Long-Term Clinical and Angiographic Outcomes in Patients with Cervico-Cranial Dissections Treated with Stent Placement: A Meta-Analysis of Case Series

Abstract

Limited clinical and angiographic data exists for patients with spontaneous or traumatic cervico-cranial dissections treated with stent placement. We reviewed clinical and angiographic data on consecutive patients admitted to our hospital with spontaneous, traumatic, and iatrogenic cervico-cranial dissections treated with stent placement to study immediate and long-term clinical and angiographic outcomes. Additional patients were identified using pertinent studies published between 1980 and 2009, using a search of the PubMed, Cochrane, and Ovid libraries. Post-procedure complications and clinical outcomes were documented. Angiographic abnormalities collected at follow-up included presence of in-stent restenosis or pseudoaneurysm. After applying our strict search criteria, four studies including our series were used in the meta-analysis, representing 46 patients (mean age [standard deviation] 47±14 years; 24 [52%] male) treated with stent placement for dissection. Overall, 72 stents were placed to treat 28 spontaneous, 11 traumatic, and 7 iatrogenic dissection patients with 51 dissections, involving 51 vessels; with a mean pre-stent stenosis of 71±26% and mean post-stent stenosis of 6±15%. The immediate and follow-up post-procedure complication rates per stent placed was 8 (11%) and 8 (11%), respectively. Among the 36 patients who underwent follow-up angiography, in-stent restenosis or pseudoaneurysms were present in 3 (8%) and 2 (6%) patients, respectively. A high rate of sustained resolution of angiographic abnormalities during long-term follow-up was noted, with a low rate of new transient ischemic attack, ischemic stroke, or death, supporting the feasibility, safety, and effectiveness of endovascular stent reconstruction.

Introduction

T he incidence of internal carotid artery dissection is 2.5–3 per 100,000, whereas it is approximately half that for vertebral artery dissection (Lee et al., 2006; Schievink et al., 1993). Cervico-cranial dissections are the underlying cause in an estimated 10–20% of ischemic strokes in young and middle-aged patients (Schievink, 2000). Medical treatment consisting of anticoagulation or antiplatelet therapy has been used to reduce thromboembolic complications following cervico-cranial arterial dissections. Cervico-cranial arterial dissections are infrequently treated with stent placement, although randomized prospective studies have not been performed comparing medical treatment to endovascular stent placement (Kremer et al., 2003).

According to the American Stroke Association's guidelines, stent placement may be considered in symptomatic patients refractory to medical management, or asymptomatic dissections with persisting hemodynamically (>70%) significant stenosis, unstable intimal flap, or enlarging pseudoaneurysm (Biousse et al., 1995; Briganti et al., 2005; Kadkhodayan et al., 2005; Schievink, 2000). However, concerns remain regarding the long-term results following stent placement, which prompted our analysis. The data provided by single-center studies are limited by small numbers of patients, demographic characteristics of patient populations, and treatment protocols. We performed this meta-analysis consisting of data derived from all available case series, of symptomatic cervico-cranial arterial dissection patients treated with stent placement, to ascertain the short- and long-term clinical and angiographic outcomes with higher precision and reflective of a broader patient population.

Methods

Data sources

A literature search of published manuscripts between 1980 and 2009 was conducted using the following computerized databases: PubMed (U.S. National Library of Medicine), Cochrane Database of Systematic Reviews (Cochrane Collaboration resources), and Ovid (Wolters Kluwer). Through the use of PubMed's MeSH service we used the following permutation of key words without any language restrictions: “dissection” and “vertebral” or “carotid” and “traumatic” or “spontaneous” or “iatrogenic” and “stent” or “endovascular” or “embolization” or “procedure” or “occlusion” or “pseudoaneurysm” and “follow up” or “angiogram” or “CTA” or “CT Angiogram” or “diagnostic subtraction angiography” or “ultrasound” not “animal model” or “case report” or “systematic review.” Similarly to previous meta-analyses, the search was also supplemented by studies identified through personal knowledge.

Study selection criteria

The studies that were included in this meta-analysis were required to have the following objective clinical information, otherwise they were excluded: (1) carotid or vertebral arterial dissection treated with endovascular stent placement, (2) 7 or more patients, (3) mechanism of dissection either spontaneous, traumatic, or iatrogenic, (4) diagnosis of dissection made either through computed tomography angiography, magnetic resonance angiography, or ultrasound (in the case of extracranial carotid arterial dissection), with confirmation by digital subtraction angiography, (5) location and number of dissections were identified, (6) total number of stents placed provided, (7) post-procedure imaging follow-up at least 1 month from the initial procedure, by either a cerebral angiogram or ultrasound to evaluate for in-stent or peri-stent stenosis, and (8) reported the clinical outcomes such as transient ischemic attack, stroke, and death during follow-up periods ranging from immediately to 1 year post-procedure, and identified the follow-up time period.

According to the American Heart Association's (AHA's) criteria, the available manuscripts included in this analysis were considered a level of evidence C and Class IIb. A level C classification represents evidence from expert opinion, case studies, or standards of care. Class IIb represents that the usefulness/efficacy of the recommendation is less well established by evidence/opinion. Since all the studies were observational studies, the manuscripts were not graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group evidence criteria (Guyatt et al., 2008). The GRADE evidence criteria uses four categories for quality of evidence: high, moderate, low, or very low. The first three categories are only applicable to randomized clinical trials, and all the available studies in our analysis were observational, limiting the value of a detailed scale. The specific indications for stent placement used by each of the reviewed manuscripts have been previously published (Ansari et al., 2008; Edgell et al., 2005; Kadkhodayan et al., 2005; Malek et al., 2000).

