Encephalitis Lethargica - Cause

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 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).

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.