Encephalitis lethargica
Encyclopedia
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 by the neurologist Constantin von Economo
in 1917. 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.
, sore throat, headache
, double vision
, delayed physical and mental response, sleep inversion
, catatonia
and lethargy. In acute 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
.
Postencephalitic Parkinson's disease
may develop after a bout of encephalitis, sometimes as long as a year after the start of the illness.
Research in 2004 suggested that the disease is due to an immune reaction
. 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 neuron
s 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).
Some researchers believe that new data supports the influenza
hypothesis, while others consider this less likely.
Jang et al. (2009) at St. Jude Children's Research Hospital
, USA, discovered that a 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.
A drug called Zolpidem
commonly used as a sleeping pill has reported success at treating encephalitis lethargica.
. Carlson writes: "By comparing the symptoms reported by seventeenth-century colonists with those of patients affected by the encephalitis lethargica epidemic of the early twentieth century, a pattern of symptoms emerges [which] supports the hypothesis that the witch-hunts of New England were a response to unexplained physical and neurological behaviors resulting from an epidemic of encephalitis."
in Agatha Christie
's book The Murder at the Vicarage
(1930), was described as suffering from this syndrome. The disease was also the subject of the 1942 German film, Die Geschichte einer kolonialen Tat.
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
. Awakenings is also the title of a 1990 movie starring Robin Williams
and Robert De Niro
based on the book. The Molly Caldwell Crosby book Asleep (2010) describes the history of the disease and the epidemic of the 1920s.
The Eighties 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 as its medical name, is attributed to the imprisonment of the sleep-master Dream
in 1916 by an occultist.
The disease is researched and mentioned in the Canadian television show ReGenesis
, in the last few episodes of the second series (2006). The disease is also 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 Encepahilitis lethargica to inflict his victims.
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
. Also known as "sleepy sickness" (though different from the sleeping sickness transmitted by the tsetse fly
Tsetse fly
Tsetse , sometimes spelled tzetze and also known as tik-tik flies, are large biting flies that inhabit much of mid-continental Africa between the Sahara and the Kalahari deserts. They live by feeding on the blood of vertebrate animals and are the primary biological vectors of trypanosomes, which...
), it was first described by the neurologist Constantin von Economo
Constantin von Economo
Constantin Freiherr von Economo was a Romanian psychiatrist and neurologist of Greek origin. He is mostly known for his discovery of encephalitis lethargica and his atlas of cytoarchitectonics.- Youth and schooling :Constantin Freiherr Economo von San Serff was born in Brăila, Romania, to Greek...
in 1917. The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless. Between 1915 and 1926, an epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
of encephalitis lethargica spread around the world; no recurrence of the epidemic has since been reported, though isolated cases continue to occur.
Symptoms
Encephalitis lethargica is characterized by high feverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, sore throat, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, double vision
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
, delayed physical and mental response, sleep inversion
Sleep inversion
Sleep inversion or sleep-wake inversion is a reversal of sleeping tendencies. Individuals suffering from sleep-wake inversion exchange diurnal habits for nocturnal habits, meaning they are active at night and sleep during the day. Sleep-wake inversion, when it is involuntary, can be a sign of a...
, catatonia
Catatonia
Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described in 1874: Die Katatonie oder das Spannungsirresein ....
and lethargy. In acute cases, patients may enter a coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
-like state (akinetic mutism
Akinetic mutism
Akinetic mutism is a medical term describing patients who tend neither to speak nor move . It is the result of severe frontal lobe injury in which the pattern of inhibitory control is one of increasing passivity and gradually decreasing speech and motion.An example of a cause of this disorder...
). Patients may also experience abnormal eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
movements ("oculogyric crises"), parkinsonism
Parkinsonism
Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
.
