Emergent extracranial internal carotid artery stenting and mechanical thrombectomy in acute ischaemic stroke

Abstract

Objective

Tandem occlusions involving both the extracranial internal carotid artery (ICA) and an intracranial artery typically respond poorly to intravenous (IV) tissue plasminogen activator (t-PA). We retrospectively review our experience with proximal ICA stenting and stent-assisted thrombectomy of the distal artery.

Methods

The data included patients that underwent carotid stenting and mechanical thrombectomy between 2012–2013. Radiographic, clinical, and procedural data were drawn from case notes, imaging records and discharge reports. Clinical outcomes were evaluated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin scale (mRs).

Results

Seven patients, with a mean age of 66.4 years and a mean admission NIHSS of 18.3, underwent this procedure and were included. Each presented with an occlusion of the proximal ICA, with additional occlusions of the ICA terminus (n = 3), middle cerebral artery (n = 5), or anterior cerebral artery (n = 1). Recanalisation of all identified occlusions was achieved in all patients, with a Thrombolysis in Myocardial Infarction (TIMI) score of 3 and a Thrombolysis in Cerebral Infarction (TICI) score >2b achieved in each case. Mean time from onset of stroke symptoms to recanalisation was 287 min; mean time from first angiography to recanalisation was 52 min. Intracranial haemorrhages occurred in two patients, with no increase in NIHSS. There were no mortalities. Mean NIHSS at discharge was 4.9, and mRs at 90 days was one in all patients.

Conclusions

Treatment of tandem extracranial ICA and intracranial occlusions in the setting of acute ischaemic stroke with extracranial carotid artery stenting followed by adjunctive intracranial mechanical thrombectomy is both safe and effective, but further evaluation of this treatment modality is necessary.

Introduction

Despite recent advances in the understanding, management and treatment of acute ischaemic stroke (AIS) it continues to represent a significant challenge, resulting in permanent disability or death. Standard first line therapy for patients presenting with AIS, within 4.5 h of symptom onset, is the administration of intravenous (IV) tissue plasminogen activator (t-PA). Whilst this is the only proven treatment, recent reports in the literature have also demonstrated successful recanalisation using endovascular methods, in particular if there is a large vessel occlusion (LVO) of either the terminal internal carotid artery (ICA) or proximal middle cerebral artery (MCA).¹

Occlusion of the extracranial ICA can also be a significant complication in the setting of AIS, and is most likely due to pre-existing atherosclerotic disease or vascular dissection. Although the combination of cervical ICA occlusion with synchronous intracranial thrombus represents only 8% of all strokes,² such occlusions are shown to be strongly associated with poor patient outcomes; Meyer et al.³ reported a good clinical outcome in only 17% of these types of cases, with a death rate as high as 55%. More recently Kim et al.⁴ reported that, despite receiving IV t-PA, only 30% of patients in this subgroup recovered to a modified Rankin scale (mRs) score of ≤2. There is only a small tendency for proximal ICA occlusions to recanalise under IV therapy:⁵ a thrombolytic-resistant proximal ICA occlusion can limit the exposure of the distal occlusion to thrombolytic drugs because of decreasing regional perfusion pressure and may physically hamper the use of mechanical thrombectomy devices for recanalisation of an intracranial thrombus. Extracranial ICA occlusions also favour stasis in the distal artery bed, increasing the chance of re-thrombosis should treatment of the distal occlusion prove successful.⁶ Historically, the management strategy for this subgroup of patients has been to emergently recanalise the intracranial vessel, either by pharmaceutical or mechanical methods, but to delay intervention to the cervical ICA disease for 4–6 weeks.⁷ However, it is well documented in the literature that these patients are at high risk of early recurrent stroke compared to other subgroups.^8,9 Furthermore, even if intracranial recanalisation is successful, early intracranial reocclusion has been reported to occur frequently and is usually associated with poor clinical outcome.^10,11 Therefore the aim of therapy should be to revascularise and stabilise the cervical occlusion with subsequent recanalisation of the intracranial ICA, particularly if mechanical thrombectomy is considered in managing the intracranial occlusion. This strategy should improve symptoms associated with AIS, prevent possible deterioration and reduce the risk of occlusion, both in the early phase and long term.

