Key Words
Carotid endarterectomy - Transient ischemic attacks - Stroke in evolution
Introduction
Carotid endarterectomy (CEA), first performed in 1953 by DeBakey[1], is an effective and recognized vascular elective procedure for symptomatic patients
with moderate or severe (≥70%) carotid stenosis and in patients with severe asymptomatic
stenosis[2]
[3]. But the best timing to perform CEA in patients with acute neurological symptoms
(repetitive transient ischemic attacks, minor stroke or stroke-in-evolution) has for
a long time been subject to controversy and is still a source of debate. In fact,
to our knowledge, there are no prospective randomized trials to determine which neurologically
unstable patient (presenting repetitive transient ischemic attacks or stroke-in-evolution),
might safely undergo urgent or delayed CEA.
In the past, the increased risks of reperfusion injury and conversion to hemorrhagic
infarction have led to the historical recommendation of delayed CEA in patients with
acute neurological symptoms. But, in recent years, most published data demonstrated
that the risk of recurrent stroke in the first few days after a transient ischemic
attack (TIA) or minor stroke appears to be much higher than previously estimated.
Rothwell et al.[4], assessed the risk of stroke at 7, 30, and 90 days first after TIA as 8, 11.5, and
17.3% respectively and after a minor stroke as 11.5, 15, and 18.5%. On the other hand,
some centers report the safety and efficacy of urgent CEA (before two weeks) after
acute minor stroke, repetitive TIAs, or stroke-in-evolution (SIE)[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]. A subanalysis of NASCET results[14]
[15] illustrates a rapid decline of the benefit of CEA over time in terms of stroke prevention
after the index focal neurological deficit (TIA or minor stroke). Recent guidelines
document that early surgery is associated with increased benefits compared with delayed
surgery for secondary stroke prevention and recommend CEA within two weeks for patients
presenting with a TIA or minor stroke[16].
We performed a prospective nonrandomized protocol for urgent (within 24 h) CEA in
neurologically unstable patients (presenting with repetitive TIA or progressing stroke)
with a symptomatic carotid stenosis of more than 70% in order to assess the safety
of this therapeutic approach.
Methods
During a five year period, we performed a single center, prospective, nonrandomized
consecutive series of urgent CEA. In accordance with the NASCET and ECST studies[3]
[2] and the Charing Cross series results[17], the following inclusion criteria have been used: symptomatic carotid stenosis of
70% or more, with unstable neurological status consisting in repetitive TIA or progressive
stroke evolving no longer than 24 hour, no impairment of consciousness, and no cerebral
infarct larger than 1.5 cm in diameter on preoperative CT scan ([Table 1]). There were no exclusion criteria except for age over 80 years. Hemorrhage seen
on the initial CT-scan eliminated the patient from the study. The term “progressing
stroke” is applied to patients with a neurological deficit that has progressed or
fluctuated over a period of at least 24 hours. The diagnosis of carotid stenosis was
based on echodoppler ultrasonography and/or selective carotid angiography. The degree
of stenosis was determined by means of the North American Symptomatic Carotid Endarterectomy
Trial (NASCET) method. All patients were examined by the same neurologist pre- and
postoperatively (PD). Neurological evaluation of the patients was blinded from the
surgeon's clinical examination to avoid under or overestimation in the patient's clinical
status.
Table 1.
Inclusion Criteria for Patient Enrollment
|
Inclusion criteria
|
|
Symptomatic carotid stenosis of 70% or more
|
|
Unstable neurological status consisting in repetitive TIA or progressive stroke evolving
no longer than 24 h
|
|
No impairment of consciousness
|
|
No cerebral infarct larger than 1.5 cm in diameter on preoperative CT-scan
|
All patients were scored by the European Stroke Scale (ESS)[18] at admission and at discharge (maximum ESS score is 100 and indicates a patient
without any neurological deficit). Barthel's index[19] was only evaluated at hospital discharge because it is impossible to determine preoperatively
patient's autonomies. It is considered that a patient is independent at home if his
score (Barthel's index) exceeds 85. The preoperative investigation included in all
cases: blood sample analysis, ECG and/or cardiac echography, chest X-ray, carotid
echo color Doppler ultrasonography, selective angiography of the carotid arteries,
and cerebral CT-scan. No MRI was performed because MRI was not accessible on an emergency
basis. From the day of the admission to the discharge from hospital, all patients
received heparin at a prophylactic dose, along with statin therapy. As CEA was performed
on an emergency basis (within the first 24 hours), no aspirin was administred preoperatively.