The case series of Hassan and associates

Our cohort was identified through a retrospective study conducted at two university-affiliated comprehensive stroke centers from January 1, 2006 to July 1, 2009 (Hassan et al., 2011). All cervico-cranial arterial dissections were identified through a search performed using the admission International Classification of Diseases-9th Revision, Clinical Modification (ICD-9-CM) codes for arterial dissection (443.2, 443.21, and 443.24). Patients with spontaneous cervico-cranial arterial dissections were included, excluding patients with iatrogenic and traumatic dissections. The diagnosis was made based on a review of the admission history, physical examination, and radiological tests. The patients were also identified using a prospectively maintained registry updated by the cerebrovascular program that tracks all patients who undergo endovascular treatment. Our case series met all of the previously mentioned study selection criteria (Hassan et al., 2011).

Data extraction

Using a pre-specified data abstraction form, two investigators (F.S. and H.Z.) independently evaluated all the studies identified through the initial search. During data abstraction, any discrepancies between the two investigators were sorted out, and if needed the opinion of a third investigator (A.E.H.) was sought; thus differences were reconciled among the three investigators. When available, the two investigators abstracted the following information: (1) study characteristics (year of publication, design, and recruitment period); (2) patient characteristics (number of patients, demographics, and clinical characteristics; Table 1); (3) eligibility (based on the above-mentioned study selection criteria); (4) types of stents used; (5) pretreatment and post-treatment angiographic results (pseudo-aneurysm and fibromuscular dysplasia); (6) initial and post-procedure percent stenosis of each affected vessel lumen; (7) immediate post-procedure complications and any follow up clinical strokes, transient ischemic attacks, and deaths from all causes as reported by the authors; (8) in-stent and/or peri-stent stenosis rates on follow-up digital subtraction angiography or B-mode ultrasound (in the case of extracranial carotid artery stent placement) at least 1 month from the initial procedure; and (9) post-stent antiplatelet regimen including duration of treatment. Patients without angiographic/B-mode ultrasound follow-up at a minimum of 1 month post-stent placement were excluded from the analysis.

Table 1.

Clinical Characteristics of the Patients Included in the Meta-analysis

Series	Patients	Patients who met inclusion criteria	Number and etiology of dissections	Total stents placed	Post-stent placement duration of antiplatelet treatment
Hassan et al. (Hassan, et al., 2011)	19	14	10 spontaneous 1 traumatic 3 iatrogenic	14 spontaneous 2 traumatic 5 iatrogenic	Aspirin (325 mg/d) and clopidogrel (75 mg/d) 1 month minimum, then aspirin (325 mg/d) continued indefinitely
Ansari et al. (Ansari et al., 2008)	9	7	4 spontaneous 2 traumatic 1 iatrogenic	9 spontaneous 2 traumatic 1 iatrogenic	Aspirin (81 mg/d) and clopidogrel (75 mg/d) for 8 weeks, then aspirin (81 mg/d) continued indefinitely
Edgell et al. (Edgell et al., 2005)	7	7	7 spontaneous	14 spontaneous	Aspirin (325 mg/d) and clopidogrel (75 mg/d) for 6 weeks, then aspirin (325 mg/d) continued indefinitely
Kadkhodayan et al. (Kadkhodayan et al., 2005)	26	11	3 spontaneous 7 traumatic 1 iatrogenic	3 spontaneous 11 traumatic 1 iatrogenic	Aspirin 325 mg/d and clopidogrel (75 mg/d) 1 month minimum, then aspirin (325 mg/d) continued indefinitely
Malek et al. (Malek et al., 2000)	10	7	5 spontaneous 2 traumatic 3 iatrogenic	9 spontaneous 1 traumatic 2 iatrogenic	Ticlopidine (250 mg bid) or clopidogrel (75 mg/d) for 6 weeks, then aspirin (325 mg/d) indefinitely

We defined immediate post-procedure complications as any complications occurring during the procedure and until the time of discharge; follow-up post-procedure complications are those that occurred after discharge.

Statistical analysis

Using the four studies including our own case series, we abstracted the age of the patient, sex, dissection type, pre-stent stenosis, post-stent stenosis, affected vessel, number of dissections, number of stents utilized per patient, and the time period in months from stent placement to last documented angiographic (digital subtraction angiography or B-mode ultrasound) assessment. The mean value with standard deviation was presented for continuous variables including age, pre-stent stenosis, post-stent stenosis, and follow-up time period. The total number of immediate procedure-related and post-procedure follow-up complications were documented and counted. Post-procedure follow-up complications were defined as any complication that occurred after the immediate procedure and within the follow-up time period. The frequency of complications was calculated in two ways: (1) complications per patient, and (2) complications per stent placed identified as complications per procedure. We also ascertained the number and types of vessels involved.

Results

The case series of Hassan and associates

Over the course of the study period, 122 patients were admitted with 75 spontaneous and 47 traumatic/iatrogenic cervico-cranial arterial dissections (Hassan et al., 2011). Endovascular stent placement was performed in 14 (19%) patients with spontaneous dissection. The mean age±standard deviation of the 14 patients was 52±16 years; 57% (n=8) were female. The patients' presenting clinical characteristics and affected vessels are summarized in Table 2a. The mean pre-procedural angiographic severity of stenosis was 74% (range 10–100%). Time to stent placement from index clinical event and/or diagnosis of dissection to endovascular treatment was 2 days to 4 months. Angiographic follow-up was available in 10 patients ranging from 26–612 days (mean period 245 days), and during this time we did not identify any in-stent stenosis and occlusion.

