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: somnolent-ophthalmoplegic,
hyperkinetic, and amyostatic-akinetic forms.
He described the now legendary postencephalitic
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
somnolent-ophthalmoplegic syndrome was the
primary expression of encephalitis lethargica.
These articles outlines the observations and
conclusions of Dr von Economo during and after
the epidemic through seminal quotations
primarily from his published works, as well as
from more recent reports.
The disease first appeared in Romania in
1915 and raged globally until 1927. (LF. Haas).
It's seem possible that the loss of hypocretin's
neurons and/or melatonin's neurons explain this
symptomatology. An Encephalitis-lethargica-like
syndrome is still prevalent and this syndrome
may be secondary to autoimmunity
against deep grey matter neurons.
Encéphalite
léthargique
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 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.
RC Dale, AJ Church, RA Surtees, AJ
Lees, JE Adcock, B Harding, BG Neville, G
Giovannoni
Brain 2004;
127;1:21-33
Since the 1916-1927 epidemic, only sporadic
cases have been described. Pathological studies
revealed an encephalitis of the midbrain and
basal ganglia, with lymphocyte (predominantly
plasma cell) infiltration. Recent examination of
archived EL brain material has failed to
demonstrate influenza RNA, adding to the
evidence that EL was not an invasive influenza
encephalitis. By contrast, the findings of
intrathecal oligoclonal bands (OCB) and
beneficial effects of steroid treatments have
provoked the hypothesis that EL may be
immune-mediated. We have recently seen 20
patients with a similar EL phenotype, 55% of
whom had a preceding pharyngitis. The patients
had remarkable similarity to the historical
descriptions of EL: sleep disorder (somnolence,
sleep inversion or insomnia), lethargy,
parkinsonism, dyskinesias and neuropsychiatric
symptoms. CSF examination commonly showed
elevated protein and OCB (75 and 69%
respectively). Investigation found no evidence
of viral encephalitis or other recognized causes
of rapid-onset parkinsonism. We investigated the
possibility that this phenotype could be a
postinfectious autoimmune CNS disorder, and
therefore similar to Sydenham's chorea.
Anti-streptolysin-O titres were elevated in 65%
of patients. Furthermore, western immunoblotting
showed that 95% of EL
patients had autoantibodies reactive against
human basal ganglia antigens.....It
is perhaps regrettable that no measurement of
Hypocretin (LCR) or Melatonin stay in this
study.
A 15-year-old boy presented with an acute
personality change 10 days after an upper
respiratory tract infection. He became extremely
anxious and worried about his safety. One week
later he had an oculogyric crisis and developed
upper-limb resting tremor and bradykinesia. This
was followed by extreme daytime somnolence,
lethargy and intractable hiccough. On
examination, he would fall asleep if not
stimulated and yawned continuously.
Pupillary responses were poorly reactive to
light and accommodation....continuation.
Encephalitis lethargica: lessons for
contemporary neuropsychiatry SR Cheyette and
JL Cummings J Neuropsychiatry
Clin Neurosci 1995; 7; 125-134
Encephalitis lethargica (von Economo's
encephalitis), pandemic from 1917 to 1926,
opened a window on the study of behavioral
consequences of infection-induced subcortical
disorder. Widely varying acute manifestations
included extrapyramidal disorders, myoclonus,
eye movement disorders, paralyses, delirium,
mood changes, inverted diurnal rhythms, and
catatonia. Major pathological changes
involved the substantia nigra, globus pallidus,
and hypothalamus. A symptom-free recovery
period was often followed by postencephalitic
disturbances, typically parkinsonism in adults
and conduct disorder in children. Occurrence of
depression, mania, obsessive-compulsive
disorder, and hyperactivity in post-encephalitic
patients anticipated current concepts of the
role of the basal ganglia in mood, personality,
and obsessional syndromes. Observations of
deferred onset and "tardy" hyperkinesias
presaged current theories of the pathophysiology
of tardive dyskinesia.
Encephalitis lethargica. A report of four
recent cases RS Howard and AJ Lees
Brain 1987; 110; 1;
19-33
Four patients are described with an
encephalitic illness identical to that described
by von Economo. Electroencephalographic, evoked
potential and autopsy data suggest that
involvement of the cerebral cortex is more
extensive than has been generally recognized.
Serological tests and viral cultures failed to
reveal the infectious agent but the presence of
oligoclonal IgG banding in the cerebrospinal
fluid in 3 of the patients during the acute
phase of the illness would be in keeping with a
viral aetiology.
«il jouit d'une
santé excellente jusqu'à dix-sept
ans, âge auquel il contracta une
encéphalite léthargique de
type soporeux compliquée d'une grippe,
qui le plongea dans un état de somnolence
(non stuporeuse) durant six mois. Sitôt
après s'être rétabli de cet
accès initial, il constata qu'il
souffrait de troubles du sommeil et de l'humeur,
et de certains désordres psychiques.
Entre 1922 et 1930, son problème
majeur fut sans doute l'inversion de son rythme
de sommeil : il avait tendance à avoir
extrêmement sommeil et à tomber
dans une sorte de torpeur le jour, et à
être, la nuit, très
énervé et insomniaque. Il fut
également sujet à de soudains
accès de bâillements, à
de la narcolepsie, à des accès de
somnambulisme et de somniloquisme, à des
paralysies se déclarant pendant le
sommeil et à des
cauchemars.»
Si cette épidémie
récidivait actuellement, comment
s'adapteraient les services d'urgence
?
