Molecular Neurobiology

, Volume 56, Issue 3, pp 1897–1907 | Cite as

Viral Triggers and Inflammatory Mechanisms in Pediatric Epilepsy

  • Luca BartoliniEmail author
  • Jane E. Libbey
  • Teresa Ravizza
  • Robert S. Fujinami
  • Steven Jacobson
  • William D. Gaillard


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.


HHV-6 Picornaviruses Seizures Inflammation Theiler’s murine encephalomyelitis virus 



Dr. Bartolini reports receiving grant support from the American Epilepsy Society and Epilepsy Foundation of America. Dr. Ravizza reports receiving grant support from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n°602102 (EPITARGET), and Fondazione Italo Monzino. Dr. Gaillard reports receiving grant support from NIH, CDC, NSF, PCORI, American Epilepsy Society, Epilepsy Foundation, CURE, and the Pediatric Epilepsy Research Foundation. Dr. Fujinami reports receiving grant support from NIH (R01NS065714).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  1. 1.Clinical Epilepsy SectionNational Institute of Neurological Disorders and Stroke, NIHBethesdaUSA
  2. 2.Division of Neuroimmunology and NeurovirologyNational Institute of Neurological Disorders and StrokeBethesdaUSA
  3. 3.Center for Neuroscience, Children’s National Medical CenterGeorge Washington UniversityWashingtonUSA
  4. 4.Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA
  5. 5.Neuroscience DepartmentIRCCS—Istituto di Ricerche Farmacologiche Mario NegriMilanItaly

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