Table 2a.

Clinical Characteristics of the Patients in Hassan and Associates' Cohort (Hassan et al., 2011)

Age/ sex	Clinical presentation	Dissection type	Lesion site	Angiographic morphology	Initial percent lesion stenosis	Stent type	Procedural complication	Follow-up percent stenosis and angiography	Follow-up complication
61/M	Horner syndrome	S	R ICA (intracranial)	IF, PA, no FMD	55	Jostent Graftmaster (Covered)	None	0; PA resolved. IVUS confirmed. DSA 9 m	None
48/M	Anterior IS	S	L ICA (extracranial)	IF, no PA, no FMD	100	Wingspan	None	0; DSA 20 m	None
31/M	Anterior IS	S	R MCA (intracranial)	IF, no PA, no FMD	100	Wingspan	None	0; DSA 5 m	None
55/M	Posterior IS	S	L VA (intracranial)	IF, no PA, no FMD	90	Neuroform	None	70% residual stenosis after initial stent placement and angioplasty; on follow-up angiogram, the in-stent lumen diameter was unchanged; following an angioplasty the stenosis improved to 40%. DSA 6 m	None
46/M	HA	S	R ICA (intracranial)	IF with stenosis and PA, no FMD	70	Enterprise	None	50% residual stenosis after initial stent placement; follow-up angiography in-stent lumen diameter was unchanged; with resolution of PA after additional coil embolization at 6 m DSA	None
58/F	Thunderclap HA	S	Junction of cavernous-supraclinoid segment of L ICA (intracranial)	IF, extracranial PA and FMD	10	Xpert	None	0, PA resolved with stent assisted coiling embolization; IVUS confirmed; DSA 7.5 m	None
25/F	Anterior IS	S	L ICA (intracranial)	IF, no PA, FMD	85	Neuroform and Wingspan	None	0; DSA 1 m	None
43/F	TIA	S	b/l ICA (extracranial)	R ICA: long dissection with stenosis and PA. L ICA: IF, PA no FMD	R: 90 L: 40	Precise X 3	None	0; R ICA and PA resolved. IVUS confirmed; DSA 3 m	None
48/F	TIA	S	R ICA and R CCA (extracranial)	IF and PA no FMD	90	Precise X 2	None	0; PA resolved. IVUS confirmed. DSA 6 m	TIA 3m
19/M	Anterior IS	T	R ICA (cervical to petrous)	PA, no FMD	90	Precise, Wingspan	Transient mild vasospasm	0, PA resolved DSA 7 m	None
58/F	Incidental patient with multiple angiograms (neuro stable)	I	Proximal L VA stenosis (V1–V2)	No PA, no FMD	90	Multi-Link Vision	None	0; DSA 3.5 m	None
72/M	Pontine stroke	I	R VA (V2) dissection	No PA, no FMD	80	Wingspan (6/20/09), Wingspan, Enterprise (6/30/09)	None, remnant false lumen distal portion of stent that led to enlarging PA	0, DSA 6 m	None
49/F	TIA following reconstruction of R ICA for inflammatory pseudo-tumor	I	R CCA	IF, no PA, no FMD	20	Precise	None	0; U/S 2 m	None
39/F	Left neck pain	S	L ICA	PA, FMD	70, L ICA, but enlarging PA (grew in size from 7/16/09 to 8/2/09)	Jostent Graftmaster	None	0; Patent, PA resolved; DSA 15 m	None

Enterprise stent (Codman Neurovascular, Raynham, Massachusetts); Jostent Graftmaster stent (Abbott, Princeton, NJ); Neuroform stent (Boston Scientific, Natick, MA); Precise stent (Cordis, Miami Lakes, FL); Wingspan stent (Boston Scientific); Xpert stent (Abbott); Multi-link Vision stent (Abbott).

M, male; F, female; R, right; L, left; ICA, internal carotid artery; IF, intimal flap; PA, pseudoaneurysm; FMD, fibromuscular dysplasia; IVUS, intravascular ultrasound; MCA, middle cerebral artery; DSA, digital subtraction angiography; IS, ischemic stroke; S, spontaneous; VA, vertebral artery; CCA, common carotid artery; m, month.

Combined analysis

The initial search identified 169 publications. After applying our search criteria, we included 4 studies and our series in the analysis, representing 46 patients (mean age±standard deviation, 47±14 years, range 19–83 years; 24 [52%] men) treated with stent placement for dissection (Ansari et al., 2008; Edgell et al., 2005; Kadkhodayan et al., 2005; Malek et al., 2000). Overall, a total of 72 stents were placed to treat 28 (61%) spontaneous, 11 (24%) traumatic, and 7 (15%) iatrogenic dissection patients. The mean (±standard deviation) pre-procedural stenosis was 71±26%, (range 0–100%), and post-stent stenosis was 6±15%, (range 0–70%) in the 51 treated vessels. The total number of patients included from each study and the post-stent antiplatelet regimens are documented in Table 1. The immediate post-procedural complication rate per procedure was 11% (n=8), similar to the follow-up post-procedure complication rate of 11% (n=8); these are described in detail below based on their respective dissection type. The overall mean angiographic or ultrasound follow-up time period per dissection treated with stent placement was 9±7 months (range 1–25 months). Among the 36 (78%) patients, representing 52 stents, who underwent follow-up angiography, in-stent restenosis or pseudoaneurysms were present in 3 (8%) and 2(6%) patients, respectively. A total of 10 out of 31 (32%) patients were found to have underlying fibromuscular dysplasia, with the majority being among the patients with spontaneous dissections. The specific clinical and angiographic results for each of the individual studies are documented in Tables 2a through 2e.

