Lethargic Encephalitis: The Mysterious ‘Sleeping Sickness’ of 1916

More than a century ago, as the Spanish flu pandemic ravaged the globe, a strange and unsettling illness emerged in Europe, leaving scientists baffled. Known as encephalitis lethargica (EL), the disease began to spread in the winter of 1916, when Austrian physician Constantin von Economo observed patients presenting with unusual neurological symptoms unlike any previously known.

Initially, patients experienced flu-like symptoms, including general weakness, mild fever, sore throat, headache, dizziness, vomiting, and chills, before the symptoms evolved into sudden and terrifying neurological manifestations. In some cases, patients died within days, as in the instance of a young woman who suffered a sudden onset of hemiplegia while returning from a musical performance, falling into unconsciousness and dying just 12 days later.

Some forms of the disease, particularly the somnolent-ophthalmoplegic variant, were characterized by profound drowsiness, with patients sleeping for long, uninterrupted hours, yet remaining aware of their surroundings. The mortality rate in this form was high, exceeding 50%, although some patients survived without long-term effects. Dr. Oliver Sacks, decades later, described patients he treated in New York in the 1960s as “aware but not fully awake; sitting motionless and speechless all day, without energy, drive, or volition, like living statues or zombies.”

As the disease progressed and spread, other forms emerged accompanied by hyperactivity, insomnia, and involuntary muscle movements affecting the face, limbs, and sometimes the eye muscles. The chronic phase was marked by symptoms resembling Parkinson’s disease, along with sleep disturbances, speech problems, breathing difficulties, and complex psychological issues. In the decades following the epidemic, some researchers estimated that as much as half of all Parkinson’s disease cases were a consequence of encephalitis lethargica.

The cause of this mysterious illness remains unknown to this day. Some scientists initially linked it to the Spanish flu pandemic, but subsequent studies showed the two diseases spread independently. More recent hypotheses suggest an enterovirus, a type of virus that includes polio and is transmitted through bodily fluids, may be responsible. However, there is currently no scientific consensus on the true cause.

By 1927, after claiming approximately half a million lives, the disease abruptly vanished. While this was welcome news for humanity, the mystery surrounding its cause leaves open the possibility of a similar illness resurfacing in the future. As one recent study concluded: “If the disease were to return in the context of another pandemic, this would be an opportunity to use modern methods to identify and understand its cause, and perhaps prevent its recurrence.”

Encephalitis lethargica remains one of the most perplexing medical enigmas of the 20th century: a deadly disease that appeared suddenly, baffled scientists with its bizarre symptoms, and serves as a stark reminder that neurological illnesses can hold secrets that remain unknown even today.

The disease is characterized by a range of symptoms, including high fever, sore throat, headache, lethargy, double vision, delayed physical and mental response, sleep inversion, and catatonia. In severe cases, patients may enter a coma-like state known as akinetic mutism. Abnormal eye movements, known as oculogyric crises, Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes, including psychosis, can also occur. A vocal tic involving compulsive screaming, called klazomania, was sometimes present.

The epidemic of encephalitis lethargica spread globally between 1915 and 1926, infecting an estimated one million or more people and directly causing over 500,000 deaths. The vast majority of survivors never fully recovered their pre-morbid health.