Although the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) demonstrated similar short and long term outcomes between the two methods of revascularisation, there was a statistically significant increase in the number of patients who had a peri-procedural stroke during carotid artery stenting (CAS).¹² Therefore, CAS is not widely practised as a method for electively revascularising the cervical ICA. However, emergent CAS is becoming necessary in order to undertake mechanical thrombectomy in patients with tandem extra- and intracranial occlusions. Recently, several studies have reported the successful use of carotid artery stenting (CAS) in the setting of acute ischaemic stroke.^13–20 Few, however, specifically describe CAS with adjunctive distal emergent thromboendarterectomy, and, as far as we know, only two studies have primarily focused on this technique of mechanical thrombectomy.^13,20 In this multi-centre retrospective analysis we describe our experience with proximal ICA stenting with stent-assisted thrombectomy of the distal artery in cases of AIS that presented with acute extracranial ICA occlusion. Mechanical thrombectomy for a distal clot through a more proximal ICA stent can be technically challenging. As such, in this study we attempt to describe our technique whilst assessing its safety and effectiveness with a view to standardise the procedure for operating physicians.

Methods

From 2009–2013, a total of 72 patients underwent endovascular treatment for acute ischaemic stroke in the two centres (58 patients at Leeds General Infirmary and 14 patients at Royal Preston Hospital). Through review of case notes, imaging records and discharge reports we retrospectively collected and analysed the data for seven patients with acute ischaemic stroke due to an intracranial occlusion with significant stenosis or complete occlusion of the extracranial ICA. Furthermore patients were only included if they had subsequently undergone both attempted revascularisation of the extracranial ICA with attempted stent placement and recanalisation of the distal ICA with mechanical thrombectomy of the occlusion.

Clinical evaluation with the National Institutes of Health Stroke Scale (NIHSS) was performed on admission and at 24 h after the procedure. The mRs was evaluated at 90 days along with discharge destination. A good clinical outcome was defined as an mRs of 0–2 whilst a poor outcome was defined at a score of greater than three. Non-contrast computed tomography (NECT) was performed on admission to assess for intracranial haemorrhage and to calculate the Alberta Stroke Program Early CT score (ASPECTS). Computed tomography (CT) angiography from the aortic arch to vertex was performed to assess the intracranial occlusion and the supra-aortic vasculature. Further NECT was performed at 24 h after treatment or sooner if the patient deteriorated clinically.

Patient selection

Patients were included in our analysis if they underwent emergent stenting of a complete or severe extracranial ICA stenosis with subsequent mechanical recanalisation of the intracranial vasculature. Five patients underwent the procedure under general anaesthesia and two procedures were performed under local anaesthesia. An experienced interventional neuroradiologist performed all endovascular procedures.

Endovascular management

The interventional treatment consisted of two steps: extracranial revascularisation followed by intracranial recanalisation.

Extracranial revascularisation

Acute occlusion of the extracranial ICA had been determined on CT angiography. A long 6-Fr guiding sheath e.g. NeuroMax (Penumbra Inc., Alameda, California, USA) was positioned in the distal common carotid artery in all cases. A 0.014-inch micro wire was used to pass the occlusion either on its own or with a microcatheter, inner diameter ≥0.021 in. If a microcatheter was used to negotiate the stenosis an exchange length 0.014-inch microwire was passed through the microcatheter and the microcatheter was then removed. A self-expanding carotid stent was deployed in the region of stenosis or occlusion over the 0.014-inch wire. In one patient there was residual stenosis following deployment of the stent and balloon angioplasty was performed with a 6 × 40-mm PowerFlex balloon (Cordis, Bridgewater, New Jersey, USA). A Wallstent (Boston Scientific, Natick, Massachusetts, USA), EverFlex (eV3 Neurovascular, Irvine, California, USA), Precise (Cordis), or Protege (eV3) was used to stent the ICA. In two cases, 3000 IU Heparin and, in three cases, 500 mg aspirin were administered IV (Aspisol, Bayer, Leverkusen, Germany). Four patients were started on oral dual anti-platelet therapy (clopidogrel and aspirin) 24 h after treatment, two patients were started on clopidogrel alone and one patient was placed on aspirin alone. Clopidogrel was stopped in Patient 7 due to an intracranial haemorrhage.

