a surveillance for restenosis justified after carotid revascularisation? A novel link between trafficking and Lewy body disorders

Is surveillance for restenosis justified after carotid
revascularisation?
A common dilemma in clinical practice is whether to
request an imaging test if the prognostic implications
of the results of the test are uncertain. An example of
such a dilemma is whether surveillance for recurrent
stenosis should be routine in patients who have
undergone carotid endarterectomy or stenting
either after an ischaemic stroke or as a preventive
procedure. Surveillance for restenosis after a carotid
revascularisation procedure is common practice in
many centres. Carotid ultrasound is usually done
within the first 6 months after the procedure, and then
at yearly intervals, to check for restenosis. In addition
to detecting restenosis, surveillance can also provide
information on patency of the contralateral internal
carotid artery. In an analysis of 4127 asymptomatic
elderly patients who underwent carotid ultrasound,1
the second most frequent reason for follow-up
imaging was previously reported carotid stenosis,
with presence of a bruit being the most common
indication.
In The Lancet Neurology, Leo H Bonati and
colleagues present data from the International
Carotid Stenting Study (ICSS), in which participants
with symptomatic carotid stenosis were randomly
allocated either stenting or endartectomy.2
Of 1713
patients enrolled, 1530 were followed up with carotid
ultrasound for a median of 4·0 years (IQR 2·3–5·0).
The cumulative 5-year risk of moderate or higher
(≥50%) restenosis was 40·7% with stenting and
29·6% with endarterectomy (unadjusted hazard
ratio [HR] 1·43, 95% CI 1·21–1·72; p<0·0001). In
patients with moderate or higher (≥50%) stenosis,
the cumulative risk of ipsilateral stroke at 6 years was
increased in the overall study population (unadjusted
HR 3·18, 95% CI 1·52–6·67; p=0·002) and in those
who underwent endarterectomy (5·75, 1·80–18·33;
p=0·003). In patients with severe (≥70%) stenosis,
risk for restenosis did not differ between treatment
groups (cumulative 5-year risk 10·6% with stenting
vs 8·5% with endarterectomy; unadjusted HR 1·20,
95% CI 0·86–1·69; p=0·27) and no increased risk
of ipsilateral stroke was noted (1·79, 0·64–4·99;
p=0·263).
Definitions of restenosis are worth considering,
particularly when comparing these results with those
of other trials. The ICSS investigators used a cutoff for
peak systolic velocity of greater than 1·3 m/s to define
moderate or higher (≥50%) stenosis and a cutoff of
greater than 2·1 m/s to define severe (≥70%) stenosis. By
contrast, the Carotid Revascularization Endarterectomy
versus Stenting Trial (CREST) used a higher threshold
(>3·0 m/s) to define severe (≥70%) stenosis.3
Some
imaging specialists recommend the higher threshold in
stented vessels because the presence of a stent alters the
elasticity of the vessel wall.4
Data from ICSS suggest that the value of information
obtained from routine surveillance after
endarterectomy or stenting is uncertain for guiding
a change in treatment. Although an increased risk of
stroke was seen in patients with at least moderate
(≥50%) stenosis, the mechanism of the stroke was
not clear, and this information could be important
because if a stroke is due to cardiac embolism or is a
lacunar stroke, then operating on the restenotic lesion
will not be helpful and could be harmful. Patients with
restenosis might have a greater likelihood of resistant
atherosclerosis compared with those without restenosis,
which could be associated with a higher likelihood of
intracranial stenosis or small-vessel pathology. Future
studies should attempt to understand the mechanism
of ipsilateral stroke in patients with restenosis. In a
previous study of 1820 patients with severe carotid
stenosis, cardioembolic events and small-vessel disease
were thought to account for close to half of subsequent
strokes.5
The practical conclusions that clinicians should
take from this study are also unclear. If a patient
has moderate or higher (≥50%) restenosis, should
medical treatment be intensified? Should more
stringent blood pressure or lipid targets be used?
