Encephalitis lethargica epidemic milestones in early sleep neurobiology researches.

Around 100 years ago, the outbreak of peculiar encephalitis promoted knowledge advancement regarding sleep and psychomotricity control. This epidemic is believed to have disappeared ten years after it started, and it remained from 1916 to 1927. Since then, only a few sporadic cases have been reported, but previously, they happened in occasional and epidemics forms. Two pioneers in describing the cases were Jean-René Cruchet and his collaborators, and Constantin Von Economo. The firsts described diffuse symptomatology, "sub-acute encephalomyelitis." However, the reports by the Austrian aristocrat had a localized aspect which was admitted by him as a new disease, "Encephalitis lethargica" (EL). In his suppositions, based on clinical and anatomopathological material analysis, von Economo found distinct centers for sleep, in the rostral hypothalamus, and wakefulness, posterior hypothalamus. He plays an essential role in new achievements about EL and sleep neurobiology comprehension. These basic structural sleep-arousal regulatory neural systems had a lasting impact on contemporary sleep research, unfolded initially mainly by Frédéric Bremer, Giuseppe Moruzzi, and Horace Winchell Magoun, based on a passive theory of sleep induction. The lasts arrived at the conception of "diffuse" and "unspecific" ascending reticular activating system (ARAS) of the brain stem. This notion was unfolding until the idea of various interconnected "waking centers" and "sleep centers" levels, and also, active sleep induction.