Neurosurg Rev DOI 10.1007/s10143-014-0541-y
REVIEW
Clinical outcomes of patients with vertebral artery dissection treated endovascularly: a meta-analysis Silvia Hernández-Durán & Christopher S. Ogilvy
Received: 30 October 2013 / Accepted: 8 February 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract The purpose of this study was to present a metaanalysis on the safety and efficacy of different endovascular modalities when treating vertebral artery dissections, since ideal treatment remains controversial. We performed a meta-analysis of 39 retrospective studies involving different treatment modalities for vertebral artery dissections in adults and obtained weighted pooled proportional outcome and mortality ratios with a random effects model. Overall, 75.11 % (confidence interval (CI) 68.89–80.84, I2 66.89 %) had excellent outcomes, 10.10 % (CI 6.83–15.56, I2 65.64 %) had good outcomes, and 13.70 % (CI 9.64–18.35, I2 60.33 %) had poor outcomes. Postoperative complications occurred in 10.52 % (CI 6.87– 14.84, I2 62.48 %), with 2.73 % (CI 1.64–4.10, I2 0.0 %) exhibiting vasospasm, 3.03 % (CI 1.88–4.46, I2 0.0 %) experiencing postoperative rebleeding, and 6.31 % (CI 3.57– 9.76, I2 60.92 %) showing ischemia. Overall mortality was 8.69 % (CI 6.13–11.64, I2 33.76 %). When compared to these overall ratios, different treatment modality subgroups did not differ significantly, except for the proximal occlusion group, with poor outcome ratio=26.96 % (difference 13.26, CI 0.02– 30.04, p=0.0403) and mortality ratio=21.36 % (difference 12.67, CI 0.94–28.86, p=0.0189). Different endovascular treatment modalities are comparatively safe and effective in the management of vertebral artery dissection. Their reduced S. Hernández-Durán : C. S. Ogilvy Neurosurgical Service, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Wang 745, Boston, MA, USA C. S. Ogilvy e-mail: [email protected]
operative time, minimal invasiveness, and overall safety render them a suitable option for intervention-amenable dissections. Keywords Vertebral artery dissection . Cervical artery dissection . Endovascular treatment . Meta-analysis
Introduction Vertebral artery dissection (VAD) has been recognized as an important cause of stroke and nontraumatic subarachnoid hemorrhage (SAH) in middle-aged patients [13, 42]. Since the natural history remains poorly understood, much controversy exists surrounding VAD treatment [2, 10, 27, 64]. Current options include conservative management, medical therapy with anticoagulants or anti-platelet agents, open surgery, or endovascular techniques [42]. Because of their reduced operative time, minimal invasiveness, and overall safety, endovascular procedures have emerged as a suitable alternative to open surgery [4]. Deconstructive techniques that sacrifice the parent vessel, such as balloon occlusion, balloon-assisted coiling, and internal coil trapping of the parent vessel, and reconstructive methods, such as proximal coil occlusion of the dissecting aneurysm, stenting, and stent-assisted coiling, are among the endovascular options. To date, there are no guidelines regarding choice of endovascular techniques for those dissections requiring intervention. We conducted a meta-analysis of retrospective studies addressing endovascular treatment of VAD to establish its overall safety and efficacy, and whether specific treatment modalities appear to be superior when managing intervention-amenable VAD.
S. Hernández-Durán University of Costa Rica School of Medicine, Ciudad Universitaria Rodrigo Facio, San Pedro de Montes de Oca, San José, Costa Rica
Materials and methods
S. Hernández-Durán (*) Apdo. 1232-1007, San José, Costa Rica e-mail: [email protected]
We conducted a literature search of published medical papers between 1990 and May 2013 through the U.S. National Library
Neurosurg Rev
of Medicine’s PubMed. The search terms were “vertebral artery dissection,” “vertebral artery dissecting aneurysms,” “cervical artery dissection,” “endovascular procedures,” “endovascular treatment,” and “endovascular technique.” We also reviewed the references to identify further relevant studies. Inclusion criteria were (1) VAD treated by means of endovascular technique, including stenting, stent-assisted coiling, parent vessel occlusion by means of coiling or balloons, balloon-assisted coiling, and proximal occlusion; (2) studies including five or more adult patients, irrespective of endovascular treatment modality; (3) diagnosis made through computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography; (4) dissection mechanism either spontaneous, traumatic, or iatrogenic; (5) location of dissection either intracranial or extracranial; (6) follow-up of at least 1 month; (7) reported clinical outcomes, preferably noting the occurrence of transient ischemic attack (TIA), ischemic or hemorrhagic stroke, rebleeding, and death during the postoperative period. Exclusion criteria were (1) dissections involving solely the basilar trunk or the posterior inferior cerebellar artery (PICA), (2) pediatric patients, (3) treatment techniques such as intraarterial thrombolytic administration and thrombectomy, and (4) insufficient information. Accordingly, in studies that included multiple treatment forms, only those patients who underwent an endovascular procedure were considered. Because no randomized-controlled trials are available, we based our review on observational studies. In order to evaluate the quality of these studies, a checklist was filled out for each manuscript, assessing whether (1) the paper was published in a peer- reviewed journal, (2) the purpose of the study was indicated, (3) there was missing information, (4) institutional affiliations were identified, (5) investigators were independent of sponsoring agencies or had any financial interests, (6) there were clear inclusion and exclusion criteria and the subjects included met said criteria, (7) the methods of diagnosis were defined and reliable, and (8) the outcomes were clearly defined. The level of evidence provided falls into the C category of the American Heart Association criteria. The following information was collected (when available) using a data extraction form: number of patients who underwent endovascular treatment, mean age of presentation, sex, comorbidities, clinical presentation, angiographic findings, dissection mechanism, site of dissection, PICA involvement, bilateral dissection, number of dissections treated, type of endovascular technique used, angiographic results, clinical outcome, and complications. Clinical presentation was classified in four categories: (1) SAH; (2) ischemia, including TIA and stroke; (3) SAH and concomitant stroke; and (4) others, including headache, neck pain, various neurological symptoms, and incidental findings.
