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Blister-like Aneurysms in Atypical Locations: A Single-Center Experience and Comprehensive Literature Review
Accepted Manuscript Blister-like aneurysms in atypical locations: a single-center experience and a comprehensive literature review S. Peschillo, M. Miscusi, A. Caporlingua, D. Cannizzaro, A. Santoro, R. Delfini, G. Guidetti, P. Missori PII:
S1878-8750(15)00749-4
DOI:
10.1016/j.wneu.2015.05.077
Reference:
WNEU 2953
To appear in:
World Neurosurgery
Received Date: 11 April 2015 Revised Date:
14 May 2015
Accepted Date: 15 May 2015
Please cite this article as: Peschillo S, Miscusi M, Caporlingua A, Cannizzaro D, Santoro A, Delfini R, Guidetti G, Missori P, Blister-like aneurysms in atypical locations: a single-center experience and a comprehensive literature review, World Neurosurgery (2015), doi: 10.1016/j.wneu.2015.05.077. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Blister-like aneurysms in atypical locations: a single-center experience and a comprehensive literature review
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Peschillo S., Miscusi M.^, Caporlingua A.*, Cannizzaro D.*, Santoro A. *, Delfini R. *, Guidetti G.§, Missori P.*
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Department of Neurology and Psychiatry, Endovascular Neurosurgery/Interventional Neuroradiology, ‘Sapienza’ University of Rome, Rome, Italy ^Department of Medico-Surgical Sciences and Biotechnologies, Neurosurgery, Sapienza University of Rome, Latina, Italy *Department of Neurology and Psychiatry, Neurosurgery, ‘Sapienza’ University of Rome, Rome, Italy §Department of Neurology and Psychiatry, Interventional Neuroradiology, ‘Sapienza’ University of Rome, Rome, Italy
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Keywords: blister-like aneurysm, cerebral aneurysm, endovascular treatment, surgical treatment, flow-diverter
Fist Author, corresponding Author
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Simone Peschillo, M.D., Ph.D.
Department of Neurology and Psychiatry, Endovascular Neurosurgery/Interventional Neuroradiology, ‘Sapienza’ University of Rome, Rome, Italy
[email protected] Policlinico Umberto I° Viale del Policlinico, 155 00100 – Roma ITALY
ACCEPTED MANUSCRIPT Abstract: Introduction: Blister-like aneurysms (BLAs) were originally described to arise typically along the non-branching segment of the dorsal wall of the internal carotid artery (ICA). However, during the last decade BLAs located in areas other than the dorsal ICA have been described.
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We present a case series of “atypical” BLAs and provide a systematic review of the literature on this subject.
Methods: We conducted a literature search using the words “blister-like aneurysms”. Studies reporting BLAs in locations other than the dorsal ICA wall were selected. Clinical presentation,
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treatment modality, complications and outcomes (modified Rankin scale, mRS, for neurological outcomes, Roy scale for radiological outcomes) were extracted from each study. We also reviewed our single-institution experience with atypical BLAs and analyzed the
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topography and outcomes of all the atypical BLAs according to each specific treatment modality.
Results: Atypical BLAs were observed in the anterior communicating, middle cerebral, basilar, posterior cerebral, anterior cerebral and posterior inferior cerebellar arteries. Sixty-five percent of the patients were treated with surgery, 30% with an endovascular approach and
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5% with a combined approach. Eighty-eight percent and 55% of the patients experienced a good outcome (mRS 0-1-2) in the endovascular and surgical group, respectively. There were two deaths in the endovascular group and two in the surgical group. Conclusion: Endovascular treatment seems to have lowered morbidity and mortality and
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provided a better outcome compared to surgical approaches. Further prospective studies must be performed to confirm such interesting results. It is important to remember that BLAs may
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also occur in sites other than the typical ICA localization.
Abbreviations: blister-like aneurysm (BLA); internal carotid artery (ICA); digital subtraction angiography (DSA); subarachnoid hemorrhage (SAH);
Highlights • Blister-like aneurysms may be found in various atypical sites • We conducted a review of the literature and our institution’s experience with atypical BLAs • Endovascular treatment seems to cause less morbidity and mortality and provide a better outcome compared to surgical approaches • In the presence of a massive SAH with negative angio-CT and DSA, we suggest exploring the whole circle of Willis
ACCEPTED MANUSCRIPT Introduction Blister-like aneurysms (BLAs), first described in 1986,[11,18] account for 0.3-1% of all intracranial aneurysms.[7] Typically, BLAs arise from the dorsal wall of the internal carotid artery (ICA) at non-branching sites, with extremely thin, fragile walls. The rates of
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intraoperative and/or postoperative rebleeding range from 33–80% in most surgical studies.[13] While the original description of BLAs involved lesions of the dorsal ICA wall, more recent case reports and small clinical series have described aneurysms with similar characteristics in atypical locations such as the middle cerebral artery (MCA), the anterior
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cerebral artery (ACA) and the basilar artery (BA).[1,5,12-14] Due to the small number of these reported cases, the clinical characteristics, outcome, and therapeutic options for these
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atypical BLAs are not well defined. Here we have performed a systematic literature review and added a few cases of our own to better define the clinical patterns, treatment options, and outcome of atypical BLAs.
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Methods
We conducted a comprehensive literature search of PubMed using the key word “blister like aneurysm”. The search was limited to articles in English language published from January 1986 to November 2014. Studies reporting BLAs in atypical locations (all locations excluding
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the ICA), regardless of the treatment strategy offered, were considered. A single investigator (D.C.) performed the literature search and selected the studies. Inclusion criteria were a case
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report or series with available data on clinical and/or angiographic outcomes and detailed treatment modalities.
We extracted the following information from each article: BLA location, rupture status, clinical presentation (Hunt Hess and Fisher grades), treatment modality (endovascular, surgical, combined, and conservative), and neurological outcome at follow-up (assessed by the modified Rankin scale, mRS). For simplification, the patients’ neurological outcome was dichotomized: group A (mRS of 0-2) and group B (mRS 3-6). Aneurysm occlusion was evaluated using the Roy scale[15] (class 1: complete obliteration; class 2: residual neck / incomplete obliteration; class 3, residual aneurysm) in the immediate postoperative period and at the last follow-up. We also conducted a review of our institution’s experience with atypical BLAs.
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Results Literature review Our literature search yielded 103 articles; 43 articles were excluded either because their
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patient populations did not include subjects with BLAs or because insufficient data were reported. Among the remaining 60 articles, 14 contained data on atypically located BLAs (all locations excluding ICA) in a total of 26 patients. The pertinent data are summarized in Table
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1.
Patients and BLA topography
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The literature search yielded a total of 335 BLAs of which 26 were located in sites other than the ICA wall (7.8% of all BLAs). All 26 patients presented with subarachnoid hemorrhage (SAH). The mean age of these patients was 53.7 years (range, 18 to 80) and there were 14 women and 12 men for a female:male ratio of 1.17. The most frequent locations were the anterior communicating artery (ACoA) (34.6%), the MCA (23%) and the BA (19.2%). Tables 1
Treatment modality
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- 3 summarize details on the location of the BLAs.
More than a half of the patients (n=17, 65%) were treated with an endovascular technique
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and eight (30%) with surgery. One patient (4%) underwent a combined approach consisting of initial surgical wrapping followed by flow diversion (this patient, n. 7, was included in the surgical group for the purpose of our analysis). The average interval from SAH to treatment
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was 3.3 days. Endovascular strategies consisted of flow diversion [10 flow diverters (FDs) in 8 patients], sole stenting (6 patients), coiling (1 patient), two or more stents + coiling (1 patient) and stent-assisted coiling (2 patients). Surgical techniques adopted included clipping (7 patients) and wrapping-clipping (1 patient). Table 4 provides details concerning antiplatelet therapy administered to patients in the endovascular group.
Complications and outcomes No periprocedural complications were reported in patients treated with endovascular techniques. In the surgical group, intraoperative rupture occurred in 25%. A favorable
ACCEPTED MANUSCRIPT outcome (mRS 0-2) was reported in 88% and 55% of patients undergoing endovascular and surgical treatment, respectively. Immediately after treatment, complete aneurysm occlusion was observed in 89% and 41% of patients undergoing surgical and endovascular treatment, respectively. At follow-up all available patients in both groups had complete aneurysm occlusion. There were two deaths
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(18%) in the endovascular group and two (22%) in the surgical group. Causes of death were vasospasm (case n. 5), rebleeding (case n. 6), acute respiratory failure (case n. 8), and
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pneumonia (case n. 20).
