Supra-aortic branches and the arteries of the upper extremity
Epidemiology, prevalence, incidence, risk factors
Annually, 1.4 million strokes occur in the Europeaan population of 715 million, leading to the deaths of 1.1 million people. Based on the pathomechanism of acute cerebral events, 80-85% of all tissue damage is ischemic and only around 15-20% is hemorrhagic in origin. Almost 30-40% of all strokes is caused by stenosis of the extracranial carotid artery.
The occurrence of over 70% carotid stenosis was at 0.3% in patients who had no known vascular stenosis; 1.9% in patients who had been previously diagnosed with coronary disease; and 3.5% in post-stroke patients. The risk factors of carotid stenosis are: age over 50 years, smoking, hyperlipidemia, cardiovascular event of a relative before the age of 60, peripheral arterial disease or coronary disease, and previous stroke or TIA. At a prevalence of 0.5‑2%, population level screening is not recommended due to being uneconomic.
Etiology, site of the stenosis
The most common disease of the supra-aortic branches (90%) is stenosis or occlusion caused by atherosclerotic plaque formation, which develops with age. Hemodynamic turbulence develops in the bifurcation of the internal and external carotid arteries, at the widening of the carotid bulb. For this reason, the initial portion of the internal carotid artery is the site of predilection for cervical arterial stenosis. The occurrence of stenosis is also somewhat more frequent at the origin of the common carotid artery and within the carotid siphon, due to various hemodynamic features and characteristics of the endothelial structure of these vascular portions.
Stroke
Definitions
According to the 1980 World Health Organization (WHO) definition stroke means the rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin. A transient ischemic attack (TIA) is defined as a similar event, which resolves within 24 hours.However, modern imaging studies clearly reveal that the duration of the symptoms and the detected circumscribed ischemic lesions are not linked to the previously determined 24-hour criterion. The 2013 American Heart Association/American Stroke Association (AHA/ASA) guideline modified the definition accordingly. In the AHA/ASA guideline, the definition is further divided into infarction and hemorrhage. According to the AHA/ ASA definition, a central nervous system infarction is: brain, spinal cord, or retinal cell death attributable to ischemia based on pathological, imaging, or other objective evidence of cerebral, spinal cord, or retinal focal ischemic injury in a defined vascular distribution; or clinical evidence of cerebral, spinal cord, or retinal focal ischemic injury based on symptoms persisting ≥24 hours or until death, and other etiologies can be excluded. Instead of the term TIA, the AHA/ASA guideline recommends taking into consideration the duration of the symptoms and the presence of definitive permanent tissue necrosis of any origin.
The definition presented by the AHA/ASA calls attention to permanent cell death as the characteristic of stroke, rather than the duration of symptoms.
The etiology of stroke
The role of carotid stenosis in ischemic stroke
The stenosis of the internal carotid artery (ICA) and/or common carotid artery (CCA) is the most common cause of ischemic focal cerebral ischemia. The aim of carotid interventions is to remove the stenosis, thus decreasing the probability of stroke.
Carotid stenosis
ICA/CCA stenosis can be defined using two generally accepted methods defined by two large, multicenter clinical studies. According to the definition by the European Carotid Surgery Trial (ECST), this is compared to the original diameter at the same level. According to the equation of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the narrowest residual lumen diameter is compared to the distal, healthy ICA portion.
The extent of the stenosis is determined with ultrasound, based on flow velocity (it can be slightly modified by morphology).
Symptoms, signs, indications for surgery
The danger of a second stroke is significantly different for symptomatic and asymptomatic carotid stenoses. Carotid duplex ultrasound is often performed due to non-specific symptoms, such as neck pain or vertigo, unconnected to carotid stenosis.
Asymptomatic carotid stenosis
According to a major 2010 study (Asymptomatic Carotid Surgery Trial – ACST), annual stroke risk is 0.7-1.1%/year in the case of asymptomatic, 60-99% ICA/CCA stenoses. Fifteen years ago the risk rate was 2.2%/year (Asymptomatic Carotid Artery Stenosis Study – ACAS). The reason of the 60% decrease in this period is the higher efficacy of drug treatments (e.g. statins). We must ask the question: why is surgery still required if the rate of stroke is this low?