For those presenting with SAH, the Hunt and Hess (HH) and Fisher and World Federation of Neurosurgical Societies (WFNS) grades were gathered and further classified into (1) low-grade, for HH grades I–III or WFNS grades 1–3, and (2) high-grade, for HH grades IV–V or WFNS grades 4–5. Angiographic results were classified as (1) complete resolution; (2) partial resolution, if partial occlusion or shrinking of the aneurysm was achieved; and (3) unsuccessful, if the dissecting aneurysm increased in size, in-stent thrombosis occurred, or the dissection recanalized. For clinical outcomes, the occurrence of postoperative ischemic events (stroke or TIA), rebleeding, vasospasm, and death were recorded. Outcome data were classified into (1) excellent, with modified Rankin scales (mRS) of 0–1, Glasgow outcome scale (GOS) of 5, or Karnofsky of 80–100; (2) good, with mRS of 2, GOS of 4, or Karnofsky of 50–70; and (3) poor, with mRS of 3–5, GOS of 1–3, or Karnofsky of 0–40. Mean values with 95 % confidence intervals (CI) were obtained for continuous variables such as age. Heterogeneity analysis was performed through the I2 statistic, which comprises the percentage of observed total variation across studies. Weighted pooled proportions with their 95 % CI were then calculated for variables such as clinical and angiographic presentation, PICA involvement, and outcome by means of MedCalc® version 12.7.0.0. A random effects model was preferred due to the effect variability between the studies. Weighted pooled proportional mortality and outcome ratios for each treatment subgroup were compared to the overall weighted pooled proportional mortality and outcome ratios by means of chi square test.
Results All studies Over 200 papers were identified through the initial literature search regarding endovascularly treated VAD. Thirty-nine studies were included in this analysis, for they met both the inclusion criteria and the quality assessment points. It should be noted that several studies included patients with carotid and basilar dissections, as well as pediatric patients. Only those patients who were relevant to this analysis were taken into consideration within those studies. A total of 637 patients were included in the 39 studies, of which 39.35 % (CI 34.83–43.95, I2 27.98 %) were females and 60.65 % (CI 56.05–65.17, I2 27.98 %) were males. Mean age was 50.18 years (CI 48.42–51.94). Only few studies mentioned patients’ comorbidities; eight [6, 11, 14, 25, 26, 30, 56, 66] of them reported hypertension in 35.21 % (CI 28.58–42.15, I2 0.0 %), while diabetes mellitus type 2 was seen in 9.09 % (CI 4.67–14.78, I2 0.0 %) in four studies [11, 25, 56, 66]. Fibromuscular dysplasia [6, 66], smoking
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[25], and dyslipidemia [11] were described in isolated studies, with incidences of 20.65 % (CI 7.20–38.74, I2 0.0 %), 26.09 %, and 13.16 %, respectively. The majority of the lesions had an intracranial location, with only 3.54 % (CI 1.68–6.04, I2 54.30 %) being cervical. PICA involvement was seen in 14.62 % (CI 8.39–22.20, I2 84.21 %). The most common clinical presentation was SAH, accounting for 75.90 % (CI 63.68–86.29, I2 91.65 %), followed by ischemia in 12.30 % (CI 7.16–18.59, I2 79.78 %), other symptoms in 9.06 % (CI 4.88–14.35, I2 77.08 %), and SAH and stroke in 1.89 % (CI 1.00–3.05, I2 0.0 %). Hemorrhages were low-grade in 73.66 % (CI 65.40– 81.16, I2 71.45 %) of the cases presenting with SAH or SAH and stroke, while 26.34 % (CI 18.84–34.60, I2 71.45 %) were high-grade. Angiographic characteristics were described in 15 studies [1, 2, 6, 11, 14, 16, 21, 25, 26, 31, 36, 37, 40, 60]. Pearl and string sign was the most common angiographic characteristic, accounting for 47.51 % (CI 24.08–71.53, I2 92.98 %). Fusiform dilation was seen in 17.28 % (CI 5.35–34.13, I2 88.60 %), aneurysmal dilation, not otherwise specified in 15.38 % (CI 3.43–33.72, I2 90.78 %), string sign in 8.78 % (CI 4.22–14.80, I2 48.74 %), and double lumen in 2.53 % (CI 0.92–4.91, I2 0.0 %). Amongst the 637 patients, eight underwent treatment for bilateral dissections [34, 53, 56]. A total of 645 lesions were therefore treated. Of these patients, 1.59 % (CI 0.79–2.66, I2 0.0 %) underwent balloon-assisted coiling [15, 40], 4.28 % (CI 1.94–7.47, I2 66.85 %) balloon occlusion [6, 15, 29, 40, 59], 58.29 % (CI 44.10–71.81, I2 92.76 %) internal trapping [1, 3, 6, 11, 15, 16, 19–21, 23–26, 28–30, 32, 33, 36, 37, 40, 43, 46, 47, 53–56, 60, 66], 6.18 % (CI 3.09–10.24, I2 72.12 %) proximal occlusion [15, 19, 20, 26, 45, 46, 54, 55, 61, 66], 11.07 % (CI 5.69–17.96, I2 84.45 %) stenting [1, 2, 5, 14, 20, 21, 25, 26, 30, 31, 33, 34, 41, 43, 53], and 9.68 % (CI 5.78– 14.46, I2 71.40 %) stent-assisted coiling [1, 2, 5, 6, 14, 20, 21, 26, 31, 