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Biographies de neurologues
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 Encephalitis lethargica.
Its sequelae and treatment
von Economo C
Translated by KO Newman
London: Oxford University Press
Influenza RNA not detected in archival brain tissues from acute encephalitis lethargica cases or in postencephalitic Parkinson cases
McCall S, Henry JM, Reid AH, Taubenberger JK
J Neuropathol Exp Neurol.
2001; 60; 11; 1121-2
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11 décembre 2003
 Les biographies de neurologues  
Baron Constantin von Economo
1876 - 1931
Cinquante ans de sommeil O Sacks
Sleep as a problem of localisation von Economo 1930 - pdf


Entre 1917 et 1925, toute l'Europe est atteinte par l'épidémie de cette encéphalite léthargique qu'identifia alors C.Von Economo (1876-1931). Elle était liée à des destructions neuronales apparaissant aujourd'hui d'origine autoimmune, le virus de la grippe n'étant plus considéré actuellement comme facteur inducteur. Les lésions sous-corticales et mésodiencéphaliques déterminaient des troubles aigus, souvent mortels, mais aussi, chez ceux qui en réchappaient, toute une série de perturbations chroniques, telles que des altérations graves de l'humeur, des manifestations dépressives ou délirantes, des mouvements anormaux (comme dans les observations rapportées ici : bâillements) à type de crises occulogyres, de parkinsonisme etc... L'unité du processus morbide et la relative constance du siège des lésions contrastaient avec le polymorphisme des manifestations cliniques, de telle sorte que certains en venaient alors à mettre en doute la réalité effective.
Les découvertes contemporaines confirment le bien-fondé des hypothèses formulées par Von Economo. L'atteinte auto-immune (cf article de 2003 ci-dessous) des ganglions de la base et de l'hypothalamus entrainait, entre autres, la raréfaction des neurones à hypocrétine, et donc tarissait, de façon transitoire ou mortelle, la sécrétion d'un des neuromédiateurs responsables de l'éveil. D'autres structures pouvaient aussi être lésées, inhibant les sécrétions de mélatonine et expliquant ainsi les inversions de rythme nycthéméral, mimant le syndrome génétique de Smith-Magenis.. (Inversion of the circadian melatonin rhythm in Smith-Magenis syndrome De Leersnyder H et al.Rev Neurol 2003; 159; 11 Suppl; 21-6)
En 2004 Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity

Constantin von Economo was known for bis achievements in microscopic anatomy of the brain as well as for bis description of an infectious disease encephalitis epidemica lethargica, which is characterized by increasing listlessness or weakness, apathy, and drowsiness, passing into coma. This disease was observed in various parts of the world between 1915 and 1926.
Economo was born in Trieste of a patricien famlly of Greek origin. His preliminary education was acquired in German schools in Trieste, and bis medical training was in Vienna, where he received bis MD degree in 1901. During his career, he worked with the Nobel Prize winner Julius Wagner von Jauregg, the physiologist Siegmund Exner, and the histologists Victor von Ebner and Josef Schaffer. Economo was also influenced by Alois Alzheimer and Emil Kraepelin.
In the Wiener klinische Wochenschrift of May 10, 1917, Economo reported his clinical investigation of a new infectious epidemic disease. Near the end of 1917, he described it as an encephalitis disseminated in small areas throughout the nervous system but showing a predilection for the gray matter of the mesencephalon. The reaction of the nervous system was described as nonhemorrhagic and nonnecrotic, but inflammatory. A few months later, its infectious character was established by experimental transmission of the disease to monkeys, with production of similar pathologic characteristics. These findings were confirmed by other investigators, and the disorder bas become known familiarly as Economo's disease.
The disease first appeared in Romania in 1915 and raged globally until 1927.Encephalitis lethargica was once a major cause of post-encephalitic Parkinson's Disease, but there have been no new cases for years. The last reported case was in 1940, though the clinical sequelae were seen for years after that. Economo was a man of independent means. He rejected the chair of psychiatry when von Jauregg retired in 1928. (LF. Haas)
A second remarkable contribution was The Cytoarchitecture of the Cerebral Cortex in Adult Man, published in 1925. This represented an exhaustive investigation of the cellular structure of the brain, which Economo had begun in 1912. A volume of 810 pages contained the description and discussion, and a companion volume comprised 112 plates showing typical photomicrographs in large scale.