Intracranial recanalisation

Once extracranial revascularisation was achieved the intracranial vasculature was imaged to determine the extent of further ICA or MCA occlusion. Since an exchange length 0.014-inch microwire was already in position distal to the cervical ICA stent, a microcatheter could be advanced over the microwire and then the long sheath 6-Fr neuromax sheath (Penumbra) or a 6-Fr guide catheter (Envoy (Cordis) or Neuron (Penumbra)) was positioned in the infrapetrous ICA distal to the stent. In some cases the neuromax was negotiated through the stent with ease over the stent delivery system or use the Powerflex angioplasty balloon to support the neuromax to pass across the stent into the distal ICA.

Mechanical thrombectomy was undertaken using either a Solitaire AB/FR stent (eV3 Neurovascular, Irvine, California, USA) or a Revive stentriever (Codman Neurovascular, Raynham, Massachusetts, USA). Regardless of the stent system used a microcatheter with an inner diameter ≥0.021 in was navigated with a 0.014-inch microwire across the occlusion. The stent was then advanced through the microcatheter and deployed within the thrombus via partial withdrawal of the microcatheter. We allowed up to five minutes for the stent to migrate into the thrombus and then retrieved the stent/microcatheter system under continuous aspiration into the long 6-Fr sheath or 6-Fr guide catheter. When necessary these steps were repeated in order to achieve complete recanalisation.

Intracranial Thrombolysis in Myocardial Infarction (TIMI) and Thrombolysis in Cerebral Infarction (TICI) scores were assessed pre- and post-recanalisation. Successful recanalisation was defined as a TIMI score ≥2 and a TICI score ≥2b. Both TIMI and TICI scores have been included because the TIMI scale best reflects recanalisation of the occluded vessel, whereas the TICI scale best reflects the reperfusion of the distal vascular bed.²¹

All patients underwent post-treatment CT scan at 24 h post procedure or sooner if symptoms deteriorated, to assess for intracranial haemorrhage or other treatment related complications.

Results

Table 1 provides an overview of the patient population and their clinical outcomes. The mean NIHSS score on admission was 18.3 ± 5.6, and all patients had a score of at least 10. The time from stroke onset to the deployment of the cervical ICA stent was 287 ± 61.6 min, and the time to both extra- and intracranial recanalisation was 258 ± 62.6 min. Intracranial haemorrhage occurred in two cases, but neither resulted in a decrease in NIHSS score. Mean procedural duration (time between first and final angiographies) was 85 ± 35.6 min, with a range of 38–152 min. Complete recanalisation of all identified occlusions was achieved in all patients.

Table 1.

Overview of patient population and outcomes.

Age/years	66.4 ± 10.7 (50–82)
Female	2/7
NIHSS score on admission	18.3 ± 5.6 (10–26)
Time from stroke symptom onset to recanalisation/min	287 ± 61.6 (204–351)
Time from stroke symptom onset to ICA lesion crossing time/min	258 ± 62.6 (174–328)
Time from first angiogram to recanalisation/min	52 ± 14.9 (30–75)
Overall recanalisation (extracranial and intracranial)	7/7 (100)
Mortality at 90 days	0/7 (0)
Intracranial haemorrhage	2/7 (29)

ICA: internal carotid artery; NIHSS: National Institutes of Health Stroke Scale. Values as mean ± standard deviation (SD) (range), n/N and n/N (%).

