The Mystery of the Sleepy Sickness

Key Takeaways

Encephalitis lethargica (EL) was a global medical mystery with unusual neurological symptoms, appearing around 1916.
Dr. Constantin von Economo documented EL's varied forms, which included severe sleepiness, involuntary movements, and catatonic states.
The pandemic affected hundreds of thousands, with a high mortality rate and many survivors experiencing chronic neurological issues.
Despite extensive research, EL's cause, spread, and disappearance remain unknown; Spanish Flu was definitively ruled out.
L-Dopa offered temporary relief for post-encephalitic Parkinsonism, but often with severe side effects and heartbreaking relapses.

Encephalitis lethargica, or 'sleepy sickness,' emerged around 1916 in Europe, affecting at least four continents by 1919.
Dr. Constantin von Economo in Vienna observed patients with symptoms inconsistent with known diagnoses like meningitis or MS.
The condition presented with initial flu-like symptoms, progressing to severe and inconsistent neurological issues, sometimes causing death within days.
Victims could freeze mid-action with eyes open, mouths agape, and hands raised, a state potentially lasting for decades.

Dr. von Economo categorized EL into three forms: somnolent-ophthalmoplegic, hyperkinetic, and amiostatic akinetic.
The somnolent-ophthalmoplegic form, the most common, involved severe sleepiness, ocular paralysis, and neuropsychiatric symptoms like catatonia.
The hyperkinetic form caused manic phases, involuntary vocalizations, jerky movements, fatigue, and reversed sleep-wake cycles.
The amiostatic akinetic form resulted in a statuesque immobility, with patients exhibiting waxy flexibility and retaining mental awareness.

Estimates for the encephalitis lethargica pandemic range from 500,000 to over a million cases globally.
The mortality rate was approximately one-third, with another third recovering and the remaining third experiencing recurrence.
Chronic EL led to post-encephalitic Parkinsonism, characterized by symptoms like mood swings, euphoria, increased libido, psychosis, and immobility.
Patients with chronic EL could exhibit excessive silliness and pun usage, along with a 'statue-like' immobility.

The chronic phase of EL often resulted in post-encephalitic Parkinsonism, distinct from Parkinson's disease due to its sudden onset.
Neurologist Oliver Sacks documented these patients in his 1966 work, which inspired the book and film 'Awakenings.'
Sacks studied 'paradoxical kinesia,' where immobile patients could move suddenly in response to stimuli like catching a ball.
The film 'Awakenings' is noted for its faithfulness to Sacks' nonfiction account of patients at Beth Abraham Hospital.

The mystery of EL's appearance around 1915-1916 and its disappearance a decade later remains unsolved despite extensive research.
Scientists initially ruled out environmental causes, specifically toxic encephalitis, due to a lack of discernible exposure patterns.
Investigations then shifted to infectious causes, considering viral infections like herpes, measles, West Nile, or influenza.
Conflicting evidence existed on its contagiousness, with anecdotal cases noted within families and institutions.

The Spanish Flu was definitively ruled out as EL's cause after genome sequencing found no correlation between the viruses.
Experiments in 1931 suggested a possible link between Streptococcus vaccination and an EL-like condition in dogs, but this was not conclusive proof.
The Matheson Commission, funded by an affected businessman, studied EL for 13 years but ultimately concluded, 'We don't know.'
This uncertainty about EL's cause and how it spread was met with significant frustration by the scientific community.

L-Dopa, a Parkinson's disease treatment developed from EL research, was discovered in the late 1960s.
The drug initially brought catatonic EL patients back to a more active state, as depicted in 'Awakenings.'
Many patients experienced severe side effects, forcing them back into catatonia, tragically aware of their condition's relapse.
While some experienced setbacks, a silver lining was that many patients eventually stabilized with L-Dopa, leading somewhat healthier lives.

In the last 75 years, only about 80 reported cases with EL-like presentations have occurred, with uncertain diagnoses.
L-Dopa is still used for tremors and rigidity, and Electroconvulsive Therapy (ECT) for severe psychiatric symptoms.
Current theories suggest EL may be an autoimmune disorder, where infection-mimicking proteins attack specific brain regions.
Dr. Von Economo, who initially suspected an infection, was nominated for a Nobel Prize three times for his EL work.