A random film of the day pulled from the archives: Awakenings, Penny Marshall's 1990 Hollywood drama starring Robert De Niro and Robin Williams. A shy doctor uses an experimental drug to bring back to life patients who spent decades in cataleptic immobility. Beautiful cinema — but behind the screenplay stands a real ward at New York's Beth Abraham Hospital and a real neurologist, Oliver Sacks, who in 1969 actually gave his patients L-DOPA.
And the cause of that stupor is even more mysterious than the film. Encephalitis lethargica, also known as sleeping sickness — a genuine pandemic from 1916–1927 that struck up to a million people and then simply vanished. Not defeated by a vaccine, not washed away by antibiotics — it dissolved. Neither the pathogen nor the reason for the epidemic's disappearance has been established to this day, a hundred years later.
This is the rarest case in medicine: an epidemic about which we know almost everything — symptoms, pathology, chronology — and simultaneously almost nothing, because we don't know the main thing. Understanding what happened then and why this isn't an abstract story but a warning was worth a separate investigation.
In the winter of 1916–1917, Viennese psychiatrist and neurologist Constantin von Economo encountered in his clinic a series of patients who couldn't fit into known diagnoses: headache, fever, and then — drowsiness transitioning into week-long and month-long sleeps from which a person could be awakened but into which they immediately fell back. In April 1917, he presented a description of the new disease to the Vienna Psychiatric Society; a few days later in France, Jean-René Cruchet published similar observations. Who was first — the debate continues to this day, but the name stuck with the Viennese version.
Then the disease started walking across the map like a front-line report: 1918 — England and France, 1919 — Canada, Central America, India, USA, 1920 — Germany and the USSR. The peak fell on the 1920s, and during the entire epidemic, by various estimates, anywhere from hundreds of thousands to a million people fell ill; statistics were so full of holes that the range of victim numbers in sources goes from a thousand to a million, and mortality — from 15 to 40%. Moreover, by some historians' estimates, up to half or even three-quarters of cases never made it into reports at all: a provincial hospital with a dying "sleeping" patient rarely wrote to the capital.
The epidemic's chronology overlapped with World War I: states exhausted by war, crowded barracks, hunger. And, of course, the Spanish flu. The coincidence of two catastrophes — 1918–1920 — led contemporaries to suspect a connection, and this hypothesis would become the main detective story of the entire history. But curiously, the first cases of sleeping sickness in Vienna appeared before the flu pandemic — a detail not to be written off too quickly.
The story also had a backstory noticed only in hindsight. In 1889–1890, northern Italy was hit by "la nona" — "grandmother": an epidemic with drowsiness and eye movement disorders, while the Russian flu of 1889–1894 was described by contemporaries as "nervous flu" with psychoses and deliriums. Shadows of the same disease flickered half a century before von Economo — the epidemic wasn't born in 1916, it flared up like a fire after a long drought.
Von Economo is a figure deserving a separate paragraph. Austrian aristocrat, author of no fewer than 27 works on encephalitis lethargica, lecturer invited to New York in 1929 and to the First International Neurological Congress in Bern in 1931, where he presented a synthesis of his ideas. He died that same year, 1931, not living to see the triumph of his own theory by less than it needed — and managed to publish its culmination as a book about the disease and its consequences.
It was autopsies of the deceased that gave him the key: the lesion in sleeping sickness was localized not just anywhere, but in the midbrain and hypothalamus — structures whose function was then almost completely unknown. On clinical observations and anatomy, von Economo built a bold model: sleep is not a passive "switching off" of the brain but an active state controlled by a separate center. He placed the sleep center in the anterior hypothalamus, the wakefulness center — in the posterior, near the oculomotor nuclei and the cerebral aqueduct. His lecture in Vienna in March 1925 was directly about this: sleep and wakefulness are active, reversible functions of a "sleep-regulatory center."
Colleagues treated the idea skeptically — it was too convenient to attribute such power to the hypothalamus. But time proved him right: research by Frédéric Bremer, Giuseppe Moruzzi, and Horace Magoun in the mid-20th century showed that the reticular formation of the brainstem indeed controls arousal, and the recent discovery of sleep neurons and orexin systems returned von Economo his "sleep center" almost according to the 1925 blueprints. The epidemic, without knowing it, paid neuroscience for half the map of sleep regulation.
Meanwhile, the disease amazed clinicians with its very forms. Von Economo distinguished three: somnolent-ophthalmoplegic (sleep for weeks transitioning into stupor and death), hyperkinetic (insomnia, chorea, wild motor outbursts), and akinetic (acute parkinsonism, catatonia, mutism). The same disease could put a person to sleep for months, deprive them of sleep — or turn them into a statue.
In 2024, the journal Brain Communications published what the epidemic had lacked for an entire century: a systematic analysis of 614 case histories from the archives of London's National Hospital for Neurology. The numbers stun even a prepared reader: motor disturbances — in 97.6% of patients, cranial nerve lesions — in 91%, sleep disorders — in 66%, psychiatric symptoms — in 54%. Median age — 29 years. This was a disease of the young and middle-aged, not the decrepit.
