Introduction

Stroke and cerebrovascular disease continue to be major causes of morbidity and permanent disability worldwide, and the result is a large financial burden on the health care systems. The majority of strokes are ischemic in nature, and it is believed that more than 20% are a result of occlusive disease of the carotid artery.1)2-10)12-18)23-31)

The treatment for extracranial carotid stenosis is aimed at preventing ischemic events caused by the embolized components of the artherosclerotic plaque or by progression to occlusion of a previously narrowed, but patent internal carotid artery.7)24)25)

It is likely that acute stroke treatment will always be time dependent, with the best outcomes achieved from the earliest interventions. However, the role of early carotid revascularization in symptomatic patients with severe carotid stenosis is still unclear.24)25) The North American Symptomatic Carotid Endarterectomy Trial (NASCET) clearly showed that the benefit of carotid endarterectomy (CEA) is maximal in symptomatic patients who are operated on within two weeks of the index event, but most specialists involved in stroke had the common fear of hemorrhagic transformation of the cerebral infarct.22) Delaying intervention probably means that patients are better selected, and this could guarantee better early outcomes, but this delay can also result in an interval stroke rate of 9% to 15%.25)

Carotid artery stenting (CAS) has recently been introduced as an acceptable alternative to CEA in high-risk patients. Although CAS was initially presented as a good alternative to CEA in high-risk patients, it has gradually evolved as a perfectly good substitute and a universal replacement for CEA in all symptomatic and asymptomatic patients. Currently, the indications for CAS continue to be in flux and they are being refined as more controlled data from large studies is being accumulated.1)3-5)7-9)12-18)20)22-26)

With this background, we evaluated and analyzed the clinical outcome of symptomatic high-risk patients with carotid stenosis and who were treated with early CAS.

Materials and Methods

From January 2008 to October 2009, we retrospectively analyzed 75 symptomatic high-risk carotid stenosis patients who had been admitted to the stroke center of our neurosurgical department and who were treated with early CAS.

The inclusion criteria (Table 1) were a recent (within 24 hours) acute hemispheric event, including minor or major stroke, and transient ischemic attack (TIA) in the vascular territory of a diseased carotid artery with documented angiographic stenosis greater than 50% according to the NASCET criteria. Minor stroke was defined as any new neurological deficit that persisted for longer than 24 hours and this was associated with a modified Rankin scale (mRS)2) of less than 3, while major stroke was defined as any new neurological deficit that persisted for longer than 24 hours and this was associated with a mRS of 3 or more.

The exclusion criteria (Table 1) were nonatherosclerotic arterial diseases such as Takayasu arteritis or arterial dissection, signs of intracranial hemorrhage documented by a computed tomography (CT) scan, loss of consciousness, the inability to achieve vascular access due to the presence of a thrombus in the common carotid artery or severe tortuosity of the common carotid artery.

All the patients were at a high medical and surgical risk for carotid endarterectomy (Table 2). The baseline evaluation included taking the medical history and neurological history, neurological images, including magnetic resonance imaging (MRI), and digital subtraction angiography (DSA). These patients were treated with early CAS as soon as possible (treatment was done within 2 weeks from the onset of symptoms).

All the patients received 100mg/day of aspirin and/or 75mg clopidogrel for at least 2 days prior to the procedure, or 300mg of clopidogrel on the day of the procedure. Heparin was administered during the procedure at a dose of 5,000 IUs, and following the procedure all the patients were given aspirin and clopidogrel for at least 30 days.

The vascular system was accessed via the femoral artery. Angiography of the diseased carotid artery was performed to confirm the lesion. An embolic protection device (EPD) was used in all the patients. A pre-dilatation balloon was carefully advanced and a stent of appropriate size and length was then placed at the lesion site. A post-dilatation balloon was not advanced, but this was required in some patients due to acute thrombus formation and/or plaque extrusion at the time of stent deployment. Post-procedure angiographies were repeated to ensure the adequacy of stent deployment, lesion dilatation and distal flow. After the procedure, brain CT routinely followed to confirm any other complications.

Three months after the procedure, a complete neurological examination (including mRS) was performed for each patient and the findings were compared to the initial pre-procedure findings. To analyze and evaluate the outcome of the procedures, the patients were divided into three groups; those who were clinically improved (a decreased mRS of 2 or more), unimproved (a decreased mRS of 1 or an unchanged mRS) and impaired (an increased mRS).

