Etats de mal épileptiques - LYON Nicolas Engrand - ANARLF
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Etats
de
mal
épileptiques
Nicolas Engrand
DIU
Neuroréanimation
LYON
31
janvier
2018
Fondation
ROTHSCHILD
-‐ PARIS
Peter W. Kaplan, MD tions. Immune therapies were used less frequently in cryptogenic cases, despit
Jong W. Lee, MD prevalence of inflammatory CSF changes.
Benjamin Legros, MD Conclusions: Autoimmune New-onset encephalitis refractory is the statusmost commonly epilepticus identified caus
Jerzy P. Szaflarski, MD,
Neurocrit Care
refractory status epilepticus, but half
Etiology, clinical remain
features, cryptogenic. Outcome at discharge
and outcome
PhD DOI 10.1007/s12028-012-9695-z proves during follow-up. Epilepsy develops in most cases. The role of anesthet
Brandon M. Westover, therapies
R E V I E Wwarrants further Nicolasinvestigation.
Gaspard, MD, Neurology ® 2015;85:1604–1613
ABSTRACT
MD, PhD PhD
m plus clonazepam
Nicolas Gaspard, MD, ABSTRACT
Objectives: The aims of this study w
Suzette M. LaRoche,
Guidelines for theMD Evaluation
GLOSSARY and PhD Management Brandon
ofTheStatus
Objectives: P.of Foreman,
aims of outcome
this study were to determine of new-onset
the etiology, clinical refractory
features, and predictors
Brandon P. Foreman,
Epilepticus
Lawrence J. Hirsch, MD CCEMRC 5MDCritical Care EEG of outcome of new-onset refractory status epilepticus.
MD Research Consortium; CEEG 5 continuous EEG; ICU 5 inten
Monitoring
Alvarez, mRS
Methods: Retrospective review of patients with Methods: Retrospective
refractory status review of
epilepticus without etiology
interquartile
Vincentrange; MD modified
Vincent
5identified Rankin
Alvarez, Scale;
MD NMDAR NMDA
5January receptor; NORSE 5 new-ons
For the Critical
M. BrophyCare EEG within 48 hours of admission between 1, 2008, and December 31, 2013,
lepticus
Gretchen Rodney• Bell Jan Claassen
epilepticus;MD
•Brian
Christian Alldredge
Cabrera Kang,
RSE 5 refractory
•
in 13status medical centers.SE
academicepilepticus;
•
The 5 identified
status
primary epilepticus;
outcome measure within poor48
wasSTESS 5hours
Status
functional ofEpilept
outcome admis
Thomas P. Bleck Tracy Glauser Suzette M. LaRoche James J. RivielloChristian
Jr. Cabrera Kang,
Monitoring Research •
Lori Shutter Michael R. Sperling David
• VGKCC
•
voltage-gated
5John
M. Treiman
• C. Probasco,
Paul M.MDVespa•
•
potassium channel complex.
at discharge (defined
•
as a
•
score .3 on the
in 13 academic medical centers. T
modified Rankin Scale).
Consortium
Neurocritical Care Society Status Epilepticus Amy C. Jongeling
Guideline Writing Committee MD
Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies
Emma Meyers, BSc were autoimmune (19%) and paraneoplastic at (18%)discharge (defined
encephalitis. Full data wereas a score
available in .3
John C. Probasco, MD
(CCEMRC) American Status epilepticus
Alyssa Espinera, BSc (SE) is the second most common neurologic emergency. Up
125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) 1
ind, phase 3 trial
Epilepsy Societydied. Guideline
Kevin F. Haas, MD Predictors of poor outcome included duration
Amy C. Jongeling Results: Ofepilepticus,
of status 130 cases, 67 (52%) re
use of anesthetics,
cases are refractory (RSE)
! Springer Science+Business Media, LLC 2012
Sarah E. Schmitt, MD
Elizabeth E. Gerard, MD
to first- and second-line treatments. New-onset RSE
and medical complications. Among the 63 patients with available follow-up
Emma Meyers, BSc
months), functional status improved in 36 (57%);were79% autoimmune
had good or fair
2,3 data (median 9
outcome (19%) and para
at last follow-
rare but challenging condition,
Teneille Gofton, MD
Alyssa Espinera, characterized BScConvulsive by the occurrence of a prolonged p
up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medica-
125 cases (62 cryptogenic). Poor o
Correspondence
Abstract Status Evidence-Based Guideline: Treatment
to epilepticus (SE) treatment strategies Peter W. Kaplan, MD
Keywords prevalenceStatus epilepticus ! of
Seizure ! Guideline ! Status
tions. Immune therapies were used less frequently in cryptogenic cases, despite a comparable
Articles
died. Predictors of poor outcome 4
vary
Dr. Gaspard: from one institution toryto seizures
another due to the with
Jong W. Lee, MD
Epilepticus in Children and Adults: Report of the Guideline
substantially EEG
Benjamin Legros, MD
! no readily
Antiepileptic Kevinidentifiable
F. Haas, MD cause in otherwise healthy individuals.
of inflammatory CSF changes.
treatment
Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset
lack of data to support one treatment over another. To and medical Outcome atcomplications.
discharge is poor but im-Among
m An, Francis Bolgert,
ngaspard@ulb.ac.be 40 adult
Jean-Marc cases have
Tréluyer, beenSarah reported,E. Schmitt, describingMD a febrile illness–related NORSE sy
Jerzy P. Szaflarski, MD, refractory status epilepticus, but half remain cryptogenic.
Committee of the
provide guidance for the acute treatment of SE in critically
PhD American Epilepsy Society months), functional status improved
proves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune
likely that some of theElizabeth cases ofE. SE Gerard, MD
ill patients, the Neurocritical Care Society organized a Introduction
Brandon M. Westover,
attributed to a “possible” encephalitis w
therapies warrants further investigation. Neurology® 2015;85:1604–1613
writing committee to evaluate the literature and develop
evidence-based and expert consensus practice guideline.
an
MD, PhD
Status MD Teneille Gofton, MD
epilepticus (SE) requires emergent, targeted treat-
up, but epilepsy developed in 37%
Prehospital treatment NORSE. with levetiracetam
Tracy Glauser,
Literature searches were conducted using MD,
1
PubMedShlomo
2,3,10,11
Suzette M. LaRoche,
andShinnar,
ment The absence ofplus
MD,to GLOSSARY
2
PhD,reduce
David Gloss, a proven
3
patientMD,morbidity clonazepam
Brian Alldredge, etiology was mandatory in the early
and PharmD, tions.
mortality.