Table 2b.

Clinical Characteristics of the Patients in Kadkhodayan and Associates' Cohort (Kadkhodayan et al., 2005)

Age/sex	Clinical presentation	Dissection type	Lesion site	Angiographic morphology	Initial percent lesion stenosis	Stent type	Procedural complications	Follow up percent stenosis and angiography	Follow-up complication
51/M	TIA	I^*	R ICA	IF, no PA	70	Wallstent	None	0; 12 m DSA	Recurrent TIA (12 m clinical)
36/F	CN palsy	T^*	L ICA	PA	60	Wallstent	None	0; Asymptomatic ipsilateral occlusion at 3.4 m DSA	None (3.4 m clinical)
56/M	TIA	S	R ICA	PA, FMD	95	Wallstent	None	0; 7.4 m DSA	Contralateral CEA, Stroke (7.4 m clinical)
45/F	None	S	R ICA	PA, no FMD	50	Smart	None	0; 2.1 m DSA	None (2.1 m clinical)
40/F	None	S	L ICA	PA, no FMD	75	Smart	None	0; 25 m DSA	None (25 m clinical)
35/F	TIA	T^*	R ICA	PA	50	Precise	None	0; 2.7 m DSA	Recurrent TIA (2.7 m clinical)
22/M	None	T^*	1st R ICA, 1st L CCA, 2nd R ICA, 2nd L CCA	PA (R ICA, L CCA)	0, 0, 0, 0	Precise, Smart, Precise, Smart X2	None, none, TIA, none	10.8 m DSA, 0, 10.8 m DSA, 0, 10.2 m DSA, 0, 10.2 m DSA	None (16 m clinical), None (16 m clinical), None (15.4 m clinical), None (15.4 m clinical
19/M	None	T^*	L ICA	PA	90	Precise	None	0; 6.2 m DSA	None (23.9 clinical)
60/M	TIA	T^*	L ICA	No PA	70	Precise	TIA	50; 11.2 m DSA	None (11.2 clinical)
42/M	TIA	T^*	L ICA	PA	99	Precise	None	0; 6.4 m DSA	None (13.4 clinical)
52/M	Horner Syndrome	T^a	L ICA	PA	25	Precise	None	0; 5.6 m DSA	None (9.5 m clinical)

Fibromuscular dysplasia was only described in the cases of spontaneous dissection.

Precise and Smart stents (Cordis, Miami Lakes, FL); Wallstent (Boston Scientific, Natick, MA).

M, male; F, female; R, right; L, left; ICA, internal carotid artery; IF, intimal flap; PA, pseudoaneurysm; FMD, fibromuscular dysplasia; DSA, digital subtraction angiography; T, traumatic; I, iatrogenic; S, spontaneous; CEA, carotid endarterectomy; CN, cranial nerve; CCA, common carotid artery; m, month; c, clinical.

Table 2c.

Clinical Characteristics of the Patients in Ansari and Associates' Cohort (Ansari et al., 2008)

Age/sex	Clinical presentation	Dissection type	Lesion site	Angiographic morphology	Initial percent lesion stenosis	Stent type	Procedural complications	Follow up percent stenosis and angiography	Follow-up complications
55/M	L ischemic stroke, L Horner syndrome	S	L ICA (cervical/ petrous)	No PA, no FMD	90	Acculink, Precise, Neuroform	None	0; 10 m DSA	None (19 m clinical)
25/M	Multiple TIAs, L ischemic stroke	T	L VA (V3)	PA, no FMD	75	Neuroform	None	0; in stent stenosis (details not specified) and thrombosis of PA at 1 year DSA	None (23 m clinical)
53/F	Flow limiting stenosis, EEG/SSEP changes	I	R ICA- Mid-cervical	No PA, FMD	95	Neuroform	None	25; 10 m DSA	None (18 m clinical)
45/F	SAH	S	L VA (V4)	No PA, dissecting aneurysm, no FMD	90	Neuroform X3	None	0; Thrombosed dissecting aneurysm, 3 m DSA	None (12 m clinical)
70/M	SAH	S	L VBA (V4-basilar)	No PA, dissecting aneurysm no FMD	65	Neuroform	None	20; Coils for enlarging 4 mm aneurysm neck remnant at 6 m DSA; PA resolved on 12, 18 m DSA follow-up	None (18 m clinical)
40/M	Occipital pain, visual TIAs	T	L VA (V4)	No PA, dissecting aneurysm no FMD	50	Neuroform	None	0, 7 m DSA	None (12 m clinical)
69/F	SAH	S	R VA (V4)	No PA, dissecting aneurysm, no FMD	50	Neuroform X2	None	0 initially but at 4 m DSA 20% in-stent stenosis	None (12 m clinical)

Acculink stent (Guidant, Santa Clara, CA); Neuroform stent (Boston Scientific; Natick, MA), Precise stent (Cordis; Miami Lakes, FL).