In the majority of cases, even if a stroke leads to significant paralysis, it has no warning or onset symptoms. According to one of the largest studies (ACST), among patients who underwent carotid endarterectomy, the number of strokes occurring within 5 years was halved (6%, including the 3% perioperative stroke rate) compared to patients receiving conservative therapy (12%).
Differences due to the patient’s sex
Based on medium-term follow-ups, it was believed that carotid reconstruction is less effective at decreasing stroke rate in women. However, in ten-year follow-ups, this difference between men and women is no longer present. The reason is that while surgical risk is similar for both groups, the annual stroke risk for women is lower with conservative treatment, and more time had to pass before the preventive effect of the surgery became significant.
More accurate risk estimation for asymptomatic patients
There are several ongoing studies attempting to more accurately determine high-risk groups among asymptomatic patients. In the future, it is likely that only asymptomatic patients with a high risk of embolism will undergo reconstruction.
There are several risk factors that should already be taken into consideration: previous symptoms (more than 6 months ago or associated with previous contralateral stenosis), stroke in the family’s medical history, stenosis progressing rapidly in size, silent ischemia verified with imaging, and embolization verified with transcranial Doppler (TCD). There are intensive ongoing studies as to whether non-invasive methods may be used to screen for plaques that have a high probability of (near) future embolization.
There are a few countries where surgery is not performed on asymptomatic patients, and the size of the stenosis which indicates surgery may differ even between centers (between 60-80%).
Symptomatic carotid stenosis
Symptomatic carotid stenosis usually means a stenosis of over 50% and symptoms implying stroke or TIA within the past 6 months in the area supplied by the carotid artery (middle cerebral artery). These may be: contralateral monoparesis, contralateral hemiparesis, contralateral hemisensory abnormality (paresthesia), dysarthria, dysphagia, aphasia, ipsilateral amaurosis fugax, or blindness. Symptoms not corresponding to carotid stenosis include syncope, vertigo, tinnitus, disorientation, amnesia.
Since the symptoms are usually caused by embolization, if the patient recently had symptoms, they face a significantly higher risk of stroke than asymptomatic patients. The risk of a new stroke exponentially decreases with time since the last symptom. Within 2 days of a TIA, the probability of stroke is 5-8% (this level of risk is approximately equivalent to 10 years of accumulated risk for asymptomatic patients). The stroke rate within two weeks is 11-25%. For this reason, guidelines recommend reconstruction within 2 weeks of TIA or minor stroke, provided there are no contraindications to surgery and the size of the vascular lesion is no greater than one third of the area supplied by the middle cerebral artery (around 3 cm in diameter). Several studies have shown that symptomatic patients who underwent carotid stent implantation had a significantly higher stroke rate than otherwise similar patients who underwent endarterectomy. Therefore, carotid stenting should only be performed on symptomatic patients if open reconstruction is contraindicated. The exact timing of endarterectomy is uncertain for symptomatic patients, due to the increased perioperative stroke rate compared to the already high stroke rate without surgery, as evidenced by several studies.
| Symptoms corresponding to carotid stenosis |
| Hemiparesis (contralateral) |
| Hemihypesthesia (contralateral) |
| Aphasia (dominant hemisphere affected) |
| Ophthalmoparesis |
| Amaurosis (ipsilateral blindness) |
| Other symptoms, particularly of the right hemisphere |
| Neglect syndrome (patient ignores one side completely) |
| Anosognosia (patient does not recognize disease, self-awareness disorder) |
| Asomatognosia |
| Symptoms that are non-carotid in origin (if solitary) |
| Unconsciousness (including syncope) |
| March of sensory deficit |
| Dizziness alone |
| Vertigo alone |
| Dysphagia /dysarthria alone |
| Amnesia alone |
| Bowel or bladder incontinence |
| Visual loss with alteration of consciousness |
| Scintillating scotomas |
| Disorientation alone |
Table 1. Symptoms of corresponding side stroke and TIA
Quality criteria for centers performing intervention
It is important to consider that the guidelines are based on studies usually performed at centers where a high number of interventions is associated with a low rate of perioperative complications. In general, carotid reconstructions should be performed in centers where the perioperative stroke rate is below 3% for asymptomatic patients and below 6% for symptomatic patients.
