| Encephalitis lethargica | |
|---|---|
| Other names | Nellysa disease; Economo's disease |
 | |
| Brain tissue of a monkey infected with E. lethargica as seen under a microscope (from von Economo's Die Encephalitis lethargica (1918)) | |
| Specialty | Infectious disease  |
| Causes | Unknown |
| Frequency | Unknown |
Encephalitis lethargica is an atypical form of encephalitis. Also known as "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly-transmitted sleeping sickness), it was first described in 1917 by the neurologist Constantin von Economo and the pathologist Jean-René Cruchet.
The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless. Between 1915 and 1926, an epidemic
of encephalitis lethargica spread around the world. Nearly five million
people were affected, a third of whom died in the acute stages. Many of
those who survived never returned to their pre-existing "aliveness".
They would be conscious and aware – yet not fully awake; they would sit motionless and speechless all day in their chairs, totally lacking energy, impetus, initiative, motive, appetite, affect or desire; they registered what went on about them without active attention, and with profound indifference. They neither conveyed nor felt the feeling of life; they were as insubstantial as ghosts, and as passive as zombies.
No recurrence of the epidemic has since been reported, though isolated cases continue to occur.
Signs and symptoms
Encephalitis lethargica is characterized by 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 (akinetic mutism). Patients may also experience abnormal eye movements ("oculogyric crises"), Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis. Klazomania (a vocal tic) is sometimes present.
Cause
Encephalitis lethargica. Its sequelae and treatment - Constantin Von Economo, 1931: front page
The causes of encephalitis lethargica are uncertain.
Some studies have explored its origins in an autoimmune response, and, separately or in relation to an immune response, links to pathologies of infectious disease — viral and bacterial, e.g., in the case of influenza, where a link with encephalitis is clear. Postencephalitic parkinsonism was clearly documented to have followed an outbreak of encephalitis lethargica following 1918 influenza pandemic; evidence for viral causation of the Parkinson's symptoms is circumstantial (epidemiologic, and finding influenza antigens in encephalitis lethargica patients), while evidence arguing against this cause is of the negative sort (e.g., lack of viral RNA in postencephalitic parkinsonian brain material).
In reviewing the relationship between influenza and encephalitis
lethargica (EL), McCall and coworkers conclude, as of 2008, that while
"the case against influenza [is] less decisive than currently perceived…
there is little direct evidence supporting influenza in the etiology of
EL," and that "[a]lmost 100 years after the EL epidemic, its etiology
remains enigmatic."
Hence, while opinions on the relationship of encephalitis lethargica to
influenza remain divided, the preponderance of literature appears
skeptical.
German neurologist Felix Stern, who examined hundreds of
encephalitis lethargica patients during the 1920s, pointed out that the
encephalitis lethargica typically evolved over time. The early symptom
would be dominated by sleepiness or wakefulness. A second symptom would
lead to an oculogyric crisis.
The third symptom would be recovery, followed by a Parkinson-like
symptom. If patients of Stern followed this course of disease, he
diagnosed them with encephalitis lethargica. Stern suspected
encephalitis lethargica to be close to polio without evidence.
Nevertheless, he experimented with the convalescent serum of survivors
of the first acute symptom. He vaccinated patients with early stage
symptoms and told them that it might be successful. Stern is author of
the 1920s definitive book Die Epidemische Encephalitis (1920 and 2nd ed. 1928). Stern was driven to suicide during the Holocaust by the German state, his research forgotten.
In 2010, in a substantial Oxford University Press compendium reviewing
the historic and contemporary views on EL, its editor, Joel Vilensky of
the Indiana University School of Medicine,
quotes Pool, writing in 1930, who states, "we must confess that
etiology is still obscure, the causative agent still unknown, the
pathological riddle still unsolved…", and goes on to offer the following
conclusion, as of that publication date:
Does the present volume solve the "riddle" of EL, which… has been referred to as the greatest medical mystery of the 20th century? Unfortunately, no: but inroads are certainly made here pertaining to diagnosis, pathology, and even treatment."
