Understanding Encephalitis Lethargica

Here’s what you’ll discover in this article:

• Encephalitis lethargica (EL) is a mysterious neurological condition that affected millions from 1917 to 1930, leading to symptoms like hypersomnia, immobility, and even death.
• Despite over a hundred years of research, the exact cause of this illness remains unclear, and it’s uncertain whether it could resurface.
• Though it coincided with the Spanish Influenza pandemic, which raises theories about a link between the two, recent analysis has explored other potential causes, such as enteroviruses and autoimmune disorders.

A bit more than a century ago, the world was grappling with a pandemic that’s quite well-known—and another that’s easily overlooked. The notable one was the Spanish Influenza (which actually started in the U.S.), sweeping across the globe from 1918 to 1920. In just two years, this strain of the influenza virus, H1N1, led to the deaths of over 50 million people worldwide, affecting about a fifth of the global population.

At the same time, a stranger—though less deadly—disease was making its presence known: encephalitis lethargica (EL). Often dubbed as “sleeping sickness,” this neurological condition typically forced patients into prolonged sleep stages. While it was not nearly as lethal as the Spanish Flu, it claimed around five hundred thousand lives between 1917 and 1930 and left many others severely impaired.

As the Spanish Flu faded from collective memory, scientists continued to grapple with the mystique surrounding this lesser-known illness. Today, many regard encephalitis lethargica as one of the most perplexing medical mysteries of the 20th century. Even over a hundred years since physician Constantin von Economo first documented it, we still lack clarity on its origins, transmission, or whether a similar outbreak could ever occur again.

One confusing aspect of the EL outbreak was its variable progression across different groups. For some, the condition was swift and fatal; for others, symptoms developed gradually. It could induce hypersomnia in some cases, while affecting activity levels in others. This ambiguity was captured in von Economo’s early observations of the illness.

“We are dealing with a kind of sleeping sickness, having an unusually prolonged course,” he noted. “The first symptoms are usually acute, with headaches and malaise. Then, a state of somnolence appears, often accompanied by active delirium. This can lead quickly to death or linger for weeks or months.”

Von Economo’s extensive writings on the subject ignited a century-long quest to understand this bewildering condition. The American Society of Microbiology describes EL as having two distinct phases. The initial phase presents flu-like symptoms, eventually leading to severe sleepiness or, in some instances, mania. Survivors then enter a chronic phase, often marked by Parkinsonism; about 50 percent of those who survived were permanently altered, with some undergoing complete personality shifts or even psychosis.

One leading theory regarding the cause of this pandemic draws parallels with the Spanish Flu. The timing and geographic overlap of the two illnesses suggest a possible connection. There were also cases of encephalitis during an influenza outbreak from 1889 to 1892 that exhibited neurological symptoms akin to EL.

Nevertheless, encephalitis lethargica continued for nearly a decade after the Spanish Flu’s decline, and later analyses of historical brain samples failed to confirm a direct relationship between the two diseases. In 2012, researchers proposed that an enterovirus might be responsible. These RNA viruses, like poliovirus, can trigger conditions leading to muscle relaxation and weakness. Some have speculated that autoimmune disorders might explain EL, but this theory struggles with the broad scope of how the disease spread.

Though the origins remain elusive, the impact of EL was deeply distressing. The last known survivor, Philip Leather, passed away at 82 in 2002, having spent most of his life unable to move in a mental institution. Today, cases of the disease are exceedingly rare; the American Society for Microbiology has only recorded about 80 incidents in the last 85 years.

This enigmatic disease may be fading from memory, but it’ll be interesting to see if it remains a footnote in history—or if it resurfaces unexpectedly.