Abstract
Objective
Symptomatic non–acute intracranial arterial occlusion (NAICO) is not uncommon. We report a single-center experience of the feasibility and safety of endovascular treatment of anterior circulation NAICO and summarize the outcomes of patient groups with successful or failed recanalization.
Methods
Patients who underwent endovascular therapy for intracranial arterial stenosis between January 2010 and May 2017 were retrospectively reviewed. Thirty-eight patients with symptomatic NAICO (symptom onset > 24 hours) in the anterior circulation were identified.
Results
Successful recanalization was achieved in 76.3% of patients (29/38). Intraprocedural events occurred in 10.5% (4/38), including intima dissection (n = 1), parent artery rupture (n = 1) and acute in-stent thrombosis (n = 2).
Mean follow-up duration after successful recanalization was 36.5 months. One patient died 68 days after the procedure because of a newly developed posterior circulation stroke. Acute reocclusion was observed in two patients (6.7%); subacute or delayed reocclusion was observed in three patients (10%). Good final outcome (modified Rankin Scale score ≤ 2) was achieved in 25 of 28 patients (89.3%) at three months.
Mean follow-up duration of the nine patients with failed recanalization was 41.4 months. Three patients underwent extra–intracranial bypass for worsening symptoms. The other six patients showed stable or improved neurological status with antiplatelet medications. Good final outcome was achieved in eight of nine patients (88.9%) at three months.
Conclusions
Endovascular revascularization can be a viable option with an acceptable safety profile in selected patients with symptomatic NAICO in the anterior circulation. Further characterization of aborted cases would facilitate proper patient selection for endovascular treatment.
Keywords: Intracranial occlusion, outcomes, stenting
Introduction
Atherosclerotic intracranial arterial steno-occlusive lesions are common causes of stroke and are associated with a high risk of recurrent stroke.1 Although the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial failed to reveal the safety and effectiveness of angioplasty and stenting for symptomatic intracranial atherosclerotic disease (70% to 99% stenosis),2 we still encountered cases with subacute or chronic intracranial steno-occlusive lesions in need of endovascular recanalization.
In the endovascular management of symptomatic intracranial steno-occlusive lesions, non–acute intracranial arterial “occlusion” (NAICO) may have less need of revascularization because of a high likelihood of collateral formation compared with intracranial “stenosis.”3 Moreover, recanalization of the completely occluded artery would be more difficult and associated with a high incidence of procedural complications; the reopened segment would be more prone to restenosis even after successful recanalization.4–6 Currently, no consensus exists on the optimal treatment of intracranial non–acute occlusive disease, especially in the setting of an evolving infarct and worsening symptoms with perfusion-diffusion mismatch on magnetic resonance imaging (MRI).3,4 Several studies on endovascular recanalization of subacute or chronic intracranial occlusion have been reported with acceptable safety profiles.4–9 However, the sample size in these studies was relatively small with a mixture of anterior and posterior circulation, and most patients were reported with successful vessel recanalization.4,6 Therefore, we cannot get instructional information for patients with failed recanalization of the occluded vessel as to whether best medical management or extra–intracranial bypass would be the priority choice for them.
In this study, we report a single-center experience on the technical feasibility and safety of endovascular treatment of symptomatic NAICO in the anterior circulation, together with the mid-term outcomes of patient groups with successful or failed recanalization.