Table 2 is a more comprehensive summary of the clinical characteristics, treatments and outcomes of the patients. The patients' medical histories were examined for any comorbidities relevant to acute ischaemic stroke – namely atrial fibrillation, hypertension, smoking history, hypercholesterolaemia and diabetes mellitus. Two patients had previous strokes: Patient 2 suffered an acute ischaemic stroke while being hospitalised for a series of transient ischaemic attacks, Patient 7 had suffered ischaemic stroke 20 years prior. A 90 day mRs score was measured at one in all seven patients, representing an excellent clinical outcome in all cases. There were no procedural complications and no thromboembolic complications due to emergent extracranial stent placement.

Table 2.

Clinical characteristics, treatments, and outcomes.

Patient no. (age/sex)	Comorbidities	Stroke history	NIHSS at admission	Occlusion site	IV t-PA	Cervical ICA stent size/mm	TIMI post-procedure	TICI post-procedure	NIHSS at discharge	Length of hospital stay/days	Discharge destination	mRs score at 90 days
1 (64/M)	E	None	21	L ICA and L MCA	Yes	Wallstent, EverFlex 7 × 50a	3	3	6	15	Home	1
2 (66/F)	HTN, S, HC	Several TIAs	23	L ICA and L tICA	No	EverFlex 8 × 60	3	2b	4	35	Home	1
3 (82/F)	HTN, E	None	14	L ICA and L M1	No	Precise 8 × 40	3	3	6	5	Home	1
4 (59/M)	S	None	10	R ICA and R tICA	No	Precise 8 × 30	3	3	0	1	Home	1
5 (50/M)	S	None	26	L ICA, L tICA, and LMCA	Yes	Precise, Protege 8 × 40a	3	3	2	10	Stroke rehabilitation centre	1
6 (63/M)	E	None	19	R ICA and R MCA	No	Wallstent 9 × 40	3	3	10	35	Stroke rehabilitation centre	1
7 (81/M)	None	1	15	L ICA, L MCA, L M2, and L A2	No	Wallstent 9 × 40	3	3	6	4	Stroke rehabilitation centre	1

E: ex-smoker; HC: hypercholesterolaemia; HTN: hypertension; ICA: internal carotid artery; IV: intravenous; L: left; MCA: middle cerebral artery; mRs: modified Rankin scale; NIHSS: National Institutes of Health Stroke Scale; R: right; S: smoker; TIA: transient ischaemic attack; tICA: terminal internal carotid artery; t-PA: tissue plasminogen activator.

^aIndicates 2^nd cervical ICA stent deployed after intracranial reperfusion.

Figure 1 shows an overview of NIHSS, TIMI scale, TICI scale and mRs on admission and at discharge.

Figure 1.

Angiographic data and clinical outcomes. On admission, none of the patients had achieved Thrombolysis in Myocardial Infarction (TIMI) or Thrombolysis in Cerebral Infarction (TICI) scores of three. At discharge, 100% patients had achieved a TIMI score of three and 85.7% (6/7) had achieved a TICI score of three, with one patient scoring 2b. Mean National Institutes of Health Stroke Scale (NIHSS) score dropped from 18.3 on admission to 4.9 at discharge. A 90-day modified Rankin scale (mRs) score ≤2 was achieved in 100% of patients.

Illustrative case

A 66-year-old female (Table 2, Patient 2) presented with left hemisphere recurrent transient ischaemic attacks in the previous 24 h. Carotid Doppler ultrasound demonstrated 70–90% left proximal ICA stenosis and she was admitted for urgent carotid endarterectomy. Sudden progression in clinical symptoms progressed with an unresolving right hemiplegia, aphasia and NIHSS score of 23. The CT scan demonstrated a hyperdense left middle cerebral artery (Figure 2(a)) and ASPECTS score of eight.

Figure 2.

A 66-year-old female presented with crescendo transient ischaemic attacks with sudden onset persistent right hemiplegia and aphasia with a National Institutes of Health Stroke Scale (NIHSS) score of 23. (a) Non-contrast computed tomography (CT) scan demonstrates hyperdense left middle cerebral artery. (b) Catheter angiography shows severe stenosis involving the left internal carotid artery (ICA) which was treated with (c) emergent placement of a 8 × 60 mm Everflex stent. (d) Catheter angiography post stenting demonstrated occlusion of the distal internal carotid artery involving the left A1 and M1 segments (T-occlusion). (e) Post thrombectomy catheter angiogram shows subsequent recanalisation of the left anterior circulation using mechanical thrombectomy.