4
CEEG 5 Immune
Ravindra Arya,
therapies were IQR 5 used
MD, DM, 1
Jacquelyn
Lawrence
Bainbridge,
J. Hirsch,
PharmD,
MD5
Mary Peter W. Kaplan,
Bare, MSPH, RN , Thomas MD
CCEMRC 5 Critical Care1 EEG Monitoring Research Consortium;
Bleck, MD, 6
W. Edwin Dodson,
continuous EEG;
MD, 7 ICU 5 intensive care unit;
or placebo plus have
committee were evaluated.LisaRecommendations clonazepam
studies meeting the criteria established by the 8 writing
suggestedinthat
Garrity, PharmD, Andy status
Controversies
For the Critical Care EEG
Jagoda, MD,9 Daniel
Monitoringdescribed
were
13
autoimmune
about
epilepticus
interquartile range;
how
Lowenstein,
epilepticus;
Research inVGKCC the
14 Jong
mRS
and
MD,
W. Lee, MD
literature
when
5
10
[1–3].John
RSE 5 refractory encephalitis
modified
to Rankin
treat Scale;
status Pellock,
SE
The epilepticus;MD,
NMDAR
have
11
4,12–14
been
5 NMDA
prevalence
James
SE 5 status
Neurocritical
5 voltage-gated potassium channel complex.
Care may emerge as a com
receptor;
epilepticus;
NORSE 5 new-onset refractory status
MD,12
Riviello,STESS of inflammatory
5 Status CSF ch
Epilepticus Severity Score;
Edward Sloan, MD, MPH, David M. Treiman, MD
(SAMUKeppra): a randomised, double-blind,
developed based on the literature1 using standardized
Division of Neurology, Consortium
Comprehensive Society
Epilepsy Status Epilepticus
Center, Cincinnati Children’s Hospital
Benjamin Legros, phase
Guideline Writing
Medical Center
3 trial Conclusions:
Committee
and University
MD
of Cincinnati College of
Autoimmune Up to 40% of encepha
Supplemental data
assessment methods from the Medicine,
American Heart Association was established
Status in 2008 to
epilepticus develop
(SE) is evidence-based
the second most expert neurologic emergency.
common SE
Cincinnati, OH (CCEMRC) 1
2
Departments of Neurology, Pediatrics, and Epidemiology and Population Health, and the Comprehensive Epilepsy Management Center, Monte-
Tréluyer,refractory status epilepticus, but ha
and Grading ofVincent
Recommendations Assessment, Develop- consensus guidelines for
cases
NY are
P.diagnosing
refractory toand
(RSE)Bolgert, managing
first- SE. Co-treatments. New-onset RSE (NORSE) is a
and second-line 2,3
at Neurology.org Navarro, Christelle Dagron,
fiore Medical Caroline
Center, Elie,Einstein
Albert Lionel Lamhaut,
College of Sophie Demeret,
Medicine, Bronx,
Jerzy
Saïk Urien, Kim An,Szaflarski,
Francis MD,
Jean-Marc
d quickly.Summary
ment,
Benzodiazepines are the only
and Evaluation systems, as well as expert opinion chairs were selected by the Neurocritical Care Society,
3
CAMC Neurology Group, Charleston, WV rare but challenging condition, characterized by the occurrence of a prolonged period of refrac-
Correspondence towith ten additional neurointensivists and Lancet Neurol 2016; of15: 47–55
Michel Baulac, Pierre Carli, for the SAMUKeppra investigators*
proves during follow-up. Epilepsy
and Clinical d
4
School of Pharmacy, University of California, San Francisco, CA
when sufficient data were lacking. Department From
5
of Clinicalthe Yale
Pharmacy, University SchoolSkaggs
University of Colorado,
Dr. Gaspard: of PhD
toryMedicine
seizures
School (N.G.,
with
of Pharmacy noand L.J.H.),
readily epileptologists
Department
identifiable
Pharmaceutical inofotherwise
causeAurora,
Sciences, Neurology,
CO Division
healthy Epilepsy
individuals. Approximately
4
N
6
from across
Departments of Neurological ngaspard@ulb.ac.be
Sciences, Neurosurgery, theand
Medicine,
40 United
adult casesStates
Anesthesiology, included
Rush
have been onMedical
University
reported, the committee.
Center, Chicago, IL
describing
NORSE a febrile illness–related
syndrome. It is 4–9
7 Comprehensive Epilepsy Center, New Haven, CT; Université Libre de Bruxelles–Hôpital Erasme
Departments of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, MO (N.G., B.L.), Brussels, Be
• Evidence-based guidelines: treatment of convulsive status
epilepticus in children and adults: reports of the guideline
comittee of the american epilepsy society.
Epilepsy current 2016;;1:48-61
• Guidelines for the evaluation and management of status
epilepticus
Neurocrit Care 2012 ;; 17 : 3-23 (Avril 2012)
• Référentiel formalisé d’experts
Réanimation, Revue neurologie, janvier 2009 / 2018
Etats
de
mal
épileptique
de
l’adulte
et
de
l’enfant.
N
Engrand
Anesth Reanim Mars
2017
EME
:
définitions
françaises
• EME :
crises
continues
ou
succession
de
crises
sans
amélioration
de
la
conscience
sur
une
période
de
30
minutes.
• EME
tonicoclonique généralisé :
crises
continues
ou
subintrantes
pendant
au
moins
cinq
minutes
(définition
opérationnelle).
• EME
larvé :
disparition
des
manifestations
motrices
mais
persistance
d’un
EME
électrique.
Evolution
d’un
EME
tonicoclonique généralisé
non
ou
« mal »
traité.
• Les
crises
sérielles :
récupération
de
la
conscience
antérieure
entre
les
crises.