Results

Of the 75 patients, 32% (n=24) had TIA, while 68% (n=51) had a minor or major stroke. All the patients were treated within 2 weeks from the onset of symptoms. The average age was 68 years (from 49 to 80 years) and most patients were male (n=67, 88%). Most of the patients treated with CAS had a history of medical disease, and more than half (52%) were current or former smokers (Table 3). The target lesion stenosis was 74.5�7.6% (Table 4).

Predilatation was performed using an undersized (usually 4.0mm diameter x 30mm to 40mm long) balloon in all the patients. A closed cell stent was implanted in the majority of 9 cases (9 Carotid Wallstent - Boston Scientific). Open cell stents were used in 65 cases (3 Acculink - Abbott Vascular, 9 Smart - Cordis, 53 Precise - Cordis). EPD was used in all the patients (14 Angioguard, 35 Spide FX, 26 FilterWire EZ). A post-dilatation balloon was not advanced, but it was required in 3 patients due to acute thrombus formation and/or plaque extrusion at the time of stent deployment.

No intra-procedural neurological complications occurred, while the minor complications were ICA vasospasm in 10% of cases and hypotension in two cases. Procedural success, defined as the absence of new cerebrovascular events at the time of discharge (including major stroke, minor stroke or TIA), was assessed to be 97.4%. One patient experienced an in-hospital new neurological event. The other non-neurological adverse events were 2 cases of aspiration pneumonia and 2 patients with acute myocardial infarction (AMI).

The adverse events in the TIA patients at three months were 2 non-neurological deaths (due to AMI and pneumonia) and 1 new stroke. At three months, 15 patients (20%) in the TIA and stroke group experienced an improvement of their initial neurologic deficit (a decreased mRS greater than 2), while the deficit remained stable in 59 patients (78.4%) and only one patient had a neurological impairment.

Discussion

Making an evidence-based choice of CAS or CEA for the treatment of severe carotid artery stenosis remains elusive and this choice is sometimes based on the operator's specialty. Moreover, the outcome of medical management for this disease is no longer clearly defined because many new pharmacologic treatments may alter the natural history of the disease. Also, many high-risk asymptomatic patients continue to be treated based on the degree of stenosis regardless of their life expectancy.3-5)7-9)12-18)22-26)

CAS has been promoted as the preferred intervention for high-risk patients. The determination of patients who are at a high-risk remains ill-defined as it has generally been a broad label applied to patients who were excluded from the NASCET and other trials.7)8)20)22-25) Although the most appropriate treatment for patients with severe comorbid illnesses, including coronary artery disease with angina, congestive heart failure, myocardial infarction within the last 6 months, chronic obstructive pulmonary disease, etc. should be considered on an individual bias, these patients are at an increased risk for complications and they may eventually be proven to be more safely treated by CAS as compared with CEA. Yet the long-term benefit of any intervention in these patients is not well documented and medical management may ultimately be the preferred treatment option.7)8)20)22-25)

The role of symptoms for selecting a procedure is gradually being defined. Symptomatic patients seem to do worse with CAS, at least as evidenced by the recent trials. Plaque characteristics such as echolucency on ultrasound or plaque hemorrhage may be more common in symptomatic patients; thus, such plaque characteristics increase the risk of CAS more than they increase the risk of CEA.24) However, the final guidelines regarding the optimum treatment for carotid artery occlusive disease will be formulated based on the data generated by prospective comparative clinical trials. In this study, we retrospectively analyzed a group of symptomatic high-risk carotid stenosis patients who had been treated with CAS.

