The dominant epidemiological feature of encephalitis lethargica was its unique time distribution. Although epidemics of encephalitic disease had occurred in conjunction with many previous influenza epidemics - 1580,1658,1673-5,1711-2,1729,1767, 1780-2, 1830-3, 1847-8, and especially 1889-92 -the global pandemic of encephalitis accompanying and following the 1918 influenza pandemic was in a class by itself with respect to virulence and sequelae. Along with its unique time distribution, 1917—26, the encephalitis lethargica epidemic, as Figure VIII.46.1 indicates, also had a pronounced seasonal predilection for the winter months. Encephalitis cases often occurred in such close conjunction with individual and community attacks of influenza that many professional and laypersons initially believed the disease to be caused by the devastatingly virulent influenza. But the fact that many cases and epidemics of encephalitis subsequently occurred at times when, and in places where, there was no discernible influenza activity generated confusion and skepticism that influenza could be the principal cause. Long latent intervals and slow viruses were not well recognized in 1918; hence encephalitis epidemics occurring a year and more after attacks of influenza were perceived as evidence against rather than supportive of influenza as the cause. Likewise, the fact that influenza was highly contagious and encephalitis was not was misinterpreted as indicating that these were unrelated diseases rather than being different manifestations of the same viral agent.

Earliest reports of epidemic encephalitis in 1917 by Constantin Economo in Vienna and by French observers differed little in substance; but Economo's provocative title, encephalitis lethargica - giving unique emphasis to one sign in the broad spectrum of clinical manifestations - gained him lasting recognition while generating ongoing diagnostic confusion.

Although these reports of encephalitis preceded the explosive general global dissemination of influenza in 1918, influenza was active in war-torn Europe during the winter of 1916-17. In 1918, in close association with the initial massive waves of influenza, encephalitis was reported in Britain, Scandinavia, Germany, the United States, and many other countries; but the greatest epidemic peaks of encephalitis occurred in 1919-20 and during subsequent winters - as shown for Seattle in Figure Vm.46.1.

Typically, encephalitis lethargica was generally distributed by age, sex, race, occupation, education, economic status, and geographic location. Ages of cases ranged from infancy to old age, with the highest attack rates among young adults; and the sexes were equally represented. Rarely was there discernible clustering of encephalitic cases within families and neighborhoods; and where such was reported, it is retrospectively apparent that the clustering arose as a result of diagnostic confusion with other causes of central nervous system disease-for example, botulism.

Attack rates for encephalitis lethargica during the pandemic years 1918-26 approached 1 case per 1,000 general population in the United States and in European countries where fairly complete records were maintained. Of those afflicted, roughly one third died during their acute illness. Extensive but less precise reports from throughout the world indicate that attack rates for encephalitis lethargica may have been similar worldwide, except in those few small populations, most notably American Samoa, where neither influenza nor encephalitis occurred during the pandemic years. Hence, the world total of encephalitis lethargica cases was probably more than 1.5 million - of whom about 500,000 died of acute illness and more died from parkinsonism and other complications following the acute illness stage.

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