Methods
Study population
NAICO was defined as angiographic complete atherosclerotic occlusion of an intracranial artery, with ischemic symptom duration longer than 24 hours from the time last seen well. We retrospectively reviewed our prospectively maintained database of patients who were intended to undergo endovascular recanalization of intracranial vessels between January 2010 and May 2017. Patients with NAICO of the anterior circulation, including distal internal carotid artery (ICA), middle cerebral artery M1 and M2 segments, were identified. Before the procedure: (1) diffusion-perfusion and/or symptom-diffusion mismatch were detected with acute stroke MRI; (2) all patients were thought to have progression of their symptoms, a change of the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points during observation with double antiplatelets. Dual-antiplatelet therapy (clopidogrel, 75 mg/days; aspirin, 100 mg/days) was taken for at least three days or given as a loading dose of clopidogrel (300 mg) and aspirin (300 mg) four hours before the progression of symptoms. Brain infarction > 1/3 of MCA territory on diffusion-weighted imaging and hemorrhage on computed tomography (CT) or MRI were deemed a contraindication for endovascular recanalization. We also excluded those with other causes of stenosis including vasculitis, dissection, moyamoya disease, or iatrogenic occlusion from the analysis. The patient selection flow diagram is provided in Figure 1. A total of 38 patients met the criteria for inclusion in this study. Institutional review board (IRB) approval was obtained (IRB no. AMC IRB 2018-0518). Informed procedural consent was obtained from the patients before they underwent endovascular treatment in each case.
Figure 1.
Patient selection flow diagram. AIS: acute ischemic stroke with symptom onset within 24 hours; NAICO: non–acute intracranial arterial occlusion; TICI: Thrombolysis in Cerebral Infarction Grading System.
Medication and endovascular treatment
The procedure was performed under local anesthesia with continuous arterial blood pressure monitoring via a radial arterial line. During the procedure, each patient received 50 to 80 IU/kg of intravenous heparin to attain an activated clotting time of approximately 250–300 seconds. An additional 1000 IU heparin per hour was given to maintain the activated clotting time. On completion of angioplasty with or without stent placement, the patient was administered a daily 75-mg oral dose of clopidogrel for a minimum of six months and a 100-mg oral daily dose of aspirin for their lifespan. For patients with failed recanalization of the occluded artery, dual-antiplatelet therapy was suggested for their lifespan and modification of the regimen was allowed in refractory patients. For patients with failed recanalization of the occluded artery who were to undergo extra–intracranial arterial bypass (EIAB) surgery, antiplatelet medication was stopped seven days before the procedure. Owing to acute exacerbations of ischemic symptoms, two patients underwent bypass surgery on antiplatelet medication after full discussion of potential hemorrhagic complications.
A 6-Fr guiding catheter (Envoy, Envoy DA, or Envoy XB DA; Codman Neurovascular, Raynham, MA, USA) was positioned in the ICA. The side arm of the guiding catheter was flushed continuously with pressurized and heparinized normal saline. Under roadmap guidance, a microcatheter (Headway 17, Terumo, Tokyo, Japan; Echelon 10, eV3 Inc, Irvine, CA, USA; or Excelsior 10, Stryker, Kalamazoo, MI, USA) and a 0.014-inch microguidewire were introduced to reach the occluded segment. The preferred microguidewires included Traxcess 14 (Microvention Terumo, Tustin, CA, USA), Transcend 14 (Boston Scientific, Natick, MA, USA) and Synchro 14 (Stryker, Fremont, CA, USA). The occlusion site was probed by carefully advancing the microguidewire. In some cases we tried passing the guidewire tip by targeting the tapered point of the blind end. When there was no specific point to target initially, we gently pushed the tip while feeling for resistance from the contact point. We tried to avoid any wavy appearance of the guidewire tip to minimize the chance of false passage. Once the guidewire passed the occluded segment, free rotating motion of guidewire tip in the vessel lumen could be observed on fluoroscopy, and then the microcatheter was advanced beyond the occluded segment over the microguidewire. We did not advance the microguidewire when there was any resistance at the occlusion or the segment distal to the occlusion, or if there was any limitation of free motion of the guidewire tip, even though the tip could pass beyond the occluded portion. In those situations, we retrieved the microguidewire down to the level of the preocclusion segment and then probing was tried again, targeting a different point at the face of the occluded portion.