A standard surgical open endarterectomy, with Javid shunt (to maintain cerebral circulation
during surgery) and prosthetic patching, was performed under general anesthesia by
the same vascular surgeon (NS) in all cases. The postoperative care was performed
in a stroke unit, with ECG, noninvasive arterial blood pressure monitoring, and transcutaneous
oxygen saturation monitoring for at least 48 hours. All the patients underwent a cerebral
CT scan before discharge, within the five days after surgery. In the postoperative
period, patients were maintained on a low dose of heparin (4000 IU) and statin therapy
together with their scheduled medications. At discharge from the hospital, antiplatelet
therapy (acetylsalicylic acid 100 mg daily) was started. During regular follow-up,
all patients were reviewed by the same neurologist (PD) and the same surgeon (NS)
independently from each other at six weeks after surgery and every six months during
the first year, and every 12 months thereafter. Assessment of outcome was based on
follow-up control examination.
Statistical Analysis
Patient details, including age, gender, and comorbidities were collected in an Excel
database (Microsoft Ltd). Categorical data were presented as absolute frequencies
and percent values. Quantitative measurements were expressed as mean ± SD. Data on
survival, neurological events, and patency was studied directly.
Results
Patients Characteristics
The study concerns 30 consecutive patients included out of a series of 638 patients
admitted to the emergency department for acute TIA or progressive stroke during a
five year period. In these 30 patients, CEA was performed within 24 hours following
the neurological event (repetitive TIA or progressive stroke). Of these, there were
12 patients presenting with repetitive TIA and 18 progressive strokes. There were
19 men and 11 women with a mean age of 71 ± 7.6 years. No patient had any neurological
deficit before the onset of repetitive TIA or progressing stroke. Baseline patient
characteristics and medical history are presented in [Table 2].
Table 2.
Patient's Characteristics and Medical History
|
No. of patients (%)
|
|
Demography
|
|
|
Mean age (y)
|
71
|
|
Men: Women
|
19 (63): 11 (37)
|
|
Neurologic clinical presentation
|
|
|
Repetitive TIA (≥ 2/24h)
|
12 (40)
|
|
Progressive stroke
|
18 (60)
|
|
Comorbidities
|
|
|
Hypertension
|
6
|
|
Diabetes
|
3
|
|
Hypercholesterolemia
|
19
|
|
Smoking history
|
14
|
|
Previous myocardial infarction
|
3
|
|
Previous TIA and/or stroke
|
0
|
Perioperative Characteristics
All patients had documented internal carotid artery stenosis of 70% or more. For patients
suffering progressive stroke (n = 18), the degree of carotid artery stenosis was 85%
or more. The mean delay of surgery after onset of the first TIA or progressive stroke
was 19.4 (±11.5) hours (range, 6–48 hours). At operation, the macroscopic examination
of the internal carotid artery in all 30 patients showed a complex ulcerated plaque
and/or an intraplaque hemorrhage.
Outcomes
One patient (5%) with initial progressive stroke developed a fatal ischemic stroke
within 24 hours after the operation, and Doppler ultrasonography performed immediately
showed very good patency of the operated carotid artery. Five (28%) of the 18 patients
with progressive stroke had an incomplete recovery with limited residual neurological
deficit and experienced no clinical improvement but none of them worsened after the
operation, whereas the 12 other patients (67%) with residual neurological deficit
(as a result of their progressive stroke) showed significant improvement of their
clinical status. The 12 patients with repetitive TIA remained free of neurological
deficit after the operation. All but one of the 18 patients with progressive stroke
had a Barthel's index over 85 at hospital discharge. The mean ESS of the 18 patients
with progressive stroke was 77.9 ± 25 at admission, and was 95.8 ± 4.6 at discharge.
All the patients underwent a cerebral CT scan within five days after surgery. No hemorrhagic
transformation of cerebral infarcts was detected. No new lesion on postoperative CT
scan was found in the 12 cases of TIA. All of the 18 progressive stroke patients had
a lacunar size lesion (<15 mm); there had been no enlargement of the lesion postoperatively
except in one case in which there was a large infarction (>2 cm). There was no reoperation
for cervical hemorrhage or wound infection. No patients developed vocal cord paralysis
due to nerve injury. Patients were discharged after a median of four days (range,
4–10 days). The mean duration of follow-up was 3.4 years (±1.2) and was 100% complete
in all patients. No residual or recurrent stenosis was documented on echo color Doppler
ultrasonography follow-up. No recurrent stroke and/or TIA, no cardiac event, and no
death occurred in this series during follow-up.