Postencephalitic Parkinson's disease
Postencephalitic parkinsonism
Post-encephalitic Parkinsonism is a disease believed to be caused by a viral illness, that triggers degeneration of the nerve cells in the substantia nigra. Overall, this degeneration leads to clinical Parkinsonism and the disease is followed by encephalitis lethargica, a condition also referred...
may develop after a bout of encephalitis, sometimes as long as a year after the start of the illness.
Cause
The cause of encephalitis lethargica is not known for certain.Research in 2004 suggested that the disease is due to an immune reaction
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. In this study, many of the people with encephalitis lethargica had experienced recent pharyngitis
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
and the authors found some evidence linking the reaction to prior streptococcal throat. They hypothesised that encephalitis lethargica, Sydenham's chorea
Sydenham's chorea
Sydenham's chorea or chorea minor is a disease characterized by rapid, uncoordinated jerking movements affecting primarily the face, feet and hands. Sydenham's chorea results from childhood infection with Group A beta-hemolytic Streptococci and is reported to occur in 20-30% of patients with...
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
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
(IgG) from patients with encephalitis lethargica binding to neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s in the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
and mid-brain. Western immunoblotting
Western blot
The western blot is a widely used analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native proteins by 3-D structure or denatured proteins by the length of the polypeptide...
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).
Some researchers believe that new data supports the influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
hypothesis, while others consider this less likely.
Jang et al. (2009) at St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital, founded in 1962, is a leading pediatric treatment and research facility focused on children's catastrophic diseases. It is located in Memphis, Tennessee. It is a nonprofit medical corporation chartered as a 501 tax-exempt organization under IRS regulations.In...
, USA, discovered that a H5N1
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
Bird Flu (strain A/VN/1203/1204) infection in mice causes severe loss of tyrosine-hydroxylase positive dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
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
H1N1
'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
) 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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. Treatment is then symptomatic. Levodopa
Levodopa
L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
(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.
A drug called Zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
commonly used as a sleeping pill has reported success at treating encephalitis lethargica.
Salem witch trials
Historian Laurie Winn Carlson has advanced the idea that encephalitis lethargica is the explanation for the symptoms of the afflicted in New England during the 17th century, which ultimately resulted in the Salem witch trialsSalem witch trials
The Salem witch trials were a series of hearings before county court trials to prosecute people accused of witchcraft in the counties of Essex, Suffolk, and Middlesex in colonial Massachusetts, between February 1692 and May 1693...
. Carlson writes: "By comparing the symptoms reported by seventeenth-century colonists with those of patients affected by the encephalitis lethargica epidemic of the early twentieth century, a pattern of symptoms emerges [which] supports the hypothesis that the witch-hunts of New England were a response to unexplained physical and neurological behaviors resulting from an epidemic of encephalitis."
Popular culture
Hawes, the curateCurate
A curate is a person who is invested with the care or cure of souls of a parish. In this sense "curate" correctly means a parish priest but in English-speaking countries a curate is an assistant to the parish priest...
in Agatha Christie
Agatha Christie
Dame Agatha Christie DBE was a British crime writer of novels, short stories, and plays. She also wrote romances under the name Mary Westmacott, but she is best remembered for her 66 detective novels and 14 short story collections , and her successful West End plays.According to...
's book The Murder at the Vicarage
The Murder at the Vicarage
The Murder at the Vicarage is a work of detective fiction by Agatha Christie and first published in the UK by the Collins Crime Club in October 1930 and in the US by Dodd, Mead and Company later in the same year...
(1930), was described as suffering from this syndrome. The disease was also the subject of the 1942 German film, Die Geschichte einer kolonialen Tat.