Besides bis work in medicine and neurology, Economo was a pioneer in aeronautics, being one of the first civil pilots and the first military pilot in the Austro-Hungarian empire.
The iliness of which Economo eventually died appeared first et the age of 45 years, when he suffered a coronary occlusion. After a slow recovery, he eventually returned to his work. He later suffered coronary embolism, the results of which were subsiding when cerebral thrombosis developed, and he died at his home in Vienna on Oct 21, 1931, at the age of 65 years. Economo was honored in 1976 by an Austrian stamp (Scott No. 1040) issued on the centenary of his birth.
Robert A. Kyle and Marc A. Shampo JAMA 1978; 240; 6; 568
von Economo Encephalitis; Morris S. Dickman; Arch Neurol. 2001; 58; 1696-1698
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Abstract : In April 1917, Dr Constantin von Economo presented his clinical and pathologic findings of a new disease-soon to be part of a worldwide epidemic-before the Vienna Psychiatric Society. He named it encephalitis lethargica. After years of careful observation, he collected and analyzed thousands of cases and classified them into 3 clinical syndromes: somnolentophthalmoplegic, hyperkinetic, and amyostatic-akinetic forms. He described the now legendary post-encephalitic Parkinsonism, noting that symptoms could emerge years after the original infection, often without signs of prodromal "flu." He emphasized the neuropathologic findings: inflammatory changes in the tegmentum of the midbrain accounting for the sleep disturbance and ocular signs. After encountering sporadic cases following the epidemic, he concluded that the somnolentophthalmoplegic syndrome was the primary expression of encephalitis lethargica. This article out lines the observations and conclusions of Dr von Economo during and affer the epidemic through seminal quotations primarily from his published works, as well as from more recent reports.
Early observations
The first case of this strange new disease appeared at the end of 1916. Under the careful observation of Dr von Economo, a well-defined syndrome complex began to emerge, characterized by disturbances of sleep and ocular motility as well as ptosis, which he described in his early monograph.
«It seems strange when sleep appears as a symptom of an illness. "Sleeping sickness" where the phenomenon of people falling asleep while eating or working was first described in two cases in our clinic in Vienna in 1916. Usually headache, nausea, and fever were followed, often the next day, by sleeping, frequently in a most uncomfortable position. One can wake them, but in severe cases, coma can rapidly lead to death. Malfunction of eye muscles, especially oculomotor dysfunction, and ptosis, was common.»
In fact, of the 13 reported cases, von Economo described 4 with ptosis, 2 with abducens palsies, and 1 each with supranuclear palsy and medial longitudinal fasciculus syndrome. Only 3 of the 13 had no ocular signs.
Historical background
von Economo may have known of accounts of similar cases -and epidemics-that were reported centuries ago, such as mendossa in Lisbon in 1521, pestilence soporeuse in Italy in 1561, and lethargy with ocular palsies in Germany in 1605. He was aware of an epidemic in Italy in the late 1800s, which may have given impetus to his major life's work.
«... a half-forgotten memory of childhood came to the fore. In 1890-1891 there occurred in connection with the then pandemic influenza in Italy a peculiar illness associated with stupor called Nona. von Economo reported that he described his own peculiar cases of stupor to his mother and asked whether she remembered the accounts of the mysterious Nona. She replied that she did»
Within months of the appearance of the first case, von Economo already had autopsy proven evidence of the neuropathology: notably widespread microscopic inflammatory foci, particularly in the gray substance of the tegmenturn of the mid brain. This was presented before the Psychiatric Society in Vienna on April 17, 1917, and named encephalitis lethargica.
«We must assume that it is from the grey matter of this region that the natural sleep function is influenced. This assumption gains all the more probability because Wernicke's encephalitis, in the wake of delirium tremens, eye muscle disturbances and somnolence appear, and hemorrhages are to be found in these same parts of the tegmentum.»