The patient was placed under general anaesthesia. Diagnostic angiogram confirmed severe stenosis of the left cervical ICA (Figure 2(b)). Emergent carotid stenting was undertaken placing 8 × 60 mm EverFlex stent (eV3) (Figure 2(c)). Subsequent balloon angioplasty also occurred due to persistent stenosis using a 6 × 40 mm PowerFlex balloon (Cordis). Angiography demonstrated a distal ICA occlusion involving both the A1 and M1 segments (T-occlusion) (Figure 2(d)). Mechanical thrombectomy was performed using a 4.5 × 22 mm Revive stent (Codman) which was retrieved under continuous aspiration. A TIMI score of three was achieved with TICI score of 2b due to a delay in parenchymal phase on angiography (Figure 2(e)). Administration of 3000 IU heparin was carried out intravenously during the procedure. The patient awoke with an NIHSS of four.

Dual anti-platelet therapy was commenced at 24 h with 40 mg aspirin and 75 mg clopidogrel. No neurological deficit was seen after the procedure with a mRs of one at three-month follow-up.

Discussion

Severe extracranial carotid disease is ubiquitous in cases of acute ischaemic stroke, accounting for 20% of them. Ten percent of such cases present with acute carotid occlusion. However, only 8% of acute strokes are caused solely by carotid disease, and they are more frequently associated with ipsilateral intracranial occlusions.² These can be distal emboli of associated atheromatous ICA occlusions. Extracranial carotid disease is even more significant in ischaemic stroke patients of ages 16–45 years, with spontaneous carotid dissection causing 10–25% of such cases.²²

More proximally arising intracranial occlusions have been shown to be strongly associated with poor outcomes in patients presenting with acute ischaemic strokes, with ICA ‘T-lesions' in particular predicting the poorest outcomes amongst anterior circulation stroke syndromes.²³ Independently, intracranial ICA occlusions have a poor natural history, carrying a mortality rate of 73% if attempts at recanalisation, either intravenous or endovascular, are unsuccessful.²⁴ Distal intracranial occlusions have been associated with somewhat better outcomes: 34% and 40% of M1 and M2 occlusions respectively result in a mRs score of ≤2 at six months, with 24% mortality.²⁵ Nevertheless, synchronous extracranial ICA occlusions compound the natural history of independent intracranial occlusions, regardless of occlusion site, resulting in poorer outcomes.

Standard first-line treatment for stroke patients is the administration of IV t-PA within 4.5 h of stroke onset. However, results have been far from successful; a meta-analysis of articles assessing vessel recanalisation revealed that IV t-PA achieved only a 46.2% recanalisation rate.²⁶ Even when the treatment is delivered swiftly post-onset, reocclusion occurs in 34% of patients.²⁷ The results of IV t-PA in acute ischaemic strokes involving carotid disease are even poorer. Complete recanalisation with IV t-PA occurred in only 9% of cases with tandem cervical ICA/MCA occlusions, as opposed to 39% in cases of sole MCA occlusion.⁴ This is likely because ICA occlusions can limit the exposure of the distal clot to thrombolytic drugs by decreasing regional perfusion pressure. Extracranial ICA occlusions also favour stasis in the distal arterial bed, increasing the chance of re-thrombosis should treatment of the distal occlusion prove successful. In strokes caused by MCA occlusions, ipsilateral severe carotid artery disease independently predicted reocclusion after IV t-PA induced recanalisation, occurring in 66% of such cases.⁶ Should lasting recanalisation be achieved with IV t-PA, only 30% of tandem ICA/MCA cases were found to have a mRs score of ≤2 after 90 days.⁴ Compounding this is the fact that ICA occlusions themselves have lower rates of recanalisation than either middle cerebral artery (MCA) or posterior circulation occlusions in all treatment methods.²⁸ As such, only 2–12% of ischaemic stroke patients with ICA occlusion achieve favourable outcomes, with 40–69% of them having severe neurologic deficit.¹⁵

