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.
The causes of encephalitis lethargica are uncertain. Though it used to be believed that it was connected to the Spanish flu epidemic, modern research provides arguments against this claim. Some studies have explored its origins in an autoimmune response, and, separately or in relation to an immune response, links to pathologies of infectious disease – viral and bacterial, such as in the case of influenza, where a link with encephalitis is clear.
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).
The German neurologist Felix Stern [de], who examined hundreds of encephalitis lethargica patients during the 1920s, noted that their encephalitis lethargica typically evolved over time:
In 2010, in a substantial compendium reviewing the historic and contemporary views on EL, it quotes a researcher, writing in 1930, who stated, "we must confess that etiology is still obscure, the causative agent still unknown, the pathological riddle still unsolved", and went on to offer the following conclusion, as of that publication date:
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.
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.[needs update]
The number of people infected during the ten years of the pandemic is unknown, but it is estimated that more than 1 million people contracted the disease, which directly caused more than 500,000 deaths. Encephalitis lethargica assumed its most virulent form between October 1918 and January 1919.
In the United States the epidemic peaked from 1920 to 1924. It is estimated that as many as one million people were diagnosed with encephalitis lethargica during the epidemic period.
The pandemic disappeared in 1927, as abruptly and mysteriously as it first appeared. The great encephalitis pandemic coincided with the 1918 influenza pandemic, and it is likely that the influenza virus potentiated the effects of the causative agent of the encephalitis or lowered resistance to it in a catastrophic way.
Many surviving patients of the 1915–1927 pandemic seemed to make a complete recovery and return to their normal lives. However, the majority of survivors subsequently developed neurological or psychiatric disorders, often after years or decades of seemingly perfect health.
Post-encephalitic syndromes varied widely: sometimes they proceeded rapidly, leading to profound disability or death; sometimes very slowly; sometimes they progressed to a certain point and then stayed at this point for years or decades; and sometimes, following their initial onslaught, they remitted and disappeared. It is also known to cause postencephalitic parkinsonism (PEP). Though often thought of as a disease of the past, it is still seen in occasional cases today.
Economo's disease at Whonamedit? http://www.whonamedit.com/synd.cfm/3356.html
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Sacks (1990), pp. 319–321 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Sacks (1990), pp. 319–321 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Sacks (1990), pp. 319–321 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Sacks (1990), pp. 319–321 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Sacks (1990), pp. 319–321 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Sacks (1990), pp. 319–321 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Sacks (1990), pp. 12–19 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Hoffman, Leslie A.; Vilensky, Joel A. (2017-08-01). "Encephalitis lethargica: 100 years after the epidemic". Brain. 140 (8): 2246–2251. doi:10.1093/brain/awx177. ISSN 0006-8950. PMID 28899018. https://doi.org/10.1093%2Fbrain%2Fawx177
Dourmashkin, R.R. (September 1997). "What caused the 1918–30 epidemic of encephalitis lethargica?". Journal of the Royal Society of Medicine. 90 (9): 515–520. doi:10.1177/014107689709000916. ISSN 0141-0768. PMC 1296535. PMID 9370993. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296535
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Reid, A.H.; McCall, S.; Henry, J.M.; Taubenberger, J.K. (2001). "Experimenting on the past: The enigma of von Economo's encephalitis lethargica". Journal of Neuropathology and Experimental Neurology. 60 (7): 663–670. doi:10.1093/jnen/60.7.663. PMID 11444794. https://doi.org/10.1093%2Fjnen%2F60.7.663
Reid, A.H.; McCall, S.; Henry, J.M.; Taubenberger, J.K. (2001). "Experimenting on the past: The enigma of von Economo's encephalitis lethargica". Journal of Neuropathology and Experimental Neurology. 60 (7): 663–670. doi:10.1093/jnen/60.7.663. PMID 11444794. https://doi.org/10.1093%2Fjnen%2F60.7.663
Hoffman, Leslie A.; Vilensky, Joel A. (2017-08-01). "Encephalitis lethargica: 100 years after the epidemic". Brain. 140 (8): 2246–2251. doi:10.1093/brain/awx177. ISSN 0006-8950. PMID 28899018. https://doi.org/10.1093%2Fbrain%2Fawx177
Sacks (1990), pp. 12–19 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Sacks (1990), pp. 12–19 - Sacks, Oliver (1990). Awakenings. Vintage Books. ISBN 978-0-375-70405-5. OCLC 21910570. https://search.worldcat.org/oclc/21910570
Ravenholt, R.T.; Foege, William H. (1982-10-16). "1918 Influenza, encephalitis lethargica, Parkinsonism". The Lancet. 320 (8303): 860–864. doi:10.1016/S0140-6736(82)90820-0. ISSN 0140-6736. PMID 6126720. S2CID 45138249. Originally published as Volume 2, Issue 8303. Archived from the original on 2021-07-12. Retrieved 2020-12-23. http://www.sciencedirect.com/science/article/pii/S0140673682908200
McCall, Sherman; Vilensky, Joel A.; Gilman, Sid; Taubenberger, Jeffery K. (May 2008). "The relationship between encephalitis lethargica and influenza: A critical analysis". Journal of Neurovirology. 14 (3): 177–185. doi:10.1080/13550280801995445. ISSN 1355-0284. PMC 2778472. PMID 18569452. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778472
Hoffman, Leslie A.; Vilensky, Joel A. (2017-08-01). "Encephalitis lethargica: 100 years after the epidemic". Brain. 140 (8): 2246–2251. doi:10.1093/brain/awx177. ISSN 0006-8950. PMID 28899018. Archived from the original on 2021-03-04. Retrieved 2020-12-23. https://academic.oup.com/brain/article/140/8/2246/3970828
Dourmashkin, R.R. (September 1997). "What caused the 1918–30 epidemic of encephalitis lethargica?". Journal of the Royal Society of Medicine. 90 (9): 515–520. doi:10.1177/014107689709000916. ISSN 0141-0768. PMC 1296535. PMID 9370993. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296535
Hoffman, Leslie A.; Vilensky, Joel A. (2017-08-01). "Encephalitis lethargica: 100 years after the epidemic". Brain. 140 (8): 2246–2251. doi:10.1093/brain/awx177. ISSN 0006-8950. PMID 28899018. https://doi.org/10.1093%2Fbrain%2Fawx177
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McMillan, Roy; Peake, Mervyn (20 July 2011) [1959]. Butcher, Sara (ed.). Titus Alone (PDF) (publishers' liner notes) (abridged, audio ed.). Germany: Naxos Audiobooks. p. 7. ISBN 978-184-379-542-1. Retrieved 2 May 2018 – via Audible.com. But the plays were not the financial winners he had hoped for, and he suffered another nervous breakdown in 1957. This led to the more evident display of the symptoms of a type of Parkinson's disease which, alongside the effects of encephalitis lethargica that he contracted in childhood, was slowly to kill him over more than a decade. — Reference guide for abridged audiobook of Titus Alone.{{cite book}}: CS1 maint: url-status (link) 978-184-379-542-1
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