Illustrative cases of our institution’s experience (table 2)
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Case 1 (figure 1)
An elderly patient was admitted after sudden onset of severe headache (H&H 2). He was found to have a Fisher 3 SAH involving the basal cisterns and the left Sylvian fissure (figure 1A). A computed tomography (CT)-angiography did not show underlying vascular anomalies (figure 1B) but a digital substraction catheter angiography (DSA) done 2 days after admission showed a BLA (1.5 x 1 mm) involving the left A1 segment (figure 1C). After multidisciplinary
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discussion of the case among vascular and endovascular neurosurgeons, it was decided to proceed with endovascular treatment. Under dual antiplatelet therapy, a stent (P64, Phenox, 3,5 x 15 mm) was placed from the M1 to the left ICA (figure 1D). At the end of the procedure
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the aneurysm was still filling (Roy scale 3). Four hours after the procedure, the patient was noted to have moderate left arm weakness and dysphasia. A repeat DSA did not show any flow alterations or evidence of thromboembolic phenomena while the BLA was still filling.
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The patient’s deficit resolved, although brain magnetic resonance imaging (MRI) documented ischemic changes in the territory of the lateral lenticulostriate arteries (figure 1E). As a repeat angiogram 2 days after the initial procedure showed persistent aneurysm filling, we decided to occlude the proximal A1 segment along with the aneurysm with coils (1.5x4 and 1x2, Target, Stryker) after navigating a microcatheter from the right ACA through the ACoA (figure 1F).
A follow-up DSA on postoperative day 7 confirmed persistent obliteration of the
aneurysm and the parent of MCA (figure 1G-H). At discharge, 2 weeks after the initial procedure, the patient did not have any new deficit (mRS 0). Brain MRI and magnetic resonance angiography done 1 month later confirmed persistent obliteration of the aneurysm and proximal left A1.
ACCEPTED MANUSCRIPT Case 2 (figure 2) An elderly patient was admitted for sudden loss of consciousness (H&H 4). On admission the patient was intubated and sedated. Head CT showed SAH in the interpeduncular and right ponto-cerebellar cisterns along with intraventricular hemorrhage (figure 2A). A dubious anomaly at the origin of the right posterior inferior cerebellar artery (PICA) was visualized on
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an angio CT-scan (figure 2B). DSA performed the following day showed a BLA of the origin of the right PICA (figure 2C). It was decided to proceed with endovascular treatment but the treatment was postponed for 5 days during which the patient was started on antiplatelet therapy (ASA 300 mg and Plavix 75 mg). The aneurysm was treated with stent-assisted
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coiling (1.5x6 Deltapaq, Codman, 1x3, Target, Stryker and Enterprise 4.5x14, Codman). Immediate angiographic control confirmed complete obliteration of the aneurysm (figure 2DE) and patency of the PICA. A control MRI the following day did not show evidence of
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periprocedural complications (figure 2F). Unfortunately the patient succumbed to pneumonia and complications of SAH on postoperative day 18 (mRS 6). Case 3 (figure 3)
A middle-aged patient was admitted after sudden loss of consciousness. Head CT-scan showed a SAH involving the right Sylvian fissure (Fisher 3) (figure 3A). CT angiography demonstrated
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a vascular anomaly of the inferior branch of the right MCA (figure 3B) and DSA confirmed a right MCA BLA (2 x 1.5 mm) (figure 3C). The BLA was treated with a FD (Silk 3x20, Balt) placed across the aneurysm’s neck (figure 3D). Immediately after placement of the FD, an
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intravenous bolus of abciximab 0.25 mg/kg was administered while clopidogrel 75 mg and aspirin 300 mg were initiated the following day. An immediate control angiogram showed persistent filling of the aneurysm. The intraoperative Roy scale was 3. On postoperative day 3
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control head and angio CT-scan showed that the stent was patent but subcortical hypodense areas were evident in the territory of the left ACA and right ACM perforators along with absent cortical sulci. An intracranial pressure probe was then positioned and recorded extremely high intracranial pressure values (40 mmHg). A right decompressive craniectomy was performed immediately. On postoperative day 14, a control DSA showed that the aneurysm was absent (Roy scale 1) along with its parent artery (figure 3 E-F). After 30 days, the patient was transferred for rehabilitation with severe disability (mRS 5).
ACCEPTED MANUSCRIPT Discussion BLAs were described for the first time in 1986 as “chimame” (blood blisters) given their particular morphology, which differed from that of the more commonly encountered saccular aneurysms. The most frequent site of origin of BLAs is the non-branching tract of the dorsal wall of the ICA and since the 1980s several reports have described BLAs in this particular
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location. However, starting from 21st century atypically located BLAs began to be reported, showing that these vascular lesions do not arise exclusively from the ICA.[1,5,12-14]
Regardless of their location, BLAs are characterized by a high risk of intraoperative rupture: the wall of the aneurysm is too fragile to clip while preserving the parent artery and, from a
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morphological point of view, they are small with a broad base making it difficult to even try placing coils in their dome. The pathogenesis of BLA is still under debate. Several mechanisms
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have been proposed, including atherosclerosis, hemodynamic stress related to hypertension and arterial dissection creating a pseudoaneurysm. Ishikawa et al. [18] performed a postmortem pathological study of BLAs, demonstrating that a BLA arose in an atherosclerotic carotid artery in the junction between sclerotic and normal carotid wall; degeneration of the internal elastic lamina was found, associated with lack of normal adventitia and fibrinous tissue at this site, causing a laceration of the internal carotid wall, suggesting that BLAs may
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be a subtype of dissecting aneurysms or pseudoaneurysms. Overall, of the 335 BLAs reported in the literature, about 7.8% occurred in atypical sites. However, adding our three cases (table 2) increased this percentage to 8.6%. In this study. the
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most frequent atypical site was the AcoA (34.6%), followed by the MCA (23%), the BA (19.2%), the PCA (15.4%) and the A2 tract and PICA (3.9%) (table 3).
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As far as concerns the type of treatment, of the 26 aneurysms considered, 30% (n=8) were treated surgically with clipping and wrapping-clipping (table 1); 65% (n=17) were treated with an endovascular procedure, using FDs, coiling, two or more stents + coiling, stent assisted coiling and no FD-stent. One patient (n. 7) was treated with a combined approach (wrapping+FD stent) and for this reason was included in the surgical treatment group. When including our three cases in the analysis, the percentage of patients treated with an endovascular procedure increased; in fact, two of our three patients were treated with FD stents (P64 and Silk) and the other was treated with stent-assisted coiling. With regards to complications, no intraprocedural complications were reported in the endovascular group, while two ruptures occurred in the surgical group; this could be related to the manipulation of vessels and placement of the clip. As far as concerns the endovascular
ACCEPTED MANUSCRIPT group, given the recent trend to treat this type of lesion with stents, FD or non-FD (14 patients in the population studied had been treated in this way, 82%), the rupture rate is decreased precisely because of the change in paradigm, from endosaccular to endovasal; retrospectively, this seems a predictor of a favorable outcome, although statistical confirmation is needed. Some thrombo-embolic complications could have been expected, but these were not reported
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to have occurred. With regards to postoperative complications, none was reported in the endovascular group, whereas there were five cases of hydrocephalus and four cases of vasospasm in the surgical group (table 1); this finding is very interesting, since it could be expected that the risk of
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vasospasm would be higher in the endovascular group, given the lack of surgical lavage of the cisterns. Vasospasm may be promoted by intraoperative rupture and, therefore an increase in the amount of blood in the subarachnoid space, as well as by surgical manipulation.
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Neurological outcome was dichotomized, dividing patients into those with mRS grades 0-2 and those with grades 3-6. The mRS scores were 0-2 in 15 patients (88%) in the endovascular group and five (55%) in the surgical group, whereas they were 3-6 in two patients (12%) in the endovascular group and four (45%) in the surgical group. These findings probably reflect the lower percentage of intraoperative and postoperative complications in the endovascular
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group. Regarding mortality rates, two patients died in the endovascular group (12%) and two in the surgical one (22%); causes of death were vasospasms (case n. 5), rebleeding (case n. 6), acute respiratory failure (case n. 8), and pneumonia (case n. 20). There were divergent results related to aneurysm occlusion status after the procedures and at
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the last follow-up: the class 1 occlusion rate in the surgical group was 89% (8/9), whereas it was only 41% (7/17) in the endovascular group. With regards to the Roy scale at follow-up
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(mean 195 days of follow-up) the class 1 occlusion rate was 100% in the surgical group and also 100% in the endovascular group, including one parent artery occlusion and one patient who did not have a follow-up because of death. These results appear to be in line with expectations; in fact, following surgery, the occlusion was complete immediately, except in patient n. 7 (table 1), in whom, despite initial wrapping with muscle and the use of fibrin glue, the angiographic picture did not change. For this reason a FD stent had to be released in the aneurysm, which gave an excellent result at follow-up.[13] In contrast, in the endovascular group, in which FD or non-FD stents are being used ever more frequently, a Roy scale class 1 result is not achieved immediately, although this does not seem to influence the later outcome. In case n. 21 (table 1), the use of two FDs between the A1-A2 tracts of both sides led to the closure of the tract of the AcoA and, therefore, a parent artery occlusion.
