PMID- 29978423 OWN - NLM STAT- MEDLINE DCOM- 20190701 LR - 20200811 IS - 1559-1182 (Electronic) IS - 0893-7648 (Print) IS - 0893-7648 (Linking) VI - 56 IP - 3 DP - 2019 Mar TI - Viral Triggers and Inflammatory Mechanisms in Pediatric Epilepsy. PG - 1897-1907 LID - 10.1007/s12035-018-1215-5 [doi] AB - Experimental and clinical findings suggest a crucial role for inflammation in the onset of pediatric seizures; this mechanism is not targeted by conventional antiepileptic drugs and may contribute to refractory epilepsy. Several triggers, including infection with neurotropic viruses such as human herpesvirus 6 (HHV-6), other herpesviruses, and picornaviruses, appear to induce activation of the innate and adaptive immune systems, which results in several neuroinflammatory responses, leading to enhanced neuronal excitability, and ultimately contributing to epileptogenesis. This review discusses the proposed mechanisms by which infection with herpesviruses, and particularly with HHV-6, and ensuing inflammation may lead to seizure generation, and later development of epilepsy. We also examine the evidence that links herpesvirus and picornavirus infections with acute seizures and chronic forms of epilepsy. Understanding the mechanisms by which specific viruses may trigger a cascade of alterations in the CNS ultimately leading to epilepsy appears critical for the development of therapeutic agents that may target the virus or inflammatory mechanisms early and prevent progression of epileptogenesis. FAU - Bartolini, Luca AU - Bartolini L AUID- ORCID: 0000-0003-2755-8218 AD - Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, NIH, Building 10, room 7-5680, 10 Center Drive, Bethesda, MD, 20814, USA. luca.bartolini@nih.gov. AD - Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, NIH, 10 Center Drive, Bethesda, MD, 20892, USA. luca.bartolini@nih.gov. AD - Center for Neuroscience, Children's National Medical Center, George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA. luca.bartolini@nih.gov. FAU - Libbey, Jane E AU - Libbey JE AD - Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA. FAU - Ravizza, Teresa AU - Ravizza T AD - Neuroscience Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156, Milan, Italy. FAU - Fujinami, Robert S AU - Fujinami RS AD - Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA. FAU - Jacobson, Steven AU - Jacobson S AD - Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, NIH, 10 Center Drive, Bethesda, MD, 20892, USA. FAU - Gaillard, William D AU - Gaillard WD AD - Center for Neuroscience, Children's National Medical Center, George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA. LA - eng GR - R01 NS065714/NS/NINDS NIH HHS/United States PT - Journal Article PT - Review DEP - 20180705 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 SB - IM MH - Epilepsy/*etiology/pathology/virology MH - Humans MH - Inflammation/*complications MH - Virus Diseases/*complications PMC - PMC7416551 MID - NIHMS1615792 OTO - NOTNLM OT - HHV-6 OT - Inflammation OT - Picornaviruses OT - Seizures OT - Theiler's murine encephalomyelitis virus COIS- Conflict of Interest The authors declare that they have no conflict of interest. EDAT- 2018/07/07 06:00 MHDA- 2019/07/02 06:00 PMCR- 2020/08/10 CRDT- 2018/07/07 06:00 PHST- 2018/03/15 00:00 [received] PHST- 2018/06/27 00:00 [accepted] PHST- 2018/07/07 06:00 [pubmed] PHST- 2019/07/02 06:00 [medline] PHST- 2018/07/07 06:00 [entrez] PHST- 2020/08/10 00:00 [pmc-release] AID - 10.1007/s12035-018-1215-5 [pii] AID - 10.1007/s12035-018-1215-5 [doi] PST - ppublish SO - Mol Neurobiol. 2019 Mar;56(3):1897-1907. doi: 10.1007/s12035-018-1215-5. Epub 2018 Jul 5.