33, 34, 41, 45, 53–55]. Angiographic results were reported in 26 studies, in which 82.81 % (CI 73.92–90.16, I2 78.60 %) achieved complete resolution. Partial resolution was seen in 9.77 % (CI 5.29– 15.42, I2 64.96 %), and angiographic results were unsuccessful in 3.92 % (CI 2.20–6.12, I2 12.31 %). Mean follow-up was 24.47 months (CI 20.23–28.92). Rabinov et al. [46] lost three patients to follow-up, while Albuquerque et al. [3] lost one, thus resulting in 633 patients for whom follow-up information was available. Of these patients, 75.11 % (CI 68.89–80.84, I2 66.89 %) had excellent outcomes, 10.10 % (CI 6.83–15.56, I2 65.64 %) had good outcomes, and 13.70 % (CI 9.64–18.35, I2 60.33 %) had poor outcomes. Postoperative complications occurred in 10.52 % (CI 6.87–14.84, I2 62.48 %), with 2.73 % (CI 1.64–4.10, I2 0.0 %) exhibiting vasospasm, 3.03 % (CI 1.88–4.46, I2 0.0 %) experiencing postoperative rebleeding,
and 6.31 % (CI 3.57–9.76, I2 60.92 %) showing ischemia. Overall mortality was 8.69 % (CI 6.13–11.64, I2 33.76 %, see Fig. 1). Extracranial dissection group Five studies [1, 16, 30, 34, 45] included 19 patients with extracranial dissections, which accounted for 3.54 % (CI 1.68–6.04, I2 54.30 %) of all the lesions. Of these patients, 51.35 % (CI 29.26–73.17, I2 19.20 %) were females, and 48.65 % (CI 26.83–70.74, I2 19.20 %) were males; 40.23 % (CI 4.20–84.62, I2 81.40 %) were spontaneous, and 59.77 % (CI 15.38–95.80, I2 81.40 %) were traumatic in etiology. Presenting symptoms were predominantly “other” (60.27 %, CI 35.34–82.64, I2 33.09 %), and ischemia accounted for 39.73 % (CI 17.36–64.66, I2 33.09 %). The preferred treatment modality in this group was stenting (62.57 %, CI 25.20–92.79, I2 71.10 %), followed by stentassisted coiling (17.84 %, CI 5.47–35.29, I2 0.0 %), internal trapping (12.21 %, CI 1.56–30.85, I2 21.96 %), balloon occlusion (9.00 %, CI 1.08–23.32, I2 0.0 %), proximal occlusion (9.00 %, CI 1.08–23.32, I2 0.0 %), and balloon-assisted coiling (5.31 %, CI 0.11–17.58, I2 0.0 %). Clinical outcomes were excellent in 79.38 % (CI 59.00– 93.98, I2 16.74 %), good in 13.50 % (CI 3.08–29.70, I2 0.0 %), and poor in 14.06 % (CI 3.36–30.44, I2 0.0 %). Complete angiographic resolution was seen in 90.11 % (CI 71.17–99.46, I2 13.18 %), while partial resolution and unsuccessful angiographic results were 9.89 % (CI 0.54–28.83, I2 13.18 %) and 5.32 % (CI 0.01–19.52, I2 0.0 %), respectively. Angiographic outcome was described in all but one study [15]. Mortality was 8.30 % (CI 0.85–22.34, I2 0.0 %), and it was seen in a stent-treated patient [5]. Treatment subgroups and comparisons Three studies had to be excluded from this subsection because individual data were not available for treatment subsets [3, 25, 56]. Results are summarized in Tables 1, 2, and 3.
Discussion Several studies and case reports have addressed the safety and efficacy of endovascular procedures in the treatment of VAD, but the amount of patients included in them is usually small. To date, only few meta-analyses and systematic literature reviews have been performed on this subject [17, 44], and while they have focused on a single endovascular treatment modality, they have included both carotid and vertebral lesions. Our study is unique, as it compares the clinical and angiographic outcomes of different endovascular modalities when treating VAD, exclusively.
Neurosurg Rev
Fig. 1 Overall mortality rate by study in patients with vertebral artery dissections treated endovascularly in weighted pooled proportions
Patient demographics and comorbidities
Clinical presentation and angiographic characteristics
Our analysis revealed that the majority of patients with VAD treated endovascularly were males, with a mean age of 51 years, coinciding with previous observations. Several risk factors have been postulated in the etiopathogenesis of VAD. Hypertension, hypercholesterolemia, diabetes mellitus, smoking, and other traditional atherosclerotic risk factors have been associated with VAD [25], but their role remains unclear [48]. Structural defects of the arterial wall due to underlying connective tissue disorders have also been linked to the development of VAD [7, 8, 51], even though specific genotypes have not been elucidated yet. Our analysis revealed only few studies mentioning patient comorbidities and possible risk factors, with hypertension being present in 35.21 % and diabetes mellitus type 2 in 9.09 % of the patients in whom comorbidities and risk factors were noted. Because of the scope and design of this study, it is not possible to derive any further contributions to this subject. However, it is well known that these comorbidities could affect the natural history of the dissection, and further studies assessing their role in VAD are needed.
