by Jonathan Rogers, Ph.D.
Imagine a pandemic that spread across the world, causing death and disability to hundreds of thousands of people.
Having lived through COVID-19, this isn’t too difficult a task.
But there was one big difference with this earlier pandemic: With COVID-19, we knew what caused it. We could give it a name (SARS-CoV-2). We could isolate it in a lab. And we could use that knowledge to develop treatments and vaccinations.
A hundred years ago, a pandemic swept around the world and we had no idea what caused it. Worse still, even today, we’re still not sure.
One of the most frightening things about this pandemic is that it didn’t just affect the body; it affected the mind. Its name was encephalitis lethargica. Around late 1916, the Austrian neurologist and psychiatrist, Constantin von Economo, noticed some unusual cases among his patients that didn’t match any existing diagnoses. The most distinctive feature was profound sleepiness. In many cases, it was so bad that affected patients could sleep for weeks on end. They could be woken briefly but would quickly lapse back into slumber.
This wasn’t all.
Many patients would have a fever and headache. About a third would die in the first few weeks of the illness. This was a tragic loss of life in Central Europe while it was embroiled in the First World War, but it wasn’t the most bizarre part of this illness.
Most people with encephalitis lethargica recovered and that’s where it starts to become really odd. Over time, many of these people started to very gradually get a different sort of illness. Their muscles would progressively become more rigid. Their hands would start to shake. Their movements would slow so much that it could take half an hour just to get to the other side of the room. They would in fact look quite a lot like people with Parkinson’s disease. Except that Parkinson’s disease usually affects people in later life. People with encephalitis lethargica would often be in their twenties and thirties, sometimes even younger.
These difficulties moving were obvious, but – when you looked beneath the surface – encephalitis lethargica wasn’t just a problem with movement. About 10% of people had a complete change in their personality. Others became unable to control their emotions. A few became psychotic, experiencing hallucinations or delusions. When we delved into these cases in more detail, what fascinated me most were those who went from being upstanding members of society or well-behaved children to – let me choose my words carefully – people who you would think about very carefully before introducing to your elderly relatives. We found a few people who started compulsively stealing. As if kleptomania wasn’t enough, a couple of patients began making unprovoked attacks on others – which was completely out of character.
We could discuss these mystifying presentations for years, but let me take you back to where we started: What caused encephalitis lethargica?
It certainly wasn’t only a psychological disorder (though the psychological aspects were very important). There were definite changes in the brains of people who died and many had prominent neurological signs.
What about some kind of toxin? Could it be that there was some poison in the environment that spread it? Well, there was certainly a lot of change happening in Europe in 1916. However, we haven’t been able to find any convincing evidence of a relationship to work with heavy metals or solvents, or even with living in a city compared to in the countryside.
One obvious possibility is an infection. It could have swept around the world, affected everyone who was vulnerable, and disappeared when sufficient immunity developed. The obvious candidate is Spanish Flu, which was circulating around the same time. It’s a fascinating theory, but there are a few holes in it. We’ve never found RNA from influenza in the brains of people with encephalitis lethargica. It also spread in the wrong direction geographically. (Despite its name, Spanish Flu actually spread from North America to Europe but was prominent in Spain after it affected the king and – through him – several important members of the Spanish government.)
What we’ve found more recently is that encephalitis lethargica looks similar in some ways to modern cases of autoimmune encephalitis. That’s when the body’s own immune system attacks cells in the brain. It doesn’t quite fit any particular form of autoimmune encephalitis, but it does fit the general pattern.
Sometimes autoimmune encephalitis can be triggered by an infection in what’s called a “hit-and-run” mechanism. A virus (or another infection) turns up and disguises itself as something else in the body. The immune system launches an attack, but it ends up hitting the cells in the body that look like the virus. This is my best guess so far as to what caused encephalitis lethargica. But I’m not sure.
If we want to keep it from happening again, we’d better work it out, though.
Jonathan Rogers, Ph.D., is a Clinical Lecturer in the Division of Psychiatry at University College London.