A stent retriever (Solitaire, Medtronic) was used in two patients (patients no. 1 and no. 18) with suspected thrombi before angioplasty. However, the thrombectomy was ineffective, revealing only a tiny piece of clot taken out in only one patient (patient no. 18). With the use of a Transcend 300 exchange guidewire, an over-the-wire balloon (Gateway, Stryker Neurovascular) or a monorail balloon (Maverick, Boston Scientific) was introduced to perform balloon angioplasty. We preferred a low-profile balloon size (1.5 mm or 2.0 mm in diameter) because we did not know the exact reference vessel size except for the proximal patent segment. Self-expandable stents (Wingspan, Stryker Neurovascular (n = 19), Neuroform, Stryker Neurovascular (n = 6), Enterprise, Codman Neuro (n = 3), and Solitaire, Medtronic (n = 1)) were deployed subsequently in most cases. Neuroform, Enterprise and Solitaire stents would be used if there was tortuousness of the proximal as well as distal cerebral vessels to the stenotic lesion, or a tight curve distal to the stenotic lesion. If there was significant stenosis limiting antegrade flow after stenting, postdilation was considered, while residual stenosis without flow abnormality was left untouched after stent placement in most cases. We finished the procedure if there was no evidence of significant recoiling or in-stent thrombosis on control angiography performed 10–20 minutes after stent placement. Termination of the procedure was decided at the individual interventionist’s discretion, regardless of the angiographic recanalization status, while also considering the safety of the procedure.
Clinical and procedural data collection
Data collected from patient medical records included vascular risk factors (hypertension, diabetes, hyperlipidemia, smoking, and history of previous stroke), presenting symptoms (stroke or transient ischemic attack (TIA)), NIHSS score on presentation, type of imaging procedure performed, brain infarct pattern, and time interval between symptom onset and angioplasty (≤2 days vs > 2 days) (Table 1).
Table 1.
Baseline demographics and characteristics.
| Procedure | Success (n = 29) | Failure (n = 9) | p value |
|---|---|---|---|
| Age (year) (mean) | 65.07±12.07 | 59.67±10.76 | 0.238a |
| Female sex (no.) (%) | 10 (34.5) | 4 (44.4) | 0.699b |
| Hypertension | 20 (69.0) | 5 (55.6) | 0.689b |
| Diabetes | 6 (20.7) | 2 (22.2) | 1.000b |
| Hyperlipidemia | 11 (37.9) | 2 (22.2) | 0.456b |
| Smoking | 14 (48.3) | 3 (33.3) | 0.476b |
| Drinking | 16 (55.2) | 2 (22.2) | 0.130b |
| Prior stroke | 3 (10.3) | 1 (11.1) | 1.000b |
| Symptom onset (days) (mean, range) | 7.97 (1–60) | 8.25 (2–15) | |
| ≤ 2 days (no.) (%) | 9 (31.0) | 1 (11.1) | 0.396b |
| >2 days (no.) (%) | 20 (69.0) | 8 (88.9) | |
| Baseline NIHSS (median) (IQR) | 6 (2–9) | 4 (3–6) | 0.410c |
| Presenting symptom pattern | |||
| Stroke | 28 (96.6) | 8 (88.9) | 0.422b |
| TIA | 1 (3.4) | 1 (11.1) | |
| Brain infarct pattern | |||
| Border zone | 19 (65.5) | 5 (55.6) | 0.866d |
| Localized cortical wedge or scattered lesions | 5 (17.2) | 2 (22.2) | |
| Perforator | 5 (17.2) | 2 (22.2) | |
| Side (right) (no.) (%) | 14 (48.3) | 0 (0.0) | 0.014b |
| Occlusion location on DSA (no.) (%) | |||
| Intracranial ICA | 7 (24.1) | 1 (11.1) | 0.252d |
| M1 | 19 (65.5) | 8 (88.9) | |
| M2 | 3 (10.3) | 0 (0.0) | |
| Previous antiplatelet medicine | 10 (34.5) | 2 (22.2) | 0.689a |
DSA: digital subtraction angiography; ICA: internal carotid artery; IQR: interquartile range; mRS, modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; TIA: transit ischemic attack.
Independent sample t-test.
