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Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease.
[cadasil]
White
matter
hyperintensities
and
lacunes
are
among
the
most
frequent
abnormalities
on
brain
magnetic
resonance
imaging
.
They
are
commonly
related
to
cerebral
small
vessel
disease
and
associated
with
both
stroke
and
dementia
.
We
examined
the
spatial
relationships
between
incident
lacunes
and
white
matter
hyperintensities
and
related
these
findings
to
information
on
vascular
anatomy
to
study
possible
mechanistic
links
between
the
two
lesion
types
.
Two
hundred
and
seventy-
six
patients
with
cerebral
autosomal
dominant
arteriopathy
with
subcortical
infarcts
and
leukoencephalopathy
(
CADASIL
)
,
a
genetically
defined
small
vessel
disease
with
mutations
in
the
NOTCH
3
gene
were
followed
with
magnetic
resonance
imaging
over
a
total
of
633
patient
years
.
Using
difference
images
and
Jacobian
maps
from
registered
images
we
identified
104
incident
lacunes
.
The
majority
(
n
=
95
;
91
.
3
%
)
of
lacunes
developed
at
the
edge
of
a
white
matter
hyperintensity
whereas
few
lacunes
were
found
to
develop
fully
within
(
n
=
6
;
5
.
8
%
)
or
outside
(
n
=
3
;
2
.
9
%
)
white
matter
hyperintensities
.
Adding
information
on
vascular
anatomy
revealed
that
the
majority
of
incident
lacunes
developed
proximal
to
a
white
matter
hyperintensity
along
the
course
of
perforating
vessels
supplying
the
respective
brain
region
.
We
further
studied
the
spatial
relationship
between
prevalent
lacunes
and
white
matter
hyperintensities
both
in
365
patients
with
CADASIL
and
in
588
elderly
subjects
from
the
Austrian
Stroke
Prevention
Study
.
The
results
were
consistent
with
the
results
for
incident
lacunes
.
Lesion
prevalence
maps
in
different
disease
stages
showed
a
spread
of
lesions
towards
subcortical
regions
in
both
cohorts
.
Our
findings
suggest
that
the
mechanisms
of
lacunes
and
white
matter
hyperintensities
are
intimately
connected
and
identify
the
edge
of
white
matter
hyperintensities
as
a
predilection
site
for
lacunes
.
Our
observations
further
support
and
refine
the
concept
of
the
white
matter
hyperintensity
penumbra
.
Diseases
Validation
Diseases presenting
"white matter hyperintensities"
symptom
22q11.2 deletion syndrome
cadasil
hereditary cerebral hemorrhage with amyloidosis
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