Recent studies on endovascular treatments for acute ischaemic stroke have not been entirely promising. The Prolyse in Acute Cerebral Thromboembolism II (PROACT II) randomised clinical trial showed that intra-arterial (IA) prourokinase had significantly better recanalisation rates and outcomes vs. IV heparin with treatment within six hours of stroke onset.¹ However, the Local vs Systemic Thrombolysis for Acute Ischaemic Stroke (SYNTHESIS Expansion) trial demonstrated no significant difference in outcomes between patients treated with IV t-PA and those treated with endovascular therapies (IA t-PA and/or mechanical thrombectomy).²⁹ The Interventional Management of Stroke III (IMS III) trial randomly assigned patients that had already received IV t-PA within three hours of onset to either receive further IV t-PA or endovascular treatment. This study was ended early as there was no significant difference in the proportion of patients that achieved a mRs ≤ 2 after 90 days between treatments.³⁰ The results did, however, suggest that additional endovascular treatment may be more effective than IV treatment alone in cases of large vessel occlusion.¹ Furthermore, the Mechanical Recanalization and Retrieval of Stroke Clots Using Embolectomy (MR RESCUE) trial, which randomly assigned patients with large vessel occlusions in the anterior circulation to either mechanical embolectomy or IV t-PA up to eight hours post-onset, found no difference in mean 90 day mRs.³¹

However, the SYNTHESIS Expansion, IMS III, and MR RESCUE trials all have significant limitations to their general applicability. Khalessi et al.³² state that randomised control trials assessing the effectiveness of IV vs IA therapies must meet three key requirements: the determination of LVO prior to randomisation, the administration of standard IV t-PA therapy to all patients, and that thrombectomy methods must meet modern standards and have adequately documented revascularisation rates. None of the three trials meet all of these criteria. Only MR RESCUE demonstrated the presence of LVO in patients before randomisation – in SYNTHESIS, vessel occlusion was not even an inclusion criterion. Modern stentriever devices were used infrequently or, in the case of MR RESCUE, not at all. The trials instead relied mostly on the older Merci Retriever and Penumbra System thrombectomy devices.^29–31 In IMS III, many IA patients received lower than standard ‘bridging' doses of IV t-PA, and IV t-PA was withheld completely to IA patients in SYNTHESIS.³² There are other drawbacks to these studies as well; possible differences in outcome between patients selected via computed tomography angiography and those via magnetic resonance angiography were not taken into account in SYNTHESIS,²⁹ and time from onset to groin puncture was over six hours in every case in MR RESCUE.³¹ A recent review of 32 studies including 1107 patients concluded that rates of recanalisation and good clinical outcome are higher when AIS due to extra- and intracranial occlusions are treated with stenting and mechanical thrombectomy, as compared to IA thrombolysis.³³

Stent-assisted revascularisation has been reported to be more successful than other endovascular therapies in several studies.²⁷ Stentrievers have reported recanalisation rates of 62–100%, while Merci and Penumbra devices have recanalisation rates of 46–69% and up to 82% respectively. The older devices also have worse rates of good outcome (mRs ≤ 2): 36% and 25% respectively, as opposed to 50% with stentriever technology. The safety of these devices is also well established; rates of symptomatic intracranial haemorrhage (SICH) are only 6–9% in larger-scale studies. The higher rate of 16–20% in smaller series is likely due to relative experience of the interventional teams. Higher rates of SICH are also associated with the use of peri-procedural anticoagulants, which we avoided in our patient group.³⁴

