European sleeping sickness: the greatest mystery of the 20th century

Dr. Jean-Baptist du Prel on the mysterious disease encephalitis lethargica, which spread worldwide in the 1920s

In the 1920s, at the same time as the Spanish flu, a mysterious sleeping sickness called encephalitis lethargica also appeared. What kind of disease is it?

Du Prel: It is a neurological disease that had reached epidemic proportions. At that time, it spread from France throughout Europe and then on to North America and the Soviet Union, and also to India. We are talking about a mysterious disease, of which until today it is not quite clear what the cause was. It had a characteristic course, so that it could be distinguished from other neurological diseases.

By 1950, this sleep epidemic affected almost a million people with serious consequences for their health. How did the disease manifest itself?

Du Prel: Classically, although there are exceptions, it manifested itself in two phases. One was an acute phase, where there were - at first, anyway - influenza-like symptoms: Fever, chills, headache and also nausea. In addition, there were often changing neurological symptoms. A lethargy, i.e. a pronounced need for sleep and on the other hand there was also a cranial nerve involvement, with which the eye mobility was limited. The oculomotor nerve, the third cranial nerve was affected, which severely limited eye mobility. And limb mobility was also handicapped. The chronic phase was characterized by Parkinson's-like symptoms, but in contrast to Parkinson's disease, in encephalitis lethargica, in addition to the typical lack of movement, there were also phases of normal mobility that could be triggered by external stimuli.

The term sleeping sickness is actually misleading. Why?

Du Prel: Because it is not sleep in the classical sense, that is, what one imagines sleep to be. On the one hand, people could be awakened very quickly from this state, and on the other hand, they were aware of everything during sleep. So this was not real sleep.

In Germany in the 1920s, the neurologist Felix Stern at the Göttingen Nervous Clinic became the leading expert on this disease. He collected valuable data on the course of the disease. But his research was banned. Why?

Du Prel: Felix Stern was an associate professor at the University in Göttingen from 1920 to 1928 and also a senior physician at the Nervenklinik there. He then moved to Kassel. He was of Jewish descent and his teaching license was revoked at that time. He then moved to Berlin and opened a private outpatient clinic there. He also tried to go abroad to continue his research, but unfortunately he did not succeed. He took his own life in 1942 because he was threatened with deportation by the Nazis. A very tragic story.

There is a movie called "Time of Awakening" with Robert de Niro and Robin Williams, based on memoirs by psychologist Oliver Sacks. In it, it is about survivors of the disease who had remained unresponsive in immobility for almost 40 years. How do the patients come back to life - at least for a short time?

Du Prel: At that time, the patients were given levodopa, also known as L-dopa, a dopamine derivative that had already been introduced for Parkinson's disease. The patients in this chronic phase had postencephalitic Parkinsonism and it was thought that perhaps L-dopa could also help there. It was then actually the case that L-dopa initially pulled people out of this lethargy, they virtually returned to a normal state. But unfortunately, this normalization did not last. Attempts were then made to increase the corresponding dose of L-dopa, but this was also unsuccessful and the patients then fell back into lethargy.

Today, the disease has disappeared. Scientists are still puzzling over the causes, aren't they?

Du Prel: Some also say that it was the greatest mystery of the 20th century. First of all, the coincidence with the Spanish flu is interesting, so initially it was also thought that it could be a special course of the Spanish flu. However, on closer examination, the epidemiological evidence was not valid because encephalitis lethargica existed before the Spanish flu. It was described in France as early as 1915, and also the spatial spread was exactly the other way around: Spanish flu came from North America to Europe and encephalitis lethargica from Europe to North America. So it didn't fit. It was also the case that some cases of the disease occurred in regions where there was no Spanish flu. At the beginning of the 21st century, the laboratory tried to investigate the disease with appropriate PCR tests, but could not find any influenza RNA. Perhaps it was too difficult to find anything after 80 years. Other germs were also considered, such as the causative agent of polio, i.e. polioviruses, as well as streptococci and, to some extent, herpes viruses. But there is no evidence. At the moment, there are three favored mechanisms of origin. One would be an infection, because it has spread epidemically, the second would be a possible environmental toxin, and the third, which science considers the most likely possibility, is an autoimmune disease. Possibly a virus that causes antibodies to be directed against the patient's own brain tissue. That is what is thought to be going on with Long Covid at the moment, so autoimmune disease. This remains an interesting and certainly exciting path for science.

Uwe Blass (interview from 18.02.2022)

Jean-Baptist du Prel is a member of the scientific staff of the Chair of Occupational Science at Bergische Universität, where he teaches, among other things, preventive medicine.