The classical clinical presentation of VAD varies depending on its location. Extracranial lesions usually have a milder course, presenting with nonspecific complaints like dizziness, vertigo, tinnitus, nausea, and vomiting or with lateral medullary or cerebellar infarctions [12, 57]. Intracranial lesions are more likely to rupture because they are more prone to extend subadventitially, since the media and adventitia laminae in the intradural portion of the artery are thinner [18]. Therefore, SAH is one of the main presenting symptoms. Another form of presentation of intracranial VAD is ischemia, which results from luminal occlusion by intramural hematoma [50]. Our analysis revealed that the most common form of presentation was SAH, accounting for 75.90 % of the cases, and 73.66 % of those hemorrhages were low-grade. It is noteworthy that the majority of the cases analyzed corresponded to intracranial dissections. When regarded separately, the extracranial group predominantly presented with other symptoms and ischemia. These findings correspond to the pathophysiological mechanisms that distinguish the dissections at these different sites. On the other hand, the most classical angiographic finding
Neurosurg Rev Table 1 Weighted pooled proportions for sex, clinical presentation, and outcomes by endovascular treatment modality of VAD patients Balloon-assisted coiling
Balloon occlusion
Internal trapping
Proximal occlusion
Stent-assisted coiling
Stenting
N studies N patients Females (CI) I2
2 4 28.87 (2.77–67.79) 0.00
5 26 46.84 (25.75–68.58) 33.42
27 373 41.69 (35.26–48.26) 35.19
10 39 44.59 (30.09–59.57) 9.29
16 48 39.36 (27.83–51.53) 0.00
14 59 35.00 (21.81–49.89) 34.57
Males (CI) I2 Age (CI) SAH (CI) I2 Ischemia (CI) I2 SAH and S (CI) I2 Others (CI) I2 LG SAH (CI) I2 HG SAH (CI) I2 Excellent (CI) I2 Good (CI) I2 Poor (CI) I2 Mortality (CI)
71.13 (32.21–91.23) 0.00 48 (22.59–73.41) 59.89 (0.01–95.67) 77.67 40.11 (4.33–99.99) 77.67 N/A
53.16 (31.45–74.25) 33.42 50 (44.81–56.00) 74.92 (37.34–98.17) 78.10 12.98 (2.06–31.24) 35.06 N/A
55.41 (40.43–69.91) 9.29 50 (39.02–60.00) 82.44 (67.70–93.37) 26.54 7.65 (1.95–16.64) 0.00 13.11 (5.22–23.87) 0.00 13.48 (5.07–25.11) 7.88 68.62 (50.57–84.14) 23.60 31.38 (15.86–49.43) 23.60 65.75 (41.17–86.50) 63.83 10.92 (3.82–21.06) 0.00 26.96 (9.94–48.58) 55.72 21.36 (10.80–34.34)
60.64 (48.47–72.17) 0.00 48 (44.80–51.45) 62.20 (47.16–76.12) 30.57 27.51 (16.69–39.87) 10.59 N/A
59.04 (43.18–74.00) 43.64 45 (42.63–47.80) 34.76 (18.69–52.87) 57.34 34.17 (20.00–49.97) 44.60 N/A
N/A N/A N/A N/A N/A N/A 59.89 (0.01–95.67) 77.67 40.11 (4.33–99.99) 77.67 9.04 (0.89–42.05) 0.00 9.04 (0.89–42.05)
58.31 (51.74–64.74) 35.19 51 (48.85–53.45) 85.01 (75.10–92.74) 82.31 6.60 (3.03–11.42) 60.19 2.11 (0.92–3.77) 1.25 12.98 (2.06–31.24) 6.32 (2.54–11.63) 35.06 67.70 78.89 (43.19–98.98) 72.26 (63.60–80.15) 63.32 62.43 21.11 (1.02–56.81) 27.74 (19.85–36.40) 63.32 62.43 84.05 (68.35–95.06) 72.49 (62.96–81.05) 9.33 72.94 9.84 10.75 (2.04–22.58) (5.89–16.86) 0.00 63.84 10.94 (2.57–24.10) 16.28 (11.00–22.37) 0.00 51.90 8.38 (0.95–22.12) 10.99 (7.52–15.02)
14.91 (7.32–24.60) 0.00 87.58 (72.12–97.33) 0.00 12.42 (2.67–27.88) 0.00 83.29 (72.30–91.94) 12.63 10.48 (4.23–19.08) 0.00 11.00 (4.57–19.75) 0.00 6.41 (1.77–13.65)
26.05 (13.52–40.98) 43.47 91.69 (73.79–99.78) 0.0 8.31 (0.22–26.21) 0.00 73.39 (57.07–86.95) 51.70 16.43 (7.13–28.62) 34.41 8.08 (2.98–15.38) 0.00 6.67 (2.13–13.48)
0.00
0.00
5.00
0.00
0.00
I2
23.65
CI confidence interval, HG high-grade, LG low-grade, SAH subarachnoid hemorrhage, SAH and S SAH and stroke
Table 2 Weighted pooled proportional mortality ratios by subgroups and comparison to overall weighted pooled proportional mortality ratio
Asterisks and bold font are meant to draw attention to the statistically-significant values
Subgroup
Proportional mortality ratio (%)
Difference (%) (95 % CI)
Significance level (p
REVIEW
Clinical outcomes of patients with vertebral artery dissection treated endovascularly: a meta-analysis Silvia Hernández-Durán & Christopher S. Ogilvy
Received: 30 October 2013 / Accepted: 8 February 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract The purpose of this study was to present a metaanalysis on the safety and efficacy of different endovascular modalities when treating vertebral artery dissections, since ideal treatment remains controversial. We performed a meta-analysis of 39 retrospective studies involving different treatment modalities for vertebral artery dissections in adults and obtained weighted pooled proportional outcome and mortality ratios with a random effects model. Overall, 75.11 % (confidence interval (CI) 68.89–80.84, I2 66.89 %) had excellent outcomes, 10.10 % (CI 6.83–15.56, I2 65.64 %) had good outcomes, and 13.70 % (CI 9.64–18.35, I2 60.33 %) had poor outcomes. Postoperative complications occurred in 10.52 % (CI 6.87– 14.84, I2 62.48 %), with 2.73 % (CI 1.64–4.10, I2 0.0 %) exhibiting vasospasm, 3.03 % (CI 1.88–4.46, I2 0.0 %) experiencing postoperative rebleeding, and 6.31 % (CI 3.57– 9.76, I2 60.92 %) showing ischemia. Overall mortality was 8.69 % (CI 6.13–11.64, I2 33.76 %). When compared to these overall ratios, different treatment modality subgroups did not differ significantly, except for the proximal occlusion group, with poor outcome ratio=26.96 % (difference 13.26, CI 0.02– 30.04, p=0.0403) and mortality ratio=21.36 % (difference 12.67, CI 0.94–28.86, p=0.0189). Different endovascular treatment modalities are comparatively safe and effective in the management of vertebral artery dissection. Their reduced S. Hernández-Durán : C. S. Ogilvy Neurosurgical Service, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Wang 745, Boston, MA, USA C. S. Ogilvy e-mail: [email protected]
