Discussion
Our study has demonstrated how changes in the patency of the SAV influence the spread of emboli in intracranial vessels through the communicating arteries. When all the SAVs were open, the overall rate of occurrence of emboli in the ipsilateral ACA territory was more than twice that in the PCA territory (29% vs 11%), and the occurrence of emboli crossing from one hemisphere to the other was a very uncommon event (1%). As a rule, occlusion of one CA during recurrent embolism significantly increased the rate of emboli crossing the midline. When the embolic source was a carotid occlusion with normal contralateral CA, the overall rate of ipsilateral ACA emboli decreased to the level of the PCA emboli and the likelihood of floating ICA thrombi increased (11%). In general, contralateral events required at least one previous anchorage in the ipsilateral MCA and were very unlikely unless one of the carotid arteries was occluded. In fact, they were most frequent when the contralateral CA was occluded and embolisms occurred through the normal lumen ipsilateral CA (37%, including contralateral ACA and MCA embolisms). In addition, an important observation in our study was that none of the emboli in the ACA occurred as a first lodge in any of the SAV conditions tested. This was also true for the PCA in the vast majority of cases.
The overall percentage values for emboli that we have found may appear high. However, studies of cerebral infarctions in animals using transcranial ultrasound have not detected lower occurrences of intracranial emboli.19 Moreover, the clot analogues used in this study were rich in RBC, which have a lower fracture toughness than fibrin-rich thrombi.18 This allowed us to produce multiple emboli from fractures of a single clot.
Consistent with the reduced rate of ipsilateral ACA involvement of emboli from an occluded carotid recorded in our study, Bogousslavsky observed sparse ACA territory infarction in patients with ipsilateral carotid occlusions (>90%) and multiple infarcts.20 One potential explanation may be the direction of flow in the A1 segment at the time embolism occurs. Reverse flow in the A1 segment to offset high-grade CA stenosis could potentially reduce ipsilateral ACA embolisms by making navigation against the flow more difficult for emboli.21 On the other hand, augmented anterograde flow in the ipsilateral A1 segment through the ACoA might facilitate ACA embolisations. This could explain why previous analyses of stroke distribution in patients have reported a higher incidence of ACA embolisms in the presence of contralateral CA stenosis or, functionally similar, contralateral A1 segment hypoplasia of the ACA.2 22 23 Our findings also support this hypothesis, with higher rates of ACA emboli being recorded when the acute multiple embolisms occurred contralateral to an occluded CA.
There have been a few reports of isolated embolisms in the ACA or PCA.15 Both distal occlusions can exhibit typical symptoms of MCA occlusion. Therefore, it may be difficult to attribute neurological symptoms to one artery or the other.24 25 Our results suggest that embolisms from the anterior circulation to ACA or PCA territories should not occur without at least one prior embolism in the ipsilateral MCA territory. Regardless of how they arrive, whether from the opposite hemisphere via the ACoA or from downstream, emboli are less likely to spontaneously dissolve in cases of restricted anterograde flow, that is, proximal arterial stenosis.16 26 This implies that in the case of bihemispheric emboli, those lodged in a hemisphere devoid of stenosis are more susceptible to lysis. Additionally, the speed of neurological recovery in patients after arterial recanalisation varies.27 28 These factors may also mask the underlying stroke aetiology in patients with multiple acute strokes and CA stenosis. In this respect, patients with a high initial National Institute of Health Stroke Scale (NIHSS) score and a single distal embolus in the ACA or PCA on imaging may still have some residual or transitory neurological symptoms from a rapidly recanalised concomitant MCA occlusion. It is unclear whether overlapping symptoms, missed infarcts on imaging or difficulties in identifying or allocating transient symptoms could contribute to possible underestimation of concomitant infarction in the MCA territory.
Our results suggest that a causal association between isolated ACA occlusion and ipsilateral extracranial CA occlusion should be approached cautiously and all other differential diagnoses considered. Furthermore, additional supporting evidence such as simultaneous ischaemia in the ipsilateral MCA territory would be helpful since in our experimental study there was no ACA involvement without prior MCA embolism. Although uncommon, it has implications for the medical therapy for acute stroke as well as for the indications and performance of mechanical thrombectomies. It is crucial to evaluate all possible routes for intracranial embolism. Endovascular procedures can be challenging in cases where chronic extracranial occlusions of the CA are asymptomatic and do not directly cause embolisms. In some cases, anterograde access through the occlusion might not be possible. Alternatively, a complex vascular access route from the opposite cerebral circulation through the small communicating arteries might be required, thereby increasing the risk of severe complications.29
Limitations
This experimental study has several limitations. The study did not explore the variations of the circle of Willis, which would undoubtedly affect the distribution of intracranial emboli. Although there was similar clot frangibility depending on the production method, there were more clot fragments when the embolic source was contralateral to carotid occlusion. While several factors could contribute to this variation (the force applied in clot injection, unnoticed variations in pump flow), the anatomical condition tested and the associated flow distribution provide a reasonable explanation. In a closed vascular model like ours, the spared flow from the contralateral carotid occlusion would be distributed to the other patent SAV, which might result in higher anterograde flow and contribute to mechanical clot fragmentation. Clot fragmentation in our study occurred as the clot passed from the common to the ICA, especially at the carotid siphon level. Differences in the tortuosity of the terminal ICA or the outflow angles of the ACA and the MCA could also affect outcomes.30 Moreover, fluctuations in the standard pump velocities used in this study could potentially influence the total count of fragments generated or, to a lesser extent, the intracranial distribution of the emboli.
We reported all macroscopic clot fragments that were anchored in the model, including recurrent emboli in the same vascular territory. Thus, the overall percentages of embolus lodges should be interpreted with caution. Microemboli were not monitored or assessed. Moreover, working with highly frangible RBC-rich clots might underestimate the rate of terminal ICA occlusion, which could in turn influence the incidence of PCA emboli in our study. Furthermore, no assessment of cerebellar emboli from the anterior circulation was feasible, in that only the vertebral arteries and both PCoA and PCA were modelled.
The histology of thrombi from carotid plaques may differ from the red thrombi used in this study, which could affect their tendency to fragment. The study focuses on assessing the haemodynamics and successive anchoring of thrombi, which may vary depending on various factors, including histology. Therefore, replication of this experimental study with other clot types or other pump hemodynamics could change the results.17