Fisher exact t-test.
Mann-Whitney U test.
Multinomial logistic regression.
The recanalization status was classified based on the Thrombolysis In Cerebral Infarction (TICI) perfusion categories for reporting purposes, and procedural success was defined as TICI 2 b or 3. Residual in-stent stenosis was also measured using the Warfarin Aspirin Symptomatic Intracranial Disease method.10 The causes of procedural failure were attributed to microguidewire/microcatheter passage failure, balloon catheter advancement failure, and stent delivery failure, with TICI ≤ 2 a. TICI ≥ 2 b achieved after balloon angioplasty was deemed a procedural success, even without stent deployment.
Periprocedural complications included guidewire perforation, intima dissection, parent artery rupture and acute in-stent thrombosis. Acute in-stent thrombosis was seen during a procedure, immediately after stenting (during the waiting period), and within 24 hours after angioplasty. Subacute reocclusion was defined as within two weeks. New or enlarged ischemic lesions after revascularization were identified on early imaging follow-up with MRI.
The mid-term clinical endpoint was defined as recurrent ischemic stroke or hemorrhage within three months. Stroke, as indicated by the presence of neurological deficits, was confirmed by a neurologist on the basis of imaging studies. The modified Rankin Scale (mRS) score at three months and the latest mRS score were recorded. Angiography, CT angiography, or MR angiography were used to determine the patency of the stented vessels.
Statistical analysis
Among those with severe intracranial stenosis, outcomes were compared between two patient groups. Baseline characteristics were summarized for patient groups as number (percentage) for categorical variables and as mean ± SD for continuous variables. Differences were compared using the t-test or Mann-Whitney U test for continuous variables, and χ2 test, Fisher exact test, or multinomial logistic regression test for categorical variables, as appropriate. All reported probability values were two sided with a tail probability value of 0.05.
Results
Among 38 patients with anterior circulation NAICO, recanalization of TICI 2 b or TICI 3 was achieved in 29 patients (76.3%) (Figure 2). Residual stenosis after recanalization was 43.4 ± 20% (range 1.5%–74.8%, n = 29) (Table 2). The recanalization procedure failed in nine patients because of (1) microguidewire passage failure (n = 7), (2) microcatheter passage failure over passed guidewire (n = 1), (3) balloon angioplasty catheter delivery failure (n = 0) and (4) stent delivery (Wingspan) failure after balloon angioplasty with TICI 2 a (n = 1) (Table 3). The failure in passage of the stent after balloon angioplasty was caused by the tortuousness of a cavernous ICA.
Figure 2.
A representative case (patient no. 36, female, age 83 years, dysarthria and right-side weakness for five days) with successful recanalization of the occluded left middle cerebral artery (MCA). (a–c) Left MCA M1 segment occlusion was detected on contrast-enhanced magnetic resonance (MR) angiography; multifocal diffusion restriction at the left centrum semiovale and diffusion-perfusion mismatch in left MCA territory were detected (perfusion shown with mean transit time images, MR perfusion). (d) Left common carotid artery angiography confirmed complete occlusion of the left M1 segment. (e) Angiography 15 minutes after stenting (balloon: Maverick, 2.0 mm × 15 mm; stent: Wingspan, 3.5 mm × 20 mm) showed patency of the stenting segment (Thrombolysis in Cerebral Infarction Grading System 2 b). (f) Follow-up computed tomography angiography seven months after the procedure showed patency of the stented vessel.
Table 2.