operative time, minimal invasiveness, and overall safety render them a suitable option for intervention-amenable dissections. Keywords Vertebral artery dissection . Cervical artery dissection . Endovascular treatment . Meta-analysis
Introduction Vertebral artery dissection (VAD) has been recognized as an important cause of stroke and nontraumatic subarachnoid hemorrhage (SAH) in middle-aged patients [13, 42]. Since the natural history remains poorly understood, much controversy exists surrounding VAD treatment [2, 10, 27, 64]. Current options include conservative management, medical therapy with anticoagulants or anti-platelet agents, open surgery, or endovascular techniques [42]. Because of their reduced operative time, minimal invasiveness, and overall safety, endovascular procedures have emerged as a suitable alternative to open surgery [4]. Deconstructive techniques that sacrifice the parent vessel, such as balloon occlusion, balloon-assisted coiling, and internal coil trapping of the parent vessel, and reconstructive methods, such as proximal coil occlusion of the dissecting aneurysm, stenting, and stent-assisted coiling, are among the endovascular options. To date, there are no guidelines regarding choice of endovascular techniques for those dissections requiring intervention. We conducted a meta-analysis of retrospective studies addressing endovascular treatment of VAD to establish its overall safety and efficacy, and whether specific treatment modalities appear to be superior when managing intervention-amenable VAD.
S. Hernández-Durán University of Costa Rica School of Medicine, Ciudad Universitaria Rodrigo Facio, San Pedro de Montes de Oca, San José, Costa Rica
Materials and methods
S. Hernández-Durán (*) Apdo. 1232-1007, San José, Costa Rica e-mail: [email protected]
We conducted a literature search of published medical papers between 1990 and May 2013 through the U.S. National Library
Neurosurg Rev
of Medicine’s PubMed. The search terms were “vertebral artery dissection,” “vertebral artery dissecting aneurysms,” “cervical artery dissection,” “endovascular procedures,” “endovascular treatment,” and “endovascular technique.” We also reviewed the references to identify further relevant studies. Inclusion criteria were (1) VAD treated by means of endovascular technique, including stenting, stent-assisted coiling, parent vessel occlusion by means of coiling or balloons, balloon-assisted coiling, and proximal occlusion; (2) studies including five or more adult patients, irrespective of endovascular treatment modality; (3) diagnosis made through computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography; (4) dissection mechanism either spontaneous, traumatic, or iatrogenic; (5) location of dissection either intracranial or extracranial; (6) follow-up of at least 1 month; (7) reported clinical outcomes, preferably noting the occurrence of transient ischemic attack (TIA), ischemic or hemorrhagic stroke, rebleeding, and death during the postoperative period. Exclusion criteria were (1) dissections involving solely the basilar trunk or the posterior inferior cerebellar artery (PICA), (2) pediatric patients, (3) treatment techniques such as intraarterial thrombolytic administration and thrombectomy, and (4) insufficient information. Accordingly, in studies that included multiple treatment forms, only those patients who underwent an endovascular procedure were considered. Because no randomized-controlled trials are available, we based our review on observational studies. In order to evaluate the quality of these studies, a checklist was filled out for each manuscript, assessing whether (1) the paper was published in a peer- reviewed journal, (2) the purpose of the study was indicated, (3) there was missing information, (4) institutional affiliations were identified, (5) investigators were independent of sponsoring agencies or had any financial interests, (6) there were clear inclusion and exclusion criteria and the subjects included met said criteria, (7) the methods of diagnosis were defined and reliable, and (8) the outcomes were clearly defined. The level of evidence provided falls into the C category of the American Heart Association criteria. The following information was collected (when available) using a data extraction form: number of patients who underwent endovascular treatment, mean age of presentation, sex, comorbidities, clinical presentation, angiographic findings, dissection mechanism, site of dissection, PICA involvement, bilateral dissection, number of dissections treated, type of endovascular technique used, angiographic results, clinical outcome, and complications. Clinical presentation was classified in four categories: (1) SAH; (2) ischemia, including TIA and stroke; (3) SAH and concomitant stroke; and (4) others, including headache, neck pain, various neurological symptoms, and incidental findings.