M, male; F, female; R, right; L, left; ICA, internal carotid artery; IF, intimal flap; PA, pseudoaneurysm; FMD, fibromuscular dysplasia; MCA, middle cerebral artery; DSA, digital subtraction angiography; IS, ischemic stroke; T, traumatic; I, iatrogenic; S, spontaneous; VA, vertebral artery; m, month; EEG, electroencephalogram; SSEP, somatosensory evoked potential; SAH, subarachnoid hemorrhage; VBA, vertebrobasilar artery.

Table 2d.

Clinical Characteristics of the Patients in Edgell and Associates' Cohort (Edgell et al., 2005)

Age/sex	Clinical presentation	Dissection type	Lesion site	Angiographic Morphology	Initial percent lesion stenosis	Stent type	Procedural complications	Follow up percent stenosis and angiography	Follow-up complications
41/F	Bi-frontal HA, neck pain	S	R ICA, L ICA^*	PA (L ICA); FMD	50	Jomed X2	None	0 (PA resolved) L ICA: 12 m DSA –patent	None
57/M	Syncope, R HH, aphasia, R hemiparesis, obtunded	S	L ICA, R ICA^*	No PA; no FMD	99	Precise	None	0 R and L ICA: 24 m U/S patent	ICH transformation 13 d after intervention
39/F	L Horner's syndrome, tinnitus, HA	S	R ICA,^* L ICA,^* L VA	PA (L ICA); FMD	70 (L ICA), 80 (R ICA), 50 ( L ICA with PA)	Precise, Tetra, Jomed	None	0, 5, 0 (L ICA PA resolved) R and L ICA: 24 m DSA- patent	None
53/M	R neck pain, severe HA	S	R ICA,^* L VA	PA X3- R ICA; no FMD	80	Wallgraft	Small, non-flow-limiting intimal tear R CCA	0% (and PA resolved) R ICA: 14 month U/S patent	None
40/F	L LE numbness	S	R ICA,^* L ICA^*	No PA; FMD	90, 90	Precise, Precise	None	10 (R ICA), 0 (L ICA) R and L ICA: 3 month U/S patent	Stable neurological exam; died 4 m later secondary to transplant complication
54/F	R UE weakness, mild expressive aphasia	S	L ICA,^* R CCA^* to R ICA,^*	No PA, FMD	70, 90	Precise; SMART, Precise	None	0 (L ICA), 0 (R CCA to ICA) L ICA and R ICA/CCA: 12 m U/S patent	None
50/F	R HA, L hemianopsia, dysarthria	S	R ICA,^* L ICA	No PA, FMD	99	Precise X2	None	0 R ICA: 6 m U/S patent	None

Jomed (Jomed Inc., Helsingborg, Sweden); Precise and Smart (Cordis Corp., Miami Lakes, FL); Tetra (Guidant Corp., Indianapolis, IN); Wallgraft (Boston Scientific Inc., Boston, MA).

, treated vessel; M, male; F, female; R, right; L, left; ICA, internal carotid artery; HH, homonymous hemianopsia; U/S, ???; ICH, ???; PA, pseudoaneurysm; FMD, fibromuscular dysplasia; DSA, digital subtraction angiography; UE, upper extremity; LE, lower extremity; S, spontaneous; VA, vertebral artery; CCA, common carotid artery; d, days.

Table 2e.

Clinical Characteristics of the Patients in Malek and Associates' Cohort (Malek et al., 2000)

Age/sex	Clinical presentation	Dissection type	Lesion site	Angiographic Morphology	Initial percent lesion stenosis	Stent type	Procedural complications	Follow-up percent stenosis and angiography or ultrasound	Follow-up complications
45/F	L HP	I	R ICA	No PA	100	Wallstent	Transient vasospasm	0 6 m U/S stent patent	None (17 m clinical)
46/F	R ptosis, R CN III palsy	I	L ICA	No PA, cavernous R ICA aneurysm	80	Wallstent	None	20 10 m U/S stent patent	Stroke at 8 months following massive uterine hemorrhage and hypotension (24 m clinical)
51/M	L eye blindness, HA	S	R ICA,^* L ICA	No PA	60	Wallstent, GFX X2 (L ICA)	None	15 3 m U/S stent patent	None (15 m clinical)
83/M	L TIA, R HP, aphasia	S	L CCA	No PA, false lumen	60	Wallstent X2	Persistent minimal filling of false lumen	20 4 m U/S stent patent	None (16 m clinical)
51/M	Aphasia, R hemiparesis	S	L ICA,^* R ICA	No PA	80	Wallstent X3 (R ICA)	None	0 9 month U/S stent patent	None (20 m clinical)
37/F	R UE hemi-paresis, Dysphasia	T	L ICA	No PA	85	Wallstent	Retro-peritoneal hematoma	0 6 m DSA-Patent	None (27 m clinical)
64/M	R hemiparesis, L ocular pain	S	L ICA	PA	70	Wallstent	None	0 6 m DSA stent-patent	None (17 m clinical)

GFX (Arterial Vascular Engineering, Santa Rosa, CA); Wallstent (Schneider; Plymouth, MN).

, treated vessel; M, male; F, female; HA, headache; TIA, transient ischemic attack; R, right; L, left; ICA, internal carotid artery; HP, hemiparesis; CN, cranial nerve; CCA, common carotid artery; PA, pseudoaneurysm; UE, upper extremity; I, iatrogenic; S, spontaneous; U/S, ultrasound; DSA, digital subtraction angiography.

