Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1598 - 1598
Опубликована: Фев. 13, 2025
Sudden
unexpected
death
in
epilepsy
(SUDEP)
is
a
critical
concern
for
individuals
suffering
from
epilepsy,
with
respiratory
dysfunction
playing
significant
role
its
pathology.
Fatal
seizures
are
often
characterized
by
central
apnea
and
hypercapnia
(elevated
CO2
levels),
indicating
failure
ventilatory
control.
Research
has
shown
that
both
human
patients
animal
models
exhibit
reduced
hypercapnic
response
the
interictal
(non-seizure)
period,
suggesting
an
impaired
ability
to
regulate
breathing
high
levels.
This
review
examines
of
chemoreceptors-specifically
retrotrapezoid
nucleus,
raphe
nuclei,
nucleus
tractus
solitarius,
locus
coeruleus,
hypothalamus
this
These
structures
sensing
maintaining
homeostasis.
Emerging
evidence
also
implicates
neuropeptidergic
pathways
within
these
chemoreceptive
regions
SUDEP.
Neuropeptides
like
galanin,
pituitary
adenylate
cyclase-activating
peptide
(PACAP),
orexin,
somatostatin,
bombesin-like
peptides
may
modulate
chemosensitivity
function,
potentially
exacerbating
during
seizures.
Understanding
mechanisms
linking
chemoreception,
control,
signaling
essential
developing
targeted
interventions
reduce
risk
SUDEP
patients.
Язык: Английский
Progressive central cardiorespiratory rate downregulation and intensifying epilepsy lead to sudden unexpected death in epilepsy in mouse model of the most common human ATP1A3 mutation
Epilepsia,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 11, 2025
Abstract
Objective
This
study
was
undertaken
to
test
the
following
hypotheses
in
Atp1a3
Mashl/+
mouse
(which
carries
most
common
human
ATP1A3
(the
major
subunit
of
neuronal
Na
+
/K
–adenosine
triphosphatase
[ATPase])
mutation,
D801N):
sudden
unexpected
death
epilepsy
(SUDEP)
occurs
during
seizures
and
is
due
terminal
apneas
some
lethal
cardiac
arrhythmias
others;
mice
have
central
cardiorespiratory
dysregulation
abnormal
respiratory
drive.
Methods
Comparison
made
littermate
wild‐type
groups
using
(1)
simultaneous
vivo
video‐telemetry
recordings
electroencephalogram,
electrocardiogram,
breathing;
(2)
whole‐body
plethysmography;
(3)
hypoglossal
nerve
recordings.
Results
In
mice,
SUDEP
consistently
occurred
that
were
more
severe
than
preterminal
seizures;
seizure
clustering
periods
preceding
SUDEP;
slowing
breathing
rate
(BR)
heart
observed
preictally
before
(4)
sequence
as
follows:
bradypnea
with
bradycardia/cardiac
arrhythmias,
then
apnea,
followed
by
arrhythmias.
Compared
wild‐type,
mutants
showed
resting
BR
variability
but
no
difference
PR,
QRS,
QTc,
or
RR
intervals;
firing
response
hypoxia;
plethysmography,
consisting
baseline
predisposition
apnea
responses
challenge.
Significance
,
an
alternating
hemiplegia
childhood
(AHC)
model,
also
a
revealing
model
‐ATPase
mutation
resulting
drive
progressive
concurrent
worsening
epilepsy.
results
from
seizure‐triggered
bradypnea/bradycardia
Because
many
epilepsy/SUDEP
models
other
etiologies
manifest
secondary
ATPase
deficiency,
future
studies
those
may
benefit
considering
possible
contributions
dysfunction
too.
Язык: Английский
Pathophysiology of SUDEP: How far are we from understanding?
Revue Neurologique,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 1, 2025
Sudden
and
unexpected
death
in
epilepsy
patients
(SUDEP)
is
the
leading
cause
of
suffering
from
drug-resistant
epilepsy.
A
significant
number
studies
have
been
conducted
both
animal
models
to
examine
initial
cascade
events
that
directly
as
well
factors
contribute
long-term
risk
SUDEP.
This
review
aims
discuss
main
pathophysiological
hypotheses
are
currently
considered
clinical
pre-clinical
Studies
highlighted
SUDEP
typically
triggered
by
a
seizure,
with
central
fatal
apnea
primary
death.
Findings
also
suggest
chronic
impairments
respiratory
regulation
may
risk,
serotonin
dysfunction
playing
key
role
associated
abnormalities.
These
insights
on
pathophysiology
better
assessment,
though
gaps
remain
understanding
precise
mechanisms
linking
transient
peri-ictal
dysfunction.
Язык: Английский
SUDEP Case-Control Study Nested in a Prospective Cohort of Drug-Resistant Focal Epilepsy
Опубликована: Янв. 1, 2025
Язык: Английский
Lethal Interactions of neuronal networks in epilepsy mediated by both synaptic and volume transmission indicate approaches to prevention
Progress in Neurobiology,
Год журнала:
2025,
Номер
249, С. 102770 - 102770
Опубликована: Апрель 19, 2025
Язык: Английский
Epilepsy Research Institute UK Sudden Unexpected Death in Epilepsy (SUDEP) workshop: Identifying the pre-clinical and clinical priorities for SUDEP research
Epilepsy & Behavior,
Год журнала:
2025,
Номер
171, С. 110473 - 110473
Опубликована: Май 22, 2025
The
Epilepsy
Research
Institute's
Mortality,
Morbidity
and
Risk
Theme
workshop
on
Sudden
Unexpected
Death
in
(SUDEP)
brought
together
a
diverse
group
of
stakeholders,
including
basic
science
researchers,
clinicians
clinical
charity
partners,
bereaved
individuals
people
with
epilepsy
to
identify
important
gaps
pre-clinical
SUDEP
research.