In the case histories themselves — ready-made pages of medical gothic novel. A teenage girl in the acute phase with "waxy flexibility," when limbs remain in any position given to them. A patient who described her condition in one word — "I felt like starch." A person who fell asleep and woke up ten weeks later. A woman scalded by a hot water bottle while sleeping. A patient who fell asleep on the go: once — on the stairs, another time — by the fireplace, where she received serious burns. A handwritten notebook of a twenty-year-old whose handwriting trembled — and whose first complaint was that he fell asleep at work.
But there were also glimpses that doctors called paradoxical kinesia: a frozen, barely moving patient suddenly catches a falling neighbor in mid-air — "in the heat of the moment" — and freezes again. One patient made stereotypical finger movements in his sleep, as if playing an invisible piano; another, a rower before his illness, walked in circles without noticing. From such details emerges the image of a disease that didn't switch a person off but desynchronized them: consciousness separated from body, sleep — from night, movement — from the desire to move.
Survivors unfolded the second act of the tragedy: after weeks or years of apparent health came postencephalitic parkinsonism — in a younger population than usual, and without the classic "pill-rolling" tremor. Median time from first symptoms to parkinsonism — 3.9 months, but in almost a third it came within a week. And in children the disease left developmental delays; by historians' estimates, psychiatric consequences — from hysteria to behavioral disorders — affected 25–90% of adult patients. The epidemic left — but its tail dragged through the wards until the very end of the century.
By 1969, Beth Abraham Hospital in New York housed the last postencephalitic patients — the last carriers of the epidemic, some of whom had spent forty or more years in immobility. Above the entrance of this facility for the chronically ill was carved an honest-to-the-point-of-cruelty: "Home for Incurables." That's where young neurologist Oliver Sacks took a position — a man who, by his own admission, was "a naturalist before a doctor," tired of therapeutic impotence.
That same year, 1969, reports appeared in The Lancet about the effectiveness of levodopa in parkinsonism, and Sacks was fired up: what would happen if you gave this dopamine precursor to people whose brains had lived forty years without dopamine? He started with a small placebo-controlled study — and saw what he himself later described as "the impossible lifting of blockade, the return of ease, grace, joy, rapture, and determination." People frozen for decades spoke, remembered their youth, sang old songs. Through the ward, essentially, went a miracle — and part of it made it into the film almost undistorted.
But the miracle had a flip side that Hollywood muted. For many patients, the effect became unstable, and then they were hit by side effects: tics, sweeping ballistic movements, oculogyric crises (involuntary upward eye turn — that very symptom from von Economo's clinic), hallucinations, emotional instability, compulsive wandering. Postencephalitic parkinsonism, it turned out, was orders of magnitude harder to manage than ordinary Parkinson's disease. Sacks honestly documented both the highs and the lows: L-DOPA returned consciousness to people but did not return life in its full sense.
From this ward grew a book — Awakenings, 1973, twenty patient histories where neurology is written with literary precision. The neurological community received it coolly, but the literary world — enthusiastically: the 1974 Hawthornden Prize, Pinter's theatrical adaptation "A Kind of Alaska," an opera, a ballet, and finally cinema. For neurology as a profession, the book became pivotal: today journals print "medical humanities" sections, and medical students in motivation letters cite Sacks more than anyone else. The ward in the "Home for Incurables" reformatted how doctors tell stories about patients.
Von Economo himself didn't believe that sleeping sickness was caused by flu, though he allowed that the pandemic "paved the way" for its pathogen. But epidemiological coincidences fed the version for decades: waves of both diseases replaced each other like phases of the moon, and the baron himself noted the return of encephalitis following the Spanish flu and their simultaneous retreat in 1922–1925. In 1927, philanthropist William Matheson even founded a commission with a promise to find the cause and cure within two years — the commission considered two main hypotheses (herpes and focal infection with Streptococcus viridans) and achieved neither.
Modern science armed itself with RT-PCR and cut the Gordian knot — no, it didn't cut it. Analysis of archival brain samples from patients who died in the acute phase (2001) found no traces of flu RNA; the 1918 virus reconstructed in 2005 in a mouse experiment stayed in the lungs and didn't reach the brain; over 11 years of observations among 22,000 cerebrospinal fluid cultures in meningoencephalitis, there wasn't a single case of flu. Working against the "Spanish flu" version was also the vector: flu went from North America to Europe, sleeping sickness — the opposite direction. And two-thirds of patients had no flu in their history at all. Yet supporters of the version still notice: clinical diagnosis of flu is unreliable, and avian strains can get into the brain through the trigeminal nerve. Case closed? More like, case left "for lack of evidence."