ACCEPTED MANUSCRIPT As far as concerns the endovascular group, it is worth commenting on anti-aggregant treatment: given that there is not a unique indication on the type of treatment to use, it is interesting to note the experiences of the various authors (table 4). In our institution, we usually start treatment with heparinization and administration of abciximab immediately after deployment of a FD, followed by postoperative dual antiplatelet therapy with aspirin and
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clopidogrel. In order to avoid potential hemorrhagic complications, if the patient needs a ventriculostomy, we place this before starting dual antiplatelet therapy. However, dual antiplatelet therapy is still controversial in the setting of acute SAH and the risk–benefit profile of potential hemorrhagic and thromboembolic complications should be considered
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carefully in deciding when to initiate such therapy.
With regards to the type of treatment, some comments should be made on the risks of endovascular management. Given the friable nature of the lesions, which can readily result in
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intraprocedural aneurysm rupture, we are particularly cautious about the use of coils as a stand-alone therapy for these small aneurysms. When possible, we prefer to deploy a FD, because it can redirect blood flow away from aneurysms, reconstructing the parent vessel. However, there are some disadvantages of using FDs in the treatment of BLAs, such as the need for dual antiplatelet therapy and the fact that the aneurysm is not immediately excluded,
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and remains at risk of re-rupture. With growing experience and increasing application of FD, several series and case reports have stressed the danger of periprocedural as well as delayed thromboembolic complications.[6,8,13] Indeed, our case series suggests that caution must be taken when applying this novel strategy to BLAs; one of our patients suffered from perforator
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occlusion, with a non-disabling persistent neurological deficit (patient 1), and another (patient 3) developed thromboembolic complications, probably due to ineffective antiplatelet
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therapy. The third patient died, but he had no complications related to the endovascular treatment (his death was due to pneumonia). Surgical treatment, too, has some shortcomings: in particular, a highly skilled surgeon, able to perform high-risk surgery, such as wrapping and by-passes, and to manage potential intra-operative rupture, is needed to treat BLAs. This study does have some limitations; it is retrospective rather than prospective, it is based only on data reported in the literature, and some articles (n=43) were excluded because they did not include cases of BLAs or did not report complete data on angiographic outcomes in cases of BLA. Furthermore, although we tried to perform a statistical analysis, the small population and fragmentation of the sample made it impossible to draw statistically meaningful conclusions.
ACCEPTED MANUSCRIPT Conclusions BLAs are complex lesions. According to our review, endovascular treatment of these lesions seems to be associated with less morbidity and mortality and a better outcome compared to surgical approaches, but further, prospective studies with long-term follow-up and statistical analysis must be performed to confirm these interesting results, in particular comparing
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admission grade, treatment technique, and Roy scale. Given the very small size of BLAs and their poor initial visibility, it is important to remember that they may occur in atypical sites other than the most common ICA localization. In the presence of a massive SAH with negative
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angio-CT and DSA, it is always prudent to explore the whole circle of Willis.
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This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Competing Interests Statement: SP is proctor for Penumbra All authors contributed to writing the article, revising the article and final approval of the article for submission to this journal. Our study complies with the Declaration of Helsinki; we performed a systematic review of the literature and patients were treated in our Institution using standard endovascular techniques that had no need for approval from an
ACCEPTED MANUSCRIPT References:
1. Andaluz N, Zuccarello M: Blister-like aneurysms of the anterior communicating artery: a retrospective review of diagnosis and treatment in five patients. Neurosurgery 62:807-811,
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2008.
2. Aydin K, Arat A, Sencer S, Hakyemez B, Barburoglu M, Sencer A, İzgi N: Treatment of ruptured blood blister-like aneurysms with flow diverter SILK stents. J Neurointerv Surg
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7:202-9, 2015.
3. Bulsara KR, Kuzmik GA, Hebert R, Cheung V, Matouk CC, Jabbour P, Hasan D, Pepper J:
ons85, 2013.
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Stenting as monotherapy for uncoilable intracranial aneurysms. Neurosurgery 73:ons80-
4. Chalouhi N, Zanaty M, Tjoumakaris S, Gonzalez LF, Hasan D, Kung D, Rosenwasser RH, Jabbour P: Treatment of blister-like aneurysms with the pipeline embolization device.
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Neurosurgery 74:527-532, 2014.
5. Consoli A, Nappini S, Renieri L, Limbucci N, Ricciardi F, Mangiafico S: Treatment of two blood blister-like aneurysms with flow diverter stenting. J Neurointerv Surg 4:e4, 2012.
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6. Grant RA, Quon JL, Bulsara KR: Oversized self-expanding stents as an alternative to flow-
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diverters for blister-like aneurysms. Neurol Res 36:351-355, 2014. 7. Ishikawa T, Nakamura N, Houkin K, Nomura M: Pathological consideration of a “blisterlike” aneurysm at the superior wall of the internal carotid artery: case report. Neurosurgery 40:403-406, 1997.
8. Lim YC, Kim BM, Suh SH, Jeon P, Kim SH, Ihn YK, Lee YJ, Sim SY, Chung J, Kim DJ, Kim DI: Reconstructive treatment of ruptured blood blister-like aneurysms with stent and coil. Neurosurgery 73:480-488, 2013. 9. Meckel S, Singh TP, Undrén P, Ramgren B, Nilsson OG, Phatouros C, McAuliffe W, Cronqvist M: Endovascular treatment using predominantly stent-assisted coil embolization
ACCEPTED MANUSCRIPT and antiplatelet and anticoagulation management of ruptured blood blister-like aneurysms. AJNR Am J Neurorad 32:764-771, 2011. 10. Morris TC, Brophy BP: Blister-like aneurysm of the anterior communicating artery. J Clin Neurosci 16:1098-1100, 2009.
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11. Nakagawa F, Kobayashi S, Takemae T, Sugita K: Aneurysms protruding from the dorsal wall of the internal carotid artery. J Neurosurg 65:303-308, 1986.
12. Peschillo S, Cannizzaro D, Missori P, Colonnese C, Santodirocco A, Santoro A, Guidetti G:
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Reconstructive endovascular treatment of a ruptured blood blister-like aneurysm of anterior communicating artery. J Neurosurg Sci June 10, 2014.[Epub ahead of print].
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13. Peschillo S, Missori P, Piano M, Cannizzaro D, Guidetti G, Santoro A, Cenzato M: Blisterlike aneurysms of middle cerebral artery: a multicenter retrospective review of diagnosis and treatment in three patients. Neurosurg Rev 38:197-203, 2014. 14. Pistocchi S, Blanc R, Bartolini B, Piotin M: Flow diverters at and beyond the level of the
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circle of Willis for the treatment of intracranial aneurysms. Stroke 43:1032-1038, 2012. 15. Roy D, Milot G, Raymond J: Endovascular treatment of unruptured aneurysms. Stroke 32:1998-2004, 2001.
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16. Rouchaud A, Saleme S, Gory B, Ayoub D, Mounayer C: Endovascular exclusion of the anterior communicating artery with flow-diverter stents as an emergency treatment for
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blister-like intracranial aneurysms. A case report. Interv Neuroradiol 19:471-478, 2013. 17. Seo DH, Lee WC, Choe IS, Park SC, Ha YS: Ruptured and unruptured aneurysms of the accessory anterior cerebral artery combined with a blood blister-like aneurysm of the anterior communicating artery. Neurol India 57:85-87, 2009. 18. Takahashi A, Suzuki J, Fujiwara S, Mizoi K, Yashimoto T: Surgical treatment of chimame (blood blister) like aneurysm at C2 portion of internal carotid artery. Surg Cereb Stroke 16:72-77, 1988.