Several studies have shown high rates of carotid recanalisation (83–100%) and clinically good outcomes with CAS in cases of carotid occlusion in acute ischaemic stroke.^13–20 Several of these studies also encountered ipsilateral intracranial occlusions, and either IA pharmacological thrombolysis, mechanical thrombectomy, or a combination of the two, were performed to the distal embolus. Mechanical methods included balloon angioplasty, stent-assisted emergent thrombectomy, aspiration, and the placement of distal filter-type protection devices.^{13–16,19,20} Table 3 compares the results of tandem occlusion treatment in these studies, excluding results for patients with single occlusions. Our results compare favourably to these attempts at adjunctive endovascular treatment to carotid artery stenting; however we have restricted ourselves to only using mechanical stent retrievers only in our patients. None of our patients received any IA thrombolytic treatment. Our higher rates of recanalisation and good clinical outcomes may, in some cases, be due to the use of more advanced thrombectomy devices. Papanagiotou et al.¹⁹ reported 18 patients with tandem ICA and intracranial occlusions. Nine of these distal occlusions were treated with the Penumbra System, while the other nine were treated with the newer Solitaire stentriever device in a procedure similar to our technique. Only three of the nine (33%) treated with the Penumbra devices achieved recanalisation of TIMI ≥2, whereas this was achieved in 100% of those treated with the Solitaire devices. Other studies, such as Jovin et al. and Dabitz et al.,^14,16 that used balloon angioplasty instead of newer stent-assisted thrombectomy devices had lower recanalisation rates, leading to poorer clinical outcomes.

Table 3.

Comparison of treatment of extracranial internal carotid artery (ICA) occlusion and distal intracranial occlusion in acute ischaemic stroke.

Study	n	Mean NIHSS on admission	Treatment of proximal occlusion	Treatment of distal occlusion	Recanalisation rates	Definition of good clinical outcome	Clinical outcome
Mishra et al., 2014	7	18.3	CAS	Stent-assisted thrombectomy	TIMI 3 and TICI ≥2b in 100%	90 day mRs ≤ 2	100%
Cohen et al., 2014	24	20.4	CAS	Stent-assisted thrombectomy with balloon angioplasty	TIMI 3 and TICI ≥2b in 79%	6 month mRs ≤ 2	70%
Stampfl et al., 2014	24	18a	CAS	Stent-assisted thrombectomy	TICI ≥2b in 63%	90 day mRs ≤ 2 or NIHSS improvement of ≥10 points	33%
Dalyai et al., 2013	11	18	CAS	Merci Retriever or Penumbra System or balloon angioplasty or IA thrombolysis	Not published	30 day mRs ≤ 2	36%
Papanagiotou et al., 2012	18	17.2b	CAS	Penumbra System or Solitaire stentriever	TIMI ≥2 in 67%	90 day mRs ≤ 2	41%b
Dabitz et al., 2007	7	21.7	CAS and/or balloon angioplasty	IA t-PA or balloon angioplasty	TIMI 3 in 43%	mRs ≤ 2 at follow-up (5–72 weeks)	88%b
Jovin et al., 2005	11	16.8	CAS	IA t-PA or balloon angioplasty	Partial or complete recanalisation in 60%	30 day mRs ≤ 2	18%

CAS: carotid artery stenting; IA: intra-arterial; n: number of patients with proximal ICA occlusion and distal intracranial occlusion; mRs: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; TICI: Thrombolysis in Cerebral Infarction; TIMI: Thrombolysis in Myocardial Infarction; t-PA: tissue plasminogen activator.

^aData presented as median value, ^bdata includes values for study patients without tandem occlusions.

The studies which used techniques most similar to ours were Stampf et al.²⁰ and Cohen et al.¹³ Stampfl et al. released a series of 24 patient cases with tandem extracranial ICA and intracranial occlusions. Twenty-one of these patients underwent a similar procedure to that which we describe, with three patients undergoing ICA stenting after intracranial thrombectomy. As well as poorer recanalisation rates and clinical outcomes (median 90 day mRs was 3.0), their rate of SICH was also higher, with four cases resulting in one death. This is likely related to the fact that 22 of 24 patients received bridging IV thrombolysis, and that GPIIb/IIIa inhibitors (tirofiban or clopidogrel) were administered before stent placement. They also reported a much longer time to recanalisation (89.8 min).

