First described by Constantin von Economo.
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Encephalitis lethargica or von Economo disease is an atypical form of encephalitis. Also known as "sleepy sickness" (though different from the sleeping sickness transmitted by the tsetse fly), it was first described in 1917 by the neurologist Constantin von Economo and the 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; no recurrence of the epidemic has since been reported, though isolated cases continue to occur.
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) is sometimes present.
Postencephalitic parkinsonism may develop after a bout of encephalitis, more commonly in the post-encephalitic phase and often after a latent period of several years.
The cause of encephalitis lethargica is not known for certain.
Research in 2004 suggested that the disease is due to an immune reaction and resulting damage to the basal ganglia. In this study, many of the people with encephalitis lethargica had experienced recent pharyngitis and the authors found some evidence linking the reaction to prior streptococcal throat. They hypothesised that encephalitis lethargica, Sydenham's chorea and PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) are mediated by variations of the post-streptococcal immune response.
There is also some evidence of an autoimmune origin with antibodies (IgG) from patients with encephalitis lethargica binding to neurons in the basal ganglia and mid-brain. Western immunoblotting showed that 95% of encephalitis lethargica patients had autoantibodies reactive against human basal ganglia antigens. By contrast, antibodies reactive against the basal ganglia were found in only 2-4% of child and adult controls (n = 173, P < 0.0001).
Jang et al. (2009) at St. Jude Children's Research Hospital, USA, discovered that an H5N1 Bird Flu (strain A/VN/1203/1204) infection in mice causes severe loss of tyrosine-hydroxylase positive dopaminergic neurons 60 days after infection by provoking a destructive autoimmune response, thus suggesting the infection by certain strains of flu might increase the risk of Parkinson's disease in humans. While Jang et al. (2009) acknowledge research that shows the virus that caused the 1918 flu pandemic (a type A influenza subtype H1N1) unlike H5N1 Bird Flu did not infect the brain, they propose that a distal infection might have provoked an autoimmune mediated destruction of dopaminergic neurons, while leaving no direct evidence of brain infection.
Treatment for encephalitis lethargica in the early stages is patient stabilization, which may be very difficult. There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement. Other patients have been less fortunate, and the disease then becomes progressive, with evidence of brain damage similar to Parkinson's disease. Treatment is then symptomatic. Levodopa (L-DOPA) and other anti-parkinson drugs often produce dramatic responses. However, in most of the patients who were given L-DOPA in the 1960s, the amelioration of the disease was short lived.
The course of encephalitis lethargica varies depending upon complications or accompanying disorders.
Notable cases include:
- Muriel "Kit" Richardson (née Hewitt), first wife of actor Sir Ralph Richardson, died of the condition in October 1942 having first shown symptoms in 1927-8.
The discovery by Oliver Sacks that L-DOPA could relieve some symptoms was described in his book Awakenings in 1973. The book was used by Harold Pinter as the basis of his one-act play A Kind of Alaska, performed in 1982 starring Judi Dench. The 1990 film Awakenings starring Robin Williams and Robert De Niro is also based on the book. The Molly Caldwell Crosby book Asleep (2010) describes the history of the disease and the epidemic of the 1920s. The 2012 novel Umbrella by Will Self centres on the occurrence of this disease and its later treatment with L-DOPA.
The 1980s US post-hardcore band Big Black recorded a song about the encephalitis lethargica epidemic called "L-Dopa" (1987).
The disease plays a prominent role in the first issue of Neil Gaiman's comic book Sandman (as featured in The Sandman: Preludes and Nocturnes, Sandman: Doll's House, and Sandman Vol. 1, 1991); the disease, usually referred to by its nickname "sleepy sickness" and only once by its medical name, is attributed to the imprisonment of the sleep-master Dream in 1916 by an occultist.
Encephalitis lethargica is researched and mentioned in the Canadian television show ReGenesis, in the last few episodes of the second series (2006). The disease is involved in one of the episodes in the American science fiction television show Alphas, called a "A short time in paradise" (2011), in which the antagonist causes Encephalitis lethargica to afflict his victims.
It is described in moderate detail in Peter Cummings' novel The Neuropathology of Zombies, in which a proposed mutated form of the disease is considered as the possible cause of a 'zombie' outbreak.
Encephalitis lethargica inspired the disease at the heart of Forrest Carr's post-apocalyptic sci-fi novel, "A Journal of the Crazy Year," and is investigated in the plot as a potential cause of the world-ending outbreak.
- synd/3356 at Who Named It?
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- Dale RC, Church AJ, Surtees RA et al. (2004). "Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity". Brain 127 (Pt 1): 21–33. PMID 14570817. doi:10.1093/brain/awh008.
- "Encephalitis lethargica" at Dorland's Medical Dictionary
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- Haeman, Jang; David Boltz; Katharine Sturm-Ramirez; Kennie R. Shepherd; Yun Jiao; Robert Webster; Richard J. Smeyne (2009-08-10). "Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration" (PDF). Proceedings of the National Academy of Sciences 106 (33): 14063–8. PMC 2729020. PMID 19667183. doi:10.1073/pnas.0900096106. Retrieved 2009-08-11.
- Blunt SB, Lane RJ, Turjanski N, Perkin GD (1997). "Clinical features and management of two cases of encephalitis lethargica". Mov. Disord. 12 (3): 354–9. PMID 9159730. doi:10.1002/mds.870120314.
- Kohnstamm P (1934). Über die Beteiligung der beiden Schichten der Substantia nigra am Prozeß der Encephalitis epidemica. J Psychol Neurol 46(1): 22-37
- Boggan, Steve (September 11, 2006). "Reborn". The Guardian. Retrieved November 25, 2012.
- Sparacino, Diane (2012). "New Awakenings". RN.COM. Retrieved November 25, 2012.
- Molly Caldwell Crosby. Asleep: The Forgotten Epidemic that Remains One of Medicine's Greatest Mysteries. New York: Berkley Books; 2010.
- National Institute of Neurological Disorders and Stroke
- Mystery of the Forgotten Plague: BBC news item about the tracing of the infectious agent in encephalitis lethargica
- The Encephalitis Society - A Global resource on Encephalitis