ACCEPTED MANUSCRIPT Figure 1 Legend: A: The CT shows grade 3 Fisher hemorrhage, involving the basal cisterns and the left Sylvian fissure; B: An angio-CT performed immediately did not reveal vascular malformations; C: DSA performed 2 days after admission revealed a small BLA (about 1.5x1 mm) at the origin
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D: A stent (P64, Phenox, 3,5 x 15 mm) was placed from the M1 to the left ICA. E: The DWI images show an ischemic area (4.4 x 1.8 cm) in the acute phase involving the lenticular nucleus, the knee and arm of the internal capsule and the head of the caudate nucleus on the left. F: As a repeat angiogram two days after the initial procedure showed persistent aneurysm filling, we decided to occlude the A1 segment along with the aneurysm with coils (1.5x4 and 1x2, Target, Stryker) after navigating a microcatheter from the right ACA through the anterior communicating artery (ACoM). G-H: Follow-up DSA on postoperative day 7 confirmed persistent obliteration of the aneurysm and the parent artery.
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Figure 2 Legend:
A: Head CT showing SAH in the interpeduncular and right ponto-cerebellar cisterns along with intraventricular hemorrhage (IVH) B: Angio-CT showed a suspicious area immediately after the origin of the right PICA. C: DSA, performed the day after, reveals a small BLA immediately after the origin of the right PICA.
Figure 3 Legend:
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D-E: The aneurysm was treated with an Enterprise 4.5x14 stent to protect the basilar artery and coils within the aneurysmal sac, with immediate occlusion of the sac, preserving the PICA. F: A control MRI (DWI, ADC and Flair sequences) the following day did not show evidence of periprocedural complications.
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A: Head CT-scan showed SAH involving the right Sylvian fissure (Fisher 3). B: Angio-CT, performed immediately after, showed a small aneurysm of the inferior bran of the right middle cerebral artery, which was then confirmed by DSA (C). D: A FD stent Silk 3x20 was released across the aneurysm’s neck. E-F: At the DSA control after 14 days, the aneurysm had disappeared (Roy scale 1) and the stent was patent.
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DIFFUSE SAH
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Figure 4: Proposed flow chart of the management of a suspected BLA
ANGIO CT NEGATIVE
DSA + 3D
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EXPLORE THE WHOLE CIRCLE OF WILLIS
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+
-
REPEAT DSA AT DAY 3-5 AFTER SAH
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TREATMENT
ENDOVASCULAR/ SURGICAL
CONTROL DSA
+
-
10-14 DAYS AFTER SAH
STOP
ACCEPTED MANUSCRIPT
2014 – Grant (6)
2013 – Bulsara (3)
2012 – Pistocchi (14)
HH grade
Location
Treatment modality
Postop. complications Hydro - Vaso
3
180
1
1
1
None
1
180
1
1
1 1
3
3
ACoA
Surgery
Clipping
Rupture
2
2
2
ACoA
Surgery
Clipping
None
3
1
1
ACoA
Surgery
Clipping
None
4
3
4
ACoA
Surgery
Clipping
Rupture
5
3
3
ACoA
Surgery
Clipping
None
6
4
3
MCA
Endovascular
None
7
3
2
MCA
Endo + Surg
Coiling Wrapping + FD (PED) Wrapping + Clipping
8
2
2
MCA
Surgery
9
1
1
MCA
Endovascular
10
1
1
PCA
Endovascular
11
1
1
PCA
Endovascular
12
1
1
MCA
Endovascular
13
1
2
PCA
Endovascular
14
1
1
PCA
Endovascular
Stenting (Neuroform) Stenting (Neuroform) Stenting (Neuroform) Stenting (Neuroform 3) Stenting (Neuroform 3) Stenting (Neuroform 3)
Outcome mRS
FU (days)
Timing (days)
Early Roy Scale
FU Roy Scale
None
0
180
11
1
Hydro - Vaso
3
180
1
1
1
Hydro - Vaso
6
180
1
1
1
Rebleeding
6
15
1
1
1
None
None
0
540
1
3
1
None
Acute respiratory failure
6
15
1
1
1
None
None
0
430
1
2
1
None
None
0
430
1
2
1
None
None
0
13,6
1
2
1
None
None
1
300
7
3
1
None
None
1
150
7
1
1
None
None
1
30
7
2
1
15
2
2
A2
Endovascular
FD x 2 (SILK)
None
None
0
14
1
3
1
16
2
2
MCA
Endovascular
FD (PED)
None
None
0
60
1
3
1
17
3
4
BA
Endovascular
SAC
None
None
0
360
/
1
1
18
2
3
BA
Endovascular
SAC
None
None
1
360
/
2
1
19
1
1
ACoA
Surgery
Clipping
None
Hydrocephalus
2
60
15
1
1
20
4
4
ACoA
Endovascular
FD (SILK)
None
Pneumonia
6
3
1
1
/
21
3
4
ACoA
FD x 2 (PED)
None
None
2
90
1
1
PAO 1
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2014 – Peschillo (12) 2013 - Rouchaud (16)
Intraop. complications
1
2011 – Meckel (9) 2009 – Morris (10)
Technique
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grade
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2014 – Peschillo (13)
Fisher
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2008 – Andaluz (1)
N
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Year - Author
Endovascular
2009 – Seo (17)
22
2
4
ACoA
Surgery
Clipping
None
Hydro - Vaso
2
/
1
1
2014 – Aydin (2)
23
/
2
BA
Endovascular
FD (SILK)
None
None
0
135
8
3
1
2014 – Chaloui (4)
24
1
2
BA
Endovascular
FD (PED)
None
None
1
14
1
2
1
2013 - Lim YC (8)
25
2
2
BA
Endovascular
Stenting x 3 (Neuroform) + Coiling
None
None
0
960
/
1
1
2012 – Consoli (5)
26
1
2
PICA
Endovascular
FD (PED)
None
None
0
180
5
1
1
Table 1: Literature review of data reported in case series. ACoA: anterior communicating artery; MCA: middle cerebral artery; PCA: posterior cerebral artery; PICA: poster inferior cerebellar artery; BA: basilar artery; SAC: stent-assisted coiling; FD: flow diverter; PED: Pipeline embolization device PAO: parent artery occlusion; Hydro: hydrocephalus; Vaso: vasospasm; FU: follow-up.
Fisher grade
HH grade
Location
Treatment modality
First procedure
Second procedure
Device
1
3
2
A1
Endovascular
FD
Coiling
P64 3.5 x 15, Phenox
2
4
4
PICA
Endovascular
SAC
None
Target, Stryker Enterprise 4.5x14, Codman
3
3
4
MCA
Endovascular
FD
Decompressive craniectomy
SILK 3 x 20, Balt
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Table 2: our single-institution case series of atypical BLAs. * days from SAH to treatment
Intraop. complications
Postoperative complications
Outcom e mRs
FU (days)
Timing (days)*
Early Roy Scale
FU Roy Scale
None
Transient neurological deficit
0
30
6
3
1 (PAO)
None
Pneumonia
6
18
5
1
-
None
thromboembolic complications, raised ICP
5
14
1
3
1
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Case
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Total
26+3
(100%)
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(3.9) (34.6) (19.2) (23) (15.4) (3.9)
335
%* of 335 0.3% 0.3% 2.7% 1.5% 2.1% 1.2% 0.6%
7.8% 8.6%* 100%
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Entire population
(%)
N 1 1 9 5 6 +1 4 1+1
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Location A1 A2 ACoA BA MCA PCA PICA
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Table 3: data concerning the location of BLAs. The column on the far right reports percentages with respect to all the BLAs described in the literature regardless of their location. A1,A2: anterior cerebral artery, tract 2; ACoA: anterior communicating artery; MCA: middle cerebral artery; PCA: posterior cerebral artery; PICA: poster inferior cerebellar artery.
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The cases reported in this manuscript are in italic and bold. * this percentage includes our three patients reported in this manuscript
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N
AP therapy (12 hours preoperatively)
N
AP therapy (until month 6 postoperatively)
N
AP beyond month 6 postoperatively
N
Heparin
12
ASA 300mg + Clopidgrel 600mg
7
ASA 300mg + Clopidogrel 75 mg
8
ASA 250mg
2
Abciximab (Reopro, Lilly)
3
ASA 250mg + Abciximab
1
ASA 250 mg
7
ASA 200mg
1
ASA
1
ASA 300mg alone Clopidogrel 150 mg alone
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-
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Intraoperative therapy
5
Clopidogrel 150mg
1
ASA 100mg
2
1
ASA 200mg
1
ASA 150 mg + Clopidogrel 75 mg
2
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Table 4: data concerning antiplatelet therapy administered to patients in the endovascular group 12 hours prior to the procedure, intraoperatively, during the first 6 postoperative months and thereafter. ASA: aspirin; AP: antiplatelet.