Restenosis
If a stenosis is detected within 1-2 months of carotid reconstruction at the same site, the commonly used term is residual stenosis. Restenosis from neointimal hyperplasia usually begins 3-6 months after the reconstruction. If restenosis occurs more than 2 years after the surgery, it is assumed to be of atherosclerotic origin.
Currently, no evidence suggests that restenosis detected during follow-up would correlate with a higher ipsilateral stroke rate than the absence of post-surgery restenosis. For this reason, it is debatable whether post-intervention ultrasonography screening has any benefits. The significant progression of stenosis in the contralateral carotid artery is a considerably more common finding during follow-up.
Diagnosis
Auscultation
Auscultation in itself is insufficient for diagnosis and should be considered a screening examination. If risk factors are present (as listed under the topic of screening), auscultation with phonendoscope above the cervical arteries is recommended. If a systolic bruit is detected, further examinations, such as carotid ultrasound, should be performed.
Duplex ultrasound
This is the preferred first-line diagnostic method due to being fast, cheap, and highly accurate, provided the person performing the examination has expertise. It provides information about morphology, as well as various flow velocities. Thus, it is suited for estimating the extent of the stenosis. Its disadvantage is that the method is subjective.
CTA and MRA
These methods are more objective than US, although their availability is more limited; however, in Hungary, CT and MRI are both universally available. Their advantages include that CTA/MRA provide suitable images for the diagnosis of the ischemic lesions of the cranial region and visualizes the blood vessels from the aortic arch to the intracranial vessels. Therefore, CTA/MRA are particularly useful for reconstruction planning. For the reasons above, interdisciplinary consensus recommends both carotid ultrasound and CTA or MRA before carotid reconstruction. If the planned intervention is carotid dilatation/stent implantation, cranial CT or MRI is recommended, as DSA is performed directly before intervention. The disadvantage of CTA/MRA is that these methods require the use of contrast medium, which may have both early and late adverse effects. CT also exposes the patient to ionizing radiation.
Treatment
The treatment of significant carotid stenosis aims at primary (asymptomatic patient) and secondary (symptomatic patient) stroke prevention.
Conservative treatment (best medical treatment, BMT)
It is recommended if the carotid stenosis is under 70% and asymptomatic. It is also the best option if the risks associated with intervention outweigh their expected preventative value, and for this reason, surgery is not performed.
Recommendation: platelet aggregation inhibitors: 100-325 mg aspirin or 1×75 mg clopidogrel and statin administered daily, along with the management of modifiable risk factors. There is no guideline that supports the use of anticoagulants.
Open surgery – carotid endarterectomy
It is recommended to perform surgery only at specialized centers where the risk of perioperative stroke is under 3% for asymptomatic patients and under 6% for symptomatic patients.
The technique of surgery
The first-line treatment is usually carotid endarterectomy, especially in the case of symptomatic patients, due to its more favourable perioperative stroke rate. The majority of surgeries are endarterectomies, the name referring to the removal of the calcified internal layer of the artery.
Potential adverse events include: perioperative stroke (embolization, occlusion), perioperative AMI, cerebral hyperperfusion syndrome, peripheral nerve damage, bleeding, hematoma, cervical hypoesthesia, and restenosis.
There is insufficient evidence concerning intraoperative shunts, the usefulness of neuromonitoring, or the types of anesthesia. Both general and locoregional anesthesia may be used.
Following surgery, lifelong statin and aspirin/clopidogrel treatment is recommended, as well as regular follow-up with regular duplex US scans.
The two main types of open surgery:
Conventional endarterectomy
A longitudinal incision is made from the healthy portion of the common carotid artery (CCA) to the portion of the ICA, followed by open endarterectomy. For wound closing, patch angioplasty yields better results than direct vascular suture.
Eversion endarterectomy
The carotid bulb is transected obliquely at the origin of the ICA. After the formation of a layer, the adventitia is everted and the plaque is removed.
