Endovascular Revascularization for Chronic Vertebral Artery Occlusion with Poor Collateral Circulation and a Large Perfusion Abnormality Identified by Automated Perfusion Imaging: A Case Report

Abstract

Objective

Endovascular revascularization is increasingly used to treat symptomatic acute intracranial vertebral artery (ICVA) occlusion, with reported clinical benefit. In contrast, chronic total occlusion (CTO) is managed primarily with conservative therapy, and the indications for and efficacy of endovascular revascularization remain uncertain.

Case Presentation

A 74-year-old man with right vertebral artery (VA) occlusion and left VA stenosis was followed at our outpatient clinic. He presented with a 40-day history of dizziness and gait disturbance. MRI showed no new acute infarction, whereas MRA demonstrated bilateral VA occlusion. However, automated perfusion imaging (RAPID; iSchemaView, Golden, CO, USA) identified a large perfusion abnormality, leading to a diagnosis of symptomatic ICVA CTO. Urgent endovascular revascularization was performed. A small postoperative cerebellar infarction developed without new neurological deficits. Symptoms on admission improved with medical therapy and rehabilitation, and he was discharged home 14 days after the procedure; the perfusion abnormality had nearly resolved. At 2 months after hospital discharge, the patient remained asymptomatic, with no symptom recurrence.

Conclusion

Endovascular revascularization for symptomatic ICVA CTO resulted in a favorable outcome. Automated perfusion imaging may help identify appropriate candidates for this treatment.

Introduction

The intracranial vertebral artery (ICVA) is a common site of intracranial arterial occlusive disease.¹⁾ Endovascular revascularization has increasingly been performed for acute occlusion within 24 hours of symptom onset, and its effectiveness has been demonstrated.²⁾ Although no consensus definition of chronic occlusion exists, an occlusion identified on imaging or persisting for more than 1 month after symptom onset is often classified as chronic total occlusion (CTO).^3,4) Endovascular revascularization for ICVA CTO may be considered a last-resort option for patients with ischemic symptoms refractory to aggressive antiplatelet therapy.^5,6) However, the timing of occlusion is frequently uncertain, and the relationship between the occlusion and symptoms is often difficult to establish. Consequently, the indications for and efficacy of endovascular revascularization remain controversial.

RAPID (iSchemaView, Golden, CO, USA) is a brain image analysis platform that rapidly evaluates perfusion abnormalities in acute cerebral ischemia, and its utility has been reported in Japan.^7–9) However, its use in ICVA CTO has not been reported, and its clinical value remains unclear. Here, we describe a case of ICVA CTO in which RAPID demonstrated a large perfusion abnormality, supporting the decision to perform endovascular revascularization, resulting in a favorable clinical outcome.

Case Presentation

A 74-year-old man developed sudden dizziness and unsteadiness and was transported to our emergency department by ambulance. His medical history included hypertension; diabetes mellitus and dyslipidemia were absent. On arrival, he was alert but complained of dizziness and gait disturbance. MRI revealed scattered acute infarctions in both cerebellar hemispheres (Fig. 1A), which were considered responsible for his symptoms. MRA suggested right vertebral artery (VA) occlusion and left VA stenosis, prompting cerebral angiography. The right VA was occluded distal to the posterior inferior cerebellar artery branch (Fig. 1B), and an embolic cerebral infarction secondary to acute occlusion of an atherosclerotic stenotic lesion was diagnosed. Moderate (57%) stenosis of the dominant left VA was confirmed using the Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) method (Fig. 1C), but distal flow was preserved; therefore, right VA revascularization was not performed. Because the lesion was considered atherosclerotic, medical therapy, including dual antiplatelet therapy with prasugrel (3.75 mg once daily) and aspirin (100 mg once daily), was initiated. His symptoms improved, and he was discharged home on dual antiplatelet therapy with outpatient follow-up.

Fig. 1. Diffusion-weighted MRI and DSA images at initial presentation. (A) Diffusion-weighted MRI showed acute infarctions in both cerebellar hemispheres. (B) Right vertebral angiography in the frontal view showed occlusion of the right VA distal to the origin of the posterior inferior cerebellar artery. (C) Left vertebral angiography in the frontal view showed moderate (57%) stenosis of the dominant left VA, as measured using the WASID method.

VA, vertebral artery; WASID, Warfarin–Aspirin Symptomatic Intracranial Disease

He remained stable without recurrence, but dizziness recurred 9 months later. Oral vestibular suppressants prescribed at a nearby otolaryngology clinic were ineffective, and symptoms gradually worsened, eventually impairing ambulation. He presented to our hospital 10 months after the initial event, approximately 40 days after dizziness onset. Examination revealed marked dizziness, unsteadiness, and cerebellar ataxia. MRI showed no new acute infarction (Fig. 2A), but MRA demonstrated occlusion of both the previously known right VA and the left VA at the site of pre-existing stenosis, with poor visualization of the basilar artery. Hemodynamic assessment with RAPID (iSchemaView) demonstrated a large volume of tissue (104 mL) with prolonged time to maximum of the residue function (Tmax) >6 seconds in the cerebellum and brainstem (Fig. 2B).

