Journal of NeuroVirology

, Volume 14, Issue 3, pp 177–185 | Cite as

The relationship between encephalitis lethargica and influenza: A critical analysis

  • Sherman McCall
  • Joel A. Vilensky
  • Sid Gilman
  • Jeffery K. Taubenberger


Since encephalitis lethargica’s (EL) prevalence in the 1920s, epidemiologic and clinical debate has persisted over whether EL was caused by, potentiated by, or merely coincident with the Spanish influenza pandemic. Epidemiologic analyses generally suggest that the disorders were coincidental. Beginning in the 1970s, modern experiments on archival brain samples mainly failed to confirm a direct relationship between influenza and EL. These experimental studies have technical limitations, e.g., the appropriateness of antibodies, polymerase chain reaction (PCR) primers and controls, and the extreme paucity and age of available material. These factors render the case against influenza less decisive than currently perceived. Nevertheless, there is little direct evidence supporting influenza in the etiology of EL. Almost 100 years after the EL epidemic, its etiology remains enigmatic, raising the possibility of a recurrence of EL in a future influenza pandemic.


bird flu epidemic encephalitis sleepy sickness von Economo’s disease 


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Copyright information

© Journal of NeuroVirology, Inc. 2008

Authors and Affiliations

  • Sherman McCall
    • 1
  • Joel A. Vilensky
    • 2
  • Sid Gilman
    • 3
  • Jeffery K. Taubenberger
    • 4
  1. 1.Department of Clinical PathologyUS Army Medical Research Institute of Infectious Diseases (USAMRIID)Fort DetrickUSA
  2. 2.Department of Anatomy and Cell BiologyIndiana University School of MedicineFort WayneUSA
  3. 3.Department of NeurologyUniversity of Michigan School of MedicineAnn ArborUSA
  4. 4.Laboratory of Infectious DiseasesNational Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesdaUSA

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