• Chez
l’enfant
: même
définitions.
Recommandations
formalisées
d’experts
Réanimation,
Revue
neurologie,
janvier
2009
EME
:
recommandations
US
• EME
tonicoclonique généralisé :
crises
continues
ou
subintrantes
pendant
au
moins
cinq
minutes
(définition
opérationnelle).
Guidelines
for
the
evaluation and
management
of
status epilepticus
Neurocrit Care
2012
;
17
:
3
-‐ 23EME
:
Classification
US
•
EME
convulsif
(EMEC)
-‐ mouvements
des
extrémités
tonicocloniques généralisés
-‐ trouble
de
la
vigilance
(coma,
léthargie,
confusion)
-‐ déficit
focal
post-‐ictal possible
Exclusion
:
EME
convulsif
focal
et
épilepsie
partielle
continue
•
EME
non
convulsif
(EMENC)
-‐ activité
épileptique
EEG
sans
signe
clinique
d’EMEC
-‐ deux
présentations
cliniques
:
-‐ wandering confusion
(AB
pronostic)
-‐ « subtle SE »
:
EMEC
vieilli
ou
cérébro-‐lésé
(coma,
confusion,
mutisme,
anorexie…
ou
agitation
délirium,
pleurs,
rires
écholalie,
NV,
nystagmus…)
•
EME
Réfractaires
(EMER)
-‐ EME
résistant
à
BZD
+
1
autre
MAE
-‐ durée
de
l’EME
≠
critère
diagEME
:
Classification
US
•
EME
convulsif
(EMEC)
-‐ mouvements
des
extrémités
tonicocloniques généralisés
-‐ trouble
de
la
vigilance
(coma,
léthargie,
confusion)
-‐ déficit
focal
post-‐ictal possible
Exclusion
:
EME
convulsif
focal
et
épilepsie
partielle
continue
•
EME
non
convulsif
(EMENC)
-‐ activité
épileptique
EEG
sans
signe
clinique
d’EMEC
Les
EME
non
convulsifs
ne
sont
pas
-‐ deux
présentations
cliniques
:
forcément
infra-‐cliniques
-‐ wandering confusion
(AB
pronostic)
-‐ « subtle SE »
:
EMEC
vieilli
ou
cérébro-‐lésé
(coma,
confusion,
mutisme,
anorexie…
ou
agitation
délirium,
pleurs,
rires
écholalie,
NV,
nystagmus…)
•
EME
Réfractaires
(EMER)
-‐ EME
résistant
à
BZD
+
1
autre
MAE
-‐ durée
de
l’EME
≠
critère
diag5
stades
d’EME
0
min
EME
imminent
(« impending »)
5
min
EME
précoce
(« early »)
15
– 20
min
EME
installé
(« established »)
30
– 40
min
EME
réfractaire
(« refractory »)
≥
24
heures
EME
super
réfractaire
(« super
refractory »)
Prasad.
Cochrane
Database Syst Rev 2014
Sep
10;9
• Etude
prospective
observationnelle
/
18
centres
• Def EME
:
crise
≥
10
min,
ou
2
crises
sans
retour
à
conscience
N
≤
10
min
• 248
patients
-‐ 177
(71
%)
pré-‐hospitalier,
15
crisent encore
à
l’admission
-‐ âge
médian
:
53
ans
(42
– 64)
-‐ hommes
60
%,
femmes
40
%
-‐ 74
%
EME
généralisés,
26
%
EME
focaux
• ATCD
épilepsie
:
48
%
ATCD
EME
: 20
%
• Evolution
EME
larvé
:
13
%• Etude
prospective
observationnelle
/
18
centres
• Def EME
:
crise
≥
10
min,
ou
2
crises
sans
retour
à
conscience
N
≤
10
min
Δ sur-‐estimation :
Encéphalopathies
post-‐anoxiques
• 248
patients
-‐ 177
(71
%)
pré-‐hospitalier,
15
crisent encore
à
l’admission
sous-‐estimation
-‐ âge
médian
:
53
: ans
EME
(42
p–artiels
64)
-‐ hommes
60
%,
femmes
EME
4N0
C%
-‐ 74
%
EME
généralisés,
26
%
EME
focaux
• ATCD
épilepsie
:
48
%
ATCD
EME
: 20
%
• Evolution
EME
larvé
:
13
%Lothman. Neurology 1990; 40 (Suppl 2)
Etat
de
mal
Tonico-‐clonique
• Figures
spécifiques
(pointes
ondes)
• Décharges
rythmiques (sans
retour
au
rythme
de
fond)
• Evoluant
(« s’organisant »)
dans
le
temps
et
dans
l’espace
RFE
EME
.
Navarro.
Réanimation 2009;
18:
33-‐43Encéphalopathie
postanoxique
Burst suppressions
de
périodicité
régulière,
ou
GPDs (bouffées
rapprochées)
RFE
EME.
Gélisse.
Réanimation
2009;18:99-‐105Burst suppression
(bouffées
suppressions)
Etiologies
-‐ barbituriques
-‐ hypothermie
≤
22
°C
-‐ encéphalopathie
post-‐anoxique
-‐ souffrance
cérébrale
majeure
• Bouffées
périodiques
-‐ Non
épileptique
lps ondes
amples
et
lentes
+
rythmes
+
rapides
-‐ EME
larvé,
stade
ultime diffuses
(si
burst =
décharge
rythmique) • Entrecoupées
de
tracé
quasi-‐nul
RFE
EME.
Navarro.
Réanimation 2009;
18:
33-‐43Etat
de
mal
non
épileptique
d’origine
psychogène
• Jusqu’à
20
%
des
patients
adressés
pour
convulsions
• Terrain :
-‐ jeunes
femmes
(60-‐80%)
-‐ « ambiance
psychiatrique »
(hystérie,
retard
mental…)
-‐ facteur
déclenchant
(stress)
-‐ patient
épileptique
20
-‐ 40%
des
cas
(ttt efficace)
Δ -‐ Ne
répondent
pas
au
TAE
-‐ Risquent
d’être
traités
comme
des
EMER
nbx séjours
en
réa
(complications
+++)
Krumholz .