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S1878-8750(15)00749-4
DOI:
10.1016/j.wneu.2015.05.077
Reference:
WNEU 2953
To appear in:
World Neurosurgery
Received Date: 11 April 2015 Revised Date:
14 May 2015
Accepted Date: 15 May 2015
Please cite this article as: Peschillo S, Miscusi M, Caporlingua A, Cannizzaro D, Santoro A, Delfini R, Guidetti G, Missori P, Blister-like aneurysms in atypical locations: a single-center experience and a comprehensive literature review, World Neurosurgery (2015), doi: 10.1016/j.wneu.2015.05.077. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Blister-like aneurysms in atypical locations: a single-center experience and a comprehensive literature review
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Peschillo S., Miscusi M.^, Caporlingua A.*, Cannizzaro D.*, Santoro A. *, Delfini R. *, Guidetti G.§, Missori P.*
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Department of Neurology and Psychiatry, Endovascular Neurosurgery/Interventional Neuroradiology, ‘Sapienza’ University of Rome, Rome, Italy ^Department of Medico-Surgical Sciences and Biotechnologies, Neurosurgery, Sapienza University of Rome, Latina, Italy *Department of Neurology and Psychiatry, Neurosurgery, ‘Sapienza’ University of Rome, Rome, Italy §Department of Neurology and Psychiatry, Interventional Neuroradiology, ‘Sapienza’ University of Rome, Rome, Italy
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Keywords: blister-like aneurysm, cerebral aneurysm, endovascular treatment, surgical treatment, flow-diverter
Fist Author, corresponding Author
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Simone Peschillo, M.D., Ph.D.
Department of Neurology and Psychiatry, Endovascular Neurosurgery/Interventional Neuroradiology, ‘Sapienza’ University of Rome, Rome, Italy
[email protected] Policlinico Umberto I° Viale del Policlinico, 155 00100 – Roma ITALY
ACCEPTED MANUSCRIPT Abstract: Introduction: Blister-like aneurysms (BLAs) were originally described to arise typically along the non-branching segment of the dorsal wall of the internal carotid artery (ICA). However, during the last decade BLAs located in areas other than the dorsal ICA have been described.
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We present a case series of “atypical” BLAs and provide a systematic review of the literature on this subject.
Methods: We conducted a literature search using the words “blister-like aneurysms”. Studies reporting BLAs in locations other than the dorsal ICA wall were selected. Clinical presentation,
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treatment modality, complications and outcomes (modified Rankin scale, mRS, for neurological outcomes, Roy scale for radiological outcomes) were extracted from each study. We also reviewed our single-institution experience with atypical BLAs and analyzed the
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topography and outcomes of all the atypical BLAs according to each specific treatment modality.
Results: Atypical BLAs were observed in the anterior communicating, middle cerebral, basilar, posterior cerebral, anterior cerebral and posterior inferior cerebellar arteries. Sixty-five percent of the patients were treated with surgery, 30% with an endovascular approach and
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5% with a combined approach. Eighty-eight percent and 55% of the patients experienced a good outcome (mRS 0-1-2) in the endovascular and surgical group, respectively. There were two deaths in the endovascular group and two in the surgical group. Conclusion: Endovascular treatment seems to have lowered morbidity and mortality and
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provided a better outcome compared to surgical approaches. Further prospective studies must be performed to confirm such interesting results. It is important to remember that BLAs may
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also occur in sites other than the typical ICA localization.
Abbreviations: blister-like aneurysm (BLA); internal carotid artery (ICA); digital subtraction angiography (DSA); subarachnoid hemorrhage (SAH);
Highlights • Blister-like aneurysms may be found in various atypical sites • We conducted a review of the literature and our institution’s experience with atypical BLAs • Endovascular treatment seems to cause less morbidity and mortality and provide a better outcome compared to surgical approaches • In the presence of a massive SAH with negative angio-CT and DSA, we suggest exploring the whole circle of Willis
ACCEPTED MANUSCRIPT Introduction Blister-like aneurysms (BLAs), first described in 1986,[11,18] account for 0.3-1% of all intracranial aneurysms.[7] Typically, BLAs arise from the dorsal wall of the internal carotid artery (ICA) at non-branching sites, with extremely thin, fragile walls. The rates of
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intraoperative and/or postoperative rebleeding range from 33–80% in most surgical studies.[13] While the original description of BLAs involved lesions of the dorsal ICA wall, more recent case reports and small clinical series have described aneurysms with similar characteristics in atypical locations such as the middle cerebral artery (MCA), the anterior
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cerebral artery (ACA) and the basilar artery (BA).[1,5,12-14] Due to the small number of these reported cases, the clinical characteristics, outcome, and therapeutic options for these
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atypical BLAs are not well defined. Here we have performed a systematic literature review and added a few cases of our own to better define the clinical patterns, treatment options, and outcome of atypical BLAs.
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Methods
We conducted a comprehensive literature search of PubMed using the key word “blister like aneurysm”. The search was limited to articles in English language published from January 1986 to November 2014. Studies reporting BLAs in atypical locations (all locations excluding
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the ICA), regardless of the treatment strategy offered, were considered. A single investigator (D.C.) performed the literature search and selected the studies. Inclusion criteria were a case
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report or series with available data on clinical and/or angiographic outcomes and detailed treatment modalities.
We extracted the following information from each article: BLA location, rupture status, clinical presentation (Hunt Hess and Fisher grades), treatment modality (endovascular, surgical, combined, and conservative), and neurological outcome at follow-up (assessed by the modified Rankin scale, mRS). For simplification, the patients’ neurological outcome was dichotomized: group A (mRS of 0-2) and group B (mRS 3-6). Aneurysm occlusion was evaluated using the Roy scale[15] (class 1: complete obliteration; class 2: residual neck / incomplete obliteration; class 3, residual aneurysm) in the immediate postoperative period and at the last follow-up. We also conducted a review of our institution’s experience with atypical BLAs.
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Results Literature review Our literature search yielded 103 articles; 43 articles were excluded either because their
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patient populations did not include subjects with BLAs or because insufficient data were reported. Among the remaining 60 articles, 14 contained data on atypically located BLAs (all locations excluding ICA) in a total of 26 patients. The pertinent data are summarized in Table
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1.
Patients and BLA topography
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The literature search yielded a total of 335 BLAs of which 26 were located in sites other than the ICA wall (7.8% of all BLAs). All 26 patients presented with subarachnoid hemorrhage (SAH). The mean age of these patients was 53.7 years (range, 18 to 80) and there were 14 women and 12 men for a female:male ratio of 1.17. The most frequent locations were the anterior communicating artery (ACoA) (34.6%), the MCA (23%) and the BA (19.2%). Tables 1
Treatment modality
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- 3 summarize details on the location of the BLAs.
More than a half of the patients (n=17, 65%) were treated with an endovascular technique
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and eight (30%) with surgery. One patient (4%) underwent a combined approach consisting of initial surgical wrapping followed by flow diversion (this patient, n. 7, was included in the surgical group for the purpose of our analysis). The average interval from SAH to treatment
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was 3.3 days. Endovascular strategies consisted of flow diversion [10 flow diverters (FDs) in 8 patients], sole stenting (6 patients), coiling (1 patient), two or more stents + coiling (1 patient) and stent-assisted coiling (2 patients). Surgical techniques adopted included clipping (7 patients) and wrapping-clipping (1 patient). Table 4 provides details concerning antiplatelet therapy administered to patients in the endovascular group.
Complications and outcomes No periprocedural complications were reported in patients treated with endovascular techniques. In the surgical group, intraoperative rupture occurred in 25%. A favorable
ACCEPTED MANUSCRIPT outcome (mRS 0-2) was reported in 88% and 55% of patients undergoing endovascular and surgical treatment, respectively. Immediately after treatment, complete aneurysm occlusion was observed in 89% and 41% of patients undergoing surgical and endovascular treatment, respectively. At follow-up all available patients in both groups had complete aneurysm occlusion. There were two deaths
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(18%) in the endovascular group and two (22%) in the surgical group. Causes of death were vasospasm (case n. 5), rebleeding (case n. 6), acute respiratory failure (case n. 8), and
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pneumonia (case n. 20).
