Thrombectomy for acute ischemic stroke patients with isolated distal internal carotid artery occlusion: a retrospective observational study

Multiple clinical trials have proven the benefit of endovascular treatment (EVT) in patients with acute ischemic stroke caused by proximal occlusions of the anterior circulation, up to as much as 24 h after stroke onset [1‐4]. For certain patients, however, the benefit of EVT remains unclear. Acute occlusion of the distal intracranial internal carotid artery (ICA) with an open ICA-terminus allows for substantial collateral flow to the middle cerebral artery (MCA) via the circle of Willis, mostly through the anterior communicating artery (ACOM). This occlusion pattern was previously described as “carotid-I occlusion” [5]. Due to the primary collateral flow, the natural history of these occlusions might be more favorable and the benefits of EVT may therefore be limited.

Several arguments can be made to either treat symptomatic patients with carotid-I occlusions with EVT or refrain from intervention and treat with intravenous thrombolysis (IVT) only, if eligible. Collateral flow in symptomatic patients with carotid-I occlusions is apparently not adequate with a risk for the development of watershed infarcts. In addition, proximal occlusion of the anterior choroidal artery branching off at the level of the distal ICA may cause internal capsule infarction, leading to worse outcome [6, 7]. Therefore, revascularization by IVT or EVT might be beneficial. However, early revascularization carries the risk of fragmentation or dislodgment of the clot into downstream territories leading to a more difficult disposition to reopen the territory involved [8]. Finally, symptoms may be caused by lacunar infarcts or distal occlusions not visible on CT-angiography (CTA), rather than the carotid-I occlusion itself. These considerations could be arguments against EVT.

As of yet, little data is available on treatment results in patients with carotid-I occlusions as they form a very small proportion of patients in stroke publications. Only 13% of all patients with carotid occlusions had the “carotid-I” configuration in the MERCI and Multi-MERCI trials [5]. Although patients with a causative occlusion of the ICA or M1 segment should receive EVT according to the current AHA/ASA Guidelines, [9] this recommendation is based on data of seven large EVT trials, where the carotid-I occlusion type was either not studied separately from other distal ICA-occlusions [10‐12] or underrepresented [13]. It is very unlikely that the carotid-I occlusion pattern was prevalent enough to be adequately represented in the treatment effect estimated in these trials, leaving the optimal treatment approach for carotid-I occlusions unclear. Therefore, we aimed to perform an exploratory comparison of EVT versus conservative treatment in patients with carotid-I occlusions.

A total of 51 patients met the inclusion criteria for this study: 41 underwent EVT (40/3352 [1%] of the MR CLEAN Registry patients; 1/500 [0.2%] of the MR CLEAN trial patients), ten did not (4 MR CLEAN trial patients, 6 local cohort) (Online Resource 1). Baseline patient characteristics compared with the overall Registry cohort are detailed in Table 1. Most patients were male (37/51; 73%). IVT was administered in 38 of 51 (75%) included patients. Four patients (8%) were treated with supportive care only. Patients did not receive IVT either due to presentation outside of the 4.5-h time window (5/13 patients [38%]) or due to contra-indications like recent surgery (1/13, 8%) for oral anticoagulation use (7/13, 54%). Baseline characteristics within each group divided by IVT-treatment are shown in Online Resource 2.

This explorative study examining the results of EVT in patients with ischemic stroke due to isolated distal internal carotid artery occlusion (“carotid-I occlusion”) suggests increased rates of functional independence and decreased mortality rates after EVT compared with conservative treatment, including IVT if patients are eligible.

Severe neurological deficits in cases of carotid-I occlusion with crossflow circulation through the circle of Willis and a patent ACA and MCA can be explained by hemodynamic dysfunction of the circle of Willis, leading to watershed infarcts, or by infarction of the anterior choroidal artery territory. Alternatively, neurological deficit in carotid-I occlusion cases may be, at least partially, explained by small cortical thrombi in the distal vasculature. However, CTP in our patients showed perfusion deficits in the entire hemisphere or multiple flow territories, making the observed loss of function more likely attributable to a proximal occlusion. Moreover, rates of functional independence in patients without successful reperfusion were considerably lower than those in patients with successful reperfusion, indicating benefit of successful removal of carotid-I thrombi.

Although EVT is a well-proven indication for large vessel occlusions including distal ICA and MCA occlusions according to most recent guidelines [9], carotid-I occlusion should be considered as a different entity. The risk of treatment is much higher in patients with a patent intracranial circulation due to the risk of distal clot migration than in patients with a complete flow arrest. When clot migration occurred during the procedure, patients in our sample showed poor outcomes. Clot migration rates may decrease over time with evolving interventional techniques, potentially resulting in further improved outcomes after EVT in future patients with carotid-I occlusions. In addition, the exact stroke target can be either restoration of the diminished hemispheric perfusion or reopening of the occluded anterior choroidal territory, occlusion of which might lead to more definitive, irreversible neurological deficits.

Current AHA/ASA guidelines do recommend EVT for patients with intracranial ICA occlusions [9]. However, these recommendations are based on the large EVT trials. Of those, the MR CLEAN (n = 500), ESCAPE (n = 316), and SWIFT PRIME (n = 196) trials only specified carotid-T, carotid-L/T, and carotid-T occlusions in their inclusion criteria, respectively, and did not describe carotid-I occlusion cases separately [10‐12]. In the REVASCAT trial (n = 206), carotid-I occlusions were mentioned as a separate group, resulting in one single patient with this occlusion type included in the control group. Since the intracranial collateral circulation is sustained in carotid-I occlusions through the circle of Willis, a more favorable natural course and smaller EVT benefit may be expected. Hence, the treatment effect of EVT in carotid-I occlusions cannot be concluded from the large EVT trial results.