Cohen et al.,¹³ also in 2014, released a series of 24 patients with extracranial ICA and intracranial tandem occlusions. This team also employed a similar technique to ours, although there are some key differences. In all cases, balloon angioplasty was used to dilate the cervical lesion before stenting, and a distal filter-type protection device was deployed in some cases. In 14 cases, balloons were again used to dilate the cervical occlusion after stent deployment, so as to minimise risk of the distal stent retriever entangling in the carotid stent. There is also a difference in post-procedural anti-platelet regimes; Cohen et al. used a 300 mg loading dose of clopidogrel. The mean time to recanalisation was 51 min. Of the patients, 58% scored <6 NIHSS points after a mean NIHSS on admission of 20.4, and 14 of 20 patients presented with a six-month mRs of 0–2. There were two deaths, both unrelated to the stroke treatment, and two patients had not reached their six-month follow-up. No cases of SICH were reported. These results compare favourably to those reported by Stampf et al., although we report better recanalisation rates and clinical outcomes.

In 2014, Kwak et al.¹⁷ reported a series of 50 consecutive patients with single intra- and extracranial ICA occlusions. Although not directly applicable to the setting of tandem extra- and intracranial occlusions, this study did show excellent results, with successful recanalisation (TICI ≥ 2) achieved 90% of cases and a good clinical outcome (mRs ≤ 2) achieved in 60%. Kwak et al. also demonstrated correlations between good clinical outcome and NIHSS on admission, whether the occlusion was atherosclerotic or cardioembolic in origin, and the location of the lesion in the ICA. Our series is unique as all patients underwent stenting of the ICA bifurcation and mechanical thrombectomy of the intracranial thrombus. We achieved good recanalisation rates and outcome compared to other studies. This is indeed very promising as many of these patients have high NIHSS scores, likely resulting in poor clinical outcomes had they not been offered endovascular treatment. Some operators may consider placing a stent after removing the clot and achieving intracranial perfusion. This may well be another option but we have preferred to stent the carotid prior to thrombectomy. We do not believe this increases the time for intracranial reperfusion significantly and in fact allows us to maintain a stable platform to achieve multiple passes for mechanical thrombectomy if needed through the guide catheter or guide sheath distal to the stent.

Antiplatelet regimen can be tricky in patients with ICA stenting and has been considered as an argument against stenting in AIS patients. This has been random and has been different depending on individual patient condition. Five patients (Patients 1–5) received intravenous aspirin on table following carotid stent placement. Two patients (Patients 1 and 5) had received IV thrombolysis in our group. Dual antiplatelet regimen or single platelet medication was started after 24-hour CT showed no evidence of bleed. Caution however needs to be encouraged regarding antiplatelet regimen in this group of patients. Encouragingly no patient developed thromboembolic complications due to emergent cervical stent placement.

Our method carries risks and drawbacks common to all endovascular and stent-based interventions. The IMS III trial confirmed the overall safety of endovascular interventions, as there was no increase in peri-procedural complications; even patients without large vessel occlusion or with prior successful recanalisation with IV t-PA underwent endovascular treatment.¹ However, the risk of distal perforation is naturally higher than with IV thrombolysis, and multiple passes with thrombectomy devices may induce vascular microdissections.³⁵ There is a risk of acute to mid-term stent failure, as well as the increased risk of haemorrhagic transformation of any infarcted brain tissue resulting from the anticoagulant and antiplatelet drugs required after stent placement.²⁷

Our study is limited in its retrospective nature, and also in the extremely small sample size. Non-random patient selection carries with it an inherent selection bias. As such, caution must be taken when interpreting our data and comparing our outcomes and results with patient groups in other studies, especially when many other articles describing CAS are also retrospective, small-series studies. Our aim has been to describe a standardised technique to ensure that endovascular treatment can occur as soon as possible with minimal delay in both proximal revascularisation and distal recanalisation. We feel that the combination of extracranial CAS followed by adjunctive intracranial mechanical thrombectomy is a safe and promising treatment modality, but large-scale randomised controlled trials are needed for it to be fully accepted.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflicts of interest

None declared.