Should reintervention be considered, in the form of
new stenting or endarterectomy? Intensified medical
treatment seems reasonable, but its efficacy has not
been proven in clinical trials of patients with a previous
stroke. Endarterectomy or stenting procedures for
asymptomatic stenosis in the general population are
Published Online
May 31, 2018
http://dx.doi.org/10.1016/
S1474-4422(18)30199-6
See Articles page 587
Comment
www.thelancet.com/neurology Vol 17 July 2018 571
Elucidating the natural history and underlying genetic
causes of Parkinson’s disease and related Lewy body
disorders is crucial in guiding our development of
therapeutic intervention strategies. Approximately
15% of patients with Parkinson’s disease report a family
history of the disease, and studies have identified or
nominated a small number of disease-associated genes
from multi-incident families. However, these genes
account for only 5–10% of familial cases of Parkinson’s
disease. As such, many more rare genetic forms probably
exist. Population-based genome-wide association studies
have also nominated 41 loci that can alter individual
susceptibility to Parkinson’s disease, and this number
continues to grow.1
In The Lancet Neurology, a study by Marialuisa Quadri
and colleagues2 nominates a mutation in the LRP10
gene as causative in a large multi-incident pedigree
from Italy, by use of single nucleotide polymorphismbased
linkage analysis and whole exome sequencing.
The LRP10 mutation 1807G→A (Gly603Arg) was
selected as the pathogenic candidate over mutations
in other genes (OR11H12 and POTEG) on the basis of
results from in silico predictive tools. It should be noted
that, when such rare genetic causes are nominated by
whole exome rather than whole genome sequencing,
there remains a possibility of missing small copy
number variants or repeats on the disease-segregating
haplotype. Subsequent gene screening and mutation
of uncertain value, so undertaking another procedure
for asymptomatic restenosis is even less persuasive
because the risk for complications from operating on a
restenotic lesion is high so the risk:benefit ratio is less
favourable for a patient with asymptomatic restenosis.6
Moreover, reintervention would typically be considered
if stenosis progresses beyond 70% but, in the current
study, those patients did not have an increased stroke
risk, although the power to detect such a difference was
limited in ICSS.
Along with defining the mechanism of stroke
associated with restenosis, future analyses should
also address the pathology of these lesions. Previous
published work has identified myointimal hyperplasia
with early recurrent stenosis and so-called typical
atherosclerotic changes in patients with late restenosis
(ie, >1 year from the index procedure). Female
sex, diabetes, dyslipidaemia, continued smoking,
and impaired cerebrovascular reactivity have been
associated with restenosis.3,7 Since predictors of
restenosis exist, a targeted imaging programme
focused on patients with the highest risk for restenosis
might be a more sensible strategy than indiscriminate
surveillance of all patients.
Guidelines from the American Heart Association and
the American Stroke Association state that routine longterm
follow-up imaging with carotid duplex ultrasound
is not warranted in patients after revascularisation.8
By identifying the group of patients at increased risk
of stroke, the current work by Bonati and colleagues
shows that there is some prognostic value to followup
imaging, but the treatment steps to address the
increased stroke risk are uncertain.
Seemant Chaturvedi
Department of Neurology, University of Miami Miller School of
Medicine, Miami, FL 33136, USA
[email protected]
I am a member of the Executive Committee for the CREST 2 and ACT 1 studies.
Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access
article under the CC BY 4.0 license.
1 Keyhani S, Cheng EM, Naseri A, et al. Common reasons that asymptomatic
patients who are 65 years and older receive carotid imaging.
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2 Bonati LH, Gregson J, Dobson J, et al. Restenosis and risk of stroke after
stenting or endarterectomy for symptomatic carotid stenosis in the
International Carotid Stenting Study (ICSS): secondary analysis of a
randomised trial. Lancet Neurol 2018; published online May 31. http://dx.
doi.org/10.1016/S1474-4422(18)30195-9.
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