Illustrative cases of our institution’s experience (table 2)
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Case 1 (figure 1)
An elderly patient was admitted after sudden onset of severe headache (H&H 2). He was found to have a Fisher 3 SAH involving the basal cisterns and the left Sylvian fissure (figure 1A). A computed tomography (CT)-angiography did not show underlying vascular anomalies (figure 1B) but a digital substraction catheter angiography (DSA) done 2 days after admission showed a BLA (1.5 x 1 mm) involving the left A1 segment (figure 1C). After multidisciplinary
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discussion of the case among vascular and endovascular neurosurgeons, it was decided to proceed with endovascular treatment. Under dual antiplatelet therapy, a stent (P64, Phenox, 3,5 x 15 mm) was placed from the M1 to the left ICA (figure 1D). At the end of the procedure
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the aneurysm was still filling (Roy scale 3). Four hours after the procedure, the patient was noted to have moderate left arm weakness and dysphasia. A repeat DSA did not show any flow alterations or evidence of thromboembolic phenomena while the BLA was still filling.
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The patient’s deficit resolved, although brain magnetic resonance imaging (MRI) documented ischemic changes in the territory of the lateral lenticulostriate arteries (figure 1E). As a repeat angiogram 2 days after the initial procedure showed persistent aneurysm filling, we decided to occlude the proximal A1 segment along with the aneurysm with coils (1.5x4 and 1x2, Target, Stryker) after navigating a microcatheter from the right ACA through the ACoA (figure 1F).
A follow-up DSA on postoperative day 7 confirmed persistent obliteration of the
aneurysm and the parent of MCA (figure 1G-H). At discharge, 2 weeks after the initial procedure, the patient did not have any new deficit (mRS 0). Brain MRI and magnetic resonance angiography done 1 month later confirmed persistent obliteration of the aneurysm and proximal left A1.
ACCEPTED MANUSCRIPT Case 2 (figure 2) An elderly patient was admitted for sudden loss of consciousness (H&H 4). On admission the patient was intubated and sedated. Head CT showed SAH in the interpeduncular and right ponto-cerebellar cisterns along with intraventricular hemorrhage (figure 2A). A dubious anomaly at the origin of the right posterior inferior cerebellar artery (PICA) was visualized on
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an angio CT-scan (figure 2B). DSA performed the following day showed a BLA of the origin of the right PICA (figure 2C). It was decided to proceed with endovascular treatment but the treatment was postponed for 5 days during which the patient was started on antiplatelet therapy (ASA 300 mg and Plavix 75 mg). The aneurysm was treated with stent-assisted
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coiling (1.5x6 Deltapaq, Codman, 1x3, Target, Stryker and Enterprise 4.5x14, Codman). Immediate angiographic control confirmed complete obliteration of the aneurysm (figure 2DE) and patency of the PICA. A control MRI the following day did not show evidence of
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periprocedural complications (figure 2F). Unfortunately the patient succumbed to pneumonia and complications of SAH on postoperative day 18 (mRS 6). Case 3 (figure 3)
A middle-aged patient was admitted after sudden loss of consciousness. Head CT-scan showed a SAH involving the right Sylvian fissure (Fisher 3) (figure 3A). CT angiography demonstrated
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a vascular anomaly of the inferior branch of the right MCA (figure 3B) and DSA confirmed a right MCA BLA (2 x 1.5 mm) (figure 3C). The BLA was treated with a FD (Silk 3x20, Balt) placed across the aneurysm’s neck (figure 3D). Immediately after placement of the FD, an
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intravenous bolus of abciximab 0.25 mg/kg was administered while clopidogrel 75 mg and aspirin 300 mg were initiated the following day. An immediate control angiogram showed persistent filling of the aneurysm. The intraoperative Roy scale was 3. On postoperative day 3
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control head and angio CT-scan showed that the stent was patent but subcortical hypodense areas were evident in the territory of the left ACA and right ACM perforators along with absent cortical sulci. An intracranial pressure probe was then positioned and recorded extremely high intracranial pressure values (40 mmHg). A right decompressive craniectomy was performed immediately. On postoperative day 14, a control DSA showed that the aneurysm was absent (Roy scale 1) along with its parent artery (figure 3 E-F). After 30 days, the patient was transferred for rehabilitation with severe disability (mRS 5).
ACCEPTED MANUSCRIPT Discussion BLAs were described for the first time in 1986 as “chimame” (blood blisters) given their particular morphology, which differed from that of the more commonly encountered saccular aneurysms. The most frequent site of origin of BLAs is the non-branching tract of the dorsal wall of the ICA and since the 1980s several reports have described BLAs in this particular
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location. However, starting from 21st century atypically located BLAs began to be reported, showing that these vascular lesions do not arise exclusively from the ICA.[1,5,12-14]
Regardless of their location, BLAs are characterized by a high risk of intraoperative rupture: the wall of the aneurysm is too fragile to clip while preserving the parent artery and, from a
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morphological point of view, they are small with a broad base making it difficult to even try placing coils in their dome. The pathogenesis of BLA is still under debate. Several mechanisms
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have been proposed, including atherosclerosis, hemodynamic stress related to hypertension and arterial dissection creating a pseudoaneurysm. Ishikawa et al. [18] performed a postmortem pathological study of BLAs, demonstrating that a BLA arose in an atherosclerotic carotid artery in the junction between sclerotic and normal carotid wall; degeneration of the internal elastic lamina was found, associated with lack of normal adventitia and fibrinous tissue at this site, causing a laceration of the internal carotid wall, suggesting that BLAs may
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be a subtype of dissecting aneurysms or pseudoaneurysms. Overall, of the 335 BLAs reported in the literature, about 7.8% occurred in atypical sites. However, adding our three cases (table 2) increased this percentage to 8.6%. In this study. the
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most frequent atypical site was the AcoA (34.6%), followed by the MCA (23%), the BA (19.2%), the PCA (15.4%) and the A2 tract and PICA (3.9%) (table 3).
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As far as concerns the type of treatment, of the 26 aneurysms considered, 30% (n=8) were treated surgically with clipping and wrapping-clipping (table 1); 65% (n=17) were treated with an endovascular procedure, using FDs, coiling, two or more stents + coiling, stent assisted coiling and no FD-stent. One patient (n. 7) was treated with a combined approach (wrapping+FD stent) and for this reason was included in the surgical treatment group. When including our three cases in the analysis, the percentage of patients treated with an endovascular procedure increased; in fact, two of our three patients were treated with FD stents (P64 and Silk) and the other was treated with stent-assisted coiling. With regards to complications, no intraprocedural complications were reported in the endovascular group, while two ruptures occurred in the surgical group; this could be related to the manipulation of vessels and placement of the clip. As far as concerns the endovascular
ACCEPTED MANUSCRIPT group, given the recent trend to treat this type of lesion with stents, FD or non-FD (14 patients in the population studied had been treated in this way, 82%), the rupture rate is decreased precisely because of the change in paradigm, from endosaccular to endovasal; retrospectively, this seems a predictor of a favorable outcome, although statistical confirmation is needed. Some thrombo-embolic complications could have been expected, but these were not reported
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to have occurred. With regards to postoperative complications, none was reported in the endovascular group, whereas there were five cases of hydrocephalus and four cases of vasospasm in the surgical group (table 1); this finding is very interesting, since it could be expected that the risk of
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vasospasm would be higher in the endovascular group, given the lack of surgical lavage of the cisterns. Vasospasm may be promoted by intraoperative rupture and, therefore an increase in the amount of blood in the subarachnoid space, as well as by surgical manipulation.
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Neurological outcome was dichotomized, dividing patients into those with mRS grades 0-2 and those with grades 3-6. The mRS scores were 0-2 in 15 patients (88%) in the endovascular group and five (55%) in the surgical group, whereas they were 3-6 in two patients (12%) in the endovascular group and four (45%) in the surgical group. These findings probably reflect the lower percentage of intraoperative and postoperative complications in the endovascular
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group. Regarding mortality rates, two patients died in the endovascular group (12%) and two in the surgical one (22%); causes of death were vasospasms (case n. 5), rebleeding (case n. 6), acute respiratory failure (case n. 8), and pneumonia (case n. 20). There were divergent results related to aneurysm occlusion status after the procedures and at
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the last follow-up: the class 1 occlusion rate in the surgical group was 89% (8/9), whereas it was only 41% (7/17) in the endovascular group. With regards to the Roy scale at follow-up
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(mean 195 days of follow-up) the class 1 occlusion rate was 100% in the surgical group and also 100% in the endovascular group, including one parent artery occlusion and one patient who did not have a follow-up because of death. These results appear to be in line with expectations; in fact, following surgery, the occlusion was complete immediately, except in patient n. 7 (table 1), in whom, despite initial wrapping with muscle and the use of fibrin glue, the angiographic picture did not change. For this reason a FD stent had to be released in the aneurysm, which gave an excellent result at follow-up.[13] In contrast, in the endovascular group, in which FD or non-FD stents are being used ever more frequently, a Roy scale class 1 result is not achieved immediately, although this does not seem to influence the later outcome. In case n. 21 (table 1), the use of two FDs between the A1-A2 tracts of both sides led to the closure of the tract of the AcoA and, therefore, a parent artery occlusion.