Spontaneous dissections

Spontaneous dissections were identified in 28 (61%) patients (mean age±standard deviation, 51±12 years, range 25–83 years; 14 [50%] were men), with a mean pre-stent stenosis of 75±20% (range 10–100%), that improved to a mean post-stent stenosis of 7±16% (range 0–70%) after treatment. A total of 47 stents were utilized to treat the 32 dissected vessels, which were involved in the following frequencies: 11 (34%) right internal carotid artery, 13 (41%) left internal carotid artery, 1 (3%) right vertebral artery, 3 (9%) left vertebral artery, 2 (6%) right common carotid artery, 1 (3%) left common carotid artery and 1 (3%) right middle cerebral artery. The immediate complication rate per patient was 7% (n=2), and the complication rate per procedure was 4% (n=2). The 2 immediate procedural complications were persistent filling of a false lumen (Malek et al., 2000), and a small non-flow-limiting vessel dissection (Edgell et al., 2005) at the site of stent placement. The follow-up complication rate per patient was 14% (n=4), and the complication rate per procedure was 8% (n=4). There were 4 follow-up complications in this group of patients, identified as a transient ischemic attack (Hassan et al., 2011), an intracerebral hemorrhage (Edgell et al., 2005) 13 days post-stent-placement, a death (Edgell et al., 2005; unrelated to stent placement), and an ischemic stroke (Kadkhodayan et al., 2005). The death occurred following a heart transplant 4 months after stent placement. Fibromuscular dysplasia was identified in 9 out of 24 patients (36%), and there were 16 (57%) pseudoaneurysms among the 28 patients. The mean angiographic or ultrasound follow-up time period per stent placed was 10±8 months, (range 1–25 months). Among the 20 patients representing 29 stents who underwent follow-up angiography, in-stent restenosis or pseudoaneurysms were present in 1 (5%) and 2 (10%) patients, respectively. Ansari and associates (Ansari et al., 2008) identified a mild myointimal hyperplasia at 4-month angiographic follow-up, leading to a 20% in-stent stenosis, in a 69-year-old woman who had 2 Neuroform stents (Boston Scientific, Natick, MA) placed to treat a right vertebral artery (V4) dissection associated with subarachnoid hemorrhage. No clinical complications were observed as far as 12 months post-stent placement (Ansari et al., 2008). Ansari and colleagues (Ansari et al., 2008) also reported a 70-year-old man with a left vertebro-basilar artery dissection, treated with a Neuroform stent, that required further coil embolization of an enlarging 4-mm aneurysm neck remnant at his 6-month angiographic follow-up, without any further complications at the 18-month clinical follow-up. Similarly, Hassan and associates (Hassan et al., 2011) reported a 46-year-old man with an intracranial right internal carotid dissection that required an Enterprise stent (Codman Neurovascular, Raynham, MA), who was found to have an enlarging pseudoaneurysm neck remnant at 6-month angiography, and was treated with coil embolization; there were no further complications at 1-year clinical follow-up.

Traumatic dissections

A total of 11 (24%) patients had traumatic dissections (mean age±standard deviation, 35±13 years, range 19–60 years; 8 [73%] men), with a mean pre-stent stenosis of 57±34%, (range 0–99%), that improved to a mean post-stent stenosis of 4±14% (range 0–50%). A total of 16 stents were utilized to repair the 12 dissected vessels, which were involved in the following frequencies: 3 (25%) right internal carotid artery, 6 (50%) left internal carotid artery, 2 (16.7%) left vertebral artery, and 1 (8%) left common carotid artery. The immediate complication rate per patient was 36% (n=4), and the complication rate per procedure was 25% (n=4). There were 4 immediate procedural complications, including a transient vasospasm at the site of stent placement (Hassan et al., 2011), 1 retroperitoneal hemorrhage (Malek et al., 2000), and 2 transient ischemic attacks (Kadkhodayan et al., 2005). The follow-up complication rate per patient was 18% (n=2), and the complication rate per procedure was 13% (n=2). The two follow-up complications were identified as an asymptomatic ipsilateral occlusion (Kadkhodayan et al., 2005) of the stent, and a transient ischemic attack (Kadkhodayan et al., 2005). The mean angiographic or ultrasound follow-up time period per stent was 7±3 months, (range 3.5–12 months). A total of 10 (91%) pseudoaneurysms were identified among these patients prior to stent placement. Among the 11 patients, representing 16 stents, who underwent follow-up angiography, 2 (18%) had in-stent restenosis, and none had pseudoaneurysm. Ansari and colleagues (Ansari et al., 2008) identified a left vertebral artery in-stent stenosis (measurements not provided) at 4-month angiography in an asymptomatic 25-year-old man, who was found to have antegrade flow across the segment treated with the stent, with transient retrograde opacification of the distal left vertebral artery and posterior inferior cerebellar artery, suggesting flow-limiting compromise of the vessel from original laceration or delayed in-stent stenosis. Among the patients reported by Kadkhodayan and associates (Kadkhodayan et al., 2005), an asymptomatic in-stent occlusion of the left internal carotid artery Wallstent (Boston Scientific) was identified in a 36-year-old woman at 3.4-months angiographic follow-up.

