Neurotherapeutics

, Volume 11, Issue 2, pp 297–310

Mechanisms of Epileptogenesis in Pediatric Epileptic Syndromes: Rasmussen Encephalitis, Infantile Spasms, and Febrile Infection-related Epilepsy Syndrome (FIRES)

  • Carlos A. Pardo
  • Rima Nabbout
  • Aristea S. Galanopoulou
Review

DOI: 10.1007/s13311-014-0265-2

Cite this article as:
Pardo, C.A., Nabbout, R. & Galanopoulou, A.S. Neurotherapeutics (2014) 11: 297. doi:10.1007/s13311-014-0265-2

Abstract

The mechanisms of epileptogenesis in pediatric epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with age-specific epileptic syndromes, such as infantile spasms and West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as infections or fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric epileptic syndromes in which acute and rapidly progressive encephalopathies preceded by fever and/or infections, such as febrile infection-related epilepsy syndrome, or in chronic progressive encephalopathies, such as Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8+ T lymphocytes and neuroglial responses has been demonstrated in Rasmussen encephalitis, although the triggering factor of these responses remains unknown. Although the beneficial response to steroids and adrenocorticotropic hormone of infantile spasms, or preceding fever or infection in FIRES, may support a potential role of neuroinflammation as pathogenic factor, no definite demonstration of such involvement has been achieved, and genetic or metabolic factors are suspected. A major challenge for the future is discovering pathogenic mechanisms and etiological factors that facilitate the introduction of novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments in these pediatric epileptic syndromes.

Keywords

West syndromeinfantile spasmsFIRESepileptogenesisRasmussen encephalitis.

Supplementary material

13311_2014_265_MOESM1_ESM.pdf (511 kb)
ESM 1(PDF 511 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2014

Authors and Affiliations

  • Carlos A. Pardo
    • 1
  • Rima Nabbout
    • 2
  • Aristea S. Galanopoulou
    • 3
  1. 1.Department of Neurology, Division of Neuroimmunology and Neuroinfectious Disorders, Center for Pediatric Rasmussen SyndromeJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Centre de Reference Epilepsies Rares, Pediatric Neurology DepartmentNecker Enfants Malades Hospital, APHP, Inserm U663, University Paris DescartesParisFrance
  3. 3.Laboratory of Developmental Epilepsy, Saul R. Korey Department of Neurology, Dominick P. Purpura Department of Neuroscience, Montefiore/Einstein Epilepsy Management CenterAlbert Einstein College of MedicineBronxUSA