Journal of Clinical Medicine,
Journal Year:
2023,
Volume and Issue:
12(6), P. 2255 - 2255
Published: March 14, 2023
The
process
of
ageing
is
characteristic
multicellular
organisms
associated
with
late
stages
the
lifecycle
and
manifested
through
a
plethora
phenotypes.
Its
underlying
mechanisms
are
correlated
age-dependent
diseases,
especially
neurodegenerative
diseases
such
as
Alzheimer’s
disease
(AD),
Parkinson’s
(PD)
multiple
sclerosis
(MS)
that
accompanied
by
social
financial
difficulties
for
patients.
Over
time,
people
not
only
become
more
prone
to
neurodegeneration
but
they
also
lose
ability
trigger
pivotal
restorative
mechanisms.
In
this
review,
we
attempt
present
already
known
molecular
cellular
hallmarks
characterize
in
association
their
impact
on
central
nervous
system
(CNS)’s
structure
function
intensifying
possible
preexisting
pathogenetic
conditions.
A
thorough
elucidative
study
will
be
able
contribute
further
development
new
therapeutic
interventions
effectively
treat
manifestations
diseases.
Acta Neuropathologica,
Journal Year:
2020,
Volume and Issue:
139(5), P. 875 - 892
Published: Feb. 11, 2020
Abstract
We
sought
to
define
the
pathological
features
of
myelin
oligodendrocyte
glycoprotein
(MOG)
antibody
associated
disorders
(MOGAD)
in
an
archival
autopsy/biopsy
cohort.
histopathologically
analyzed
2
autopsies
and
22
brain
biopsies
from
patients
with
CNS
inflammatory
demyelinating
diseases
seropositive
for
MOG-antibody
by
live-cell-based-assay
full
length
MOG
its
conformational
form.
MOGAD
(ages
52
67)
demonstrate
spectrum
histopathological
observed
within
(median
age,
10
years;
range,
1–66;
56%
female).
Clinical,
radiologic,
laboratory
characteristics
course
(78%
relapsing)
are
consistent
MOGAD.
pathology
is
dominated
coexistence
both
perivenous
confluent
white
matter
demyelination,
over-representation
intracortical
demyelinated
lesions
compared
typical
MS.
Radially
expanding
slowly
smoldering
as
seen
MS,
not
present.
A
CD4+
T-cell
reaction
granulocytic
infiltration
predominates.
Complement
deposition
present
all
active
lesions,
but
a
preferential
loss
observed.
AQP4
preserved,
absence
dystrophic
astrocytes,
variable
axonal
destruction.
pathologically
distinguished
AQP4-IgG
NMOSD,
shares
some
overlapping
MS
ADEM,
suggesting
transitional
pathology.
selective
protein
suggest
humoral
mechanisms
involved,
however
argue
against
endocytic
internalization
antigen.
Parallels
MOG-EAE
may
be
amplification
factor
that
augments
possibly
via
complement
mediated
destruction
or
ADCC
phagocytosis.
Frontiers in Immunology,
Journal Year:
2019,
Volume and Issue:
10
Published: Nov. 29, 2019
The
Bacillus
Calmette-Guérin
(BCG)
is
a
live
attenuated
tuberculosis
vaccine
that
has
the
ability
to
induce
non-specific
cross-protection
against
pathogens
might
be
unrelated
target
disease.
Vaccination
with
BCG
reduces
mortality
in
newborns
and
induces
an
improved
innate
immune
response
microorganisms
other
than
Mycobacterium
tuberculosis,
such
as
Candida
albicans
Staphylococcus
aureus.
Innate
cells,
including
monocytes
natural
killer
(NK)
cells
contribute
this
unspecific
protection
way
independent
of
memory
T
or
B
cells.
This
phenomenon
associated
memory-like
known
"trained
immunity".
Epigenetic
reprogramming
through
histone
modification
regulatory
elements
particular
genes
been
reported
one
mechanisms
induction
trained
immunity
both,
humans
mice.
Indeed,
it
shown
vaccination
changes
methylation
pattern
histones
specific
circulating
leading
"trained"
state.
Importantly,
these
modifications
can
lead
expression
and/or
repression
are
related
increased
secondary
infections
after
vaccination,
pathogen
recognition
faster
inflammatory
responses.