Discussion
Timing of CEA in patients with acute neurological symptoms still remains a challenging
but unresolved problem[5]
[6]
[7]
[20]. The management uncertainty can be explained by the inability to predict who is
at higher early risk of a recurrent stroke after a cerebrovascular event (TIA or stroke).
Interestingly, a subanalysis of the NASCET results has revealed that the benefit of
CEA versus medical treatment is greatest if the symptomatic carotid artery stenosis
is operated within two weeks following the index neurological event[14]
[15]. Among the medically treated patients, the risk of ipsilateral stroke is highest
immediately after the initial ischemic event and subsequently drops dramatically[17].
In recent years, several studies ([Table 3]) have shown very good results and outcomes for urgent CEA procedures. In the Charing
Cross series[17], 19 patients suffering from progressing stroke and 14 patients presenting with repetitive
TIA underwent urgent CEA (all patients were operated within 48 hours after the onset
of symptoms). There was a good evolution in all but three cases. All the patients
had a small infarct size (<2.0 cm) on preoperative CT scan, were conscious, and had
a mild neurological deficit. The criteria for the selection of our patients have been
chosen in the light of the results of the Charing Cross series. The choice of these
criteria was based on the assumption that a severe neurological deficit or impaired
consciousness often implies a large infarction in progress, eventually but not yet
visualized on early cerebral CT scan, leading to a higher risk of postoperative bleeding
because of hyperperfusion in a large ischemic brain area. In our study, using these
criteria, all but one patient had a good outcome. One patient suffered a fatal stroke
due to postoperative enlargement of the existing small cerebral infarction. Intraoperative
embolization was probably the cause because Doppler ultrasonography performed immediately
showed very good patency of the operated carotid artery.
Table 3.
Results of Urgent CEA (within 15 d) Reported Recently in the Literature
|
Author and year
|
No. of patients
|
Mean interval between symptom and CEA
|
In-Hospital mortality rate
|
Complications (stroke rate)
|
|
Gertler et al., 1994[21]
[*]
|
52
|
<24 h
|
0%
|
2.0%
|
|
Schneider et al., 1999[22]
[a]
|
43
|
≤72 h
|
0%
|
0%
|
|
Brandl et al., 2001[23]
[a]
|
16
|
<24 h
|
0%
|
–
|
|
Gay et al., 2002[11]
[*]
|
21
|
<24 h
|
9.5%
|
–
|
|
Huber et al., 2003[24]
[*]
|
67
|
2 d
|
3.0%
|
13%
|
|
Sbariga et al., 2006[10]
[a]
|
96
|
1.5 d
|
2%
|
0%
|
|
Karkos et al., 2007[8]
[b]
|
42
|
3 d
|
4.8%
|
4.8%/19%
|
|
Bazan et al., 2008[6]
[*]
|
764
|
–
|
2.0%
|
2.88%/3.1%
|
|
Ballotta et al., 2008[25]
[a]
|
102
|
8 d
|
0%
|
0%
|
|
Gorlitzer et al., 2009[9]
[*]
|
28
|
4 d
|
0%
|
0%
|
|
Leseche et al., 2011[12]
[13]
[a],[b]
|
91
|
5 d
|
0%
|
0%
|
|
Dorigo et al., 2011[26]
[*]
|
75
|
<24 h
|
2.7%
|
–
|
|
Capoccia et al., 2012[27]
[*]
|
48
|
<24 h
|
2.0%
|
2.0%
|
|
Present study
[*]
|
30
|
<24 h
|
3.3%
|
3.3%
|
* Mixed study including patients with acute stroke and TIA.
a Study concerns patients with acute ischemic stroke.
b Study concerns patients with crescendo TIA.
Gertler et al.[21] reported their experience in neurologically unstable patients with carotid stenosis
presenting with crescendo TIA and SIE, of whom only one patient (2.7%) worsened his
neurological deficit after CEA within 24 hours. Based on these good results, they
recommend urgent CEA. Most recently, Leseche et al.[12]
[13] reported excellent outcome of urgent CEA in the acute phase of SIE and crescendo
TIA, with no perioperative stroke or death. The mean delay to surgery from initial
examination was five days. For patients operated for SIE, a complete neurological
recovery was observed in 81% of patients, while 19% maintained a residual deficit.
No patient presented a worsening of his deficit following urgent CEA. In a meta-analysis
of 47 studies on carotid surgery published between 1980 and 2008, Rerkasem et al.[20] found no excess operative risk for early (urgent) CEA versus delayed CEA.