The advantages of eversion endarterectomy are: it does not require patch angioplasty, non-autologous materials are not required (fewer infections and late patch degenerations), less embolization occurs, and late restenosis is less likely. Its disadvantages are: shunting is more difficult, as the endarterectomy must be at least partially completed before the insertion of the shunt, which complicates the securing of the distal intimal step.
Endovascular intervention
Stent implantation and angioplasty are treatment options when the stenosis is over 70%; cardiovascular risk is high; the patient’s medical history includes previous neck surgery or radiotherapy; restenosis has developed in the carotid artery after past intervention; or the patient has a contralateral recurrent nerve lesion.
Although old age should theoretically increase the risk associated with surgery, experience shows that above the age of 80, the stroke risk of endovascular intervention is higher than the risk associated with open surgery. This is likely caused by the calcification of the aortic arch and the proximal CCA segment.
Stent implantation should be performed at interventional centers with high level of expertise. The arterial system may be punctured at the femoral artery, the radial artery, or the brachial artery. Filter protection is recommended by several experts, but no clear evidence is available. Following intervention, 1×75 mg clopidogrel is recommended for a minimum of 1 month, and the patient must receive lifelong aspirin and statin treatment.
Prophylactic carotid reconstruction before general elective surgery
For major non-cardiovascular surgeries, the average perioperative stroke rate is 0.7%. If the patient has at least 5 risk factors (age, coronary disease, renal insufficiency, hypertension, smoking, BMI> 35 kg/m2, COPD, previous TIA), the risk of stroke rises to 1.9%. In these cases, the majority of strokes are ischemic and originate from cardiac embolization.
If the risk of hemorrhagic complications is not too high, ASA and statin treatment should be continued for as long as possible.
Prophylactic vascular reconstructive surgery is not indicated in case of <70% asymptomatic ICA stenosis.
It is not necessary to perform carotid ultrasound for ruling out the possibility of carotid stenosis if there are no indications for carotid screening; that is, if none of the following are present: age over 50 years, smoking, peripheral arterial disease, diagnosed coronary disease, or any past stroke/TIA.
Dissection
Carotid dissection has been continuously increasing in number with an incidence of 2.5‑3/100,000 individuals. In the case of stroke patients, incidence is 2-3% (20% if the patient is under 30), and the incidence is 1.2% if the patient suffered traumatic injury.
Predisposing factors include various connective tissue diseases, fibromuscular dysplasia and minor neck traumas.
Acute symptoms of arterial dissections include:
cerebral ischemia associated with the occlusion caused by the detached intima and the false and true lumens created by the intimal flap
thromboembolism caused by embolus on the intimal flap
cerebral hypoperfusion
The most common symptoms are stroke, TIA, unilateral Horner’s syndrome, accompanied by neck pain and headache.
Carotid duplex US has low diagnostic sensitivity, thus CTA, MRA, possibly DSA imaging is recommended.
Treatment should primarily rely on conservative drug treatment (thrombocyte aggregation inhibitors, anticoagulants). If there are symptoms indicating recurrence, intervention should be considered in the form of stent implantation; however, literature data differs on whether this is necessary.
Aneurysm
Occurrence: 4% of peripheral aneurysms occur in the extracranial carotid system. The disease is diagnosed using carotid US, the most common indication being a palpable pulsatile swelling on the neck. Less commonly, it is diagnosed in connection to neurological symptoms, or due to compressing nearby peripheral nerves and veins. The first-line diagnostic choice is ultrasound, followed by CTA/MRA which are necessary for surgical treatment planning. The usual treatment of an aneurysm is surgical resection and reconstruction, and it should be performed at a specialized center.
Tumor (carotid body tumor, chemodectoma, carotid body paraganglioma)
Carotid paraganglioma is rare and it usually occurs in women aged 40-50. Its main symptom is a slowly growing swelling on the neck. It may be diagnosed using US, CTA, or MRI. It has a distinctive appearance, and imaging morphology provides a certain diagnosis. Hypervascularized tumors may cause life-threatening bleeding during histological sampling. Treatment is usually surgical resection, which should be performed at a specialized center.