Neurologist
2002
;
8
:
51-‐6
Walker.
QJM
1996
;
89
:
913-‐20
Benbadis.
Neurology 2001
;
57
:
915-‐7Etat
de
mal
non
épileptique
d’origine
psychogène
• Eléments
cliniques
en
faveur :
-‐ présence
de
témoins
-‐ fermeture
des
yeux
(Se
96%,
Sp 98%),
résistance
à
l’ouverture
des
yeux,
évitement
du
regard
lors
de
la
rotation
de
la
tête
-‐ Opisthotonos,
roulements
de
tête,
poussée
pelvienne
-‐ mouvements
amples,
désorganisés,
exubérants,
sans
systématisation
neuro,
trop
régulier,
touchant
le
tronc
-‐ absence
de
phase
tonique
-‐ contact
possible
avec
le
patient,
ROS
-‐ absence
de
confusion
post
critique
-‐ absence
de
désaturation
artérielle
pendant
les
crises
-‐ pleurs
en
fin
de
crise
-‐ pas
traumatisme,
de
chute
de
langue
ni
de
perte
d’urine
-‐ bonne
tolérance
des
doses
élevées
de
BZDEtiologies
chez
l’adulte
Epileptique
connu
EME
inaugural
-‐ sous-‐dosage
en
MAE
(non
observance,
-‐ AVC
(à
la
phase
aiguë
ou
modification
de
traitement,
interaction
séquellaire)
médicamenteuse…
-‐ troubles
métaboliques
(hNa hGies
-‐ intoxication
ou
sevrage
alcoolique hCa)
-‐ prescription
de
médicaments
pro-‐ -‐ tumeurs
et
infections
convulsivants
-‐ infection
intercurrente
• Après
60
ans
:
AVC
à
sa
phase
aiguë
(AIC,
HIP,
HSA,
TVC)
DeLorenzo.
Neurology 1996;46:1029-‐35
Martingale.
Emerg Med
Clin
N
Am.
2011;29:15-‐27
Legriel.
CCM
2010;38:2295-‐2303Immune therapies were used less frequently in cryptogenic cases, despite a comparable
extensive evaluation
ence of inflammatory CSF changes. Etiology No. (%)
New-onset
usions: Autoimmune refractory
encephalitis is the status epilepticus
most commonly identified causeNonparaneoplastic
of new-onset autoimmune
Cryptogenic 67 (52)
25 (19)
tory status epilepticus, but half
Etiology, clinical remain
features, cryptogenic. Outcome at discharge isAnti-NMDA
and outcome poor receptor
but im- 7 (5)
s during follow-up. Epilepsy develops in most cases. The role of anestheticsAnti-VGKC and immune
complex 5 (4)
SREAT 5 (4)
pies warrants further Nicolasinvestigation.
Gaspard, MD, Neurology ABSTRACT ® 2015;85:1604–1613
Cerebral lupus 4 (3)
PhD Objectives: The aims of this study wereAnti-GAD65 to determine the etiology, clinical 3 (2) fe
Nicolas Gaspard, MD, ABSTRACT
SARY PhD Brandon
Objectives: The aims P.of Foreman,
this study were to determine of outcome
the etiology, clinical of new-onset
features, and predictorsrefractory status epilepticus.
Anti-striational 1 (1)
Brandon P. Foreman, of outcome of new-onset refractory status epilepticus.
C 5MD Critical Care EEG Monitoring MD Research Consortium; CEEG 5 continuous EEG; ICU 5 intensive care unit; IQR 5
Paraneoplastic 23 (18)
MD • 52
pVincent
ics
d48’incidences
:
2Methods:
8
January
eNMDA
t
61,5
ans
Alvarez, mRS
Methods: Retrospective review of patients with refractory Retrospective
status epilepticus without review of patients
etiology with refractory status9 (7) epilep
artile
Vincentrange; modified
identified withinRankin hoursScale;
Alvarez, MD
of admission NMDAR
between5 receptor;
2008, NORSE
and December 5 new-onset Anti-NMDA
31, 2013, refractory status
receptor
cus;Christian Cabrera Kang,
RSE 5 refractory in 13status medical centers.SE
academicepilepticus; The 5 status
primary identified
epilepticus;
outcome measure within
wasSTESSpoor48 5hours
functional Status
outcomeofEpilepticus
admission between
Severity
Anti-VGKC Score;
complex January 1, 2008, 3 (2) and
MD Christian Cabrera Kang,
voltage-gated
5John C. Probasco, MD potassium channel complex.
at discharge (defined as a score .3 on the
in 13 academic medical centers. TheAnti-Hu
modified Rankin Scale).
primary outcome measure was poo
• 64
%
f emmes
3 (2)
Amy C. Jongeling Results: MD
Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies
were autoimmune (19%) and paraneoplastic at discharge (defined
data wereas a score .3 on the modified Rankin Scale).2 (2)
Anti-VGCC
Emma Meyers, BSc (18%) encephalitis. Full available in
John C. Probasco, MD
epilepticus
Alyssa Espinera, BSc (SE)
died.
is the
Predictors
second
of poor
most
outcome
common
included Results:
duration of
neurologic
125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) 1
Of
status 130
epilepticus, cases,
use
emergency.
of 67 (52%)
anesthetics,
Up to
remained 40%
Anti-CRMP5
of SE
cryptogenic. The most
1 (1)
commo
Kevin F. Haas, MD
areSarahrefractory • Encéphalite
Amy C. Jongeling
E. Schmitt, MD (RSE) to first- and second-line treatments.
and medical complications. à
Among A c anti
the 63 N
patients MDA
with :
available 2 5
%
2,3
follow-up
d es
New-onset
data (median 9
Anti-Ro
RSE (NORSE)
1 (1)
is a encephalitis.4 (3)Full d
Elizabeth E. Gerard, MD months), Emma functional Meyers, BSc in 36 (57%);
status improved were 79% had autoimmune
good or fair outcome (19%) and paraneoplastic
at last follow- Seronegative (18%)
utTeneille
challenging
Gofton, MD non
condition,
up, cryptogéniques
but epilepsy
characterized by125 the cases occurrence
developed in 37% with most survivors (92%) remaining on antiseizure medica-
of a prolonged
(62 cryptogenic). period
Poor outcome ofoccurred
Infection-relatedrefrac- in 77 of 12510cases (8)
Peter W. Kaplan, MD tions. Alyssa
Immune Espinera,
therapies wereBSc used less frequently in cryptogenic cases, despite a comparable
eizures
Jong W. Lee, with MD no prevalence
readilyKevin identifiable
of inflammatory CSF changes.
