The centennial lesson of encephalitis lethargica.

We commemorate the centenary of Constantin von Economo's description of encephalitis lethargica, a mysterious disease that had a significant effect on 20th-century neuroscience. In the acute phase, encephalitis lethargica was marked by intractable somnolence, which von Economo attributed to lesions in the diencephalon, thereby paving the way for future efforts to localize the regulation of sleep in the subcortical brain. At the same time, neuropathologic findings in postencephalitic parkinsonism affirmed the role of the substantia nigra in the pathophysiology of parkinsonism. The occurrence of psychiatric symptoms in patients with encephalitis lethargica-such as mood disorders, obsessive-compulsive behavior, and bradyphrenia-drew attention to the organic basis of mental illness.