Iatrogenic dissections

A total of 7 (15%) patients were identified with iatrogenic dissections (mean age±standard deviation, 53±9 years, range 45–72 years; 2 [29%] men), with a mean pre-stent stenosis of 76±27%, (range 20–100%), that improved to a mean post-stent stenosis of 6±11%, (range 0–25%). A total of 9 stents were used to treat the 7 dissected vessels, which were involved in the following frequencies: 3 (43%) right internal carotid artery, 1 (14%) left internal carotid artery, 1 (14%) right vertebral artery, 1 (14%) left vertebral artery, and 1 (14%) right common carotid artery. The immediate complication rate per patient was 29% (n=2), and the complication rate per procedure was 22% (n=2). The two immediate procedural complications were a transient vasospasm (Malek et al., 2000) and a pseudoaneurysm formation (Hassan et al., 2011) at the site of stent placement. The follow-up complication rate per patient was 29% (n=2), and the complication rate per procedure was 22% (n=2). The two follow-up complications in this group of patients were identified as an ischemic stroke (Malek et al., 2000) and a transient ischemic attack (Kadkhodayan et al., 2005). The mean angiographic or ultrasound follow-up time period per stent placed was 10±8 months (range 2–12 months). There were no pseudoaneurysms identified among these patients, but 1 out of 4 patients (25%) had fibromuscular dysplasia; we could not comment on the two patients identified in the study by Malek and associates (Malek et al., 2000).

Subgroup analysis

A subgroup analysis evaluating the immediate and post-procedure event rate of ischemic stroke and transient ischemic attack, death, and stent occlusion, among the three groups of patients revealed there were no immediate procedure-related deaths or ischemic strokes. The rate of immediate transient ischemic attack per patient was 4% (n=2), and transient ischemic attack per procedure was 3% (n=2), which were seen in the traumatic dissection patients. The rates of post-procedure complications were: transient ischemic attack 11% (n=5), death 2% (n=1), and stent occlusion 2% (n=1) per patient. Similarly, the following were the rates of post-procedure complications: transient ischemic attack 7% (n=5), death 1% (n=1), and stent occlusion 1% (n=1) per procedure.

A further analysis compared the mean age, pre- and post-stent stenosis, and the immediate and post-procedure complication rates of the patients with spontaneous dissection to the aggregate of traumatic and iatrogenic dissection patients. A total of 18 (39%) patients were identified with a total of 19 iatrogenic or traumatic dissections (mean age±standard deviation, 42±15 years, range 19–72 years; 10 [56%] men), with a mean pre-stent stenosis of 65±32%, (range 0–100%), that improved to a mean post-stent stenosis of 5±13% (range 0–50%). A total of 25 stents were used to treat the 19 dissected vessels, which were involved in the following frequencies: 6 (32%) right internal carotid artery, 7 (37%) left internal carotid artery, 1 (5%) right vertebral artery, 3 (16%) left vertebral artery, 1 (5%) right common carotid artery, and 1 (6%) left common carotid artery. The rate of immediate transient ischemic attack per patient was 11% (n=2), and transient ischemic attack per procedure was 8% (n=2); there were no immediate ischemic strokes or deaths. The rates of post-procedure transient ischemic attacks were 17% (n=3), and asymptomatic stent occlusions 6% (n=1) per patient. Similarly, the rates of post-procedure transient ischemic attacks were 12% (n=3), and asymptomatic stent occlusion 4% (n=1) per procedure. There were no follow-up deaths among this group.

Discussion

This study is unique in comparison to other studies evaluating the safety and effectiveness of endovascular stent treatment of cervico-cranial arterial dissections, because a stringent set of clinical parameters were used in order to identify the long-term angiographic and clinical details associated with stent placement. Many studies document stent patency on follow-up, but lack measurements relating to the pre- and post-stent stenosis values and rates of stent restenosis. Overall, we found that stent restenosis and occlusion were infrequent occurrences among the three types of dissections. This study further enhances the literature on this subject by providing aggregate data for patients treated for similar indications to be used as points of reference to assist future clinicians faced with making a decision to treat a dissection using stent placement. Without combining data from multiple studies, aggregate data with an acceptable level of precision of measurement is not possible with single-center studies alone, due to the low utilization rate of stents for treating dissections. The current combined analysis provides relatively reliable estimates of angiographic results following stent placement with long-term patency rates and associated clinical event rates.

The results enable clinicians to provide their patients or families an objective description of the short- and long-term risk:benefit profile of stent placement. The immediate post-procedural complication rate per stent placed was 11% (n=8), which was similar to the follow-up post-procedural complication rate of 11% (n=8), which included one asymptomatic stent occlusion (Kadkhodayan et al., 2005) among the 46 patients that had angiographic/ultrasound follow-up. However, the overall complication rate reflects the inclusion of any clinical event that may not actually have a direct connection to the stent. Based on our subgroup analyses, it can be argued that the actual complication rate is lower if the complications related only to the stent were included. When comparing the spontaneous to the aggregate traumatic and iatrogenic dissection patients, it appears that the aggregate traumatic and iatrogenic patients treated with stent placement are at increased risk for immediate and follow-up complications, despite being started on similar dual antiplatelet regimens.