Carotid revascularization reduces the risk of stroke in patients with recent symptomatic stenosis. Analysis of the pooled data from the European Carotid Surgery Trial and the NASCET clearly showed that the benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as the delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.22)24)

The Surgical Treatment of Acute Cerebral Ischemia (STACI) study has shown that patients whose neuro-imaging studies document a recent, limited cerebral infarction in the early hours after a stroke can safely undergo very early CEA (1.5 days after the stroke).25) However, this study also warns that if patients are strictly selected for early CEA after an acute stroke, then early surgery incurs risks similar to the risks of elective surgery. Setacci et al. have demonstrated that patients with acute symptoms can undergo CAS within a short time from an event, but this is subject to stabilizing their neurological status.25) Their strategy was to perform a cerebral scan at least 24 hours after symptom onset to evaluate the evolution of the ischemic lesion, and then to wait until clinical and instrumental stabilization of the ischemic lesion had occurred before proceeding with revascularization. With regard to patient selection based on the neurological status and instrumental findings, they indicated that early treatment with protected carotid stenting is both feasible and safe in selected patients with a first episode or recurrent TIA or minor stroke. In our study, the symptomatic high-risk carotid stenosis patients were treated with early CAS as soon as possible (treatment was done within 2 weeks from the onset of symptoms). These treatments can reduce the morbidity of early recurrent stroke after TIA and strokes to an acceptable level.

The data proposed in this study has several limitations. This was a retrospective review of clinical data and so no uniform protocol for treatment existed between the operations or the medical institutions. This was not a randomized trial of CAS versus surgical or medical therapy and so no comparison to either modality can be made. Finally, this study reflects the experiences of a relatively small group of interventionalists and it is possible that longer follow-up may change the outcome of our patients.

Conclusion

Our data indicates that urgent assessment and early initiation with a combination of existing preventive treatments can reduce the morbidity of early recurrent stroke after TIA and minor or major stroke to an acceptable level. Further follow-up is required to determine the long-term outcome, but these results have immediate implications for providing service and public education about TIA and minor or major stroke.

References 

11) Berg-Drammer E, Henkes H, Weber W, Berlit P, Kuhne D. Percutaneous transluminal angioplasty of intracranial artery stenosis : clinical results in 24 patients. Neurosurg Focus 5:1-14, 1998

12) Bonita R, Beaglehole R : Modification of Rankin scale. recovery of motor function after stroke. Stroke 19:1497-1500, 1988

13)  Bussiers M, Pelz DM, Kalapos P, Lee D, Gulka I, Leung A, et al. Results using a self-expanding stent alone in the treatment of severe symptomatic carotid bifurcation stenosis. J Neurosurg 109:454-460, 2008

14)  Das S, Bendok BR, Getch CC, Awad I, Batjer HH. Update on current registries and trials of carotid artery angioplasty and stent placement. Neurosurg Focus 18:1-6, 2005

15)  Fessler RD, Wakhloo AK, Lanzio G, Qureshi AI, Guterman LR, Hopkins LN, et al. Stent placement for vertebral artery occlusive disease : preliminary clinical experience. Neurosurg Focus 5:1-8, 1998

16) Ghogawala Z, Westerveld M, Amin-Hanjani S. Cognitive outcomes after carotid revascularization : The role of cerebral emboli and hypoperfusion. Neurosurgery 62:385-395, 2008

17)  Grant A, White C, Ansel G, Bacharach M, Mezger C, Velez C, et al. Safety and efficacy of carotid stenting in the very elderly. Catheter Cardiovasc Interv 10:1-5, 2010

18)  Iihara K, Murao K, Sakai N, Yamada N, Nagata I, Miyamoto S, et al. Outcome of carotid endarterectomy and stent insertion based on grading of carotid endarterectomy risk : a 7-year prospective study. J Neurosurg 105:546-554, 2006

19)  Komotar RJ, Mocco J, Wilson DA, Connolly ES, Lavine SD, Meyers PM, et al. Current endovascular treatment options for intracranial carotid artery atherosclerosis. Neurosurg Focus 18:1-4, 2005

10)  Komotar RJ, Mocco J, Wilson DA, Connolly ES, Lavine SD, Meyers PM, et al. The natural history of intracranial carotid artery atherosclerosis. Neurosurg Focus 18:1-3, 2005

11) Kwon YK, Kim EM, Lee CY. Stent-assisted angioplasty for symptomatic radiation-induced carotid stenosis. J Korean Neurosurg Soc 41:327-329, 2007

12)  Lanzino G, Fessler RD, Mericle RA, Wakhloo AK, Guterman LR, Hopkins LN, et al. Angioplasty and stenting for carotid artery stenosis : indications, techniques, results, and complications. Neurosurg Focus 5:1-23, 1998