Treatment modalities and clinical outcomes.
| Procedure | Success (n = 29) | Failure (n = 9) | p value |
|---|---|---|---|
| Endovascular treatment (no.) (%) | |||
| Microguidewire passage | 31 (81.6) | – | |
| Microcatheter passage | 30 (78.9) | – | |
| Angioplasty | 30 (78.9) | – | |
| Stenting | 29 (76.3) | – | |
| Post balloon dilation | 4 (10.5) | – | |
| Intraarterial tirofiban | 3 (7.9) | – | |
| TICI > 2 b | 29 (76.3) | – | |
| Residual stenosis (%) (range) | 43.4 ± 20.0 (1.5–74.8) | – | – |
| Complications (no.) (%) | 4 (10.5) | ||
| Guidewire perforation | 0 (0.0) | 0 (0.0, n = 9) | – |
| Dissection | 1 (3.4) | 0 (0.0, n = 1)c | – |
| In-stent thrombosis | 2 (6.9) | 0 (0.0, n = 1)† | – |
| Rupture of parent artery | 1 (3.4) | 0 (0.0, n = 1)c | – |
| Intracerebral hemorrhage | 0 (0.0) | 0 (0.0, n = 1)c | – |
| In-stent reocclusion (no.) (%) | |||
| Acute reocclusion (<24 hours) | 2 (6.9) | 0 (0.0, n = 1)c | – |
| Subacute reocclusion (24 hours–2 weeks) | 1 (3.4) | 0 (0.0, n = 1)c | – |
| Mid-term reocclusion (2 weeks–3 months) | 0 (0.0, n = 28)d | 0 (0.0, n = 1)c | – |
| Delayed reocclusion (>3 months) | 2 (7.1, n = 28)d | 0 (0.0, n = 1)c | – |
| New or enlarged lesion on early DWI (<48 hours) | 7 (24.1) | 0 (0.0, n = 1)c | – |
| NIHSS at discharge (median) (IQR) | 3 (2–7) | 5 (4–8) | 0.184a |
| Mortality at three months (no.) (%) | 1 (3.4) | 0 (0.0, n = 9) | 1.000b |
| mRS 0–2 at three months | 25 (89.3, n = 28)d | 8 (88.9, n = 9) | 1.000b |
| Recurrent stroke (24 hours–3 months) | 1 (3.6, n = 28)d | 1 (11.1, n = 9) | 1.000b |
DWI: diffusion-weighted imaging; IQR: interquartile range; mRS: modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; TICI: Thrombolysis in Cerebral Infarction Grading System. All procedures were performed under local anesthesia.
Mann-Whitney U test.
Fisher exact test.
Indicates only one patient with TICI 2a.
One death.
Table 3.
Patients with procedural failure.
| No. | Sex | Age | NIHSS | TTP (days) | Lesion location | Cause for procedure failure | Events within three months | mRS at three months |
|---|---|---|---|---|---|---|---|---|
| 1 | M | 65 | 6 | 15 | Left M1 | Microguidewire passage failure | No recurrent stroke on antiplatelet medication | 2 |
| 2 | M | 72 | 0 | 10 | Left M1 | Microguidewire passage failure | EIAB->partial brain salvage | 4 |
| 3 | F | 68 | 8 | 2 | Left M1 | Microguidewire passage failure | EIAB->improved brain perfusion | 2 |
| 4 | F | 42 | 2 | 11 | Left M1 | Microguidewire passage failure | No recurrent stroke on antiplatelet medication | 0 |
| 5 | M | 57 | 10 | 3 | Left M1 | Microguidewire passage failure | No recurrent stroke on antiplatelet medication | 1 |
| 6 | M | 53 | 5 | 3 | Left M1 | Stent deployment failure with TICI 2a | No recurrent stroke on antiplatelet medication | 1 |
| 7 | F | 46 | 3 | 3 | Left M1 | Microcatheter passage failure | No recurrent stroke on antiplatelet medication | 1 |
| 8 | F | 64 | 3 | 13 | Left ICA | Microguidewire passage failure | No recurrent stroke on antiplatelet medication | 1 |
| 9 | M | 70 | 4 | 4 | Left M1 | Microguidewire passage failure | EIAB->improved brain perfusion | 1 |
EIAB: extra–intracranial arterial bypass surgery; F: female; ICA: internal carotid artery; M: male; M1: middle cerebral artery M1 segment; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; TTP: time to procedure; TICI: Thrombolysis in Cerebral Infarction Grading System.