Multiple indications have been used for selecting patients for endovascular stent treatment of cervico-cranial dissections. In theory, the stent supports and expands the true lumen of the dissected artery, realigning the intimal flap, and trapping the subintimal hematoma. Stent endothelialization gradually occurs with intimal healing and hematoma resorption between 28 and 96 days (Grewe et al., 2000; Van Belle et al., 1997; Verheye et al., 1999). For patients with dissections, stent placement has become an option for patients with transient ischemic attack or ischemic stroke despite antiplatelet or anticoagulant treatment (Bejjani et al., 1999; Cerutti et al., 2010; Edgell et al., 2005; Janjua et al., 2006), patients with new ischemic symptoms secondary to the presence of expanding pseudoaneurysms (Cohen et al., 2005; Edgell et al., 2005), and to assist in the control of bleeding in cases of intracranial pseudoaneurysm/aneurysm rupture (Duke et al., 1997; Kadkhodayan et al., 2005). Kadkhodayan and colleagues (Kadkhodayan et al., 2005) treated cervico-cranial dissections if the dissection and/or pseudoaneurysm caused a high-grade stenosis by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria for symptomatic patients (Barnett et al., 1998), or Asymptomatic Carotid Atherosclerosis Study (ACAS; Executive Committee for the Asymptomatic Carotid Atherosclerosis Study, 1995) criteria for asymptomatic patients. In patients with a pseudoaneurysm and no stenosis, treatment was performed if stent placement could prevent distal emboli arising from the pooling of blood (Kadkhodayan et al., 2005). Stent placement has also been considered when a patient has a contraindication to anticoagulation, contralateral internal carotid artery occlusion or stenosis in a patient who was neurologically unstable, or had clinical evidence of hemodynamic insufficiency, documented poor collateral circulation, and need for elective occlusion of the contralateral internal carotid artery for aneurysm treatment (Malek et al., 2000).

Multiple retrospective case reports and series have demonstrated the effectiveness and relative safety of endovascular reconstruction of cervical (Ahn et al., 2005; Bejjani et al., 1999) and vertebro-basilar arterial (Malek et al., 1999; Price et al., 1998) dissections through stent placement. A comprehensive retrospective analysis of 13 studies (n=62), representing 63 extracranial internal carotid artery dissections, was performed by Donas and associates (Donas et al., 2008), which included 28 (45%) patients with traumatic, 21 (37%) patients with spontaneous, and 13 (21%) patients with iatrogenic dissections. The technical success rate was 100% (63 of 63 procedures). The primary and 1-year patency rate of the stents and/or stent-grafts was 100%. The overall major adverse cardiovascular event rate was 13%: 7 patients with ischemic stroke at < 30 days post-procedure, and 1 transient ischemic attack 30 days post-procedure. The total follow-up mortality rate was 0%. The mean follow-up period was 15.7±8.7 months (range 5.6–38.3 months; median 13.5 months; Donas et al., 2008). In comparison to the rates for immediate procedure-related complications, follow-up mortality, and post-procedure-related complications identified by Donas and colleagues (Donas et al., 2008), our rates were similar, but we captured all the angiographic and procedure-related complications not captured in the previous meta-analysis due to the inclusion of all reported complications. However, a subgroup analysis among our patients revealed a similar combined rate per person of follow-up ischemic stroke and transient ischemic attack (5 [11%]), among the three groups.

When managing a patient with a spontaneous or traumatic dissection who has had a stent placed, our data suggest that traumatic dissection patients are at increased risk for immediate and follow-up complications, despite being started on similar dual antiplatelet regimens. The traumatic dissection patients were younger and had less pre-stent stenosis, although both groups appeared to have complete resolution of the vessel architecture following stent reconstruction, as demonstrated by post-stent stenosis measurements. Transcranial Doppler ultrasound studies have shown a high frequency of intracranial microemboli in patients with carotid artery dissections, supporting the idea that most ischemic events are secondary to embolization of a thrombus (versus hemodynamic compromise of cerebral perfusion; Albuquerque et al., 2002; Kadkhodayan et al., 2005). Traumatic dissections may expose larger regions of the vessel endothelium, leading to an increase in thrombus formation, which may be disrupted during the initial stent placement and embolize. Similarly, despite attempting to completely cover the traumatically-dissected vessel segment with the stent, a portion of the edge of the dissected segment may remain exposed, potentially creating a site that is at risk for myointimal proliferation, leading to in-stent/peri-stent stenosis and/or occlusion, as well as a site from which micro-thrombi can embolize due to its exposure to the blood, leading to activation of the coagulation cascade.

Study limitations

This analysis was based on retrospective, observational studies with a small sample size, in whom endovascular stent reconstruction was used to treat extracranial and intracranial arterial dissections affecting the carotid and vertebral arterial vasculature. Further distinction is not always possible because the dissected segment extends from the extracranial segment into the contiguous intracranial segment, requiring stent placement in both sets of arteries. However, we provided the indications for treatment, which may be more helpful in interpreting the risk:benefit ratio in individual patients. The sample size is small due to the stringent inclusion criteria we applied. Due to the paucity of studies, we could not apply the rigorous criteria used for a systematic review or meta-analysis (Mandrekar et al., 2011). The necessary parameters documented were chosen as those that are required to provide relatively reliable estimates of angiographic results following stent placement with long-term patency rates and associated clinical event rates. The use of endovascular stents for reconstruction of spontaneous arterial dissection is an off-label use. Although stent placement is not considered to be first-line treatment for arterial dissections, several criteria were used to select patients for stent placement, which is reflective of varying practice paradigms at each institution. There are no uniformly accepted criteria for patient selection for endovascular treatment. A variety of stents were utilized, based on the commercial availability and judgment of the treating endovascular physicians. Due to our small sample size, we grouped the extracranial and intracranial carotid and vertebral dissections treated with stent placement together.

Conclusion

In this meta-analysis, a low rate of new transient ischemic attack, ischemic stroke, or death was observed in patients who had cranio-cervical dissections treated with stent placement with resolution of angiographic abnormalities during long-term follow-up. Similarly, there was a low rate of stent restenosis and occlusion, supporting the feasibility, safety, and effectiveness of endovascular stent reconstruction of cervico-cranial arterial dissections.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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