Encephalitis lethargica

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Encephalitis lethargica
Other namesNellysa disease; Economo's disease
Economo1918h.PNG
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   OOjs UI icon edit-ltr-progressive.svg
CausesUnknown
FrequencyUnknown

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 [1] [2] and the pathologist Jean-René Cruchet. [3]

Contents

The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless. [4] Between 1915 and 1926, [5] 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. [6]

No recurrence of the epidemic has since been reported, though isolated cases continue to occur. [7] [8]

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. [4] [9] In severe cases, patients may enter a coma-like state (akinetic mutism).[ citation needed ] Patients may also experience abnormal eye movements ("oculogyric crises"), [10] Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis.[ citation needed ] Klazomania (a vocal tic) is sometimes present. [11]

Cause

Encephalitis lethargica. Its sequelae and treatment - Constantin Von Economo, 1931: front page Encephalitis-livre.png
Encephalitis lethargica. Its sequelae and treatment - Constantin Von Economo, 1931: front page

The causes of encephalitis lethargica are uncertain. [12]

Some studies have explored its origins in an autoimmune response, [4] and, separately or in relation to an immune response, links to pathologies of infectious disease — viral and bacterial, [4] e.g., in the case of influenza, where a link with encephalitis is clear. [13] 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). [13] 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." [8] Hence, while opinions on the relationship of encephalitis lethargica to influenza remain divided, the preponderance of literature appears skeptical. [8] [14]

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. [15]

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." [16]

Subsequent to publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic. [17] In 2012, Oliver Sacks acknowledged this virus as the probable cause of the disease. [18] Other sources have suggested Diplococcus as a cause. [19]

History

Occurrences

Retrospective diagnosis tentatively suggests numerous accounts of encephalitis lethargica throughout history:

The Encephalitis Lethargica Pandemic of 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. [21] 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." [21] Just ten days before von Economo's breakthrough in Vienna, Jean-René Cruchet described forty cases of "subacute encephalomyelitis" in France. [21]

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. [21] 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. [21]

Aftermath of the Pandemic (Postencephalitic Syndromes)

Many surviving patients of the 1915-1926 encephalitis lethargica pandemic seemed to make a complete recovery and return to their normal lives. However, the majority of survivors 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. [22] Postencephaltic Parkinsonism is perhaps the most widely recognized of such syndromes.

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." [23]

Treatment

L-DOPA Levodopa.png
L-DOPA

Modern treatment approaches to encephalitis lethargica include immunomodulating therapies, and treatments to remediate specific symptoms. [24] [ non-primary source needed ]

There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement. [25] [ non-primary source needed ] The disease becomes progressive, with evidence of brain damage similar to Parkinson's disease. [26] [ non-primary source needed ][ needs update ]

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. [27] [28]

Notable cases

Notable cases include:

Related Research Articles

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Encephalitis Brain disease that is characterized as an acute inflammation of the brain with flu-like symptoms

Encephalitis is inflammation of the brain. The severity can be variable with symptoms including headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

Spanish flu 1918 pandemic of H1N1 influenza virus

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Coprolalia is involuntary swearing or the involuntary utterance of obscene words or socially inappropriate and derogatory remarks. Coprolalia comes from the Greek κόπρος (kópros), meaning "dung, feces", and λαλιά (laliā́) "speech", from λαλεῖν (laleîn) "to talk".

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Post-encephalitic Parkinsonism is a disease believed to be caused by a viral illness that triggers degeneration of the nerve cells in the substantia nigra. Overall, this degeneration leads to clinical parkinsonism.

Oculogyric crisis (OGC) is the name of a dystonic reaction to certain drugs or medical conditions characterized by a prolonged involuntary upward deviation of the eyes. The term "oculogyric" refers to the bilateral elevation of the visual gaze, but several other responses are associated with the crisis. Epilepsy can manifest as oculogyric seizures, also called versive seizures.

Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.

Akinetic mutism is a medical term describing patients tending neither to move (akinesia) nor speak (mutism). Akinetic mutism was first described in 1941 as a mental state where patients lack the ability to move or speak. However, their eyes may follow their observer or be diverted by sound. Patients lack most motor functions such as speech, facial expressions, and gestures, but demonstrate apparent alertness. They exhibit reduced activity and slowness, and can speak in whispered monosyllables. Patients often show visual fixation on their examiner, move their eyes in response to an auditory stimulus, or move after often repeated commands. Patients with akinetic mutism are not paralyzed, but lack the will to move. Many patients describe that as soon as they 'will' or attempt a movement, a 'counter-will' or 'resistance' rises up to meet them.

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Klazomania refers to compulsive shouting; it has features resembling the complex tics such as echolalia, palilalia and coprolalia seen in tic disorders, but has been seen in people with encephalitis lethargica, alcohol abuse and carbon monoxide poisoning. It was first reported by L. Benedek in 1925 in a patient with postencephalitic parkinsonism. Little is known about the condition, and few cases have been reported.

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Constantin von Economo Romanian psychiatrist and neurologist

Constantin Freiherr von Economo was an Austrian psychiatrist and neurologist of Romanian origin and Greek descent. He is mostly known for his discovery of encephalitis lethargica and his atlas of cytoarchitectonics of the cerebral cortex.

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References

  1. Economo's disease at Who Named It?
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  3. Cruchet, R; Moutier, J; Calmettes, A (1917). "Quarante cas d'encéphalomyélite subaiguë" [Forty cases of (subacute) encephalitis lethargica]. Bull Soc Med Hôp (in French). Paris. 41: 614–6.
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  33. Demetrios J. Sahlas (2003). "Dementia With Lewy Bodies and the Neurobehavioral Decline of Mervyn Peake". Arch. Neurol. 60 (6): 889–92. doi:10.1001/archneur.60.6.889. PMID   12810496.
  34. McMillan, Roy; Peake (20 July 2011) [1959]. Butcher Sara (ed.). Publisher's Liner Notes on Mervyn Peake for 'Titus Alone' (Liner Notes/ Reference Guide for Abridged Audiobook of Titus Alone). Audible.com (PDF, Liner Notes) (Abridged, Audio ed.). Germany: Naxos Audiobooks. p. 7. ISBN   978-184-379-542-1 . Retrieved 2 May 2018. But the plays were not the financial winners he had hoped for, and he suffered another nervous breakdown in 1957. This led to the more evident display of the symptoms of a type of Parkinson’s Disease which, alongside the effects of encephalitis lethargica that he contracted in childhood, was slowly to kill him over more than a decade.

Further reading

Classification
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