Acta Neuropathologica

, Volume 131, Issue 2, pp 211–234 | Cite as

Infections, inflammation and epilepsy

  • Annamaria Vezzani
  • Robert S. Fujinami
  • H. Steve White
  • Pierre-Marie Preux
  • Ingmar Blümcke
  • Josemir W. Sander
  • Wolfgang LöscherEmail author


Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing structural or functional derangement of brain physiology may lead to seizures, and different conditions may express themselves solely by recurrent seizures and thus be labelled “epilepsy.” Worldwide, epilepsy is the most common serious neurological condition. The range of risk factors for the development of epilepsy varies with age and geographic location. Congenital, developmental and genetic conditions are mostly associated with the development of epilepsy in childhood, adolescence and early adulthood. Head trauma, infections of the central nervous system (CNS) and tumours may occur at any age and may lead to the development of epilepsy. Infections of the CNS are a major risk factor for epilepsy. The reported risk of unprovoked seizures in population-based cohorts of survivors of CNS infections from developed countries is between 6.8 and 8.3 %, and is much higher in resource-poor countries. In this review, the various viral, bacterial, fungal and parasitic infectious diseases of the CNS which result in seizures and epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as well as the role of experimental models to study mechanisms of epileptogenesis induced by infectious agents, is reviewed. The sterile (non-infectious) inflammatory response that occurs following brain insults is also discussed, as well as its overlap with inflammation due to infections, and the potential role in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures is reviewed. Potential strategies to prevent epilepsy resulting from brain infections and non-infectious inflammation are also considered.


Seizures Epileptogenesis Central nervous system Cytokines Meningitis Encephalitis Neuroinfectiology Virus Bacteria Fungi Parasites 



AV and WL have received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 602102 (EPITARGET). WL’s research is supported by the Niedersachsen-Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony (Germany) and AV’s research by the Fondazione Monzino. RSF is supported by NIH R01 NS065714. JWS is based at the UCLH/UCL Comprehensive Bio-Medical Research Centre which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. JWS receives research support from the Dr. Marvin Weil Epilepsy Research Fund and the UK Epilepsy Society. IB received funding from the European Union’s Seventh Framework Program under Grant Agreement No. 602531 (DESIRE). We thank Dr. Ingo Gerhauser, Christopher Käufer and Dr. Sonja Bröer for preparing the photomicrographs in Fig. 11, Drs. Arturo Carpio Rodas, Indran Davagnanam and Chandrashekar Hoskote for providing brain images of patients, and Profs. Wolfgang Brück, Roland Nau and Thomas Henze for providing brain sections or photomicrographs of patients. We are grateful to Dr. Gail S Bell for critically reviewing the manuscript.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Annamaria Vezzani
    • 1
  • Robert S. Fujinami
    • 2
  • H. Steve White
    • 3
  • Pierre-Marie Preux
    • 4
    • 5
    • 6
  • Ingmar Blümcke
    • 7
  • Josemir W. Sander
    • 8
    • 9
  • Wolfgang Löscher
    • 10
    • 11
    Email author
  1. 1.Department of NeuroscienceIRCCS-“Mario Negri” Institute for Pharmacological ResearchMilanItaly
  2. 2.Department of PathologyUniversity of UtahSalt Lake CityUSA
  3. 3.Department of PharmacologyUniversity of UtahSalt Lake CityUSA
  4. 4.INSERM UMR1094, Tropical NeuroepidemiologyLimogesFrance
  5. 5.Institute of Neuroepidemiology and Tropical NeurologySchool of Medicine, University of LimogesLimogesFrance
  6. 6.Center of Epidemiology, Biostatistics, and Research Methodology, CHU LimogesLimogesFrance
  7. 7.Department of NeuropathologyUniversity Hospital ErlangenErlangenGermany
  8. 8.NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of NeurologyLondonUK
  9. 9.Stichting Epilepsie Instellingen Nederland (SEIN)HeemstedeThe Netherlands
  10. 10.Department of Pharmacology, Toxicology, and PharmacyUniversity of Veterinary MedicineHannoverGermany
  11. 11.Center for Systems NeuroscienceHannoverGermany

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