Previous studies on carotid-I occlusions report on a limited number of patients. First, Liebeskind et al. described nine carotid-I occlusion cases treated with the Merci Retrieval System [5]. They reported a lower rate of functional independence at 90 days of 38%, possibly due to the use of an older generation thrombectomy device. Second, a recent study by Kim et al. assessed treatment results in a Korean population with ICA occlusion and patent collateral MCA flow, with or without additional intracranial occlusions [15]. They included eight patients with carotid-I occlusions treated with medical treatment only and 27 treated with EVT, but unfortunately, no outcome data on the carotid-I subgroup was presented. Third, a recent study in a Japanese population found poorer outcomes in carotid-I occlusion patients with clot migration before or during EVT, corresponding to our observations on clot migration [16].

Good collateral flow through the ACOM or PCOM can effectively sustain the viability of the brain parenchyma without causing any kind of neurological deficit in carotid-I occlusions, as is observed in balloon occlusion testing before permanent occlusion of the ICA to treat carotid aneurysms [17]. Without prior balloon occlusion testing, approximately 70% of patients will remain asymptomatic [17]. Hence, approximately 70% of the general population can be expected to not show any clinical symptoms in case of an acute distal carotid-I occlusion. If a patient presents with an acute neurological deficit and a carotid-I occlusion, this implies hypoperfusion. Hypoperfusion in this setting can be caused by failure of the collateral system, with or without concomitant cortical infarction due to distal thrombi. Patients with more severe strokes at baseline can hence be expected to have more circle of Willis anomalies, as was confirmed in this study’s imaging readings. Even in situations where only minor deficits are present, prolonged hypoperfusion may finally lead to progressive neurological deficits if treatment is withheld [18‐22]. Also, carotid-I occlusions secondary to atherosclerotic plaque may be more challenging technically and lead to less favorable outcome rates compared with carotid-I occlusions of embolic origin [23].

Theoretically, CTP imaging could depict the extent of the territory at risk, pointing to the necessity of urgent revascularization of the distal ICA, even if all intracranial arteries are patent on CTA. CTP could also show perfusion deficits in the internal capsule and other AChA-related territories. Unfortunately, CTP imaging was only available in one third of EVT-treated patients. Hypoperfusion on CTP, as measured by both CBF and CBV, could give support to start EVT, although the results in our patient sample should be interpreted cautiously given that in our population only 6/17EVT-treated patients showed hypoperfusion on CTP.

If no CTP imaging is available, CTA can show lack of enhancement of the choroid plexus, pointing to a perfusion problem in the AChA territory [22]. Presence of a clot at the distal ICA can occlude the origin of the AChA. Emboli or insufficient collateral supply can subsequently cause infarction in the posterior limb of the internal capsule and the basal ganglia parts supplied by the AChA. Ischemia in this territory can lead to severe neurological deficits such as hemiplegia (pyramidal tract), hemianesthesia (thalamus and thalamo-cortical fibers), and hemianopia (optic tract, lateral geniculate body, or geniculo-calcarine tract).

Usually, AChA origin occlusions do not lead to clinical sequelae because of the connections in the choroid fissure with the choroidal branches from the PCA [24]. The tolerance of AChA occlusion correlates with absence of AChA infarction or restriction of ischemia to the medial temporal artery area only [25]. Especially in case of anatomical variations of the AChA and PCA territories (illustrative case), an AChA origin occlusion could lead to enlargement of the ischemic area including involvement of the medial part of the temporal, occipital, and parietal lobes, resulting in a more profound neurological deficit. The illustrative case represents the Takahashi Type 2 variation: an anomalous temporal artery supplying the infero-medial part of the temporal lobe [26].

Several limitations of the current study should be noted. First, although to our knowledge this study describes the largest cohort of patients with carotid-I occlusions published so far, the low number of patients may result in accidental findings. Second, selection bias may have occurred in the non-EVT-treated group due to the retrospective, non-randomized nature of our data: the EVT-treated group was probably selected based on a more favorable profile in their baseline characteristics. We observed a lower age, lower pre-stroke mRS, and lower baseline NIHSS in EVT-treated patients. This could also explain the observation that patients with unsuccessful reperfusion (eTICI 0–1) showed better functional outcome than patients in the non-EVT group. Third, occlusion location was scored on CTA in this study, whereas DSA can more accurately show occlusion pattern and patency of small branches. However, since the decision to treat endovascularly is made based on CTA in daily practice, we believe that this approach is more realistic and clinically applicable. Fourth, we have no data on recanalization status of non-EVT-treated patients, nor post-treatment parameters like blood pressure fluctuation, which was reported to be associated with penumbral tissue loss in non-recanalized patients [27]. Fifth, we excluded patients in whom isolated extracranial ICA occlusions were the cause of stroke. This was done to homogenize our study sample and focus on intracranial carotid-I occlusions, specifically. The patient group with acute ischemic stroke and isolated extracranial ICA occlusions poses a currently relevant clinical topic for further study. Finally, our findings are based on observational data. Ideally, randomized data without selection bias would be necessary to confirm the effect of EVT in patients with carotid-I occlusion and acute neurological deficit, though these data will be difficult to acquire due to the low prevalence of carotid-I occlusions. Our observations can serve as hypothesis generating for future studies on this topic.

In our population, we found overall improved outcomes after EVT in patients with a carotid-I occlusion and acute clinical symptoms, though the patients in our study sample with unsuccessful reperfusion or unsuccessfully retrieved distal emboli after EVT showed poor clinical outcomes. Our data suggest that EVT should be considered in carotid-I occlusion patients, though additional, ideally randomized, research would be necessary to confirm these findings.