Collectively,
the
highlighted
recommendations
for
future
research
address
several
identified
need
develop
infrastructures
that
utilise
data-driven
approaches
reduce
risk.
National
global
cross-institution
collaborations
will
be
fundamental
driving
these
efforts
forward.
Язык: Английский
Seizure‐related death exhibits a circadian rhythm independent of seizure timing or sleep in a mouse model of Dravet syndrome
The Journal of Physiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 2, 2025
Abstract
Sudden
unexpected
death
in
epilepsy
(SUDEP)
is
the
most
extreme
consequence
of
epilepsy.
SUDEP
typically
occurs
at
night.
Because
humans
sleep
night,
these
nighttime
deaths
are
often
attributed
to
seizures
arising
from
sleep.
Nocturnal
mice
also
experience
more
seizure‐associated
during
nighttime.
This
could
represent
timing
that
under
circadian
control.
To
examine
this,
male
and
female
Scn1a
R1407X/+
mice,
a
model
epileptic
encephalopathy
Dravet
syndrome,
which
patients
spontaneous
result
death,
were
housed
constant
darkness
seizure
associated
was
assessed.
We
found
sudden
following
persists
peaks
subjective
rhythm
independent
potentially
fatal
frequently
occurred
while
awake.
Potentially
resulted
prolonged
unconsciousness,
exhibited
peaking
These
findings
provide
support
for
regulation,
sleep,
risk
death.
Nighttime
may
increase
via
multiple
mechanisms,
as
evident
by
peak
profoundly
impaired
consciousness
image
Key
points
epilepsy,
or
SUDEP,
devastating
outcome
intractable
Converging
lines
evidence
indicate
there
time‐of‐day
preference
with
occurring
Several
animal
models
syndrome
(DS),
including
one
employed
our
study,
recapitulate
key
features
DS
patients,
high
rate
seizure‐related
Here,
we
removed
light/dark
photocycles,
housing
animals
darkness,
identify
preponderance
suggesting
this
regulation.
further
carefully
characterize
vs
.
non‐fatal
prove
be
useful
biomarkers
predict
become
fatal.
Язык: Английский
Sudden unexpected death in epilepsy: respiratory vs. cardiac contributions
Cardiovascular Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 7, 2024
Abstract
Sudden
unexpected
death
in
epilepsy
(SUDEP)
poses
a
significant
risk
to
life
expectancy
for
individuals
with
epilepsy.
Mechanistic
insight,
while
incomplete,
has
advanced
through
clinical
observational
studies
and
animal
models.
Yet
we
lack
preventative
therapies,
which
will
depend
on
understanding
SUDEP
mechanisms.
Recurrent
convulsive
seizures
are
the
major
factor.
Cardiorespiratory
dysfunction
precedes
SUDEP,
but
whether
cardiac
arrhythmias
proximate
culprits
remains
be
determined.
Here,
highlight
recent
data
from
mouse
models
that
provide
increasing
support
respiratory
depression
decreasing
evidence
tachyarrhythmia-induced
SUDEP.
Further,
review
genetic
chemoconvulsant
have
enabled
deeper
how
initiated
central
nervous
system
propagate
autonomic
drive
seizure-induced
subsequent
rather
than
supporting
arrhythmia
cause.
Ongoing
research
continue
identify
predictive
biomarkers,
improve
models,
translate
basic
into
precision
medicine
approaches.
Identifying
brainstem
circuits
vulnerable
apnoea
enable
therapeutic
interventions
enhance
quality
of
Язык: Английский
Seizures and premature death in mice with targeted Kv1.1 deficiency in corticolimbic circuits
Brain Communications,
Год журнала:
2024,
Номер
7(1)
Опубликована: Дек. 24, 2024
Abstract
Sudden
unexpected
death
in
epilepsy
(SUDEP)
is
the
leading
cause
of
epilepsy-related
death,
likely
stemming
from
seizure
activity
disrupting
vital
brain
centres
controlling
heart
and
breathing
function.
However,
understanding
SUDEP's
anatomical
basis
mechanisms
remains
limited,
hampering
risk
evaluation
prevention
strategies.
Prior
studies
using
a
neuron-specific
Kcna1
conditional
knockout
mouse
model
SUDEP
identified
primary
importance
brain-driven
contributing
to
sudden
cardiorespiratory
dysregulation;
yet,
underlying
neurocircuits
have
not
been
identified.
Using
Emx1-Cre
driver,
we
generated
new
lacking
excitatory
neurons
cortex,
hippocampus,
amygdala
select
vagal
afferents.
To
test
whether
absence
Kv1.1
forebrain
corticolimbic
circuits
sufficient
induce
spontaneous
seizures,
premature
mortality
dysfunction,
performed
survival
EEG,
ECG,
plethysmography
(EEG-ECG-Pleth)
recordings.
We
demonstrate
mice.
During
monitoring,
fortuitously
captured
one
event,
which
showed
generalized
tonic-clonic
that
initiated
respiratory
dysfunction
culminating
failure.
In
addition,
observed
abnormalities
are
common
during
non-fatal
seizures
mice,
but
mostly
absent
interictal
periods,
implying
ictal,
interictal,
impairment
as
more
reliable
indicator
risk.
These
results
point
critical
neural
substrates
affirm
seizure-related
cardiac
failure
death.
Язык: Английский