The discovery by Oliver Sacks
Oliver Sacks
Oliver Wolf Sacks, CBE , is a British neurologist and psychologist residing in New York City. He is a professor of neurology and psychiatry at Columbia University, where he also holds the position of Columbia Artist...
that L-DOPA could relieve some symptoms was described in his book Awakenings
Awakenings (book)
Awakenings is a 1973 non-fiction book by Oliver Sacks. It recounts the life histories of those who had been victims of the 1920s encephalitis lethargica epidemic. Sacks chronicles his efforts in the late 1960s to help these patients at the Beth Abraham Hospital in the Bronx, New York. The...
in 1973. The book was used by Harold Pinter
Harold Pinter
Harold Pinter, CH, CBE was a Nobel Prize–winning English playwright and screenwriter. One of the most influential modern British dramatists, his writing career spanned more than 50 years. His best-known plays include The Birthday Party , The Homecoming , and Betrayal , each of which he adapted to...
as the basis of his one-act play A Kind of Alaska
A Kind of Alaska
A Kind of Alaska is a one-act play written in 1982 by Harold Pinter , the 2005 Nobel Laureate in Literature.-Summary:A middle-aged woman named Deborah, who has been in a comatose state for thirty years as a result of contracting sleeping sickness, awakes with a mind still that of a sixteen-year-old...
, performed in 1982 starring Judi Dench
Judi Dench
Dame Judith Olivia "Judi" Dench, CH, DBE, FRSA is an English film, stage and television actress.Dench made her professional debut in 1957 with the Old Vic Company. Over the following few years she played in several of William Shakespeare's plays in such roles as Ophelia in Hamlet, Juliet in Romeo...
. Awakenings is also the title of a 1990 movie starring Robin Williams
Robin Williams
Robin McLaurin Williams is an American actor and comedian. Rising to fame with his role as the alien Mork in the TV series Mork and Mindy, and later stand-up comedy work, Williams has performed in many feature films since 1980. He won the Academy Award for Best Supporting Actor for his performance...
and Robert De Niro
Robert De Niro
Robert De Niro, Jr. is an American actor, director and producer. His first major film roles were in Bang the Drum Slowly and Mean Streets, both in 1973...
based on the book. The Molly Caldwell Crosby book Asleep (2010) describes the history of the disease and the epidemic of the 1920s.
The Eighties US post-hardcore band Big Black
Big Black
Big Black was an American punk rock band from Evanston, Illinois, active from 1981 to 1987. Founded by singer and guitarist Steve Albini, the band's initial lineup also included guitarist Santiago Durango and bassist Jeff Pezzati, both of Naked Raygun...
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
Neil Gaiman
Neil Richard Gaiman born 10 November 1960)is an English author of short fiction, novels, comic books, graphic novels, audio theatre and films. His notable works include the comic book series The Sandman and novels Stardust, American Gods, Coraline, and The Graveyard Book...
's comic book Sandman (as featured in The Sandman: Preludes and Nocturnes
The Sandman: Preludes and Nocturnes
Preludes & Nocturnes is the first trade paperback collection of the comic book series The Sandman, published by DC Comics. It collects issues #1-8...
, Sandman: Doll's House, and Sandman Vol. 1, 1991); the disease, usually referred to by its nickname "sleepy sickness" and only once as its medical name, is attributed to the imprisonment of the sleep-master Dream
Dream (comics)
Dream is the fictional protagonist of DC Comics' Vertigo comic book series The Sandman, written by Neil Gaiman. One of the seven Endless, inconceivably powerful beings older and greater than gods, Dream is both lord and personification of all dreams and stories, all that is not in reality...
in 1916 by an occultist.
The disease is researched and mentioned in the Canadian television show ReGenesis
ReGenesis
ReGenesis is a Canadian television program produced by The Movie Network and Movie Central in conjunction with Shaftesbury Films. The series, which ran for four seasons, revolves around the scientists of NorBAC , a fictional organization with a lab based in Toronto...
, in the last few episodes of the second series (2006). The disease is also involved in one of the episodes in the American science fiction television show Alphas
Alphas
Alphas is an American science fiction dramatic television series created by Zak Penn and Michael Karnow. The series follows a group of people with superhuman abilities, known as "Alphas", as they work to prevent crimes committed by other Alphas....
, called a "A short time in paradise" (2011), in which the antagonist causes Encepahilitis lethargica to inflict his victims.
External links
- 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