Foremost among recorded encephalitis epidemics was the global pandemic of encephalitis lethargica that emerged in and from Europe during the last years of the Great War and occurred in successive waves throughout the world during the following decade. Although the diagnosis of encephalitis lethargica is sometimes applied to sporadically occurring cases of inflammation of the brain having a strong lethargic or stuporous aspect, this discussion focuses upon the encephalitis pandemic that accompanied and followed the 1918 influenza pandemic.

Clinical Manifestations and Pathology

Clinically, encephalitis lethargica was characterized by diffuse involvement of the brain and spinal cord, producing practically the entire range of the signs and symptoms of neurological disease. Sometimes occurring in close conjunction with respiratory-spread influenza, but more often after a long interval, encephalitis patients developed an illness usually characterized by the triad signs of fever, lethargy, and disturbances of eye movement, along with a broad range of other signs and symptoms. These included headache, tremor, weakness, depression, delirium, convulsions, the inability to articulate ideas, coordinate movements, or recognize the importance of sensory stimuli, as well as psychosis and stupor. Oculogyric crisis (eyeballs fixed in one position for a period of time) and other disorders of eye movement, the most frequent sign of localized damage to the nervous system, were present in three-fourths of the cases. Lethargy, another common symptom, in some patients lasted only a few days, but in others it persisted for weeks and months or until death from comatose respiratory failure. Not infrequently, spasmodic twitching and severe psychic and behavior changes persisted long after the acute illness.