However, less favorable outcome after urgent CEA in neurologically unstable patients
has been reported by other investigators. These studies demonstrated a higher rate
of perioperative complications after urgent CEA in neurologically unstable patients
(presenting crescendo TIA and SIE) compared with delayed CEA. Karkos et al.,[7] in a meta-analysis, reported a 16.9% perioperative stroke rate and a 20% combined
stroke/death rate for urgent CEA after stroke-in-evolution. Considering crescendo
TIA, the analysis revealed a more favorable outcome (6.5% perioperative stroke rate
and a 9% combined stroke/death). In a meta-analysis done by Bond et al.[28] and Halm et al.[29], the operative risk of CEA increases when it is performed after stroke-in-evolution
(a 14.0% 30-day stroke/death rate), compared to a 2.8% 30-day stroke/death rate after
CEA for asymptomatic carotid artery stenosis.
This rather elevated morbidity-mortality should be balanced against the stroke risk
in these neurologically unstable patients if surgery had not been performed. Actually,
no randomized controlled trial has been done comparing the outcome of crescendo TIA
and stroke-in-evolution treated medically versus urgently operated.
Early CEA for symptomatic severe carotid stenosis (≥70%) in neurologically unstable
patients may be justified by the instability of the lesion, in order to prevent a
subsequent complete or more severe stroke. In all of our patients, an ulcerative or
hemorrhagic plaque was discovered intraoperatively. Urgent removal of this unstable
embolic source has some logic. An arbitrary 2-week delay for CEA probably exceeds
the risk of urgent CEA and may expose the neurologically unstable patient to a risk
of recurrent or more disabling stroke, or to an occlusion of the internal carotid
artery. Before starting our prospective study, in some cases with a small cerebral
lesion, we had chosen medical treatment before performing urgent surgery. Unfortunately
in some cases, we observed fatal neurological events a few days later, after the first
neurological events (unpublished data).
In contemporary literature, there exists consensus that a patient presenting with
an acute, nondisabling neurological deficit with complete or partial recovery should
benefit from a carotid endarterectomy without delay. For the high-risk group of neurologically
unstable patients (crescendo TIA and SIE), who often present with subocclusive stenosis
with friable ulcerated plaque, the current available literature data are less conclusive.
Some series reporting a rather high perioperative morbidity-mortality seem to discourage
urgent CEA in this setting. However, in our small experience, and in some centers
of excellence, the operative outcome of urgent CEA in neurologically unstable patients
was favorable. The creation of a “Stroke Unit” could favor the management and development
of urgent CEA while allowing better selection and management of these unstable patients.
Limitations of the Study
Our results should be interpreted in light of several limitations. First, the number
of patients enrolled in this single center prospective study is too small to give
definite conclusions. This was the reason why a formal statistical analysis was not
performed. However, due to the heterogeneity and paucity of data in the literature,
subject to controversy and still a source of debate, our experience may add to the
management of these unstable neurological patients. Second, it is important to note
that our study is not randomized. Although randomized trials are certainly the gold
standard in clinical study, in neurologically unstable patients, such a trial is difficult
for ethical reasons.
Conclusion
Our consecutive series shows that urgent CEA can be performed safely in selected patients
with an evolving or unstable neurological deficit. It also confirms the relevance
of some previously noticed criteria for the prognosis of urgent CEA, such as a normal
level of consciousness, the absence of large cerebral infarction on preoperative cerebral
CT scan, and the limited severity of the neurological deficit before the operation.
We may recommend surgery within 24 hours for all symptomatic patients with unstable
plaques diagnosed by imaging tools. Urgent CEA seems to us to be justified by the
fact that a symptomatic carotid stenosis is an unstable lesion and waiting may lead
to the development of another stroke that is more disabling for the patient. The perioperative
risk can be reduced with better diagnostic strategies and must be balanced against
the natural history if surgery is not performed. Only a large randomized multicenter
prospective trial will be able to conclusively assess the effectiveness and outcome
of urgent CEA in neurologically unstable patients.
Dr. Sakalihasan and colleagues show us that prompt open surgical therapy for recurrent
TIAs or unstable stroke in evolution can lead to excellent clinical outcomes and apparent
salvage of at-risk cerebral tissue. They have taken a courageous posture. While not
a large-scale randomized study, this report gives an important “real world” glimpse
at what can be accomplished with aggressive, non-timid surgical care. We look forward
to watching their experience grow based on these very favorable institutional results.
It is important to note that the operated patients were selected from among hundreds
of patients presenting during the time interval of this study; clinical judgment in
patient selection, in addition to the stated inclusion and exclusion criteria, likely
was an important factor in attaining favorable results.
