Stroke: Spatial relationship between white matter hyperplasia and lacunature: A 14-year follow-up study of the RUN DMC cohort in Nijmegen, the Netherlands

Small-vessel disease of the brain (SVD) is the most important vascular factor leading to cognitive impairment and dementia and causes up to 25% of ischemic
strokes.
It often appears in neuroimaging in older people, such as leukohyperplasia (WMHs) and cavities
of presumed vascular origin.
Knowledge downloaded from the evolution of SVDs, such as eventful fissures, contributes to a better understanding of the origins and consequences
of SVDs.
However, the underlying mechanisms leading to eventful lacunarity remain largely unknown
.
This is because in the case of sporadic SVD, event fissures are difficult to capture because they are usually asymptomatic and have a low incidence and therefore require large prospective magnetic resonance imaging (MRI) studies and long-term follow-up
.

Figure 1: Cover image of the paper

The anatomical location of the new fissure may provide additional information
about the underlying mechanism.
For example, basilar ganglia lesions have a proximal source of embolism (e.
g.
, carotid stenosis, atrial fibrillation) more often than hemipal center lesions, whereas an event fissure located in the center of the semioval may involve hypoperfusion
.
At the same time, a study of patients with cerebral autosomal dominant artery disease with subcortical infarction and white matter encephalopathy (CADASIL) found that > 90% of the occasional lacuna occurred at the boundary of WMH, suggesting a link
between WMH and the development of lacuna.

However, since this study was conducted in single-gene SVD, external validity is limited
.
The authors tried to confirm their findings in patients with sporadic SVD, but this relationship was only observed
in old lacunae due to the lack of new lacunae.
Whether this can be generalized to the event fissure is unknown
.
The low proportion of fissures occurring in the original WMH indicates that only a very small number of regions in WMH change/transform into cavitations, which is hypothesized to be one of
the mechanisms of subcortical white matter fissures.
This has aroused interest that the different etiologies of fissures have not been investigated to date
in terms of their spatial relationship to WMH.

Thus, Fang Yi et al.
of the University of Nijmegen, the Netherlands, evaluated the spatial distribution patterns of lacunae that occurred in a large sporadic SVD cohort (RUN DMC) with 14 years of follow-up and their relationship
to WMH.
First, they described the characteristics of the emerging fissure, layered
by their anatomical location and spatial relationship to pre-existing WMH.
Secondly, the relationship between
baseline SVD imaging markers, WMH progression and fracture occurrence was explored.

Prospective single-center Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) is being recruited for baseline assessment in 2006 and follow-up in 2011, 2015 and 2020
.
2011, 2015 and 2020
.
382 participants who underwent at least 2 MRI scans of the brain were included
.

The spatial relationship
between the new lacuna, the subcortical white matter located and the new venturative lacuncle of WM was systematically determined.
The spatial relationship between subcortical white matter and WMH is determined
using visual scoring scales.
Adjusted multiple logistic regression and linear mixed-effects regression models were used to assess associations
between baseline markers of small vessel disease.

Progression and fissures
occur in WMH.
Participants
with atrial fibrillation were excluded from the multivariate analysis.
Results: Forty-three patients (mean age 66.
5±8.
2 years, 37.
2% female) found 80 occasional fissures
at a mean follow-up of 11.
2±3 months.
The follow-up was 11.
2±3.
3 years (incidence 10.
0 per 1000 person-years).

Figure 2: Graph of paper results

60% of the resulting fissures are in white matter, and 48.
9% of them are not linked
to the previously existing WMH.
Baseline WMH volume (HR = 2.
5 [95% CI, 1.
6-4.
2]).

After adjusting for age, sex, and vascular risk factors, fissures
can be predicted.
Progression of WMH is independent of age, sex, baseline WMH volume, and vascular risk factors (odds ratio, 3.
2 [95% CI, 1.
5-6.
9]).

Baseline WMH volume and progression rates were higher
in participants exposed to pre-existing cavities.

No differences
in vascular risk factors were observed in WMH in terms of location or relationship to pre-existing WMH.

The significance of this study is that it found that two different distribution patterns of the lacuna-WMH relationship may indicate different underlying mechanisms, one of which may be more closely related
to similar pathophysiology of WMH.
The longitudinal relationship between WMH and fissures further supports a reasonable sharing mechanism
between these two key markers.

Spatial Relation Between White Matter Hyperintensities and Incident Lacunes of Presumed Vascular Origin: A 14-Year Follow-Up Study.
_Stroke_.
Published online October 3, 2022:10.
1161/STROKEAHA.
122.
039903.
doi:[10.
1161/STROKEAHA.
122.
039903](https://doi.
org/10.
1161/STROKEAHA.
122.
039903)