Candidate number two appeared in 2012: Dourmashkin's team found virus-like particles in neurons of classic EL cases, which electron microscopy, immunohistochemistry (staining with antibodies to polio and coxsackie viruses), and molecular analysis point to an enterovirus — a relative of polio. A fragment of unique viral RNA 97 base pairs long, positive PCR reactions in other cases, clean controls. Beautiful — but no one has really managed to replicate the work on new material: only a handful of brains from the epidemic survived, and no consensus formed.
The third line — autoimmune — grew from observations that the disease might not be viral at all, but immune. In 2004, Dale and colleagues described 20 modern patients with a picture indistinguishable from historical EL: sleep disorders, parkinsonism, psychoses; 55% had sore throat beforehand, most had elevated levels of streptococcal infection markers, in the CSF — oligoclonal bands (75%) and signs of deep gray nuclei inflammation on MRI. Immunity attacking the body's own basal ganglia after infection — like rheumatic fever, only in the brain. A 2023 review brought these lines together: EL was probably an autoimmune encephalitis triggered by some viral trigger — and that's precisely why the pathogen is "cleaned out" of tissues: by the time of inflammation, the virus itself is no longer there.
Tellingly, even the 2024 analysis of 614 cases confirmed the lack of understanding: almost half the histories formally fit criteria for possible autoimmune encephalitis, but only 0.5% — criteria for its best-known type (NMDA receptor). Old cases don't resemble anything modern. The authors end with a phrase that is the quintessence of the topic: the real mystery of sleeping sickness is its etiology, which after a hundred years of research "remains unsolved."
The epidemic's anomaly isn't limited to how it came. What's scarier is how it left: gradually, starting in 1926, and by the early 1930s — completely. Neither vaccination nor treatment capable of affecting the epidemic's course existed. None of the hypotheses explains the disappearance itself: if flu left — why did encephalitis cases that didn't match geographically or historically leave? If an enterovirus is to blame — why hasn't it caused pandemics since? If an autoimmune trigger — why hasn't humanity's immunity encountered it again in a century?
There are hypotheses — all uncomfortable. The pathogen strain died out on its own, as virus lineages that lost their niche die out; something changed in the environment — nutrition, childhood infections, the immune background of a generation that survived war and hunger; the pathogen didn't go anywhere but changed its "handwriting" and now causes other, blurred syndromes. In favor of the latter are sporadic controversial "modern EL" cases — but, as 2023 reviewers honestly write, extending the diagnosis "encephalitis lethargica" to sporadic cases is an unjustified stigma while the epidemic's cause remains unestablished: they're trying to abolish the term for sporadic pictures to avoid mixing the unsolved with the unsolved.
Until the epidemic is explained, the question "will it return" is not rhetorical. Authors of the critical analysis of the flu version directly warn: keeping an open mind means avoiding complacency in the face of possible recurrence during a new flu pandemic; the return of EL itself would give science a chance to establish the cause with modern methods. After COVID-19 with its described cases of autoimmune encephalitis, this thought sounds not like fantasy but like a working scenario: a trigger virus comes and goes, and the mystery remains in the immune memory of an individual patient.
Pandemic science knows such a warning under the name "Disease X": the main lesson of encephalitis lethargica is that a pathogen that cannot be found is impossible to defeat — and that an epidemic doesn't have to leave a viral signature to leave a million broken lives. Sleeping sickness is a real precedent of Disease X from the past: proof that such things happen not in scenarios but in history.
First — about memory. Medicine loves to celebrate victories: smallpox, polio in developed countries, the first gene therapy. But sleeping sickness is a reminder that epidemics can simply leave without leaving a victor, and then the story about them erases faster than the lives of the last survivors end. We know about it because someone in 1969 gave elderly people in the "Home for Incurables" a pill and honestly described what happened next — not because science solved the mystery. The century-long unsolved nature of EL is not a technical detail but a hole in our understanding of what can happen to humanity at all.
Second — about the price of miracles. The L-DOPA story is instructive precisely because it's not Hollywood: awakening after forty years of sleep is not a happy ending but presenting a person with their own life that was stolen from them. Some patients would say it was worth everything; others — that awareness of the loss became a second illness. Sacks understood this before everyone and made the main character not the pill but observation — which, essentially, is the best thing a doctor can do in the face of the unsolved.
Third — about method. Three research lines (flu, enterovirus, autoimmunity) over a hundred years didn't refute each other but came together in a "trigger + immune catastrophe" model that looks plausible precisely because it explains both the impossibility of finding the virus and the strange selectivity of the lesion. This is a beautiful engineering lesson: when a mystery can't be solved directly, systems of views converge not where they looked for the cause but where the consequences intertwine.
And the last, honest doubt. There always remains the possibility that we're cutting the history wrong altogether: that the "sleeping sickness" of 1916–1927 was not one disease but several — just as the "nervous flu" of the nineteenth century was, most likely, its shadow. If so, then there's no pathogen not because it's hidden but because there were several. Perhaps that's precisely why the epidemic disappeared so tracelessly: not one disease left but an era that gave birth to them.