Intraprocedural events occurred in four of 38 patients (10.5%), including microguidewire perforation (n = 0), dissection (n = 1), parent artery rupture (n = 1) and acute in-stent thrombosis (n = 2). Intima dissection (n = 1) was detected in one patient with right distal ICA occlusion. After balloon angioplasty, an intimal flap observed in the vessel lumen was treated with stent placement. Parent artery rupture (n = 1) occurred in one patient with left M1 in-stent occlusion (the only patient with in-stent occlusion in this study). After successful recanalization of the occluded segment, contrast leakage was observed in the delayed phase of the angiogram. Mild subarachnoid hemorrhage was detected on CT, and was absorbed in five days without a neurological deficit. Elastic recoiling after balloon angioplasty was not uncommon in this group (n = 5), and the affected vessels maintained good patency with stent placement. Acute in-stent thrombosis (n = 2) was detected in two patients, one with M2 stenting and one with distal ICA stenting. The recommended loading and maintenance doses of intravenous tirofiban (Aggrastat, Medicure Pharma, USA) were used in one patient with suspected thrombosis following balloon angioplasty (n = 1) and in two patients with acute in-stent thrombosis immediately after stenting (n = 2). However, acute in-stent reocclusion was still observed in the patient with M2 stenting, together with increased extent of acute infarction.
Mean follow-up time for patients with successful recanalization was 36.5 months (range, 2–84 months), and follow-up angiographies were available in 24 patients. One patient died 68 days after the procedure because of a newly developed, unrelated posterior circulation stroke. Acute reocclusion was observed in two patients with major stroke. Subacute reocclusion was observed in one patient who received M2 stenting and was associated with intraprocedural acute in-stent thrombosis (patient no. 17). Although tirofiban infusion during the procedure cleared the thrombus, subacute reocclusion still occurred in this patient. Delayed reocclusion was observed in another two patients in association with TIA and major stroke, respectively (the reocclusion time was more than three months in both patients; therefore, they did not meet the mid-term clinical endpoint in this study) (Table 4). Overall in-stent reocclusion was more frequent in MCA M2 segment angioplasty (three of three) than in M1 segment and distal ICA angioplasty (2 of 26) (odds ratio = 13.0, 95% confidence interval 3.4–49.2) (Table 4). Good final outcome (mRS score ≤2) was achieved in 25 of 28 patients (89.3%) at three months (Table 2).
Table 4.
Summary of target arterial reocclusion after recanalization.
| No. | Sex | Age | NIHSS | TTP (days) | Lesion location | Residual stenosis (%) | TICI | Events within three months | mRS (three months) | Imaging of reocclusion |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M | 42 | 8 | 1.5 | Right M1 | 73.8 | 2b | Recurrent stroke | 3 | 16 hours |
| 2 | F | 88 | 9 | 7 | Left M2 | 37.8 | 2b | None | 1 | 9 months |
| 3 | M | 57 | 5 | 1 | Right M2 | 32.7 | 2b | Recurrent stroke | 1 | 4 days |
| 4 | F | 55 | 0 | 60 | Left M1 | 37.4 | 2b | Recurrent stroke | 0 | 4 months |
| 5 | F | 77 | 9 | 1 | Right M2 | 52.3 | 2b | Recurrent stroke | 3 | 10 hours |
F: female; M: male; M1: middle cerebral artery M1 segment; M2: middle cerebral artery M2 segment; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; TIA: transit ischemic attack; TICI: Thrombolysis in Cerebral Infarction Grading System; TTP: time to procedure.
Mean follow-up time for the nine patients with failed recanalization was 41.4 months (range, 3–82 months) (Table 3). Three patients with failed angioplasty underwent EIAB surgery for neurological worsening. Two of these three patients showed good results (Figure 3), and one had a major stroke postoperatively (patient no. 4). Five patients had good collateral flow on cerebral angiography, and showed stable or improved neurological status during the in-hospital period. None of these five patients took antiplatelet drugs previously, though symptom progression was observed four hours after a loading dose of antiplatelet medicine before the procedure, no stroke event was reported during follow-up on antiplatelet medications (Figure 4). The patient with stent delivery failure after balloon angioplasty had no ischemic event on antiplatelet medications, and angiography follow-up showed patency of affected vessels until 65 months. Good final outcome (mRS score ≤2) was achieved in eight of nine patients (88.9%) at three months (Table 2).
