Encephalitis lethargica and an unresolved epidemic

A syndrome beyond unusual sleep

Physician Constantin von Economo described encephalitis lethargica during the First World War era.^[1] Cases appeared in many countries through the 1920s, with different patterns of excessive sleep, wakefulness, eye-movement problems, psychiatric symptoms, and movement disorders.^[1] The exact global number of affected people is unknown; a review in Brain calls estimates above one million uncertain rather than a settled count.^[1]

A 2024 study reviewed 614 historical cases and found a broad mix of motor, cranial-nerve, eye, sleep and psychiatric features.^[3] That helps explain why the popular description “sleeping sickness” is incomplete. A memorable symptom can obscure a syndrome whose historical diagnosis depended on a cluster of findings.

Survivors and selected historical records

Some people died during the acute illness. Others later developed post-encephalitic parkinsonism, a profound slowing and rigidity that became familiar to many readers through Oliver Sacks’s Awakenings.^[1] That later syndrome should not be treated as the experience of every survivor. Historical diagnosis was variable, and the relationship between acute cases and later movement disorders is part of why retrospectively counting a single epidemic is difficult.

The 2024 researchers applied eligibility criteria to hospital notes, creating a defined series rather than a global count.^[3] Such records can clarify the clinical pattern while reflecting who reached that institution and what doctors wrote down. They cannot retrospectively identify every unrecorded case or prove that all later similar illnesses share one cause.

What levodopa could change

Von Economo’s 1917 publication gave the disorder a name and brought together cases that had initially looked unrelated.^[1] Decades later, Sacks treated post-encephalitic patients with levodopa; some showed dramatic short-term changes in movement and responsiveness, the subject of Awakenings.^[1] Responses were variable and often difficult to sustain, so levodopa did not cure encephalitis lethargica. It could temporarily alter consequences of a long-past neurological illness.

Levodopa’s effects on movement addressed post-encephalitic parkinsonism long after the acute disease. A response to that drug could demonstrate a modifiable neurological consequence without identifying what initiated the illness decades earlier. Improvement and subsequent adverse effects therefore belong to treatment history, not proof of a particular infectious explanation.

A cause still under investigation

Influenza was long proposed as a cause because the epidemic overlapped the 1918 pandemic, but a direct link has not been established.^[1] Reviews also consider viral and autoimmune mechanisms. The 2023 review “Encephalitis lethargica. What is still wrong?” concludes that both the causative agent and neuropathological pattern remain unknown.^[2]

The 2024 analysis regarded autoimmune encephalitis as a plausible explanation while distinguishing typical historical cases from present-day NMDA-receptor encephalitis.^[3] Similarity to a known disease can guide research without making the diseases identical. Limited old specimens and uncertain classification continue to constrain a definitive explanation.