Encephalitis lethargica: lessons for contemporary neuropsychiatry

Encephalitis lethargica (von Economo's encephalitis), pandemic from 1917 to 1926, opened a window on the study of behavioral consequences of infection-induced subcortical disorder. Widely varying acute manifestations included extrapyramidal disorders, myoclonus, eye movement disorders, paralyses, delirium, mood changes, inverted diurnal rhythms, and catatonia. Major pathological changes involved the substantia nigra, globus pallidus, and hypothalamus. A symptom-free recovery period was often followed by postencephalitic disturbances, typically parkinsonism in adults and conduct disorder in children. Occurrence of depression, mania, obsessive-compulsive disorder, and hyperactivity in post-encephalitic patients anticipated current concepts of the role of the basal ganglia in mood, personality, and obsessional syndromes. Observations of deferred onset and "tardy" hyperkinesias presaged current theories of the pathophysiology of tardive dyskinesia.