Encephalitis lethargica, an infectious disorder that only once appeared in epidemic form (1916-1926), is largely forgotten now. But this curious illness provided significant insights into brain function that still have relevance today.
Most people who have heard of the “sleepy sickness”, as encephalitis lethargica (EL) was popularly known, are acquainted only with its curious sufferers as elderly nursing home patients who appeared frozen in time.
But the illness provoked a flood of publications throughout the 1920s and 1930s, as its kaleidoscopic combination of neurologic and psychiatric phenomena provided insights into brain function that had previously been the subject of speculation.
These insights have had an enduring impact upon both neurology and psychiatry.
Anatomy of a disease
Encephalitis lethargica was initially a puzzling, but seemingly simple disorder. After a period of general unease, the victim presented double vision (diplopia), deep somnolence, and sometimes mild fever.
But the “sleep” that gave the disorder its popular name was rather unusual – while the body presented all the signs of slumber, the sleeper remained aware of her surroundings.
Any romanticism one might have attached to this apparently benign disorder, however, was soon dispelled by two facts.
First, around a third of encephalitis lethargica sufferers died during this acute phase, usually of respiratory failure.
Autopsies confirmed what the symptoms had implied – patients suffered from an inflammation confined to a small region at the base of the brain.
And the recovery of those who survived was an illusion, as encephalitis lethargica proved to be a multi-stage disorder.
The second phase was marked by a general loss of concentration and interest in life, giving a vague sensation that the patient was not the person they had once been.
But this period, which resembled chronic fatigue syndrome, was the calm before the storm.
Unbeknownst to the victim, localized neurodegeneration proceeded apace through the first phase, and after an interval – lasting between a few days and 30 years – post-encephalitic parkinsonism (PEP) emerged.
Unmistakable and irreversible, PEP consigned the young sufferers (mostly between 15 and 35 years of age) to decades of disability.
For those who had not yet passed adolescence, the second period was marked by pathologic changes of character that approached the psychopathic.
Younger children, between 5 and 10 years old, might merely irritate with their clinginess; their impaired concentration; their incessant restlessness and need for noise; and their lack of consideration for others – not unlike current attention deficit disorders.
But as they grew in strength, their incorrigible impulsiveness escalated in violence and they posed a danger to themselves and others.
Errant behaviours included cruelty to anyone who crossed them; destructiveness; lying; and self-mutilation including, in one example, removal of eyes.
When they reached adolescence, these patients manifested inappropriate and excessive sexuality, including sexual assault without regard for age or gender.
Bizarrely, these children were driven by impulsiveness, not self interest. Thefts, for example, were not undertaken for personal benefit and stolen goods were often immediately forgotten, or given away.
Patients often expressed genuine remorse for their actions, explaining they recognized their wrongdoing but had been compelled to act as they did.
Some children improved after adolescence, but in many the only brake on their bad behavior was the parkinsonism that developed as they entered adulthood.
Those not confined to hospital with parkinsonism often proceeded to a life of habitual criminality – mostly theft in men, prostitution in women, but also ranging up to rape and murder.
This phenomenon encouraged many countries to re-examine laws regarding legal responsibility in those whose actions were curtailed neither by encouragement nor prison, but who nonetheless maintained a sense of what was socially appropriate.
Post-encephalitic parkinsonism was the neurologic side of the third, interminable phase of the disease. This phase enabled the discovery of the essential lesion of the substantia nigra in parkinsonism.
The psychiatric facets of this phase were no less significant. A peculiar lack of internal drive separating the patient from their world was typical.
Despite normal intelligence, these patients could not summon the will power to execute their wishes.
More insightful sufferers described how neither their perceptions nor their own thoughts were associated with the required emotional content that permitted exercise of their will.
Patients could appreciate that a pianist played with great technical skill, for instance, but no longer sensed the beauty of the music.
One described an increased sense of empathy – recognition of others’ feelings – but reduced sympathy – the emotional response to this recognition.
This inability to interact with the world, combined with their inexpressive, immobile parkinsonian face and their muscular rigidity, lent them the aspect of a puppet or statue.
All this while the sufferers' minds remained active.
The only consolation was that this same apathy often meant the sufferers were not overly depressed by their illness or by the prospect of a life in an institution (remembering that these young patients might live for another half century or more).
Impact on medical science
The profound psychiatric changes in both children and adults suffering encephalitis lethargica challenged assumptions that the cerebral cortex was the seat of all the higher human functions, including the sense of self.
Despite severe psychiatric changes, it was the brainstem that was damaged in these patients, not the cortex.
The so-called “lizard brain” that humans inherited from their pre-mammalian forebears bore the brunt of the disease, not the higher brain centres assumed to be the seat of functions once attributed to the human soul.
An even greater challenge was posed by the minority of patients who developed conditions that were difficult to distinguish from catatonic or paranoid schizophrenia.
This provoked a long debate concerning the degree to which schizophrenia might be as much a motor disorder as a psychiatric condition.
This debate was also fuelled by the fact that many symptoms then regarded as “hysteric” were also seen in encephalitis lethargica, suggesting that hysteria was as much a motor disorder, like Parkinson’s disease, as a psychiatric condition.
Encephalitis lethargica gradually disappeared during the 1930s, but its lessons continued to have an impact.
It had demonstrated that an infectious disease could elicit not only neurologic consequences, but also severe behavioral and psychiatric changes.
An infectious origin for multiple sclerosis had been long suspected and the suspicion was hardened by the experience of encephalitis lethargica.
More recently, there has been discussion about the involvement of cytomegalovirus and Toxoplasma gondii infection in schizophrenia, as well as the contribution of herpes virus type 1 in Alzheimer’s disease, and of Borna virus in mood disorders.
Equally significant is that encephalitis lethargica made it clear that it is not possible to topographically or functionally disentangle the psychic and neurologic aspects of the brain.
The central nervous system functions, not as a series of parallel modules, but as an integrated whole.