Is Artery-artery Embolisation Another Pull Factor For Carotid Endarterectomy In Asymptomatic Patients?

Asymptomatic Internal carotid artery (ICA) stenoses are quite clinically vital, with 2%-9% of the general population found to have asymptomatic stenoses 50%³⁴. Since they can induce shower embolism , with distal embolisation of the thrombus therein, as attested by several case reports^{1 2}. Artery-Artery embolism might result in more devastating consequences than the initial asymptomatic carotid event itself. Due to anatomical cues, the internal carotid artery directly gives the middle cerebral artery (MCA). Middle Cerebral Artery Syndrome, aka occlusion of the artery, can be induced if there is a stenotic lesion at the ICA. It carries high mortality, reaching 28% in a trial³. There is also a possibility of embolisation to the anterior cerebral artery, despite not being as common. Abundant evidence is proffered on whether asymptomatic patients with ICA stenoses should be treated. However, can artery-artery embolisation be another pull-factor?

According to current literature, the Asymptomatic Carotid Emboli Study states that merely 16% of patients with asymptomatic carotid disease has emboli presented, where 13% therein had ipsilateral stroke in a 2-year follow-up period²⁰. No specific literature is found which clearly states the direct relationship between MCA syndrome (and/or ACA syndrome) and ICA stenoses, let alone the prevalence of such a phenomenon. However, artery-artery embolisation cannot be neglected due to its consequences. The severe consequences of MCA occlusion are very well-documented^{9 10 11}, including reduced experience of positive emotions, hemiparesis, sensory loss and ataxia. SH Jang et al¹³ has stated that after complete middle cerebral artery infarction, 70% of patients were able to walk independently but no patient achieved functional hand recovery. Aphasia usually accompanies left hemispheric lesions (presence of Wernicke s and Broca s Areas), whereas anosognosia and sensory neglect occur on the right hemisphere¹². For anterior cerebral artery occlusion, Motor dysfunction (n=91) was recorded as the commonest symptom as stated by a Korean study⁷. Other possible symptoms reported by the study include hypobulia/apathy (n=43), urinary incontinence (n=30) and grasp reflex (n=25). Therefore, the severe effects of arterial occlusion following artery-artery embolisation should also be factored into consideration when deciding if the patient should receive prophylactic treatment.

One might wonder why the MCA is highlighted in such an occasion, since shower embolism can also affect, per logic, the anterior cerebral artery (ACA), which is affirmed by research⁴. Anatomically speaking⁵, the MCA supplies the majority of the lateral hemispheres, apart from the medial portions of the frontal and parietal lobes, as well as the inferior part of the temporal lobe. Lateral lenticulostriate branches from segment M1 also supply the majority of the basal ganglia. This, as contrasted to the more minute vascular territory of ACA, including part of the basal ganglia and the frontal lobes, has highlighted its significance when occluded. It is easier for the MCA to be affected first during shower embolisation from ICA stenoses due to its direct inheritance in trajectory. This is proven by a Neurology article⁷, which states the rareness of ICA-ACA embolisation in ACA occlusion aetiology (n=6/100). The ACAs are also less vulnerable to infarction due to collateral supply through the anterior communicating artery, which is only absent in 5% of patients as identified by surgery⁸. Moreover, MCA infarctions are much more common than ACA infarctions in the first place, as according to a Spanish cohort⁶. The same study shows higher in-hospital mortality rate in MCA stroke as compared to its ACA counterpart (MCA stroke = 17.3%, ACA Stroke = 7.8%). However, as a collective issue, artery-artery embolisation is certainly a factor for concern.

There are three major factors to be accounted when deciding whether to commence on therapy and what type of therapy specifically with regard to the risk of artery-artery embolism: the degree of stenosis, the location of the stenosis, the morphology of the atheromatous plaque.

Furthermore, logically speaking, if the degree of stenosis increases, the chance of stroke increases regardless of territory due to possible artery-artery embolism from an initial atheromatous event. However, controversial data are presented in the literature. AG den Hartog et al²¹ divides patients with asymptomatic ICA stenosis according to the degree of stenosis (50%-99% and 70%-99%) and there is no significant increase in ischaemic stroke risk (hazard ratio, 1.5 95% confidence interval, 0.7 3.5). Inzitari et al³⁵ initially states a positive correlation between stroke risk and degree of asymptomatic ICA stenosis, but the risk decreases for stenotic degrees between 94% and 99%. It is postulated that cardio-embolism might be a mechanism therein. This renders clinical decision-making even more difficult since treatment decisions should also be based on predisposing heart conditions, where the degree of asymptomatic ICA stenosis does not necessarily reflect the likelihood of artery-artery embolisation.

One further note is the location of the carotid stenosis. It is not mentioned much in literature as to the variations of stroke risk with a shift in location of the stenotic event throughout the ICA. The ICA is divided into 7 portions. Due to differences in trajectory and anatomical distances, any C7 stenosis for instance, might bear greater risk of ICA-MCA embolism with respect to C1 or C2. The closer the portion affected is to the Circle of Willis, the higher the probability of which neighbouring vessels are affected. This can hopefully aid clinicians to decide, upon diagnosis of where the stenotic event(s) is/are throughout the ICA, whether treatment is required with additional concern over altered risk of artery-artery embolisation.