Figure 3.
A patient (female, age 68 years, symptom onset 48 hours) with M1 occlusion treated with extra–intracranial arterial bypass (EIAB). (a) Multifocal acute infarction in the left middle cerebral artery (MCA) territory. (b) Diffusion-perfusion mismatch at the left MCA territory was detected (perfusion shown with mean transit time (MTT) images magnetic resonance perfusion). (c–e) Abrupt occlusion in the left M1 segment and fusiform aneurysmal dilation of the left terminal internal carotid artery and left M1; partial leptomeningeal collateral of the left MCA territory from anterior cerebral artery and posterior cerebral artery leptomeningeal collaterals. (f–g) Good patency through left EIAB, and symmetric perfusion of the brain (perfusion shown with MTT, computed tomography perfusion).
Figure 4.
A patient (patient no. 3, female, age 68 years, with dysarthria and right-side weakness for 48 hours) with middle cerebral artery (MCA) occlusion treated with medical therapy. (a) Multifocal diffusion restriction at the left corona radiata, subcortical area of frontal lobe and insular area. (b and c) An occlusive lesion in the left MCA M1 segment with leptomeningeal collateral from the left posterior cerebral artery and anterior cerebral artery. (d) The recanalization of the left M1 occlusion was aborted because of severe resistance from the microguidewire. (e) The second day after the procedure, a slightly increased subacute infarct involving the left MCA territory was observed; slight hypoperfusion in the left MCA territory was detected (perfusion shown with mean transit time images, magnetic resonance perfusion). The patient was stable with antiplatelet medication.
Discussion
The present study demonstrated that endovascular recanalization can be a viable option with an acceptable safety profile in selected patients with symptomatic subacute or chronic atherosclerotic intracranial artery occlusion in the anterior circulation. Good outcome (mRS score ≤ 2) was observed in 89.3% of patients three months after successful recanalization of an occlusion.
Despite safety concerns about probing completely occluded intracranial arteries, recanalization was performed with an acceptable rate of procedure-related events. Different from angioplasty for a stenotic artery, recanalization of occluded arterial segments requires a certain degree of experience and more sophisticated technique.11 Great caution is required in probing the segment since the microcatheter-supported microguidewire passage of the occluded segment has the risk of vessel perforation. In our limited experience, the initial response to the first gentle push on the blind end indicated whether passage would be easy or challenging. Guidewire passage tended to be easier when there was a tapered end, regardless of the eccentricity. The resistance feedback from the guidewire and the guidewire tip motion provided much tactile information for the operator. Nonresistive passage might be the most desirable situation. In most cases of guidewire passage failure, the tip of the microguidewire could not pass beyond the blind end or at most advanced a very short distance. Some cases showed persistent resistance from the guidewire tip, even after passing the suspected distal point of the occlusion. In that situation, we observed the motion of the tip carefully for any limitation of motion that could be due to false passage through the arterial wall. Since procedural failure in this study was mainly caused by anatomic obstacles, we did not analyze the effect of the length of occlusion and the shape of occlusion on technical success. Although the therapeutic strategy for acute intracranial atherosclerosis-related occlusions is mechanical thrombectomy followed by balloon angioplasty and permanent stent deployment, only two patients in the current study received thrombectomy; these individuals were suspected to have significant in situ thrombus formation. Different from acute atherosclerosis-related occlusions, NAICOs usually show a long and slow symptom progression period, which may represent in situ occlusion instead of an acute thrombus formation. Therefore, stent retrieval may not be necessary as in atherosclerosis-related occlusions.12