Fig. 2. Diffusion-weighted MRI and automated perfusion imaging at the 2nd admission and after endovascular revascularization. (A) Diffusion-weighted MRI at the 2nd admission showed no new acute infarction. (B) Preprocedural automated perfusion imaging showed 104 mL of hypoperfused tissue with Tmax >6 seconds in the vertebrobasilar and posterior cerebral artery territories. (C) Diffusion-weighted MRI on postoperative day 1 showed a small new infarction in the left cerebellar hemisphere after endovascular revascularization.

Tmax, time to maximum of the residue function

Cerebral angiography confirmed bilateral VA occlusion. The vertebrobasilar segment extending from the VA occlusion site to the basilar artery proximal to the anterior inferior cerebellar artery was visualized through collateral flow from dural branches and the anterior spinal artery via numerous muscular branches (Fig. 3A and 3B). No collateral flow through the posterior communicating arteries was observed. In the late phase, the bilateral posterior cerebral arteries and the basilar artery distal to the anterior inferior cerebellar artery were retrogradely visualized through leptomeningeal anastomoses (Fig. 3C).

Fig. 3. DSA images and 3D rotational angiography before and during endovascular revascularization. (A) Left vertebral angiography in the frontal view showed occlusion at the site of the previously documented stenosis and collateral opacification of the distal VA and proximal basilar artery through muscular branches. (B) Right vertebral angiography in the frontal view showed persistent occlusion of the right VA. (C) Left internal carotid angiography in the lateral view demonstrated retrograde flow to the posterior cerebral arteries and basilar artery (arrow) through a leptomeningeal anastomosis (arrowheads). (D) Left vertebral angiography in the frontal view showed the Headway 21 microcatheter advanced into the distal basilar artery through the occluded segment. (E) Left vertebral angiography in the frontal view during balloon angioplasty. The balloon was inflated a total of 8 times using a 2.0 × 10 mm Unryu balloon catheter. (F) 3D rotational angiography of the left VA demonstrated revascularization of the occluded segment, with restoration of antegrade flow to the basilar artery apex.

Headway 21, Terumo Neuro, Aliso Viejo, CA, USA; Unryu, Kaneka Medix, Osaka, Japan; VA, vertebral artery

Based on the clinical course, symptoms, and imaging findings, left VA occlusion at symptom onset was considered to have caused posterior circulation hypoperfusion, resulting in progressive ischemic symptoms. Because 40 days had elapsed since symptom onset, CTO was strongly suspected, and the occluded segment was relatively long. However, symptoms progressed despite ongoing dual antiplatelet therapy, and the lesion was judged to represent symptomatic CTO refractory to medical therapy. Poor collateral circulation and a large perfusion abnormality raised concern for further neurological deterioration and severe cerebral infarction. After informed consent was obtained, endovascular revascularization was performed.

The 4Fr short sheath placed in the right femoral artery for angiography was exchanged for a 7Fr long sheath, and a 7Fr Fubuki catheter (Asahi Intecc, Aichi, Japan) was advanced into the left VA. A 5Fr Esperance catheter (Wallaby Medical, Laguna Hills, CA, USA) was advanced to the occlusion site, and aspiration was attempted; however, no thrombus was retrieved, and the occlusion persisted. The lesion was firm, suggesting chronic occlusion. Attempts to cross the lesion using a Headway 21 microcatheter (Terumo Neuro, Aliso Viejo, CA, USA) and a Synchro Select Support guidewire (Stryker Neurovascular, Fremont, CA, USA) were unsuccessful. After switching to a CHIKAI black microguidewire (Asahi Intecc), the occlusion was crossed successfully, and the Headway 21 catheter was advanced to the distal basilar artery (Fig. 3D). Using a 315-cm CHIKAI exchange wire (Asahi Intecc), the Headway 21 was exchanged for an Unryu 2.0 × 10 mm balloon catheter (Kaneka Medix, Osaka, Japan), and the balloon was inflated a total of 8 times (Fig. 3E). The efficacy of distal protection in ICVA CTO has not been established, and it was therefore not used in this case. The occluded segment was recanalized, restoring antegrade flow (Fig. 3F). Because no recoil was observed after a 15-minute waiting period, the procedure was completed without intracranial stenting.

MRI performed the following day showed a small new cerebellar infarction (Fig. 2C). Intraprocedural embolism was most strongly suspected, but no new neurological deficits developed. Dizziness improved with medical therapy and rehabilitation. The patient regained independent ambulation and was discharged home 14 days after the procedure. Before discharge, MRI showed no additional infarction. Follow-up DSA performed on postoperative day 12 demonstrated no restenosis or reocclusion at the recanalized site (Fig. 4A), preserved antegrade flow, and disappearance of the previously observed collateral circulation (Fig. 4B). RAPID performed on postoperative day 13 showed marked improvement, with the volume of tissue with prolonged Tmax >6 seconds reduced to 3 mL (Fig. 4C). Two months after discharge, the patient remained asymptomatic, and no symptom recurrence has occurred since discharge.