Clinical presentation
Usually associated with the influenza epidemic that claimed more than 30 million lives, tens of thousands of cases of encephalitis were reported during and after the first World War. von Economo was the first to recognize and classify 3 distinct clinical forms.
«Every epidemic of encephalitis lethargica is characterized by the predominance of a certain combination of symptoms.... We are able to distinguish three forms of pathological syndromes which embrace the great majority of cases.... These three syndromes under which encephalitis lethargica has appeared most frequently hitherto are the somnolent-ophthalmoplegic, the hyperkinetic, and the amyostatic-akinetic (the so-called Parkinsonism ).»
Somnolent-Ophthalmoplegic «The prodromal phenomena consists of general discomfort, shivering, headache, and slight pharyngitis. The temperature is generally only a little raisedto slightly above 98'C.... Within the next few days, somnolence begins to predominate. The patients left to themselves fall asleep in the act of sitting and standing, and even while walking, or during meals with food in the mouth.... if aroused, they wake up quickly and completely, are oriented and fully conscious ... but soon drop back to sleep. Sleep in this form may last for weeks or even months but frequently deepens to a state of most intense stupor or even a comatose condition which may terminate fatally after some days or weeks.
Generally, during the first days of the illness (cranial nerve) palsies appear. Ptosis is one of the first and most frequent symptoms. The frequent bilateral occurrence of ocular palsies, incomplete usually asymmetrical, suggest that it is, in most cases, a nuclear palsy. Rarely observed are supranuclear paralyses, paresis of convergence, nystagmus, optic neuritis, papilledema, pupillary disturbances, and even Argyll Robertson's sign.
Hyperkinetic : In the winter of 1920, there was observed a very large group of hyperkinetic cases, first in Italy then Austria. Chorea and hemichorea as well as myoclonic twitches which were observed may degenerate into wild jactations.
On the other hand, it may find its mental expression in a general, curions restlessness of an anxious or hypomanic type. In most of these cases, there is a very distinct sleep disturbance and generally the condition is one of troublesome sleeplessness.
Amyostatic-Akinetic :Third place in order of frequency, the amyostatic-akinetic form, is characterized by a rigidity, without a real palsy and without symptoms arising from the pyramidal tract. This form of encephalitis lethargica is particularly common in the chronic cases, dominating the clinical picture as Parkinsonism. I reserve the name "Parkinsonism" though symptomatically identical with the amyostatic-akinetic form, rather for the chronic cases. To look at these patients one would suppose them to be in a state of profound secondary dementia. Emotions are scarcely noticeable in the face, but they are mentally intact.»
Writing in 1929, toward the end of the devastating worldwide epidemic, von Economo concluded that the somnolent-ophthalmoplegic form was the primary expression of encephalitis lethargica. If it ever recurred again, be reasoned that it would be in this form.
«Now that the great epidemics of encephalitis lethargica are over, we meet with isolated sporadic acute cases every year. It is interesting to note that these sporadic cases of encephalitis lethargica, occurring at a time when there is no epidemic, are mostly of the somnolent-ophthalmoplegic form. Therefore, it appears probable that the somnolent-ophthalmoplegic form should bc regarded as the basic form proper of encephalitic lethargica.»
Geographic-specific syndromes : As the disease ravaged Europe, von Economo recognized particular combinations of symptoms and syndromes, in various countries and cities especially hard-hit by the epidemic and classified them accordingly.
Prognosis : Encephalitis lethargica was quickly recognized as a serious, lethal discase. Aside front a very high mortality rate, many patients were left with significant disabilities.
«The prognosis of clinically welldocumented cases of encephalitis lethargica is: 40% mortality, 14% complete tecovery, 26% recovery with defect, but able to work, and 20% chronic4nvalidity. Encephalitic lethargica must in every case bc regarded as a serious and dangerous disease.»
Chronic parkinsonism : As early as 1920 von Economo bcgan observing cases that had apparently recovered fully, only to be stricken with parkinsonian features months, or even years, later.