For those presenting with SAH, the Hunt and Hess (HH) and Fisher and World Federation of Neurosurgical Societies (WFNS) grades were gathered and further classified into (1) low-grade, for HH grades I–III or WFNS grades 1–3, and (2) high-grade, for HH grades IV–V or WFNS grades 4–5. Angiographic results were classified as (1) complete resolution; (2) partial resolution, if partial occlusion or shrinking of the aneurysm was achieved; and (3) unsuccessful, if the dissecting aneurysm increased in size, in-stent thrombosis occurred, or the dissection recanalized. For clinical outcomes, the occurrence of postoperative ischemic events (stroke or TIA), rebleeding, vasospasm, and death were recorded. Outcome data were classified into (1) excellent, with modified Rankin scales (mRS) of 0–1, Glasgow outcome scale (GOS) of 5, or Karnofsky of 80–100; (2) good, with mRS of 2, GOS of 4, or Karnofsky of 50–70; and (3) poor, with mRS of 3–5, GOS of 1–3, or Karnofsky of 0–40. Mean values with 95 % confidence intervals (CI) were obtained for continuous variables such as age. Heterogeneity analysis was performed through the I2 statistic, which comprises the percentage of observed total variation across studies. Weighted pooled proportions with their 95 % CI were then calculated for variables such as clinical and angiographic presentation, PICA involvement, and outcome by means of MedCalc® version 12.7.0.0. A random effects model was preferred due to the effect variability between the studies. Weighted pooled proportional mortality and outcome ratios for each treatment subgroup were compared to the overall weighted pooled proportional mortality and outcome ratios by means of chi square test.
Results All studies Over 200 papers were identified through the initial literature search regarding endovascularly treated VAD. Thirty-nine studies were included in this analysis, for they met both the inclusion criteria and the quality assessment points. It should be noted that several studies included patients with carotid and basilar dissections, as well as pediatric patients. Only those patients who were relevant to this analysis were taken into consideration within those studies. A total of 637 patients were included in the 39 studies, of which 39.35 % (CI 34.83–43.95, I2 27.98 %) were females and 60.65 % (CI 56.05–65.17, I2 27.98 %) were males. Mean age was 50.18 years (CI 48.42–51.94). Only few studies mentioned patients’ comorbidities; eight [6, 11, 14, 25, 26, 30, 56, 66] of them reported hypertension in 35.21 % (CI 28.58–42.15, I2 0.0 %), while diabetes mellitus type 2 was seen in 9.09 % (CI 4.67–14.78, I2 0.0 %) in four studies [11, 25, 56, 66]. Fibromuscular dysplasia [6, 66], smoking
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[25], and dyslipidemia [11] were described in isolated studies, with incidences of 20.65 % (CI 7.20–38.74, I2 0.0 %), 26.09 %, and 13.16 %, respectively. The majority of the lesions had an intracranial location, with only 3.54 % (CI 1.68–6.04, I2 54.30 %) being cervical. PICA involvement was seen in 14.62 % (CI 8.39–22.20, I2 84.21 %). The most common clinical presentation was SAH, accounting for 75.90 % (CI 63.68–86.29, I2 91.65 %), followed by ischemia in 12.30 % (CI 7.16–18.59, I2 79.78 %), other symptoms in 9.06 % (CI 4.88–14.35, I2 77.08 %), and SAH and stroke in 1.89 % (CI 1.00–3.05, I2 0.0 %). Hemorrhages were low-grade in 73.66 % (CI 65.40– 81.16, I2 71.45 %) of the cases presenting with SAH or SAH and stroke, while 26.34 % (CI 18.84–34.60, I2 71.45 %) were high-grade. Angiographic characteristics were described in 15 studies [1, 2, 6, 11, 14, 16, 21, 25, 26, 31, 36, 37, 40, 60]. Pearl and string sign was the most common angiographic characteristic, accounting for 47.51 % (CI 24.08–71.53, I2 92.98 %). Fusiform dilation was seen in 17.28 % (CI 5.35–34.13, I2 88.60 %), aneurysmal dilation, not otherwise specified in 15.38 % (CI 3.43–33.72, I2 90.78 %), string sign in 8.78 % (CI 4.22–14.80, I2 48.74 %), and double lumen in 2.53 % (CI 0.92–4.91, I2 0.0 %). Amongst the 637 patients, eight underwent treatment for bilateral dissections [34, 53, 56]. A total of 645 lesions were therefore treated. Of these patients, 1.59 % (CI 0.79–2.66, I2 0.0 %) underwent balloon-assisted coiling [15, 40], 4.28 % (CI 1.94–7.47, I2 66.85 %) balloon occlusion [6, 15, 29, 40, 59], 58.29 % (CI 44.10–71.81, I2 92.76 %) internal trapping [1, 3, 6, 11, 15, 16, 19–21, 23–26, 28–30, 32, 33, 36, 37, 40, 43, 46, 47, 53–56, 60, 66], 6.18 % (CI 3.09–10.24, I2 72.12 %) proximal occlusion [15, 19, 20, 26, 45, 46, 54, 55, 61, 66], 11.07 % (CI 5.69–17.96, I2 84.45 %) stenting [1, 2, 5, 14, 20, 21, 25, 26, 30, 31, 33, 34, 41, 43, 53], and 9.68 % (CI 5.78– 14.46, I2 71.40 %) stent-assisted coiling [1, 2, 5, 6, 14, 20, 21, 26, 31, 33, 34, 41, 45, 