Several studies have reported acceptable safety profiles for recanalization of intracranial atherosclerotic occlusions. The technical success rates of these studies have ranged from 80% to 100%. However, these studies usually included not only patients with anterior circulation intracranial artery occlusion, but also those with posterior circulation lesions.4–8,11 As there are differences in vascular anatomy, blood hemodynamics, tolerance to ischemic conditions, and remedial treatments between anterior and posterior circulations, it seems more reasonable to report the results separately. According to our data, revascularization of an occluded vertebrobasilar artery is associated with a higher success rate (90.3%, 28 of 31, data not shown) than that of the anterior circulation (78.9% in this study). The reasons for lower technical success rates in the anterior circulation require further investigation, with inclusion of posterior circulation lesions.13
Acute/subacute in-stent thrombus formation and long term in-stent restenosis are important concerns in patients with intracranial stenting.1,14 In our series, in-stent reocclusion was noted in five patients (Table 4), and M2 stenting indicated a high risk of reocclusion. Owing to the small size of the M2 segment and concern about vessel rupture, a small-caliber balloon was usually chosen to perform angioplasty, which could lead to incomplete dilation of target vessels. Therefore, residual stenosis after stenting in small lumen arteries may be a risk factor for reocclusion.14 In a report of seven patients with MCA occlusion who were treated with angioplasty beyond the bifurcation, despite a good clinical outcome with mean mRS 0.3 (range, 0–1), follow-up angiography was unable to show patency in the stented vessel after the procedure.5 In another study of 10 patients with acute M2 occlusion treated with intracranial stenting using the Wingspan stent system, one acute thrombotic event was reported.15
In this study, we followed up nine technical failure cases with imaging and/or clinical outcomes. Seven of the nine failed patients did not take antiplatelet medication before the onset of ischemic symptoms. Though a loading dose of antiplatelet medicine did not prevent the progression of symptoms in the seven patients before the procedure, five of them maintained relatively good hemodynamic status on standard medical therapy after failed recanalization of the occluded vessels, and their condition became stable or improved without further endovascular or surgical intervention. Maybe longer observation before the decision of endovascular treatment after initiation of antiplatelet medication is needed, and thresholds of diffusion-perfusion mismatch imaging and diffusion-clinical mismatch for clinical decision making should be established in the future. Another patient with TICI 2 a after balloon angioplasty (who did not take antiplatelet medication previously) showed no subsequent ischemic events with antiplatelet medication, and angiography follow-up showed improved patency of the affected vessel. We decided to send the remaining three (one of the three did not take antiplatelet medication previously) patients for bypass surgery because of exacerbation of symptoms, even with standard medical therapy. Unfortunately one had a large brain infarction despite successful bypass surgery, which may have been caused by hypoperfusion secondary to hypotension during general anesthesia for surgery.16,17
There are several limitations. This was a nonrandomized study with a small sample size, and we did not compare this cohort with NAICO patients who did not undergo the endovascular procedure. The sample size may be insufficient to enable generalization of the safety and effectiveness of endovascular recanalization in symptomatic NAICO. Further study should aim to provide an objective result. The primary message of this report was that endovascular recanalization is technically feasible. However, because of the recent advent of new and improved devices such as distal access or intermediate catheters, the procedural difficulty should be less than before. Several self-expendable stents used in this study were indicated only for stent-assisted coil embolization of aneurysms. Since the outcomes of off-label use of these self-expendable stents were not bad, it may support the potential of using stents (e.g. Neuroform, Enterprise or Solitaire) with less radial expansible force than the Wingspan stent system.18
Conclusions
Endovascular revascularization can be a viable option with an acceptable safety profile in selected patients with symptomatic NAICO in the anterior circulation. In patients with failed angioplasty, EIAB surgery could be performed in selected cases. Further characterization of aborted cases would be helpful in proper patient selection for endovascular treatment.
Footnotes
Z.Y.J. and Y.S.S. contributed equally to this work and should be considered co-first authors.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
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