Fig. 4. Follow-up DSA on postoperative day 12 and automated perfusion imaging on postoperative day 13 after endovascular revascularization. (A) Left vertebral angiography in the frontal view on postoperative day 12 showed no restenosis or reocclusion at the recanalized site and preserved antegrade flow to the basilar artery and both posterior cerebral arteries. (B) Left internal carotid angiography in the lateral view on postoperative day 12 showed disappearance of the previously observed retrograde flow to the posterior cerebral arteries and basilar artery. (C) Automated perfusion imaging on postoperative day 13 showed that the volume of hypoperfused tissue with Tmax >6 seconds had decreased from 104 mL before treatment to 3 mL.

Tmax, time to maximum of the residue function

Discussion

The ICVA is highly susceptible to atherosclerotic stenotic and occlusive disease, often involving both VAs.^5,6,10) Consequently, posterior circulation hypoperfusion may cause dizziness, gait disturbance, dysarthria, blurred vision, and faintness, substantially reducing quality of life. Patients with poor collateral circulation are also at increased risk of recurrent cerebral infarction and poor outcomes. Determining the timing of occlusion is often challenging. Gao et al. reported a mean interval of 40 days (range, 18–365 days) from symptom onset to treatment and 29 days (range, 1–120 days) from ICVA CTO diagnosis to treatment, highlighting this uncertainty.⁵⁾ In the present case, oral vestibular suppressants were prescribed after dizziness onset, but symptoms progressed, and imaging was performed 40 days after symptom onset.

Standard treatment for ICVA CTO includes antiplatelet therapy and vascular risk factor control; however, these measures may not adequately improve hypoperfusion, and outcomes are often poor. In the New England Medical Center Posterior Circulation registry, 21% of patients receiving maximal medical therapy developed severe disability or died during follow-up.¹¹⁾ Therefore, endovascular revascularization has been attempted for ICVA CTO refractory to medical therapy. In a mini-review of 6 studies, Zhang reported an 85.7% recanalization rate. However, peri-procedural complications included ischemic events in 17.6%, hemorrhagic events in 37.5% of symptomatic and asymptomatic cases combined, and 1 death.³⁾ Lesion length and occlusion duration increase procedural difficulty, but definitive treatment indications remain undefined.

Endovascular revascularization is well established for symptomatic acute ICVA occlusion.^5,6,10) However, when symptom onset is uncertain or substantially delayed, determining treatment eligibility remains difficult. In such cases, CT perfusion or MRI diffusion–perfusion imaging is recommended to evaluate the ischemic core and cerebral perfusion status.^7–9) RAPID (iSchemaView) is an automated postprocessing system that rapidly estimates hypoperfused tissue with prolonged Tmax >6 seconds. It was used in the DAWN and DEFUSE 3 trials and has demonstrated clinical utility in Japan.^7–9)

Although the present case involved chronic occlusion, RAPID identified a large posterior circulation perfusion abnormality involving the brainstem and cerebellum, supporting the decision to perform revascularization. Postoperative RAPID demonstrated a marked reduction in the volume of tissue with prolonged Tmax >6 seconds, retrospectively suggesting improved perfusion after treatment. To our knowledge, this is the first reported ICVA CTO case in which RAPID guided the decision to perform endovascular revascularization. These findings suggest that, in addition to lesion length and occlusion duration, RAPID-based hemodynamic assessment may help identify appropriate candidates for revascularization.

However, several limitations should be considered. Compared with the anterior circulation, posterior circulation Tmax values are often prolonged even without steno-occlusive disease and vary according to vascular anatomy.¹²⁾ In posterior circulation infarction, qualitative assessment of software-generated perfusion maps may be more sensitive and accurate than automated quantitative analysis.¹³⁾ Furthermore, CT perfusion mismatch in patients with intracranial large artery occlusive disease may represent benign oligemia rather than critically hypoperfused tissue at risk of infarction; therefore, RAPID findings should be interpreted cautiously.¹⁴⁾ Although positron emission tomography and single photon emission CT are established methods for evaluating cerebral perfusion in chronic occlusive disease, their availability is limited. Because these modalities were unavailable at our institution and the patient’s symptoms were progressing, RAPID was used as an alternative for perfusion assessment.

Overall, RAPID should not be considered a definitive criterion for treatment selection in ICVA CTO but rather one component of a comprehensive clinical assessment. Prospective studies are needed to validate its role in treatment decision-making.

Conclusion

ICVA CTO remains a therapeutic challenge; however, endovascular revascularization may improve outcomes in carefully selected patients. Assessment of perfusion abnormality using RAPID (iSchemaView) may assist in selecting candidates for endovascular revascularization, although further studies are needed to establish its clinical value.

Disclosure Statement

The authors declare that they have no conflicts of interest.