ACCEPTED MANUSCRIPT As far as concerns the endovascular group, it is worth commenting on anti-aggregant treatment: given that there is not a unique indication on the type of treatment to use, it is interesting to note the experiences of the various authors (table 4). In our institution, we usually start treatment with heparinization and administration of abciximab immediately after deployment of a FD, followed by postoperative dual antiplatelet therapy with aspirin and
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clopidogrel. In order to avoid potential hemorrhagic complications, if the patient needs a ventriculostomy, we place this before starting dual antiplatelet therapy. However, dual antiplatelet therapy is still controversial in the setting of acute SAH and the risk–benefit profile of potential hemorrhagic and thromboembolic complications should be considered
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carefully in deciding when to initiate such therapy.
With regards to the type of treatment, some comments should be made on the risks of endovascular management. Given the friable nature of the lesions, which can readily result in
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intraprocedural aneurysm rupture, we are particularly cautious about the use of coils as a stand-alone therapy for these small aneurysms. When possible, we prefer to deploy a FD, because it can redirect blood flow away from aneurysms, reconstructing the parent vessel. However, there are some disadvantages of using FDs in the treatment of BLAs, such as the need for dual antiplatelet therapy and the fact that the aneurysm is not immediately excluded,
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and remains at risk of re-rupture. With growing experience and increasing application of FD, several series and case reports have stressed the danger of periprocedural as well as delayed thromboembolic complications.[6,8,13] Indeed, our case series suggests that caution must be taken when applying this novel strategy to BLAs; one of our patients suffered from perforator
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occlusion, with a non-disabling persistent neurological deficit (patient 1), and another (patient 3) developed thromboembolic complications, probably due to ineffective antiplatelet
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therapy. The third patient died, but he had no complications related to the endovascular treatment (his death was due to pneumonia). Surgical treatment, too, has some shortcomings: in particular, a highly skilled surgeon, able to perform high-risk surgery, such as wrapping and by-passes, and to manage potential intra-operative rupture, is needed to treat BLAs. This study does have some limitations; it is retrospective rather than prospective, it is based only on data reported in the literature, and some articles (n=43) were excluded because they did not include cases of BLAs or did not report complete data on angiographic outcomes in cases of BLA. Furthermore, although we tried to perform a statistical analysis, the small population and fragmentation of the sample made it impossible to draw statistically meaningful conclusions.
ACCEPTED MANUSCRIPT Conclusions BLAs are complex lesions. According to our review, endovascular treatment of these lesions seems to be associated with less morbidity and mortality and a better outcome compared to surgical approaches, but further, prospective studies with long-term follow-up and statistical analysis must be performed to confirm these interesting results, in particular comparing
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admission grade, treatment technique, and Roy scale. Given the very small size of BLAs and their poor initial visibility, it is important to remember that they may occur in atypical sites other than the most common ICA localization. In the presence of a massive SAH with negative
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angio-CT and DSA, it is always prudent to explore the whole circle of Willis.
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This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Competing Interests Statement: SP is proctor for Penumbra All authors contributed to writing the article, revising the article and final approval of the article for submission to this journal. Our study complies with the Declaration of Helsinki; we performed a systematic review of the literature and patients were treated in our Institution using standard endovascular techniques that had no need for approval from an
ACCEPTED MANUSCRIPT References:
1. Andaluz N, Zuccarello M: Blister-like aneurysms of the anterior communicating artery: a retrospective review of diagnosis and treatment in five patients. Neurosurgery 62:807-811,
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2008.
2. Aydin K, Arat A, Sencer S, Hakyemez B, Barburoglu M, Sencer A, İzgi N: Treatment of ruptured blood blister-like aneurysms with flow diverter SILK stents. J Neurointerv Surg
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7:202-9, 2015.
3. Bulsara KR, Kuzmik GA, Hebert R, Cheung V, Matouk CC, Jabbour P, Hasan D, Pepper J:
ons85, 2013.
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Stenting as monotherapy for uncoilable intracranial aneurysms. Neurosurgery 73:ons80-
4. Chalouhi N, Zanaty M, Tjoumakaris S, Gonzalez LF, Hasan D, Kung D, Rosenwasser RH, Jabbour P: Treatment of blister-like aneurysms with the pipeline embolization device.
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Neurosurgery 74:527-532, 2014.
5. Consoli A, Nappini S, Renieri L, Limbucci N, Ricciardi F, Mangiafico S: Treatment of two blood blister-like aneurysms with flow diverter stenting. J Neurointerv Surg 4:e4, 2012.
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6. Grant RA, Quon JL, Bulsara KR: Oversized self-expanding stents as an alternative to flow-
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diverters for blister-like aneurysms. Neurol Res 36:351-355, 2014. 7. Ishikawa T, Nakamura N, Houkin K, Nomura M: Pathological consideration of a “blisterlike” aneurysm at the superior wall of the internal carotid artery: case report. Neurosurgery 40:403-406, 1997.
8. Lim YC, Kim BM, Suh SH, Jeon P, Kim SH, Ihn YK, Lee YJ, Sim SY, Chung J, Kim DJ, Kim DI: Reconstructive treatment of ruptured blood blister-like aneurysms with stent and coil. Neurosurgery 73:480-488, 2013. 9. Meckel S, Singh TP, Undrén P, Ramgren B, Nilsson OG, Phatouros C, McAuliffe W, Cronqvist M: Endovascular treatment using predominantly stent-assisted coil embolization
ACCEPTED MANUSCRIPT and antiplatelet and anticoagulation management of ruptured blood blister-like aneurysms. AJNR Am J Neurorad 32:764-771, 2011. 10. Morris TC, Brophy BP: Blister-like aneurysm of the anterior communicating artery. J Clin Neurosci 16:1098-1100, 2009.
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11. Nakagawa F, Kobayashi S, Takemae T, Sugita K: Aneurysms protruding from the dorsal wall of the internal carotid artery. J Neurosurg 65:303-308, 1986.
12. Peschillo S, Cannizzaro D, Missori P, Colonnese C, Santodirocco A, Santoro A, Guidetti G:
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Reconstructive endovascular treatment of a ruptured blood blister-like aneurysm of anterior communicating artery. J Neurosurg Sci June 10, 2014.[Epub ahead of print].
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13. Peschillo S, Missori P, Piano M, Cannizzaro D, Guidetti G, Santoro A, Cenzato M: Blisterlike aneurysms of middle cerebral artery: a multicenter retrospective review of diagnosis and treatment in three patients. Neurosurg Rev 38:197-203, 2014. 14. Pistocchi S, Blanc R, Bartolini B, Piotin M: Flow diverters at and beyond the level of the
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circle of Willis for the treatment of intracranial aneurysms. Stroke 43:1032-1038, 2012. 15. Roy D, Milot G, Raymond J: Endovascular treatment of unruptured aneurysms. Stroke 32:1998-2004, 2001.
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16. Rouchaud A, Saleme S, Gory B, Ayoub D, Mounayer C: Endovascular exclusion of the anterior communicating artery with flow-diverter stents as an emergency treatment for
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blister-like intracranial aneurysms. A case report. Interv Neuroradiol 19:471-478, 2013. 17. Seo DH, Lee WC, Choe IS, Park SC, Ha YS: Ruptured and unruptured aneurysms of the accessory anterior cerebral artery combined with a blood blister-like aneurysm of the anterior communicating artery. Neurol India 57:85-87, 2009. 18. Takahashi A, Suzuki J, Fujiwara S, Mizoi K, Yashimoto T: Surgical treatment of chimame (blood blister) like aneurysm at C2 portion of internal carotid artery. Surg Cereb Stroke 16:72-77, 1988.
