Encephalitis lethargica: could this disease be recognised if the epidemic recurred?

In 1973 Oliver Sacks published Awakenings, a book describing his evaluation of the effects of L-DOPA on postencephalitic parkinsonian patients at a chronic care facility in New York City. Their initial favourable response was so dramatic, and was described so well, that in 1990 the book was made into an award-winning film of the same name with Robin Williams portraying Dr Sacks and Robert De Niro one of the patients. Dr Sacks himself made a less well known documentary film, also called Awakenings, which depicted the patients themselves. In the book and both films, these engaging patients were “frozen in time.” All of them had initially suffered from encephalitis lethargica, a mysterious, devastating epidemic disease of the early part of the twentieth century that probably killed about 500,000 people worldwide (figs 1 and 2).1 Although some recent experimental and historical analyses have concluded that encephalitis lethargica was unlikely to have been related to the 1918 Spanish influenza epidemic, which most likely resulted from a mutation of the H1N1 virus, we think the available data are insufficient to eliminate influenza as the cause. Thus, there is a possibility that, should the H5N1 virus mutate so that it too becomes directly contagious between humans, and a bird-based influenza epidemic occurs, encephalitis lethargica will reappear.