53–55]. Angiographic results were reported in 26 studies, in which 82.81 % (CI 73.92–90.16, I2 78.60 %) achieved complete resolution. Partial resolution was seen in 9.77 % (CI 5.29– 15.42, I2 64.96 %), and angiographic results were unsuccessful in 3.92 % (CI 2.20–6.12, I2 12.31 %). Mean follow-up was 24.47 months (CI 20.23–28.92). Rabinov et al. [46] lost three patients to follow-up, while Albuquerque et al. [3] lost one, thus resulting in 633 patients for whom follow-up information was available. Of these patients, 75.11 % (CI 68.89–80.84, I2 66.89 %) had excellent outcomes, 10.10 % (CI 6.83–15.56, I2 65.64 %) had good outcomes, and 13.70 % (CI 9.64–18.35, I2 60.33 %) had poor outcomes. Postoperative complications occurred in 10.52 % (CI 6.87–14.84, I2 62.48 %), with 2.73 % (CI 1.64–4.10, I2 0.0 %) exhibiting vasospasm, 3.03 % (CI 1.88–4.46, I2 0.0 %) experiencing postoperative rebleeding,
and 6.31 % (CI 3.57–9.76, I2 60.92 %) showing ischemia. Overall mortality was 8.69 % (CI 6.13–11.64, I2 33.76 %, see Fig. 1). Extracranial dissection group Five studies [1, 16, 30, 34, 45] included 19 patients with extracranial dissections, which accounted for 3.54 % (CI 1.68–6.04, I2 54.30 %) of all the lesions. Of these patients, 51.35 % (CI 29.26–73.17, I2 19.20 %) were females, and 48.65 % (CI 26.83–70.74, I2 19.20 %) were males; 40.23 % (CI 4.20–84.62, I2 81.40 %) were spontaneous, and 59.77 % (CI 15.38–95.80, I2 81.40 %) were traumatic in etiology. Presenting symptoms were predominantly “other” (60.27 %, CI 35.34–82.64, I2 33.09 %), and ischemia accounted for 39.73 % (CI 17.36–64.66, I2 33.09 %). The preferred treatment modality in this group was stenting (62.57 %, CI 25.20–92.79, I2 71.10 %), followed by stentassisted coiling (17.84 %, CI 5.47–35.29, I2 0.0 %), internal trapping (12.21 %, CI 1.56–30.85, I2 21.96 %), balloon occlusion (9.00 %, CI 1.08–23.32, I2 0.0 %), proximal occlusion (9.00 %, CI 1.08–23.32, I2 0.0 %), and balloon-assisted coiling (5.31 %, CI 0.11–17.58, I2 0.0 %). Clinical outcomes were excellent in 79.38 % (CI 59.00– 93.98, I2 16.74 %), good in 13.50 % (CI 3.08–29.70, I2 0.0 %), and poor in 14.06 % (CI 3.36–30.44, I2 0.0 %). Complete angiographic resolution was seen in 90.11 % (CI 71.17–99.46, I2 13.18 %), while partial resolution and unsuccessful angiographic results were 9.89 % (CI 0.54–28.83, I2 13.18 %) and 5.32 % (CI 0.01–19.52, I2 0.0 %), respectively. Angiographic outcome was described in all but one study [15]. Mortality was 8.30 % (CI 0.85–22.34, I2 0.0 %), and it was seen in a stent-treated patient [5]. Treatment subgroups and comparisons Three studies had to be excluded from this subsection because individual data were not available for treatment subsets [3, 25, 56]. Results are summarized in Tables 1, 2, and 3.
Discussion Several studies and case reports have addressed the safety and efficacy of endovascular procedures in the treatment of VAD, but the amount of patients included in them is usually small. To date, only few meta-analyses and systematic literature reviews have been performed on this subject [17, 44], and while they have focused on a single endovascular treatment modality, they have included both carotid and vertebral lesions. Our study is unique, as it compares the clinical and angiographic outcomes of different endovascular modalities when treating VAD, exclusively.
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Fig. 1 Overall mortality rate by study in patients with vertebral artery dissections treated endovascularly in weighted pooled proportions
Patient demographics and comorbidities
Clinical presentation and angiographic characteristics
Our analysis revealed that the majority of patients with VAD treated endovascularly were males, with a mean age of 51 years, coinciding with previous observations. Several risk factors have been postulated in the etiopathogenesis of VAD. Hypertension, hypercholesterolemia, diabetes mellitus, smoking, and other traditional atherosclerotic risk factors have been associated with VAD [25], but their role remains unclear [48]. Structural defects of the arterial wall due to underlying connective tissue disorders have also been linked to the development of VAD [7, 8, 51], even though specific genotypes have not been elucidated yet. Our analysis revealed only few studies mentioning patient comorbidities and possible risk factors, with hypertension being present in 35.21 % and diabetes mellitus type 2 in 9.09 % of the patients in whom comorbidities and risk factors were noted. Because of the scope and design of this study, it is not possible to derive any further contributions to this subject. However, it is well known that these comorbidities could affect the natural history of the dissection, and further studies assessing their role in VAD are needed.