F. Haas, MD cause indied.otherwisePredictors healthyof poor outcome 4included
individuals. EBV
Approximately duration of status epilepticus 2 (2)
Benjamin Legros, MD Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset VZV 2 (2)
ult PhD cases have been
Jerzy P. Szaflarski, MD, reported,
Sarah
refractory status E. Schmitt,describing
epilepticus, butMD
a and
febrile
half remain cryptogenic. medical
Outcome atcomplications.
illness–related discharge is poor but im-Among the 63 4–9
NORSE syndrome. patients
It is with available follo
CMV 1 (1)
Elizabeth
warrants E. Gerard, MDNeurology months), functional status improved inWNV36 (57%); 79% had good or
proves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune
fair o
that some
Brandon M. Westover,
of the
therapies
cases of SE
further
attributed
investigation. ®
to a “possible”
2015;85:1604–1613
encephalitis would qualify as 1 (1)
MD, PhD
Teneille Gofton, MD up, but epilepsy developed in 37% with mostpneumoniae
Mycoplasma survivors (92%) remaining 2 (2) o
SE. 2,3,10,11
Suzette
The absence
M. LaRoche, MD GLOSSARY
of a proven etiology tions. was
CEEG 5 Immune
mandatory therapies in were
the early series
IQR 5 used less
but somein cryptogenic 1cases,
frequently
Syphilis (1)
Lawrence J. Hirsch, MD CCEMRC Peter W. Kaplan, MD
5 Critical Care EEG Monitoring Research Consortium; continuous EEG; ICU 5 intensive care unit;
suggested
Monitoring Research
that VGKCC
For the Critical Care EEG
autoimmune
epilepticus;
Jong
RSE 5 refractory status
W. Lee,
5 voltage-gated MD
potassium
encephalitis
interquartile range; mRS 5 modified Rankin Scale; NMDAR 54,12–14
epilepticus; SE 5 status
channel complex.
may
epilepticus; STESS 5 Status emerge
NMDA receptor; NORSE 5 new-onset refractory status
prevalence of inflammatory asScore;CSF
Epilepticus Severity a common
changes.
Toxoplasmacause
gondii of 1 (1)
Consortium Others 5 (4)
(CCEMRC) Status Benjamin
epilepticus (SE) Legros,
is the second MDmost common Conclusions:
neurologic emergency.
1 Autoimmune Up to 40% of encephalitis
SE SESA
is the most commonly identified
2 (2)
casesJerzy
are refractory (RSE) to first- and second-linerefractory status epilepticus, but halfLeptomeningeal
treatments. New-onset RSE (NORSE) is a remain cryptogenic. Outcome at dis
2,3
P. Szaflarski, MD, carcinomatosis 2 (2)
rare but challenging condition, characterized by the occurrence of a prolonged period of refrac-
PhD cause proves during follow-up. Epilepsy
and Clinical develops in most
anddiseasecases. The role 1 (1)of an
Correspondence to Creutzfeldt-Jakob
Yale University School of
Dr. Gaspard: toryMedicine
seizures (N.G.,
with L.J.H.),
no readily Department
identifiable inofotherwise
Neurology, healthyDivision
4
of Epilepsy
individuals. Approximately Neurophysiology
ensive Epilepsy Center, 40 adult cases have been reported,Libre describing a febrile illness–related NORSE syndrome. It is
4–9
therapies warrants further investigation.
ngaspard@ulb.ac.be
New Haven,
Brandon CT;M. Université
Westover, de Bruxelles–Hôpital Erasme (N.G., B.L.), Brussels, Belgium; University
Neurology
Abbreviations: CMV 5 ofcytomegalovirus;
® 2015;85:1604–1613
CRMP5 5 collaps-Immune therapies were used less frequently in cryptogenic cases, despite a comparable
ence of inflammatory CSF changes.
New-onset
usions: Autoimmune refractory
encephalitis is the status epilepticus
most commonly identified cause of new-onset
tory status epilepticus, Etiology, clinical but half features, remain cryptogenic. Outcome at discharge is poor but im-
and outcome
s during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune
pies warrants further Nicolas investigation.
Gaspard, MD, Neurology ABSTRACT ® 2015;85:1604–1613
PhD Objectives: The aims of this study were to determine the etiology, clinical fe
Nicolas Gaspard, MD, ABSTRACT
SARY PhD Brandon
Objectives: The aims P.of Foreman,
this study were to determine of outcome of new-onset
the etiology, clinical features, and predictors refractory status epilepticus.
Brandon P. Foreman, of outcome of new-onset refractory status epilepticus.
C 5MD Critical Care EEG Monitoring MD Research Consortium; CEEG 5 continuous EEG; ICU 5 intensive care unit; IQR 5
Alvarez, mRS
Methods: Retrospective review of patients with Methods:
refractory status Retrospective
epilepticus without etiology review of patients with refractory status epilep
artile
Vincentrange; MD modified
Vincent
5identified withinRankin hoursScale;
Alvarez,
48 MD
of admission NMDARbetween5 January NMDA receptor;
1, 2008, and December NORSE 31, 2013,5 new-onset refractory status
Christian Cabrera Kang,
cus;MD RSE 5 refractory in 13status medical centers.SE
academicepilepticus; The 5 status
primary identified
outcome epilepticus;
measure within poor48
wasSTESS 5hours
functionalStatus
outcome ofEpilepticus
admissionSeverity
between January 1, 2008, and
Score;
Christian Cabrera Kang,
voltage-gated
C. Probasco, MD potassium channel complex.
at discharge (defined as a score on the
in 13 academic medical centers. The primary outcome measure was poo
modified Rankin Scale).