Subsequent to publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic. In 2012, Oliver Sacks acknowledged this virus as the probable cause of the disease. Other sources have suggested Diplococcus as a cause.
Diagnosis
There
have been several proposed diagnostic criteria for encephalitis
lethargica. One, which has been widely accepted, includes an acute or
subacute encephalitic illness where all other known causes of
encephalitis have been excluded. Another diagnostic criterion, suggested
more recently, says that the diagnosis of encephalitis lethargica "may
be considered if the patient’s condition cannot be attributed to any
other known neurological condition and that they show the following
signs: Influenza-like signs; hypersomnolence (hypersomnia), wakeability, ophthalmoplegia (paralysis of the muscles that control the movement of the eye), and psychiatric changes."
The Great Encephalitis Pandemic (1915-1926)
In the winter of 1916–1917, a "new" illness suddenly appeared in Vienna
and other cities, and rapidly spread world-wide over the next three
years. Earlier reports appeared throughout Europe as early as the winter
of 1915–1916, but communication about the disease was slow and chaotic,
given the varied manifestation of symptoms and difficulties
disseminating information in wartime. Until Constantin von Economo identified a unique pattern of damage among the brains of deceased patients and introduced the unifying name encephalitis lethargica, reports of the protean disease came in under a range of names: botulism, toxic ophthalmoplegia, epidemic stupor, epidemic lethargic encephalitis, acute polioencephalitis, Heine-Medin disease, bulbar paralysis, hystero-epilepsy, acute dementia, and sometimes just "an obscure disease with cerebral symptoms." Just ten days before von Economo's breakthrough in Vienna, Jean-René Cruchet described forty cases of "subacute encephalomyelitis" in France.
In the ten years that the pandemic raged, nearly five million
people's lives were taken or ravaged. Encephalitis lethargica assumed
its most virulent form between October 1918 and January 1919. The
pandemic disappeared in 1927 as abruptly and mysteriously as it first
appeared. The great encephalitis pandemic coincided with the 1918 influenza pandemic,
and it is likely that the influenza virus potentiated the effects of
the encephalitis virus or lowered resistance to it in a catastrophic
way.
Aftermath of the Pandemic (1927-1967)
In the aftermath of the pandemic
(between 1927 and 1967), many surviving patients seemed to make a
complete recovery and return to their normal lives. However, the
majority of them subsequently developed neurological or psychiatric
disorders, often after years or decades of seemingly perfect health.
Post-encephalitic syndromes varied widely: sometimes they proceeded
rapidly, leading to profound disability or death; sometimes very slowly;
sometimes they progressed to a certain point and then stayed at this
point for years or decades; and sometimes, following their initial
onslaught, they remitted and disappeared.
Treatment
Modern treatment approaches to encephalitis lethargica include
immunomodulating therapies, and treatments to remediate specific
symptoms.
There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement. The disease becomes progressive, with evidence of brain damage similar to Parkinson's disease.
Treatment is then symptomatic. Levodopa (L-DOPA) and other anti-Parkinson drugs often produce dramatic responses; however, most people given L-DOPA experience improvements that are short lived.
Notable cases
Notable cases include:
- Muriel "Kit" Richardson (née Hewitt), first wife of actor Sir Ralph Richardson, died of the condition in October 1942, having first shown symptoms in 1927–28.
- There is speculation that Adolf Hitler may have had encephalitis lethargica when he was a young adult (in addition to the more substantial case for Parkinsonism in his later years).
- Mervyn Peake (1911–1968), author of the Gormenghast books, began his decline towards death which was initially attributed to encephalitis lethargica with Parkinson's disease-like symptoms, although others have later suggested his decline in health and eventual death may have been due to Lewy body dementia.
- Rosita Renard (1894–1949), Chilean pianist, contemporary of Claudio Arrau and student of Martin Krause.
- Those described in the book Awakenings by the British neurologist Oliver Sacks.
