Encephalitis lethargica (EL) is an atypical form of encephalitis. Also known as "von Economo Encephalitis", "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly–transmitted sleeping sickness), it was first described in 1917 by neurologist Constantin von Economo and pathologist Jean-René Cruchet. The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless. Between 1915 and 1926, an epidemic of encephalitis lethargica spread around the world. The exact number of people infected is unknown, but it is estimated that more than one million people contracted the disease during the epidemic, which directly caused more than 500,000 deaths. Most of those who survived never recovered their pre-morbid vigor.

thumb|right|Neurologist Constantin von Economo (upper left photo) and the patients

Signs and symptoms

Encephalitis lethargica is characterized by high fever, sore throat, headache, lethargy, double vision, delayed physical and mental response, sleep inversion and catatonia. In severe cases, patients may enter a coma-like state (akinetic mutism). Patients may also experience abnormal eye movements ("oculogyric crises"), Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis. Klazomania, a vocal tic involving compulsive screaming, is sometimes present.

Approximately a third of the affected children experienced change of behavior, with many of them becoming "delinquents". Boys between the ages of 5 and 18 years were the most affected. Symptoms include change of personality, restlessness, irregular sleeping habits, emotional instability manifesting as irritability, crying spells, and temper tantrums, including impulsivity, and unpredictability, what Economo described as "moral insanity". More extreme cases include aggression and "shameless sexual activity". Children under the age of 5 years suffered severe developmental delays. Delays were also present in children between 5 and 14 years of age, even though the claims are controversial.

It is estimated that 25–90% of adults also suffered from psychological problems, including hysteria and abnormal behavior and movement. A large minority of patients described having bradyphrenia. Though it used to be believed that it was connected to the Spanish flu epidemic, modern research provides arguments against this claim.

Postencephalitic Parkinsonism was clearly documented to have followed an outbreak of encephalitis lethargica following the 1918 influenza pandemic; evidence for viral causation of the Parkinson's symptoms is circumstantial (epidemiologic, and finding influenza antigens in encephalitis lethargica patients), while evidence arguing against this cause is of the negative sort (for example, lack of viral RNA in postencephalitic Parkinsonian brain material).

Hence, while opinions on the relationship of encephalitis lethargica to influenza remain divided, the preponderance of literature appears skeptical.

The German neurologist , who examined hundreds of encephalitis lethargica patients during the 1920s, noted that their encephalitis lethargica typically evolved over time:

  • The early symptoms would be dominated by sleepiness or wakefulness.
  • A second symptom would lead to an oculogyric crisis.
  • The third symptom would be recovery, followed by a Parkinson-like syndrome.

If patients of Stern followed this course of disease, he diagnosed them with encephalitis lethargica. Stern suspected encephalitis lethargica to be close to poliomyelitis, but had no evidence. Nevertheless, he experimented with the convalescent serum of survivors of the first acute syndrome. He vaccinated patients with early-stage symptoms, telling them that it might be successful. Stern is the author of the definitive book, '.

In 2010, in a substantial compendium

After the publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic.

In 2012, Oliver Sacks, the author of the book Awakenings, about institutionalized survivors, acknowledged this virus as the probable cause of the disease. Other sources have suggested Streptococcus pneumoniae as a cause.

Diagnosis

There have been several proposed diagnostic criteria for encephalitis lethargica. One, which has been widely accepted, includes an acute or subacute encephalitic illness where all other known causes of encephalitis have been excluded. Another diagnostic criterion, suggested more recently, says that the diagnosis of encephalitis lethargica "may be considered if the patient's condition cannot be attributed to any other known neurological condition and that they show the following signs: influenza-like signs; hypersomnolence (hypersomnia), wakeability, ophthalmoplegia (paralysis of the muscles that control the movement of the eye), and psychiatric changes".

Others describe lethargy, "mask-like faces", excess blood in the meninges, and other general neurological symptoms.

Treatment

thumb|[[L-DOPA]]

Modern treatment approaches to encephalitis lethargica include immunomodulating therapies and treatments to remediate specific symptoms.

There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement. The disease becomes progressive, with evidence of brain damage similar to that of Parkinson's disease.

Treatment is then symptomatic. L-DOPA (Levodopa) and other anti-Parkinson drugs often produce dramatic responses; however, most people given <small>L</small>-DOPA experience improvements that are short-lived.

History

Occurrences

Retrospective diagnosis tentatively suggests various historical outbreaks of encephalitis lethargica:

  • In 1580, Europe was swept by a serious febrile and lethargic illness that led to Parkinsonism and other neurological sequelae.
  • From 1673 to 1675, a similar serious epidemic occurred in London, which Thomas Sydenham described as . it was officially recognized as a distinct disease in 1917.

Neurologist Constantin von Economo published a paper in April&nbsp;1917 describing some of the cases he encountered in the winter months of 1916–1917. It is also known to cause postencephalitic parkinsonism (PEP).

  • Mervyn Peake (1911–1968), author of the Gormenghast books, began his decline towards death which was initially attributed to encephalitis lethargica with Parkinson's disease–like symptoms, although others have later suggested his decline in health and eventual death may have been due to Lewy body dementia.
  • Those described in the book Awakenings by the British neurologist Oliver Sacks.
  • Jane Norton Grew Morgan, wife of J. P. Morgan Jr., died of encephalitis lethargica in 1925. At the time, doctors attributed her encephalitis to having contracted influenza during the 1918 pandemic.

See also

  • Idiopathic disease
  • Idiopathic chronic fatigue
  • Chronic fatigue syndrome
  • Fever of unknown origin

References

Further reading

  • Describes the history of the disease, and the epidemic of the 1920s.
  • — item about the tracing of the infectious agent in encephalitis lethargica