The classical clinical presentation of VAD varies depending on its location. Extracranial lesions usually have a milder course, presenting with nonspecific complaints like dizziness, vertigo, tinnitus, nausea, and vomiting or with lateral medullary or cerebellar infarctions [12, 57]. Intracranial lesions are more likely to rupture because they are more prone to extend subadventitially, since the media and adventitia laminae in the intradural portion of the artery are thinner [18]. Therefore, SAH is one of the main presenting symptoms. Another form of presentation of intracranial VAD is ischemia, which results from luminal occlusion by intramural hematoma [50]. Our analysis revealed that the most common form of presentation was SAH, accounting for 75.90 % of the cases, and 73.66 % of those hemorrhages were low-grade. It is noteworthy that the majority of the cases analyzed corresponded to intracranial dissections. When regarded separately, the extracranial group predominantly presented with other symptoms and ischemia. These findings correspond to the pathophysiological mechanisms that distinguish the dissections at these different sites. On the other hand, the most classical angiographic finding
Neurosurg Rev Table 1 Weighted pooled proportions for sex, clinical presentation, and outcomes by endovascular treatment modality of VAD patients Balloon-assisted coiling
Balloon occlusion
Internal trapping
Proximal occlusion
Stent-assisted coiling
Stenting
N studies N patients Females (CI) I2
2 4 28.87 (2.77–67.79) 0.00
5 26 46.84 (25.75–68.58) 33.42
27 373 41.69 (35.26–48.26) 35.19
10 39 44.59 (30.09–59.57) 9.29
16 48 39.36 (27.83–51.53) 0.00
14 59 35.00 (21.81–49.89) 34.57
Males (CI) I2 Age (CI) SAH (CI) I2 Ischemia (CI) I2 SAH and S (CI) I2 Others (CI) I2 LG SAH (CI) I2 HG SAH (CI) I2 Excellent (CI) I2 Good (CI) I2 Poor (CI) I2 Mortality (CI)
71.13 (32.21–91.23) 0.00 48 (22.59–73.41) 59.89 (0.01–95.67) 77.67 40.11 (4.33–99.99) 77.67 N/A
53.16 (31.45–74.25) 33.42 50 (44.81–56.00) 74.92 (37.34–98.17) 78.10 12.98 (2.06–31.24) 35.06 N/A
55.41 (40.43–69.91) 9.29 50 (39.02–60.00) 82.44 (67.70–93.37) 26.54 7.65 (1.95–16.64) 0.00 13.11 (5.22–23.87) 0.00 13.48 (5.07–25.11) 7.88 68.62 (50.57–84.14) 23.60 31.38 (15.86–49.43) 23.60 65.75 (41.17–86.50) 63.83 10.92 (3.82–21.06) 0.00 26.96 (9.94–48.58) 55.72 21.36 (10.80–34.34)
60.64 (48.47–72.17) 0.00 48 (44.80–51.45) 62.20 (47.16–76.12) 30.57 27.51 (16.69–39.87) 10.59 N/A
59.04 (43.18–74.00) 43.64 45 (42.63–47.80) 34.76 (18.69–52.87) 57.34 34.17 (20.00–49.97) 44.60 N/A
N/A N/A N/A N/A N/A N/A 59.89 (0.01–95.67) 77.67 40.11 (4.33–99.99) 77.67 9.04 (0.89–42.05) 0.00 9.04 (0.89–42.05)
58.31 (51.74–64.74) 35.19 51 (48.85–53.45) 85.01 (75.10–92.74) 82.31 6.60 (3.03–11.42) 60.19 2.11 (0.92–3.77) 1.25 12.98 (2.06–31.24) 6.32 (2.54–11.63) 35.06 67.70 78.89 (43.19–98.98) 72.26 (63.60–80.15) 63.32 62.43 21.11 (1.02–56.81) 27.74 (19.85–36.40) 63.32 62.43 84.05 (68.35–95.06) 72.49 (62.96–81.05) 9.33 72.94 9.84 10.75 (2.04–22.58) (5.89–16.86) 0.00 63.84 10.94 (2.57–24.10) 16.28 (11.00–22.37) 0.00 51.90 8.38 (0.95–22.12) 10.99 (7.52–15.02)
14.91 (7.32–24.60) 0.00 87.58 (72.12–97.33) 0.00 12.42 (2.67–27.88) 0.00 83.29 (72.30–91.94) 12.63 10.48 (4.23–19.08) 0.00 11.00 (4.57–19.75) 0.00 6.41 (1.77–13.65)
26.05 (13.52–40.98) 43.47 91.69 (73.79–99.78) 0.0 8.31 (0.22–26.21) 0.00 73.39 (57.07–86.95) 51.70 16.43 (7.13–28.62) 34.41 8.08 (2.98–15.38) 0.00 6.67 (2.13–13.48)
0.00
0.00
5.00
0.00
0.00
I2
23.65
CI confidence interval, HG high-grade, LG low-grade, SAH subarachnoid hemorrhage, SAH and S SAH and stroke
Table 2 Weighted pooled proportional mortality ratios by subgroups and comparison to overall weighted pooled proportional mortality ratio
Asterisks and bold font are meant to draw attention to the statistically-significant values
Subgroup
Proportional mortality ratio (%)
Difference (%) (95 % CI)
Significance level (p
