
Nicholas J C
NJ
D000818:Animals; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D009474:Neurons / Q000502:physiology / Q000821:virology; D012640:Seizures / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015398:Signal Transduction / Q000276:immunology*; D014780:Viruses / Q000276:immunology*