«Parkinsonism may develop in immediate sequence after the amyostatic form ... as well as 4 or 5 years after an apparenty complete recovery fron acute encephalitic lethargica. The acute stage may have been slight or serious; it is of no importance in indicating the probable development of later symptoms. Often we see cases where such sequelae develop with no history of a previous acute phase.»
Oculogyric crises : Without doubt, the oculogyric crisis was the one of the outstanding features of postencephalitic parkinsonism, which intrigued clinicians for decades.
«Of particular interest are the visual fits, described by French authors as "crises ocuogyres" (van Bogaert, Bing, and Schwartz, Marinesco and Radovici), in English as "tonic eye-fits" or, more commonly, as oculogyric crises. They consist of tome visual convulsions, occurring in fits and generally lasting ony a few minutes, during which the patients as a rule look upwards and sideways.... Frequently, the convulsive twisting of the eyes is also accompanied by other convulsive movements, such as contortion of the head in the direction of vision, tonic stretching of the neck, even of the trunk and extremities...»
Recent observations
While reports of presumed Economo encephalitis or postencephalitic Parkinson disease unrelated to the 1917-1927 pandemic have appeared in the medical literature in the past 30 years, most of them have lacked either an adequate documentation of encephalitis lethargica or a convincing causal relationship between the encephalitis and subsequent neurologic sequelae. In one series, in almost every case, the parkinsonian symptoms and signs first appeared 20 to 40 years after the encephalitis.
Howard and Lees, however, carefully documented 4 cases in 1987. While failing to identify the viral agent, they found positive oligoclonal banding in 3, performed postmortern examinations in 1, and formulated specific diagnostic criteria:
«We propose that a number of clinical features ... as major criteria supporting the diagnosis of encephalitis lethargica. It should comprise an acute or subacute encephalitic illness . . . [with] three of the following major criteria: (1) signs of basal ganglia involvement, (2) oculogyric crises, (3) ophthalmoplegia, (4) obsessive-compulsive behavior, (5) akinetic mutism, (6) central respiratory irregularities and (7) somnolence and/or sleep inversion.»
Duvoisin and Yahr, in 1965, published a review of their patients with postencephalitic parkinsonism. They sunveyed the literature for a similar syndrome caused by known viruses and could find no association with any known neurotropic viral agent:
«The rare association of a progressive Parkinsonim syndrome such as is understood by the term Parkinson's Discase with any [ known] type of viralencephalitis ... bas not be shown to be more than coincidental.»
More than 30 years later, one of the authors again reviewed published reports and concluded that despite the advent of modern virology, the failure to isolate the causative agent continues to cast a shadow of doubt on all reported cases:
«Presumed cases of von Economo's disease parkinsonism have been reported in small numbers since 1970. The clinical and, when available, the pathological data are fairly convincing. However lacking a specific confirmation, the doubt will remain concerning the authenticity of the diagnosis.»
  • Von Economo C. Encephalitis Lethargica. Wien Klin Weshr. 1917; 30; 581-583
  • Von Econom. C. Die Enœphalitis lethargica Dr C. Von Economo. Leipzig und Wein, Germany: Franz Deuticke 1918.
  • Von Economo C, Wagner Jauregg V. Baron Constantin von Economo: His Life and Work. Burlington, Vt: Free Press Interstate Corp; 1937.
  • Von Economo C. Encephalitis Lethargica, its Sequelae and Treatment. Translated by K.O. Newman, Oxford University Press. London, England; 1931.
  • Wenning G, Jellinger K, Litvan I. Supranuclear gaze palsy and eyelid apraxia in post-encephalitic parkinsonism. J Neural Transm. 1997;104:845-854.
  • Howard R, Lees A. Encephalitic lethargica: a report of four recent cases. Brain 1987; 110; 19-28
  • Duvoisin R, Yahr M. Encephalitic and parkinsonism. Arch Neurol. 1965; 12; 227-243.
  • Casals J, Elizan T, Yahr M. Postencephalitic parkinsonism-a review. J Neural Transm. 1998; 105:645-652
Baron Constantin von Economo1876 - 1931

Sleep as a problem of localisation von Economo 1930 - pdf