Was encephalitis lethargica a post-influenzal or some other phenomenon? Time to re-examine the problem

Encephalitis lethargica (EL) was first reported in 1917 in central Europe. It became epidemic in the winter of 1918/1919 concurrently with the pandemic of influenza, and by then had reached Russia and North America. It spread throughout the world in epidemic form, mainly in the succeeding winters, up to 1927. By then about 65000 cases had been reported, although the true number worldwide can only be guessed at. EL mortality was about 30% in the acute stage, and similar during recurrences. Half of the survivors had persistent or recurrent neuro-psychiatric illness, with Parkinsonism a frequent end stage. Most contemporary observers attributed EL to a virus and some believed it was specifically a post-influenzal complication. The epidemiology of EL mostly points to an infective cause, e.g. a seasonal respiratory or gastrointestinal virus with infrequent encephalitic expression but the ability to persist, flare and progressively damage the brain. However, any link with the influenza virus strain of 1918/1919 remains hypothetical. The aetiological theories that have been applied to EL are reviewed and the question is raised whether broader laboratory investigation might now reveal a continuing low endemicity of EL and identify its cause.