Encephalitis lethargica: 100 years after the epidemic
Leslie A. Hoffman Joel A. Vilensky
Brain, Volume 140, Issue 8, 1 August 2017, Pages 2246?2251, https://doi.org/10.1093/brain/awx177
Published:
14 July 2017
Article history
Encephalitis lethargica is a neurological syndrome that spread across Europe and then the world beginning in the winter of 1916?17, and continuing into the 1930s. Although the exact number of people afflicted with encephalitis lethargica during the epidemic period is unknown, it is estimated to be more than one million worldwide (Ravenholt and Foege, 1982). Those who survived were sometimes left with lingering and permanent neurological sequelae that rendered them nearly akinetic. Although 100 years have elapsed since the beginning of the epidemic period, many questions remain about this mysterious illness: What causes it? How is it transmitted? Could an epidemic happen again?
Leslie A. Hoffman Joel A. Vilensky
Brain, Volume 140, Issue 8, 1 August 2017, Pages 2246?2251, https://doi.org/10.1093/brain/awx177
Published:
14 July 2017
Article history
Encephalitis lethargica is a neurological syndrome that spread across Europe and then the world beginning in the winter of 1916?17, and continuing into the 1930s. Although the exact number of people afflicted with encephalitis lethargica during the epidemic period is unknown, it is estimated to be more than one million worldwide (Ravenholt and Foege, 1982). Those who survived were sometimes left with lingering and permanent neurological sequelae that rendered them nearly akinetic. Although 100 years have elapsed since the beginning of the epidemic period, many questions remain about this mysterious illness: What causes it? How is it transmitted? Could an epidemic happen again?
Dale and colleagues, in a later paper (Dale et al., 2009), seemed to rescind the PANDAS hypothesis, and instead proposed that encephalitis lethargica, specifically the hyperkinetic form, was an autoimmune disorder caused by antibodies against NMDA receptors. Anti-NMDA receptor encephalitis is an autoimmune encephalitis that is commonly associated with ovarian teratomas in young females. It has a striking resemblance to encephalitis lethargica in its symptomatology and often begins with an influenza-like prodrome. Similarly, narcolepsy has been found to result from antibodies against aquaporin-4 in hypothalamic neurons. Furthermore, several European countries reported an increase in cases of narcolepsy following influenza vaccination or infection with influenza during the 2009 H1N1 influenza pandemic, which could explain the apparent connection between Spanish influenza and encephalitis lethargica following World War I. All of these observations point to an auto-immunological trigger as a potential cause of CNS disorders, and lend additional credibility to the autoimmune hypothesis.