13077
cases, %
d ’EMER
oencephalitis.
u
TheEmostMESR
.3
5John
Amy C. Jongeling Results: Of
were
•
MD
autoimmune (19%)
67 (52%)
and
remained cryptogenic.
paraneoplastic at
(18%) discharge
common identified etiologies
(defined
Full data wereas a score
available in .3 on the modified Rankin Scale).
Emma Meyers, BSc
John C. Probasco, MD
epilepticus
Alyssa Espinera, BSc (SE) is the second most common neurologic emergency. Up to 40% of SE
125 cases (62 cryptogenic). Poor outcome
died. Predictors of poor outcome included duration
occurred
Results:
in 77
of status
of 125 cases
Ofepilepticus,
130 cases,
(62%), and 28 (22%) 1
67 (52%) remained cryptogenic. The most commo
use of anesthetics,
Kevin F. Haas, MD Amy C. Jongeling
areSarahrefractory
Elizabeth E. Gerard, MD
and medical
• 5
Emma Meyers, BSc
months), functional M
complications.
status AE
E. Schmitt, MD (RSE) to first- and second-line treatments. Among
improved ( nb
the
in 36
63
m
(57%);wereédian)
patients
79%
with available
autoimmune
had good or fair
2,3
follow-up
outcome
New-onset
data
(19%)
at
(median
last and
follow-
9
RSE (NORSE)(18%)
paraneoplastic is a encephalitis. Full d
utTeneille
challenging
Gofton, MD
Peter W. Kaplan, MD
condition, characterized by125 the cases occurrence
up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medica-
tions.Alyssa
Immune Espinera,
therapies wereBSc
(62 cryptogenic).
used less frequently in cryptogenic cases, despite a comparable
of a prolonged period ofoccurred
Poor outcome refrac- in 77 of 125 cases
eizures
Jong W. Lee, with MD no prevalence
readily
Kevin identifiable
of inflammatory CSF changes.
F. Haas, MD cause died.
in otherwise Predictors healthy of poor outcome 4included
individuals. duration of status epilepticus
Approximately
Benjamin Legros, MD
ultJerzyPhD
cases have
P. Szaflarski, MD, been Sarah
refractory
•statusE.Pronostic
reported, Schmitt, describing
epilepticus, butMD
:
a and
Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset
febrile
half remain cryptogenic. medical
Outcome atcomplications.
illness–relateddischarge is poor but im-Among the 63 4–9
NORSE syndrome. patients
It is with available follo
warrants-‐ mortalité
2015;85:1604–1613
:
2a 2
%
Elizabeth E. Gerard, MDNeurology months), functional
proves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune
status improved in 36 (57%); 79% had good or fair o
that some
Brandon M. Westover,
of the
therapies
cases of SE
further
attributed
investigation. ®
to “possible” encephalitis would qualify as
up, but epilepsy developed in 37% with most survivors (92%) remaining o
of-‐a provenmRS etiology >
3
tions.
:
CEEG
3was 9
%mandatory
MD, PhD
Teneille Gofton, MD
SE. 2,3,10,11
Suzette
The absence
M. LaRoche, MD GLOSSARY
5 Immune therapies in were the early series but some
IQR 5 used less frequently in cryptogenic cases,
Lawrence J. Hirsch, MD CCEMRC Peter W. Kaplan, MD
5 Critical Care EEG Monitoring Research Consortium; continuous EEG; ICU 5 intensive care unit;
suggested
Monitoring Research
that autoimmune
epilepticus;
VGKCC Jong -‐
RSE 5 refractory
W. Lee,
5 voltage-gated
épilepsie
status
MD
potassium
encephalitis
For the Critical Care EEG interquartile range; mRS 5 modified Rankin Scale; NMDAR 54,12–14
epilepticus; SE 5 status
channel complex.
t ardive
may :inflammatory
emerge
3Epilepticus
7
%Severity
NMDA receptor; NORSE 5 new-onset refractory status
prevalence
epilepticus; STESS of
5 Status
dasScore;
es
a scommon
CSF urvivants
changes. cause of
Consortium
(CCEMRC) StatusBenjamin
epilepticus (SE) Legros,
is the secondMDmost common Conclusions: neurologic emergency.
1 Autoimmune Up to 40% of encephalitis
SE is the most commonly identified
casesJerzy
are refractory (RSE) to first-MD, and second-line refractory
treatments. status New-onset epilepticus,
RSE (NORSE) is a but half remain cryptogenic. Outcome at dis
2,3
P. Szaflarski,
rare but challenging condition, characterized by the occurrence of a prolonged period of refrac-
PhD cause proves during follow-up. Epilepsy
and Clinical develops in most cases. The role of an
Correspondence to
Yale University School of
Dr. Gaspard: toryMedicine
seizures (N.G.,
with L.J.H.),
no readily Department
identifiable inofotherwise
Neurology, Division
healthy
4
individuals. of Epilepsy
Approximately Neurophysiology and
ensive Epilepsy Center, 40 adult cases have been reported,Libre describing a febrile illness–related NORSE syndrome. It is
4–9
therapies warrants further investigation.
ngaspard@ulb.ac.be
New Haven,
Brandon CT;M. Université
Westover, de Bruxelles–Hôpital Erasme (N.G., B.L.), Brussels, Belgium; University
Neurology of ® 2015;85:1604–1613EME
inaugural
:
imagerie
en
urgence
• Scanner
cérébral
sans
± avec
PdC ou
IRM
si
-‐ signes
de
localisation
-‐ crise
initiale
partielle
(clinique
et
électrique)
-‐ notion
de
traumatisme
crânien
-‐ notion
de
néoplasie
-‐ notion
d’immunodépression
(VIH,
corticothérapie.
.
.)
-‐ cause
demeurant
obscure
-‐ âge
>
40
ans
-‐ nécessité
de
PL
Recommandations
formalisées
d’experts
Réanimation,
Revue
neurologie,
janvier
2009
Etude
multicentrique
française
:
TDM
ou
IRM
=
90
%
Legriel.