In
review,
we
will
discuss
BCG-induced
acquisition
potential
heterologous
effects
recombinant
vaccines.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: April 7, 2022
It
has
been
noticed
in
recent
years
that
the
unfavorable
effects
of
gut
microbiota
could
exhaust
host
vigor
and
life,
yet
knowledge
theory
are
just
beginning
to
be
established.
Increasing
documentation
suggests
microbiota–gut–brain
axis
not
only
impacts
brain
cognition
psychiatric
symptoms
but
also
precipitates
neurodegenerative
diseases,
such
as
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
multiple
sclerosis
(MS).
How
blood–brain
barrier
(BBB),
a
machinery
protecting
central
nervous
system
(CNS)
from
systemic
circulation,
allows
risky
factors
derived
translocated
into
seems
paradoxical.
For
unique
anatomical,
histological,
immunological
properties
underpinning
its
permeable
dynamics,
BBB
regarded
biomarker
associated
with
neural
pathogenesis.
The
permeability
mice
rats
caused
by
GM
dysbiosis
raises
question
how
metabolites
change
causes
pathophysiology
neuroinflammation
neurodegeneration
(NF&ND)
aging,
pivotal
multidisciplinary
field
tightly
immune
chronic
inflammation.
If
all,
microbiota-induced
inflammation
(GM-SCI)
mainly
refers
excessive
mucosal
immunity
dysregulation,
which
is
often
influenced
dietary
components
age,
produced
at
interface
intestinal
(IB)
or
exacerbated
after
IB
disruption,
initiates
various
common
diseases
along
dispersal
routes,
eventually
impairs
integrity
cause
NF&ND
aging.
To
illustrate
roles
affected
inflammatory
“leaky”
resulting
their
metabolites,
we
reviewed
selected
publications,
including
role
barrier,
influences
on
permeability,
NF&ND,
add
depth
bridging
inflammation,
plausible
mechanism
indispensable
for
corruption
was
highlighted;
namely,
maintenance
cues
cytokines,
may
help
understand
play
major
Frontiers in Neurology,
Journal Year:
2020,
Volume and Issue:
11
Published: Aug. 21, 2020
Comorbidities
in
patients
with
multiple
sclerosis
(MS)
has
become
an
area
of
increasing
interest
the
recent
years.
A
comorbidity
is
defined
as
any
additional
disease
that
coexists
individual
a
given
index
and
not
obvious
complication
disease.
The
aim
this
review
to
describe
current
evidence
regarding
range
comorbidities
population
MS
reported
different
countries
knowledge
about
influence
on
clinical
features
therapeutic
challenges
MS.
Certain
are
more
prevalent
people
such
depression,
anxiety,
cerebro-
cardiovascular
diseases
certain
autoimmune
disorders
diabetes,
thyroid
inflammatory
bowel
previous
perception
trend
toward
lower
overall
risk
cancer
appears
be
challenged,
but
there
no
higher
occurrence
malignancies
may
modify
presentation
MS,
have
implications
for
treatment
choice,
adherence
outcome.
Several
comorbid
conditions
associated
increased
disability
progression,
including
hypertension
chronic
obstructive
pulmonary
common
from
time
diagnosis
account
some
heterogeneity
observed
diagnostic
delay,
presentation,
degree
rate
health
care
utilisation,
working
ability,
employment
status
quality
life.
Coexisting
polypharmacy
increase
complexity
patient
management
poses
major
challenges,
particularly
number
immunosuppressive
disease-modifying
therapies.
Neurodegeneration
and
astrocytic
activation
are
pathologic
hallmarks
of
progressive
multiple
sclerosis
(MS)
can
be
quantified
by
serum
neurofilament
light
chain
(sNfL)
glial
fibrillary
acidic
protein
(sGFAP).
We
investigated
sNfL
sGFAP
as
tools
for
stratifying
patients
with
MS
based
on
progression
disease
activity
status.We
leveraged
our
Comprehensive
Longitudinal
Investigation
at
the
Brigham
Women's
Hospital
(CLIMB)
natural
history
study,
which
includes
clinical,
MRI
data
samples
collected
over
more
than
20
years.
included
a
confirmed
Expanded
Disability
Status
Scale
(EDSS)
score
≥3
that
corresponds
classifier
high
risk
underlying
pathology.
analyzed
within
6
months
from
EDSS
corresponding
baseline
visit.
