Encephalitis lethargica

Ravindra Kumar Garg MD (Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.)
Matthew Lorincz MD PhD, editor. (Dr. Lorincz of the University of Michigan has no relevant financial relationships to disclose.)
Originally released December 8, 2006; last updated July 10, 2017; expires July 10, 2020

This article includes discussion of encephalitis lethargica, epidemic encephalitis, and von Economo disease. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Encephalitis lethargica was a mysterious epidemic disease of the 1920s and 1930s that was better known as the “sleepy” or “sleeping” sickness. It is associated with the subsequent development of postencephalitic parkinsonism, a condition that was popularized in Oliver Sacks' 1973 book, Awakenings, and the 1990 movie of the same name. Encephalitis lethargica evolved to have many manifestations other than a “lethargic type,” including types that were primarily characterized by insomnia and/or movement disorders. Differentiating points from idiopathic Parkinson disease include young age of onset, oculogyric crises, altered sleep-wake cycle, respiratory disturbances, and pyramidal signs. Pathologically, there is diffuse involvement of gray matter of the brain dominantly, the diencephalon, and the mesencephalon. There has been extensive debate about a possible role of the “Spanish” H1N1 influenza A pandemic virus in the development of encephalitis lethargica, but this relation has not yet been established. Several case reports suggested that infection with atypical enterovirus can result in a picture similar to encephalitis lethargica. MR signal abnormalities in the substantia nigra, thalamus, hippocampus, and subcortical white matter of the frontal lobes have been described. No definite treatment is available. Prognosis is variable. In some patients, extrapyramidal sequelae persist lifelong.

Key points

 

• Encephalitis lethargica is an acute polio-encephalitis of largely of unknown etiology.

 

• Encephalitis lethargica can only be diagnosed clinically.

 

• Oculogyric crises were not associated with acute cases during the epidemic period.

 

• Differentiating points from Parkinson disease are young age of onset, oculogyric crises, altered sleep cycle, respiratory disturbances, and pyramidal signs.

 

• Putative cases have linked the hyperkinetic form of the condition with NMDAR-Ab encephalitis.

 

• Although no clear data link encephalitis lethargica with influenza, such a linkage is still supported by some data and some clinicians.

Historical note and terminology

On April 17, 1917, at a meeting of the Vienna Society for Psychiatry and Neurology, Dr. Constantin von Economo described a new disease, encephalitis lethargica (von Economo 1931). Shortly thereafter, von Economo published his first article on the disease (von Economo 1917). He described a series of cases in which the patients exhibited “a kind of sleeping sickness” with an unusually prolonged course. Headache and malaise were the first symptoms followed by somnolence often associated with delirium, from which the patient could be easily awakened. This state could rapidly lead to death or could persist for long periods, either progressing to coma or ending with recovery. These signs were generally accompanied by paralysis in some of the cranial nerves, especially those affecting the eye. Ptosis was a typical sign. Von Economo concluded that he believed the disease was an “encephalitis,” with the variability relating to variations in neural localization of the causative agent.

The disease then began appearing in increasing frequency throughout the world, with official figures showing peaks of about 10,000 cases in 1920 and 1924 (Neal 1929), with a possible total mortality of 500,000 cases (Ravenholt and Foege 1982) during the entire epidemic period, which lasted until about 1940. Sporadic reports of encephalitis lethargica cases have continued to appear since then.

During the epidemic period, the signs and symptoms of the disease rapidly increased so that eventually 28 “types” had been described, with signs and symptoms encompassing virtually every neurologic system (Vilensky and Gilman 2006), including some that were antithetical to von Economo's original description (eg, an “insomnia” type). Kroker convincingly argued that curing encephalitis lethargica became the foremost aim of American neurology (especially New York City neurologists) during this period, and that the secondary goal of this effort was to increase significantly the prominence and potential of American neurology (Kroker 2004). Thus, there may have been some political aspects to the large number of encephalitis lethargica diagnoses. This possible overdiagnosis was also noted during the epidemic period (Ford 1937).

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