Morphology of the atheromatous plaque can influence chances of ulceration and most importantly, artery-artery embolism. Ultrasound is the primary diagnostic modality^{28 36}. A Stroke Journal article³² has stated the limitations of assessing lesion vulnerability of high-risk patients using carotid MRI. Such morphology can be categorised in various ways, one being either homogenous or heterogenous. Homogeneity is defined as where the plaque shows regularity and smoothness whereas heterogeneity, identification of areas of different echogenicity³⁰. Alternatively, A. Gupta et al³³ states there is a significant positive relationship between predominantly echolucent plaques and risk of future ipsilateral stroke (for all stenotic severities: relative risk [RR], 2.31, 95% CI, 1.58-3.39, P<.001). Peak cap stress and thickness of fibrous cap are also deemed as categories of differentiation³¹. Such classification can further stratify asymptomatic patients according to the instability of their atheromatous lesions over the ICA. Treatment can be subsequently given to asymptomatic patients with plaques anchoring high risk of embolisation.

Different treatment modalities can be opted according to individual factors, such as the ones mentioned above. There are three major modalities: medical, stenting and endarterectomy. Since neurosurgery, most notably decompressive craniectomy, is construed alternatively as a modality of final resort, it does not have a major bearing in this case. Generally speaking, it is discovered that, during a mean follow-up period of 3.6 years, a first vascular event occurred in 253 out of 2684 patients with asymptomatic ICA stenosis³⁵. JA Beckman¹⁵ has stated that medical therapy can reduce stroke risk for such patients to approximately 1% per year. Whether this includes the stroke risk incurred from artery-artery embolisation is unknown since most authors focus on eventual internal carotid artery syndrome. Best medical treatment currently includes¹⁶ lifestyle modification, anti-platelet (aspirin as suggested by American guidelines¹⁸), anti-lipid (statin) and blood pressure-monitoring therapy. Of which, a relevant trial¹⁷ highlights the more paramount roles played by antiplatelet therapy and blood-pressure control. Much of the risk highlighted in aggressive medical therapy is presented in the anti-platelet component. Patrono et al¹⁹ records a trial proving that the risk of having major bleeds after aspirin treatment is 1-2 events / 1000 patients, which is double that of the placebo group.

Current guidelines^{24 25} suggest that asymptomatic patients with 60% of ICA stenoses should receive carotid revascularisation, i.e. by either stenting or endarterectomy. However, trials can be conducted to see if the threshold should be lowered in light of other factors possibly contributing to higher artery-artery embolism, like high-risk plaque morphology. There are various trials comparing relative risks and benefits between stenting and endarterectomy in patients with internal carotid artery stenosis. However, very little literature focuses on comparisons of stroke/death risk between medical treatment and either or both of endarterectomy and stenting²⁰. The ACT Trial²² mentions that, for asymptomatic patients with ICA stenoses bearing no high risk of surgical complications, there were no significant differences between endarterectomy and stenting, up to 5 years of follow-up, in procedure-unrelated stroke, all-stroke and death. In a similar trial, CREST²³, investigators have reported that endarterectomy and stenting present with non-significant differences in risk of 4-year stroke or death.

The risks of such treatment modalities should also be taken into account, despite the promising results shown above. Noiphithak R et al²⁶ states that certain factors to be heeded: patient status (especially those with severe cardiac disease) and surgical anatomy for endarterectomy plaque morphology and vessel anatomy for stenting due to elevated risk of distal embolisation during manipulation. Such risks are rather arbitrary since they depend on the expertise of surgeons and individual anthropometric factors, affecting overall benefit of the modality. According to Brajesh K Lal et al²⁹, during a 2-year follow-up period, restenosis and occlusion were infrequent and the rates were similar after carotid stenting and carotid endarterectomy despite there being no differentiation between asymptomatic patients and those who had history of transient ischaemic attack(s) in the cohort. Some risk-calculation scores are established for aiding the clinician to determine if the asymptomatic patient bears high risk of peri-procedural death or stroke, like CEA-8²⁷.

Summarising current literature, there are different studies performed on the relative risks and benefits of medical therapy, carotid stenting and carotid endarterectomy. However, different factors can influence whether a treatment modality should be adopted. Should an asymptomatic patient with 50% ICA stenosis be admitted to stenting / endarterectomy despite its being lower than 60%, the aforementioned threshold? The risk of artery-artery embolisation, especially the devastating effects of MCA occlusion, aka Middle Cerebral Artery Syndrome, should be heeded despite its not being a major aftermath of asymptomatic ICA disease, for instance as compared to direct ICA stroke. The degree of stenosis, plaque morphology and location of the stenotic event mentioned afore are rather crucial in determining the risk of artery-artery embolism. Larger trials can verify and take into account the risks of artery-artery embolism amidst performing different treatment modalities to asymptomatic patients with ICA stenoses, hopefully aiding the clinician to decide whether to initiate, and what type, of treatment as deemed appropriate.