Encephalitis lethargica

Encephalitis lethargica or von Economo disease is an atypical form of encephalitis. Also known as "sleepy sickness" or as "sleeping 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.

Symptoms
Encephalitis lethargica is characterized by high fever, 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.

Cause
The cause of encephalitis lethargica is not known for certain.

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 strep 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).

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
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.

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 trials. 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
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 disease plays a prominent role in the first issue of Neil Gaiman's comic book Sandman (as featured in The Sandman: Preludes and Nocturnes and Sandman Vol. 1); 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. Hawes, the curate in Agatha Christie's book 'The Murder at the Vicarage', was described as suffering from this syndrome.

The disease is researched and mentioned in the Canadian television show ReGenesis, in the last few episodes of the second series.

The disease is also the subject of the 1942 German film, Die Geschichte einer kolonialen Tat.