13)  Lanzino G, Mericle RA, Lopes DK, Wakhloo AK, Guterman LR, Hopkins LN, et al. Percutaneous transluminal angioplasty and stenting for recurrent carotid artery stenosis. Neurosurg Focus 5:1-9,1998

14)  Lee CY, Yim MB. Primary stent therapy for symptomatic intracranial atherosclerotic stenosis : 1-year follow-up angiographic and midterm clinical outcomes. J Neurosurg 105:235-241,2006

15)  Levy EL, Ecker RD, Thompson JJ, Rosella PA, Hanel RA, Guterman LR, et al. Toward clinical equipoise : the current case for carotid angioplasty and stent placement. Neurosurg Focus 18:1-8,2005

16)  Levy EL, Hanel RA, Bendok BR, Boulos AS, Hartney ML, Guterman LR, et al. Staged stent-assisted angioplasty for symptomatic intracranial vertebrobasilar artery stenosis. J Neurosurg 97:1294-1301, 2002

17)  Levy EL, Hanel RA, Boulos AS, Bendok BR, Kim SH, Gibbons KJ, et al. Comparison of procedure complications resulting from direct stent placement compared with those due to conventional and staged stent placement in the basilar artery. J Neurosurg 99:653-660, 2003

18)  Levy EL, Hanel RA, Lau T, Koebbe CJ, Levy N, Padalino DJ, et al. Frequency and management of recurrent stenosis after carotid artery stent implantation. J Neurosurg 102:29-37, 2005

19) Lylyk P, Cohen JE, Ceratto R, Ferrario A, Miranda C. Endovascular reconstruction of intracranial arteries by stent placement and combined technique. J Neurosurg 97:1306-1313,2002

20)  Meyer FB. Overview : carotid endarterectomy compared with angioplasty. Neurosurg Focus 18:1-3, 2008

21)  Nederkoorn PJ, Brown MM. Optimal cut-off criteria for duplex ultrasound for the diagnosis of restenosis in stented carotid arteries : review and protocol for a diagnostic study. BMC Neurol 9:1-7, 2009

22) North American Symptomatic Carotid Endarterectomy Trial (NASCET) Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325:445-453, 1991

23)  Park ST, Kim JK, Yoon KH, Park SO, Park SW, Kim JS, et al. Atherosclerotic carotid stenoses of apical versus body lesions in high-risk carotid stenting patients. AJNR Am J Neuroradiol:1-7, 2010

24) Rabih AC, Makaroun MS. Current indications for carotid angioplasty and stenting. Perspect Vasc Surg Endovasc Ther 20:239-245,2008

25) Setacci C, Donato G, Chisci E, Stacci F, Italy S. Carotid artery stenting in recently symptomatic patient : a single center experience. Ann Vasc Surg:1-5,2009

26)  Steinfort B, Ng PP, faulder K, Harrington T, Grinnel V, Sorby W, et al. Midterm outcomes of paclitaxel-eluting stents for the treatment of intracranial posterior circulation stenoses. J Neurosurg 106:222-225,2007

27) Taha MM, Maeda M, Sakaida H, Kawaguchi K, Toma N, Yamamoto A, et al. Cerebral ischemic lesions detected with diffusion-weighted magnetic resonance imaging after carotid artery stenting : comparison of several anti-embolic protection devices. Neurol Med Chir (Tokyo) 49:386-393, 2009

28) Terada T, Tsuura M, Matsumoto H, Masuo O, Tsumoto T, Yamaga H, et al. Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery : percutaneous transluminal angioplasty compared with stent placement. J Neurosurg 98:491-497, 2003

29) Theron J, Guimaraens L, Coskun O, Sola T, Martin JB, Rufenacht DA, et al. Complications of carotid angioplasty and stenting. Neurosurg Focus 5:1-20, 1998

30)  Vajda Z, Miloslavski E, Guthe T, Schmid E, Schul C, Albes G, et al. Treatment of intracranial atherosclerotic arterial stenoses with a balloon-expandable cobalt chromium stent (coroflex blue) : procedural safety, efficacy, and midterm patency. Neuroradiology:1-7, 2009

31)  Yoon SM, Jo KW, Baik MW, Kim YW. Delayed carotid wallstent shortening resulting in restenosis following successful carotid artery angioplasty and stenting. J Korean Neurosurg Soc 46:495-497, 2009