Patients
who
further
developed
6-month
disability
(6mCDP)
were
classified
progressors.
stratified
into
active/nonactive
new
brain/spinal
cord
lesions
or
relapses
in
2
years
before
during
follow-up.
Statistical
analysis
log-transformed
sGFAP/sNfL
assessed
association
demographic,
features
associations
future
disability.We
257
had
an
average
4.0
median
follow-up
after
7.6
was
higher
(adjusted
β
=
1.21;
95%
CI
1.04-1.42;
p
0.016),
first
1.17;
1.01-1.36;
0.042).
not
increased
presence
activity.
Higher
levels,
but
associated
6mCDP
hazard
ratio
[HR]
1.71;
1.19-2.45;
0.004).
The
stronger
low
HR
2.44;
1.32-4.52;
0.005)
nonactive
prior
sample.Higher
levels
correlated
subsequent
progression,
particularly
patients,
whereas
reflected
acute
Thus,
may
used
to
stratify
clinical
research
studies
trials
inform
care.
Journal of Neurology,
Journal Year:
2022,
Volume and Issue:
269(10), P. 5382 - 5394
Published: May 24, 2022
Abstract
Multiple
sclerosis
(MS)
is
a
chronic
and
progressive
neurological
disease
that
characterized
by
neuroinflammation,
demyelination
neurodegeneration
occurring
from
the
earliest
phases
of
may
be
underestimated.
MS
patients
accumulate
disability
through
relapse-associated
worsening
or
progression
independent
relapse
activity.
Early
intervention
with
high-efficacy
disease-modifying
therapies
(HE-DMTs)
represent
best
window
opportunity
to
delay
irreversible
central
nervous
system
damage
MS-related
hindering
underlying
heterogeneous
pathophysiological
processes
contributing
progression.
In
line
this,
growing
evidence
suggests
early
use
HE-DMTs
associated
significant
greater
reduction
not
only
inflammatory
activity
(clinical
relapses
new
lesion
formation
at
magnetic
resonance
imaging)
but
also
progression,
in
terms
accumulation
clinical
compared
delayed
HE-DMT
escalation
strategy.
These
beneficial
effects
seem
acceptable
long-term
safety
risks,
thus
configuring
this
treatment
approach
as
most
positive
benefit/risk
profile.
Accordingly,
it
should
mandatory
treat
people
case
prognostic
factors
suggestive
aggressive
disease,
advisable
offer
an
after
diagnosis,
taking
into
account
drug
profile,
severity,
and/or
radiological
activity,
patient-related
factors,
including
possible
comorbidities,
family
planning,
patients’
preference
agreement
EAN/ECTRIMS
AAN
guidelines.
Barriers
for
include
concerns
safety,
challenges
management
initiation
monitoring,
negative
preferences,
restricted
access
according
guidelines
regulatory
rules,
sustainability.
However,
these
barriers
do
apply
each
none
appear
insuperable.
The Lancet Regional Health - Europe,
Journal Year:
2024,
Volume and Issue:
44, P. 100977 - 100977
Published: Aug. 23, 2024
SummaryMultiple
sclerosis
is
a
chronic,
inflammatory,
and
neurodegenerative
disease
of
the
central
nervous
system
major
cause
neurological
disability
in
young
adults.
Its
prevalence
incidence
are
increasing,
it
has
been
estimated
at
over
2.8
million
cases
worldwide,
addition
to
recent
trends
towards
shift
MS
older
ages,
with
peak
estimates
sixth
decade
life.
Although
historically
relapsing
progressive
phases
have
considered
separate
clinical
entities,
evidence
progression
independent
relapse
activity
(PIRA)
led
reconsideration
multiple
as
continuum,
which
features
variably
coexist
from
earliest
stages
disease,
challenging
traditional
view
course.
In
this
Series
article,
we
provide
an
overview
how
description
course
epidemiological
Europe
evolved.
For
purpose,
focus
on
concept
PIRA,
discussing
its
potential
main
mechanism
by
patients
acquire
disability,
definition
varies
between
studies,
ongoing
research
field.
We
emphasise
importance
incorporating
assessment
hidden
manifestations
into
patient
management
help
uncover
quantify
PIRA
phenomenon
possible
implications
for
future
changes
classification
disease.
At
same
time,
insights
overcoming
challenges
identifying
defining
adopting
new
understanding
MS.