CCM
2010;38:2295-‐2303EME
inaugural
:
PL en
urgence
• Ponction
lombaire si
:
-‐ contexte
infectieux
(fièvre…
)
-‐ immunodépression
(VIH,
corticoïde)
-‐ recherche
étiologique
négative
• Sans
retarder
le
traitement
anti-‐infectieux
(acyclovir,
ATB)
pléiocytose
modérée
15-‐20
%
des
cas,
hors
infection
Recommandations
formalisées
d’experts
Réanimation,
Revue
neurologie,
janvier
2009
• Etude
multicentrique
française
:
PL
=
53
%
Legriel.
CCM
2010;38:2295-‐2303
Enquête
étiologique
négative
<
10
%
des
casMolécules
antiépileptiques
Inhibition
présynaptique Inhibiteurs
rcp GLUT
Lévétiracétam Topiramate (rcp AMPA)
Lamotrigine
Agonistes
GABA
Benzodiazépines
Barbituriques
Vigabatrine
glutamate GABA Tiagabine
NMDA
Na+ K+
repolarisation
dépolarisation Cl-
Ca+
Stabilisateurs
de
membrane
Phénytoine
Valproate
Carbamazépine,
Oxcarbazépine
Topiramate
Lamotrigine
Duncan,
Lancet
2006;367:1087-‐100Benzodiazépines
délai
d’action durée
d’action demi-‐vie
d’élimination
DIAZEPAM 1
à
3
min 15
à
20
min 20
à
40
h
CLONAZEPAM 1
à
3
min 6
à
8
h 26
à
42
h
LORAZEPAM <
5
min 6
à
12
h 15
h
MIDAZOLAM <
1
à
1,5
min 15
min
à
4
h 1,3
à
3,5
h
Liposolubilité importante
:
-‐ grand
volume
de
distribution
(#
2
l/kg)
-‐ demi-‐vie
contextuelle(mécanisme ?)
Valproate
Usage thérapeutique :
• Dose
de
charge
20
à
40
mg/kg
en
5
min
,
puis
1
à
1,5
mg/kg/h
Premier choix dans les crises généralisées avec
8
• absence
Efficace,
tolérance
rou les crises
espiratoire
généralisées myocloniques
et
hémodynamique
• Adulte
Actif
/
enfantégalement dans les autres types de crises généra
Peut
• Attention
: être associé en multithérapie
Antiépileptiques, anticonvulsiva
-‐ Inhibiteur
enzymatique
-‐ Hépatotoxicité (cytolyse)
-‐ Hyperamoniémie +
hyperlactatémie (déficit
en
carnitine)
-‐ Encéphalopathie
sans
hyperamoniémie
-‐ Troubles
hémostase
:
thrombopénie,
déficit
facteur
XIII
-‐ Tératogénicité
Cotariu. Clin Chem 1988 ; 34 : 890-‐7
Bédry. Réanimation 2004 ; 13 : 324-‐33Phénobarbital
/
(fos)phénytoine
Phénobarbital
(15mg/kg) (fos)phénytoine (20-‐30
mg/kg)
Intérêts :
-‐ efficacité Intérêts :
-‐ efficacité
-‐ rapidité
d’action
(20
min) -‐ non
dépresseur
central
Inconvénients :
Inconvénients :
-‐ ± dépression
vigilance
et
respiratoire -‐ troubles
de
conduction,
dépresseur
-‐ CI
:
IRs sévère myocardique
-‐ inducteur
enzymatique -‐ délai
d’action
-‐ tératogène -‐ inducteur
enzymatique
-‐ tératogène
• Fosphénytoine (pH
9)
vs
phénytoine (pH
12)
?
-‐ meilleure
tolérance
veineuse,
et
compatibilité
avec
autres
médicaments
-‐ ne
nécessite
pas
de
VVP
de
gros
calibre
ou
de
VVC
Mais
:
-‐ autant
de
complications
C/V
et
induction
enzymatique
-‐ même
délai
d’action
in
fine
(30
min)
-‐ posologies
compliquées
-‐ prix
DeToledo. Drug Saf 2000 ; 22 : 459-‐66Lévétiracétam EW Lévétiracétam
N
Mécanisme d’action :
• Dose
de
charge
20
à
40
mg/kg
en
15
min
(max
Inhib.4500
releasemg),
puis
500
à
2000
mg
x2/j
vésiculaire? Chimie : pyrolidone, équiv
cyclisé. Enantiomèr
• Intérêts
:
-‐ mécanisme
d’action
à
part
Usage thérapeutique :
Crises partielles
-‐ pharmacocinétique
(biodisponibilité,
absence
d’interactions
médicamenteuses)
Introduit récemment (2001), il n’est que en
-‐ tolérance
hémodynamique,
respiratoire
seconde intention et uniquement chez l’adulte
• Attention
: Particularités : 8
Prometteur
-‐ troubles
neuro-‐psychiatriques (confusion,
! Trèsvertiges,
sédation,
peu d’effets indésirables, pas
décompensation
psy)
-‐ clairance
augmentée
en
réanimationd’interactions médicamenteuses.
Note : 1 à 3 x 1g/ jour à 2,5 euros le comprimé de 1g...
Antiépileptiques, anticonvuls
• Enfants
:
-‐ TB
tolérance
-‐ Dose
de
charge
:
25-‐50
mg/kg
W Vigabatrine
Brophy.
Neurocrit Care
2012
;
17
:
3
– 23
NEGlauser.
Epilepsy current 2016
;
16
:
48-‐61
Spencer.
Pharmacotherapy
2011
;
31
:
934-‐41
Chimie : analogi
Kirmani.