ACCEPTED MANUSCRIPT Figure 1 Legend: A: The CT shows grade 3 Fisher hemorrhage, involving the basal cisterns and the left Sylvian fissure; B: An angio-CT performed immediately did not reveal vascular malformations; C: DSA performed 2 days after admission revealed a small BLA (about 1.5x1 mm) at the origin
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D: A stent (P64, Phenox, 3,5 x 15 mm) was placed from the M1 to the left ICA. E: The DWI images show an ischemic area (4.4 x 1.8 cm) in the acute phase involving the lenticular nucleus, the knee and arm of the internal capsule and the head of the caudate nucleus on the left. F: As a repeat angiogram two days after the initial procedure showed persistent aneurysm filling, we decided to occlude the A1 segment along with the aneurysm with coils (1.5x4 and 1x2, Target, Stryker) after navigating a microcatheter from the right ACA through the anterior communicating artery (ACoM). G-H: Follow-up DSA on postoperative day 7 confirmed persistent obliteration of the aneurysm and the parent artery.
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Figure 2 Legend:
A: Head CT showing SAH in the interpeduncular and right ponto-cerebellar cisterns along with intraventricular hemorrhage (IVH) B: Angio-CT showed a suspicious area immediately after the origin of the right PICA. C: DSA, performed the day after, reveals a small BLA immediately after the origin of the right PICA.
Figure 3 Legend:
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D-E: The aneurysm was treated with an Enterprise 4.5x14 stent to protect the basilar artery and coils within the aneurysmal sac, with immediate occlusion of the sac, preserving the PICA. F: A control MRI (DWI, ADC and Flair sequences) the following day did not show evidence of periprocedural complications.
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A: Head CT-scan showed SAH involving the right Sylvian fissure (Fisher 3). B: Angio-CT, performed immediately after, showed a small aneurysm of the inferior bran of the right middle cerebral artery, which was then confirmed by DSA (C). D: A FD stent Silk 3x20 was released across the aneurysm’s neck. E-F: At the DSA control after 14 days, the aneurysm had disappeared (Roy scale 1) and the stent was patent.
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DIFFUSE SAH
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Figure 4: Proposed flow chart of the management of a suspected BLA
ANGIO CT NEGATIVE
DSA + 3D
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EXPLORE THE WHOLE CIRCLE OF WILLIS
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+
-
REPEAT DSA AT DAY 3-5 AFTER SAH
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TREATMENT
ENDOVASCULAR/ SURGICAL
CONTROL DSA
+
-
10-14 DAYS AFTER SAH
STOP
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2014 – Grant (6)
2013 – Bulsara (3)
2012 – Pistocchi (14)
HH grade
Location
Treatment modality
Postop. complications Hydro - Vaso
3
180
1
1
1
None
1
180
1
1
1 1
3
3
ACoA
Surgery
Clipping
Rupture
2
2
2
ACoA
Surgery
Clipping
None
3
1
1
ACoA
Surgery
Clipping
None
4
3
4
ACoA
Surgery
Clipping
Rupture
5
3
3
ACoA
Surgery
Clipping
None
6
4
3
MCA
Endovascular
None
7
3
2
MCA
Endo + Surg
Coiling Wrapping + FD (PED) Wrapping + Clipping
8
2
2
MCA
Surgery
9
1
1
MCA
Endovascular
10
1
1
PCA
Endovascular
11
1
1
PCA
Endovascular
12
1
1
MCA
Endovascular
13
1
2
PCA
Endovascular
14
1
1
PCA
Endovascular
Stenting (Neuroform) Stenting (Neuroform) Stenting (Neuroform) Stenting (Neuroform 3) Stenting (Neuroform 3) Stenting (Neuroform 3)
Outcome mRS
FU (days)
Timing (days)
Early Roy Scale
FU Roy Scale
None
0
180
11
1
Hydro - Vaso
3
180
1
1
1
Hydro - Vaso
6
180
1
1
1
Rebleeding
6
15
1
1
1
None
None
0
540
1
3
1
None
Acute respiratory failure
6
15
1
1
1
None
None
0
430
1
2
1
None
None
0
430
1
2
1
None
None
0
13,6
1
2
1
None
None
1
300
7
3
1
None
None
1
150
7
1
1
None
None
1
30
7
2
1
15
2
2
A2
Endovascular
FD x 2 (SILK)
None
None
0
14
1
3
1
16
2
2
MCA
Endovascular
FD (PED)
None
None
0
60
1
3
1
17
3
4
BA
Endovascular
SAC
None
None
0
360
/
1
1
18
2
3
BA
Endovascular
SAC
None
None
1
360
/
2
1
19
1
1
ACoA
Surgery
Clipping
None
Hydrocephalus
2
60
15
1
1
20
4
4
ACoA
Endovascular
FD (SILK)
None
Pneumonia
6
3
1
1
/
21
3
4
ACoA
FD x 2 (PED)
None
None
2
90
1
1
PAO 1
EP
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2014 – Peschillo (12) 2013 - Rouchaud (16)
Intraop. complications
1
2011 – Meckel (9) 2009 – Morris (10)
Technique
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grade
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2014 – Peschillo (13)
Fisher
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2008 – Andaluz (1)
N
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Year - Author
Endovascular
2009 – Seo (17)
22
2
4
ACoA
Surgery
Clipping
None
Hydro - Vaso
2
/
1
1
2014 – Aydin (2)
23
/
2
BA
Endovascular
FD (SILK)
None
None
0
135
8
3
1
2014 – Chaloui (4)
24
1
2
BA
Endovascular
FD (PED)
None
None
1
14
1
2
1
2013 - Lim YC (8)
25
2
2
BA
Endovascular
Stenting x 3 (Neuroform) + Coiling
None
None
0
960
/
1
1
2012 – Consoli (5)
26
1
2
PICA
Endovascular
FD (PED)
None
None
0
180
5
1
1
Table 1: Literature review of data reported in case series. ACoA: anterior communicating artery; MCA: middle cerebral artery; PCA: posterior cerebral artery; PICA: poster inferior cerebellar artery; BA: basilar artery; SAC: stent-assisted coiling; FD: flow diverter; PED: Pipeline embolization device PAO: parent artery occlusion; Hydro: hydrocephalus; Vaso: vasospasm; FU: follow-up.
Fisher grade
HH grade
Location
Treatment modality
First procedure
Second procedure
Device
1
3
2
A1
Endovascular
FD
Coiling
P64 3.5 x 15, Phenox
2
4
4
PICA
Endovascular
SAC
None
Target, Stryker Enterprise 4.5x14, Codman
3
3
4
MCA
Endovascular
FD
Decompressive craniectomy
SILK 3 x 20, Balt
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Table 2: our single-institution case series of atypical BLAs. * days from SAH to treatment
Intraop. complications
Postoperative complications
Outcom e mRs
FU (days)
Timing (days)*
Early Roy Scale
FU Roy Scale
None
Transient neurological deficit
0
30
6
3
1 (PAO)
None
Pneumonia
6
18
5
1
-
None
thromboembolic complications, raised ICP
5
14
1
3
1
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Total
26+3
(100%)
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(3.9) (34.6) (19.2) (23) (15.4) (3.9)
335
%* of 335 0.3% 0.3% 2.7% 1.5% 2.1% 1.2% 0.6%
7.8% 8.6%* 100%
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Entire population
(%)
N 1 1 9 5 6 +1 4 1+1
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Location A1 A2 ACoA BA MCA PCA PICA
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Table 3: data concerning the location of BLAs. The column on the far right reports percentages with respect to all the BLAs described in the literature regardless of their location. A1,A2: anterior cerebral artery, tract 2; ACoA: anterior communicating artery; MCA: middle cerebral artery; PCA: posterior cerebral artery; PICA: poster inferior cerebellar artery.
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The cases reported in this manuscript are in italic and bold. * this percentage includes our three patients reported in this manuscript
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N
AP therapy (12 hours preoperatively)
N
AP therapy (until month 6 postoperatively)
N
AP beyond month 6 postoperatively
N
Heparin
12
ASA 300mg + Clopidgrel 600mg
7
ASA 300mg + Clopidogrel 75 mg
8
ASA 250mg
2
Abciximab (Reopro, Lilly)
3
ASA 250mg + Abciximab
1
ASA 250 mg
7
ASA 200mg
1
ASA
1
ASA 300mg alone Clopidogrel 150 mg alone
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Intraoperative therapy
5
Clopidogrel 150mg
1
ASA 100mg
2
1
ASA 200mg
1
ASA 150 mg + Clopidogrel 75 mg
2
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Table 4: data concerning antiplatelet therapy administered to patients in the endovascular group 12 hours prior to the procedure, intraoperatively, during the first 6 postoperative months and thereafter. ASA: aspirin; AP: antiplatelet.
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