Pediatr
Mécanisme Neurol: 2009
;
41
:
37-‐9
d’action Enantiomère0
min
EME
imminent
(« impending »)
5
min
EME
précoce
(« early »)
15
– 20
min
EME
installé
(« established »)
30
– 40
min
EME
réfractaire
(« refractory »)
≥
24
heures
EME
super
réfractaire
(« super
refractory »)
Benzodiazépines
en
1ère ligne
Etude Comparaison Type
étude n Patients Efficacité /
conclusion
Leppik, LZP
IV -‐ DZP
IV Double
81 adultes LZP IV =
DZP
IV
JAMA
1983
aveugle
Chamberlain, MDZ
IM
-‐ DZP
IV Sans
24 enfants MDZ
IM
=
DZP
IV
Pediatr Emerg Care
1997 aveugle
Alldredge,
DZP
IV
-‐ LZP
IV -‐ plac Double
205 adultes LZP
IV
=
DZP
IV
>
N
Engl J
Med
2001 aveugle extra-‐hospitalier placébo
Mc
Intyre,
MDZ
buccal-‐ DZP
rectal Sans
219 enfants MDZ
buccal >
DZP
IR
Lancet
2005 aveugle
Silbergleit, MDZ
IM -‐ LZP
IV Double
893 adultes
et
MDZ
IM =
LZP
IV
N
Engl J
Med
2012 aveugle enfants (16
%)
Chamberlain, LZP
IV -‐ DZP
IV Double
273 enfants LZP
IV =
DZP
IV
JAMA
2014 aveugle
Momen, MDZ
IM -‐ DZP
IR Sans
100 enfants MDZ
IM = DZP
IV
Eur J
Paediatr Neurol 2015 aveugle
Etudes
prospectives
randomiséesSafety and efficacy of buccal midazolam versus rectal
diazepam for emergency treatment of seizures in children:
a randomised controlled trial
ergency treatment of acute febrile and afebrile
John McIntyre, Sue Robertson, Elizabeth Norris, Richard Appleton,William P Whitehouse, Barbara Phillips, Tim Martland, Kathleen Berry,
Jacqueline Collier, Stephanie Smith, Imti Choonara
Lancet 2005; 366: 205–10
fficacy ofSummary
these drugs.
Background Rectal diazepam and buccal midazolam are used for emergency treatment of acute febrile and afebrile
See Comment page 182
Lancet 2005; 366: 205–10
(epileptic) seizures in children. We aimed to compare the safety and efficacy of these drugs. See Comment page 182
Academic Division of Child
Academic Division of Child
-‐ 219
crises
tonico cloniques
aux
urgences,
Methods A multicentre, randomised controlled trial was undertaken to compare buccal midazolam with rectal Health, University of
n to compare buccal midazolam with à
15
arectal
diazepam for emergency-room treatment of children aged 6 months and older presenting to hospital with active
chez
177
enfants
de
6
mois
ns
seizures and without intravenous access. The dose varied according to age from 2·5 to 10 mg. The primary endpoint
Health, University of
Nottingham, Derbyshire
Children’s Hospital, Uttoxeter
Road, Derby DE22 3DT, UK
was therapeutic success: cessation of seizures within 10 min and for at least 1 hour, without respiratory depression
s and older presenting to hospital with active Nottingham, Derbyshire
(J McIntyre FRCPCH,
requiring intervention. Analysis was per protocol. S Robertson RSCN,
Prof I Choonara MD); Emergency
Findings Consent was obtained for 219 separate episodes involving 177 patients, who had a median age of 3 years Children’s Hospital, Uttoxete
Department, Alder Hey
age fromrectal2·5 tobuccal,
10difference mg. The primary endpoint
Children’s Hospital, Liverpool,
(IQR 1–5) at initial episode. Therapeutic success was 56% (61 of 109) for buccal midazolam and 27% (30 of 110) for UK (E Norris RSCN,
-‐ MDZ
diazepam (percentage #
0 ,5
29%, m
95% g/kg
CI 16–41).(Analysing
2,5
à
1 0
only m g,
initial entre
episodes
The rate of respiratory depression did not differ between groups. When centre, age, known diagnosis of epilepsy, use
la
ajsimilar
revealed oue
result.
eRoad,
t
la
gencive)
Derby DE22 3DT, UK
B Phillips FRCPCH); Department
of Paediatric Neurology, Alder
at least 1ofregression,
hour,
antiepileptic drugs, without vstreatment, andrespiratory
prior length of seizure before treatment
buccal midazolam was more effective than rectal diazepam.
depression
were adjusted for with logistic
(J McIntyre FRCPCH,
Hey Children’s Hospital,
Liverpool, UK
(R Appleton FRCPCH);
DZP
rectal,
#
0,5
mg/kg
(2,5
à
10
mg) S Robertson RSCN,
Department of Child Health,
University of Nottingham,
Interpretation Buccal midazolam was more effective than rectal diazepam for children presenting to hospital with
Nottingham, UK
acute seizures and was not associated with an increased incidence of respiratory depression. (W P Whitehouse FRCPCH);
Introduction infections. Intranasal midazolam has also been used
13
Prof I Choonara MD); Emergen
Department of Paediatric
Neurology, Royal Manchester
Department, Alder Hey
Children’s Hospital,
Tonic-clonic seizures requiring emergency drug for children with epilepsy and might be easier to 14
-‐ Exclusion
:
enfants
in children, p erfusés
administer(lorazépam)
77 patients, who had aof median age can ofalso be3given years
Manchester, UK
treatment are a common problem and and more effective than rectal diazepam. 15,16
(T Martland MRCPCH);
convulsive status epilepticus causes significant mortality Midazolam via the buccal or
and morbidity. Immediate management
1
cessation
a continuingcrise
pré-‐hospitalier
sublingual route. Buccal midazolam is well absorbed Children’s Hospital, Liverpoo
17
Emergency Department,
Birmingham Children’s
for buccal midazolam and
terminate 27%
the 30 of 40(30 of14 children
110) for
Hospital, Birmingham, UK
seizure follows the basic principles of emergency care and might be easier for carers to administer. It stopped
with the role of drug treatment being to seizures in with severe UK (E Norris RSCN,
epilepsy and
(K Berry FRCPCH); School of
Nursing, University of
seizure promptly and safely. Ideally, a drug would be easy seems at least as effective as rectal diazepam for acute Nottingham, Nottingham, UK
g only initial episodes
antiseizure (anticonvulsant)
-‐ Objectif
revealed
action. Benzodiazepines
:
cessation
are Thea similar
to give, effective, and safe, and would have a long-lasting seizures. It has proved effective across a range of ages.
purpose
18
of this study was result.
to compare the efficacy
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